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Imaginal progenitors in Drosophila are known to arrest in G2 during larval stages and proliferate thereafter . Here we investigate the mechanism and implications of G2 arrest in progenitors of the adult thoracic tracheal epithelium ( tracheoblasts ) . We report that tracheoblasts pause in G2 for ~48–56 h and grow in si...	Every organism begins as a single cell . That cell , and all the other cells it generates over time , need to divide at the right time and in the right place to develop into an adult . As they do so , they pass through the stages of the cell cycle . As cells prepare to divide they enter into the first growth phase , G1...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2018	Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila
Bacterial populations vary in their stress tolerance and population structure depending upon whether growth occurs in well-mixed or structured environments . We hypothesized that evolution in biofilms would generate greater genetic diversity than well-mixed environments and lead to different pathways of antibiotic resi...	A bacterium known as Acinetobacter baumannii causes serious lung infections in people with weakened immune systems . These illnesses are becoming more common largely because A . baumannii is increasingly developing resistance to antibiotics . Inside the airways , individual A . baumannii cells can stick together and co...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle
Hitherto , membralin has been a protein of unknown function . Here , we show that membralin mutant mice manifest a severe and early-onset motor neuron disease in an autosomal recessive manner , dying by postnatal day 5–6 . Selective death of lower motor neurons , including those innervating the limbs , intercostal musc...	As new proteins are built inside a cell , many will pass into a structure called the endoplasmic reticulum for processing . There , the proteins are folded into the specific three-dimensional shapes that allow them to carry out their respective jobs . Sometimes the folding process goes awry , leading to a build-up of u...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	The critical role of membralin in postnatal motor neuron survival and disease
Insect herbivores use different cues to locate host plants . The importance of CO2 in this context is not well understood . We manipulated CO2 perception in western corn rootworm ( WCR ) larvae through RNAi and studied how CO2 perception impacts their interaction with their host plant . The expression of a carbon dioxi...	Living deep in the ground and surrounded by darkness , soil insects must rely on the chemicals released by plants to find the roots they feed on . Carbon dioxide , for example , is a by-product of plant respiration , which , above ground , is thought to attract moths to flowers and flies to apples; underground , howeve...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2021	Plant-associated CO2 mediates long-distance host location and foraging behaviour of a root herbivore
During vertebrate embryogenesis , dorsal-ventral patterning is controlled by the BMP/Chordin activator/inhibitor system . BMP induces ventral fates , whereas Chordin inhibits BMP signaling on the dorsal side . Several theories can explain how the distributions of BMP and Chordin are regulated to achieve patterning , bu...	Animals start life as clumps of cells that ultimately give rise to complex structures and organs . Over a century of research has revealed a small number of proteins that are crucial for complex structures to form from these clumps , including one protein called BMP . Different levels of BMP instruct cells to give rise...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "computational", "and", "systems", "biology" ]	2017	Dynamics of BMP signaling and distribution during zebrafish dorsal-ventral patterning
DNA methylation is an essential epigenetic mark whose role in gene regulation and its dependency on genomic sequence and environment are not fully understood . In this study we provide novel insights into the mechanistic relationships between genetic variation , DNA methylation and transcriptome sequencing data in thre...	Variations occur throughout our genome . These variations can cause genes to be expressed ( switched on ) in slightly different ways among individuals . Moreover , the same gene can also be expressed in different ways in different cells within an individual . A third level of variation is supplied by epigenetic markers...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2013	Passive and active DNA methylation and the interplay with genetic variation in gene regulation
The sensory and supporting cells ( SCs ) of the organ of Corti are derived from a limited number of progenitors . The mechanisms that regulate the number of sensory progenitors are not known . Here , we show that Fibroblast Growth Factors ( FGF ) 9 and 20 , which are expressed in the non-sensory ( Fgf9 ) and sensory ( ...	Mammalian ears contain several structures that are involved in hearing . Within the inner ear is a spiral-shaped structure called the cochlea . This contains an array of cells called sensory hair cells that convert sound vibrations into electrical signals , which are then conveyed to the brain . Sounds of differing pit...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2015	Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling
The role of the hippocampus in spatial cognition is incontrovertible yet controversial . Place cells , initially thought to be location-specifiers , turn out to respond promiscuously to a wide range of stimuli . Here we test the idea , which we have recently demonstrated in a computational model , that the hippocampal ...	The hippocampus is one of the most easily recognizable structures in the brain owing to its characteristic seahorse-like shape . Brain imaging studies in the 1990s famously showed the hippocampus to be larger in London taxi drivers than in other people , suggesting that it plays a role in spatial navigation . This was ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Reconceiving the hippocampal map as a topological template
Cardiovascular regulation is integral to life . Animal studies have identified both neural and endocrine pathways , by which the central nervous system adjusts cardiac output and peripheral vascular resistance to changing physiological demands . The outflow of these pathways is coordinated by various central nervous re...	Stand up too fast and you know what happens next . You will feel faint as the blood rushes away from your head . Gravity pulls the blood into your legs , and your blood pressure drops . To correct this imbalance , the brain sends nerve impulses telling the heart to beat faster and the outer blood vessels to tighten . T...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "neuroscience" ]	2020	Deciphering the neural signature of human cardiovascular regulation
Proteins persist longer in the fossil record than DNA , but the longevity , survival mechanisms and substrates remain contested . Here , we demonstrate the role of mineral binding in preserving the protein sequence in ostrich ( Struthionidae ) eggshell , including from the palaeontological sites of Laetoli ( 3 . 8 Ma )...	The pattern of chemical reactions that break down the molecules that make our bodies is still fairly mysterious . Archaeologists and geologists hope that dead organisms ( or artefacts made from them ) might not decay entirely , leaving behind clues to their lives . We know that some molecules are more resistant than ot...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "biochemistry", "and", "chemical", "biology" ]	2016	Protein sequences bound to mineral surfaces persist into deep time
Among various advantages , their small size makes model organisms preferred subjects of investigation . Yet , even in model systems detailed analysis of numerous developmental processes at cellular level is severely hampered by their scale . For instance , secondary growth of Arabidopsis hypocotyls creates a radial pat...	Our understanding of the living world has been advanced greatly by studies of ‘model organisms’ , such as mice , zebrafish , and fruit flies . Studying these creatures has been crucial to uncovering the genes that control how our bodies develop and grow , and also to discover the genetic basis of diseases such as cance...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2014	Automated quantitative histology reveals vascular morphodynamics during Arabidopsis hypocotyl secondary growth
Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment . This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years . The role of the microenvironment in regulating the survival and pr...	Breast cancer is the second-leading cause of cancer-related deaths in women . Recurrence of breast-cancer five or more years after initial diagnosis and treatment causes more than half of these deaths . This suggests that some tumor cells survived treatment and persisted undetected . These residual tumor cells may not ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation", "cancer", "biology" ]	2019	CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors
During outbreaks of high-consequence pathogens , airport screening programs have been deployed to curtail geographic spread of infection . The effectiveness of screening depends on several factors , including pathogen natural history and epidemiology , human behavior , and characteristics of the source epidemic . We de...	International air travel has contributed to the spread of several recent disease epidemics . For example , travelers infected with severe acute respiratory syndrome ( or SARS ) in 2003 carried the disease around globe . One infected air traveler can carry a disease to a new continent: in 2014 , a man infected with Ebol...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "epidemiology", "and", "global", "health" ]	2015	Effectiveness of traveller screening for emerging pathogens is shaped by epidemiology and natural history of infection
Agricultural soil harbors a diverse microbiome that can form beneficial relationships with plants , including the inhibition of plant pathogens . Pseudomonas spp . are one of the most abundant bacterial genera in the soil and rhizosphere and play important roles in promoting plant health . However , the genetic determi...	Potato scab and blight are two major diseases which can cause heavy crop losses . They are caused , respectively , by the bacterium Streptomyces scabies and an oomycete ( a fungus-like organism ) known as Phytophthora infestans . Fighting these disease-causing microorganisms can involve crop management techniques – for...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]	2021	Pan-genome analysis identifies intersecting roles for Pseudomonas specialized metabolites in potato pathogen inhibition
In cell culture , genetically identical cells often exhibit heterogeneous behavior , with only ‘lineage primed’ cells responding to differentiation inducing signals . It has recently been proposed that such heterogeneity exists during normal embryonic development to allow position independent patterning based on ‘salt ...	How genetically identical cells develop into distinct cell types is one of the fundamental questions in biology . Certain molecules are known to act as signals that tell progenitor cells what type of cell they should become . The position of a cell within an embryo can determine which of these signals it is exposed to ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2013	Developmental lineage priming in Dictyostelium by heterogeneous Ras activation
Goal-directed attention is usually studied by providing individuals with explicit instructions on what they should attend to . But in daily life , we often use past experiences to guide our attentional states . Given the importance of memory for predicting upcoming events , we hypothesized that memory-guided attention ...	At any given moment , humans are bombarded with a constant stream of new information . But the brain can take in only a fraction of that information at once . So how does the brain decide what to pay attention to and what to ignore ? Many laboratory studies of attention avoid this issue by simply telling participants w...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Preparation for upcoming attentional states in the hippocampus and medial prefrontal cortex
Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength . Synapses contain two pools of receptors , immobilized and diffusing receptors , both of which are confined to post-synaptic elements . Here we show that immobile and diffusing GABAA receptors are stabilized by distinct ...	Behaviors ranging from movement to memory are dependent on the activity of extensive networks of cells called neurons . Within these networks , neurons communicate across junctions called synapses . The arrival of an electrical signal called an action potential at the ‘presynaptic’ neuron on one side of the synapse tri...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	A network of autism linked genes stabilizes two pools of synaptic GABAA receptors
Khoomei is a unique singing style originating from the republic of Tuva in central Asia . Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone . The biomechanics of this biphonation are not well-understood . Here , we use sound analysis , dynamic...	The republic of Tuva , a remote territory in southern Russia located on the border with Mongolia , is perhaps best known for its vast mountainous geography and the unique cultural practice of “throat singing” . These singers simultaneously create two different pitches: a low-pitched drone , along with a hovering whistl...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems" ]	2020	Overtone focusing in biphonic tuvan throat singing
Speech perception presumably arises from internal models of how specific sensory features are associated with speech sounds . These features change constantly ( e . g . different speakers , articulation modes etc . ) , and listeners need to recalibrate their internal models by appropriately weighing new versus old evid...	People can distinguish words or syllables even though they may sound different with every speaker . This striking ability reflects the fact that our brain is continually modifying the way we recognise and interpret the spoken word based on what we have heard before , by comparing past experience with the most recent on...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Integrating prediction errors at two time scales permits rapid recalibration of speech sound categories
Maintaining a healthy body weight requires an exquisite balance between energy intake and energy expenditure . To understand the genetic and environmental factors that contribute to the regulation of body weight , an important first step is to establish the normal range of metabolic values and primary sources contribut...	Maintaining a healthy weight requires the body to balance energy intake and expenditure . The body converts food to energy through a process called energy metabolism . Genetic and environmental factors can affect energy metabolism and energy balance contributing to conditions like obesity . To better understand metabol...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2020	A big-data approach to understanding metabolic rate and response to obesity in laboratory mice
Slow-wave sleep is an optimal opportunity for memory consolidation: when encoding occurs in the presence of a sensory cue , delivery of that cue during sleep enhances retrieval of associated memories . Recent studies suggest that cues might promote consolidation by inducing neural reinstatement of cue-associated conten...	It may not always feel like it , but we encounter an incredible volume of new information every day . We experience so much that it is not feasible to remember every detail . The brain's process for reorganizing memories – keeping some secure and discarding others – is known as memory consolidation . There are ways of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Odor-evoked category reactivation in human ventromedial prefrontal cortex during sleep promotes memory consolidation
About 300 loss-of-function mutations in the IKs channel have been identified in patients with Long QT syndrome and cardiac arrhythmia . How specific mutations cause arrhythmia is largely unknown and there are no approved IKs channel activators for treatment of these arrhythmias . We find that several Long QT syndrome-a...	Every heartbeat relies on an electric wave that travels through the heart . This wave must reach different parts of the heart in a specific sequence to ensure that the heart muscle cells contract in a coordinated manner . Such coordinated contractions enable the heart to pump enough blood around the body . By allowing ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations
Intracellular ion channels are essential regulators of organellar and cellular function , yet the molecular identity and physiological role of many of these channels remains elusive . In particular , no ion channel has been characterized in melanosomes , organelles that produce and store the major mammalian pigment mel...	Melanin is a pigment found in our skin , eyes and hair . Individuals who are unable to make or store melanin , a condition known as albinism , have unusually pale features and problems with vision . The pigment helps to protect us from harmful UV radiation , and so individuals with albinism also have an increased risk ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	An intracellular anion channel critical for pigmentation
mir-17-92 , a potent polycistronic oncomir , encodes six mature miRNAs with complex modes of interactions . In the Eμ-myc Burkitt’s lymphoma model , mir-17-92 exhibits potent oncogenic activity by repressing c-Myc-induced apoptosis , primarily through its miR-19 components . Surprisingly , mir-17-92 also encodes the mi...	The role of genes , in very simple terms , is to be transcribed into messenger RNA molecules , which are then translated into strings of amino acids that fold into proteins . Each of these steps is extremely complex , and a wide range of other molecules can speed up , slow down , stop or otherwise disrupt the expressio...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2013	A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis
Chemical modification of the gRNA and donor DNA has great potential for improving the gene editing efficiency of Cas9 and Cpf1 , but has not been investigated extensively . In this report , we demonstrate that the gRNAs of Cas9 and Cpf1 , and donor DNA can be chemically modified at their terminal positions without losi...	There are several different technologies that can be used to make specific changes to particular genes in cells . These “gene editing” approaches have the potential to help humans in a variety of different ways , for example , to treat diseases that presently have no cure , or to improve the nutritional quality of crop...	[ "Abstract", "Introduction", "Results", "and", "discussions", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "short", "report" ]	2017	Synthetically modified guide RNA and donor DNA are a versatile platform for CRISPR-Cas9 engineering
Genetic regulation of gene expression underlies variation in disease risk and other complex traits . The effect of expression quantitative trait loci ( eQTLs ) varies across cell types; however , the complexity of mammalian tissues makes studying cell-type eQTLs highly challenging . We developed a novel approach in the...	DNA sequences that differ between individuals often change the activation pattern of genes . That is , they change how , when , or why genes switch on and off . We call such DNA sequences 'expression quantitative trait loci' , or eQTLs for short . Many of these eQTLs affect biological traits , but their effects are not...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2021	Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
A defining feature of mitochondria is their maternal mode of inheritance . However , little is understood about the cellular mechanism through which paternal mitochondria , delivered from sperm , are eliminated from early mammalian embryos . Autophagy has been implicated in nematodes , but whether this mechanism is con...	Mitochondria are commonly referred to as the 'powerhouses' of animal cells because these structures provide the majority of the energy in most cells . People inherit their mitochondria from their mother , and not their father . This is because the father's mitochondria , which are delivered by sperm to the egg , are de...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1
Habit formation is a behavioral adaptation that automates routine actions . Habitual behavior correlates with broad reconfigurations of dorsolateral striatal ( DLS ) circuit properties that increase gain and shift pathway timing . The mechanism ( s ) for these circuit adaptations are unknown and could be responsible fo...	From biting fingernails to the daily commute , habits are sets of actions that can be completed almost without thinking and that are difficult to change or stop . Behavioral neuroscientists refer to habits as “stimulus-response” behaviors , and know that forming a new habit requires a region deep within the brain calle...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior
The formation of imprinted memories during a critical period is crucial for vital behaviors , including filial attachment . Yet , little is known about the underlying molecular mechanisms . Using a combination of behavior , pharmacology , in vivo surface sensing of translation ( SUnSET ) and DiOlistic labeling we found...	Shortly after hatching , a chick recognizes the sight and sound of its mother and follows her around . This requires a type of learning called imprinting , which only occurs during a short period of time in young life known as the “critical period” . This process has been reported in a variety of birds and other animal...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Translational control of auditory imprinting and structural plasticity by eIF2α
The RIG-I-like receptors RIG-I , LGP2 , and MDA5 initiate an antiviral response that includes production of type I interferons ( IFNs ) . The nature of the RNAs that trigger MDA5 activation in infected cells remains unclear . Here , we purify and characterise LGP2/RNA complexes from cells infected with encephalomyocard...	A virus is basically molecules of DNA or RNA inside a protein shell , and in order to reproduce , it must infect a living cell and take control of it . However , the attacked cell will fight back and try to eliminate the invader . Activation of this so-called innate immune response requires the host cells to recognize ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2014	Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells
Bradykinin ( Bk ) is a potent inflammatory mediator that causes hyperalgesia . The action of Bk on the sensory system is well documented but its effects on motoneurons , the final pathway of the motor system , are unknown . By a combination of patch-clamp recordings and two-photon calcium imaging , we found that Bk str...	When we accidentally place our hand on a hot stove , we normally experience a painful sensation that starts with the sensory nerves under our skin . These nerves respond by transmitting electrical impulses to our brain , where the painful sensation is then processed . At the same time , these impulses are also transmit...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin
Understanding chromatin function requires knowing the precise location of nucleosomes . MNase-seq methods have been widely applied to characterize nucleosome organization in vivo , but generally lack the accuracy to determine the precise nucleosome positions . Here we develop a computational approach leveraging digesti...	Plants , animals and other eukaryotes wrap their DNA around complexes of proteins called histones to form repeating units known as nucleosomes . The interaction between histones and DNA is strong , and so the DNA region inside a nucleosome has limited access to other proteins , including those that drive the expression...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]	2016	A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution
Calcium ( Ca2+ ) dysregulation is a hallmark of heart failure and is characterized by impaired Ca2+ sequestration into the sarcoplasmic reticulum ( SR ) by the SR-Ca2+-ATPase ( SERCA ) . We recently discovered a micropeptide named DWORF ( DWarf Open Reading Frame ) that enhances SERCA activity by displacing phospholamb...	The heart is a muscular organ that contracts regularly to pump blood around the body , ensuring that nutrients and oxygen are carried to the cells and organs . Heart failure is a disease where the heart muscle becomes weakened , does not beat as strongly , and cannot pump blood as well as it should . Eventually , the h...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	The DWORF micropeptide enhances contractility and prevents heart failure in a mouse model of dilated cardiomyopathy
Polyploidization , the increase in genome copies , is considered a major driving force for speciation . We have recently provided the first direct in planta evidence for polyspermy induced polyploidization . Capitalizing on a novel sco1-based polyspermy assay , we here show that polyspermy can selectively polyploidize ...	Ever since Darwin published his most famous book on the theory of evolution , scientists have sought to identify the mechanisms that drive the formation of new species . This is especially true for plant biologists who have long been fascinated by the extraordinary diversity of flowering plants . Many species of flower...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2020	Selective egg cell polyspermy bypasses the triploid block
Arthropod-borne rickettsial pathogens cause mild and severe human disease worldwide . The tick-borne pathogen Rickettsia parkeri elicits skin lesions ( eschars ) and disseminated disease in humans; however , inbred mice are generally resistant to infection . We report that intradermal infection of mice lacking both int...	Tick bites allow disease-causing microbes , including multiple species of Rickettsia bacteria , to pass from arthropods to humans . Being exposed to Rickettsia parkeri , for example , can cause a scab at the bite site , fever , headache and fatigue . To date , no vaccine is available against any of the severe diseases ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2021	Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis
Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy . We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data . Our method integrates novel gene expression profiles from each major ...	Malignant tumors do not only contain cancer cells . Normal cells from the body also infiltrate tumors . These often include a variety of immune cells that can help detect and kill cancer cells . Many evidences suggest that the proportion of different immune cell types in a tumor can affect tumor growth and which treatm...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "tools", "and", "resources", "cancer", "biology" ]	2017	Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis . Their inhibition is predicted to have pleiotropic effects , but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors . We discovered two series of potent chemical probes with high selectiv...	Healthy cells in the human body can become cancerous if they gain genetic mutations that allow them to rapidly grow and divide . Some types of cancer respond better to drug treatments than others and tumors often develop resistance to a particular drug treatment after a while . Because of this , researchers are always ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2016	Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases
APC , a key negative regulator of Wnt signaling in development and oncogenesis , acts in the destruction complex with the scaffold Axin and the kinases GSK3 and CK1 to target βcatenin for destruction . Despite 20 years of research , APC's mechanistic function remains mysterious . We used FRAP , super-resolution microsc...	An embryo starts off as a small ball of stem cells , each of which has the potential to become any type of cell in the body . Adult organs and tissues also contain small numbers of stem cells that can replace old or damaged cells . In both of these processes , stem cells need to ‘decide’ when they should start to chang...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	A novel GSK3-regulated APC:Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient βcatenin destruction
Actin filaments assemble inside the nucleus in response to multiple cellular perturbations , including heat shock , protein misfolding , integrin engagement , and serum stimulation . We find that DNA damage also generates nuclear actin filaments—detectable by phalloidin and live-cell actin probes—with three characteris...	In animals , plants , and other eukaryotic organisms , a cell's DNA is contained within a structure called the nucleus , which separates it from the rest of the interior of the cell . Filaments of a protein called actin are normally found outside the nucleus , where they help give the cell its overall shape and organiz...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	DNA damage induces nuclear actin filament assembly by Formin-2 and Spire-1/2 that promotes efficient DNA repair
Distinct microbial ecosystems have evolved to meet the challenges of indoor environments , shaping the microbial communities that interact most with modern human activities . Microbial transmission in food-processing facilities has an enormous impact on the qualities and healthfulness of foods , beneficially or detrime...	Many microbes—including bacteria and fungi—can affect the food and drink we consume , for better and for worse . Some spoil food , making it less tasty or even harmful to health . However , microbes can also be important ingredients: for example , yeast ferments malted barley sugars to make the alcohol and flavor of be...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "ecology", "microbiology", "and", "infectious", "disease" ]	2015	Mapping microbial ecosystems and spoilage-gene flow in breweries highlights patterns of contamination and resistance
Grasping requires translating object geometries into appropriate hand shapes . How the brain computes these transformations is currently unclear . We investigated three key areas of the macaque cortical grasping circuit with microelectrode arrays and found cooperative but anatomically separated visual and motor process...	In order to grasp and manipulate objects , our brains have to transform information about an object ( such as its size , shape and position ) into commands about movement that are sent to our hands . Previous work suggests that in primates ( including humans and monkeys ) , this transformation is coordinated in three k...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Object vision to hand action in macaque parietal, premotor, and motor cortices
Like other intracellular fusion events , the homotypic fusion of yeast vacuoles requires a Rab GTPase , a large Rab effector complex , SNARE proteins which can form a 4-helical bundle , and the SNARE disassembly chaperones Sec17p and Sec18p . In addition to these proteins , specific vacuole lipids are required for effi...	All cells are enclosed with a membrane that is made of phospholipid molecules , and many of the structures found inside cells—such as the vacuoles in plant and fungal cells—are also enclosed with a phospholipid membrane . To form a membrane , the phospholipid molecules—which have a phosphate head and two fatty acid tai...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2014	Membranes linked by trans-SNARE complexes require lipids prone to non-bilayer structure for progression to fusion
Conjugative transfer of the integrative and conjugative element ICEclc in Pseudomonas requires development of a transfer competence state in stationary phase , which arises only in 3–5% of individual cells . The mechanisms controlling this bistable switch between non-active and transfer competent cells have long remain...	Mobile DNA elements are pieces of genetic material that can jump from one bacterium to another , and even across species . They are often useful to their host , for example carrying genes that allow bacteria to resist antibiotics . One example of bacterial mobile DNA is the ICEclc element . Usually , ICEclc sits passiv...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]	2020	An analog to digital converter controls bistable transfer competence development of a widespread bacterial integrative and conjugative element
Before the outbreak that reached the Americas in 2015 , Zika virus ( ZIKV ) circulated in Asia and the Pacific: these past epidemics can be highly informative on the key parameters driving virus transmission , such as the basic reproduction number ( R0 ) . We compare two compartmental models with different mosquito rep...	Zika virus is an infectious disease primarily transmitted between people by mosquitoes . While most people develop mild flu-like symptoms , infection during pregnancy can interfere with how the baby’s head and brain develop . Until recently , the virus had only been seen sporadically in Africa and Asia , but since 2007...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2016	Structure in the variability of the basic reproductive number (R0) for Zika epidemics in the Pacific islands
The internal N6-methyladenosine ( m6A ) methylation of eukaryotic nuclear RNA controls post-transcriptional gene expression , which is regulated by methyltransferases ( writers ) , demethylases ( erasers ) , and m6A-binding proteins ( readers ) in cells . The YTH domain family proteins ( YTHDF1–3 ) bind to m6A-modified...	HIV infection is a global health challenge . The antiviral drugs that are currently available limit the ability of the virus to multiply in infected individuals , but they rarely eliminate the virus entirely . A better understanding of how HIV behaves in the cell would help researchers to find a cure for persistent HIV...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2016	N6-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression
Many studies are uncovering functional roles for long noncoding RNAs ( lncRNAs ) , yet few have been tested for in vivo relevance through genetic ablation in animal models . To investigate the functional relevance of lncRNAs in various physiological conditions , we have developed a collection of 18 lncRNA knockout stra...	The mammalian genome is comprised of DNA sequences that contain the templates for proteins , and other DNA sequences that do not code for proteins . The coding DNA sequences are transcribed to make messenger RNA molecules , which are then translated to make proteins . Researchers have known for many years that some of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2013	Multiple knockout mouse models reveal lincRNAs are required for life and brain development
Testosterone products are prescribed to males for a variety of possible health benefits , but causal effects are unclear . Evidence from randomized trials are difficult to obtain , particularly regarding effects on long-term or rare outcomes . Mendelian randomization analyses were performed to infer phenome-wide effect...	Men experience a gradual decline in their testosterone levels as they grow older . However , the effects of testosterone and the consequences of supplementation on the human body have been unclear . Scientists use so-called randomized controlled trials to establish cause-and-effect and to reduce bias . In these experim...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "genetics", "and", "genomics" ]	2020	Effects of lifelong testosterone exposure on health and disease using Mendelian randomization
Many plants attract and reward pollinators with floral scents and nectar , respectively , but these traits can also incur fitness costs as they also attract herbivores . This dilemma , common to most flowering plants , could be solved by not producing nectar and/or scent , thereby cheating pollinators . Both nectar and...	Flowering plants have evolved a number of different approaches to reproduction . Some use their own pollen and self-fertilize , while others use pollen from other nearby plants . This fertilization by other plants is called ‘outcrossing’ and introduces new genetic variation into each generation , which is extremely imp...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "ecology", "short", "report", "plant", "biology" ]	2015	How scent and nectar influence floral antagonists and mutualists
After the European colonization of the Americas , there was a dramatic population collapse of the Indigenous inhabitants caused in part by the introduction of new pathogens . Although there is much speculation on the etiology of the Colonial epidemics , direct evidence for the presence of specific viruses during the Co...	The arrival of European colonists to the Americas , beginning in the 15th century , contributed to the spread of new viruses amongst Indigenous people . This led to massive outbreaks of disease , and millions of deaths that caused an important Native population to collapse . The exact viruses that caused these outbreak...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]	2021	Ancient viral genomes reveal introduction of human pathogenic viruses into Mexico during the transatlantic slave trade
The process by which visual information is incorporated into the brain’s spatial framework to represent landmarks is poorly understood . Studies in humans and rodents suggest that retrosplenial cortex ( RSC ) plays a key role in these computations . We developed an RSC-dependent behavioral task in which head-fixed mice...	When moving through a city , people often use notable or familiar landmarks to help them navigate . Landmarks provide us with information about where we are and where we need to go next . But despite the ease with which we – and most other animals – use landmarks to find our way around , it remains unclear exactly how ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Representation of visual landmarks in retrosplenial cortex
Polyunsaturated fatty acids ( PUFAs ) in phospholipids affect the physical properties of membranes , but it is unclear which biological processes are influenced by their regulation . For example , the functions of membrane arachidonate that are independent of a precursor role for eicosanoid synthesis remain largely unk...	Membranes made of molecules called lipids surround every living cell and also form compartments inside the cell . There are hundreds of different lipid molecules that can be found in membranes . The amount of each type within the membrane can vary , which affects the flexibility and other physical properties of the mem...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2015	Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
Intermediate filament ( IF ) proteins , including nuclear lamins and cytoplasmic IF proteins , are essential cytoskeletal components of bilaterian cells . Despite their important role in protecting tissues against mechanical force , no cytoplasmic IF proteins have been convincingly identified in arthropods . Here we sh...	Different proteins exist to support the stability of animal cells . The intermediate filament proteins are an important example . One type – called lamins – stabilizes the nucleus ( the structure within an animal cell that stores most of its DNA ) , while another forms scaffold-like structures in the rest of cell . The...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology" ]	2016	Novel origin of lamin-derived cytoplasmic intermediate filaments in tardigrades
SUMO-modification of nuclear proteins has profound effects on gene expression . However , non-toxic chemical tools that modulate sumoylation in cells are lacking . Here , to identify small molecule sumoylation inhibitors we developed a cell-based screen that focused on the well-sumoylated substrate , human Liver Recept...	Proteins in cells carry out diverse tasks . One way in which this diversity is achieved by proteins is through the attachment of molecular tags . SUMO is one such tag that can reversibly attach to proteins and alter their activity . The modification of proteins by SUMO is known as sumoylation , and it regulates many pr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "tools", "and", "resources" ]	2015	A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver
We describe the computational design of proteins that bind the potent analgesic fentanyl . Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds , followed by design of the surrounding residues to optimize binding affinity . Co-crystal structures of the highest ...	Many small molecules , including toxins and some medicines , have flexible structures , which makes it difficult to detect and/or neutralize them . The pain medication fentanyl , for example , can rotate to adopt many shapes . In recent years , fentanyl drug abuse has become increasingly common , and the drug is often ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "computational", "and", "systems", "biology" ]	2017	Computational design of environmental sensors for the potent opioid fentanyl
Existing genetic methods of neuronal targeting do not routinely achieve the resolution required for mapping brain circuits . New approaches are thus necessary . Here , we introduce a method for refined neuronal targeting that can be applied iteratively . Restriction achieved at the first step can be further refined in ...	In humans – as well as flies and most other animals – the brain controls how we move and behave , and regulates heartbeat , breathing and other core processes . To perform these different roles , cells known as neurons form large networks that quickly carry messages around the brain and to other parts of the body . In ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2020	Cre-assisted fine-mapping of neural circuits using orthogonal split inteins
Direct lineage conversion of adult cells is a promising approach for regenerative medicine . A major challenge of lineage conversion is to generate specific cell subtypes . The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells , glucagon+ α-cells , and somatostatin+ δ-cells . ...	In mammals , the pancreas is responsible for controlling blood sugar by secreting insulin from specialized β-cells . Other cells in the pancreas , called δ-cells and α-cells , secrete other hormones to assist the β-cells . Diabetes is caused when this system breaks down: either the body attacks its own β-cells ( type I...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2014	In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes
Apoptosis is a prominent metazoan cell death form . Yet , mutations in apoptosis regulators cause only minor defects in vertebrate development , suggesting that another developmental cell death mechanism exists . While some non-apoptotic programs have been molecularly characterized , none appear to control developmenta...	Embryos make numerous new cells as they develop , but also destroy many cells to remove the faulty ones and to ensure that tissues grow to the right size and shape . This deliberate form of cell death must be precisely regulated to prevent too many cells or healthy cells , from being destroyed . Understanding the molec...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans
Engineered allosteric regulation of protein activity provides significant advantages for the development of robust and broadly applicable tools . However , the application of allosteric switches in optogenetics has been scarce and suffers from critical limitations . Here , we report an optogenetic approach that utilize...	Cells need to sense and respond to their environment . To do this , they have dedicated proteins that interpret outside signals and convert them into appropriate responses that are only active at a specific time and location within the cell . However , in many diseases , including cancer , these signaling proteins are ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology", "tools", "and", "resources" ]	2020	Light-regulated allosteric switch enables temporal and subcellular control of enzyme activity
Tryparedoxin peroxidases , distant relatives of glutathione peroxidase 4 in higher eukaryotes , are responsible for the detoxification of lipid-derived hydroperoxides in African trypanosomes . The lethal phenotype of procyclic Trypanosoma brucei that lack the enzymes fulfils all criteria defining a form of regulated ce...	Plants , animals and fungi all belong to a group of organisms known as eukaryotes . Their cells host a variety of compartments , with each having a specific role . For example , mitochondria are tasked with providing the energy that powers most of the processes that keep the cell alive . Membranes delimit these compart...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death
Hallmark social activities of humans , such as cooperation and cultural learning , involve eye-gaze signaling through joint attentional interaction and ostensive communication . The gaze-signaling and related cooperative-eye hypotheses posit that humans evolved unique external eye morphologies , including uniformly whi...	From an early age , we are able to detect the direction others are looking in ( known as eye-gaze ) and make eye contact with each other to communicate . The front of the human eye has a large white area known as the sclera that surrounds the darker colored iris and pupil in the center . Compared to us , chimpanzees an...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2022	Experimental evidence that uniformly white sclera enhances the visibility of eye-gaze direction in humans and chimpanzees
The Zika virus has emerged as a global public health concern . Its rapid geographic expansion is attributed to the success of Aedes mosquito vectors , but local epidemiological drivers are still poorly understood . Feira de Santana played a pivotal role in the Chikungunya epidemic in Brazil and was one of the first urb...	Mosquitoes can transmit viruses that cause Zika , dengue and several other tropical diseases that affect humans . Zika virus usually causes mild symptoms , but it is thought that infection during pregnancy can lead to brain abnormalities , including microcephaly , where babies are born with an abnormally small head . R...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2017	Epidemiological and ecological determinants of Zika virus transmission in an urban setting
Spiroplasma poulsonii is a maternally transmitted bacterial endosymbiont that is naturally associated with Drosophila melanogaster . S . poulsonii resides extracellularly in the hemolymph , where it must acquire metabolites to sustain proliferation . In this study , we find that Spiroplasma proliferation specifically d...	All animals host a large number of harmless microbes . Often the two partners involved in these interactions will depend on each other to thrive: microbes support important host functions and in return the host provides a safe place to live and a continuous supply of food . Many microbes that are intimately associated ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2014	Insect endosymbiont proliferation is limited by lipid availability
Discrete populations of brain cells signal heading direction , rather like a compass . These ‘head direction’ cells are largely confined to a closely-connected network of sites . We describe , for the first time , a population of head direction cells in nucleus reuniens of the thalamus in the freely-moving rat . This n...	Whether it is foraging for food or finding its way back to its nest , an animal often needs to know which direction it is heading in . Some neurons in a mammal’s brain have been shown to act like a compass , and send out nerve impulses whenever the animal points its head in a certain direction . For example , some of t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2014	Nucleus reuniens of the thalamus contains head direction cells
The activation of the dodecameric Ca2+/calmodulin dependent kinase II ( CaMKII ) holoenzyme is critical for memory formation . We now report that CaMKII has a remarkable property , which is that activation of the holoenzyme triggers the exchange of subunits between holoenzymes , including unactivated ones , enabling th...	How do fleeting signals passing through the neurons of our brains become memories that can last for years or even decades ? An enzyme called CaMKII is known to have an important role in the formation of memories . CaMKII adds phosphate groups to proteins—a process that is called phosphorylation—and is itself activated ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Activation-triggered subunit exchange between CaMKII holoenzymes facilitates the spread of kinase activity
At vertebrate neuromuscular junctions ( NMJs ) , the synaptic basal lamina contains different extracellular matrix ( ECM ) proteins and synaptogenic factors that induce and maintain synaptic specializations . Here , we report that podosome-like structures ( PLSs ) induced by ubiquitous ECM proteins regulate the formati...	Voluntary movement relies on skeletal muscle cells and nerve cells being able to communicate with one another . This communication occurs at a specialized region called the neuromuscular junction , or NMJ for short . These junctions are surrounded by a meshwork of proteins , known as the matrix , which structurally sup...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2020	Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs
Mesenchymal stem cells ( MSCs ) and osteolineage cells contribute to the hematopoietic stem cell ( HSC ) niche in the bone marrow of long bones . However , their developmental relationships remain unclear . In this study , we demonstrate that different MSC populations in the developing marrow of long bones have distinc...	During the earliest phases of development , the embryo is formed by groups of stem cells that can develop into all the different types of tissue in the body—from bones to brain tissue . Later in life , small stockpiles of adult stem cells are found in various tissues and provide a reservoir of new cells available for r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2014	The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function
Adipose tissue is a key determinant of whole body metabolism and energy homeostasis . Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective . Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the ...	The growing rates of obesity and related metabolic diseases are a major public health concern worldwide . People who are overweight or obese are at increased risk for a range of diseases including diabetes and heart disease , which may reduce their quality of life and shorten their lifespans . Obese people have more , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2014	Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network
Cell-type specification through differential genome regulation is a hallmark of complex multicellularity . However , it remains unclear how this process evolved during the transition from unicellular to multicellular organisms . To address this question , we investigated transcriptional dynamics in the ichthyosporean C...	All living animals are descended from a single-celled ancestor , and understanding how these ancestors became the first multicellular animals remains a major challenge in the field of evolutionary biology . An early breakthrough towards this goal was the realization that , even though they’re mostly single-celled organ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2015	Complex transcriptional regulation and independent evolution of fungal-like traits in a relative of animals
The medial subnucleus of the amygdala ( MeA ) plays a central role in processing sensory cues required for innate behaviors . However , whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown . Our previous studies revealed that the telencephalic preoptic area ( POA ...	Within the brain , a set of interconnected structures called the limbic system is involved in emotion , motivation and memory . This system – and in particular a structure called the medial amygdala – also contributes to behavioral drives that help an animal to survive and reproduce . These include the drive to avoid p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues
Since 2015 , the World Health Organisation ( WHO ) recommends immediate initiation of antiretroviral therapy ( ART ) for all HIV-positive patients . Epidemiological evidence points to important health benefits of immediate ART initiation; however , the policy’s impact on the economic aspects of patients' lives remains ...	Human immunodeficiency virus ( HIV ) is an incurable virus that attacks the immune system and affects around 39 million people worldwide . Once diagnosed , HIV can be treated with antiretroviral therapy ( ART ) to limit its effects and stop it spreading to other people . HIV rates vary across the world , but the Africa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "medicine" ]	2020	A stepped-wedge randomised trial on the impact of early ART initiation on HIV-patients’ economic outcomes in Eswatini
Microtubule dynamics and polarity stem from the polymerization of αβ-tubulin heterodimers . Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate α- and β-tubulin assembly into heterodimers and maintain the soluble tubulin pool in the cytoplasm , but their physical mechanisms are unknown . Here , we ...	Cells contain a network of protein filaments called microtubules . These filaments are involved in many biological processes; for example , they help cells keep the right shape , and they help to transport proteins and other materials inside cells . Two proteins called α-tubulin and β-tubulin are the building blocks of...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics
Sleep loss can severely impair the ability to perform , yet the ability to recover from sleep loss is not well understood . Sleep regulatory processes are assumed to lie exclusively within the brain mainly due to the strong behavioral manifestations of sleep . Whole-body knockout of the circadian clock gene Bmal1 in mi...	We spend nearly one third of our lives asleep . Sleep plays a critical role in human health and is regulated by multiple brain regions . Genes are some of the factors that control sleep . Recent studies have shown that mice in which a gene called Bmal1 had been completely removed , sleep more than mice that still have ...	[ "Abstract", "Introduction", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2017	Bmal1 function in skeletal muscle regulates sleep
Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum . How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood . In this study , we used transgenic mice expressing GFP in specific subsets of Purkin...	The human brain is essentially organised into modules made from groups of connected neurons . A part of the brain at the back of the head , called the cerebellum , is organised into particularly well-defined modules and is important for fine-tuning and learning new movements . However , it is not clear if the pattern o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Stereotyped spatial patterns of functional synaptic connectivity in the cerebellar cortex
The tumor suppressor protein Scribble ( SCRIB ) plays an evolutionary conserved role in cell polarity . Despite being central for its function , the molecular basis of SCRIB recruitment and stabilization at the cell cortex is poorly understood . Here we show that SCRIB binds directly to the CH1 domain of β spectrins , ...	Proteins found in cells often have more than one role . Scribble is one such multi-tasking protein that is found in a diverse range of species , including fruit flies and humans . Although Scribble commonly helps to ensure that the components of a cell are in their correct locations , its exact roles vary between speci...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "short", "report", "biochemistry", "and", "chemical", "biology" ]	2015	Spectrin binding motifs regulate Scribble cortical dynamics and polarity function
In the course of global climate change , Central Europe is experiencing more frequent and prolonged periods of drought . The drought years 2018 and 2019 affected European beeches ( Fagus sylvatica L . ) differently: even in the same stand , drought-damaged trees neighboured healthy trees , suggesting that the genotype ...	Climate change is having a serious impact on many ecosystems . In the summer of 2018 and 2019 , around two thirds of European beech trees were damaged or killed by extreme drought . It is critical to keep these beech woods healthy , as they are central to the survival of over 6 , 000 other species of animals and plants...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "genetics", "and", "genomics" ]	2021	Genomic basis for drought resistance in European beech forests threatened by climate change
The Drosophila embryo transiently exhibits a double-segment periodicity , defined by the expression of seven 'pair-rule' genes , each in a pattern of seven stripes . At gastrulation , interactions between the pair-rule genes lead to frequency doubling and the patterning of 14 parasegment boundaries . In contrast to ear...	The basic body plan of an animal is set up in the early embryo , where key developmental genes are expressed in specific patterns across the organism . These patterns emerge from the way in which the proteins encoded by these genes act to regulate each other’s expression . The fruit fly Drosophila is often used as a si...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "developmental", "biology", "computational", "and", "systems", "biology" ]	2016	Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network
Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model , which emphasizes the primacy of PDF-containing neurons , and a cell-autonomous model for circadian phase adjustment . We identify five different circadian ( E ) neurons that are a major...	Most animals have daily rhythms of activity: some are awake during the day and asleep at night , whilst others are more active at night , or during the twilight hours around dawn and dusk . These cycles of activity are driven by an internal body clock , which is reset in response to external cues , like light and tempe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	PDF neuron firing phase-shifts key circadian activity neurons in Drosophila
Continuous adaptation allows survival in an ever-changing world . Adjustments in the synaptic coupling strength between neurons are essential for this capability , setting us apart from simpler , hard-wired organisms . How these changes can be mathematically described at the phenomenological level , as so-called ‘plast...	Our brains are incredibly adaptive . Every day we form memories , acquire new knowledge or refine existing skills . This stands in contrast to our current computers , which typically can only perform pre-programmed actions . Our own ability to adapt is the result of a process called synaptic plasticity , in which the s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2021	Evolving interpretable plasticity for spiking networks
Synaptic currents display a large degree of heterogeneity of their temporal characteristics , but the functional role of such heterogeneities remains unknown . We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells ( UBCs ) , which generate intrinsic mossy fibers relaying vestibular inputs t...	Whether walking , riding a bicycle or simply standing still , we continually adjust our posture in small ways to prevent ourselves from falling . Our sense of balance depends on a set of structures inside the inner ear called the vestibular system . These structures detect movements of the head and relay this informati...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit
In the inner plexiform layer ( IPL ) of the mouse retina , ~70 neuronal subtypes organize their neurites into an intricate laminar structure that underlies visual processing . To find recognition proteins involved in lamination , we utilized microarray data from 13 subtypes to identify differentially-expressed extracel...	A nervous system comprises complex circuits of neurons connected by junctions called synapses . These connections need to develop in a highly specific manner , which means neurons need to be able to recognize one another and ‘figure out’ with which neighboring neuron or neurons they should form connections . Neurons do...	[ "Abstract", "Introduction", "Results", "Discussion", "Conclusions", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]	2015	An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina
Exchange of extracellular cystine for intracellular glutamate by the antiporter system xc− is implicated in numerous pathologies . Pharmacological agents that inhibit system xc− activity with high potency have long been sought , but have remained elusive . In this study , we report that the small molecule erastin is a ...	Sugars , fats , amino acids , and other nutrients cannot simply diffuse into the cell . Rather , they must be transported across the cell membrane by specific proteins that stretch from one side of the cell membrane to the other . One such ‘transporter’—system xc−—is of special interest . This transporter imports one m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis
LINE-1 ( L1 ) is an autonomous retrotransposon , which acted throughout mammalian evolution and keeps contributing to human genotypic diversity , genetic disease and cancer . L1 encodes two essential proteins: L1ORF1p , a unique RNA-binding protein , and L1ORF2p , an endonuclease and reverse transcriptase . L1ORF1p con...	Almost half of the human genome consists of DNA strings that have been copied and pasted from one part of the genome to another many thousands of times . These strings of DNA are called mobile genetic elements . Mobile elements can disrupt important genes , causing disease and cancer , but they can also drive evolution...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Human LINE-1 retrotransposition requires a metastable coiled coil and a positively charged N-terminus in L1ORF1p
Recent developments in detector hardware and image-processing software have revolutionized single particle cryo-electron microscopy ( cryoEM ) and led to a wave of near-atomic resolution ( typically ∼3 . 3 Å ) reconstructions . Reaching resolutions higher than 3 Å is a prerequisite for structure-based drug design and f...	Proteins perform many critical tasks within cells , and to do so , they must first fold into specific shapes . Being able to visualize these shapes can help scientists to understand how proteins work , and help them create drugs that can interact with the proteins to treat diseases . The past few years have seen the ra...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "structural", "biology", "and", "molecular", "biophysics" ]	2015	2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy
Identifying individuals who are at high risk of cancer due to inherited germline mutations is critical for effective implementation of personalized prevention strategies . Most existing models focus on a few specific syndromes; however , recent evidence from multi-gene panel testing shows that many syndromes are overla...	Genetic mutations that increase cancer risk can be passed down from parents to their children , which can affect families across many generations . In these families , multiple members may be affected by different types of cancer , and these cancers often develop at an early age . Unaffected family members are often re...	[ "Abstract", "Introduction", "Discussion" ]	[ "tools", "and", "resources", "genetics", "and", "genomics", "cancer", "biology" ]	2021	Multi-syndrome, multi-gene risk modeling for individuals with a family history of cancer with the novel R package PanelPRO
When spinal circuits generate rhythmic movements it is important that the neuronal activity remains within stable bounds to avoid saturation and to preserve responsiveness . Here , we simultaneously record from hundreds of neurons in lumbar spinal circuits of turtles and establish the neuronal fraction that operates wi...	Where and how are rhythmic movements , such as walking , produced ? Many neurons , primarily in the spinal cord , are responsible for the movements , but it is not known how the activity is distributed across this group of cells and what type of activity the neurons use . Some neurons produce regular patterns of “spiki...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Lognormal firing rate distribution reveals prominent fluctuation–driven regime in spinal motor networks
Inflammatory osteolysis is governed by exacerbated osteoclastogenesis . Ample evidence points to central role of NF-κB in such pathologic responses , yet the precise mechanisms underpinning specificity of these responses remain unclear . We propose that motifs of the scaffold protein IKKγ/NEMO partly facilitate such fu...	The human skeleton contains over 200 bones that together act as an internal framework for the body . Over our lifetime , the body constantly removes older bone tissue from the skeleton and replaces it with new bone tissue . This “bone remodeling” also controls how bones are repaired after being damaged by injuries , di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine" ]	2020	Inflammatory osteolysis is regulated by site-specific ISGylation of the scaffold protein NEMO
The prokaryotic tubulin homolog FtsZ polymerizes into protofilaments , which further assemble into higher-order structures at future division sites to form the Z-ring , a dynamic structure essential for bacterial cell division . The precise nature of interactions between FtsZ protofilaments that organize the Z-ring and...	New cells form when existing cells divide . When a cell divides it narrows at one point , which eventually allows it to split in two . This basic process of division happens in cells from all species , although they do not all use the same mechanisms to achieve it . In bacteria , a structure called the Z-ring guides wh...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Lateral interactions between protofilaments of the bacterial tubulin homolog FtsZ are essential for cell division
RNA interference defends against viral infection in plant and animal cells . The nematode Caenorhabditis elegans and its natural pathogen , the positive-strand RNA virus Orsay , have recently emerged as a new animal model of host-virus interaction . Using a genome-wide association study in C . elegans wild populations ...	Most organisms—from bacteria to mammals—have at least a rudimentary immune system that can detect and defend against pathogens , particularly viruses . This defense mechanism , which is known as the innate immune system , uses sensor proteins to recognize viral RNA , and then mobilizes other immune components to attack...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2013	A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity
Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions ( NMJs ) . Multiple mechanisms contribute to NMJ repair and maintenance; however muscle stem cells ( satellite cells , SCs ) , are deemed to have little impact on these processes . Therefore , the applicability of SC studies to attenuat...	New muscle fibers are made throughout our lives to replace those that have been damaged by normal wear and tear , and to meet new physical demands . These new muscle fibers develop from a pool of muscle stem cells . To create and maintain fully working muscles , nerve cells called motor neurons must also properly attac...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "cell", "biology" ]	2015	Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions
Opioids , agonists of µ-opioid receptors ( µORs ) , are the strongest pain killers clinically available . Their action includes a strong central component , which also causes important adverse effects . However , µORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful...	There are very few treatments available for people suffering from strong or long-lasting pain . Currently , substances called opioids – which include the well-known drug morphine – are the strongest painkillers . However , these drugs also cause harmful side effects , which makes them less useful . Like all drugs , opi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels
After an initial stage of local analysis within the retina and early visual pathways , the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects . The mechanisms underlying this perceptual organization process are only p...	When we look at an object , we perceive it as a whole . However , this is not how the brain processes objects . Instead , cells at early stages of the visual system respond selectively to single features of the object , such as edges . Moreover , each cell responds to its target feature in only a small region of space ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Serial grouping of 2D-image regions with object-based attention in humans
As the biodiversity crisis continues , we must redouble efforts to understand and curb pressures pushing species closer to extinction . One major driver is the unsustainable trade of wildlife . Trade in internationally regulated species gains the most research attention , but this only accounts for a minority of traded...	In the last few decades , exotic pets have become much more common . In the UK in 2008 , reptiles and amphibians were more popular than dogs , with over eight million in captivity . But while almost all pet cats and dogs are born and bred in captivity , exotic pets are often taken from the wild , putting species and th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2021	Gaps in global wildlife trade monitoring leave amphibians vulnerable
The intracellular iron transfer process is not well understood , and the identity of the iron transporter responsible for iron delivery to the secretory compartments remains elusive . In this study , we show Drosophila ZIP13 ( Slc39a13 ) , a presumed zinc importer , fulfills the iron effluxing role . Interfering with d...	Iron is essential for life . Amongst its many important roles , iron is crucial for producing collagen—the protein that provides both strength and elasticity to bones , tendons , ligaments , and skin . Like many other proteins , collagens are produced inside the endoplasmic reticulum—an organelle inside the cell that i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	The metal transporter ZIP13 supplies iron into the secretory pathway in Drosophila melanogaster
Using cryo-electron microscopy ( cryo-EM ) , we determined the structure of the Escherichia coli 70S ribosome with a global resolution of 2 . 0 Å . The maps reveal unambiguous positioning of protein and RNA residues , their detailed chemical interactions , and chemical modifications . Notable features include the first...	Inside cells , proteins are produced by complex molecular machines called ribosomes . Techniques that allow scientists to visualize ribosomes at the atomic level , such as cryogenic electron microscopy ( cryo-EM ) , help shed light on the structure of these molecular machines , revealing details of how they build prote...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2020	Structure of the bacterial ribosome at 2 Å resolution
The Turing reaction-diffusion model explains how identical cells can self-organize to form spatial patterns . It has been suggested that extracellular signaling molecules with different diffusion coefficients underlie this model , but the contribution of cell-autonomous signaling components is largely unknown . We deve...	Developing embryos initially consist of identical cells that specialize over time to create the different parts of the adult animal . More than sixty years ago , Alan Turing proposed that this spontaneous breaking of uniformity could be controlled by two molecules that interact with each other and move by diffusion at ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "developmental", "biology", "tools", "and", "resources" ]	2016	High-throughput mathematical analysis identifies Turing networks for patterning with equally diffusing signals
Despite anatomical similarities , there are differences in susceptibility to cardiovascular disease ( CVD ) between primates; humans are prone to myocardial ischemia , while chimpanzees are prone to myocardial fibrosis . Induced pluripotent stem cell-derived cardiomyocytes ( iPSC-CMs ) allow for direct inter-species co...	Understanding why some people get heart disease and others do not could help scientists find better ways to treat or prevent the condition . Genetics likely plays a role , and one way to identify genes that are important for heart health is to compare genes in humans and their closest evolutionary relatives , the chimp...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2019	A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees
G protein gated inward rectifier K+ ( GIRK ) channels open and thereby silence cellular electrical activity when inhibitory G protein coupled receptors ( GPCRs ) are stimulated . Here we describe an assay to measure neuronal GIRK2 activity as a function of membrane-anchored G protein concentration . Using this assay we...	Signals from outside of a cell can alter the activity inside the cell . This process often involves members of a large family of proteins called G protein-coupled receptors ( GPCRs ) that are found on the surface of many cells in the body . When these receptors are activated they release a G protein on the inside of th...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "Methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Cooperative regulation by G proteins and Na+ of neuronal GIRK2 K+ channels
The Alphaproteobacteria is an extraordinarily diverse and ancient group of bacteria . Previous attempts to infer its deep phylogeny have been plagued with methodological artefacts . To overcome this , we analyzed a dataset of 200 single-copy and conserved genes and employed diverse strategies to reduce compositional ar...	The Alphaproteobacteria form one of the most abundant groups of bacteria on Earth , and one that is closely linked to all complex forms of life . Many bacteria within this class live inside the cells of other organisms . For example , mitochondria – the powerhouses of animal , plant and other eukaryotic cells – evolved...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2019	An updated phylogeny of the Alphaproteobacteria reveals that the parasitic Rickettsiales and Holosporales have independent origins
Temporal continuity of object identity is a feature of natural visual input and is potentially exploited – in an unsupervised manner – by the ventral visual stream to build the neural representation in inferior temporal ( IT ) cortex . Here , we investigated whether plasticity of individual IT neurons underlies human c...	A bear is a bear , regardless of how far away it is , or the angle at which we view it . And indeed , the ability to recognize objects in different contexts is an important part of our sense of vision . A brain region called the inferior temporal ( IT for short ) cortex plays a critical role in this feat . In primates ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Unsupervised changes in core object recognition behavior are predicted by neural plasticity in inferior temporal cortex
How positional information instructs adult tissue maintenance is poorly understood . Planarians undergo whole-body regeneration and tissue turnover , providing a model for adult positional information studies . Genes encoding secreted and transmembrane components of multiple developmental pathways are predominantly exp...	Some animals can regrow tissues that have been amputated . A group of flatworms called planarians are often used as a model to study the regeneration process because they are able to restore any lost tissue or even an entire animal from tiny pieces of the body . For regeneration to be successful , it is important to en...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2016	Two FGFRL-Wnt circuits organize the planarian anteroposterior axis

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