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Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood . This study proposes a novel ‘ratio’ model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populat...	The human immunodeficiency virus ( HIV ) remains an ongoing global pandemic . There is currently no cure for HIV , but antiretroviral therapies can keep the virus in check and allow individuals with HIV to live longer , healthier lives . These drugs work in two ways . They block the ability of the virus to multiply and...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "microbiology", "and", "infectious", "disease" ]	2021	A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART
Synaptic transmission consists of fast and slow components of neurotransmitter release . Here we show that these components are mediated by distinct exocytic proteins . The Caenorhabditis elegans unc-13 gene is required for SV exocytosis , and encodes long and short isoforms ( UNC-13L and S ) . Fast release was mediate...	Neurons communicate with one another at junctions called synapses . When an electrical signal known as an action potential travels along a neuron and arrives at a synapse , the neuron releases a package of transmitter chemicals into the synapse . These chemicals then diffuse across the gap and bind to receptors on a se...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2013	UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans
Human organogenesis is when severe developmental abnormalities commonly originate . However , understanding this critical embryonic phase has relied upon inference from patient phenotypes and assumptions from in vitro stem cell models and non-human vertebrates . We report an integrated transcriptomic atlas of human org...	Individual organs and tissues form in human embryos during the first two months of pregnancy . Any errors during this crucial stage of human development can result in miscarriage or serious birth defects . Yet remarkably little is known about how this process works . What is known has been inferred from studies of how ...	[ "Abstract", "Introduction", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology", "tools", "and", "resources" ]	2016	An integrative transcriptomic atlas of organogenesis in human embryos
Bacterial mRNAs are organized into operons consisting of discrete open reading frames ( ORFs ) in a single polycistronic mRNA . Individual ORFs on the mRNA are differentially translated , with rates varying as much as 100-fold . The signals controlling differential translation are poorly understood . Our genome-wide mR...	Proteins make up much of the biological machinery inside cells and perform the essential tasks needed to keep each cell alive . Cells contain thousands of different proteins and the instructions needed to build each protein are encoded in genes . However , these instructions cannot be used directly to manufacture the p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "microbiology", "and", "infectious", "disease" ]	2017	Operon mRNAs are organized into ORF-centric structures that predict translation efficiency
The endoplasmic reticulum ( ER ) -localized Hsp70 chaperone BiP affects protein folding homeostasis and the response to ER stress . Reversible inactivating covalent modification of BiP is believed to contribute to the balance between chaperones and unfolded ER proteins , but the nature of this modification has so far b...	Newly made proteins are unstructured chains of amino acids that must fold into particular shapes to work effectively . Proteins that are destined to be exported from the cell undergo folding in a compartment of the cell called the endoplasmic reticulum . This folding is assisted by chaperones ( which are themselves als...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2015	AMPylation matches BiP activity to client protein load in the endoplasmic reticulum
Subcellular asymmetry directed by the planar cell polarity ( PCP ) signaling pathway orients numerous morphogenetic events in both invertebrates and vertebrates . Here , we describe a morphogenetic movement in which the intertwined socket and shaft cells of the Drosophila anterior wing margin mechanosensory bristles un...	Our right and left hands are mirror images of each other and cannot be precisely superimposed . This property , known as chirality , is vital for many tissues and organs to form correctly in humans and other animals . For example , fruit flies have hair-like sensory organs on the edges of their wings known as bristles ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2020	Prickle isoforms determine handedness of helical morphogenesis
Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease ( Dawidowicz 1987; Phillips et al . , 2009; Liu et al . , 2013 ) . In this study , we present an intriguing counter-example by demonstrating that in the center of the human...	Every cell is surrounded by a membrane made primarily of molecules called lipids . This membrane protects the cell and controls which molecules pass into and out of it . To keep the membrane in good working order , its lipids are regularly broken down and replaced with fresh molecules . However , some cells—such as the...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology" ]	2015	No turnover in lens lipids for the entire human lifespan
White adipose tissue ( WAT ) inflammation contributes to the development of insulin resistance in obesity . While the role of adipose tissue macrophage ( ATM ) pro-inflammatory signalling in the development of insulin resistance has been established , it is less clear how WAT inflammation is initiated . Here , we show ...	Although inflammation can be good for the body and help fight off infection , in certain cases it can also be harmful . When immune cells switch on at the wrong time , they can cause damage to cells and tissues . Fat tissue has its own population of immune cells called adipose tissue macrophages that remove dead fat ce...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2019	Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity
The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration . We have sequenced the genome allowing annotation of all key signaling pathways , transcription factors , and non-coding RNAs that will enhance ongoing functional studies . Pa...	The marine crustacean known as Parhyale hawaiensis is related to prawns , shrimps and crabs and is found at tropical coastlines around the world . This species has recently attracted scientific interest as a possible new model to study how animal embryos develop before birth and , because Parhyale can rapidly regrow lo...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "tools", "and", "resources", "genetics", "and", "genomics" ]	2016	The genome of the crustacean Parhyale hawaiensis, a model for animal development, regeneration, immunity and lignocellulose digestion
Genome-wide association studies have found variation within the complement factor H gene family links to host susceptibility to meningococcal disease caused by infection with Neisseria meningitidis ( Davila et al . , 2010 ) . Mechanistic insights have been challenging since variation within this locus is complex and bi...	Meningitis is a potentially life-threatening condition whereby the membranes that cover and protect the brain and spinal cord become inflamed . Often meningitis is caused by a viral or bacterial infection—such as infection by a bacterium called Neisseria meningitidis , also known as meningococcus . However , not everyo...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2014	Competition between antagonistic complement factors for a single protein on N. meningitidis rules disease susceptibility
Mucin 5AC ( MUC5AC ) is secreted by goblet cells of the respiratory tract and , surprisingly , also expressed de novo in mucus secreting cancer lines . siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line ( HT29-18N2 ) revealed new proteins , including a Ca2+-activated channel...	Goblet cells are specialized cells that produce proteins called mucins , which combine with water , salt and other proteins to form mucus , the slippery fluid that protects the respiratory and digestive tracts from bacteria , viruses and other pathogens . However , a defect in the production of one particular type of m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2013	TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells
Brief experiences while a memory is consolidated may capture the consolidation , perhaps producing a maladaptive memory , or may interrupt the consolidation . Since consolidation occurs during sleep , even fleeting experiences when animals are awakened may produce maladaptive long-term memory , or may interrupt consoli...	Throughout our waking lives we are exposed to a continuous stream of experiences . Some of these experiences trigger changes in the strength of connections between neurons in the brain and begin the process of forming memories . However , these initial memory traces are fragile and only a small number will become long-...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process
The biological players involved in angiogenesis are only partially defined . Here , we report that endothelial cells ( ECs ) express a novel isoform of the cell-surface adhesion molecule L1CAM , termed L1-ΔTM . The splicing factor NOVA2 , which binds directly to L1CAM pre-mRNA , is necessary and sufficient for the skip...	Growing tumors stimulate the formation of new blood vessels to supply the oxygen and nutrients the cancerous cells need to stay alive . Stopping tumors from forming the blood vessels could therefore help us to treat cancer . To do so , we need to understand how different proteins control when and how blood vessels deve...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2019	A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing
Aberrant activation of anaplastic lymphoma kinase ( ALK ) has been described in a range of human cancers , including non-small cell lung cancer and neuroblastoma ( Hallberg and Palmer , 2013 ) . Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand ( s ) is a critical issue . He...	Cells have receptor proteins on their surface that enable them to detect changes in their environment and communicate with other cells . Signal molecules bind to a segment of the receptor called the extracellular domain that faces out from the cell . This can result in the activation of another domain in the receptor t...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology" ]	2015	FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
In mammalian cells three closely related cavin proteins cooperate with the scaffolding protein caveolin to form membrane invaginations known as caveolae . Here we have developed a novel single-molecule fluorescence approach to directly observe interactions and stoichiometries in protein complexes from cell extracts and...	If you could look closely enough at the surface of some animal cells , especially fat or muscle cells , you would see that they are covered with pocket-like indents called ‘caveolae’ . These structures are thought to help the cells communicate with the outside world , but they can also be used by viruses to gain entry ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Single-molecule analysis reveals self assembly and nanoscale segregation of two distinct cavin subcomplexes on caveolae
The flexible control of sequential behavior is a fundamental aspect of speech , enabling endless reordering of a limited set of learned vocal elements ( syllables or words ) . Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that in...	Human speech and birdsong share numerous parallels . Both humans and birds learn their vocalizations during critical phases early in life , and both learn by imitating adults . Moreover , both humans and songbirds possess specific circuits in the brain that connect the forebrain to midbrain vocal centers . Humans can f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Songbirds can learn flexible contextual control over syllable sequencing
SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes . Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory , accompanied with loss of spines from distal dendrites of hippocampal CA1 p...	Neurons are the building blocks of the nervous system . These cells generally consist of a round portion called the cell body and a long cable-like axon . The cell body bears numerous branches called dendrites , which are in turn covered in spines . Neurons communicate with one another at junctions – or synapses – that...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2017	Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory
Supergene regions maintain alleles of multiple genes in tight linkage through suppressed recombination . Despite their importance in determining complex phenotypes , our empirical understanding of early supergene evolution is limited . Here we focus on the young ‘social’ supergene of fire ants , a powerful system for d...	Red fire ants ( Solenopsis invicta ) are native to South America , but the species has spread to North America , Australia and New Zealand where it can be an invasive pest . A reason for this species’ invasiveness types of colonies : one with a single egg-laying queen and another with several queens . However , it is n...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "evolutionary", "biology" ]	2020	Genomic architecture and evolutionary antagonism drive allelic expression bias in the social supergene of red fire ants
Septins are guanine nucleotide-binding proteins that polymerize into filamentous and higher-order structures . Cdc42 and its effector Gic1 are involved in septin recruitment , ring formation and dissociation . The regulatory mechanisms behind these processes are not well understood . Here , we have used electron micros...	Septins are proteins that provide structural support for cells as they divide . Yeast cells are known to have seven types of septins , which have been widely studied , and 13 different septins have been identified in human cells , although they all seem similar to those found in yeast . Mutations in the genes that carr...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	The role of Cdc42 and Gic1 in the regulation of septin filament formation and dissociation
Signal propagation from the cell membrane to a promoter can induce gene expression . To examine signal transmission through sub-cellular compartments and its effect on transcription levels in individual cells within a population , we used the Wnt/β-catenin signaling pathway as a model system . Wnt signaling orchestrate...	Cells in an animal’s body must communicate with one another to coordinate many processes that are essential to life . One way that cells do this is by releasing molecules that bind to receptors located on the surface of others cells; this binding then triggers a signaling pathway in the receiving cell that passes infor...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2016	Quantifying β-catenin subcellular dynamics and cyclin D1 mRNA transcription during Wnt signaling in single living cells
Acute Myeloid Leukemia ( AML ) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective white blood cell differentiation . Its pathogenesis comprises subversion of transcriptional regulation , through mutation and by hijacking normal chromatin regulation . Kat2a is a histone acetylt...	Less than 30% of patients with acute myeloid leukaemia – an aggressive cancer of the white blood cells – survive five years post-diagnosis . This disease disrupts the maturation of white blood cells , resulting in the accumulation of immature cells that multiply and survive but are incapable of completing their maturat...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cancer", "biology" ]	2020	Loss of Kat2a enhances transcriptional noise and depletes acute myeloid leukemia stem-like cells
Many developing neurons transition through a multi-polar state with many competing neurites before assuming a unipolar state with one axon and multiple dendrites . Hallmarks of the multi-polar state are large fluctuations in microtubule-based transport into and outgrowth of different neurites , although what drives the...	Nerve cells ( also known as neurons ) connect with each other to form complex networks through which signals are carried around the body . Signals are received by branch-like projections called dendrites , pass through the cell body and then pass along a long projection called the axon before being transmitted to the d...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation
The characterization of prostate epithelial hierarchy and lineage heterogeneity is critical to understand its regenerative properties and malignancies . Here , we report that the transcription factor RUNX1 marks a specific subpopulation of proximal luminal cells ( PLCs ) , enriched in the periurethral region of the dev...	The prostate is part of the reproductive organs in male mammals . Many of the cells lining the inside of the prostate – known as ‘luminal cells’ – need hormones to survive . Certain treatments for prostate cancer , including surgical and chemical castration , lead to fewer hormones reaching the prostate , which shrinks...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology" ]	2020	RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development
Mitochondrial dysfunction is associated with a spectrum of human disorders , ranging from rare , inborn errors of metabolism to common , age-associated diseases such as neurodegeneration . How these lesions give rise to diverse pathology is not well understood , partly because their proximal consequences have not been ...	Mitochondria are found within virtually all of our body’s cells and are best known as their power plants . Damaged mitochondria cause many diseases in humans – from rare , inherited metabolic disorders that cause symptoms including muscle weakness and developmental problems , to age-related diseases such as diabetes an...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2016	Mitochondrial dysfunction remodels one-carbon metabolism in human cells
Most neurogenesis in the mammalian brain is completed embryonically , but in certain areas the production of neurons continues throughout postnatal life . The functional properties of mature postnatally generated neurons often match those of their embryonically produced counterparts . However , we show here that in the...	Most of your brain cells were born before you were . But in mammals , including humans , some of these brain cells , also known as nerve cells or neurons , are created after birth . These later-generated neurons are often extremely similar to their counterparts produced in the womb , and also seem to perform a similar ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron
Fundamental gaps remain in our understanding of how immunity to malaria develops . We used detailed clinical and entomological data from parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic P . falciparum as a function of age an...	Malaria kills around 500 , 000 children every year . The disease occurs when an infected mosquito bites a human and passes on a Plasmodium parasite . One parasite in particular , Plasmodium falciparum , is responsible for most malaria-related deaths across the globe . A person can be infected by P . falciparum many tim...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2018	Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure
There is great interest in understanding human olfactory experience from a principled and quantitative standpoint . The comparison is often made to color vision , where a solid framework with a three-dimensional perceptual space enabled a rigorous search for the underlying neural pathways , and the technological develo...	Scientists are interested in the number of colors , sounds and smells we can distinguish because this information can shed light onto how our brains process these senses both in health and disease . It is relatively straightforward to determine how many colors we can see or sounds we can hear because these stimuli are ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2015	On the dimensionality of odor space
People who inject drugs ( PWID ) account for some of the most explosive human immunodeficiency virus ( HIV ) and hepatitis C virus ( HCV ) epidemics globally . While individual drivers of infection are well understood , less is known about network factors , with minimal data beyond direct ties . 2512 PWID in New Delhi ...	Understanding the social and spatial relationships that connect people is a key element to stop the spread of infectious diseases . These networks are particularly relevant to combat epidemics among populations that are hard to reach with public health interventions . Network-based approaches , for example , can help t...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "epidemiology", "and", "global", "health", "medicine" ]	2021	Role of direct and indirect social and spatial ties in the diffusion of HIV and HCV among people who inject drugs: a cross-sectional community-based network analysis in New Delhi, India
Photoreceptors are the most numerous and metabolically demanding cells in the retina . Their primary nutrient source is the choriocapillaris , and both the choriocapillaris and photoreceptors require trophic and functional support from retinal pigment epithelium ( RPE ) cells . Defects in RPE , photoreceptors , and the...	Cells use a sugar called glucose as fuel to provide energy for many essential processes . The light-sensing cells in the eye , known as photoreceptors , need tremendous amounts of glucose , which they receive from the blood with the help of neighboring cells called retinal pigment epithelium ( RPE ) cells . Without a r...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2016	Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration
Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity . This symptom results from accumulation of porphyrins , tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light , in the skin of affected individuals . Here we report tha...	Porphyrias are rare diseases that involve ring-shaped molecules called porphyrins accumulating in various parts of the body . Porphyrins are produced as part of the normal process that makes an important molecule called heme , which is required to transport oxygen . However , high levels of porphyrins can be toxic . Fo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2016	Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias
The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes . We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems . Bioinformatics analysis revealed that sulfhydrated cysteines are part of...	Proteins play essential roles in almost every aspect of a cell’s life , and also contribute to the structure and function of body tissues and organs . Cells and tissues adapt to their continuously changing environments by regulating the activity of their proteins . For example , proteins that are not fully active immed...	[ "Abstract", "Introduction", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2015	Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response
Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains . Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition ( HI ) assay . Here , we exte...	Every year , seasonal influenza , commonly called flu , infects up to one in five people around the world , and causes up to half a million deaths . Even though the human immune system can detect and destroy the virus that causes influenza , people can catch flu many times throughout their lifetimes because the virus k...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2014	Integrating influenza antigenic dynamics with molecular evolution
The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans , where it is important in driving cell fate and directing differentiation of various cell types . However , we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian developme...	We start life as a single cell , which immediately begins to divide to form an embryo that will eventually contain all the different kinds of cells found in the adult body . During the first few rounds of cell division , embryonic cells can become any type of adult cells , but also form the placenta , the organ that su...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2019	Transitions in cell potency during early mouse development are driven by Notch
Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations , and use this structural flexibility to bind specifically to multiple partners . However , we lack an understanding of how an interface can select some ligands , but not others . Here , we present a molecular dynamics approach to identi...	Many proteins need to interact with other proteins to carry out their various tasks in cells . Such interactions are essential for almost all biological processes and are often disrupted in disease . Cells have thousands of different types of proteins and each has a unique shape that determines which other proteins it ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems", "computational", "and", "systems", "biology" ]	2017	Probing protein flexibility reveals a mechanism for selective promiscuity
Gene expression noise is an evolvable property of biological systems that describes differences in expression among genetically identical cells in the same environment . Prior work has shown that expression noise is heritable and can be shaped by selection , but the impact of variation in expression noise on organismal...	Single-celled organisms that reproduce by dividing , like yeast , can create whole populations of genetically identical cells . However , some differences will exist among such cells , even when they have all experienced the same environment . These differences are known as “noise” . By definition , noise is not caused...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2018	Fitness effects of altering gene expression noise in Saccharomyces cerevisiae
Suction is widely used by animals for strong controllable underwater adhesion but is less well understood than adhesion of terrestrial climbing animals . Here we investigate the attachment of aquatic insect larvae ( Blephariceridae ) , which cling to rocks in torrential streams using the only known muscle-actuated suct...	Suction cups are widely used to attach objects to surfaces in bathrooms and kitchens . They work well on tiles and other smooth surfaces , but do not stick well to rougher materials like brick or wood because they are unable to form an air-tight seal . Researchers have been searching for ways to improve these cups by s...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "physics", "of", "living", "systems" ]	2021	Extreme suction attachment performance from specialised insects living in mountain streams (Diptera: Blephariceridae)
The extensive use of mollusc shell as a versatile raw material is testament to its importance in prehistoric times . The consistent choice of certain species for different purposes , including the making of ornaments , is a direct representation of how humans viewed and exploited their environment . The necessary taxon...	Just like people do today , prehistoric humans liked to adorn themselves with beautiful objects . Shells , from creatures like clams and snails , were used to decorate clothing or worn as jewelry at least as far back as 100 , 000 years ago . Later people used shells as the raw materials to make beads or bracelets . Lea...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Methods" ]	[ "evolutionary", "biology", "biochemistry", "and", "chemical", "biology" ]	2019	'Palaeoshellomics’ reveals the use of freshwater mother-of-pearl in prehistory
Neurons in sensory cortex are tuned to diverse features in natural scenes . But what determines which features neurons become selective to ? Here we explore the idea that neuronal selectivity is optimized to represent features in the recent sensory past that best predict immediate future inputs . We tested this hypothe...	A large part of our brain is devoted to processing the sensory inputs that we receive from the world . This allows us to tell , for example , whether we are looking at a cat or a dog , and if we are hearing a bark or a meow . Neurons in the sensory cortex respond to these stimuli by generating spikes of activity . With...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Sensory cortex is optimized for prediction of future input
Concentrative nucleoside transporters ( CNTs ) are responsible for cellular entry of nucleosides , which serve as precursors to nucleic acids and act as signaling molecules . CNTs also play a crucial role in the uptake of nucleoside-derived drugs , including anticancer and antiviral agents . Understanding how CNTs reco...	DNA molecules are made from four bases—often named ‘G’ , ‘A’ , ‘C’ , and ‘T’—that are arranged along a backbone made of sugars and phosphate groups . Chemicals called nucleosides are essentially the same as these four building blocks of DNA ( and other similar molecules ) but without the phosphate groups . Proteins cal...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters
Any organism faces sensory and cognitive limitations which may result in maladaptive decisions . Such limitations are prominent in the context of groups where the relevant information at the individual level may not coincide with collective requirements . Here , we study the navigational decisions exhibited by Paratrec...	Ants forage to find food and bring it back to the colony . If they come across food items that are too large or heavy for a single individual to carry , some species are able to form teams to cooperatively carry these items to the nest . This collective navigation process hinges on the navigational abilities of the ind...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "computational", "and", "systems", "biology" ]	2016	A locally-blazed ant trail achieves efficient collective navigation despite limited information
Categorization has been associated with distributed networks of the primate brain , including the prefrontal cortex ( PFC ) and posterior parietal cortex ( PPC ) . Although category-selective spiking in PFC and PPC has been established , the frequency-dependent dynamic interactions of frontoparietal networks are largel...	A brain that could store only exact experiences would bog us down with details . We have instead evolved to be able to detect the common elements in different experiences and group them into meaningful categories . This imbues the world with meaning . We can recognize and respond appropriately to objects , situations a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Synchronous beta rhythms of frontoparietal networks support only behaviorally relevant representations
Adequate responses to noxious stimuli causing tissue damages are essential for organismal survival . Class IV neurons in Drosophila larvae are polymodal nociceptors responsible for thermal , mechanical , and light sensation . Importantly , activation of Class IV provoked distinct avoidance behaviors , depending on the ...	Animals often need to get away quickly from dangers in their environment , such as temperatures that are hot enough to damage their tissues . As such , an animal’s brain often encodes automatic ‘avoidance responses’ to signs of danger , which help the animal move away from harm . The nervous system of a fruit fly larva...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Neuronal processing of noxious thermal stimuli mediated by dendritic Ca2+ influx in Drosophila somatosensory neurons
The first point of our body’s contact with tactile stimuli ( innocuous and noxious ) is the epidermis , the outermost layer of skin that is largely composed of keratinocytes . Here , we sought to define the role that keratinocytes play in touch sensation in vivo and ex vivo . We show that optogenetic inhibition of kera...	The skin is the largest sensory organ of the body , and the first point of contact with the outside world . Whether it is being pinched or caressed , the skin’s sense of touch informs organisms about their surroundings and allows them to react appropriately . Nerve cells present in the skin capture information about to...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling
Mutualism is of fundamental importance in ecosystems . Which factors help to keep the relationship mutually beneficial and evolutionarily successful is a central question . We addressed this issue for one of the most significant mutualistic interactions on Earth , which associates plants of the leguminosae family and h...	Rhizobia are soil bacteria that are able to form a symbiotic relationship with legumes – plants that include peas , beans and lentils . The bacteria move into cells in the roots of the plant and cause new organs called nodules to form . Inside the nodules the bacteria multiply before being released to the soil again . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2017	Spatio-temporal control of mutualism in legumes helps spread symbiotic nitrogen fixation
Understanding how patterning influences cell behaviors to generate three dimensional morphologies is a central goal of developmental biology . Additionally , comparing these regulatory mechanisms among morphologically diverse tissues allows for rigorous testing of evolutionary hypotheses . Zebrafish skin is endowed wit...	Hair , feathers or scales cover the skin of most land animals . Despite their apparent diversity , these appendages share many features: they are mainly formed of the protein keratin , are produced by the topmost layer of the skin and they start to form with skin cells moving inwards to form a pit . Across species , th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2018	Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development
Neurons recorded in behaving animals often do not discernibly respond to sensory input and are not overtly task-modulated . These non-classically responsive neurons are difficult to interpret and are typically neglected from analysis , confounding attempts to connect neural activity to perception and behavior . Here , ...	Neurons encode information in the form of electrical signals called spikes . Certain neurons increase the rate at which they produce spikes under specific circumstances , e . g . , whenever an animal hears a particular sound . These neurons are said to be 'classically responsive' . But not all neurons behave in this wa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2019	Spike-timing-dependent ensemble encoding by non-classically responsive cortical neurons
Neurogenesis in Drosophila occurs in two phases , embryonic and post-embryonic , in which the same set of neuroblasts give rise to the distinct larval and adult nervous systems , respectively . Here , we identified the embryonic neuroblast origin of the adult neuronal lineages in the ventral nervous system via lineage-...	Fruit flies undergo a process called metamorphosis in which they change from a maggot or larva into an adult fly . These two life stages look and behave differently and appear to have strikingly different nervous systems . The relationship between the two nervous systems has been most extensively studied in the ventral...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2016	Lineage mapping identifies molecular and architectural similarities between the larval and adult Drosophila central nervous system
The gene regulatory network ( GRN ) is the central decision‐making module of the cell . We have developed a theory called Buffered Qualitative Stability ( BQS ) based on the hypothesis that GRNs are organised so that they remain robust in the face of unpredictable environmental and evolutionary changes . BQS makes stro...	The genomes of living organisms consist of thousands of genes , which produce proteins that perform many essential functions . Cells receive signals from both their internal and external environments , and respond by changing how they express their genes . This allows a cell to make the right amount of different protei...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2014	Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks
Many animal species , including insects , are capable of acoustic duetting , a complex social behavior in which males and females tightly control the rate and timing of their courtship song syllables relative to each other . The mechanisms underlying duetting remain largely unknown across model systems . Most studies o...	When performing a duet , human singers listen to each other and also use other cues like tapping and nodding to keep in time . Duets are also found in the courtship rituals of some animals , but unlike human duetters—who tend to sing at the same time—the male and female animals take turns singing back and forth in quic...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Acoustic duetting in Drosophila virilis relies on the integration of auditory and tactile signals
Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity , but it is unclear whether this precision is shared at presynaptic terminals . Presynaptic homeostatic plasticity ( PHP ) stabilizes neurotransmission at the Drosophila neuromuscular junction , where a retrograde enhanc...	Everything we think and do is the result of communication between neurons . This communication takes place at junctions called synapses . When two nerve cells or neurons communicate at a synapse , the output terminal of the first cell releases a chemical called a neurotransmitter . This binds to receiver proteins , or ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation
Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers , but their mechanism of action has remained structurally uncharacterized . Here , we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA difH , representin...	Similar to humans , bacteria store their genetic material in the form of DNA and arrange it into structures called chromosomes . In fact , most bacteria have a single circular chromosome . Bacteria multiply by simply dividing in two , and before that happens they must replicate their DNA so that each of the newly forme...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]	2016	Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending
How cancer cells globally struggle with a chemotherapeutic insult before succumbing to apoptosis is largely unknown . Here we use an integrated systems-level examination of transcription , translation , and proteolysis to understand these events central to cancer treatment . As a model we study myeloma cells exposed to...	Many cancer treatments work by causing cancer cells to enter an advanced stage of a process known as programmed cell death or apoptosis . When a cell begins apoptosis , it takes a series of metabolic steps–such as fragmenting its DNA or reducing its volume–that eventually kills it . The cancer cells in tumours are able...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2013	Global cellular response to chemotherapy-induced apoptosis
Adolescents are especially prone to drug addiction , but the underlying biological basis of their increased vulnerability remains unknown . We reveal that translational control by phosphorylation of the translation initiation factor eIF2α ( p-eIF2α ) accounts for adolescent hypersensitivity to cocaine . In adolescent (...	Drug addiction a is major mental health problem that presents a huge financial , social and legal burden worldwide . Adolescents are notoriously prone to drug abuse and addicts typically begin using drugs at a young age . However , an explanation for why young people are particularly vulnerable to the effects of addict...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine
Mechanoelectrical transduction by hair cells commences with hair-bundle deflection , which is postulated to tense filamentous tip links connected to transduction channels . Because direct mechanical stimulation of tip links has not been experimentally possible , this hypothesis has not been tested . We have engineered ...	In animals with backbones , the inner ear is responsible for both hearing and balance . Sound waves and head movements apply a mechanical force to hair cells inside the inner ear . This causes the cells to produce electrical signals that ultimately communicate information about the sound or movement to the brain . The ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "physics", "of", "living", "systems", "neuroscience" ]	2016	Direct mechanical stimulation of tip links in hair cells through DNA tethers
Small molecule inhibitors of site-specific O-glycosylation by the polypeptide N-acetylgalactosaminyltransferase ( ppGalNAc-T ) family are currently unavailable but hold promise as therapeutics , especially if selective against individual ppGalNAc-T isozymes . To identify a compound targeting the ppGalNAc-T3 isozyme , w...	Complex cascades of interactions between different molecules regulate every process in the body . Enzymes are critical for this , because they act as ‘catalysts’ to speed up chemical reactions in a cell . Each type of enzyme has a specific role . The enzyme ppGalNAc-T3 , for example , attaches sugar molecules onto cert...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "cell", "biology", "cancer", "biology" ]	2017	Inhibitor of ppGalNAc-T3-mediated O-glycosylation blocks cancer cell invasiveness and lowers FGF23 levels
G-quadruplexes ( G4 ) are extremely stable secondary structures forming stacks of guanine tetrads . DNA G4 structures have been extensively studied , however , less is known about G4 motifs in mRNAs , especially in their coding sequences . Herein , we show that Aven stimulates the mRNA translation of the mixed lineage ...	To make a protein , the DNA sequence that encodes it is first copied to make a molecule of messenger RNA ( or mRNA for short ) . The mRNA is then used as a set of instructions to assemble a protein in a process called translation . Both DNA and RNA molecules can fold into particular shapes . One such structure is known...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2015	Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes
The flat Golgi cisterna is a highly conserved feature of eukaryotic cells , but how is this morphology achieved and is it related to its function in cargo sorting and export ? A physical model of cisterna morphology led us to propose that sphingomyelin ( SM ) metabolism at the trans-Golgi membranes in mammalian cells e...	The Golgi complex is a hub inside cells that transports many proteins to various parts of the cell . It also receives freshly made proteins and modifies them to help them mature into their final active forms . The complex is made up of a stack of disc-like membrane structures called cisternae . Are the shapes of the ci...	[ "Abstract", "Introduction", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2017	Sphingomyelin metabolism controls the shape and function of the Golgi cisternae
Voltage-dependent Ca2+ channels ( Cavs ) are indispensable for coupling action potentials with Ca2+ signaling in living organisms . The structure of Cavs is similar to that of voltage-dependent Na+ channels ( Navs ) . It is known that prokaryotic Navs can obtain Ca2+ selectivity by negative charge mutations of the sele...	Electrical signals in the brain and muscles allow animals – including humans – to think , make memories and move around . Cells generate these signals by enabling charged particles known as ions to pass through the physical barrier that surrounds all cells , the cell membrane , at certain times and in certain locations...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2020	A native prokaryotic voltage-dependent calcium channel with a novel selectivity filter sequence
The amylase gene ( AMY ) , which codes for a starch-digesting enzyme in animals , underwent several gene copy number gains in humans ( Perry et al . , 2007 ) , dogs ( Axelsson et al . , 2013 ) , and mice ( Schibler et al . , 1982 ) , possibly along with increased starch consumption during the evolution of these species...	Many mammals can digest starch by using an enzyme called amylase , but different species eat different amounts of starchy foods . Amylase is released by the pancreas , and in certain species such as humans , it is also created by the glands that produce saliva , allowing the enzyme to be present in the mouth . There , ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "genetics", "and", "genomics" ]	2019	Independent amylase gene copy number bursts correlate with dietary preferences in mammals
Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish . How these circuits operate together to generate the various swimming movements during development remains to be clarified . In this study , we iteratively built models of developing zebrafish spinal circuits coupled t...	The spinal cord is a column of nerve tissue that connects the brain to the rest of the body in vertebrate animals . Nerve cells in the spinal cord , called neurons , help to control and coordinate the body’s movements . As the spinal cord develops , new neurons are born and new connections are made between neurons and ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Modeling spinal locomotor circuits for movements in developing zebrafish
hIAPP fibrils are associated with Type-II Diabetes , but the link of hIAPP structure to islet cell death remains elusive . Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells , leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP . U...	In Type-II Diabetes , an individual’s cells fail to respond correctly to the hormone insulin , leaving them unable to counteract high levels of sugar in the blood . Another hormone , human islet amyloid polypeptide ( hIAPP ) , works with insulin to regulate blood sugar levels . hIAPP is an amyloid protein , which means...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2017	Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity
Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells , the cells lining the interior of blood vessels . Expansion of vascular networks arises through sprouting angiogenesis , a process involving extensive cell rearrangements and collective cel...	When a new blood vessel is created , a leader cell branches out from the lining of an existing vessel before being joined by other cells moving together in the same direction . A protein called Wnt5a regulates this process by helping the cells to orient themselves and finely coordinating their migration , but the exact...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2019	Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration
Co-opting the cellular machinery for protein production is a compulsory requirement for viruses . The Cricket Paralysis Virus employs an Internal Ribosomal Entry Site ( CrPV-IRES ) to express its structural genes in the late stage of infection . Ribosome hijacking is achieved by a sophisticated use of molecular mimicry...	Viruses cannot replicate themselves , but instead depend on components of the host cell for their own survival . Once a virus successfully enters a cell , it must use part of the cell’s machinery – specifically the ribosomes – to produce its own proteins . Ribosomes normally make the cell’s proteins by reading instruct...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Dual tRNA mimicry in the Cricket Paralysis Virus IRES uncovers an unexpected similarity with the Hepatitis C Virus IRES
In budding yeast , a single cenH3 ( Cse4 ) nucleosome occupies the ∼120-bp functional centromere , however conflicting structural models for the particle have been proposed . To resolve this controversy , we have applied H4S47C-anchored cleavage mapping , which reveals the precise position of histone H4 in every nucleo...	DNA is tightly packaged in cells for a variety of reasons—to allow it to fit inside the nucleus , to protect it from damage , and to help control the production of proteins from genes . The basic unit of packaged DNA is called a nucleosome , which consists of DNA wrapped around a structure formed by two pairs of four d...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2014	The budding yeast Centromere DNA Element II wraps a stable Cse4 hemisome in either orientation in vivo
In the early days of HIV treatment , drug resistance occurred rapidly and predictably in all patients , but under modern treatments , resistance arises slowly , if at all . The probability of resistance should be controlled by the rate of generation of resistance mutations . If many adaptive mutations arise simultaneou...	In the early days of HIV therapy , the strains of the virus that infected patients frequently evolved drug resistance and the therapies would often eventually fail . These treatments generally involved using a single anti-viral drug . Nowadays , better therapies involving combinations of several anti-viral drugs are av...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2016	More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1
Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain ( PD ) that promotes virulence by detecting the macrophage phagosome . PhoQ activity is repressed by divalent cations and induced in environments of acidic pH , limited divalent cations , and cationic antimicrobial peptides ( CAMP ) . Previously , i...	Salmonella bacteria cause illnesses in humans , such as food poisoning and typhoid fever . In response to a Salmonella infection , immune cells known as macrophages detect and engulf the bacteria . The conditions inside the macrophage ( which include an acidic pH and high levels of antimicrobial molecules ) can destroy...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2015	Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence
The membrane-bound transcription factor ATF6α is activated by proteolysis during endoplasmic reticulum ( ER ) stress . ATF6α target genes encode foldases , chaperones , and lipid biosynthesis enzymes that increase protein-folding capacity in response to demand . The off-state of ATF6α is maintained by its spatial separ...	Newly made proteins must be folded into specific three-dimensional shapes before they can perform their roles in cells . Many proteins are folded in a cell compartment called the endoplasmic reticulum . The cell closely monitors the quality of the work done by this compartment . If the endoplasmic reticulum has more pr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Ceapins inhibit ATF6α signaling by selectively preventing transport of ATF6α to the Golgi apparatus during ER stress
Fossils were thought to lack original organic molecules , but chemical analyses show that some can survive . Dinosaur bone has been proposed to preserve collagen , osteocytes , and blood vessels . However , proteins and labile lipids are diagenetically unstable , and bone is a porous open system , allowing microbial/mo...	The chances of establishing a real-world Jurassic Park are slim . During the fossilization process , biological tissues degrade over millions of years , with some types of molecules breaking down faster than others . However , traces of biological material have been found inside some fossils . While some researchers be...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Cretaceous dinosaur bone contains recent organic material and provides an environment conducive to microbial communities
Generative models , such as predictive coding , posit that perception results from a combination of sensory input and prior prediction , each weighted by its precision ( inverse variance ) , with incongruence between these termed prediction error ( deviation from prediction ) or surprise ( negative log probability of t...	Our perception of the world is not only based on input from our senses . Instead , what we perceive is also heavily altered by the context of what is being sensed and our expectations about it . Some researchers have suggested that perception results from combining information from our senses and our predictions . This...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Neural signatures of perceptual inference
Cephalopods have evolved nervous systems that parallel the complexity of mammalian brains in terms of neuronal numbers and richness in behavioral output . How the cephalopod brain develops has only been described at the morphological level , and it remains unclear where the progenitor cells are located and what molecul...	Octopuses have evolved incredibly large and complex nervous systems that allow them to perform impressive behaviors , like plan ahead , navigate and solve puzzles . The nervous system of the common octopus ( also known as Octopus vulgaris ) contains over half a billion nerves cells called neurons , similar to the numbe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2021	Identification of neural progenitor cells and their progeny reveals long distance migration in the developing octopus brain
Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory . Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging . Here , we explicitly tested this assumption in two independent large test datasets ( UK Bio...	Scientists who study the brain and aging are keen to find an effective way to measure brain health , which could help identify people at risk for dementia or memory problems . One popular marker is ‘brain age’ . This measurement uses a brain scan to estimate a person’s chronological age , then compares the estimated br...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change
Ribosome biogenesis is a complex and energy-demanding process requiring tight coordination of ribosomal RNA ( rRNA ) and ribosomal protein ( RP ) production . Given the extremely high level of RP synthesis in rapidly growing cells , alteration of any step in the ribosome assembly process may impact growth by leading to...	When yeast cells are growing at top speed , they can make 2 , 000 new ribosomes every minute . These enormous molecular assemblies are the protein-making machines of the cell . Building new ribosomes is one of the most energy-demanding parts of cell growth and , if the process goes wrong , the results can be catastroph...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2019	A ribosome assembly stress response regulates transcription to maintain proteome homeostasis
Current models successfully describe the auditory cortical response to natural sounds with a set of spectro-temporal features . However , these models have hardly been linked to the ill-understood neurobiological changes that occur in the aging auditory cortex . Modelling the hemodynamic response to a rich natural soun...	It can often be difficult for an older person to understand what someone is saying , particularly in noisy environments . Exactly how and why this age-related change occurs is not clear , but it is thought that older individuals may become less able to tune in to certain features of sound . Newer tools are making it ea...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Temporal selectivity declines in the aging human auditory cortex
During cortical synaptic development , thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections . How thalamocortical synapses are formed and maintained in this competitive environment is unknown . Here , we show that astrocyte-secreted protein hevin is requ...	The central nervous system—which is made up of the brain and spinal cord—processes information from all over the body . The information travels through cells called neurons , which connect to each other at junctions called synapses . A single neuron can receive information from many different places because it is cover...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2014	Astrocytes refine cortical connectivity at dendritic spines
Exposure to stress increases the risk of developing mood disorders . While a subset of individuals displays vulnerability to stress , others remain resilient , but the molecular basis for these behavioral differences is not well understood . Using a model of chronic social defeat stress , we identified region-specific ...	High levels of stress do not have the same effect on everybody: some individuals can show resilience and recover quickly , while other struggle to cope . Scientists have started to investigate how these differences may find their origin in biological processes , mainly by focusing on the role of neurons . However , neu...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "research", "communication", "neuroscience" ]	2019	Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice
GPCRs regulate all aspects of human physiology , and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands . Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations . To address this deficit , we gene...	Almost every aspect of the human body – from our senses to our moods – depends , in one way or another , on a large family of proteins called G-protein-coupled receptors . These receptor proteins , known as GPCRs for short , detect signals from outside the cell and trigger activity within the cell . This allows cells t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2017	Ligand modulation of sidechain dynamics in a wild-type human GPCR
Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin . We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability . We created mutant viruses that incorporate most of the ≈104 amino-ac...	Influenza is a major threat to human health largely because the flu virus evolves rapidly to escape recognition by the immune system . These ongoing changes also explain why flu vaccines become less effective over time and need to be reformulated every year . Hemagglutinin is a protein on the surface of the flu virus t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2014	The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin
We previously discovered histones bound to cytosolic lipid droplets ( LDs ) ; here we show that this forms a cellular antibacterial defense system . Sequestered on droplets under normal conditions , in the presence of bacterial lipopolysaccharide ( LPS ) or lipoteichoic acid ( LTA ) , histones are released from the dro...	Histones are proteins found in large numbers in most animal cells , where their primary job is to help DNA strands fold into compact and robust structures inside the nucleus . In vitro , histones are very effective at killing bacteria , and there is some evidence that histones secreted from cells provide protection aga...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2012	A novel role for lipid droplets in the organismal antibacterial response
When unperturbed , somatic stem cells are poised to affect immediate tissue restoration upon trauma . Yet , little is known regarding the mechanistic basis controlling initial and homeostatic ‘scaling’ of stem cell pool sizes relative to their target tissues for effective regeneration . Here , we show that TEAD1-expres...	Skeletal muscles are primarily composed of cells called muscle fibers , which attach to bones via tendons . These muscle fibers contract to help move the body . Muscle also contains a population of muscle stem cells that repair injured tissue . Normally , in adult skeletal muscle , these stems cells are in a resting st...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2016	Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency
Eukaryotic genomes are organized dynamically through the repositioning of nucleosomes . Isw2 is an enzyme that has been previously defined as a genome-wide , nonspecific nucleosome spacing factor . Here , we show that Isw2 instead acts as an obligately targeted nucleosome remodeler in vivo through physical interactions...	DNA encodes the genetic instructions for life in a long , flexible molecular chain that is packaged up neatly to fit inside cells . Short sections of DNA are wound around proteins to form bundles called nucleosomes , and then spun into chromatin fibres , a more compact form of DNA . While nucleosomes are a fundamental ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]	2021	Basis of specificity for a conserved and promiscuous chromatin remodeling protein
Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex ( MHC ) class I-specific chaperone . We sought to determine whether , like tapasin , TAPBPR can also influence MHC class I peptide...	Our immune system protects us from infections and destroys cells that are turning cancerous . A group of proteins called MHC class I molecules are essential for this protection . These molecules let the immune system know what is going on inside our cells by displaying chopped up fragments of proteins ( or peptides ) o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2015	TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst
Ammonium serves as key nitrogen source and metabolic intermediate , yet excess causes toxicity . Ammonium uptake is mediated by ammonium transporters , whose regulation is poorly understood . While transport can easily be characterized in heterologous systems , measuring transporter activity in vivo remains challenging...	Ammonium provides a vital source of nitrogen for bacteria , fungi and plants , and is produced by animals as a waste product of metabolism . High levels of ammonium can be toxic , so all organisms need to control their uptake or excretion of this substance . Ammonium transporters , which are highly conserved from bacte...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "cell", "biology" ]	2013	Fluorescent sensors reporting the activity of ammonium transceptors in live cells
Proper kinetochore-microtubule attachments , mediated by the NDC80 complex , are required for error-free chromosome segregation . Erroneous attachments are corrected by the tension dependence of kinetochore-microtubule interactions . Here , we present a method , based on fluorescence lifetime imaging microscopy and För...	When a cell divides , each new cell that forms needs to contain a complete set of DNA , which is stored in structures called chromosomes . So first , the chromosomes duplicate , and the two copies are held together . A protein structure known as a kinetochore then forms on each copy of the chromosome . The kinetochores...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	Measuring NDC80 binding reveals the molecular basis of tension-dependent kinetochore-microtubule attachments
Cell fate determination during development often requires morphogen transport from producing to distant responding cells . Hedgehog ( Hh ) morphogens present a challenge to this concept , as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells . While ...	Each cell in a developing embryo receives information that determines what type of body structure it will form . In fruit flies , this information is partly given by a protein called Hedgehog . In the embryo cells that receive it , Hedgehog can trigger a series of events which activate certain genes and thereby regulat...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2018	Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
PP2A-B56 is a serine/threonine phosphatase complex that regulates several major mitotic processes , including sister chromatid cohesion , kinetochore-microtubule attachment and the spindle assembly checkpoint . We show here that these key functions are divided between different B56 isoforms that localise to either the ...	The cells in our body are a hive of activity , but that activity must be kept under control . This is never more critical than when a cell divides , because unchecked cell division can lead to cancer . Fortunately , enzymes called kinases and phosphatases exist to control the countless proteins in a cell; these enzymes...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2019	Division of labour between PP2A-B56 isoforms at the centromere and kinetochore
Visual perception across a broad range of light levels is shaped by interactions between rod- and cone-mediated signals . Because responses of retinal ganglion cells , the output cells of the retina , depend on signals from both rod and cone photoreceptors , interactions occurring in retinal circuits provide an opportu...	The inner surface at the back of the eye is called the retina and contains two types of light-sensitive cells: rod cells and cone cells . Rods outnumber cones by roughly twenty to one and are responsible for vision under low light levels . Cone cells , by contrast , provide detailed vision in bright light , as well as ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	A simple retinal mechanism contributes to perceptual interactions between rod- and cone-mediated responses in primates
Ecological variation influences the appearance and maintenance of tool use in animals , either due to necessity or opportunity , but little is known about the relative importance of these two factors . Here , we combined long-term behavioural data on feeding and travelling with six years of field experiments in a wild ...	There is currently much debate about the origins of animal culture , including why some animals have acquired the ability to use tools . Ecological problems often lead to the innovation of new tools . For example , a particular desirable food item may not be reachable without using a tool , or environmental conditions ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "ecology" ]	2016	Travel fosters tool use in wild chimpanzees
Gene copy number alterations , tumor cell stemness , and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer ( HGSOC ) recurrence . Stem phenotypes involving Wnt-β-catenin , aldehyde dehydrogenase activities , intrinsic platinum resistance , and tumorsphere formation are h...	Ovarian cancer is one of the deadliest types of cancer in women . There are two main reasons for the aggressiveness of this cancer . First , ovarian cancer cells can spread to other parts of a woman’s body before she has been diagnosed , where the cells grow as tiny clumps or spheres of tumor cells , also called tumors...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2019	FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy
Learning about temporal structure is adaptive because it enables the generation of expectations . We examined how the brain uses experience in structured environments to anticipate upcoming events . During fMRI ( functional magnetic resonance imaging ) , individuals watched a 90 s movie clip six times . Using a hidden ...	Anticipating future events is essential . It allows individuals to plan and prepare what they will do seconds , minutes , or hours in the future . But how the brain can predict future events in both the short-term and long-term is not yet clear . Researchers know that the brain processes images or other sensory informa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Anticipation of temporally structured events in the brain
As we navigate through the world , eye and head movements add rotational velocity patterns to the retinal image . When such rotations accompany observer translation , the rotational velocity patterns must be discounted to accurately perceive heading . The conventional view holds that this computation requires efference...	When strolling along a path beside a busy street , we can look around without losing our stride . The things we see change as we walk forward , and our view also changes if we turn our head—for example , to look at a passing car . Nevertheless , we can still tell that we are walking in a straight-line because our brain...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Role of visual and non-visual cues in constructing a rotation-invariant representation of heading in parietal cortex
Intermediate filaments ( IF ) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology , motility , and signal transduction . Dysregulation of IFs causes a wide range of human diseases , including skin disorders , cardiomyopathies , lipodystrophy , and neuropathy . Despite this pa...	Like the body's skeleton , the cytoskeleton gives shape and structure to the inside of a cell . Yet , unlike a skeleton , the cytoskeleton is ever changing . The cytoskeleton consists of many fibers each made from chains of protein molecules . One of these proteins is called vimentin and it forms intermediate filaments...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton
Drosophila has helped us understand the genetic mechanisms of pattern formation . Particularly useful have been those organs in which different cell identities and polarities are displayed cell by cell in the cuticle and epidermis ( Lawrence , 1992; Bejsovec and Wieschaus , 1993; Freeman , 1997 ) . Here we use the patt...	Fly larvae grow in an unusual way . Most embryos grow by increasing the number of cells in the embryo , but fly larvae grow by increasing the size of their cells . The epidermal cells in the growing larvae secrete a hard skin or cuticle that is renewed three times as they grow . This cuticle is decorated with teeth cal...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2014	Plasticity of both planar cell polarity and cell identity during the development of Drosophila
RET can be activated in cis or trans by its co-receptors and ligands in vitro , but the physiological roles of trans signaling are unclear . Rapidly adapting ( RA ) mechanoreceptors in dorsal root ganglia ( DRGs ) express Ret and the co-receptor Gfrα2 and depend on Ret for survival and central projection growth . Here ...	During development , cells send and receive numerous signaling molecules . In order to trigger a biological response , such signaling molecules must first bind to a specific receptor protein , often located on the cell surface . These receptor proteins can either work alone or with partner proteins called co-receptors ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2015	Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors
Electron microscopy-based connectomics aims to comprehensively map synaptic connections in neural tissue . However , current approaches are limited in their capacity to directly assign molecular identities to neurons . Here , we use serial multiplex immunogold labeling ( siGOLD ) and serial-section transmission electro...	In the nervous system , cells called neurons connect to each other to form large “neural” networks . The most powerful method that is currently available for tracing neurons and mapping the connections between them is called electron microscopy . This requires slicing brain tissue into ultrathin sections , which are th...	[ "Abstract", "Introduction", "Results", "Discussion", "M" ]	[ "neuroscience" ]	2015	A serial multiplex immunogold labeling method for identifying peptidergic neurons in connectomes
Malate and lactate dehydrogenases ( MDH and LDH ) are homologous , core metabolic enzymes that share a fold and catalytic mechanism yet possess strict specificity for their substrates . In the Apicomplexa , convergent evolution of an unusual LDH from MDH produced a difference in specificity exceeding 12 orders of magni...	How are new genes created ? Most of the mutations in the genome of an organism place the organism at some sort of disadvantage , but a small number confer an advantage . The beneficial changes are usually retained by subsequent generations and can ultimately lead to the creation of new genes . An example is the gene th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases
The development of outgrowths from plant shoots depends on formation of epidermal sites of cell polarity convergence with high intracellular auxin at their centre . A parsimonious model for generation of convergence sites is that cell polarity for the auxin transporter PIN1 orients up auxin gradients , as this spontane...	Plants , unlike animals , are able to grow and develop throughout their lives . New leaves and flowers are made from outgrowths that constantly form at the tip of growing shoots . Groups of cells in the outer layer of the shoot tip arrange a protein called PIN1 so that it is more abundant on the cell surfaces that face...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2016	Formation of polarity convergences underlying shoot outgrowths
Calcium ions ( Ca2+ ) are essential for many cellular signaling mechanisms and enter the cytosol mostly through voltage-gated calcium channels . Here , using high-speed Ca2+ imaging up to 20 kHz in the rat layer five pyramidal neuron axon we found that activity-dependent intracellular calcium concentration ( [Ca2+]i ) ...	Nerve cells communicate using tiny electrical impulses called action potentials . Special proteins termed ion channels produce these electric signals by allowing specific charged particles , or ions , to pass in or out of cells across its membrane . When a nerve cell ‘fires’ an action potential , specific ion channels ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling
Parasitic helminths infect over a billion humans . To survive in the low oxygen environment of their hosts , these parasites use unusual anaerobic metabolism — this requires rhodoquinone ( RQ ) , an electron carrier that is made by very few animal species . Crucially RQ is not made or used by any parasitic hosts and RQ...	Parasitic worms infect more than a billion people worldwide , using a range of tricks to survive inside the human body . Some species can live for weeks inside the gut , a place with almost no oxygen . Yet exactly how they manage this is remains unclear . Scientists know that parasitic worms have an unusual way of maki...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway
Hematopoietic stem cells ( HSCs ) must ensure adequate blood cell production following distinct external stressors . A comprehensive understanding of in vivo heterogeneity and specificity of HSC responses to external stimuli is currently lacking . We performed single-cell RNA sequencing ( scRNA-Seq ) on functionally va...	Most organs in the human body are maintained by a type of immature cells known as adult stem cells , which ensure a constant supply of new , mature cells . Adult stem cells monitor their environment through external signalling molecules and replace damaged cells as needed . Stem cell therapy takes advantage of the rege...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2021	External signals regulate continuous transcriptional states in hematopoietic stem cells
In vitro selection of antibodies allows to obtain highly functional binders , rapidly and at lower cost . Here , we describe the first fully synthetic phage display library of humanized llama single domain antibody ( NaLi-H1: Nanobody Library Humanized 1 ) . Based on a humanized synthetic single domain antibody ( hs2dA...	Antibodies are proteins that form part of an animal’s immune system and can identify and help eradicate infections . These proteins are also needed at many stages in biological research and represent one of the most promising tools in medical applications , from diagnostics to treatments . Traditionally , antibodies ha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "tools", "and", "resources", "immunology", "and", "inflammation" ]	2016	NaLi-H1: A universal synthetic library of humanized nanobodies providing highly functional antibodies and intrabodies

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