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Myopathies decrease muscle functionality . Mutations in ryanodine receptor 1 ( RyR1 ) are often associated with myopathies with microscopic core-like structures in the muscle fiber . In this study , we identify a mouse RyR1 model in which heterozygous animals display clinical and pathological hallmarks of myopathy with...	Skeletal muscle covers our skeleton and allows us to move around . One disorder that leads to weakness in skeletal muscle—known as central core disease—can leave affected infants ‘floppy’ and delay the development of motor skills such as sitting , crawling , and walking . While no cure or treatment currently exists for...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Potassium dependent rescue of a myopathy with core-like structures in mouse
The extracellular matrix ( ECM ) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis . Here , we show that the Endoplasmic Reticulum ( ER ) -resident protein anterior gradient-2 ( AGR2 ) , a soluble protein-disulf...	Cancer cells multiply abnormally fast and therefore produce protein molecules faster than normal cells . To avoid becoming stressed by this overproduction , cancer cells make use of proteins that fold the new proteins inside the cell . One of these protein folders is called anterior gradient-2 ( or AGR2 for short ) and...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2016	Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties
Neurofibromatosis type 1 ( NF1 ) is an autosomal dominant disorder whose neurodevelopmental symptoms include impaired executive function , attention , and spatial learning and could be due to perturbed mesolimbic dopaminergic circuitry . However , these circuits have never been directly assayed in vivo . We employed th...	About one in 3 , 500 people have a genetic disorder called neurofibromatosis type 1 , often shortened to NF1 , making it one of the most common inherited diseases . People with NF1 may have benign and cancerous tumors throughout the body , learning disabilities , developmental delays , curvature of the spine and bone a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Optical dopamine monitoring with dLight1 reveals mesolimbic phenotypes in a mouse model of neurofibromatosis type 1
G-quadruplexes ( G4 ) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro , but the sequence and structural features dictating their formation and function in vivo remains uncertain . Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence . We isolated...	Molecules of DNA encode the information needed to build cells and keep them alive . DNA is made of two strands that contain several different chemical groups known as bases arranged in different orders , like letters and words in a phrase . Generally , two DNA strands wrap around each other to make a three dimensional ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]	2017	Non-Canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae
Previous studies of laboratory strains of budding yeast had shown that when gene copy number is altered experimentally , RNA levels generally scale accordingly . This is true when the copy number of individual genes or entire chromosomes is altered . In a recent study , Hose et al . ( 2015 ) reported that this tight co...	DNA inside cells is packaged into structures called chromosomes . Different species can have different numbers of chromosomes , but when any cell divides it must allocate the right number of chromosomes to each new cell . If this process goes wrong , cells end up with too many or too few chromosomes . The presence of e...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2016	No current evidence for widespread dosage compensation in S. cerevisiae
Actin-related protein 2/3 ( Arp2/3 ) complex activation by nucleation promoting factors ( NPFs ) such as WASP , plays an important role in many actin-mediated cellular processes . In yeast , Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission . Here we used genetics and q...	Actin is one of the most abundant proteins in yeast , mammalian and other eukaryotic cells . It assembles into long chains known as filaments that the cell uses to generate forces for various purposes . For example , actin filaments are needed to pull part of the membrane surrounding the cell inwards to bring molecules...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2017	Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo
To survive challenging environments , animals acquired the ability to evaluate food quality in the intestine and respond to nutrient deficiencies with changes in food-response behavior , metabolism and development . However , the regulatory mechanisms underlying intestinal sensing of specific nutrients , especially mic...	Animals are able to sense changes in the quality of their diet , which allows them to adapt to environments where the availability of nutrients fluctuates . For example , if a food lacks essential nutrients , or contains toxic molecules , animals can avoid it . If food is scarce , they can alter their metabolism to com...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2017	A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth
Eukaryotic genes generate multiple RNA transcript isoforms though alternative transcription , splicing , and polyadenylation . However , the relationship between human transcript diversity and protein production is complex as each isoform can be translated differently . We fractionated a polysome profile and reconstruc...	To produce a protein , a gene’s DNA is first copied to make molecules of messenger RNA ( mRNA ) . The mRNAs pass through a molecular machine known as the ribosome , which translates the genetic code to make a protein . Not all of an mRNA is translated to make a protein; the “untranslated” regions play crucial roles in ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "computational", "and", "systems", "biology" ]	2016	Tunable protein synthesis by transcript isoforms in human cells
We introduce an Interaction- and Trade-off-based Eco-Evolutionary Model ( ITEEM ) , in which species are competing in a well-mixed system , and their evolution in interaction trait space is subject to a life-history trade-off between replication rate and competitive ability . We demonstrate that the shape of the trade-...	A patch of rain forest , a coral reef , a pond , and the microbes in our guts are all examples of biological communities . More generally , a community is a group of organisms that live together at the same place and time . Many communities are composed of a large number of different species , and this diversity is mai...	[ "Abstract", "Introduction", "Model", "Results", "Discussion" ]	[ "ecology", "computational", "and", "systems", "biology" ]	2018	Trade-off shapes diversity in eco-evolutionary dynamics
Prp3 is an essential U4/U6 di-snRNP-associated protein whose functions and molecular mechanisms in pre-mRNA splicing are presently poorly understood . We show by structural and biochemical analyses that Prp3 contains a bipartite U4/U6 di-snRNA-binding region comprising an expanded ferredoxin-like fold , which recognize...	Proteins are built following instructions contained within the DNA of gene sequences . This genetic information is copied into short-lived molecules , called messenger RNAs ( or mRNAs ) , which move away from the DNA and are then decoded by the molecular machines that build proteins . However , mRNA sequences often hav...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	A composite double-/single-stranded RNA-binding region in protein Prp3 supports tri-snRNP stability and splicing
Mutations , deletions , and changes in copy number of mitochondrial DNA ( mtDNA ) , are observed throughout cancers . Here , we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project . We observe a tendency for some cancers , especially of the bladder , breast , and kidney ...	Within each cell of your body lie hundreds or thousands of mitochondria . These structures are perhaps best known for making energy , but mitochondria also play roles in processes like the immune response and cell signaling . However , in the mutant cells that form cancerous tumors , these roles can be subverted and al...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "cancer", "biology" ]	2016	Mitochondrial DNA copy number variation across human cancers
We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life . In particular , we analyze the shape of telomere length distributions underlying stem cell behavior within individuals . Our mathematical model shows that these distributions contain a fingerprint of the progr...	Human cells die off regularly due to normal wear and tear , aging or injury . To replace these cells , humans maintain pockets of tissue specific stem cells that can develop into one of several different types of specialized cell . For example , stem cells in the bone marrow can develop into red blood cells , white blo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "computational", "and", "systems", "biology" ]	2015	Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions
Colorectal cancer ( CRC ) is a major cause of human death . Mortality is primarily due to metastatic organ colonization , with the liver being the main organ affected . We modeled metastatic CRC ( mCRC ) liver colonization using patient-derived primary and metastatic tumor xenografts ( PDX ) . Such PDX modeling predict...	Colorectal cancer , also known as bowel cancer , is the second most deadly cancer in the United States , where it affects over 140 , 000 people each year . This cancer often spreads to the liver , in a process known as metastasis . To do this , the colorectal cancer cells must survive the low oxygen levels found in the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2019	PCK1 and DHODH drive colorectal cancer liver metastatic colonization and hypoxic growth by promoting nucleotide synthesis
The biotrophic fungus Ustilago maydis causes smut disease in maize with characteristic tumor formation and anthocyanin induction . Here , we show that anthocyanin biosynthesis is induced by the virulence promoting secreted effector protein Tin2 . Tin2 protein functions inside plant cells where it interacts with maize p...	The production of agricultural crop plants is severely hindered by bacteria , viruses , and fungi that have developed their own strategies to colonize these plants and obtain nutrients from them . Some pathogens kill the plants they colonize , but ‘biotrophic pathogens’ employ sophisticated strategies to manipulate the...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "microbiology", "and", "infectious", "disease" ]	2014	A secreted Ustilago maydis effector promotes virulence by targeting anthocyanin biosynthesis in maize
The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors . While clonal selection in response to particular antigens has been studied in detail , it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire . Here , using mathematical m...	The human immune system develops a memory of pathogens that it encounters over its lifetime , allowing it to respond quickly to future infections . It does this partly through T cells , white blood cells that can recognize different pathogens . During an infection , the T cells that recognize the specific pathogen atta...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "physics", "of", "living", "systems", "immunology", "and", "inflammation" ]	2020	Early life imprints the hierarchy of T cell clone sizes
Stable mutualism between a host and its resident bacteria requires a moderated immune response to control bacterial population size without eliciting excessive inflammation that could harm both partners . Little is known about the specific molecular mechanisms utilized by bacterial mutualists to temper their hosts’ res...	Animals , including humans , harbor vast numbers of bacteria inside our digestive tracts . But rather than wage constant war , we have learned to coexist peacefully , and many of these bacteria are important to keep us healthy . Our immune system controls the number of bacteria , but in some diseases , this balance fai...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]	2018	A bacterial immunomodulatory protein with lipocalin-like domains facilitates host–bacteria mutualism in larval zebrafish
Caenorhabditis elegans is a powerful model for studying gene regulation , as it has a compact genome and a wealth of genomic tools . However , identification of regulatory elements has been limited , as DNA-binding motifs are known for only 71 of the estimated 763 sequence-specific transcription factors ( TFs ) . To ad...	Many scientists use ‘model’ species—such as the fruit fly or a nematode worm called Caenorhabditis elegans—in their research because these organisms have useful features that make it easier to carry out many experiments . For example , C . elegans has a smaller genome compared to many other animals , which is useful fo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]	2015	Mapping and analysis of Caenorhabditis elegans transcription factor sequence specificities
Purified microtubules have been shown to align along the static magnetic field ( SMF ) in vitro because of their diamagnetic anisotropy . However , whether mitotic spindle in mammalian cells can be aligned by magnetic field has not been experimentally proved . In particular , the biological effects of SMF of above 20 T...	Nowadays , a number of methods can be used to ‘look’ inside the body to investigate potential health problems . One of these is a technique called magnetic resonance imaging ( MRI ) that uses magnetic fields that are several hundred times stronger than a fridge magnet ( or over 10 , 000 times stronger than the Earth’s ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "physics", "of", "living", "systems" ]	2017	27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells
Pyomyositis is a severe bacterial infection of skeletal muscle , commonly affecting children in tropical regions , predominantly caused by Staphylococcus aureus . To understand the contribution of bacterial genomic factors to pyomyositis , we conducted a genome-wide association study of S . aureus cultured from 101 chi...	Certain bacteria that normally live on the skin or in the nose without causing problems can sometimes lead to diseases elsewhere in the body . For example , the bacterium Staphylococcus aureus can cause blood infections or a severe and painful infection of the muscle called pyomyositis , which is very common in childre...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]	2019	Panton–Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS
The mechanisms that regulate growth and size of the regenerating limb in tetrapods such as the Mexican axolotl are unknown . Upon the completion of the developmental stages of regeneration , when the regenerative organ known as the blastema completes patterning and differentiation , the limb regenerate is proportionall...	Humans’ ability to regrow lost or damaged body parts is relatively limited , but some animals , such as the axolotl ( a Mexican salamander ) , can regenerate complex body parts , like legs , many times over their lives . Studying regeneration in these animals could help researchers enhance humans’ abilities to heal . O...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology" ]	2021	Neural control of growth and size in the axolotl limb regenerate
CRISPR adaptation immunizes bacteria and archaea against viruses . During adaptation , the Cas1-Cas2 complex integrates fragments of invader DNA as spacers in the CRISPR array . Recently , an additional protein Cas4 has been implicated in selection and processing of prespacer substrates for Cas1-Cas2 , although this me...	Many people have now heard of CRISPR , or CRISPR-Cas9 , as a gene editing technology . Yet CRISPR evolved in bacteria to protect them against viral infections . While parts of the CRISPR system are now being widely used , the research community still does not know everything about how the system operates in its natural...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2019	The Cas4-Cas1-Cas2 complex mediates precise prespacer processing during CRISPR adaptation
Human standing balance relies on self-motion estimates that are used by the nervous system to detect unexpected movements and enable corrective responses and adaptations in control . These estimates must accommodate for inherent delays in sensory and motor pathways . Here , we used a robotic system to simulate human st...	When standing , neurons in the brain send signals to skeletal muscles so we can adjust our movements to stay upright based on the requirements from the surrounding environment . The long nerves needed to connect our brain , muscles and sensors lead to considerable time delays ( up to 160 milliseconds ) between sensing ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	Learning to stand with unexpected sensorimotor delays
Vertebrate centrioles normally propagate through duplication , but in the absence of preexisting centrioles , de novo synthesis can occur . Consistently , centriole formation is thought to strictly rely on self-assembly , involving self-oligomerization of the centriolar protein SAS-6 . Here , through reconstitution of ...	Cells pass on their characteristics or “traits” to new generations in the form of DNA molecules . DNA provides the instructions to make proteins , which may then assemble into larger structures without using any external templates in a process called self-assembly . However , when a cell divides , DNA is not the only e...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "cell", "biology" ]	2015	De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly
Anaerobic thermophiles inhabit relic environments that resemble the early Earth . However , the lineage of these modern organisms co-evolved with our planet . Hence , these organisms carry both ancestral and acquired genes and serve as models to reconstruct early metabolism . Based on comparative genomic and proteomic ...	Life may have arisen on our planet as far back as four billion years ago . Unlike today , the Earth’s atmosphere at the time had no oxygen and an abundance of volcanic emissions including hydrogen , carbon dioxide and sulfur gases . These dramatic differences have led scientists to wonder: how did the ancient microorga...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "microbiology", "and", "infectious", "disease" ]	2017	Insight into the evolution of microbial metabolism from the deep-branching bacterium, Thermovibrio ammonificans
Naive B cells co-express two BCR isotypes , IgM and IgD , with identical antigen-binding domains but distinct constant regions . IgM but not IgD is downregulated on autoreactive B cells . Because these isotypes are presumed to be redundant , it is unknown how this could impose tolerance . We introduced the Nur77-eGFP r...	To defend an organism against invaders such as viruses and bacteria , cells of the immune system need to recognize and respond to foreign microbes . However , these immune cells must also avoid attacking ‘self’ – for example , the healthy tissues of the body – as this could lead to autoimmune disease . B cells are a ty...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2018	IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate
Diploid transgenic organisms are either hemi- or homozygous . Genetic assays are , therefore , required to identify the genotype . Our AGameOfClones vector concept uses two clearly distinguishable transformation markers embedded in interweaved , but incompatible Lox site pairs . Cre-mediated recombination leads to hemi...	Researchers frequently use model organisms , such as mice , zebrafish and various insect species , to understand biological processes – with the underlying idea that discoveries made can be applied to other species too . A common technique is genetic manipulation , in which a foreign gene is inserted into the chromosom...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology", "tools", "and", "resources" ]	2018	A universal vector concept for a direct genotyping of transgenic organisms and a systematic creation of homozygous lines
Most AAA+ remodeling motors denature proteins by pulling on the peptide termini of folded substrates , but it is not well-understood how motors produce grip when resisting a folded domain . Here , at single amino-acid resolution , we identify the determinants of grip by measuring how substrate tail sequences alter the ...	Proteins are the workhorses of the body , fulfilling many roles essential for life processes . These molecules are made up of hundreds or thousands of small units called amino acids , which attach to each other to form a long chain . The exact sequence of amino acids determines how the protein will then fold to acquire...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2019	Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding
Horizontal gene transfer ( HGT ) and gene loss result in rapid changes in the gene content of bacteria . While HGT aids bacteria to adapt to new environments , it also carries risks such as selfish genetic elements ( SGEs ) . Here , we use modelling to study how HGT of slightly beneficial genes impacts growth rates of ...	Most animals , including humans , inherit genes from their parents . However , bacteria and other microorganisms can also acquire genes from members of the same generation . This process , called horizontal gene transfer ( HGT for short ) , allows bacteria to quickly adapt to new environments . For example , rather tha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "computational", "and", "systems", "biology" ]	2020	Slightly beneficial genes are retained by bacteria evolving DNA uptake despite selfish elements
Plants have evolved intracellular immune receptors to detect pathogen proteins known as effectors . How these immune receptors detect effectors remains poorly understood . Here we describe the structural basis for direct recognition of AVR-Pik , an effector from the rice blast pathogen , by the rice intracellular NLR i...	Plant diseases reduce harvests of the world's most important food crops including wheat , rice , potato , and corn . These diseases are important for both global food security and local subsistence farming . To fight these diseases , crops ( like all plants ) have an immune system that can detect the telltale molecules...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Structural basis of pathogen recognition by an integrated HMA domain in a plant NLR immune receptor
Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells . However , the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood . Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in...	Neurons communicate with one another at junctions called synapses , which are typically formed between the dendrite of one neuron and the axon terminus of another . The dendrites are protrusions coming out of the cell body that receive inputs from other cells; the axon is a cable-like structure that enables neurons to ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall
Glia in the central nervous system engulf neuron fragments to remodel synapses and recycle photoreceptor outer segments . Whether glia passively clear shed neuronal debris or actively prune neuron fragments is unknown . How pruning of single-neuron endings impacts animal behavior is also unclear . Here , we report our ...	Neurons are tree-shaped cells that receive information through endings connected to neighbouring cells or the environment . Controlling the size , number and location of these endings is necessary to ensure that circuits of neurons get precisely the right amount of input from their surroundings . Glial cells form a lar...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2021	Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior
Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans . There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segreg...	Influenza viruses , commonly called flu , infect millions of people and animals every year and occasionally causes pandemics in humans . The immune system can neutralise flu viruses by recognising the proteins on the virus surface , generically referred to as antigens . These antigens change as flu viruses evolve to es...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2016	The global antigenic diversity of swine influenza A viruses
Ciliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion . In ciliary swimmers , ciliary beating , arrests , and changes in beat frequency are often coordinated across extended or discontinuous surfaces . To understand how such coordination is achieved , we studied the ciliat...	The oceans contain a wide variety of microscopic organisms including bacteria , algae and animal larvae . Many of the microscopic animals that live in water use thousands of beating hair-like projections called cilia instead of muscles to swim around in the water . Understanding how these animals move will aid our unde...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the Platynereis larva
In Huntington’s disease , a mutated version of the huntingtin protein leads to cell death . Mutant huntingtin is known to aggregate , a process that can be inhibited by the eukaryotic chaperonin TRiC ( TCP1-ring complex ) in vitro and in vivo . A structural understanding of the genesis of aggregates and their modulatio...	Huntington’s disease is an inheritable neurodegenerative disorder that typically begins in mid-adulthood . It initially affects muscle coordination and progresses to include psychiatric symptoms and cognitive decline , leading to premature death . The disease is caused by a mutation in the huntingtin gene , which codes...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	TRiC’s tricks inhibit huntingtin aggregation
Bruton's tyrosine kinase ( Btk ) , a Tec-family tyrosine kinase , is essential for B-cell function . We present crystallographic and biochemical analyses of Btk , which together reveal molecular details of its autoinhibition and activation . Autoinhibited Btk adopts a compact conformation like that of inactive c-Src an...	The human immune system is our defense against a variety of intruders , including bacteria , viruses , and other microbes , and provides our body with long-lasting protection against these invaders . B-cells—one type of immune cell—produce proteins called antibodies that can recognize microbes from previous invasions ....	[ "Abstract", "Introduction", "Results", "and", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate
AAA+ unfoldases are thought to unfold substrate through the central pore of their hexameric structures , but how this process occurs is not known . VAT , the Thermoplasma acidophilum homologue of eukaryotic CDC48/p97 , works in conjunction with the proteasome to degrade misfolded or damaged proteins . We show that in t...	Proteins perform many important jobs inside cells . Each protein is made of a chain of building blocks called amino acids that fold together to form precise shapes . Old , damaged or poorly constructed proteins tend to be harmful to cells so it is important that they are recycled . Ring-shaped enzymes called AAA+ unfol...	[ "Abstract", "Introduction", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2017	Structure of a AAA+ unfoldase in the process of unfolding substrate
For intracellular pathogens , residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients . The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole . How this large polymer accumulates there is unknown . We reveal that host glycogen stores shift ...	Chlamydia trachomatis is the most common sexually transmitted bacteria that causes disease . Infections often do not produce any obvious symptoms , but can lead to infertility or other severe problems if left untreated . This microbe is also the leading cause of blindness by an infectious agent . The bacteria grow in t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]	2016	Sequestration of host metabolism by an intracellular pathogen
In a presynaptic nerve terminal , synaptic strength is determined by the pool of readily releasable vesicles ( RRP ) and the probability of release ( P ) of each RRP vesicle . These parameters are controlled at the active zone and vary across synapses , but how such synapse specific control is achieved is not understoo...	Nerve cells in the brain communicate with one another at connections known as synapses: one nerve cell releases signaling molecules called neurotransmitters into the synapse , which are then sensed by the second cell . For the brain to work correctly , it is important that the nerve cells control when and how much neur...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	ELKS controls the pool of readily releasable vesicles at excitatory synapses through its N-terminal coiled-coil domains
Neurotransmitter corelease is emerging as a common theme of central neuromodulatory systems . Though corelease of glutamate or GABA with acetylcholine has been reported within the cholinergic system , the full extent is unknown . To explore synaptic signaling of cholinergic forebrain neurons , we activated choline acet...	Neurons communicate with one another at junctions called synapses . When an electrical signal arrives at the presynaptic cell , it triggers the release of molecules called neurotransmitters into the synapse . These molecules then bind to receptor proteins on the postsynaptic cell , starting a chain of events that leads...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	Corelease of acetylcholine and GABA from cholinergic forebrain neurons
Biological age measurements ( BAs ) assess aging-related physiological change and predict health risks among individuals of the same chronological age ( CA ) . Multiple BAs have been proposed and are well studied individually but not jointly . We included 845 individuals and 3973 repeated measurements from a Swedish po...	Everyone ages , but how aging affects health varies from person to person . This means that how old someone seems or feels does not always match the number of years they have been alive; in other words , someone’s “biological age” can often differ from their “chronological age” . Scientists are now looking at the physi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health" ]	2020	Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up
Enhancers constitute one of the major components of regulatory machinery of metazoans . Although several genome-wide studies have focused on finding and locating enhancers in the genomes , the fundamental principles governing their internal architecture and cis-regulatory grammar remain elusive . Here , we describe an ...	DNA contains regions known as genes , which may be “transcribed” to produce the RNA molecules that act as templates for building proteins and regulate cell activity . Proteins called transcription factors can bind to specific sequences of DNA to influence whether nearby genes are transcribed . For example , so-called e...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2016	Quantitative perturbation-based analysis of gene expression predicts enhancer activity in early Drosophila embryo
The colon hosts gut microbes and glucagon-like peptide 1 secreting cells , both of which influence glucose homeostasis . We tested whether colectomy is associated with development of type 2 diabetes . Using nationwide register data , we identified patients who had undergone total colectomy , partial colectomy , or proc...	The large intestine helps people process the food that has not been digested and absorbed in the small intestine . It houses billions of bacteria that break down food , especially fibers . It also produces hormones that may help control blood sugar after eating . People with type 2 diabetes , who have difficulty contro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine" ]	2018	Increase in clinically recorded type 2 diabetes after colectomy
RirA is a global regulator of iron homeostasis in Rhizobium and related α-proteobacteria . In its [4Fe-4S] cluster-bound form it represses iron uptake by binding to IRO Box sequences upstream of RirA-regulated genes . Under low iron and/or aerobic conditions , [4Fe-4S] RirA undergoes cluster conversion/degradation to a...	Virtually all life forms require iron to survive , yet too much of the metal can be catastrophic . In healthy cells , many systems regulate this delicate balance . For instance , when a protein called RirA is active in Rhizobium bacteria , it can sense high levels of the metal and helps to shut down the production of p...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2019	Mechanisms of iron- and O2-sensing by the [4Fe-4S] cluster of the global iron regulator RirA
Nucleotide-sugar transporters ( NSTs ) are critical components of the cellular glycosylation machinery . They transport nucleotide-sugar conjugates into the Golgi lumen , where they are used for the glycosylation of proteins and lipids , and they then subsequently transport the nucleotide monophosphate byproduct back t...	The cells in our body are tiny machines which , amongst other things , produce proteins . One of the production steps involves a compartment in the cell called the Golgi , where proteins are tagged and packaged before being sent to their final destination . In particular , sugars can be added onto an immature protein t...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2019	Structural basis for mammalian nucleotide sugar transport
Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty . Excitatory granule cells , the most numerous neuron type in the brain , are especially vulnerable and likely instigate disease by impairing the function of their targets , the Purkinje cells . Here , we use regional ...	Preterm infants have a higher risk of developing movement difficulties and neurodevelopmental conditions like autism spectrum disorder . This is likely caused by injuries to a part of the brain called the cerebellum . The cerebellum is important for movement , language and social interactions . During the final weeks o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2021	Maturation of Purkinje cell firing properties relies on neurogenesis of excitatory neurons
Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates . Yet , their regulation is only incompletely understood . We recently identified myotubularin related protein-2 ( Mtmr2 ) , a phosphoinositide ( PI ) phosphatase , in the native Piezo2 interactome of murine dorsal root ganglia ( D...	We often take our sense of touch for granted . Yet , our every-day life greatly depends on the ability to perceive our environment to alert us of danger or to further social interactions , such as mother-child bonding . Our sense of touch relies on the conversion of mechanical stimuli to electrical signals ( this is kn...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons
Actin has well established functions in cellular morphogenesis . However , it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium , in particular when cells have to respond to acute signals . Here , we characterize a rapid and transient actin reset in response to increase...	Our skeleton plays a vital role in giving shape and structure to our body , it also allows us to make coordinated movements . Similarly , each cell contains a microscopic network of structures and supports called the cytoskeleton that helps cells to adopt specific shapes and is crucial for them to move around . Unlike ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Calcium-mediated actin reset (CaAR) mediates acute cell adaptations
In fluctuating environments , switching between different growth strategies , such as those affecting cell size and proliferation , can be advantageous to an organism . Trade-offs arise , however . Mechanisms that aberrantly increase cell size or proliferation—such as mutations or chemicals that interfere with growth r...	Cells make different proteins to perform different tasks . Each protein is a long chain of building blocks called amino acids that must fold into a particular shape before it can be useful . Some proteins can fold in more than one way , a normal form and a ‘prion’ form . Prions are unusual in that they can force normal...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2021	A prion accelerates proliferation at the expense of lifespan
Divergence in gene regulation can play a major role in evolution . Here , we used a phylogenetic framework to measure mRNA profiles in 15 yeast species from the phylum Ascomycota and reconstruct the evolution of their modular regulatory programs along a time course of growth on glucose over 300 million years . We found...	The incredible diversity of living creatures belies the fact that their genes are quite similar . In the 1970s Mary-Claire King and Allan Wilson proposed that a process called gene regulation—which determines when , where and how genes are expressed as proteins—is responsible for this diversity . Four decades later , t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "evolutionary", "biology" ]	2013	Evolutionary principles of modular gene regulation in yeasts
Eukaryotes package DNA into nucleosomes that contain a core of histone proteins . During DNA replication , nucleosomes are disrupted and re-assembled with newly synthesized histones and DNA . Despite much progress , it is still unclear why higher eukaryotes contain multiple core histone genes , how chromatin assembly i...	As a cell prepares to divide , it goes through four distinct stages . First , it grows in size ( G1 phase ) ; next it copies its entire DNA content ( S phase ) ; then it grows some more ( G2 phase ) ; and , last , it splits into two new cells ( M phase ) . During S phase , groups of histone proteins that normally stick...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2014	Histone supply regulates S phase timing and cell cycle progression
Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks ( DSBs ) through a poorly understood mechanism . Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/A...	DNA is constantly under assault from harmful chemicals; some of which are produced inside the cell , while others come from outside of the cell . Breaks that form across both strands in a DNA double helix are considered the most dangerous type of DNA damage , and can cause a cell to die or become cancerous if they are ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2015	Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae
Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation . To address this question , we conducted a multicenter study of 60 healthy humans , half of whom received general anesthesia for 3 hr and half of whom served as awake controls...	Anesthesia is a state of reversable , controlled unconsciousness . It has enabled countless medical procedures . But it also serves as a tool for scientists to study how the brain regains consciousness after disruptions such as sleep , coma or medical procedures requiring general anesthesia . It is still unclear how ex...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "medicine", "neuroscience" ]	2021	Recovery of consciousness and cognition after general anesthesia in humans
Unpaired ligands are secreted signals that act via a GP130-like receptor , domeless , to activate JAK/STAT signalling in Drosophila . Like many mammalian cytokines , unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues . However , the importance of this effect ...	The immune system helps animals fend off infections , but it also has a role in controlling the body’s metabolism – that is , the chemical reactions that sustain life . For instance , in fruit flies , high-fat diets can trigger the immune system , which results in cells becoming resistant to the hormone insulin and not...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "immunology", "and", "inflammation" ]	2020	Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila
TRPV1 channels are gated by a variety of thermal , chemical , and mechanical stimuli . We used optical recording of Ca2+ influx through TRPV1 to measure activity and mobility of single TRPV1 molecules in isolated dorsal root ganglion neurons and cell lines . The opening of single TRPV1 channels produced sparklets , rep...	Cells rely on proteins called receptors to keep them informed about what is going on around them . These receptors , which are embedded in the surface of the cell , detect and respond to specific chemical signals . It is known that receptors move around the cell surface as they search for particular chemical signals , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2015	Activity and Ca2+ regulate the mobility of TRPV1 channels in the plasma membrane of sensory neurons
Local accumulation of oskar ( osk ) mRNA in the Drosophila oocyte determines the posterior pole of the future embryo . Two major cytoskeletal components , microtubules and actin filaments , together with a microtubule motor , kinesin-1 , and an actin motor , myosin-V , are essential for osk mRNA posterior localization ...	One of the most fundamental steps of embryonic development is deciding which end of the body should be the head , and which should be the tail . Known as 'axis specification' , this process depends on the location of genetic material called mRNAs . In fruit flies , for example , the tail-end of the embryo accumulates a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2020	Competition between kinesin-1 and myosin-V defines Drosophila posterior determination
The integrated stress response ( ISR ) attenuates the rate of protein synthesis while inducing expression of stress proteins in cells . Various insults activate kinases that phosphorylate the GTPase eIF2 leading to inhibition of its exchange factor eIF2B . Vanishing White Matter ( VWM ) is a neurological disease caused...	Cells must be able to respond to their changing environment in order to survive . When cells encounter particularly unfavorable conditions , they often react by activating a so-called ‘stress’ response . A group of proteins collectively known as eIF2B helps to regulate this response . In a severe neurological condition...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]	2019	eIF2B activator prevents neurological defects caused by a chronic integrated stress response
Natural sounds can be characterised by their spectral content and temporal modulation , but how the brain is organized to analyse these two critical sound dimensions remains uncertain . Using functional magnetic resonance imaging , we demonstrate a topographical representation of amplitude modulation rate in the audito...	The arrival of sound waves at the ear causes the fluid inside a part of the ear known as the cochlea to vibrate . These vibrations are detected by tiny hair cells and transformed into electrical signals , which travel along the auditory nerve to the brain . After processing in the brainstem and other regions deep withi...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "neuroscience" ]	2015	The topography of frequency and time representation in primate auditory cortices
Genetic and environmental factors , such as metals , interact to determine neurological traits . We reasoned that interactomes of molecules handling metals in neurons should include novel metal homeostasis pathways . We focused on copper and its transporter ATP7A because ATP7A null mutations cause neurodegeneration . W...	People need a source of copper in their diet because this nutrient is used to produce the pigment in hair and skin , the connective tissue in tendons and ligaments , and some of the small molecules that allow brain cells to communicate . There is an ideal range of copper that allows cells to carry out these processes ....	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2017	The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors
The importance of genome replication has inspired detailed crystallographic studies of enzymatic DNA/RNA polymerization . In contrast , the mechanism of nonenzymatic polymerization is less well understood , despite its critical role in the origin of life . Here we report the direct observation of nonenzymatic RNA prime...	Enzymes speed up chemical reactions that are essential to life . Most enzymes are proteins , but some are molecules of ribonucleic acid or RNA . Like DNA , RNA is made from a chain of building blocks called nucleotides . In modern organisms , protein-based enzymes build RNAs by linking nucleotides together , while the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2018	Crystallographic observation of nonenzymatic RNA primer extension
Visual projection neurons ( VPNs ) provide an anatomical connection between early visual processing and higher brain regions . Here we characterize lobula columnar ( LC ) cells , a class of Drosophila VPNs that project to distinct central brain structures called optic glomeruli . We anatomically describe 22 different L...	Many animals rely heavily on what they can see to interact with the world around them . But how does the brain use such visual information to guide behavior ? Light-sensitive neurons in the eye cannot distinguish between the visual signals associated with , say , an approaching predator or a source of food . Yet the br...	[ "Abstract", "Introduction", "Results", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Visual projection neurons in the Drosophila lobula link feature detection to distinct behavioral programs
Myelination of axons facilitates rapid impulse propagation in the nervous system . The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging . However , the molecular cause of many pathological features , including the frequently observed myelin outfoldings , remained unknown . Using label...	Normal communication within the brain or between the brain and other parts of the body requires information to flow quickly around the nervous system . This information travels along nerve cells in the form of electrical signals . To speed up the signals , a part of the nerve cell called the axon is frequently wrapped ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction
Wiscott Aldrich Syndrome protein ( WASP ) deficiency results in defects in calcium ion signaling , cytoskeletal regulation , gene transcription and overall T cell activation . The activation of WASP constitutes a key pathway for actin filament nucleation . Yet , when WASP function is eliminated there is negligible effe...	The immune system is made up of several types of cells that protect the body against infection and disease . Immune cells such as T cells survey the body and when receptors on their surface encounter infected cells , the receptors activate the T cell by triggering a signaling pathway . The early stages of T cell recept...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2015	Actin foci facilitate activation of the phospholipase C-γ in primary T lymphocytes via the WASP pathway
Group II introns are mobile ribozymes that are rare in bacterial genomes , often cohabiting with various mobile elements , and seldom interrupting housekeeping genes . What accounts for this distribution has not been well understood . Here , we demonstrate that Ll . LtrB , the group II intron residing in a relaxase gen...	Proteins , the molecular workhorses of the cell , are encoded by genes within the DNA . A given gene is often formed of several portions of coding DNA , the exons , which are separated by sections of non-coding DNA called introns . When it is expressed , the entire gene , including the introns , is ‘copied’ into a mole...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology" ]	2018	Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting
A defining feature of the brain is the ability of its synaptic contacts to adapt structurally and functionally in an experience-dependent manner . In the human cortex , however , direct experimental evidence for coordinated structural and functional synaptic adaptation is currently lacking . Here , we probed synaptic p...	The brain has an enormous capacity to adapt to its environment . This ability to continuously learn and form new memories thanks to its malleability , is known as brain plasticity . One of the most important mechanisms behind brain plasticity is the change in both the structure and function of synapses , the points of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	All-trans retinoic acid induces synaptic plasticity in human cortical neurons
Inhibition plays a crucial role in neural signal processing , shaping and limiting responses . In the auditory system , inhibition already modulates second order neurons in the cochlear nucleus , e . g . spherical bushy cells ( SBCs ) . While the physiological basis of inhibition and excitation is well described , thei...	In humans and other animals , small differences in the time at which a sound arrives at each ear are crucial for determining the location of the sound . Neurons in the first processing station of the brain – the cochlear nucleus – receive information about sounds ( or “inputs” ) from the ears . They then produce electr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Inhibition in the auditory brainstem enhances signal representation and regulates gain in complex acoustic environments
Assessing the behavioral relevance of the hippocampal theta rhythm has proven difficult , due to a shortage of experiments that selectively manipulate phase-specific information processing . Using closed-loop stimulation , we triggered inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in freely...	Around 15 years ago , an imaging study compared the brains of London taxi drivers—who need to know their way around one of the biggest cities in the world—with those of the general public , and found that a structure called the hippocampus was routinely larger in the taxi drivers . This finding was consistent with prev...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus
Glycosyltransferases ( GTs ) are prevalent across the tree of life and regulate nearly all aspects of cellular functions . The evolutionary basis for their complex and diverse modes of catalytic functions remain enigmatic . Here , based on deep mining of over half million GT-A fold sequences , we define a minimal core ...	Carbohydrates are one of the major groups of large biological molecules that regulate nearly all aspects of life . Yet , unlike DNA or proteins , carbohydrates are made without a template to follow . Instead , these molecules are built from a set of sugar-based building blocks by the intricate activities of a large and...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "computational", "and", "systems", "biology" ]	2020	Deep evolutionary analysis reveals the design principles of fold A glycosyltransferases
Recent hypotheses have posited that orbital frontal cortex ( OFC ) is important for using inferred consequences to guide behavior . Less clear is OFC’s contribution to goal-directed or model-based behavior , where the decision to act is controlled by previous experience with the consequence or outcome . Investigating O...	As we go about our daily lives , we do not simply react to the world around us . Instead we build up mental representations of the world and use these to guide our behavior . For example , we know that if we are hungry we can go into the kitchen to get a slice of our favorite cake . But we also adapt our behavior when ...	[ "Abstract", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Orbital frontal cortex updates state-induced value change for decision-making
Membrane trafficking is essential to fundamental processes in eukaryotic life , including cell growth and division . In plant cytokinesis , post-Golgi trafficking mediates a massive flow of vesicles that form the partitioning membrane but its regulation remains poorly understood . Here , we identify functionally redund...	Cells are surrounded by a plasma membrane , and when a cell divides to create two new cells , it must grow a new membrane to keep the two new cells apart . Animal cells and plant cells tackle this challenge in different ways: in animal cells the new membrane grows inwards from the surface of the cell , whereas the new ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "cell", "biology" ]	2014	Delivery of endocytosed proteins to the cell–division plane requires change of pathway from recycling to secretion
Despite recent improvements in microscope technologies , segmenting and tracking cells in three-dimensional time-lapse images ( 3D + T images ) to extract their dynamic positions and activities remains a considerable bottleneck in the field . We developed a deep learning-based software pipeline , 3DeeCellTracker , by i...	Microscopes have been used to decrypt the tiny details of life since the 17th century . Now , the advent of 3D microscopy allows scientists to build up detailed pictures of living cells and tissues . In that effort , automation is becoming increasingly important so that scientists can analyze the resulting images and u...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods", "Note", "in", "proof" ]	[ "computational", "and", "systems", "biology", "tools", "and", "resources", "neuroscience" ]	2021	3DeeCellTracker, a deep learning-based pipeline for segmenting and tracking cells in 3D time lapse images
Deep understanding of tooth regeneration is hampered by the lack of lifelong replacing oral dentition in most conventional models . Here , we show that the bearded dragon , one of the rare vertebrate species with both polyphyodont and monophyodont teeth , constitutes a key model for filling this gap , allowing direct c...	All multicellular organisms , from lizards to humans , must be able to repair and regrow damaged tissue . This includes not only healing after an injury , but also replacing parts of the body that suffer wear and tear . For example , many animals shed and replace worn out teeth throughout their life , but the number of...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2019	The alternative regenerative strategy of bearded dragon unveils the key processes underlying vertebrate tooth renewal
In multicellular organisms , cells adopt various shapes , from flattened sheets of endothelium to dendritic neurons , that allow the cells to function effectively . Here , we elucidated the unique shape of cells in the cornified stratified epithelia of the mammalian epidermis that allows them to achieve homeostasis of ...	The skin surface – known as the epidermis – is made up of sheets of cells that are stacked up in layers . One of the roles of the skin is to provide a protective barrier that limits what leaks into or out of the body . A particular layer of the epidermis – referred to as the stratum granulosum – is primarily responsibl...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape
Sleep has been conserved throughout evolution; however , the molecular and neuronal mechanisms of sleep are largely unknown . The hypothalamic hypocretin/orexin ( Hcrt ) neurons regulate sleep\wake states , feeding , stress , and reward . To elucidate the mechanism that enables these various functions and to identify s...	Sleep appears to be essential for all animals . The loss of a type of brain cell called the Hypocretin/Orexin ( Hcrt ) neurons causes the sleep disorder narcolepsy , which disturbs sleep patterns . These neurons also control several other fundamental behaviors and activities , including eating and processing rewards , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator Kcnh4a
The re-assembly of chromatin following DNA replication is a critical event in the maintenance of genome integrity . Histone H3 acetylation at K56 and phosphorylation at T45 are two important chromatin modifications that accompany chromatin assembly . Here we have identified the protein kinase Pkc1 as a key regulator th...	Prior to cell division , DNA must be copied so that each new cell gets a complete copy of the cell’s genetic instructions . But DNA is so long that it is stored in a heavily compacted form in the nucleus of the cell , with the strands of DNA coiled around several proteins called histones . Before the DNA is copied , it...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "genetics", "and", "genomics" ]	2015	Protein kinase C coordinates histone H3 phosphorylation and acetylation
Seizures are often followed by sensory , cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks . Here we show that seizures result in a severe hypoxic attack confined to the postictal period . We measured brain oxygenation in localized areas from f...	It has long been known that after an epileptic seizure , individuals often experience an extended period of impairments that affect how the brain works . Because the brain is organized so that specific tasks happen in particular areas , seizures that affect areas of the brain that control movement are often followed by...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent
Motor learning occurs through interactions between the cerebellar circuit and cellular plasticity at different sites . Previous work has established plasticity in brain slices and suggested plausible sites of behavioral learning . We now reveal what actually happens in the cerebellum during short-term learning . We mon...	Practice makes perfect in many areas of life , such as playing sport or even just drinking coffee from a cup without spilling any . Our brains can learn and improve these motor skills through trial , error and learning , with such “motor learning” depending on the cerebellum , a part of the brain that helps to coordina...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2013	Interaction of plasticity and circuit organization during the acquisition of cerebellum-dependent motor learning
Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles . This system may have evolved together with high heart rates to support their endothermic state ( warm-bloodedness ) and is seemingly lacking in ectothermic vertebrates from which first mammals ...	Mammals and birds are referred to as ‘warm-blooded’ animals , because they maintain a constant high body temperature . This requires a lot of energy , so their bodies need to be well supplied with blood at all times . The hearts of mammals and birds contain two important structures that help them do this . The first is...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2018	Specialized impulse conduction pathway in the alligator heart
Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world . The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences , but within-host gen...	The COVID-19 pandemic has had major health impacts across the globe . The scientific community has focused much attention on finding ways to monitor how the virus responsible for the pandemic , SARS-CoV-2 , spreads . One option is to perform genetic tests , known as sequencing , on SARS-CoV-2 samples to determine the g...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "genetics", "and", "genomics" ]	2021	Patterns of within-host genetic diversity in SARS-CoV-2
Rho-associated kinases 1 and 2 ( ROCK1/2 ) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton , but their role in proliferation and cancer initiation or progression is not known . Here , we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proli...	Animal cells contain a structure called the cytoskeleton , which helps give the cells their shape . This structure can rapidly disassemble and reassemble , which enables cells to change their shape , move and divide into two . Many proteins are involved in controlling these processes . In particular , two proteins call...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods", "Statistical", "analysis" ]	[ "cell", "biology", "cancer", "biology" ]	2016	Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis
Pancreatic adenosquamous carcinoma ( PASC ) is an aggressive cancer whose mutational origins are poorly understood . An early study reported high-frequency somatic mutations affecting UPF1 , a nonsense-mediated mRNA decay ( NMD ) factor , in PASC , but subsequent studies did not observe these lesions . The correspondin...	Cancer is a group of complex diseases in which cells grow uncontrollably and spread into surrounding tissues and other parts of the body . All types of cancers develop from changes – or mutations – in the genes that affect the pathways involved in controlling the growth of cells . Different cancers possess unique sets ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "cancer", "biology" ]	2021	The origins and consequences of UPF1 variants in pancreatic adenosquamous carcinoma
Expanded GGGGCC repeats in the first intron of the C9orf72 gene represent the most common cause of familial amyotrophic lateral sclerosis ( ALS ) , but the mechanisms underlying repeat-induced disease remain incompletely resolved . One proposed gain-of-function mechanism is that repeat-containing RNA forms aggregates t...	Molecules of ribonucleic acid ( or RNA for short ) have many roles in cells , including acting as templates to make proteins . RNA is made of building blocks called nucleotides that are assembled to form strands . The precise order of the nucleotides in an RNA molecule can have a dramatic effect on the role that RNA pl...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2017	Suppression of C9orf72 RNA repeat-induced neurotoxicity by the ALS-associated RNA-binding protein Zfp106
Protein abundance differs from a few to millions of copies per cell . Trypanosoma brucei presents an excellent model for studies on codon bias and differential gene expression because transcription is broadly unregulated and uniform across the genome . T . brucei is also a major human and animal protozoal pathogen . He...	Genes are made up of DNA , which contains all the information and instruction needed to build an organism . This information is stored as a genetic code consisting of four bases: adenine ( A ) , cytosine ( C ) , guanine ( G ) and thymine ( T ) . The order of these bases and their different combinations serves as a blue...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2018	Codon usage bias controls mRNA and protein abundance in trypanosomatids
Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum . Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes , where they can scavenge host heme to meet metabolic needs . Nevertheless , heme biosynthesis in pa...	Malaria is a devastating infectious disease that is caused by single-celled parasites called Plasmodium that can live inside red blood cells . Several important proteins from these parasites require a small molecule called heme in order to work . The parasites have enzymes that make heme via a series of intermediate st...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "microbiology", "and", "infectious", "disease" ]	2015	Deconvoluting heme biosynthesis to target blood-stage malaria parasites
Transporters from bacteria to humans contain inverted repeat domains thought to arise evolutionarily from the fusion of smaller membrane protein genes . Association between these domains forms the functional unit that enables transporters to adopt distinct conformations necessary for function . The small multidrug resi...	Cells are bound by a thin membrane layer that protects the cell’s interior from the outside environment . Within this layer are various transporter proteins that control which substances are allowed in and out of the cell . These transporters actively move substances across the membrane by loading cargo on one side of ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2019	Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations
Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories . Kidney progenitors originate within the intermediate mesoderm ( IM ) , but the pathways that set the boundaries of the IM are poorly understood . Here , we show that the bHLH transcription factor Hand2 limits the size of...	The human body is made up of many different types of cells , yet they are all descended from one single fertilized egg cell . The process by which cells specialize into different types is complex and has many stages . At each step of the process , the selection of cell types that a cell can eventually become is increas...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2016	Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm
In all living organisms , ribosomes translating membrane proteins are targeted to membrane translocons early in translation , by the ubiquitous signal recognition particle ( SRP ) system . In eukaryotes , the SRP Alu domain arrests translation elongation of membrane proteins until targeting is complete . Curiously , ho...	Proteins are built as long chain-like molecules . First , a length of DNA is copied to make a messenger RNA ( or mRNA ) molecule , which then binds to a large molecular complex called a ribosome . The ribosome reads and translates the code in the mRNA sequence to build a protein chain , which then folds into a specific...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2014	mRNA-programmed translation pauses in the targeting of E. coli membrane proteins
An extracellular matrix of Fibronectin adheres the neural tube to the two flanking columns of paraxial mesoderm and is required for normal vertebrate development . Here , we find that the bilaterally symmetric interfaces between the zebrafish neural tube and paraxial mesoderm function as optimally engineered adhesive l...	In embryos , the spinal cord starts out as a flat sheet of cells that curls up to form a closed cylinder called the neural tube . The folding tube is attached to the surrounding tissues through an extracellular matrix of proteins and sugars . Overlapping strands of a protein from the extracellular matrix called Fibrone...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2020	Fibronectin is a smart adhesive that both influences and responds to the mechanics of early spinal column development
The leishmaniases are vector-borne diseases that have a broad global distribution throughout much of the Americas , Africa , and Asia . Despite representing a significant public health burden , our understanding of the global distribution of the leishmaniases remains vague , reliant upon expert opinion and limited to p...	Each year 1–2 million people are diagnosed with a tropical disease called leishmaniasis , which is caused by single-celled parasites . People are infected when they are bitten by sandflies carrying the parasite , and often develop skin lesions around the bite site . Though mild cases may recover on their own or with tr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2014	Global distribution maps of the leishmaniases
A central question is how specificity in cellular responses to the eukaryotic second messenger Ca2+ is achieved . Plant guard cells , that form stomatal pores for gas exchange , provide a powerful system for in depth investigation of Ca2+-signaling specificity in plants . In intact guard cells , abscisic acid ( ABA ) e...	Plant leaves have tiny openings or pores called stomata , which allow carbon dioxide , water vapor and other gases to diffuse in and out of the plant . Two cells called guard cells surround each stoma and control the opening and closing of the pore . If a plant is losing excessive amounts of water , for example during ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2015	Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells
The coordinated action of the auxin-sensitive Aux/IAA transcriptional repressors and ARF transcription factors produces complex gene-regulatory networks in plants . Despite their importance , our knowledge of these two protein families is largely based on analysis of stabilized forms of the Aux/IAAs , and studies of a ...	Auxin is a plant hormone that regulates many aspects of growth and development . It does so by promoting the degradation of proteins called the Aux/IAAs . These proteins normally act to keep genes switched off by interacting with another family of proteins called ARFs that can bind directly to the genes . Some ARFs act...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "plant", "biology" ]	2016	Constitutive auxin response in Physcomitrella reveals complex interactions between Aux/IAA and ARF proteins
The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases . Much of the most basic biology of this organelle is poorly understood , even basic mechanisms , such as control of growth and resorption . We show that the activity of the anaphase-promoting com...	The majority of cells in the human body have small hair-like structures that project from the cell surface . These structures , known as primary cilia , are involved in sensing light and touch , and they are also required for an organism to develop normally . Defects in cilia result in a wide range of human diseases th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium
Human tactile afferents provide essential feedback for grasp stability during dexterous object manipulation . Interacting forces between an object and the fingers induce slip events that are thought to provide information about grasp stability . To gain insight into this phenomenon , we made a transparent surface slip ...	Each fingertip hosts thousands of nerve fibers that allow us to handle objects with great dexterity . These fibers relay the amount of friction between the skin and the item , and the brain uses this sensory feedback to adjust the grip as necessary . Yet , exactly how tactile nerve fibers encode information about frict...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	High-resolution imaging of skin deformation shows that afferents from human fingertips signal slip onset
The resection of DNA strand with a 5´ end at double-strand breaks is an essential step in recombinational DNA repair . RecJ , a member of DHH family proteins , is the only 5´ nuclease involved in the RecF recombination pathway . Here , we report the crystal structures of Deinococcus radiodurans RecJ in complex with deo...	DNA encodes information that cells need to create the molecules and proteins that are essential for life . It is therefore vital that damaged DNA is repaired rapidly and accurately . Some DNA-damaging agents , such as gamma radiation , break both strands of the DNA double helix , which can be fatal to cells if not repa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	Structural basis for DNA 5´-end resection by RecJ
To optimize fitness a plant should monitor its metabolism to appropriately control growth and defense . Primary metabolism can be measured by the universally conserved TOR ( Target of Rapamycin ) pathway to balance growth and development with the available energy and nutrients . Recent work suggests that plants may mea...	Plants , like all organisms , must invest their resources carefully . Growing new roots or shoots may allow a plant to better exploit its environment . But a plant should never leave itself vulnerable to disease . As such , there must be a balance between allocating resources to growth or to defense . Brassicas like ca...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2017	An evolutionarily young defense metabolite influences the root growth of plants via the ancient TOR signaling pathway
Adult stem cells continuously undergo self-renewal and generate differentiated cells . In the Drosophila ovary , two separate niches control germ line stem cell ( GSC ) self-renewal and differentiation processes . Compared to the self-renewing niche , relatively little is known about the maintenance and function of the...	An animal or plant has many different types of cells that have specific roles in the life of the organism . These cells are organized into tissues . In most tissues in adult animals , small groups of cells called stem cells are responsible for replacing the other cells that have been lost due to disease , injury , or a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2015	Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche
Physiological adaptation to proteotoxic stress in the endoplasmic reticulum ( ER ) requires retrotranslocation of misfolded proteins into the cytoplasm for ubiquitination and elimination by ER-associated degradation ( ERAD ) . A surprising paradox emerging from recent studies is that ubiquitin ligases ( E3s ) and deubi...	Cells make proteins inside a structure called the endoplasmic reticulum . However , some of these proteins cannot fold into the correct shape , so cells rely on a process called the ERAD pathway to degrade and eliminate these faulty proteins . First , however , the misfolded proteins must be moved from the endoplasmic ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation
Type 1 diabetes ( T1D ) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring α cells are preserved . Viral infections by coxsackieviruses ( CVB ) may contribute to trigger autoimmunity in T1D . Cellular permissiveness to viral infection is modulated by innate antiviral responses...	Type 1 diabetes is caused by a person's immune system attacking the cells in their pancreas that produce insulin . This eventually kills off so many of these cells—known as beta cells—that the pancreas is unable to make enough insulin . As a result , individuals with type 1 diabetes must inject insulin to help their bo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2015	Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells
Calcium in the flagellum controls sperm navigation . In sperm of marine invertebrates and mammals , Ca2+ signalling has been intensely studied , whereas for fish little is known . In sea urchin sperm , a cyclic nucleotide-gated K+ channel ( CNGK ) mediates a cGMP-induced hyperpolarization that evokes Ca2+ influx . Here...	Mammalian sperm cells fertilize egg cells inside the female’s body; while for fish and other marine animals it is common for fertilization to take place outside in the environment . In general , sperm cells become attracted to egg cells by various chemical or physical signals . Sperm detect these cues and generate elec...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	A K+-selective CNG channel orchestrates Ca2+ signalling in zebrafish sperm
Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels . We describe here the presence of mechanically activated currents in melanoma cells that are dependent on TMEM87a , which we have renamed Elkin1 . He...	When cells receive signals about their surrounding environment , this initiates a chain of signals which generate a response . Some of these signalling pathways allow cells to sense physical and mechanical forces via a process called mechanotransduction . There are different types of mechanotransduction . In one pathwa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2020	TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration
In the mouse , Period-2 ( Per2 ) expression in tissues peripheral to the suprachiasmatic nuclei ( SCN ) increases during sleep deprivation and at times of the day when animals are predominantly awake spontaneously , suggesting that the circadian sleep-wake distribution directly contributes to the daily rhythms in Per2 ...	Circadian rhythms are daily cycles in behavior and physiology which repeat approximately every 24 hours . The master regulator of these rhythms is located in a small part of the brain called the supra-chiasmatic nucleus . This brain structure regulates the timing of sleep and wakefulness and is also thought to control ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2021	The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2

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