elife.txt

Bacteria are a group of bacteria that live in the environment . They are able to adapt to their environment by modifying their sugars , proteins , and other molecules . These changes can be made by proteins with a membrane-bound acyltransferase domain , which is found in all living organisms . The acylation of sugars is essential for many processes , including symbiosis , resistance to viruses and antimicrobials and biosynthesis of antibiotics ; however , the structure and mechanism of these proteins are largely unknown . In bacteria , a protein called OafB is involved in a wide range of processes . It is a member of the family of proteins called the AcylTransferases . This family of enzymes is found on the surface of bacteria and is responsible for modifying sugars in many different ways . However , it is not clear how the acetyl group from the bacterial OabB protein is regulated . To address this question , Liu et al . developed a computational model of the structure of the bacterium , OapB , using a combination of molecular dynamics simulations and experimental data . Using this model , they identified a new fold for the AT3 domain .
Honey bees are a group of insects that live in the wild . They are able to explore a wide range of flowers , including flowers that provide nectar and pollen . The bee must decide whether a flower should be explored for nectar or whether it is not worth landing on . This decision is made by a bee’s brain , which can be mapped to known pathways in the insect brain . However , it was not clear how the bee makes such a decision . To address this question , Chen et al . used a computer model to study the decision-making process of honey bee larvae . In the model , the larvae were allowed to fly in a controlled flight arena that varied the likelihood of a stimulus offering reward and punishment , as well as the quality of evidence for the stimuli . When the larval flight arena was switched on , a reward would be offered , while a punishment would be given , depending on the quality and reliability of the evidence for a response . These results showed that the honeybee decision making process was more sophisticated than previously thought , and that it was more sensitive to changes in available evidence and reward likelihood . Moreover , fast acceptances were more likely to be correct than slower acceptances , suggesting that the evidence threshold for decision making changes dynamically with
Metformin is the most commonly prescribed drug for type 2 diabetes . It is also the most frequently used drug for aging . However , it is not clear how metformin affects the longevity of humans . One way to find out is to look at the genes that are involved in the production of ether lipids , which are a group of fatty molecules that are found in the blood . These lipid molecules are known to be involved in a number of different processes , including lipid biosynthesis , lipid production , and lipid metabolism . But it was not clear exactly how these processes are linked to longevity . To address this question , Wang et al . used a nematode worm called Caenorhabditis elegans to study the role of genes involved in producing ether-lipids in the lifespan of the worms . The experiments show that a protein called fard-1/FAR1 is required for the production and production of these molecules . Further experiments showed that reducing the amount of fard-1 in the cells reduced the lifespans of the animals . This suggests that fard1 plays a role in regulating the activity of the mitochondria , the organelles that transport energy from the body to the cells . Wang , Chen el . ’s findings suggest that far
The gut of mammals is a complex community of microbes that are able to provide a range of services to their hosts , including food , water , and shelter . Understanding how the gut microbiome is organized and maintained is essential to understanding how the microbiomes affect the health of humans and other animals . However , it is not clear whether the relationship between bacteria in the gut is universal across hosts or personalized to individual hosts . To answer this question , Xu et al . used a mathematical model to analyze the abundance of bacteria in baboons over 13 years . This revealed that most bacterial abundance correlations are weak , negative , or universal . Moreover , the most common bacterial correlations were weak and negative . In contrast , in humans , most of the bacterial relationships were similar across hosts and were stronger than one data set from human adults . These results suggest that the universality of bacterial associations across hosts may be important for determining the composition of the microbe community , as well as for designing interventions to improve host health . The findings of Yükseff , Zheng , Wang , Liu , Zhang el . suggest that , although the bacteriophages are universal , they are not universal across humans . Further work is now needed to
Gamma oscillations are a phenomenon that is thought to be important for many cognitive processes . These oscillation patterns are triggered by the activity of neurons in the brain , which are connected to each other by a process called feedback inhibition . This process is known as “winner-take-all” , and it is thought that the brain uses feedback inhibition to control how the brain processes sensory information . However , it is not clear how these oscillators work . To address this question , Wang et al . studied the olfactory cortex of awake mice . The experiments show that breathing is important for generating gamma rhythms in the piriform cortex , a region of the brain that processes smells . In the experiments , the mice breathed for a few seconds , followed by another few seconds of breathing . Wang , Zhao el . found that breathing leads to a series of gammin oscillation events in the cortex . When the mice were awake , they were able to detect odors in their noses , but not in their eyes . Furthermore , when the mice had been awakened for several minutes , their brains were unable to detect smells at all . Further experiments showed that , in addition to triggering feedback inhibition in the area of the 
The replication of eukaryotic genomes is a highly coordinated spatiotemporal program , but the mechanisms establishing which domains replicate early versus late in different cell types remain incompletely understood . Intercalary heterochromatin domains are very late in both diploid chromosomes of dividing cells and in endoreplicating polytene chromatin where they are also underreplicated . Drosophila SNF2-related factor SUUR imparts locus-specific underreplication of polytenene chromosomes . However , its mechanism of action remains obscure . Here , we developed a novel method termed MS-Enabled Rapid protein Complex Identification ( MERCI ) to isolate a stable stoichiometric native complex SUMM4 that comprises SUur and a chromatid boundary protein Mod ( Mdg4 ) -67 . 2 . Mod ( Mod ) is required for a normal spatial distribution of SUUM4 in vivo . SuUR and Mod ( mdg 4 ) together mediate the activities of gypsy insulator that prevent certain enhancer–promoter interactions and establish euchromatin–heterochromatin barriers in the genome . Furthermore , SuUR or mod ( s
The biological age in adults is often understood as representing general health and resilience , but the conceptual interpretation of accelerated biological age is unclear . We aimed to clarify the relationship of accelerating biological age , assessed through two established biological age indicators , telomere length and DNA methylation age – two established markers , and two novel candidate biological age markers – to child developmental outcomes , including growth and adiposity , cognition , behavior , lung function and the onset of puberty , among European school-age children participating in the HELIX exposome cohort . The study population included up to 1173 children , aged between 5 and 12 years , from study centres in the UK , France , Spain , Norway , Lithuania , or Greece . Telomerelength was measured through qPCR , blood DNA mRNA , gene expression was measured using microarray . DNA hemispheric age was assessed using Horvath’s skin and blood clock , while novel blood transcriptome and ‘immunometabolic’ clocks were derived and tested in a subset of children assessed six months after the main follow-up visit . Among associations with health risk factors , higher birthweight was associated with greater immunometabolic  age . Smok exposure was associated to greater DNA mel
Asthma is a complex disorder caused by a variety of mechanisms . Many genes associated with asthma explain only a fraction of its heritability . Most genome-wide association studies ( GWASs ) used a broad definition of ‘doctor-diagnosed asthma’ , thereby diluting genetic signals by not considering asthma heterogeneity . The objective of our study was to identify genetic associates of childhood wheezing phenotypes jointly derived using unbiased analysis of data collected from birth to 18 years in 9568 individuals from five UK birth cohorts . Forty-four independent SNPs were associated with early-onset persistent , 25 with pre-school remitting , 33 with mid-childhood remitted , and 32 with late-onset wheeze . We identified a novel locus on chr9q21 . 13 ( close to annexin 1 [ANXA1] , P6 . 7  10-9 ) , associated exclusively with early–onset persistent wheEZing . Finally , in a murine model of house dust mite ( HDM )-induced allergic airway disease , we demonstrated that anxa1 protein expression increased and anxi1 mRNA was significantly induced in lung tissue following HDM exposure .
The ability of plants to adapt to their surroundings is a key feature of cropping systems . However , it is not clear how these adaptations can be achieved . For example , the ability of a crop to grow more than two species in the same field during the same period can be affected by the presence of different species . This can lead to a reduction in competition and/or facilitation between the crops , which can result in a decrease in yield . Intercropping is an important approach to improve agricultural sustainability , but it has been difficult to study the impact of intercropping on crop yields . To address this question , Xu et al . used a combination of genetic and biochemical approaches to study intercroping in the field of wheat . The experiments show that when the plants were growing in the similar community type as their parents did in the previous two generations , they were able to reduce competition or facilitation . In addition , in fertilized conditions , these plants were more likely to grow taller phenotypes with lower leaf dry matter content . These results provide the first empirical evidence for the potential of parental diversity affecting plant–plant interactions , species complementarity and ecosystem functioning of the following generations in annual cropping . Further studies are needed to assess the context–dependence of these findings .
Many animals live in complex social groups , in which interactions range from intense competition to cooperation . Coordination is essential for maintaining cohesion between group members , avoiding conflicts , and achieving individual and joint action goals . However , it is not clear how individuals learn to coordinate their actions . To investigate this question , Liu et al . developed a system where two individuals seated face-to-face to engage in game-theoretical tasks on a shared transparent touchscreen display ( ‘transparent games’ ) . The experiments show that human and macaque pairs develop coordinated behavior and adopt dynamic turn-taking to equalize the payoffs . All macaques learned to coordinate dynamically after training with a human confederate . This pair selected the faster agent’s preferred option , which was captured by modeling the visibility of the partner’s action before one’s own movement . Thus , dynamic coordination is not restricted to humans , but can occur on the background of different social attitudes and cognitive capacities in rhesus monkeys , suggesting that dynamic coordination can arise on the basis of differences in social attitudes , cognitive capacities and behavior . These results illustrate how dynamic coordination may emerge and maintain when agents can observe and time their mutual actions , while taking into account the history of interactions with and between these individuals .
Ovarian development requires the combination of germ cells and several types of somatic cells . Among these , granulosa cells play a key role in follicle formation and support for oogenesis . Whereas efficient protocols exist for generating human primordial germ cell-like cells ( hPGCLCs ) from human induced pluripotent stem cells ( hiPSCs , or hiPScs – hGSCs - hPSCs- ) , the method of generating granULOSA-like cell ( HOPC ) has been elusive . Here , we report that simultaneous overexpression of two transcription factors ( TFs ] can direct the differentiation of hi PSCs to granulate cells , and we elucidate the regulatory effects of several granular-related TF proteins . Our HOPACs have transcriptomes similar to human fetal ovarian cells and recapitulate key ovarian phenotypes . When aggregated with hSGSCs and hPOPCs we form ovary-like organoids ( ovaroids ” ) and support hOGCLC development from the primgratory to the gonadal stage as measured by induction of DAZL expression . This model system
The skin of humans is a mixture of pigments , which are produced by the sun and the sun’s ultraviolet radiation . The skin pigments are influenced by the environment , and the genetic variation that influences skin pigmentation is thought to be the most likely reason for the convergent evolution of lighter skin color in European and East Asian/Native American populations . However , it is not clear how the genetic admixture of Native American and European populations affects the pigmentation of skin . To address this question , Xu et al . studied 458 genomes from individuals residing in the Kalinago Territory of the Caribbean . This revealed that 55% Native American , 32% African and 12% European genetic ancestry , the highest Native American genetic assimilation among Caribbean populations to date . Skin pigmentation ranged from 20 to 80 melanin units averaging 46 . Three albino individuals were determined to be homozygous for a multi-nucleotide polymorphism OCA2NW273KV contained within a haplotype of African origin; its allele frequency was 0 . 03 and single allele effect size was –8 . 6 , respectively . Native American genotypes by itself reduced pigmentation by more than 20 melanocyte units ( range
Diabetes is a chronic metabolic disease that has emerged as a global public health problem . It is caused by the accumulation of reactive oxygen species ( ROS ) in the blood . The levels of ROS are thought to increase the risk of developing diabetes . However , it is not clear exactly how these ROS contribute to diabetes , and how they do so . To address this question , Sun et al . compared exercise and antioxidant intervention on type 2 diabetic rats . This revealed that both of these two approaches could promote glucose catabolism and inhibit gluconeogenesis through activation of hepatic AMP-activated protein kinase ( AMPK ) signaling . Both of these interventions could promote redox balance in the liver . In contrast , antioxidant intervention achieved a low-level balance by inhibiting oxidative stress . Overall , these results indicate that both exercise or antioxidant intervention improve blood glucose control in diabetes by promoting a balance between antioxidant activity and oxidant damage . These findings provide theoretical evidence for the precise management of diabetes by antioxidants and exercise . They also suggest that the AMPk signaling activation , combined with oxygen damage markers , could act as sentinel biomarkers , reflecting the threshold of reoxidative balance that is linked to effective glucose control .
The escape trajectory of a predator is a measure of the angle at which the predator approaches the prey . This angle is measured as the angle relative to the predator’s approach path . Previous models predicted a single escape trajectory; however , many species show highly variable escape trajectory with multiple preferred directions . Although such a high variability may confer unpredictability to avoid predation , the reasons why animals prefer specific multiple escape trajectorys remain unclear . To address this question , Weihs et al . developed a novel mathematical model that incorporates the time required for prey to turn and the predator's position at the end of its attack . The optimal escape trajectory was determined by maximizing the time difference between arrival at the edge of the safety zone between the preyer and the predator . By fitting the model to the experimental data of fish Pagrus major , we were able to produce various patterns of escape trajectory observed in other species ( e . g . insects and frogs ) . These results open new avenues of investigation for understanding how animals choose their escape trajectory from behavioral and neurosensory perspectives . In the future , it will be important to understand how animals select their escape route from behavioral or neurosensoric perspectives , as well as how they use their brains to detect and respond to predators .
Human pluripotent stem cells ( hPSCs ) are a type of stem cell that can be used to study human diseases . These cells are made up of a protein called Cas9 , which is fused to a DNA molecule called a reverse transcriptase ( nCas9-RT ) , and an extended PE guide RNA ( pegRNA ) extension . Once reverse transcribed , this extension is used as a repair template to introduce precise designer mutations at the target site . However , it is not clear how the PE components are able to perform this task . To address this question , Hockemeyer et al . have developed a new method called prime editing ( or PE for short ) that uses a combination of enzymes and a double-strand break repair enzyme . The enzymes are fused together to form a complex , multicomponent editing system . When the enzymes bind to each other , they fuse together to make a long RNA molecule . This RNA is then translated into a template that is then used to repair the broken DNA . After the repair is complete , the PE guides RNA ends up being used as templates to insert the correct mutations into the target . In addition , a chemically modified peg
Multiple myeloma is a type of cancer that affects about 10% of the world’s population . It is caused by the uncontrolled proliferation of monoclonal plasma cells ( PCs ) , which are found in the bloodstream , and are responsible for the majority of all cancers . The Revised International Staging System ( R-ISS ) was developed to identify patients at different stages of the disease , with different outcomes and treatment response . However , little is known about the heterogeneity of the tumour cells in the patient’s tumour . To address this question , Wang et al . created a single-cell transcriptome atlas to compare the expression patterns of different types of PCs among patients . This revealed that a novel cytotoxic plasma cell population exhibited with NKG7 positive was obviously enriched in stage II patients , while a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus infection . Furthermore , ribonucleotide reductase regulatory subunit M2 was found to promote proliferation of MM cell lines , suggesting that RRM2 may serve as a detrimental marker in MM . Further studies are now needed to understand the role of CD8+ T cells and NKT
The CRISPR system is a type of protein that can be used to bind to and cleave a large number of different RNA molecules . This RNA is then used as a template to make a protein , which can then be used by other proteins to make new proteins . The CRIPR system can also be used in the laboratory to make proteins that are not needed by the host . One type of CRIS PR system is called Cas7-11 , and it is made up of four different parts , each of which can be inserted into a single protein . Cas-7-11 is able to engulf the RNA , but it is not clear how it does this . To investigate this , Wang et al . used a technique called cryo-electron microscopy to examine the structure of the active Cas 7-11 protein – which is made of four parts – and found that it resembles the backbone of the multi-subunit enzymes . In addition , the structure revealed that the four parts of the protein are arranged in an extended form . However , it was not clear what role these parts play in the processing of the molecule , or how they interact with each other . Further experiments showed that the three parts of Cas07-11 are similar to those found in other CRIS
The diversity of a species is important for the ecosystem to function and contribute to its own benefit . However , the effects of genetic diversity on the productivity of varying species are not well understood . For example , it is not clear how genetic diversity affects plant productivity , but it is possible that genetic diversity can have a negative effect on productivity . To address this question , Wang et al . used a tree species  genetic diversity experiment to study how genetic variation affects tree productivity in a variety of species . The experiments show that genetic variation increases tree productivity by increasing the number of species in the tree , reducing the diversity of the soil fungi , and reducing herbivory . Furthermore , genetic diversity also reduces soil fungal diversity , which is a common feature of plants . This suggests that both species and genetic diversity should be considered in afforestation . In the future , more studies will be needed to understand the impact of genetic variation on tree productivity and how it affects the productivity and productivity of different species of trees . A better understanding of the relationship between genetic diversity and tree productivity will help us to better predict the consequences of biodiversity loss and prioritize the different aspects of biodiversity conservation efforts .
Proteins are a group of molecules that interact with each other to form complexes . These interactions are known as interactions . However , it is not clear how these interactions occur , and how they are able to be detected in live cells . One way to study interactions between proteins is to use a technique called single-particle tracking . This technique uses a fluorescent dye called rhodamine to track the movement of individual proteins , but it is difficult to track these molecules at the same time . To do this , a dye called proximity-assisted photoactivation ( or PAPA for short ) is used . PAPA can be used to track proteins in living cells , while still detecting interactions between the two proteins . Previous studies have shown that PAPA works by reactivating one of the two fluorophores from a dark state . Now , Wang et al . have used PAPA to track and identify interactions between two proteins in live live cells using a new technique called proximity assisted photoactivated ( PAPA ) . The experiments show that PPA can be applied to a subpopulation of proteins in which two different labels are in proximity . In addition , PAPA detected the expected correlation between androgen receptor self-association and chromatin binding at the single-cell level . Together , these
The effect of calcium supplementation on bone mineral accretion in young populations ( 35 years ) is inconclusive . To comprehensively summarize the evidence for the effect of Calcium supplementation in young population ( i . e . young people ) , this is a systematic review and meta-analysis . The Pubmed , Embase , ProQuest , CENTRAL , WHO Global Index Medicus , Clinical Trials .gov , World Health Organization , China National Knowledge Initiative ( CNKI ) and Wanfang Data databases were systematically searched from database inception to April 25 , 2021 . Randomized clinical trials assessing the effects of calcium supplements on bone minerals density ( BMD ) or bone mineral content ( BMC ) in people under 35 years old were analyzed . Moderate certainty of evidence showed that calcium supplementing was associated with the accrretion of BMD and BMC in femoral neck ( standardized mean difference [SMD] 0 . 627 , 95% confidence interval [CI] 0-0 , 338–0  . 915; SMD 0. 364 , 095–0 595; respectively ) as well as total body ( SMD = 0: 330 , 995 CI 0-006–
The virus that causes influenza is a life-threatening disease that affects millions of people each year . The virus is made up of eight different viral RNA segments , each of which is encapsidated by molecules of nucleoprotein along its length . Each of these segments is then transcribed to make a protein , which is then used to make the viral genome . This process is called viral inclusion , and it is important to understand how this process works . Many viruses , such as influenza A virus ( IAV ) , are able to form viral inclusions in the cytosol of their host cells . However , it is not clear how these viruses can harden their inclusions . To address this question , Xu et al . used a technique called X-ray crystallography to study the properties of the influenza IAV inclusions and found that they could be hardened by changing the valency of the viral proteins . These proteins are known to interact with each other , but it was not clear if these interactions were more efficient than changing the concentration or temperature of the virus inside the cell . Further experiments showed that , when the virus was exposed to the virus , the inclusions were harder to harden than when they were exposed to a higher temperature . Moreover , this was not the case when the
The axons of the nematode C . elegans are made of a complex of filaments called microtubules . These filaments are arranged in a manner that allows them to move along the cell membrane , which is important for the cell to communicate with the rest of the body . Kinesins , a family of proteins , are found in many organisms and have been implicated in many diseases . However , it is not clear how kinesin-4 is able to control the length of the microtubular filaments in the worm . To address this question , Liu et al . used a technique called X-ray crystallography to examine the structure of the KLP-12 protein . This protein binds to a protein called tubulin , and it helps to bend the ends of the filaments to prevent them from forming . The experiments show that the bending effect of the motor domain of the protein is in between the elongation and shrinking forms of the end of the fibers and that the curvature of the ends is between the two . Further experiments showed that the motordomain of the mutant worm KLP12 is also required for the length control of the cell . Liu and Liu have now shown that the mutant mutant kLP-12
The embryo of a fruit fly is made up of specialized cells called germline stem cells . These cells are able to produce many different types of cells , including oocytes , sperm , and eggs . The embryos of the fruit fly are shaped like a zygote , with a very short chromosome , which allows the stem cells to grow and divide . However , the embryo does not have a complete set of genes , so it is not clear how the embryo develops . To investigate this question , Liu et al . used a technique called X-ray crystallography to study the development of the embryos in fruit flies . This revealed that the embryo’s germline cells are very similar to the embryonic zygotes , but that they do not change over evolutionary time . Instead , they become cystoblasts that produce daughter cells that develop into nurse cells and ovary . In the embryo , these daughter cells are called cystoblasts and are surrounded by a layer of chromatin called pericentromeric H3K9me3 . When a transposable element , called Polycomb , enters the cell , it can repress the gene that encodes a protein called Neijre
The development of a plant is a complex process that requires the coordinated movement of many different parts of the plant . For example , the development of the flowers is regulated by the circadian clock , which generates daily rhythms in physiology and behavior , and also by developmental oscillators , such as the segmentation clock . In sunflowers , for instance , hundreds of individual florets are tightly packed onto a disk , forming ring-like structures called pseudowhorls . These structures are made up of hundreds of cells , each of which undergoes several stages of maturation . When a flower develops in the early stages of flower development , it is surrounded by a cluster of cells called a ‘segmentation clock’ . The sex of the sexes is controlled by the time of day , but it is not clear how this clock works . To address this question , Wang et al . studied sunflowers grown in the laboratory . This revealed that the timing of flower anthesis in sunflowers is synchronized with the time when the flowers are ready to be produced . However , when flowers are produced in the late stages , they are arranged in clusters called ‘pseudomonas’ , or ‘rings’ for short .
The nematode Caenorhabditis elegans is a model organism for studying how organisms cope with the threat of reactive chemicals . The worms are able to sense temperature and respond to it by releasing a chemical called hydrogen peroxide . This chemical is known to cause damage to the cell membranes of the worm , which is essential for life . However , it is not clear how the nemanths respond to this threat . To address this question , Wang et al . used a technique called X-ray crystallography to study how a group of worm cells respond to the presence of high temperatures . These experiments show that a pair of neurons in a worm’s brain detect high temperatures and activate specific defenses . When the neurons detect high temperature , these defenses are activated by a hormone called insulin . In the future , this work will help to understand how worm species respond to a threat of a reactive chemical . For example , if a person is exposed to high temperatures in their environment , they may be more likely to develop a protective immune response . If this is the case , then it may be possible to develop drugs that target the cells that are exposed to higher temperatures , such as insulin or IGF1 .
The immune system is a complex system that includes the immune system , immune cells , and other cells . It is important to understand how this system works , because it can lead to diseases such as cancer , autoimmune disorders , or autoimmune diseases . In the body , cells divide to produce different types of antibodies . Each type of antibody is made up of two copies of the same protein , called antibodies , which are then copied to form a new protein . This process , known as class switch recombination , generates antibodies that are different from those that are produced by the same cell . When a cell divides , the proteins that make up the antibodies are copied to make new proteins . However , it is not clear how these proteins work . To investigate this question , Wang et al . used a technique called X-ray crystallography to study the role of two enzymes that are involved in the removal of DNA double-strand breaks . The experiments show that cells that lack two of these enzymes – called senataxin and RNase H2 – have a higher rate of forming DNA double strand breaks than cells that do not . Further experiments showed that , in the absence of sensetaxin , DNA breaks are more likely to form at the immunoglobulin heavy-chain
The severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) is continuously evolving , and the emergence of new variants has caused successive waves of coronovirus disease 2019 ( COVID-19 ) . Large-scale populations in the world have been vaccinated with COVIDS-19 vaccines , however , breakthrough infections of SARS–CoV-1 are still growing rapidly due to the occurrence of immune-evasive variants . It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants and to better prevent the pandemonium of these viruses . Here , we present a mosaic-type trimeric form of spike receptor-binding domain ( mos-tri-RBD ) as a broad-specrum vaccine candidate , which carries the key mutations from Omicron and other circulating variants in the virus . Tests in rats showed that the designed mos -tri RBD was able to elicit potent cross-neutralizing antibodies against not only O microfilaments but also other immune-valves . Neutralizing antibody ID50 titers were substantially higher than those induced by homo-tri/RBD ( containing homologous RBDs from prototype strain ) or the BIBP inactivated CO
Malaria is a disease caused by the protozoan parasite Plasmodium falciparum . It is the deadliest to humans , and the current antimalarial drugs used in combination therapies are under threat . The parasites infect red blood cells , which are the main source of blood , to digest the blood’s main protein , hemoglobin . P . falcipal parasite proteins are found in red blood cell compartments called vacuoles , where they are broken down by enzymes called aminopeptidases . One of these enzymes , called PfA-M17 , has been implicated in the last step of the parasite’s digestive process . However , it was not clear whether Pf A-M-17 is essential for parasite survival . To address this question , Xu et al . used genetic and biochemical approaches to study the role of this enzyme in parasite growth . In the experiments , PfM17 was genetically engineered to inhibit the activity of another enzyme , known as PfC-M18 . This enzyme was found to be essential for the survival of the malaria parasite . Moreover , the mutant parasite had multiple compartments in their digestive system , many of which were likely to originate from hemoglobine . Further experiments showed that
Early hematopoiesis is a continuous process in which hematomocytes gradually differentiate toward specific lineages . Aging and myeloid malignant transformation are characterized by changes in the composition and regulation of hemmatocytes . In this study , we used single-cell RNA sequencing ( scRNA-seq ) to characterize an enriched population of human hematocytes obtained from young and elderly healthy individuals . Based on their transcriptional profile , a detailed analysis of gene set enrichment analysis revealed changes in progenitor compartments during aging , and differences in their functionality , as evidenced by gene set inference . Next , using a reference population of healthy cells as a model , We analyzed s RNA-Seq data obtained from patients with myelodysplastic syndrome ( MDS ) and detected specific alterations of the expression dynamics of genes involved in erythroid differentiation in all patients with MDS such as TRIB2 . Furthermore , the comparison between transcriptional programs and GRNs regulating normal HSPCs and MDS cells allowed identification of regulons that were specifically active in MDS cases such as POU2F2 , RUNX1 , or SMAD1 . Our findings demonstrate that the combination of single cell technologies with
Honey bees are a group of insects that live in colonies . They are able to learn to avoid odors that are irrelevant to their survival , and to avoid those that are harmful to their health . Honey beers have a tendency to avoid certain smells , such as rotten eggs , when they encounter an odor they have experienced before . However , if a odor is not associated with an important consequence , it can delay learning about that odor . This is called latent inhibition , or ‘latent inhibition’ . In honey bee colony cells , the tyramine receptor gene AmTYR1 is known to be involved in this type of learning . The gene encodes a receptor that is found in the nucleus of the brain . When a bee is exposed to a smell that is harmful to its health , its response to that smell is delayed , which can lead to behavioural differences . Previous studies have shown that a gene called AmtyR1 regulates the activity of a region of the genome called the CNS . But it was not clear how this gene affects the ability of the bee to learn about the smell . To address this question , Liu et al . used a combination of genetic and biochemical approaches to study the role of Amt
The airway is a large , swollen , and crowded tissue that contains many different types of cells . These cells are arranged in a way that allows them to respond to different stimuli . For example , the airway secretory cells in the trachea of the lungs produce a chemical called choline , which is released into the air . This chemical binds to molecules in the airways , but it is not clear how these molecules interact with each other . To investigate this question , researchers have developed a technique called autofluorescence imaging ( or AFIL for short ) that uses a fluorescent tag to detect the activity of a specific cell type in real time . However , current methods only allow the study of three or four cell types at a time , making it difficult to identify individual cells in real-time . Now , Liu et al . have used this technique to identify all seven types of airway epithelial cells in mice . The experiments show that this technique can be used to identify seven different cell types simultaneously , even in the absence of an invasive technique . Furthermore , this technique is able to detect changes in the shape of the cells , such as changes in their size or shape , in response to a particular stimulus . Further experiments also show that
Heart failure is the leading cause of death worldwide . The heart is unable to regenerate after injury , and it is therefore important to understand how the heart works . A protein called Mettl3 is a methyltransferase that methylates adenosine , a chemical that is found in the cell membrane . Mettle3 is involved in many processes , including the production of proteins , such as methylation of RNA , which is essential for the formation of new cells . However , it is not clear how Mettll3 regulates the production and activity of methylated RNAs . To address this question , Liu et al . studied the role of m6A in heart regeneration in mice . Mice that had been genetically engineered to have a mutation in the gene that encodes a protein called Fgf16 were able to grow and regenerate their heart . In the experiments , the mice were injected with a drug that inhibits the activity of the enzyme . When the drug was activated , these mice had fewer heart cells and grew more slowly than normal mice when they were born . This increased heart regeneration was also seen in mice that had a mutant version of FgF16 . These mice had more heart cells compared to normal mice ,
The risk of second primary cancers ( SPC ) is increasing after the first primary cancer is diagnosed and treated . The underlying causal relationship remains unclear . We conducted a pan-cancer association ( 26 cancers ) study in the Surveillance , Epidemiology , and End Results ( SEER ) database ( non-Hispanic whites , n=459 ,136 , European whites and non-Hespanic blacks . Our results showed that the standardized incidence ratio ( SIR ) was the risk of SPCs in cancer survivors based on the incidence in the general population . Furthermore , the causal effect was evaluated by two-sample Mendelian Randomization ( MR , 13 FPCs – UKB , UKB = 459 136 ) and robust analysis ( radial MR and Causal Analysis Using Summary Effect estimates , CAUSE ) . In particular , patients initially diagnosed with oral pharyngeal cancer would have an increased risk of non-Hodgkin lymphoma ( SRISEER = 1 . 18 , 95%Confidence Interval [CI]:1 . 05–1 , 31 , 6 . 90  10-3 ) or ovary cancer ( SSRSEER=
The human eye is a powerful tool for determining the value of an item . In humans , this is done by moving the focus of their eyes between the options , and in nonhuman primates , such as macaque monkeys , it is common for them to choose between multiple items based on their perceived value . However , recent studies in humans suggest that these shifts in gaze influence choice , manifesting as a bias in favor of the items that are viewed first , viewed last , or viewed for the overall longest duration in a given trial . This suggests a mechanism that links gaze behavior to the neural computations underlying value-based choices . To develop a suitable animal model of this behavior , Liu et al . created a new task for monkeys that captures the essential features of the human paradigms in which gaze biases have been observed . Using this task , the monkeys were shown to be more likely to choose the first item that they view than the item they look at just prior to indicating their decision . Furthermore , using a sequential sampling model framework previously used to describe gaze bias in humans—the first time this framework has been used to assess value-related decision mechanisms in other species . Together , these findings suggest a common mechanism that can explain gaze-related change in decision-making across species
Most phytophagous insect species specialize on a few or a single host plant . In contrast , some species display a remarkably large diet breadth , with host plants spanning several families and many species . It is unclear , however , whether this phylogenetic genelogism is supported by a generic metabolic use of common host chemical compounds ( ‘metabolic genealism’ ) or alternatively by distinct uses of diet-specific compounds ( “multi-host metabolic specialism” ) . Here , we simultaneously investigated the metabolomes of fruit diets and of individuals of a generalist phytophagious species , Drosophila suzukii , that developed on them . We found that the consumption of biochemically dissimilar diets resulted in a canalized , generic response from generalist individuals , consistent with the metabolic genelogalism hypothesis . Furthermore , many diet-species metabolites , such as those related to the particular color , odor , or taste of diets , were not metabolized . As a result , while individuals were mostly similar across diets; the detection of their particular diet was straightforward . Our study thus supports the view that dietary genelogists may emerge from a passive , adaptive use of various resources , contrary to more widespread views of
The bacterium Yersinia pestis is a parasite that causes plague in humans and other animals . It is transmitted by fleas , which are a common source of disease in humans . The Y . pestis parasite lives in a biofilm that surrounds the flea foregut , where it can be used as a model to study the evolution of the parasite . This biofilm is made up of a small protein called rcsA , and a gene that encodes a protein called RcsD . Previously , it was known that a mutation in the gene that codes for RcSD was an important step in the development of the pathogen , but it was not clear how it did so . To address this question , Xu et al . used a combination of genetic and biochemical techniques to identify a frameshift mutation in RcCsD that led to a change in the protein . In the experiments , the mutation changed the protein’s structure , making it more likely that the protein would be able to bind to the phosphorylated form of the Rccs signalling pathway . Further experiments revealed that this frameshift change in recombination of the gene , known as pseudogenization , resulted in
The peer review process is a crucial step in the publication of scientific research . It helps ensure the quality and validity of scientific work . However , concerns have been raised regarding the subjectivity in this process . Many studies have found evidence that the process is subject to subjectivity , which may affect the fairness and accuracy of evaluations . In particular , some studies have shown that the language used in a scientific paper can be manipulated by artificial intelligence ( AI ) , a type of artificial intelligence that can be used to analyze the language of a given paper . But it is not clear how AI can perform this task . To investigate this issue , Wang et al . examined over 500 publicly available peer review reports from 200 published neuroscience papers in 2022–2023 . The results showed that AI could perform the task better than traditional lexicon- and rule-based language models , and that most reviews for these published papers were favorable . Furthermore , the results also showed that female first authors received less polite reviews than their male peers , suggesting a gender bias in reviewing . Further , published papers with a female senior author received more favorable reviews than published papers without a male senior author , for which I discuss potential causes . Together , these findings highlight the importance of transparent peer review in studying equitability in scientific publishing .
Colorectal cancer is the third most common cancer and the second leading cause of cancer-related death worldwide . Surgical resection of the primary colorectomal tumor is the mainstay of treatment . However , up to 50% of these patients often develop life-threatening liver metastatic disease in the following years . This is because the liver is a barrier that protects the tumor from the immune system . The liver is also a good place to study the effects of chemotherapy , but it is not clear how this barrier works . To address this question , Wang et al . used a mouse model of liver metastatization to study how the immune response to interferon-alpha ( IFN ) affects the liver . In the experiments , the mice were treated with a combination of chemotherapy and a drug called ibuprofen , which is injected into the bloodstream of the tumor cells . IFN- was able to stimulate the growth of liver sinusoidal endothelial cells ( or LSECs for short ) , a type of cell that surrounds the hepatic vessels . These cells are known to be important for the formation of a vascular barrier that prevents the spread of the cancer to the liver and prevents it from spreading to other organs in the body . Wang 
Influenza A viruses are a group of viruses that cause a wide range of diseases in humans , birds , and pigs . Influenza viruses can also cause severe respiratory disease in humans and other animals . In the United States , influenza A virus infections are one of the top health concerns for the US swine industry , as they severely reduce pig health and subsequently the profitability and sustainability of the pork industry . Vaccination is widely used in North American pig breeding herds , but it is difficult to assess the impact of vaccination on the emergence of influenza A viruses . This is because the virus can spread among vaccinated and unvaccinaTED pig populations . However , it is not clear how vaccination affects the virus’ ability to replicate in the pig population . To address this question , Xu et al . used a technique called X-ray crystallography to directly sequence bronchoalveolar lavage fluid ( BALF ) samples collected from the lungs of pig-infected and non-vaccined pig groups . The experiments revealed 54 viruses that were reassortant . These viruses were grouped in 17 single and 16 mixed genotypes and were found to be more common in prime-boost vaccinations than nonvaccinates . Furthermore , the virus
The hippocampus is a brain region that contains place cells that fire when visiting specific locations in space . These cells are known as place cells , and they are thought to store memories of experiences that are remembered rather than perceived and forgotten . However , it is not clear how place cells store memories for aversive experiences . One possibility is that place cells can remap their positional patterns in response to memories of a traumatic event , such as a footshock . Previous studies have shown that place cell remapping occurs after a shock , but it was not clear whether this occurs after the shock itself . Now , Liu et al . have used a technique called in vivo calcium imaging to study place cells in rats . In the experiments , rats were trained to prefer a short path over a long path for obtaining food reward , then trained to avoid the short path by delivering a mild shock . The rats were then exposed to a drug that impaired avoidance learning . When the rats were exposed to an amnestic drug , place cells were remapped significantly more following remembered events than after forgotten shocks . Place cells were also less likely to move toward or away from the shock when exposed to neutral barriers , suggesting that reorganization of place cell populations may play a role in storing memories
HIV-1 infection results in the activation of inflammasome that may facilitate viral spread and establishment of viral reservoirs . We evaluated the effects of the caspase-1 inhibitor VX-765 on HIV-1 in humanized NSG mice engrafted with human CD34+ hematopoietic stem cells . Expression of caspasein-1 , NLRP3 , and IL-1 was increased in lymph nodes and bone marrow between day 1 and 3 after HIV-1 infections . IFI16 and AIM2 expression peaked at day 24 and coincided with increased IL-18 levels , increased viral load and CD4+ T cell loss in blood . Treatment with VX-756 significantly reduced TNF- at day 11 , TNF-1 at day 22 , CD4 + T cells , viral load , HIV-1 DNA in the spleen , total HIV-1 genome in the blood , as well as total HIV-DNA in the plasma . Our study provides new insights into the mechanisms of HIV-1 replication and the development of therapeutic strategies towards HIV cure . The potential of this strategy is to prevent CD4-T cell depletion and reduce immune activation , virus load and the HIV-1 reservoir formation .
The loss of a partner is often cited as one of the most traumatic experiences in a person’s life . However , for most people , the severity of the loss and its maladaptive effects subside over time via an understudied adaptive process . Like humans , prairie voles ( Microtus ochrogaster ) form opposite-sex pair bonds , and upon partner separation , they show stress phenotypes that diminish over time . In this study , researchers used a technique called RNA sequencing to examine the gene expression patterns of two different pairs of prairie volels . The experiments show that , despite the fact that the pair bonds are still intact , their transcriptional signatures erode over time and that these changes are associated with gliogenesis and myelination . Further experiments revealed that a group of genes , known as glia , are involved in the loss of pair bonding . These findings suggest that glial cells are a key player in the formation of new pair bonds and that the aging process may be a major contributor to the deterioration of the bond . This work provides new insights into how a vole’s ability to form a new pair bond is shaped by the loss or loss of its partner .
The human body is made up of many different types of muscles , including the thigh , knee , and ankle . Infants can move their legs in many different ways , but the mechanisms that enable them to do so are not well understood . For example , infants have a small number of basic motor patterns , called locomotor primitives , that allow them to move their lower limbs . However , it is not clear how these primitives are activated during early development . To address this question , Xu et al . studied 18 infants who were born between 4 days and 14 months old . The experiments show that infants develop a limited number of primitives during the first few months of life . These primitives can be activated by the infants as soon as they are born , or they can become activated in the second few months after birth . This suggests that the infant’s motor system is able to activate a few primitives early on in life , before they become more active . In the future , this could help researchers to better understand how infants learn to move and explore their bodies . Future studies are needed to determine whether infants can develop fewer primitives as they develop . A better understanding of infants’ motor development could help to develop new treatments for diseases such as Parkinson’s disease .
Typhoid is a disease caused by Salmonella enterica serovar Typhi ( Typhi ) , which is transmitted by the bite of infected mosquitoes . The World Health Organization ( WHO ) estimates that approximately 1 . 5 million people are at risk of infection with Typhi each year . This is the largest collection of Typhi genome sequences to date ( n=13 , 000 ) and represents the largest genome sequence collection to date . We analysed the genomes of more than 1 , 500 Typhi strains across the globe , and identified a number of determinants of antimicrobial resistance , including ciprofloxacin non-susceptibility ( >1 resistance determinant ) in South Asia and Eastern/Southern Africa . In other regions , distinct genotypes dominate and have independently evolved AMR . Data gaps remain in many parts of the world and we show the potential of travel-associated sequences as a means to provide informal ‘sentinel’ surveillance for such locations . Our data indicate that high-level cisplatin resistance is widespread across geographies and variants , with high levels of drug-resistant ( XDR ) Typhi becoming dominant in Pakistan ( 70% in 2020 ) but has not yet become established elsewhere . Azithromycin resistance mutations were detected
Plants have evolved mechanisms through which seasonal cues coordinate the transition to flowering . One of the significant environmental factors affecting flowering time of plants adapted to temperate climates is the temperature changes during the seasons , and plants have evolved complex sensory mechanisms to monitor the surrounding temperature to properly control the timing of flowering and tolerate thermal stress . COOLAIR , a cold-induced antisense RNA transcribed from the FLC locus , has been proposed to facilitate FLC silencing . Here , we show that C-repeat ( CRT ) /dehydration-responsive elements ( DREs ) at the 3′-end of FLC and CRT/DRE-binding factors ( CBFs , CBF-binders ) are required for cold-mediated expression of COOLair . CBF levels increase gradually during vernalization , but COOLAR levels decrease in later phases as FLC chromatin transitions to an inactive state to which CBF can no longer bind . We also demonstrate that cbfs and FLCCOOLAIR mutants exhibit a normal vernaization response despite their inability to activate COOLA expression during cold , suggesting that COOLAQ is not required for the vernalsization process .
The virus that causes HIV is transmitted to humans by a virus called HIV-1 . This virus is transmitted by the blood of infected people , and it can cause serious health problems , such as heart attacks and strokes . The virus can also spread to other parts of the body , including the brain , spinal cord and spinal cord . However , it is not clear how the virus spreads to other tissues . One way to find out is to use next-generation sequencing ( or next generation sequencing for short ) , which is a technique that can be used to study the DNA sequences of viruses . Previous studies have shown that HIV-1 can spread in the blood , but it was not clear whether it spreads in different tissues , especially in the CNS . Now , Wang et al . have used this technique to study HIV-1 in three patients who had been treated with antiretroviral therapy ( ART ) for a period of time . These patients were taken to a hospital to undergo autopsy , where they were examined for the presence of HIV-1 cells in their blood . In the experiments , HIV-1-infected cells were found in several different tissues in the patients’ blood: lymph nodes , gastrointestinal and genitourinary tissue , the basal ganglia and the frontal lobe 
Circadian clocks are highly conserved time-keeping machines that control 24 hr oscillations in gene expression , physiological function , and behavior . Many disease states are associated with loss of circadian regulation . How and when circadian clock failure during pathogenesis remains largely unknown because it is currently difficult to monitor tissue-specific clock function in intact organisms . Here , we developed a method to directly measure the transcriptional oscillation of distinct neuronal and peripheral clocks in live , intact Drosophila , which we term Locally Activatable BioLuminescence , or LABL . Using this method , We observed that specific neuron and peripheral circadian rhythms exhibit distinct transcriptional properties . Loss of the receptor for PDF , a circadian neurotransmitter critical for the function of the brain clock , disrupts circadian locomotor activity but not all tissue- specific circadian counterclocks , but does not affect the rest of the clock . We also demonstrate that distinct clocks exhibit differences in their loss of oscillatory amplitude or their change in period , depending on their anatomical location , mutation or fly age . Our results demonstrate that LABL is an effective tool that allows rapid , affordable , direct real-time monitoring of individual clocks within vivo .
The endosome is a compartment within the cell that stores and transports proteins and other lipids . It is made up of a complex of proteins called retromer and VARP . Retromer is able to sort cargo from the endosomal compartment and then recycle it . In yeast , the VARP protein is mutated in a gene that encodes a protein called Vrl1 . This gene encodes the retromer protein , but it is not known how it works . To investigate this , Liu et al . used a technique called X-ray crystallography to study the role of the yeast VARP homolog in VINE . The experiments show that VINE forms an obligate complex with Vin1 , a member of the VPS9-domain GEF family . VINE is found in the membranes of the cell , where it redistributes a mannose 6-phosphate receptor-like protein . Vin1 recruits the VINE complex to the membrane , and it then recruits another protein called Vin1 to the cell membrane . These findings reveal a new role for VINE in the recycling of proteins and lipid cargo at the endofosome . Further work is now needed to understand how VINE works and how it interacts with other proteins , including VARP and Vps
The interactions between fish and other fish are important for understanding and predicting how global climate change impacts marine ecosystems . However , tracking and quantifying interactions of marine fish species is practically difficult especially under field conditions , and thus , how temperature influences their interaction strengths is poorly understood . To address this problem , Wang et al . used quantitative fish environmental DNA ( eDNA ) metabarcoding on 550 seawater samples collected twice a month from 11 coastal sites for 2 years in the Boso Peninsula , Japan . Using nonlinear time series analytical tools , they analyzed the data from 550 fish samples collected over 2 years . The results showed that , although there was a large variation , water temperature influenced fish–fish interaction strengths . In particular , the interaction strengths of Halichoeres tenuispinis and Microcanthus strigatus increased strongly with water temperature; while those of Engraulis japonicus and Girella punctata decreased strongly . This study demonstrates a practical research framework to study the effects of environmental variables on the interaction strength of marine communities in nature , which would contribute to understanding and forecasting natural marine ecosystem dynamics . It also suggests that an increase in water temperature may change the interactions of fish species in a complex way .
The eggshells of dinosaurs are a valuable resource for studying the evolution of the fossils . However , it is not clear how these eggs were formed , or how they evolved , and how they have shaped over time . To investigate this question , Xu et al . used electron backscatter diffraction to study the eggshell shapes and crystallography of dinosaur eggs . The experiments show that all the rhea- and tinamou-style morphotypes of palaeognath eggs are homologous , while the ostrich-style eggshell appears to represent the ancestral state of the dinosaur eggshell . In addition , the egg shells of non-avian dinosaurs , such as the avian , are still extinct and flourishing today as the most speciose land-vertebrate lineage . These findings are important for understanding the evolutionary history of modern and extinct dinosaur eggs and will help other fields where palaeraeontological and zooarchaeology can be used to compare and contrast ancient and modern dinosaur eggs with each other . Further work is now needed to identify the origins of the morphological features of the eggs , as well as the origin of the structures that they contain . This will help us to understand how the fossil egg
The sound of a mouse’s vocalizations is a powerful tool for studying how animals communicate and navigate . It can be used to track the movements of other animals , such as bats , frogs and mice . However , it is not always possible to reliably attribute the sound to its emitter . This is especially true for animals that communicate with humans , as they are often able to communicate with other animals by using ultrasonic signals . In this study , researchers used a new system called Hybrid Vocalization Localizer ( or HyVL for short ) , which integrates a high-resolution camera with high-quality microphones . The system was then used to study courtship interactions between mice , and found that male mice and female mice vocalize in starkly different positions relative to each other . When two male mice interact with one female , one of the males takes a dominant role in the interaction , both in terms of the vocalization rate and the location relative to the female . These findings suggest that the hybrid system can significantly improve the precision with which social communication between rodents can be studied . Furthermore , the system is affordable , open-source , easy to set up , can be integrated with existing setups and reduces the required number of experiments and animals .
The muscles of the body are made up of a series of long filaments called myofibrils . These filaments span the entire length of the muscle fibres , and they are made of specialized proteins called titins – which are found in all animals . The titiin proteins are found at the ends of the filaments - and they help to anchor the filament to the myosin filament . In vertebrates , the sarcomeric structure of sarcomeres is similar to that of vertebrate muscles . However , it is not clear how the stin proteins in fruit flies are arranged . To address this question , Lemke et al . used a technique called DNA-PAINT super-resolution microscopy to identify the specific domains of the two proteins in the fly flight muscle . This revealed that Sallimus and Projectin are located at the beginning of the A-band of the fly muscle , while the ends overlap at the end of the I-band/A-band border . Together , these findings reveal a staggered organisation of two proteins that may help to stably anchor SallimUS at the MyoSin filament and hence ensure efficient force transduction during flight .
Cells are made of a complex network of filaments that form a structure called a sphere . These filaments are arranged in a way that allows the cell to move , move and move around . The spheres can also be shaped into different shapes . For example , cells called neutrophils can move in response to a chemical called cytokines , which are produced by a group of cells called eukaryotic cells . When a cell divides , it is able to move around the cell . However , if the cell loses its shape , the sphere will become stiffer . This can lead to the cell becoming more rigid and unable to divide properly . It is also important to measure the properties of individual cells in order to understand how they work . One way to measure these properties is to use a technique called microfluidics . Microfluics can be made from a small amount of water , and can be pumped into the cell via a channel . If the cell is suspended in the channel , this can cause it to deform , or it can become truncated . But it is not clear how this happens . To address this question , Wang et al . developed a new method that can measure the viscoelastic properties
Mitochondria are the most abundant cells in the human body , but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy . Here , we determined that the rare mitofusin ( MFN ) 2 R400Q mutation is 15–20 over-represented in clinical cardiomyopathies , whereas this specific mutation is not reported as a cause of Charcot–Marie–Tooth disease type 2A ( CMT2A ) . We interrogated the enzymatic , biophysical , and functional characteristics of MFN2 Q400 versus wild-type and CMT2-causing MFN2-mutants . All MFN1 mutants had impaired mitochondrial fusion , the canonical MFN2/MFN2 function . Compared to MFP2 T105M that lacked catalytic GTPase activity and exhibited normal activation-induced changes in conformation , MFN 2 R 400Q and M376A had normal GTPAP activity with impaired conformational shifting . By contrast to Mfn2 t105M and M476A , mitochondrial Q400 was uniquely defective in recruiting Parkin to mitochondria . CRISPR editing of the R400q mutation into the mouse Mfc2 gene induced perinatal heartmyopathy with no other organ involvement
The first few weeks of life in mice are a crucial time in the development of the nervous system . This is particularly important for young mice , as they are exposed to a wide range of olfactory cues . For example , odors of the same-sex adult mice can delay their maturation . However , it is not clear whether odor signals can also have a sex-specific effect on mice’s lifespan . To investigate this question , Bartke et al . studied the lifespan of mice in the laboratory by exposing them to odor molecules from adult female mice . The experiments showed that female mice were more likely to be able to live longer than male mice if they were given a small amount of odor . Female mice were also less likely to die when they were exposed to the odor of males , but they were not more likely than males to die . Mice with a mutation in the gene that encodes a protein called Go , which is found in the brain , were less prone to dying . These findings suggest that young mice are susceptible to changes in their lifespan , and that these changes may have long-lasting effects on their health . In the future , these findings could be used to develop new treatments for diseases caused by odor-related diseases , such as
Sleep is a complex process that involves many different types of brain cells , including neurons , muscle cells and nerve cells . These cells are activated by chemicals called designer receptors , which are found on the surface of the brain . This activates a protein called clozapine-N-oxide ( or CNO for short ) , a neurotransmitter that helps to control the brain’s activity . CNO is injected into the brain by a drug called DREADD , but it is not known how it affects sleep . It has been suggested that the effects of CNO on sleep could be due to the chemical molecules that bind to the CNO receptor . However , it was not clear how CNO affects the sleep of mice . To address this question , Liu et al . used a technique called electroencephalography ( EEG ) and electromyography to study sleep in mice injected with CNO . The experiments showed that the mice’s sleep was disrupted when CNO was applied to their brains . In particular , the mice were less able to move their eyes during sleep compared to normal mice , suggesting that CNO may have a role in the sleep-related changes . Further experiments revealed that C21 – a compound that is commonly used in sleep research –
The ability of bacteria to sense and respond to chemical signals is crucial for many biological processes , including foraging in marine environments and human health and disease . This is particularly important for bacteria that are found in the oceans , such as bacteria in the sand , algae , and fungi . In addition , bacterial chemotaxis is a process by which bacteria sense and react to chemical stimuli in order to survive and reproduce . However , it is not well understood how bacteria respond to these stimuli and how they do so . To address this question , researchers have developed a device called a microfluidic multiplexed device ( MCD ) . The MCD uses a technique called serial dilution to simultaneously perform six parallel bacterial experiments , which span five orders of magnitude in chemostimulant concentration on a single chip . Moreover , the MCD can be used to measure the response of different bacterial species to different chemoattractants and chemorepellents . These results show that MCD is able to significantly accelerate the screening process for chemical signals . Further work is now needed to develop a more efficient , high-throughput method for detecting chemical signals in bacteria . A future challenge will be to find out whether MCD could be used in a similar way to
The nervous system is a complex network of cells that is made up of many different types of cells , including neurons , muscles , and nerve cells . The neural crest cells are an essential part of the nervous system , but they also form many other types of tissues , such as the brain and spinal cord . In the embryo , these cells undergo a series of events that culminate in the formation of the neural tube . These events are coordinated by a network of gene regulatory networks , known as GRNs , that regulate the expression of genes . However , it is not clear how these networks work . To address this question , Wang et al . used a technique called single-cell RNA-sequencing to identify genes that are involved in the regulation of the GRN . This revealed that a protein called Elavl1 binds to and stabilizes RNA molecules , which are then translated into proteins . Using a combination of RNA sequencing , RNA immunoprecipitation and proximity ligation assays to identify the genes that control the formation and maintenance of the crest . Further experiments showed that Elavel1 regulates the production of a hormone called Draxin , an inhibitor of the Wnt signaling pathway , by stabilizing the RNA molecule . Wang 
The ability to breathe is essential for life . The brainstem is the brain’s main sensory organ , and it is surrounded by a network of neurons called the preBötzinger complex . These neurons generate the rhythm and pattern of breathing , while the motor neurons in the spinal cord control the movement of the diaphragm muscle during inspiration . In the brain , these motor neurons are called phrenic motor neurons ( MNs ) , which are responsible for generating the rhythm of breathing and controlling muscle contractions . However , it is not clear how these two types of motor neurons work together to generate a robust breathing output . To address this question , Wang et al . studied mice that had been genetically engineered to lack both type I and type II cadherins in their brain . This revealed that two different types of CaDherin are required for the formation of the MN cell body and the cell topography , but that they do not work together in the same way . Moreover , if the mice were infected with either type I or type II CaDHERINs during a critical developmental window , they would die , leading to a loss of breathing output and a reduction in the number of MN cells bursting . Further experiments showed that these two caDHERINS work together
Misinformation is a powerful tool for spreading information . It has been suggested that misinformation spreads through social media platforms , where people can receive rewards for sharing information , and vice versa . However , it is not clear how the spread of misinformation can be prevented . To address this question , Chen et al . studied 951 participants over six experiments . The results showed that a slight change to the incentive structure of social media sites , such as that rewards and punishments are contingent on information veracity , produces a considerable increase in the discernment of shared information compared to the proportion of false information shared . This increase in discerning behavior is associated with an increase in weight assigned to evidence consistent with a discernment bias . These findings offer evidence for an intervention that could be adopted to reduce misinformation spreading , which in turn could reduce violence , vaccine hesitancy and political polarization , without reducing engagement . In the future , the findings could be used to develop new ways to prevent misinformation from spreading . For example , these findings could lead to the development of more effective vaccines , as well as reducing the risk of vaccine-related misinformation being spread .
Microtubules are filaments of proteins that help to transport cargoes from one cell to the next . They are made up of filaments that curl outwards from the disassembling tips of microtubes , which pull the sister chromatids apart . This forces the chromosomes apart and allows the cell to divide . However , it is not clear how these microtubular filaments generate such force . To investigate this question , Liu et al . used a technique called X-ray crystallography to measure the working strokes generated by the curling protofilaments in yeast cells . The experiments show that the curls of the microtubulin filaments can be increased by adding magnesium , a magnesium-rich mineral , to the filaments . These results suggest that the energy stored in the filament lattice is conserved throughout evolution , and that the amount of energy stored within the filament can be tuned to suit the needs of the cell . Further experiments are now needed to determine how the energy that is stored in microtubulates is used to generate the force generated . In the future , these findings could be used to develop new drugs that can increase the efficiency of microtubulations in humans and other animals .
The hagfishes are a group of jawless vertebrates that have a row of slime glands along each side of their body . Each gland produces and stores gland thread cells , which are found on the surface of the fish’s skin . When attacked , these glands produce a soft , fibrous slime that can be used to defend themselves against predators . However , it is not clear how the slime developed , and how it evolved . To address this question , Wang et al . used a technique called X-ray crystallography to study the tissue that surrounds the glands of the Hagfish . The experiments show that the skin contains a dense layer of cells called epidermal thread cells that produce threads and mucus , as well as a layer of thread cells in the rest of the body , called the skin epidermis . These cells are surrounded by a thick layer of tissue that is covered by thread cells from the skin , a process known as thread gene duplication and diversification . This suggests that thread genes evolved in parallel with the evolution and evolution of the sliming glands in the fish . Further studies are now needed to determine how the threads evolved and how they evolved to form slime . In the future , this will help us to understand how the
Temporal lobe epilepsy ( TLE ) is the most common form of drug-resistant epilepsia in adults and is the leading cause of death in children . There are no pharmacological disease-modifying treatments with an enduring effect to mitigate the seizures and comorbidities of established chronic temporal lobelepsy ( KA ) . This study aimed to evaluate for disease modifying effects of sodium selenate treatment in the chronically epileptic rat post-status epileptus ( SE ) model of drug resistance . We performed a multi-omics/pre-clinical analysis of post-mortem brain tissue to identify potential pathways associated with modified disease outcomes . Telomere length was investigated as a novel surrogate marker of epilepietic disease severity in our current study . The results showed that sodium selenate treatment was associated with mitigation of measures of disease severity at 8 weeks post-treatment cessation; reducing the number of spontaneous seizures ( p 0 . 05 ) and cognitive dysfunction ( q = 0 , 05–1 , 8–9 , 7–8 , 9–10 , 11–12 , 13–14 , 15–17 , 18–19 , 19–20 , 20–21 , 26–27
Fragility fracture is a direct consequence of osteoporosis , just as stroke is . Fracture , especially hip fracture , is associated with an increased risk of mortality , but mortality is not part of doctor-patient communication . Here , we introduce a new concept called ‘Skeletal Age’ as the age of an individual’s skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an individual . We used the Danish National Hospital Discharge Register which includes the whole-country data of 1 , 667 , 339 adults in Denmark born on or before January 1 – 1950 , who were followed up to December 31 , 2016 for incident low-trauma fracture and mortality . Skeletal age is defined as the sum of chronological age and the number of years of life lost ( YLL ) associated with a fracture . Cox’s proportional hazards model was employed to determine the hazard of mortality associated with specific fracture for a given risk profile , and the rash was then transformed into YL using the Gompertz law of mortality using the gompentz law of fracture sensitivity . During the median follow-up period of 16 years , there had been 307 , 870 fractures and 122 , 744 post-frac
The brain is a complex organ that is able to perform many different tasks , including analyzing the structure and function of the brain . While several conventional tools have been optimized to handle human brain data , there have been no generalizable methods for extracting brain tissue for multimodal MRI data from rodents , nonhuman primates , and humans . Therefore , developing a flexible and generalizzable method for extraction of brain tissue across species would allow researchers to analyze and compare experiment results more efficiently . Here , we propose a domain-adaptive and semi-supervised deep neural network , named the Brain Extraction Net ( BEN ) , to extract brain tissues across species , MRI modalities , or MR scanners . We have evaluated BEN on 18 independent datasets and evaluated it on 18 independently tested datasets including 783 rodent , 246 nonhuman primate MRI scans and 4601 human MR scans for its robustness and accuracy . Our proposed method not only provides a generalized solution for extraction across species but also significantly improves the accuracy of atlas registration , thus benefiting the downstream processing tasks . As a novel fully automated deep-learning method , BEN is designed as an open-source software to enable high-throughput processing of neuroimaging data across species in preclinical and clinical
Candida albicans is a fungal pathogen that causes a wide range of infections in humans . It is also one of the most common human fungal infections , and can cause life-threatening infections when the immune system is weakened or when there is damage to epithelial barriers . Heme is an iron-rich molecule that can be used as a source of iron in many environments , including the animal host environment . The fungus uses a family of proteins called CFEM hemophores to capture heme from host proteins and transfer it across the cell wall to the cell membrane , to be utilized as iron or iron source . However , it is not clear how these proteins work . To address this question , Xu et al . used a technique called X-ray crystallography to identify two proteins that are involved in the transport of heme . These proteins , Frp1 and Frp2 , are found on the surface of the cell , but they do not have an extracellular substrate-binding domain . Instead , they are able to redistribute hemine to the plasma membrane in the presence of a chemical called hemin , which is toxic to the cells . This suggests that these proteins form a complex that evolved from the ferric reductase
The bacterium Vibrio cholerae is the causative agent of the diarrheal cholerophobic disease , which is caused by the bacteria that cause the disease . The bacterial species are able to adapt to changing environments , and this adaptation is enabled by two proteins called ToxR and ToxS . These proteins are found at the inner membrane of the bacterial cell , where they interact with a variety of environmental stimuli , including bile acid , to trigger a series of survival strategies . However , it was not clear how these proteins interact with each other . Now , Liu et al . have used a technique called X-ray crystallography to reveal the structure of the ToxRS protein complex . This revealed that the two protein complexes bind to each other in a way that is similar to that of VtrAC , a family of proteins known as co-components . ToxRNA is a protein that is found in the outer membrane of bacterial cells , but it is not known how it interacts with other proteins in the cell . In addition , the structure revealed that a part of the protein that binds to ToxA is only folded when it is bound to the protein . Further experiments revealed that ToxAS is the only protein in the
The hippocampus is a brain region that supports memory and memory . It is found in the brains of many different species , including humans . The humpback , for example , is responsible for storing memories of past events , and it is also involved in imagining future events . However , it is not clear how the humbback connects with other parts of the brain . To address this question , Xu et al . used a technique called track-density imaging to study the connections between the cortex and the anterior–posterior axis of the human humpuccinoma . This revealed that the cortex is more connected to the anterior than to the posterior . In addition , the cortex has a greater degree of connectivity with the posterior than with the anterior . Moreover , these regions are more densely connected than previously thought , suggesting that they are more likely to be involved in memory and spatial navigation . These findings provide new insights into how specific regions along the anterior and posterior axes are associated with different cortical inputs/outputs . Further work is now needed to understand how these regions interact with each other and how they are connected to each other .
Parkinson’s disease ( PD ) is a progressive neurodegenerative disease that is characterized by progressive loss of motor control and impaired coordination . The disease is caused by a recurrent accumulation of inflammatory mediators , including interferons . Activation of the STING pathway is activated after detection of cytoplasmic dsDNA by cGAS ( cyclic GMP-AMP synthase ) as part of the innate immunity defence against viral pathogens and TBK1 mutations are associated with familial amyotrophic lateral sclerosis . To test whether STING activation is sufficient to induce neurodegeneration , we analysed a mouse model that expresses the constitutively active STING variant N153S . We focused on dopaminergic neurons , which are particularly sensitive to stress and represent a circumscribed population that can be precisely quantified . Neuroinflammation was quantified by staining astroglia and microglia , by measuring mRNAs and proteins and nuclear translocation of transcription factors . These neuroinflammatory markers were already elevated in juvenile mice although at this age the number of dopepinrgic neurons was still unaffected , thus preceding the degeneration of doppin-sensitive neurons . More neuroinflammatory marker were blunted in mice de
Cancer is a disease that affects millions of people worldwide . The majority of cancers are treated with drugs that kill tumor cells . However , the majority of patients do not respond to these drugs , and relapses of resistant tumors can occur . This is partly because the tumor cells are cloned , which means that they are not able to be killed by the immune system . In some cases , these clones can be used to create new tumors , but it is not clear how these re-clones work . To address this question , Xu et al . studied mice and human cancer cells that had been genetically engineered to produce a type of immune cell called a cytotoxic T-cell . These mice were then injected with a drug that kills tumor cells in a way that is similar to the way that a T-blast would kill a tumor cell . Xi el . found that these mice had a unique cell-in-cell structure that was resistant to the treatment of other types of cancer , including melanoma and breast cancer . While the outer cells of these cells are often killed by reactive T cells , they remain intact and disseminate into single tumor cells once the T cells are no longer present . Further experiments showed that these cells
The brain is a complex machine that processes information , and it is able to process information in a way that is not only intuitive but also logical . It is also able , in some cases , to process the information in the form of images . For example , a person can use a computer to process a picture , or a human can use it to process an image . This ability is known as Theory of Mind . In humans , this ability is referred to as ToM . However , research on nonhuman primates has yielded inconsistent results . One such species , the marmoset , is highly social , so it has been difficult to study how it processes ToM in humans . To investigate this question , Wang et al . studied the brain activity of two different species of monkeys , Callithrix jacchus and Marmora , as they watched Frith-Happé animations . Both monkeys and humans exhibited longer fixations on one of the triangles in ToM animations than in other conditions , but did not observe the same pattern of longer overall fixation duration on the ToM scenarios . Furthermore , both species activated extensive and comparable brain networks when viewing ToM and Random animated scenes . These findings expand our understanding of nonhuman primate cognitive abilities 
Stem cells are the cells that make up the body . They are made up of a group of cells called neurons , which are able to divide and become different types of cells . These cells are called neural progenitor cells , and they are responsible for forming the nervous system . When a stem cell divides , it produces a protein called Polycomb Repressive Complex 2 ( or PRC2 for short ) . This protein binds to a region of the DNA called H3K27me3 , a repressive mark on histones that is important for gene expression . However , when a gene is expressed in a cell that is not differentiated into a different type of cell , the transcription of that gene can be slowed down . Therefore , stem cells need to be fine-tuned in order to allow their progenitors to transition from a state of undifferentiated to an active state . A protein called FruitlessC is a key player in this process , but it is not clear how it does this . To address this question , Wang et al . used a technique called X-ray crystallography to study how fruitlessC regulates the activity of many genes in neural stem cells from flies . The experiments show that fruitless C bind to
Apoptosis is a process that removes damaged or old cells from the body . It is regulated by a group of cells called phagocytes , which are found in the liver and other organs . These cells are then removed from the hepatocytes to ensure that they do not cause inflammation or damage to the liver . However , it is not clear how apoptotic cells are cleared . To investigate this question , Wang et al . used a technique called X-ray crystallography to study the role of neutrophils in the clearance of hepatic cells in mice . The experiments show that neutrophil cells are a type of professional phagocytic cell that is thought to be excluded from the removal of dead cells . Instead , they burrowed directly into the dead cells and ingested them from the inside . This process , known as perforocytosis , is referred to as a “housekeeping” process . In humans , a number of autoimmune diseases , such as autoimmune liver disease , have been linked to defects in neutrophil clearance . Moreover , the autoimmune disease that is caused by autoimmune conditions is similar to the one seen in autoimmune patients . Therefore , these findings suggest that the neutrophil-mediated removal of 
The muscles of the body are made up of a network of nerve cells called motor neurons . These neurons communicate with each other via a series of connections called synapses . When a nerve cell receives a signal from another neuron , it sends this signal to the next neuron in the network . This process is called motor control , and it is thought that the activity of motor neurons in the spinal cord is controlled by a complex network of interneurons . However , little is known about how the networks of motor and premotor neurons are organized . Rabies virus ( RabV ) is a virus that causes rabies in humans and other animals , but it is not clear how these networks work . To address this question , Hultborn et al . used a technique called retrograde monosynaptic tracing to map the connections between motor neurons and motor neuron networks in mice . The experiments show that , in contrast to previous studies , premotor and motor neurons do not interact in the same way . Instead , they interact in different ways . For example , if a premotor neuron is involved in the movement of the foot , the premotor nerve is more likely to be involved in flexing the foot than it is in extending it . In contrast , when a motor
Resting-state fMRI ( rsfMRI ) is a powerful tool for non-invasively investigating brain-wide functional connectivity in both healthy and diseased conditions . It measures blood-oxygen-level-dependent ( BOLD ) signal , which can be measured by a technique called resting state MRI . However , it is not clear how the activity of the brain is affected by respiration . To address this question , Wang et al . used a combination of biochemical and electrophysiological techniques to record the electrical activity in the brain of rats . The experiments show that respiration is indeed associated with changes in brain activity , and that slow respiration variations are linked to a network of brain connections that is mediated by gamma-band neural activity . Intriguingly , this respiration-related brain network disappears when brain wide neural activity is silenced at an isoelectrical state , while the respiratory activity is maintained . This suggests that the brain has a role in regulating the activity in this network . Further experiments will be needed to investigate how the brain responds to the effects of respiration on the brain . These findings may help us to understand how the nervous system works and how it affects our health .
Bats are specialized predators that hunt multiple types of prey . Some of these prey types are only available sequentially , e . g . over seasons , while others are available simultaneously . Predators that switch between multiple prey type are predicted to ignore low profitability prey when more profitable prey are present and abundant , and only switch between them if there is a perceived prospect of increased profitability . However , testing such fundamental predictions in the wild is greatly complicated by the difficulties of measuring encounter rates and capturing successes to estimate prey profitability of individual predator-prey interactions . Here , Chen et al . used a biologging approach on echolocating bats as a model to test the hypothesis that greater mouse-eared bats make immediate foraging decisions based on prey costs and changes in the environment . The experiments show that bats use two foraging strategies with similar average nightly captures of 25 small , aerial insects and 29 large , ground-dwelling insects per bat , but with much higher capture success in the air ( 76% vs . 30% ) . But owing to the 3–20 times larger ground prey and 85% of the nightly food acquisition comes from ground preies . This suggests that prey switching matched to environmental dynamics plays a key role in covering the energy
Humans are a group of animals that are able to move their hands in a manner that is unique to them . This is known as right-handedness , and it has long been thought that humans were born with a right hand . However , it has been difficult to study the evolution of right-handedness in non-human primates , which have a wide range of hand movements . To address this question , Xu et al . combined data from 1786 individuals from 38 species of anthropoid primates with published literature reports . The results showed that human right- handedness is an unparalleled extreme among anthropoism , but that it is rare among nonhuman primate species . Moreover , the patterns of hand preference in nonhuman primate species were not consistent with any of the predictions made by previous studies . Instead , they were highly variable . In particular , terrestrial primates tend to display weaker hand preferences than arboreal species , suggesting that unique selective pressures gave rise to the unusual hand preferences of our species – a measure of hand preferences that has often been overlooked in the past . These results challenge popular ideas on primate handedness evolution , including the postural origins hypothesis . Furthermore , these findings point to a potential adaptive benefit of disparate lateralization strength in primates that
Williams–Beuren syndrome is a rare genetic disorder that affects the brain and the heart . It is caused by a deletion of a region of the genome that contains 26–28 genes . The disease is characterized by mild-to-moderate intellectual disability and hypersocial phenotype , while the most life-threatening features are cardiovascular abnormalities . There are no drugs to directly ameliorate the main traits of this disorder . One potential drug target is the endocannabinoid system ( ECS ) , which is important for both cognitive and cardiovascular function . However , there are no pharmacological treatments to directly alleviate the main features of WBS . This suggests that the ECS could be a potential druggable target in this syndrome . To address this question , Xu et al . studied the components of ECS in the complete deletion ( CD ) mice . Mice that had been genetically engineered to have a complete deletion were more socially active than normal mice , and showed a hypersociable personality . These mice showed no preference for social novelty and had poor short-term object-recognition performance . Moreover , these mice showed alterations in the brain cannabinoid type-1 receptor ( CB1R ) that were not detectable in the normal mice and that
The identity of the larval , pupal , and adult stages depends on the sequential expression of the transcription factors chinmo , Br-C , E93 , e9 . However , how these transcription factors determine temporal identity in developing tissues is poorly understood . In this study , we report on the role of the juvenile specifier chinmo in larval and imaginal tissues during fly development . Interestingly , the absence of chimo during metamorphosis is critical for proper adult differentiation . We also provide evidence that , in contrast to the well-known role of chinmo as a pro-oncogene , br-C and E93 act as tumour suppressors . Finally , our results suggest that the function of chinho as juvenile specifieer is conserved in hemimetabolous insects as its homolog has a similar role in Blatella germanica . Taken together , these results suggest the sequential regulation of the different organs that constitute the adult organism by the transcription factor Chinmome . These findings may help us to understand how developmental stages are regulated during development , which may lead to the development of novel therapeutic strategies .
Cells use a variety of different reactions to make energy . For example , a cell can convert a chemical called ATP into a molecule called NAD . This process is called co-substrate cycling , and it is common in many parts of the cell . Co-substrates can also be converted into other molecules , such as proteins , which can be used as energy or electron carriers . However , there are also other molecules that can act as cycled compounds . In particular , some of these molecules are known as energy carriers , but there are many other metabolites that can also act as cycling compounds in different parts of central metabolism . Here , Liu et al . have developed a mathematical framework to analyse the effect of co-conversion on metabolic fluxes . The framework is based on a combination of mathematical methods and experimental data . It allows the analysis of the effects of the co-constrate cycle on the flux of a reaction , as well as the kinetics of the enzyme that catalyses that reaction . Liu and Liu found that the additional limit on converting a co-stable reaction is a function of the total pool size and turnover rate of the cycled co-component . Further experiments showed that this additional limit is imposed by the total number of enzyme
The articular cartilage is a tissue that is made up of a group of cells called chondrocytes . These cells are found in the limbs of mammals , and they are responsible for the formation of cartilage . However , it is not clear how these cells develop into cartilage and how they do so . To address this question , Wang et al . used a technique called X-ray crystallography to study how a protein called nuclear factor of activated T-cells cytoplasmic 1 ( NFATc1 ) is involved in cartilage development . The experiments show that a gene called Col2a1 is important for cartilage to develop , but it is also important for the development of other cartilage types , such as the cartilage of the knee . This gene is known to be involved in a number of different processes , including chondrogenesis , which is the process by which cartilage develops , as well as the formation and differentiation of cartilaginous tendons . In the future , this information could help to develop new treatments for diseases such as osteoarthritis and osteoporosis . Moreover , a better understanding of the molecular mechanisms that underlie cartilage formation will help us to develop more effective treatments for these conditions .
Photosystem II ( PSII ) is a photochemical system that uses the energy from red light to split water and reduce quinone , an energy-demanding process based on chlorophyll a ( Chl-a ) photochemistry . Two types of cyanobacterial PSI I can use chloroplast d ( ChL-d ) and chloroplasm f ( chlorL-f ) to perform the same reactions using lower energy , far-red light . We show that both types have a comparable efficiency in enzyme turnover , forward electron transfer , back-reactions and photodamage . The results are explained by the differences in the redox tuning of the electron transfer cofactors Phe and QA and in the number and layout of the chlorophrells that share the excitation energy with the primary electron donor . PSI II has adapted to lower energy in two distinct ways , each appropriate for its specific environment but with different functional penalties . Our results show that photosystem II has evolved to reduce energy in three distinct ways: ( i ) all types of PSI have similar enzyme turnover efficiency; ( b ) the modified energy gaps on the acceptor side of ChL d-PSII favour recombination via PD1+Phe- repopulation , leading to increased
The skeletal system is an elaborate organ mainly containing bone , bone marrow , and other connective tissues . The skeleton contains at least 12 types of cell lineages arising from the mesenchymal stem cells ( MSCs ) and hematopoietic stem cells , which determine the homeostasis of bone and bone . These lineages are referred to as osteogenic and myeloid lineage cells . However , it is not clear how osteocytes regulate these lineage cell specificities . To address this question , Xu et al . studied mice that had been genetically engineered to have fewer osteogenic cells than normal mice . This led to severe sarcopenia , osteoporosis and degenerative kyphosis . Moreover , the mice were unable to differentiate into osteoclastogens , or osteoblasts . Further experiments showed that the osterocytes in these mice had a senescence-associated secretory phenotype . In addition , these mice were less able to develop osteogenesis . Furthermore , they had less B cells compared to normal mice and had fewer B cells in their lymphopoiesis , leading to a decrease in the number of B cells
The ability of organisms to adapt to changes in their environment is a fundamental question in biology . For example , animals can adapt to changing environments by taking multiple mutations . This redundancy at the genetic level can make it difficult to understand how different mutations can lead to similar fitness gains . In this study , researchers used the Escherichia coli long-term evolution experiment ( LTEE ) as a model to study how mutations in different genes can help organisms adapt to different environments . The experiments were carried out over 50 , 000 generations , with 12 replicated populations evolving in parallel . Each clone had a different set of genes , but all evolved clones had more mRNA molecules . Interestingly , despite few shared mutations at the gene level , the clonies from replicate populations were remarkably similar in their gene expression patterns . Furthermore , most of the changes were due to changes at the transcriptional level with very few translational changes . Finally , changes in the genes that control the expression of downstream genes were found to be more common than changes in gene expression . These results provide insights into the repeatability of evolution and provide insight into how evolution can repeat itself .
The liver is a large organ that contains many different types of cells , including stem cells . These cells are able to divide and divide in a process called cell division . However , it is not clear how these cells communicate with each other to help them divide . One way to study this process is to use a mouse model of liver regeneration . This model is used to study how stem cells respond to stress , such as chemotherapy . In mice , stem cells divide in clusters , which are similar to the cells that divide in cancer . But it is unclear how these clusters are formed . To investigate this question , Liu et al . used a technique called super-resolution electron microscopy to study stem cells in mice . The experiments show that the stem cells of mouse liver regenerate when the signaling pathway that controls cell division is disrupted . Cells that lack the signalling pathway are more sensitive to drugs that inhibit the cell division process . Further experiments showed that the cells in the livers of mice that lack a signaling protein called Shp2-Ras-Erk are less sensitive to the effects of drugs , suggesting that they may have a similar mechanism of stress response . Furthermore , the cells from mice that do not have the signal transduction pathway are less susceptible to the drugs . Liu and Liu also found that
Ciliopathies are a group of neurodegenerative diseases that manifest from sensory abnormalities to syndromic disorders with multi-organ pathologies . Photoreceptor cell death is a major cause of incurable blindness in retinal ciliopathies , which are caused by mutations in the cilia-centrosomal gene CEP290 . To identify drug candidates to maintain photoreceptoral survival , we performed an unbiased , high-throughput screening of over 6000 bioactive small molecules using retinal organoids differentiated from induced pluripotent stem cells ( iPSC ) of rd16 mouse , a model of Leber congenital amaurosis ( LCA ) type 10 caused by mutants in CEP90 . We identified five non-toxic positive hits , including the lead molecule reserpine , that maintained photorespector development and survival in rpC-derived retinal organisms derived from iPSC-derived induced Pluripotency Stem Cells ( LSCs ) . Reserpinen also improved photoReceptors in retina derived form from LCA10 patients and in mouse retina in vivo . Further investigation uncovered dysregulation of autophagy associated with compromised primary cilium biogenesis in patient organ
The bee gut microbiota is a group of microorganisms that contributes to the metabolism of plant metabolites . In this study , we show that amygdalin , a cyanogenic glycoside found in honey bee-pollinated almond trees , can be metabolized by both bees and members of the gut microbes . We found strains of Bifidobacterium , Bombilactobacillus , and Gilliamella that can degrade amy Glycine . The degradation mechanism appears to vary since only a few strains produce prunasin as an intermediate . Finally , our study identified a glycoside-degrading enzyme , glycoside hydrolase family 3 ( GH3 ) , which is expressed in Escherichia coli and detects prune as a byproduct when expressing this enzyme in E . coli . Our study provides new insights into the role of gut bacteria in the degradation of xenobiotics and provides a new model for understanding the mechanisms of bee physiology . This study will help us to understand how the gut bacteria degrade potentially toxic molecules and how they contribute to bee health .
Candida albicans is a fungus that causes a wide range of infections , including invasive candidiasis . The fungi can infect the skin , mouth , vagina and gut , and can cause severe invasive infections . Candida albincans can cause serious infections in humans , but the mechanisms by which it causes these infections are not well understood . One of the most important factors that cause invasive fungal infections is the virulence factor candidalysin . This fungum is able to damage the membranes of the cell , which are the main barrier that surrounds the cells . However , it is not clear how the fungium uses this mechanism to damage membranes . To address this question , Xu et al . used a technique called atomic force microscopy to study the structure of a protein called CL . CL is made up of two loops , each of which is attached to a string . When the loops are attached to the string , they form pores . These pores are formed by a process called oligomerization , in which a single loop is added to each loop . Using this technique , the bacterial cells were exposed to the solution of the bacterium , where the pore was formed . In
The human body is made up of many different types of cells , and each cell has its own unique set of genes . These genes are known as ‘genetic markers’ , which can be used to predict how the body will respond to a particular treatment . For example , if a person has a genetic marker , they may be more likely to be treated with a specific drug , such as analgesia . However , it is not clear how this personalisation can improve the effectiveness of a treatment , or how it can be applied to other conditions . To investigate this question , Liu et al . asked 102 adults in two groups to receive painful heat stimulations on their forearms . During half of the stimulations , the machine purportedly delivered an electric current to reduce their pain . The participants were either told that the machine was personalised to their genetics or that it was effective in reducing pain generally . Participants told that a personalised treatment improved their pain intensity than the control group in both the feasibility study ( standardised =0 . 50 ) and the pre-registered double-blind confirmatory study ( 2=85 ) . In both studies , participants were asked to either tell the machine that the personalised therapy was a placebo or that the treatment was effective
The brain contains many different types of neurons . In mammals , the brain contains a group of neurons called excitatory neurons , which are able to communicate with each other and to communicate . However , in fruit flies , these neurons are referred to as sister neurons – which are more likely to form connections within a shared microcircuit . This is because the neurons in the spinal cord and cerebellum of the fruit fly have different levels of Notch , a neurotransmitter that helps to control the activity of the brain . These neurons are also known as NotchON and NotchOFF . Both neurons are found in the brains of mammals and in vertebrates , but it is not clear how these neurons integrate into the spinal circuits . To investigate this question , Wang et al . used a technique called in vivo labeling to study the connections between sister neurons in zebrafish . The experiments show that the neurons that produce Notch on their own are similar to those that produce a protein called Vsx1 , and that they communicate with one another . Further experiments showed that the cells that produce the Notch protein are connected to a number of different targets , such as the brain and spinal cord . Moreover , when the neurons are in close proximity to each other , they receive input from different sources
Neurons communicate with each other by forming connections called synapses . These connections are made up of many different types of neurons , and each neuron has a specific type of synaptic connection . When a neuron receives a signal from another neuron , the activity of that neuron changes . This changes the strength of the connections between the two neuron’s connections , which can lead to seizures . However , it is not clear how the changes in the strength and strength of these connections are regulated . To investigate this question , Wang et al . used a technique called calcium imaging to measure the activity in the neurons of mice that had been genetically engineered to lack the PARbZIP family of transcription factors . The experiments show that when the mice were exposed to calcium for a long period of time , they had a stronger response to the calcium deprivation . In addition , when the animals were given a calcium supplement , their activity was much stronger . Further experiments revealed that two genes , Hlf and Tef , are important for regulating the activity levels of the neurons in the mice . Together , these findings suggest that the activity level of these genes is regulated in a way that prevents the neuron from reverting to its normal state . Future studies are now needed to
The lung is a major organ of the mammalian body . It is home to many important progenitor cells , including SOX9 , ID2 , and Irx , which are able to generate both airway and alveolar epithelium , but are selective progenitors of alveal epithelial cells later in development . Molecular mechanisms by which these transcription factors and other signaling pathways control chromatin state to establish and maintain cell-type identity are not well-defined . Herein , we analyze paired gene expression ( RNA-Seq ) and chromosomal accessibility ( ATAC ) data from SOX09+ epithelia during embryonic development in Mus musculus . Widespread changes in chromatid accessibility were observed between E11 . 5 and E16 .5 , particularly at distal cis-regulatory elements ( e .g . enhancers ) . Gene regulatory network ( GRN ) inference identified a common GRN implicating phosphoinositide 3-kinase ( PI3K ) signaling in the developmental regulation of sox9+ progeny cells . Consistent with this model , conditional ablation of PI 3K signaling resulted in
Multiple sclerosis is a disease that affects millions of people worldwide . It is caused by a build-up of plaques in the brain , which can lead to a progressive loss of memory . The disease is characterized by progressive changes to the brain’s ability to remember information , and it is often difficult to diagnose . One of the most common symptoms of multiple syphilis is the loss of working memory , a process that is often referred to as ‘working memory’ . In MS , the brain stores information in a ‘slot’ state , but it is not clear how the brain allocates resources to this state . To address this question , Wang et al . used a series of experiments to study working memory in MS patients . This revealed that working memory is mainly affected by errors in remembering information . However , this is not the case in MS . Instead , it is thought that errors in recalling information are more common in MS than in healthy controls . Further experiments showed that the memory-guided localization ( MGL ) task was better at distinguishing healthy control from relapsing-remitting MS compared to sequential presentation tasks . These findings provide new insights into the organization of the working memory system in MS and provide new insight into the underlying mechanisms of the disease . Future studies will
The nervous system is the first line of defense against pain , and it is essential for all animals to survive . However , it is not clear how the nervous system controls nociception . In mammals , the central nervous system plays a key role in regulating numbness , but it is unclear whether the brain also plays . Fruit flies , for example , have a nociceptors that detect harmful stimuli , which triggers a response that is regulated by a neuropeptide called Drosulfakinin . This protein is a homolog of cholecystokinin ( CCK ) , a protein that has been implicated in chronic pain pathogenesis . Previous studies have shown that the CCK system is also involved in controlling nocism in mammals . Now , Liu et al . have found that fruit fly neurons in the brain , called nociceptor neurons , are inhibited by the neuropeptidal Dsk . The experiments show that the DSK-mediated inhibition is mediated by the descending pathway of neurons . Further experiments revealed that DSK and its receptors are involved in a pathway that inhibits nociceptive responses . These findings suggest that nocicidal responses are regulated in the Dros
Plants produce a variety of compounds that are used to fight off fungi . Some of these compounds are known as chemotherapeutics , and some are also used to treat diseases caused by fungus infections . However , it is not clear how some funguses can overcome the toxicity of these chemicals . To address this question , Liu et al . used a technique called ribosome profiling to study a plant-parasite interaction . This revealed that a bacterium called Aglaia , which infects cucumbers and other plants , produces a chemical called rocaglates . Rocaglates bind to a protein called translation initiation factor ( eIF ) , a key regulator of translation . Inhibiting translation of the enzymes involved in translation is one of the most important steps in a cell’s life cycle . The eIF4A protein is a member of the genus Ophiocordyceps . It is found in the leaves and stems of cucumber plants . Liu and Liu have now identified a new bacteriophage , Colletotrichum orbiculare , that is able to overcome the toxic effects of rochaglate . Collettric
The brain is a complex machine that can respond to a variety of stimuli , from light to sound . It is therefore important to understand how the brain responds to these different stimuli in order to make informed decisions about how to behave . For example , if a stimulus is present at a particular point in time , the brain will respond with a binary decision about whether it will be present or absent . However , it is not clear how this decision is made , and how it affects the brain’s ability to respond to the stimulus . One approach to studying the brain is called continuous psychophysics , which is based on the assumption that a sensory stimulus generates an internal representation that is corrupted by Gaussian variability . This internal representation is then compared to an external representation . The results of this analysis can be used to predict how well the brain performs a task , but it is still difficult to use this approach . To address this problem , Wang et al . have developed a computational analysis framework that combines Bayesian inverse optimal control with behavioural simulations . These simulations show that this approach can recover the thresholds of perceptual variability , as well as the subjective beliefs about the stimulus’s dynamics . Furthermore , this approach is able to estimate the costs of behavior , even in experiments seemingly
The brain is a complex machine that processes information about the world around us . For example , the brain processes information in the form of a map , which is then used to make decisions . However , it is not clear how the brain makes decisions based on this information , or how it adapts to changes in the environment . To answer this question , researchers have developed a model that predicts that a decision will be made when the accumulated evidence for an option reaches a fixed value or threshold . This threshold is known as a commitment threshold , and it is important to understand how this threshold changes over time . Previous studies have shown that the brain can adapt to changing conditions , such as the weather , by adjusting the amount of evidence accumulated during a single decision . But how does the brain adapt to these changes ? To address this issue , Xu et al . used a combination of computer simulations and experimental data to develop a new model of decision commitment . The model was then tested on a task that involved a human being deciding whether to go through the park or through town . In the experiments , volunteers were asked to decide whether they would like to go to the park . When the volunteers were given a choice , they had to choose between the two options . If the volunteers chose the latter ,
The world’s biodiversity is threatened by human activities , such as agriculture , climate change , invasive species and chemical pollution . Despite efforts from scientists and regulators , biodiversity has been lost at an alarming rate in the past century , leading to what some have called the sixth mass extinction – biodiversity loss caused by human population growth and activities . However , until now , it was not clear how biodiversity changes over time and space . To address this question , Chen et al . have developed a computational model that explains the relationship between biodiversity dynamics and abiotic change through time , space and time . The model was applied to a freshwater ecosystem with a known history of human impact , and it was then used to study 100 years of community-level biodiversity . This revealed that the freshwater community assemblage and functionality changed over time without returning to its original state . Insecticides and fungicides – combined with extreme temperature events and precipitation – explained up to 90% of the functional biodiversity changes . These changes were not observed when using traditional quality indices ( e . G . Trophic Diatom Index ) . Chen 
The brain is able to predict the position of moving objects , but it is not clear how this process works . One possibility is that the brain can compensate for these delays by using information from the past to predict what is happening in the present . This idea is called prediction . In motion perception , the brain receives information about moving objects from the visual system . However , this information is only available to the brain for a short period of time , and this time is required for the brain to process the information . Previous studies have shown that prediction can be used to compensate for the delays accumulated early in the processing of information , which is important for catching prey , escaping predators and avoiding falling rocks . But how can the brain overcome this fundamental problem and keep up with an ever-changing world ? To address this question , Liu et al . studied electroencephalographic data from the brains of mice and rats . The experiments show that the activity of the brain during early visual processing is much faster than the activity during later processing . Further experiments showed that the earliest activity of moving stimuli was activated much earlier than the first activity of unpredictable flashes . These results suggest that prediction is a core goal of the central nervous system and that it may be a way to overcome this problem . Future studies are now needed to investigate whether this idea can be
Humans are believed to be the only species in the animal kingdom where knowledge learning can be achieved symbolically , mostly through language , in addition to sensory channels such as vision and touch . However , language experiences may contribute to the process by which knowledge is stored in the human brain . One common view shared by the modern neurocognitive theories of semantics is that semantic knowledge is encoded in the distributed brain areas encompassing high-level sensorimotor areas , and potential hub regions that bind such sensory-derived representations . This suggests that language experience may play a role in forming human neural semantic structures beyond nonverbal sensory experiences . But how does language experience influence the neural representations of semantic knowledge ? To address this question , Wang et al . used a unique human model with varying amounts and qualities of early language exposure: early deaf adults who were born to hearing parents and had reduced early exposure and delayed acquisition of any natural human language ( speech or sign ) , with early dean adults who acquired sign language from birth as the control group that matches on nonlinguistic sensory experience . The dean adult with reduced early speech exposure , compared with the dean control group , showed reduced semantic sensitivity in both multivariate pattern ( semantic structure encoding ) and univariate ( abstractness effect ) analyses . These results provide positive evidence that
The hippocampus is a brain region that is involved in storing memories . It is also involved in processing information about the environment . For example , a rodent running toward a goal will activate a group of neurons called place cells , which are activated in a sequential pattern during a behavioral episode . These place cells then reactivate , repeating the same pattern that was activated during the previous behavior . However , it is not clear how these place cells are able to perform this task . To address this question , Wang et al . studied place cells in rats that had been trained to run towards a target . The experiments show that place cells can change their firing rate between replay events of two different contexts . This changes the rate at which the place cells respond to a particular stimulus , and it can be used to discriminate between contexts in the brain . Further experiments showed that the rate of place cells is influenced by the location of the target , but not by the time it is activated . Furthermore , when the rats ran toward the same target a second time , place cells were more likely to respond to the same stimulus . Therefore , the results suggest that the brain has two complementary neural representations available for memory processing . In addition , these two representations may help us to understand how the brain processes
The mitochondria are the cells that make up the cell’s energy . They are responsible for storing and storing energy , but they also play a key role in regulating the production of proteins and other molecules , which are essential for life . One of the most common mitochondrial diseases is leigh syndrome , a condition that affects approximately 9% of the world’s population . Leigh syndrome is caused by a mutation in the gene that encodes a protein called PARL . This protein is found in the mitochondria of many organisms , including humans and animals . However , it is not clear how PARL affects the mitochondria and how it causes the disease . To investigate this question , Aitken et al . studied mice that lack the PARL protein in their mitochondria . The experiments show that mice lacking PARL develop severe mitochondrial defects during meiosis , when spermatocytes are unable to produce sperm . These defects are caused by defects in mitochondrial homeostasis and are linked to defects in GPX4 , the enzyme that produces coenzyme Q . Further experiments showed that PARL deficiency leads to the death of the arrested cells , leading to the formation of a lipid-peroxidant-dependent process that causes the cells to die . In the future ,
The liver is the nexus of many metabolic pathways , including those of glucose , fatty acids ( FAs ) , and cholesterol . In health , these metabolites are distributed to peripheral tissues while preventing long-lasting accumulation in the liver . Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled , the mechanisms by which they alleviate liver injury have only been scarcely addressed . Here , we aimed to uncover the mechanisms underlying the protective effects of FGF21 on NASH using APOE*3-Leiden . CETP mice , an established model for human-like metabolic diseases , were overexpressing FGF-21 , followed by administration of a high-fat high-cholesterol diet for 23 weeks . FGF 21 prevented hepatic lipotoxicity , as evidenced by reduced Kupffer cell activation , diminished monocyte infiltration , decreased accumulation of monocyte-derived macrophages , which correlated with less hepatic fibrosis as demonstrated by reduced collagen accumulation . Collectively , FGF23 prevents hepatomegaly heparothelial damage through combined endocrine and autocrine signaling , respectively , that prevents Kupfer cell activating and lowers the presence of 
The brain is a complex system that is able to produce many different behaviors . For example , the brain is involved in a variety of processes , such as learning , memory , and movement . Neuroscientists have studied the brain in diverse species , from flies to humans . These experiments have allowed scientists to study how the brain works , but it is not clear how these experiments can be used to create a coherent model of the brain . To address this problem , researchers have developed a new tool called Neurodata Without Borders ( NWB ) . This tool enables researchers to use the data collected from various experiments to generate a more complete picture of the activity of neurons . The goal of NWB is to make it easier for researchers to share and reuse the data . It also allows researchers to create new versions of the tool , which can then be used in the future . In addition , NWB can be adapted to use different types of experiments , so that researchers can use it in different ways . However , it is still not fully understood how NWB works . Now , Liu et al . have developed an open-source software that enables scientists to use NWB to create and reuse neurophysiology data from diverse species and species . First , they created a tool that allows scientists to share , analyze 
Influenza A virus is a common cause of respiratory tract disease , and it can cause severe symptoms such as fever , loss of appetite and excessive sleepiness . However , if the virus infects the brain , it can also cause long-lasting neurological problems , such as encephalitis lethargica and narcolepsy . The brain is the central nervous system that controls the immune system , but it is not clear how the brain responds to the virus . To investigate this question , Wang et al . used a technique called single-nucleus RNA sequencing ( or snRNA-seq for short ) to extract the brain from mice that had been infected with an H1N1 influenza strain . This revealed that the immune cells in the brain were more active at 3 days after the virus had infected the mice . In addition , the brain was more active in microglia , which are cells that help to maintain the energy balance in the body . These cells are also involved in the production of proteins and other molecules that are needed for the body to work properly . Moreover , these cells were also less active in the environment , suggesting that they may be able to prevent the virus from infecting the brain and causing the symptoms of the flu . Further experiments are now needed to
The ovaries of fruit flies are a major source of food for many animals , including humans . The ovary is made up of cells called follicular epithelia , which are surrounded by a layer of tissue called the mesenchymal layer . These cells are able to change their polarity in response to changes in the environment , but it is not clear how these changes can lead to tumors . To address this question , Wang et al . used a technique called single-cell RNA sequencing to study the ovules of fruit fly larvae . This revealed that a gene called Keap1 is required for the cells to form a multilayered structure . However , it was not clear whether this gene is also involved in the formation of the multilayered structures . Further experiments showed that the cells that formed the multilayers were more invasive than normal cells . Furthermore , the cells were more likely to have a mutation in the gene that encodes a protein called Nrf2 , a signaling protein that helps cells to divide and divide . Overall , these findings provide new insights into the molecular mechanisms that underlie the development of ovarian tumors and may help to develop new treatments for cancer .
Humans learn from their environment either directly by interacting with it or indirectly by seeking information about it from social sources such as conspecifics . This process , which is known as non-social learning , is important for our ability to adapt and change behaviour . The degree of confidence in the information obtained through either route should determine the impact that it has on our behavior . However , it is not clear how this learning process works . To address this question , Wang et al . used a combination of brain imaging and computer simulations to investigate whether and how the brain processes information about the environment . In the experiments , participants were asked to rate their confidence about the information they received from other people , and whether they were confident that they would be able to change their behaviour if they were given information about social as opposed to other people’s information . Despite matching exactly the statistical features of social and non-social conditions , confidence judgements were more accurate and less changeable when they were made about social information sources . Furthermore , differences in the patterns of activity in the same areas encoded identities of social sources compared to non–social information sources in humans . These findings provide a new insight into how humans learn about their environment and may help us to develop better ways to learn from others . Future studies are now needed to investigate how these differences are related to how we learn about the
Neurotransmitter release is triggered by brief and local elevations of intracellular Ca2+ with remarkably high sensitivity . How this is molecularly achieved is unknown . Synaptotagmins confer the Ca2 + sensitivity of neurotransmitters release , but biochemical measurements reported Ca2*/PI ( 4 , 5 ) P2 affinities too low to account for synaptic function . Here , we devise a model based on this positive allosteric stabilization and the assumptions that ( 1 . ) synaptotags exert a synchronized action on the energy barrier for vesicle fusion by 5 kBT , and that ( 2 ) the effect of multiple ( typically three ) synapsins on this energy barrier is additive . Our results indicate that each synaptometagmin engages in a stable state , thereby allowing the synchronization of several ( typically 3 ) exocytosis . Furthermore , mutations altering synaptomics’s allostatic properties may show dominant-negative effects , even though synaptopsins act independently on the energetic barrier and that dynamic changes of synaptocytes may have dominant negative effects . These findings provide a new understanding of the mechanism of neuronal communication .
Sauropterygia was a taxonomically and ecomorphologically diverse clade of Mesozoic marine reptiles spanning the Early Triassic to the Late Cretaceous . Saurophores are traditionally divided into two groups representing two markedly different body plans – the short-necked , durophagous Placodontia and the long-necker Eosauropterygians . However , the early evolutionary history of sauropterids and their phylogenetic relationships with other groups within Diapsida are still incompletely understood . Here , we report a new sauropherygian from the Early triassic ( Olenekian ) of South China – Prosaurosphargis yingzishanensis gen . et sp . de novo . representing the earliest known occurrence of the group . An updated phyloenetic analysis focussing on the interrelationships among diapses recovers sauroptrygians as nested within saurhelminths , forming a group with eosarthropods to the exclusion of placodonts and Eusaurus and Palatodonta . Furthermore a cla
DNA methylation is a common feature of DNA , and it is often associated with a variety of biological processes . However , the contribution of a shared genetic predisposition to smoking is typically not accounted for . In this study , we exploited a strong within-family design , that is , a discordant monozygotic twin design . We analysed data from 769 monozygous twin pairs ( mean age = 36 years , range = 18–78 , 70% female ) , including pairs concordant for current or former smoking and 13 differentially methylated CpGs between current smoking twins and their genetically identical co-twin who never smoked . Top sites include multiple Cpgs in CACNA1D and GNG12 , which encode subunits of an calcium voltage-gated channel and G protein , respectively . These proteins interact with the nicotinic acetylcholine receptor , suggesting that methylating levels at these CqGs might be reactive to nicotine exposure . Our results suggest that differences in smoking level exposure for monozygote twins who are both current smokers but differ in the number of cigarettes they smoke are reflected in their DNA phenotypes . This study provides new insights into the molecular mechanisms underlying
The retina is a part of the brain that is responsible for detecting and processing visual information . It is made up of hundreds of different types of cells , each of which is able to send signals to the brain via the optic nerve . In the eye , these signals are processed by a network of cells called retinal ganglion cells . These cells are known as retinal decoders . However , it is not clear how the retina works in vivo . To address this question , Wang et al . used a technique called X-ray crystallography to record the activity of the retina in the eye of mice . The experiments show that the retina responds to light more efficiently than in anesthetized animals , but that it does so in an awake state . This means that the neurons in the retina communicate with the brain in a way that is similar to that seen in anesthesia . Furthermore , the retina also responds more efficiently to changes in light , such as changes in color , contrast , and motion . Further experiments showed that this is because the retina uses a dense coding system , rather than sparse coding , as has been assumed from experiments in animals . Future work is now needed to understand how the visual system works in the brain , which will help us to better understand how our eyes work
Paraformaldehyde ( PFA ) is one of the most commonly used fixatives to create covalent cross-linking between biomolecules , for example , proteins and nucleic acids . PFA nonselectively ‘fixes’ or ‘cross-links’ proteins to preserve a snapshot of biomolecular transactions in vivo . In this study , we compared images , before and after fixation , of cells expressing intrinsically disordered proteins that are able to undergo liquid–liquid phase separation ( LLPS ) . We found that PFA fixation can both enhance and diminish putative LPS behaviors . For specific proteins , fixation may even cause their droplet-like puncta to artificially appear in cells that do not have any detectable puncta in the live condition . Fixing cells in the presence of glycine , a molecule that modulates fixation rates , can reverse the fixation effect from enhancing to diminishing LLP S behavior . Simulations based on the model suggest that protein localization in fixed cells depends on an intricate balance of protein–protein interaction dynamics , the overall rate of fixation and notably the difference between fixation speeds of different proteins . Consistent with simulations and live-cell single-molecule imaging experiments , our work
Urinary tract infections are a major health problem in women . They are caused by bacteria that cause a variety of diseases , including cystic fibrosis and meningitis . The majority of urinary tract infections occur in women who do not take any antibiotics . However , some women do not respond well to antibiotic treatment , which can lead to recurrence of the infection . In some cases , the bacteria can re-infect the bladder , causing the bladder to fill up with urine . This is known as a relapse , and it is important to understand how the bacteria respond to antibiotic therapy . One way to study the bacteria’s response to antibiotics is to use a device called a bladder-chip . These devices can be used to track the growth of bacteria in the bladder during early stages of infection , but it is not possible to monitor the bacteria in real time . To do this , Wang et al . created a computer model of the human bladder that mimics how bacteria grow inside the bladder and how the bladder fills and voids when the bladder is filled . Using a technique called time-lapse microscopy , they show that the bacteria quickly recruit neutrophils to the sites of infection and that they do not prevent the bacteria from forming intracellular bacterial communities . Wang
Ammonium is essential for all forms of life . It is made up of a group of amino acids called glutamate , which is a key component of the building blocks of all living things . The amino acids are then converted to a form of nitrogen called NH4+ by a network of enzymes called transaminases . These enzymes are involved in the conversion of nitrogen into NH3 , a molecule that can be used to make proteins and nucleic acids . However , it is not clear how these enzymes work . To address this question , Liu et al . created a strain of Escherichia coli that was able to produce amines from the amino acids that are present in the cell . This strain was then used to study how amino acids can be added to the cell’s amination network . In the experiments , several amino acids were added to each of the enzymes . Some of these amino acids , such as aspartate , were also added , and some of them were removed from the enzyme . Further experiments showed that the enzyme AspC was a major connector between many amino acids and the amino acid , while others were added by other amino acids such as glycine , serine , or alanine . Finally , aspart
Coral reefs are a major source of carbon for the corals and other marine organisms that live in the oceans . The algae that live on the coral reefs provide the algae with carbon , which is then used to build the coral . However , it is not clear how the algae release carbon from the algae to the host . To investigate this question , Xu et al . used a symbiotic algae called Breviolum sp . to study the release of carbon from algae . This algae is found on the surface of corals , and it is thought that the algae are responsible for releasing carbon into the environment . When the algae were grown in the laboratory , the algae released a chemical called glucose and galactose into the atmosphere . These molecules are known as monosaccharides , but it was not known how these molecules are released into the ocean . Now , Zhou , Wang el . – including some of the researchers involved in the previous work – show that the algal algae release a compound called glucopyranoside into the water . Cellulase is a enzyme that breaks down the cell wall of an algal cell . It is important to understand how algal cells release these molecules , because they are important for the growth of coral reef ecosystems 
Nephronophthisis ( NPHP ) is a ciliopathy characterized by renal fibrosis and cyst formation , and accounts for a significant portion of end stage renal disease in children and young adults . In mice , global knockout of Invs leads to renal phenotypes and cysts . However , the precise contribution of different cell types and the relationship between epithelial cysts and interstitial fibrillation remains undefined . Here , we generated and characterized cell-type-specific knockout mouse models of invs , investigated the impact of removing cilia genetically on proximal and stromal cyst formation and evaluated the effect of the histone deacetylase inhibitor valproic acid ( VPA ) on InvS mutants and compared the effects of VPA on the InvSFlox/flox;Cdh16-Cre mutant kidney . We found that removing the cilium in InvFlox/Flox;Foxd1-CRE mice resulted in renal cyst formation but did not result in cyst formation up to the young adult stage . Furthermore , VPA reduced cyst burden , decreased cell proliferation and ameliorated kidney function decline . Our results reveal the critical role of renal epitelia in NP HP and suggest the possibility of
The extinct sea cow ( Hydrodamalis gigas ) was a whale-sized marine mammal that manifested profound morphological specializations to exploit the harsh coastal climate of the North Pacific . Yet despite first-hand accounts of their biology , little is known regarding the physiological adjustments underlying their evolution to this environment . Here , we show that the adult-expressed hemoglobin ( Hb ) of this sirenian is a fixed amino acid replacement at an otherwise invariant position ( /82LysAsn ) that alters multiple aspects of Hb function . First , our functional characterization of recombinant sirenic Hb proteins demonstrates that the Hb-O2 affinity of this sub-Arctic species was less affected by temperature than those of living ( sub ) tropical sea cows . This phenotype presumably safeguarded O2 delivery to cool peripheral tissues and largely arises from a reduced intrinsic temperature sensitivity of the H . gigaS protein . Additional experiments on H , giga S . 22 mutant Hb further reveal this exchange renders Steller’s sea cow Hb unresponsive to the potent intraerythrocytic allosteric effector 2 , 3-diphosphoglycerate
The fruit fly Drosophila melanogaster is a model organism for studying the development of the nervous system . It is able to grow in a variety of ways , including in the laboratory , in vivo , and in the lab . In the fruit fly , the cells that make up the fly’s nervous system are referred to as ‘cells’ . These cells are made up of a protein called RasV12 , which is activated when the cells are growing . This protein helps the cells to grow and survive , but it is not clear how this helps the fruit flies to grow . To investigate this , Chen et al . used a technique called cloning to create a series of cell lines that were derived from a single cell line . The cells were then grown in the same way as normal cells , with a restriction on the number of cells in each line , so that the cells could be grown in different ways . When a hormone called ecdysone was added , these cells matured into active muscle cells . However , when the hormone was added to the cells from the mesoderm , they were unable to mature into active muscles . Further experiments showed that these cells had a higher level of expression of genes that are important for muscle development .
The respiratory tract , brain , and reproductive systems are lined by specialized cells called multiciliated cells . These cells contain tens to hundreds of motile cilia that collectively beat to drive fluid flow across epithelial surfaces . Each cilium is templated by a centriole or basal body , which docks at the plasma membrane and extends a ciliary axoneme . In cycling cells , a single new centriolo is created on the wall of each of the two parents . However , in MCCs , this process is tightly controlled so that only one new centrole is produced on the surface of each parent . This process is known as centrioler amplification . Polo-like kinase 4 ( PLK4 ) is a protein that is essential for the assembly of centriolels . Previous studies have shown that PLK1 is required for the formation of the centrioleles . But it was not clear whether PLK2 also plays a role in the assembly process . To address this question , Liu et al . used genetically engineered mice to study the role of PLK3 in the formation and assembly of apical multicilia . The experiments show that PKK4 is required to form the centolio and that it is also
Endometrial tissue is a tissue that is surrounded by a layer of tissue called the endometrium . This layer is made up of cells called mesenchymal cells , which are found on the surface of the tissue . These cells are known as stromal fibroblasts , and they are thought to be involved in the repair of the damaged tissue , but it is not clear how these cells are incorporated into the newly formed tissue after the wound has healed . To investigate this question , Xu et al . used a mouse model of the repair process and three transgenic lines of mice . The experiments show that a group of mesensemal cells called perivascular cells ( or NG2/CSPG4+ for short ) are involved in this process . Using a technique called scRNAseq , they identified a new population of stromally derived cells that are able to form a protective layer on the newly repaired tissue and help to restore the integrity of the wound . Further experiments showed that these cells can also become incorporated in the newly re-epithelialised tissue and contribute to the rapid restoration of an intact epithelium . In the future , these findings could be used to develop new treatments for other diseases such as Asherman’s syndrome , endovarian
The diversity of microbes in a population is often a result of the ability of a species to adapt to changing environmental conditions . This diversity can be achieved by a combination of genetic and environmental factors , such as the presence of spores , or by recombination between a pair of insertion sequences . These elements can alter the structure of the genome , which can lead to the formation of new species . However , it is not clear how these changes can occur , and how they can be used to increase the fitness of the population . To investigate this question , Wang et al . studied a bacterium called Burkholderia thailandensis . The experiments show that a group of inserted sequences called RecA , known as IS elements , duplicate a region of DNA that contains 157 coding sequences that are important for the growth of the bacteria . Using a technique called PCR , the sequences were analyzed to see if they were able to duplicate the region . In the experiments , two IS elements were added to the DNA , resulting in the DNA being duplicated by RecA and recombined . When the DNA was duplicated , one copy of the region was advantageous for the bacteria to grow in the biofilm , while
Translation is a process that requires multiple components – including tRNA molecules , tribosomes , and rRNA molecules—to perform their roles . The redundancy in these components is often qualitative , whereby some components can functionally compensate for others . However , we lack empirical measurements of the fitness costs and benefits of redundancies in translation components . We manipulated redundant in multiple translation components of Escherichia coli by deleting 28 genes , 3 tR modifying systems , 4 rRRNA operons in various combinations . Our results show that redundance in trRNA pools is beneficial when nutrients are plentiful and costly under nutrient limitation . This dietary cost stems from upper limits to translation capacity and growth rate and therefore varies as a function of the maximum growth rate attainable in a given niche . Importantly , these effects are also contingent upon interactions across translation components ( indicating a layered hierarchy from copy number to expression and downstream processing ) . Overall , our results indicate both positive and negative selection in translation component evolution , depending on a species’ evolutionary history with feasts and famines .
The COVID-19 pandemic has caused a significant change in the way that scientists work . The virus has been able to evolve from a single virus to a large number of different strains . This has led to the discovery of new strains of the virus , which can be used to study the evolution of other viruses . However , it is not clear how this process works . One way to understand how the virus evolves is to look at the genomes of other organisms , such as humans , and compare these genomes to those of any other organism on Earth . To do this , researchers have developed tools that allow them to explore a tree of SARS-CoV-2 genomes in a web browser . These tools allow researchers to search for mutations that occur in the genome of a given organism . They can then use these mutations to identify new variants that have been introduced into the genome . Now , Chen et al . have developed Taxonium , a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes in the browser for the first time . It links each node to associated metadata and supports mutation-annotated trees that capture all known genetic variation in the dataset . Taxonum can either be run entirely locally in the web browser or as a desktop application 
The post-transcriptional regulation of RNA allows for the fine tuning of the expression of genetic information . The post transcriptional regulation is regulated by interactions between RNA regulatory elements and RNA binding proteins ( RBPs ) . RNA localization is a complex process , and the mechanistic details behind the localization of a given RNA are not well understood . Here , we show that RNA/RBP interactions that regulate RNA spatial distribution in one cell type predictably regulate localization in other cell types with vastly different morphologies . We found that mRNAs encoding ribosomal proteins ( RP ) were strongly localized to the basal pole of human intestinal epithelial cells . In both cell types , the regulatory activity of this motif was dependent on it being in the 5′ UTR of the transcript , was abolished upon perturbation of the RNA-binding protein LARP1 and was reduced upon inhibition of kinesin-1 . These findings identify the first RNA element known to regulate RF localization across the apicobasal axis of epitelial cells , establish LARP1/LARP1 as an RNA locator and demonstrate that similar mechanisms may be transporting RNAs to these morphologically distinct locations .
The human body is a complex organ , with many different types of cells . Some cells , such as the lung , have a unique identity , while others do not . This is known as a loss of cell type identity . However , it is not clear whether this loss of identity is caused by a fundamental property of aging . To answer this question , researchers often use single-cell RNA sequencing ( or scRNAseq for short ) , a technique that can be used to measure the activity of individual cells in a tissue . But it is difficult to compare existing datasets to those of older people . Now , Liu et al . have developed a new computational tool called Decibel , which combines four commonly used methods for quantifying age-related transcriptional noise . The tool , called Scallop , is based on the fact that cells with a higher Scallop membership score are more stable , and that the number of cells in the lung is higher than that of the rest of the population . In addition , the tool was applied to seven aging datasets , suggesting that aging is not a universal hallmark of age . Further work is needed to understand how the aging process affects the composition of the lung and other organs in the human body .
Cancer is a disease that affects millions of people worldwide . It is caused by a combination of genetic and environmental factors , which can lead to the formation of tumours that are resistant to chemotherapy . However , it is not clear how these tumours are able to resist chemotherapy , and how they do so . To address this question , researchers have developed a technique called WILD-seq . This technique uses a gene called NRF2 to track the activity of a protein called BET . Then , the genes are transcribed into a molecule called asparagine . These genes are then analyzed to find out how the tumours respond to treatment . Previous studies have shown that a drug called L-asparaginase can be used to treat triple-negative breast cancer , but it was not known how this drug works . Now , Liu et al . have used this technique to study the effects of treatment on tumours in mice . In the experiments , mice were genetically engineered to have a mutation in the gene that encodes the protein as paragines . When the mice were treated with the drug , they were more sensitive to the drug than normal . Further experiments showed that the mice had a higher level of resistance to the treatment compared to normal mice , suggesting that the tumour
The testes of mammals are the organs that produce eggs and sperm . In mammals , a protein called DMRT1 is required for the development of the ovaries , which are a group of cells in the uterus that produce egg cells . However , it is not clear how this protein is involved in determining whether a fetus is a male or a female . To address this question , Liu et al . used a technique called CRISPR/Cas9 to remove the protein from a third species of mammal , the rabbit . The experiments show that a gene called SOX9 is required to make the gonads of a rabbit’s testis . This gene is also required for a process called meiosis , in which a cell divides to produce a new egg cell . Moreover , mice that lack the gene have a higher risk of developing infertility . These findings suggest that , unlike humans , animals with mutations in the gene that encodes SOX09 are more likely to develop infertile . Further work is now needed to determine if the mutations that cause these phenotypes are related to human diseases , such as cancer .
Obesity is a major health problem worldwide , and it is caused by the consumption of high-fat diets . High-fat food is accompanied by a high risk of developing diabetes , heart disease , cancer , or other diseases . The consumption of too much or too little fat can lead to obesity , but it is not clear how this causes the disease . A protein called cytoidine 5'-triphosphate synthase ( CTPS ) is involved in the production of CTP , which is essential for the synthesis of lipids and other molecules . CTPS is found in bacteria , archaea and eukaryotes . In the fruit fly Drosophila melanogaster , CTPS has been shown to be involved in regulating body weight and starvation resistance . However , it was not clear if CTPS also plays a role in the development of obesity . To address this question , Liu et al . used a technique called X-ray crystallography to study the role of CTPS in the growth of cytoophidia in larval adipocytes of fruit flies . This revealed that , in addition to being important for the growth and development of adipose tissue , the cytoopsids also play 
The embryo is made up of two layers of cells called the mesoderm and the endoderm . The mesendoderm is formed by a layer of proteins called Nodal , which is produced by the TGF- family of proteins . Nodals bind to receptors on the surface of the cell called Type I/II Activin receptors . These receptors are known to be involved in regulating the development of the embryo , but it is not clear whether these receptors also play a role in the development or distribution of Nodales . To address this question , Xu et al . used a technique called CRISPR F0 to knock down the genes that encode the receptors for three different types of Nodeal receptors in zebrafish . This revealed that the two types of receptors that are involved in the distribution and distribution of the Nodal signal are not present in the embryos of the frog . Instead , the two type I receptors and two type II receptors work together to control the distribution of nodal through the embryo and to regulate the development . However , it was not clear how these two receptors interact with each other to control Nodation . Further experiments showed that the type I , type II , and type III receptors do not interact directly with Nod
The immune system is a complex system that controls the immune system’s response to infection . It is made up of many different types of cells , each of which has a specific role . For example , a cell can respond to a viral infection by producing a protein called type I interferon ( IFN-I ) . This protein is produced by a group of cells called fibroblasts , which are found in many different tissues and organs . When a virus infects a person , it triggers an immune response , known as a “response response” . However , this response is not always instantaneous , and it can lead to serious diseases , such as cancer , heart disease and cancer . To understand how the immune response is regulated , researchers need to understand how cells decide to respond to the virus . One way to do this is to use a technique called the Luria–Delbrück fluctuation test . In this test , the number of cells that respond to an infection is compared to the amount of time it takes for the virus to enter the body . The experiments show that a small fraction of the population of cells responds to an attack , but only a few percent of the cells respond to it . Moreover , some of these cells respond
The microtubules ( MTs ) are built from -/-tubulin dimers and used as tracks by kinesin and dynein motors to transport a variety of cargos , such as mRNAs . Tubulins are subjected to several post-translational modifications ( PTMs ] . Glutamylation is one of them , and it is responsible for adding one or more glutamic acid residues as branched peptide chains to the C-terminal tails of both  and  tubulin . However , very little is known about the specific modifications found on the different tubuline isotypes in vivo and the role of these PTM in MT transport and other cellular processes in vesicle . In this study , we found that in Drosophila ovaries , glutamylation of Tub84B and a D B/D isotypic . Interestingly , the ovarian TB/D , TD67C , is not glutasomelated . The C-term of TTLL5 is required for the mono- and poly-glutamylation of ovarian TT84B/
The development of multiple chromosome-scale reference genome sequences in many taxonomic groups has yielded a high-resolution view of the patterns and processes of molecular evolution . However , leveraging information across multiple genomes remains a significant challenge in nearly all eukaryotic systems . These challenges range from studying the evolution of chromostructure , to finding candidate genes for quantitative trait loci , and testing hypotheses about speciation and adaptation . Here , we present GENESPACE , which addresses these challenges by integrating conserved gene order and orthology to define the expected physical position of all genes across multiple genomics . We demonstrate this utility by dissecting presence–absence , copy-number , structural variation at three levels of biological organization: spanning 300 million years of vertebrate sex chromus evolution , across the diversity of the Poaceae ( grass ) plant family , as well as among 26 maize cultivars , using the methods to build and visualize syntenic orthologie in the GENEPACE R package . The methods to construct and visualize Syntenic Orthology in the GNU Gene Family and Synteny Program offer a substantial addition to existing gene family and synteny programs , especially in polyploid , outbred , or other
Bacteria are a group of microbes that live in a variety of environments . Many of these communities are composed of multiple species of bacteria , which can interact with each other to produce unique compounds , increase virulence , and increase antibiotic resistance . One community associated with negative healthcare outcomes consists of Pseudomonas aeruginosa and Staphylococcus aureus . When co-cultured , these bacteria reduce the growth and growth of S . albicans . However , when found in vivo , both species can co-exist . Previous work has noted that this may be due to altered gene expression or mutations , but little is known about how the growth environment could influence the co-existence of these two species . Here , Xu et al . used mathematical modeling and experimentation to show that changes to the carbon source in growth media affect the ratio of ATP to growth rate for both species , an metric called absolute growth . As a growth environment increases , the absolute growth for one species will increase . This is due to interactions between growth , metabolism and metabolism-altering factors produced by the bacteria . Finally , by altering the spatial structure in the community , they show that the relationship between absolute growth and the final population composition can be perturbed
The vast majority of the information in the scientific literature is derived from interactions between different species . However , many of these interactions are not well understood , and it is difficult to understand how these interactions occur . To improve access to this knowledge , researchers have developed a tool called the Pathogen–Host Interactions database ( PHI-base ) , which allows researchers to curate the information about interactions between species based on their genetic information . This tool can be used by researchers to study the effects of a variety of pathogens , including viruses , bacteria , fungi , insects and other organisms . The tool can also be used to identify the genes that are involved in the interactions between the pathogen and its host . For example , it can help researchers to identify genes that affect the ability of the bacteria to cause disease . Researchers can then use this information to improve their understanding of the relationship between the bacteria and their hosts . In this way , scientists can better understand how the bacteria interact with their hosts and how they are able to survive and multiply in the environment . It is also possible to use this knowledge to improve the quality of research , as well as to make it easier for researchers to use it for their own research . Now , Liu et al . have created a new tool that can help scientists curate information on interactions between
The human genome contains a large number of genes that are expressed in different ways . These genes are often referred to as enhancers , which control the activity of specific genes in the cell . However , it is not clear how these genes are regulated , and how they affect the expression of other genes . To address this question , researchers have used a technique called genome-wide association studies ( GWAs ) to study the effect of genetic variants on enhancer activity . GWAS is a gene that is expressed in a specific cell type . This gene is transcribed into a protein called transcription factor ( TF ) . TFs are proteins that bind to specific regions of the genome , such as the DNA , where they are found . When a TF is binded to an enhancer , the TF then binds to the enhancer and activates the gene . It is not known exactly how TF binding affects enhancer function , but it is known that a number of sequence variants can alter the binding and activity of enhancer proteins . Now , Li et al . have used genetically modified mice to identify thousands of DNA variants that affect the activity and binding of transcription factor . The experiments show that the AP-1 family of transcription factors are required for the binding of 
The immune system is a complex system that helps to protect the body from viruses . It is also important for the virus to be able to replicate in the host , which is able , in part , to protect itself from the immune system . Viruses can interact with proteins in the cell to promote their replication . These interactions can either benefit the host or the virus , and can lead to the evolution of new antiviral proteins . However , it is not clear how these interactions are regulated . To address this question , Liu et al . studied a protein called ninein-like ( NINL ) , a key component of the dynein protein complex . The experiments show that , unlike other genes encoding components of active complexes , the ninein gene has evolved under recurrent positive selection over evolutionary time . In particular , ninein has evolved in a way that is unique among genes that encode components of the active complex , particularly in its carboxy-terminal cargo-binding region . This suggests that ninein may play a role in the immune response against viruses , as well as in the development of anti-viral immune responses . Furthermore , when ninein is knocked out , cells are more susceptible to viral infection , suggesting that it may be a target
The cytoskeleton is a structure that is essential for the movement of cells . It is made up of four different types of protein , each of which is able to form a network . These proteins are known as actin isoforms , and they are found in many different tissues , including the heart and skeletal muscle . However , it is not clear how these different forms of actin interact with each other . To address this question , Wang et al . used a technique called cryo-electron microscopy to study the structure of three different forms ( -actin , 2-actin and 3- actin ) of the actin filaments that form in the skeletal muscles of mice . The experiments revealed that the three forms of  actin are different from each other in that they have different conformations . In particular , the N-terminus of the  form shifts closer to the surface of the filament , which allows it to interact with the myosin motor . This enables it to bind to the filaments of other proteins , such as the motor proteins . Further experiments showed that a protein called ß-Actin binds to a region of the protein called the N terminus , where it interacts with a motor protein called myo
Transgenesis is the introduction of foreign DNA into a genome . While there are many uses for transgenesis , in practice most can be grouped into those inserting a small number of known sequences and those introducing many sequence variants from experimental libraries . However , the need for library transgenesis has effectively restricted these approaches to single-cell models . Here , we present Transgenic Arrays Resulting in Diversity of Integrated Sequences ( TARDIS ) , a simple yet powerful approach to large-scale transgenesis that overcomes typical limitations encountered in multicellular systems . We demonstrate the power of this system using engineered , split selectable TARVIS sites in Caenorhabditis elegans to generate a large set of individually barcoded lineages and transcriptional reporter lines from predefined promoter libraries , and we find that this approach increases transformation yields up to approximately 1000-fold over current single-step methods . Although we demonstrate the utility of this approach using C . eleggans , it is in principle adaptable to any system where experimentally generated genomic loci landing pads and diverse , heritable DNA elements can be generated .
Bacteria are able to survive in the environment by forming a membrane that is made of a variety of molecules . These molecules are then transported to the cell’s interior via a series of steps , called the ‘outer membrane’ . The outer membrane is made up of two layers , each of which contains a protein called a ribosome , which moves across the inner membrane to form the outer membrane . This process is called ‘translocation’ , and it involves a number of proteins , including chaperones , proteases and other enzymes . However , it is not clear how these proteins interact with each other , or how they form large complexes that can be used to study biological processes . To address this question , Liu et al . developed a deep learning algorithm that can identify interactions between proteins in the outer envelope of Escherichia coli cells . It was then used to predict the structures of the proteins that form the inner envelope . Liu and Liu then used this information to predict how the proteins interact . Among the predictions , the proteins were found to interact with one another , but not with other proteins . Further experiments showed that these interactions were not only expected but also unexpected . For example , some of the interactions were unexpected , suggesting that the proteins could be 
Dopamine is a chemical messenger that is released from the brain into the environment . It is released by neurons in the midbrain , which are responsible for regulating the activity of the brain . The dopamine neuron is located in the striatum , a region in the brain that contains many different types of neurons . These neurons are connected to each other by a network of connections called synapses . When a neuron receives a signal from another neuron , it releases another neurotransmitter called glutamate , or GABA , to the axon . GABA is released through a protein called neurexins . However , the molecular mechanisms that regulate the release of glutamates and GABA from the DA neuron are not well understood . To address this question , Wang et al . used mice that had been genetically engineered to remove all of the proteins that are found in DA neurons , and then injected these mice with a drug called amphetamine . In the experiments , these mice were able to move normally , but they were also unable to communicate with other neurons in their brain , such as the basal ganglia . This was due to the loss of two proteins , called DAT and VMAT2 ,
Mobile health ( mHealth ) interventions , which require ownership of mobile phones , are being investigated throughout Africa . We estimate the percentage of individuals who own mobile phones in 33 African countries , identify a relationship between ownership and proximity to a health clinic ( HC ) , and quantify inequities in ownership . Using national representative data collected in 2017–2018 from 44 , 224 individuals in Round 7 of the Afrobarometer surveys , we find 82% of individuals in 33 countries own mobile phone: 42% BPs and 40% SPs . Individuals who live close to an HC have higher odds of ownership than those who do not ( aOR: 1 . 31 , Bayesian 95% highest posterior density [HPD] region]: 2 . 24–1 . 39 ) and , amongst mobile phone owners , nearly three times the odds of owning an SP . The probability of ownership decreases with age , peak in 26–40 year olds , then decreases; individuals under 30 are more likely to own an SP than a BP . If the digital devices needed for mhealth interventions are not equally available within the population ( which we have found is the current situation , our findings are likely to propagate already existing in the population .
Severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) is a life-threatening viral infection that can cause severe respiratory distress syndrome ( SRS ) . The virus is transmitted by the bite of a sand fly , which is transmitted to humans by a mosquito . SARS is endemic in many parts of the world , including the United Kingdom , Australia , and New Zealand . Infection with SARS can lead to severe respiratory syndrome , a condition known as COVID-19 . It is estimated that approximately 1 . 5 million people in the UK are at risk of developing SARS . However , it is not clear how high levels of SARS anti-Spike antibodies are associated with increased protection against future infection . Here , we analysed the association between antibody levels following SARS vaccination and: ( 1 ) SARS infection following vaccination ( s ); ( 2 ) health , socio-demographic , SARS–coV-2 infection and vaccination variables . We found that individuals with the lowest 20% of antibody levels at initial testing had threefold greater odds of infection over the next 6–9 months compared to the top 20% . Individuals identified as at increased risk of complication through the UK ‘Shielded Patient List’ had consistently greater odds ( two- to fourfold )