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In embryonic stem cells ( ESCs ) , the Tip60 histone acetyltransferase activates genes required for proliferation and silences genes that promote differentiation . Here we show that the class II histone deacetylase Hdac6 co-purifies with Tip60-p400 complex from ESCs . Hdac6 is necessary for regulation of most Tip60-p40...	Embryonic stem cells are cells that are able to transform into many other types of cells , such as blood cells and skin cells , as well as being able to divide in order to produce more stem cells . Mature cells lack this ability , which is called pluripotency , which is why there is so much interest in using embryonic ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "chromosomes", "and", "gene", "expression" ]	2013	Hdac6 regulates Tip60-p400 function in stem cells
During mammalian development , the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates . Here , we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2 , the first marker of pluripotency in the mouse early embryo . W...	As an embryo develops , its cells divide , grow and migrate in specific patterns to build an organized collection of cells that go on to form our tissues and organs . One of the first steps – well before the embryo has implanted into the womb – is to allocate cells to make part of the placenta . Once this process is co...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2018	HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo
In pig production , inefficient feed digestion causes excessive nutrients such as phosphorus and nitrogen to be released to the environment . To address the issue of environmental emissions , we established transgenic pigs harboring a single-copy quad-cistronic transgene and simultaneously expressing three microbial en...	The bodily waste that pigs produce contains high levels of chemicals that can damage the environment , such as nitrogen and phosphorus . For example , when excessive amounts of these two compounds make their way into the water , they can cause blue-green algae to grow too much , which asphyxiates other life in the wate...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "tools", "and", "resources", "microbiology", "and", "infectious", "disease" ]	2018	Novel transgenic pigs with enhanced growth and reduced environmental impact
Experience alters brain structure , but the underlying mechanism remained unknown . Structural plasticity reveals that brain function is encoded in generative changes to cells that compete with destructive processes driving neurodegeneration . At an adult critical period , experience increases fiber number and brain si...	Everything that you experience leaves its mark on your brain . When you learn something new , the neurons involved in the learning episode grow new projections and form new connections . Your brain may even produce new neurons . Physical exercise can induce similar changes , as can taking antidepressants . By contrast ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	A Toll-receptor map underlies structural brain plasticity
Nutritional restriction leads to protein translation attenuation that results in the storage and degradation of free mRNAs in cytoplasmic assemblies . In this study , we show in Drosophila S2 cells that amino-acid starvation also leads to the inhibition of another major anabolic pathway , the protein transport through ...	Proteins are needed by living cells to perform vital tasks and are made from building blocks called amino-acids . However , if a cell is starved of amino-acids , protein assembly comes to a halt , and if cells are deprived of amino acids for a long time , the cell may die . To survive short periods of amino-acid starva...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2014	A stress assembly that confers cell viability by preserving ERES components during amino-acid starvation
MicroRNAs ( miRNAs ) are important regulators of stem and progenitor cell functions . We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells ( BCSCs ) as compared to the non-tumorigenic breast cancer cells . In this study , we report that miR-142 efficiently recruits the APC m...	Messenger RNA molecules take the information encoded in a gene's DNA sequence and turn it into instructions for building a protein . However , if certain smaller molecules of RNA—called microRNAs—bind to a messenger RNA molecule , they ‘silence’ it , which prevents the information in the messenger RNA from being transl...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2014	miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway
In high-income countries , one’s relative socio-economic position and economic inequality may affect health and well-being , arguably via psychosocial stress . We tested this in a small-scale subsistence society , the Tsimane , by associating relative household wealth ( n = 871 ) and community-level wealth inequality (...	Poverty is bad for health . People living in poverty are more likely to struggle to afford nutritious food , lack access to health care , or be overworked or stressed . This may make them susceptible to chronic diseases , contribute to faster aging , and shorten their lifespans . In high-income countries , there is gro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "medicine" ]	2021	Do wealth and inequality associate with health in a small-scale subsistence society?
Predicting evolutionary change poses numerous challenges . Here we take advantage of the model bacterium Pseudomonas fluorescens in which the genotype-to-phenotype map determining evolution of the adaptive ‘wrinkly spreader’ ( WS ) type is known . We present mathematical descriptions of three necessary regulatory pathw...	Predicting evolution might sound like an impossible task . The immense complexity of biological systems and their interactions with the environment has meant that many biologists have abandoned the idea as a lost cause . But despite this , evolution often repeats itself . This repeatability offers hope for being able t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "genetics", "and", "genomics" ]	2019	Predicting mutational routes to new adaptive phenotypes
Tumors often co-exist with T cells that recognize somatically mutated peptides presented by cancer cells on major histocompatibility complex I ( MHC-I ) . However , it is unknown why the immune system fails to eliminate immune-recognizable neoplasms before they manifest as frank disease . To understand the determinants...	T cells are specialized agents of the immune system that can detect and attack tumors . They spot their target by identifying small pieces of proteins – or antigens – at the surface of diseased cells . In particular , they can recognize the new and abnormal antigens that a cancer cell often displays . Yet , cells that ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2018	Rejection of immunogenic tumor clones is limited by clonal fraction
A considerable proportion of mammalian gene expression undergoes circadian oscillations . Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms . We have investigated how microRNAs ( miRNAs ) contribute to core clock and clock-controlled gene expression using mice in which miRNA ...	The rising and setting of the sun have long driven the schedules of humans and other mammals . This 24-hr cycle influences many behavioural and physiological changes , including alertness , body temperature , and sleep . A region in the brain acts as a master clock that regulates these daily cycles , which are called c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2014	MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale
Spinal and bulbar muscular atrophy ( SBMA ) is a progressive neuromuscular disease caused by polyglutamine expansion in the androgen receptor ( AR ) protein . Despite extensive research , the exact pathogenic mechanisms underlying SBMA remain elusive . In this study , we present evidence that Nemo-like kinase ( NLK ) p...	Spinal and bulbar muscular atrophy ( SBMA ) is an inherited disease that eventually leads to degeneration in motor neurons and weakness in muscles . It is caused by a specific genetic mutation in the gene that encodes the androgen receptor protein , which leads to the production of a mutant protein that is larger than ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy
Diverse features of sensory stimuli are selectively processed in distinct brain areas . The relative recruitment of inhibitory and excitatory neurons within an area controls the gain of neurons for appropriate stimulus coding . We examined how such a balance of inhibition and excitation is differentially recruited acro...	The visual cortex is the part of the brain responsible for the conscious sense of vision . It is made up of multiple connected areas , and each area has a different expertise for analyzing images . The areas exchange information about the outside world via connections between cells called neurons . Communication betwee...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Recruitment of inhibition and excitation across mouse visual cortex depends on the hierarchy of interconnecting areas
Serostudies are needed to answer generalizable questions on disease risk . However , recruitment is usually biased by age or location . We present a nationally-representative study for dengue from 70 communities in Bangladesh . We collected data on risk factors , trapped mosquitoes and tested serum for IgG . Out of 586...	Dengue is a mosquito-borne virus that infects millions of people each year . Often the countries most affected by the virus , such as Bangladesh , do not have the resources needed to tackle the disease . For resources sent to these countries to have the greatest impact , it is important to know which areas are most aff...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "epidemiology", "and", "global", "health" ]	2019	Nationally-representative serostudy of dengue in Bangladesh allows generalizable disease burden estimates
Increasing evidence highlights the important roles of microRNAs in mediating p53’s tumor suppression functions . Here , we report miR-139-5p as another new p53 microRNA target . p53 induced the transcription of miR-139-5p , which in turn suppressed the protein levels of phosphodiesterase 4D ( PDE4D ) , an oncogenic pro...	The human body is kept mostly free from tumors by the actions of so-called tumor suppressor genes . One such gene encodes a protein called p53 , which prevents tumors from growing by regulating the activity of many other genes that either inhibit cell growth or cause cells to die . For example , p53 regulates genes tha...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2016	Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation
The interrelationship between endogenous microbiota , the immune system , and tissue regeneration is an area of intense research due to its potential therapeutic applications . We investigated this relationship in Schmidtea mediterranea , a model organism capable of regenerating any and all of its adult tissues . Micro...	Regeneration , the ability to replace missing or damaged tissue , has fascinated biologists for years and has inspired a new direction for the medical field . Figuring out how some animals easily accomplish this while others do not may help us to develop new therapies that enhance regeneration in humans . Previous work...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "microbiology", "and", "infectious", "disease" ]	2016	Pathogenic shifts in endogenous microbiota impede tissue regeneration via distinct activation of TAK1/MKK/p38
Glutamate delta ( GluD ) receptors belong to the ionotropic glutamate receptor family , yet they don’t bind glutamate and are considered orphan . Progress in defining the ion channel function of GluDs in neurons has been hindered by a lack of pharmacological tools . Here , we used a chemo-genetic approach to engineer s...	Neurotransmitters are chemicals released by the body that trigger activity in neurons . Receptors on the surface of neurons detect these neurotransmitters , providing a link between the inside and the outside of the cell . Glutamate is one of the major neurotransmitters and is involved in virtually all brain functions ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]	2020	Probing the ionotropic activity of glutamate GluD2 receptor in HEK cells with genetically-engineered photopharmacology
Proteasomes are central regulators of protein homeostasis in eukaryotes . Proteasome function is vulnerable to environmental insults , cellular protein imbalance and targeted pharmaceuticals . Yet , mechanisms that cells deploy to counteract inhibition of this central regulator are little understood . To find such mech...	Cells have numerous methods for removing proteins that have been damaged or are no longer needed . One of these methods is carried out by a large protein complex called the proteasome . Because of its central role in maintaining protein balance , drugs that stop the proteasome functioning often kill cancer cells grown ...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "cell", "biology" ]	2015	Compromising the 19S proteasome complex protects cells from reduced flux through the proteasome
Huntington's disease ( HD ) represents an important model for neurodegenerative disorders and proteinopathies . It is mainly caused by cytotoxicity of the mutant huntingtin protein ( Htt ) with an expanded polyQ stretch . While Htt is ubiquitously expressed , HD is characterized by selective neurodegeneration of the st...	Huntington's disease is an inherited disorder of the central nervous system . Symptoms typically begin between the ages of 30 and 50 , and initially include clumsiness and uncontrollable movements , as well as personality changes and mood swings . Symptoms worsen over time and life expectancy is usually around 10 to 25...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	A striatal-enriched intronic GPCR modulates huntingtin levels and toxicity
FANCI:FANCD2 monoubiquitination is a critical event for replication fork stabilization by the Fanconi anemia ( FA ) DNA repair pathway . It has been proposed that at stalled replication forks , monoubiquitinated-FANCD2 serves to recruit DNA repair proteins that contain ubiquitin-binding motifs . Here , we have reconsti...	Bone marrow is the spongy tissue inside bones that produces blood cells . Fanconi anemia is the most common form of inherited bone marrow death and affects children and young adults . In this disease , bone marrow cells cannot attach a protein tag called ubiquitin to another protein called FANCD2 . When DNA becomes dam...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2020	Monoubiquitination by the human Fanconi anemia core complex clamps FANCI:FANCD2 on DNA in filamentous arrays
DNA replication is a fundamental biological process . The initial step in eukaryotic DNA replication is the assembly of the pre-initiation complex , including the formation of two head-to-head hexameric helicases around the replication origin . How these hexameric helicases interact with their origin dsDNA remains unkn...	When a cell divides to form a new cell , it must also copy its DNA . An important step for starting DNA replication is to break or “melt” the bonds between the two strands of DNA that make up the double helix . This happens at a specific site on the DNA called the replication origin , and allows double-stranded DNA to ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA
Sucrose’s sweet intensity is one attribute contributing to the overconsumption of high-energy palatable foods . However , it is not known how sucrose intensity is encoded and used to make perceptual decisions by neurons in taste-sensitive cortices . We trained rats in a sucrose intensity discrimination task and found t...	Imagine you wake up in the morning , and you pour yourself and your loved one coffee . They like it with two sugars but you only with one . Our ability to distinguish different sweet intensities allows us to detect how much sugar is in the coffee . It also helps us to predict the amount of energy present in foods and i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Sucrose intensity coding and decision-making in rat gustatory cortices
Adipose tissue is crucial for the maintenance of energy and metabolic homeostasis and its deregulation can lead to obesity and type II diabetes ( T2D ) . Using gene disruption in the mouse , we discovered a function for a RhoA-specific guanine nucleotide exchange factor PDZ-RhoGEF ( Arhgef11 ) in white adipose tissue b...	Obesity is a growing public health concern around the world , and can lead to the development of type 2 diabetes , heart disease and cancer . Both genetics and environmental factors such as diet contribute to obesity . Fat cells are essential to good health , but the excess accumulation of fat cells in obese people inv...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods", "Supplementary", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2015	The Rho-guanine nucleotide exchange factor PDZ-RhoGEF governs susceptibility to diet-induced obesity and type 2 diabetes
Histamine-dependent and -independent itch is conveyed by parallel peripheral neural pathways that express gastrin-releasing peptide ( GRP ) and neuromedin B ( NMB ) , respectively , to the spinal cord of mice . B-type natriuretic peptide ( BNP ) has been proposed to transmit both types of itch via its receptor NPRA enc...	An itch is a common sensation that makes us want to scratch . Most short-term itches are caused by histamine , a chemical that is released by immune cells following an infection or in response to an allergic reaction . Chronic itching , on the other hand , is not usually triggered by histamine , and is typically the re...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2021	BNP facilitates NMB-encoded histaminergic itch via NPRC-NMBR crosstalk
Expansion of biliary epithelial cells ( BECs ) during ductular reaction ( DR ) is observed in liver diseases including cystic fibrosis ( CF ) , and associated with inflammation and fibrosis , albeit without complete understanding of underlying mechanism . Using two different genetic mouse knockouts of β-catenin , one w...	The liver has an incredible capacity to repair itself or ‘regenerate’ – that is , it has the ability to replace damaged tissue with new tissue . In order to do this , the organ relies on hepatocytes ( the cells that form the liver ) and bile duct cells ( the cells that form the biliary ducts ) dividing and transforming...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "medicine" ]	2021	β-Catenin-NF-κB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction
The axolotl can regenerate multiple organs , including the brain . It remains , however , unclear whether neuronal diversity , intricate tissue architecture , and axonal connectivity can be regenerated; yet , this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian cen...	Humans and other mammals have a very limited ability to regenerate new neurons in the brain to replace those that have been injured or damaged . In striking contrast , some animals like fish and salamanders are capable of filling in injured brain regions with new neurons . This is a complex task , as the brain is compo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "neuroscience" ]	2016	Adult axolotls can regenerate original neuronal diversity in response to brain injury
Many animals use visual signals to estimate motion . Canonical models suppose that animals estimate motion by cross-correlating pairs of spatiotemporally separated visual signals , but recent experiments indicate that humans and flies perceive motion from higher-order correlations that signify motion in natural environ...	Many animals have evolved the ability to estimate the speed and direction of visual motion . They use these estimates to judge their own motion , so that they can navigate through an environment , and to judge how other animals are moving , which allows them to avoid predators or detect prey . In the 1950s , a physicis...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Nonlinear circuits for naturalistic visual motion estimation
Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes . Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling . Here , we perform an activity-based proteomic ana...	The brain is made up of many types of cells . These include the neurons that transmit messages throughout the nervous system , and microglia , which act as the first line of the brain’s immune defense . The activity of both neurons and microglia can be influenced by molecules called endocannabinoids that bind to protei...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]	2016	A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation
The precise assembly of inner ear hair cell stereocilia into rows of increasing height is critical for mechanotransduction and the sense of hearing . Yet , how the lengths of actin-based stereocilia are regulated remains poorly understood . Mutations of the molecular motor myosin 15 stunt stereocilia growth and cause d...	Sound is detected by the cochlea , a coiled structure encapsulated within the inner ear of humans and other mammals . Inside this organ , intricate arrays of sensory hair cells are stimulated by sound to generate neural signals that are transmitted to the brain . The ‘hairs’ that give hair cells their name are actually...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2015	The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing
In the human brain , a default mode or task-negative network shows reduced activity during many cognitive tasks and is often associated with internally-directed processes , such as mind wandering and thoughts about the self . In contrast to this task-negative pattern , we show increased activity during a large and dema...	The default mode network is a network in the brain that is often active when we think about ourselves , reminiscence about the past or just let our minds wander . However , this network—which involves many different regions of the brain—usually becomes inactive when we focus on a specific cognitive task . Now Crittende...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Recruitment of the default mode network during a demanding act of executive control
Human natural killer ( NK ) cells are defined as CD56+CD3− . Despite its ubiquitous expression on human NK cells the role of CD56 ( NCAM ) in human NK cell cytotoxic function has not been defined . In non-immune cells , NCAM can induce signaling , mediate adhesion , and promote exocytosis through interactions with foca...	The immune system deploys different cell types to take out cancer cells . True to their name , one type of immune cell known as natural killer cells kills tumor target cells by releasing toxic proteins that kill the harmful cells . In humans , these immune cells are defined , among other things , by the presence of a p...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2020	CD56 regulates human NK cell cytotoxicity through Pyk2
Temperate bacteriophages are viruses that can incorporate their genomes into their bacterial hosts , existing there as prophages that refrain from killing the host cell until induced . Prophages are largely quiescent , but they can alter host phenotype through factors encoded in their genomes ( often virulence factors ...	Animals and plants can all fall prey to viruses – and so can bacteria . The viruses that infect bacteria are called bacteriophages ( or phages for short ) , and they are found everywhere bacteria live and probably outnumber bacteria by at least ten to one . While some phages quickly kill every bacterial cell they infec...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "microbiology", "and", "infectious", "disease" ]	2019	Phage integration alters the respiratory strategy of its host
The emergence of drug resistance can defeat the successful treatment of pathogens that display high mutation rates , as exemplified by RNA viruses . Here we detail a new paradigm in which a single compound directed against a ‘dominant drug target’ suppresses the emergence of naturally occurring drug-resistant variants ...	Treating a viral infection with a drug sometimes has an unwanted side effect—the virus quickly becomes resistant to the drug . Viruses whose genetic information is encoded in molecules of RNA mutate faster than DNA viruses and are particularly good at developing resistance to drugs . This is because the process of copy...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2014	Dominant drug targets suppress the emergence of antiviral resistance
In order to produce movements , muscles must act through joints . The translation from muscle force to limb movement is mediated by internal joint structures that permit movement in some directions but constrain it in others . Although muscle forces acting against constrained directions will not affect limb movements ,...	Although most of us will never achieve the grace and dexterity of professional ballerina Misty Copeland , we each make sophisticated , complex movements every day . Even simple movements often involve coordinating many muscles throughout the body . Moreover , because we have so many muscles , there are often multiple w...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Adaptation after vastus lateralis denervation in rats demonstrates neural regulation of joint stresses and strains
A LOV ( Light , Oxygen , or Voltage ) domain containing blue-light photoreceptor ZEITLUPE ( ZTL ) directs circadian timing by degrading clock proteins in plants . Functions hinge upon allosteric differences coupled to the ZTL photocycle; however , structural and kinetic information was unavailable . Herein , we tune th...	Many living organisms track the 24-hour cycle of day and night via collections of proteins and other molecules that together act like an internal clock . These clocks , also known as circadian clocks , help these organisms to predict regular changes in their environment , like light and temperature , and adjust their a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2017	Kinetics of the LOV domain of ZEITLUPE determine its circadian function in Arabidopsis
Successfully completing the S phase of each cell cycle ensures genome integrity . Impediment of DNA replication can lead to DNA damage and genomic disorders . In this study , we show a novel function for NDE1 , whose mutations cause brain developmental disorders , in safeguarding the genome through S phase during early...	The brain is a complex organ with many different cell types that each have specialized functions . Mutations in genes that control how the brain develops can have serious consequences—and one of the most important genes involved in the development of the human brain is called NDE1 . Individuals who inherit mutated copi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]	2014	The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation
How different helicase families with a conserved catalytic ‘helicase core’ evolved to function on varied RNA and DNA substrates by diverse mechanisms remains unclear . In this study , we used Mss116 , a yeast DEAD-box protein that utilizes ATP to locally unwind dsRNA , to investigate helicase specificity and mechanism ...	Living cells store their genetic material as DNA , which can be copied to make another molecule called RNA . DNA consists of two strands that are wound around each other in a double helix . RNA is made in a similar way to DNA , but it is usually present as a single strand that folds into a three-dimensional structure t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Molecular insights into RNA and DNA helicase evolution from the determinants of specificity for a DEAD-box RNA helicase
Alvinocaridid shrimps are emblematic representatives of the deep hydrothermal vent fauna at the Mid-Atlantic Ridge . They are adapted to a mostly aphotic habitat with extreme physicochemical conditions in the vicinity of the hydrothermal fluid emissions . Here , we investigated the brain architecture of the vent shrimp...	Oceanic vents are areas where hot gases and liquids emerge from cracks and chimneys on the seafloor . These fluids can be as hot as 350°C and are rich in potentially toxic chemicals . Nevertheless , they are the key energy source of many animals that make the vents their home . Vents can be found thousands of meters un...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Neuroanatomy of a hydrothermal vent shrimp provides insights into the evolution of crustacean integrative brain centers
NRF2 is emerging as a major regulator of cellular metabolism . However , most studies have been performed in cancer cells , where co-occurring mutations and tumor selective pressures complicate the influence of NRF2 on metabolism . Here we use genetically engineered , non-transformed primary murine cells to isolate the...	Cancers form in humans and other animals when cells of the body develop mutations that allow them to grow and divide uncontrollably . The set of chemical reactions happening inside cancer cells , referred to as “metabolism” , can be very different to metabolism in the healthy cells they originate from . Some of these d...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cancer", "biology" ]	2019	Cysteine dioxygenase 1 is a metabolic liability for non-small cell lung cancer
Do developmental systems preferentially produce certain types of variation that orient phenotypic evolution along preferred directions ? At different scales , from the intra-population to the interspecific , the murine first upper molar shows repeated anterior elongation . Using a novel quantitative approach to compare...	Over time species develop random mutations in their genetic sequence that causes their form to change . If this new form increases the survival of a species it will become favored through natural selection and is more likely to get passed on to future generations . But , the evolution of these new traits also depends o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2020	Developmental variability channels mouse molar evolution
Ubiquitination by HECT E3 enzymes regulates myriad processes , including tumor suppression , transcription , protein trafficking , and degradation . HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins . The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin ...	Ubiquitin is a small protein that can be covalently linked to other , ‘target’ , proteins in a cell to influence their behavior . Ubiquitin can be linked to its targets either as single copies or as polyubiquitin chains in which several ubiquitin molecules are bound end-on-end to each other , with one end of the chain ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
Ataxia-telangiectasia mutated ( ATM ) protein kinase regulates the DNA damage response ( DDR ) and is associated with cancer suppression . Here we report a cancer-promoting role for ATM . ATM depletion in metastatic cancer cells reduced cell migration and invasion . Transcription analyses identified a gene network , in...	Damaged DNA threatens the normal activity of living cells , so cells use a number of mechanisms to ensure that this damage is repaired . When DNA is damaged , an enzyme called ATM activates several other proteins that ultimately lead to the DNA being repaired . Problems with detecting and repairing damaged DNA have bee...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2015	ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion
Actin-based thin filament arrays constitute a fundamental core component of muscle sarcomeres . We have used formation of the Drosophila indirect flight musculature for studying the assembly and maturation of thin-filament arrays in a skeletal muscle model system . Employing GFP-tagged actin monomer incorporation , we ...	Muscles owe their ability to contract to structural units called sarcomeres , and a single muscle fiber can contain many thousands of these structures , aligned one next to the other . Each mature sarcomere is made up of precisely arranged and intertwined thin filaments of actin and thicker bundles of motor proteins , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	The Drosophila formin Fhos is a primary mediator of sarcomeric thin-filament array assembly
In the developing mammalian brain , differentiating neurons mature morphologically via neuronal polarity programs . Despite discovery of polarity pathways acting concurrently with differentiation , it's unclear how neurons traverse complex polarity transitions or how neuronal progenitors delay polarization during devel...	During the formation of the brain , developing neurons are faced with a logistical problem . After newborn neurons form they must change in shape and move to their final location in the brain . Despite much speculation , little is known about these processes . Neurons mature via the activity of several pathways that co...	[ "Abstract", "Introduction", "Result", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2016	Zeb1 controls neuron differentiation and germinal zone exit by a mesenchymal-epithelial-like transition
No evidence has shown whether insect-borne viruses manipulate the c-Jun N-terminal kinase ( JNK ) signaling pathway of vector insects . Using a system comprising the plant virus Rice stripe virus ( RSV ) and its vector insect , the small brown planthopper , we have studied the response of the vector insect’s JNK pathwa...	There are over a thousand different viruses that infect plants . Many plant viruses are transmitted by insects that feed on the plants , much as mosquitoes spread diseases between people when feeding on blood . Often the plant virus can replicate inside the cells of the insect . However , unlike in the plant hosts , th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2017	The c-Jun N-terminal kinase pathway of a vector insect is activated by virus capsid protein and promotes viral replication
Chromatin remodeling processes are among the most important regulatory mechanisms in controlling cell proliferation and regeneration . Drosophila intestinal stem cells ( ISCs ) exhibit self-renewal potentials , maintain tissue homeostasis , and serve as an excellent model for studying cell growth and regeneration . In ...	Most tissues can generate new cells to repair damage or replace worn-out cells . The new cells are often generated from stem cells—cells that can either reproduce themselves or mature into other types of cells . In the fruit-fly Drosophila , for example , intestinal stem cells in the midgut are capable of producing mor...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2013	Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling
Mesial temporal lobe epilepsy ( mTLE ) is the most common focal epilepsy in adults and is often refractory to medication . So far , resection of the epileptogenic focus represents the only curative therapy . It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity ....	Roughly one percent of people in the world suffer from epilepsy , a disorder in which individuals experience seizures due to abnormal electrical activity in the brain . Seizures can vary from brief episodes of amnesia or déjà-vu to convulsions and loss of consciousness . In adults , the most common form of epilepsy is ...	[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]	[ "neuroscience" ]	2017	Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy
How myoblast populations are regulated for the formation of muscles of different sizes is an essentially unanswered question . The large flight muscles of Drosophila develop from adult muscle progenitor ( AMP ) cells set-aside embryonically . The thoracic segments are all allotted the same small AMP number , while thos...	Muscle tissues must grow and change to accommodate the needs of an animal at various stages in its life . For example , fruit flies begin life as larvae and their muscles must help them move their soft bodies . Later , when the flies mature into adults , the muscles must provide power for flight and support for the ins...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2014	Identification of a new stem cell population that generates Drosophila flight muscles
Dentate neural stem cells produce neurons throughout life in mammals . Sonic hedgehog ( Shh ) is critical for maintenance of these cells; however , the perinatal source of Shh is enigmatic . In the present study , we examined the role of Shh expressed by hair follicles ( HFs ) that expand perinatally in temporal concor...	Although most of the neurons in the brain have been made by the time we are born , new neurons develop throughout life in part of the brain called the hippocampus . These neurons are thought to help with learning and forming memories . Conditions such as depression and Alzheimer's disease have been linked to not being ...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "developmental", "biology", "neuroscience" ]	2015	Epithelial cells supply Sonic Hedgehog to the perinatal dentate gyrus via transport by platelets
Heterochromatin , a highly compact chromatin state characterized by histone H3K9 methylation and HP1 protein binding , silences the underlying DNA and influences the expression of neighboring genes . However , the mechanisms that regulate heterochromatin spreading are not well understood . In this study , we show that ...	The DNA in the nucleus of a cell is wrapped around histone proteins to form a compact structure known as chromatin . Chromatin's structure can control how the genes in DNA are expressed . Loosely packed chromatin contains active genes , whereas densely packed chromatin ( also called ‘heterochromatin’ ) contains silence...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2015	Rapid epigenetic adaptation to uncontrolled heterochromatin spreading
During Drosophila embryonic nervous system development , neuroblasts express a programmed cascade of five temporal transcription factors that govern the identity of cells generated at different time-points . However , these five temporal genes fall short of accounting for the many distinct cell types generated in large...	As a nervous system develops , stem cells generate different types of nerve cells at different times . This series of events follows a fixed schedule in developing embryos , and even a single stem cell that is removed and then grown outside the body will follow the same schedule . This strongly suggests that stem cells...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "neuroscience" ]	2016	Neuronal cell fate diversification controlled by sub-temporal action of Kruppel
Many primary sensory cilia exhibit unique architectures that are critical for transduction of specific sensory stimuli . Although basic ciliogenic mechanisms are well described , how complex ciliary structures are generated remains unclear . Seminal work performed several decades ago provided an initial but incomplete ...	To survive , animals must constantly gather information about their surroundings and then decide how to respond . Animals rely on cells called sensory neurons to help them perceive and process this information , and these neurons in most animals have smaller structures called cilia that help them to gather this informa...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans
Patterns of spatial positioning of individuals within microbial communities are often critical to community function . However , understanding patterning in natural communities is hampered by the multitude of cell–cell and cell–environment interactions as well as environmental variability . Here , through simulations a...	Microorganisms such as bacteria , archaea and tiny eukaryotes are found throughout the biosphere . Some of these microorganisms are pathogens that cause diseases in animals , while others provide nutrients , including essential amino acids and vitamins; there are also microorganisms that have critical roles in recyclin...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2013	Strong inter-population cooperation leads to partner intermixing in microbial communities
Cell-cell communication via gap junctions regulates a wide range of physiological processes by enabling the direct intercellular electrical and chemical coupling . However , the in vivo distribution and function of gap junctions remain poorly understood , partly due to the lack of non-invasive tools with both cell-type...	For the tissues and organs of our bodies to work properly , the cells within them need to communicate with each other . One important part of cellular communication is the movement of signals – usually small molecules or ions – directly from one cell to another . This happens via structures called gap junctions , a typ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2019	PARIS, an optogenetic method for functionally mapping gap junctions
Inhibitions and antagonists of L-type Ca2+ channels are important to both research and therapeutics . Here , we report C-terminus mediated inhibition ( CMI ) for CaV1 . 3 that multiple motifs coordinate to tune down Ca2+ current and Ca2+ influx toward the lower limits determined by end-stage CDI ( Ca2+-dependent inacti...	All cells need calcium ions to stay healthy , but having too many calcium ions can interfere with important processes in the cell and cause severe problems . Proteins known as calcium channels on the cell surface allow calcium ions to flow into the cell from the surrounding environment . Cells carefully control the ope...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2017	Cooperative and acute inhibition by multiple C-terminal motifs of L-type Ca2+ channels
Anthracycline-induced cardiotoxicity ( ACT ) is a key limiting factor in setting optimal chemotherapy regimes , with almost half of patients expected to develop congestive heart failure given high doses . However , the genetic basis of sensitivity to anthracyclines remains unclear . We created a panel of iPSC-derived c...	Many cancers , including leukaemia , lymphoma and breast cancer , are treated with potent chemotherapy drugs such as anthracyclines . However , anthracyclines have strong side effects known as anthracycline cardiotoxicity , which affect the health of the heart . Almost half of the patients given high doses of anthracyc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2018	Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes
The coordination of activity across neocortical areas is essential for mammalian brain function . Understanding this process requires simultaneous functional measurements across the cortex . In order to dissociate direct cortico-cortical interactions from other sources of neuronal correlations , it is furthermore desir...	Behavior and cognition – the process of thought – emerge from computations that occur within vast networks of neurons in the brain . Within these networks , neurons may communicate with their neighbours in the same brain region as well as with distant counterparts in remote brain regions . Neuroscientists have studied ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Long-range population dynamics of anatomically defined neocortical networks
How proteins control the biogenesis of cellular lipid droplets ( LDs ) is poorly understood . Using Drosophila and human cells , we show here that seipin , an ER protein implicated in LD biology , mediates a discrete step in LD formation—the conversion of small , nascent LDs to larger , mature LDs . Seipin forms discre...	Living organisms often store energy in the form of fat molecules called triglycerides . Enzymes in a compartment of the cell called the endoplasmic reticulum catalyze the chemical reactions needed to make these triglycerides . The cell then stores the triglycerides in a different structure called the lipid droplet . Li...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Seipin is required for converting nascent to mature lipid droplets
Clathrin-mediated endocytosis is an evolutionarily ancient membrane transport system regulating cellular receptivity and responsiveness . Plasmalemma clathrin-coated structures range from unitary domed assemblies to expansive planar constructions with internal or flanking invaginated buds . Precisely how these morpholo...	Cells can take proteins and other molecules that are either embedded in , or attached to , their surface membrane and move them inside via a process called endocytosis . This process often involves a protein called clathrin working together with numerous other proteins . Early on , a complex of four proteins , called t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2014	A clathrin coat assembly role for the muniscin protein central linker revealed by TALEN-mediated gene editing
Vertebrate neck musculature spans the transition zone between head and trunk . The extent to which the cucullaris muscle is a cranial muscle allied with the gill levators of anamniotes or is instead a trunk muscle is an ongoing debate . Novel computed tomography datasets reveal broad conservation of the cucullaris in g...	Muscles in the head and trunk ( main body ) form from different parts of the embryo , and their development uses different genes . Trunk muscles are derived from somites – paired blocks of cells arranged in segments on either side of the midline ( which divides the body into left and right halves ) . By contrast , cell...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "evolutionary", "biology" ]	2016	Evolution of the head-trunk interface in tetrapod vertebrates
Colistin is an antibiotic of last resort , but has poor efficacy and resistance is a growing problem . Whilst it is well established that colistin disrupts the bacterial outer membrane ( OM ) by selectively targeting lipopolysaccharide ( LPS ) , it was unclear how this led to bacterial killing . We discovered that MCR-...	Antibiotics are life-saving medicines , but many bacteria now have the ability to resist their effects . For some infections , all frontline antibiotics are now ineffective . To treat infections caused by these highly resistant bacteria , clinicians must use so-called ‘antibiotics of last resort’ . These antibiotics in...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2021	Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane
We study the effects of inbreeding in a dioecious plant on its interaction with pollinating insects and test whether the magnitude of such effects is shaped by plant individual sex and the evolutionary histories of plant populations . We recorded spatial , scent , colour , and rewarding flower traits as well as pollina...	Destroying habitats can reduce the size of local populations of many plants and animals . For plants , a smaller population means a greater chance of inbreeding , where individual plants that are closely related to each other mate and produce offspring . Inbreeding often results in offspring that are weaker than their ...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "ecology", "evolutionary", "biology" ]	2021	Inbreeding in a dioecious plant has sex- and population origin-specific effects on its interactions with pollinators
Many mammalian cancer cell lines depend on glutamine as a major tri-carboxylic acid ( TCA ) cycle anaplerotic substrate to support proliferation . However , some cell lines that depend on glutamine anaplerosis in culture rely less on glutamine catabolism to proliferate in vivo . We sought to understand the environmenta...	Cancer cells need to consume certain nutrients in order to grow , and some cancer drugs work by affecting the ability of the cells to use these nutrients . For decades researchers have grown cancer cells in petri dishes with standard nutrient formulations ( also known as tissue culture ) , but the nutrients available t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2017	Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition
In many organisms , it remains unclear how X chromosomes are specified for dosage compensation , since DNA sequence motifs shown to be important for dosage compensation complex ( DCC ) recruitment are themselves not X-specific . Here , we addressed this problem in C . elegans . We found that the DCC recruiter , SDC-2 ,...	The DNA inside living cells is organized in structures called chromosomes . In many animals , females have two X chromosomes , whereas males have only one . To ensure that females do not end up with a double dose of the proteins encoded by the genes on the X chromosome , animals use a process called dosage compensation...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2017	Cooperation between a hierarchical set of recruitment sites targets the X chromosome for dosage compensation
Concussion is associated with a myriad of deleterious immediate and long-term consequences . Yet the molecular mechanisms and genetic targets promoting the selective vulnerability of different neural subtypes to dysfunction and degeneration remain unclear . Translating experimental models of blunt force trauma in C . e...	Concussion is a type of traumatic brain injury that results from a sudden blow or jolt to the head . Symptoms can include a passing headache , dizziness , confusion or sensitivity to light , but experiencing multiple concussions can have drastic repercussions in later life . Studies of professional athletes have shown ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2021	Glycolytic preconditioning in astrocytes mitigates trauma-induced neurodegeneration
Restoring somatosensory feedback to people with limb amputations is crucial to improve prosthetic control . Multiple studies have demonstrated that peripheral nerve stimulation and targeted reinnervation can provide somatotopically relevant sensory feedback . While effective , the surgical procedures required for these...	Even some of the most advanced prosthetic arms lack an important feature: the ability to relay information about touch or pressure to the wearer . In fact , many people prefer to use simpler prostheses whose cables and harnesses pass on information about tension . However , recent studies suggest that electrical stimul...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2020	Sensory restoration by epidural stimulation of the lateral spinal cord in upper-limb amputees
The two partners required for sexual reproduction are rarely the same . This pattern extends to species which lack sexual dimorphism yet possess self-incompatible gametes determined at mating-type regions of suppressed recombination , likely precursors of sex chromosomes . Here we investigate the role of cellular signa...	Sexual reproduction , from birds to bees , relies on distinct classes of sex cells , known as gametes , fusing together . Most single cell organisms , rather than producing eggs and sperm , have similar sized gametes that fall into distinct ‘mating types’ . However , only sex cells belonging to different mating types c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "computational", "and", "systems", "biology" ]	2019	Evolution of asymmetric gamete signaling and suppressed recombination at the mating type locus
The anterior thalamic nucleus ( ATN ) is thought to play an important role in a brain network involving the hippocampus and neocortex , which enables human memories to be formed . However , its small size and location deep within the brain have impeded direct investigation in humans with non-invasive techniques . Here ...	Memories , both the mundane and the significant , play an integral role in our daily lives . Scientists have long sought to establish exactly how our memories are formed; how does an experience , with its sights , sounds and feelings , become a mental representation stored within our brain ? One way to investigate this...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation
Vaccination of cattle against bovine Tuberculosis ( bTB ) has been a long-term policy objective for countries where disease continues to persist despite costly test-and-slaughter programs . The potential use of vaccination within the European Union has been linked to a need for field evaluation of any prospective vacci...	Bovine tuberculosis is an infectious disease of livestock and wildlife in many parts of the world . It also can spread to humans . In the United Kingdom ( UK ) , infected cattle and badgers contribute to its spread . To control bovine tuberculosis , cattle are tested and infected animals are slaughtered . Badgers in ar...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "computational", "and", "systems", "biology" ]	2018	The intractable challenge of evaluating cattle vaccination as a control for bovine Tuberculosis
Keratinocytes , the predominant cell type of the epidermis , migrate to reinstate the epithelial barrier during wound healing . Mechanical cues are known to regulate keratinocyte re-epithelialization and wound healing; however , the underlying molecular transducers and biophysical mechanisms remain elusive . Here , we ...	The skin is the largest organ of the body . It enables touch sensation and protects against external insults . Wounding of the skin exposes the body to an increased risk of infection , disease and scar formation . During wound healing , the cells in the topmost layer of the skin , called keratinocytes , move in from th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2021	Spatiotemporal dynamics of PIEZO1 localization controls keratinocyte migration during wound healing
Replicative aging in yeast is asymmetric–mother cells age but their daughter cells are rejuvenated . Here we identify an asymmetry in pH between mother and daughter cells that underlies aging and rejuvenation . Cytosolic pH increases in aging mother cells , but is more acidic in daughter cells . This is due to the asym...	Aging is a part of life—but its biological basis and , in particular , how aged cells give rise to young offspring ( or progeny ) has not been clearly established for any organism . Budding yeast is a microorganism that is a valuable model to understand aging in more complex organisms like humans . Budding yeast cells ...	[ "Abstract", "Main", "text", "Materials", "and", "methods" ]	[ "developmental", "biology", "short", "report", "cell", "biology" ]	2014	Mother-daughter asymmetry of pH underlies aging and rejuvenation in yeast
The directed evolution of biomolecules to improve or change their activity is central to many engineering and synthetic biology efforts . However , selecting improved variants from gene libraries in living cells requires plasmid expression systems that suffer from variable copy number effects , or the use of complex ma...	Over the course of billions of years , natural evolution has produced new proteins and adapted existing ones so that they work better . Scientists have learned how to use the principles that underlie evolution to similarly engineer proteins in the laboratory . This process , known as directed evolution , is a powerful ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Selection of chromosomal DNA libraries using a multiplex CRISPR system
The Rho GTPase Rac1 activates the WAVE regulatory complex ( WRC ) to drive Arp2/3 complex-mediated actin polymerization , which underpins diverse cellular processes . Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy . Surprisingly , Rac1 is not located at the binding site on the...	Our cells contain a network of filaments made up of a protein called actin . Just like the skeleton that supports our body , the actin ‘cytoskeleton’ gives a cell its shape and strength . Actin filaments are also critical for many other processes including enabling cells to move and divide . The assembly of actin filam...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2017	Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites
Assessing the imminence of threatening events using environmental cues enables proactive engagement of appropriate avoidance responses . The neural processes employed to anticipate event occurrence depend upon which cue properties are used to formulate predictions . In serial compound stimulus ( SCS ) conditioning in m...	If you notice the skies above you becoming darker , your first thought might be to seek shelter . Experience will have taught you that darkening skies are often a sign of an approaching storm . Learning to recognise changes that occur prior to an unpleasant event can help us avoid danger . But this is not the only stra...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Stimulus salience determines defensive behaviors elicited by aversively conditioned serial compound auditory stimuli
The sense of smell enables animals to react to long-distance cues according to learned and innate valences . Here , we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe , an olfactory neuropil similar to the vertebrate olfactory bulb . We found a canonical circuit w...	Our sense of smell can tell us about bread being baked faraway in the kitchen , or whether a leftover piece finally went bad . Similarly to the eyes , the nose enables us to make up a mental image of what lies at a distance . In mammals , the surface of the nose hosts a huge number of olfactory sensory cells , each of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	The wiring diagram of a glomerular olfactory system
The mechanism that leads to liquid-liquid phase separation ( LLPS ) of the tau protein , whose pathological aggregation is implicated in neurodegenerative disorders , is not well understood . Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding whether LLPS is an equ...	Proteins make up much of the machinery of cells and perform many roles that are essential for life . Some important proteins – known as intrinsically disordered proteins – lack any stable three-dimensional structure . One such protein , called tau , is best known for its ability to form tangles in the brain , and a bui...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2019	Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions
In presynaptic boutons , calcium ( Ca2+ ) triggers both neurotransmitter release and short-term synaptic plasticity . Whereas synaptotagmins are known to mediate vesicle fusion through binding of high local Ca2+ to their C2 domains , the proteins that sense smaller global Ca2+ increases to produce short-term plasticity...	Brain function is dependent upon the rapid transfer of information from one brain cell to the next at junctions known as synapses . When an electrical signal called an action potential is generated by the cell before the synapse , the presynaptic cell , it triggers an influx of calcium ions into that cell . These ions ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2014	Protein kinase C is a calcium sensor for presynaptic short-term plasticity
The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies . Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs , providing their role...	Tumours form when cells lose control of their growth . Usually , cells produce signals that control how much and how often they divide . But if these signals become faulty , cells may grow too quickly or multiply too often . For example , a group of proteins known as MYC proteins activate growth genes in a cell , but t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2021	MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1
Tumors frequently exhibit aberrant glycosylation , which can impact cancer progression and therapeutic responses . The hexosamine biosynthesis pathway ( HBP ) produces uridine diphosphate N-acetylglucosamine ( UDP-GlcNAc ) , a major substrate for glycosylation in the cell . Prior studies have identified the HBP as a pr...	Inside tumors , cancer cells often have to compete with each other for food and other resources they need to survive . This is a key factor driving the growth and progression of cancer . One of the resources cells need is a molecule called UDP-GlcNAc , which they use to modify many proteins so they can work properly . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2021	Glutamine deprivation triggers NAGK-dependent hexosamine salvage
Effective perceptual decisions rely upon combining sensory information with knowledge of the rewards available for different choices . However , it is not known where reward signals interact with the multiple stages of the perceptual decision-making pathway and by what mechanisms this may occur . We combined electrical...	Identifying how an object is moving in three-dimensional ( 3D ) space depends upon a brain region known as V5/MT . The neurons that make up area V5/MT form groups that each have a ‘preference’ for a particular direction of movement and a particular 3D depth . If a group of neurons detects its preferred direction of mov...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Reward modulates the effect of visual cortical microstimulation on perceptual decisions
Myelination is a biosynthetically demanding process in which mTORC1 , the gatekeeper of anabolism , occupies a privileged regulatory position . We have shown previously that loss of mTORC1 function in Schwann cells ( SCs ) hampers myelination . Here , we genetically disrupted key inhibitory components upstream of mTORC...	Neurons transmit electrical impulses throughout our body along cable-like structures called axons . Similar to electric cables , the axons are enveloped in an insulating sheath called myelin , which makes the impulses travel faster down the axon . If myelin does not form correctly or gets lost later in life , it can le...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2017	Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system
Understanding how humans represent others’ pain is critical for understanding pro-social behavior . ‘Shared experience’ theories propose common brain representations for somatic and vicarious pain , but other evidence suggests that specialized circuits are required to experience others’ suffering . Combining functional...	The ability to experience others’ pain is a cornerstone of empathy , and binds us together in times of hardship . However , we have not yet fully understood the complex interactions in the brain that make people empathetic to others’ suffering . One possibility is that we experience others’ pain through the activation ...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "neuroscience" ]	2016	Somatic and vicarious pain are represented by dissociable multivariate brain patterns
Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell , contributing to neurodegeneration and other diseases . Protein aggregates are also formed within the endoplasmic reticulum ( ER ) , although the fate of ER protein aggregates , specifically during cell division , is not we...	Many species of yeast form new cells by a process known as budding in which a small daughter cell ‘buds’ out of a larger mother cell . Mothers can only produce a limited number of buds before they die of old age . However , age is reset in the daughters to ensure that they are fully rejuvenated when born . Therefore , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	The ER Stress Surveillance (ERSU) pathway regulates daughter cell ER protein aggregate inheritance
The microbialization of coral reefs predicts that microbial oxygen consumption will cause reef deoxygenation . Here we tested this hypothesis by analyzing reef microbial and primary producer oxygen metabolisms . Metagenomic data and in vitro incubations of bacteria with primary producer exudates showed that fleshy alga...	Rising water temperatures , pollution and other factors are increasingly threatening corals and the entire reef ecosystems they build . The potential for corals to resist and recover from the stress these factors cause ultimately depends on their ability to compete against fast-growing fleshy algae that can rapidly tak...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology" ]	2019	Biophysical and physiological processes causing oxygen loss from coral reefs
When microbes acquire new abilities through horizontal gene transfer , the genes and pathways must function under conditions with which they did not coevolve . If newly-acquired genes burden the host , their utility will depend on further evolutionary refinement of the recombinant strain . We used laboratory evolution ...	Many microbes can rapidly evolve to adapt to new or extreme habitats . Most often the characteristics that develop via evolution result from individuals inheriting new combinations of genes from their parents . However , many species can also acquire new genes through a process called horizontal gene transfer , where o...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2014	Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post–transfer refinement
Bruton’s tyrosine kinase ( BTK ) is targeted in the treatment of B-cell disorders including leukemias and lymphomas . Currently approved BTK inhibitors , including Ibrutinib , a first-in-class covalent inhibitor of BTK , bind directly to the kinase active site . While effective at blocking the catalytic activity of BTK...	Treatments for blood cancers , such as leukemia and lymphoma , rely heavily on chemotherapy , using drugs that target a vulnerable aspect of the cancer cells . B-cells , a type of white blood cell that produces antibodies , require a protein called Bruton’s tyrosine kinase , or BTK for short , to survive . The drug ibr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2020	Differential impact of BTK active site inhibitors on the conformational state of full-length BTK
The auditory pathway faithfully encodes and relays auditory information to the brain with remarkable speed and precision . The inner hair cells ( IHCs ) are the primary sensory receptors adapted for rapid auditory signaling , but they are not thought to be intrinsically tuned to encode particular sound frequencies . He...	Many animals’ survival depends on them accurately and quickly identifying sounds in their environment . In animals with backbones , cells with hair-like projections ( called hair cells ) inside the ear convert information collected from sound waves into electrical signals . These signals are then transmitted to the bra...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Membrane properties specialize mammalian inner hair cells for frequency or intensity encoding
Cell division is essential to expand , shape , and replenish epithelia . In the adult small intestine , cells from a common progenitor intermix with other lineages , whereas cell progeny in many other epithelia form contiguous patches . The mechanisms that generate these distinct patterns of progeny are poorly understo...	The body has an impressive ability to renew itself by replacing old and damaged cells with new ones . This can happen rapidly; for example , the lining of the intestine renews itself approximately every five days . The lining contains many different cell types , which exchange important signals with their neighbors . T...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2018	Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia
Many epithelial cancers show cell cycle dysfunction tightly correlated with the overexpression of the serine/threonine kinase Aurora A ( AURKA ) . Its role in mitotic progression has been extensively characterised , and evidence for new AURKA functions emerges . Here , we reveal that AURKA is located and imported in mi...	Structures called mitochondria power cells by turning oxygen and sugar into chemical energy . Each cell can have thousands of mitochondria , which work together to supply changing energy demands . They can fuse together or break apart , forming networks that change size and produce different amounts of energy . Getting...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2018	Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
Malaria transmission relies on the production of gametes following ingestion by a mosquito . Here , we show that Ca2+-dependent protein kinase 4 controls three processes essential to progress from a single haploid microgametocyte to the release of eight flagellated microgametes in Plasmodium berghei . A myristoylated i...	Malaria is caused by parasites called Plasmodium , which are carried between humans by infected mosquitoes . The parasite needs to move between its insect and human hosts to complete its life cycle , and efforts to stop the spread of malaria are now focussed on blocking this movement . In the blood of infected humans ,...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]	2017	Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis
Prevention of relapses is a major challenge in treating anxiety disorders . Fear reinstatement can cause relapse in spite of successful fear reduction through extinction-based exposure therapy . By utilising a contextual fear-conditioning task in mice , we found that reinstatement was accompanied by decreased c-Fos exp...	Anxiety disorders affect millions of people worldwide . While many people with anxiety disorders can recover with appropriate treatment , about 40% of these individuals will encounter a relapse of their condition . Researchers can investigate the causes of relapses by creating animal models of the processes involved . ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Prefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits
Mitochondrial division is important for mitochondrial distribution and function . Recent data have demonstrated that ER–mitochondria contacts mark mitochondrial division sites , but the molecular basis and functions of these contacts are not understood . Here we show that in yeast , the ER–mitochondria tethering comple...	Mitochondria generate most of the energy used by cells , and they also play key roles in cellular growth , death , and differentiation . They are evolutionarily derived from bacteria and have retained their own DNA and protein translation system , but they are also dependent on the cell for their growth and replication...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2013	ER-associated mitochondrial division links the distribution of mitochondria and mitochondrial DNA in yeast
In contrast to transcriptional regulation , the function of alternative splicing ( AS ) in stem cells is poorly understood . In mammals , MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however , little is known about the in vivo significance of this regulation . We studied AS in a p...	Stem cells are specialized cells found in all animals that can develop into several different types of mature cells . Stem cells are therefore well suited for maintaining organs that are in heavy use , such as the intestine , and for regenerating tissues that are prone to injury , like the skin . One reason why stem ce...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2016	Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians
Asia is considered an important source of influenza A virus ( IAV ) pandemics , owing to large , diverse viral reservoirs in poultry and swine . However , the zoonotic origins of the 2009 A/H1N1 influenza pandemic virus ( pdmH1N1 ) remain unclear , due to conflicting evidence from swine and humans . There is strong evi...	In 2009 a new influenza virus jumped from pigs to humans and spread very rapidly , causing an initial outbreak in Mexico and becoming a global pandemic in just a few months . Although the most straightforward explanation is that the virus originated in swine in Mexico , several studies suggested that this was unlikely ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2016	Origins of the 2009 H1N1 influenza pandemic in swine in Mexico
Nonribosomal peptides represent a large class of metabolites with pharmaceutical relevance . Pteridines , such as pterins , folates , and flavins , are heterocyclic metabolites that often serve as redox-active cofactors . The biosynthetic machineries for construction of these distinct classes of small molecules operate...	Many bacteria produce small molecules that can be used as a basis for developing new drugs . The instructions for the pathways that make these molecules are stored in the genome – the complete set of genetic material – of the bacteria . With the advancements in genome sequencing over the last decade , these instruction...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "genetics", "and", "genomics" ]	2017	Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster
Over two-thirds of integral membrane proteins of known structure assemble into oligomers . Yet , the forces that drive the association of these proteins remain to be delineated , as the lipid bilayer is a solvent environment that is both structurally and chemically complex . In this study , we reveal how the lipid solv...	A cell’s outer membrane is made of molecules called lipids , which band together to form a flexible thin film , just two molecules thick . This membrane is dotted with proteins that transport materials in to and out of cells . Most of these membrane proteins join with other proteins to form structures known as oligomer...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2021	Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states
The majority of human breast cancer is estrogen receptor alpha ( ER ) positive . While anti-estrogens/aromatase inhibitors are initially effective , resistance to these drugs commonly develops . Therapy-resistant tumors often retain ER signaling , via interaction with critical oncogenic coregulator proteins . To addres...	Around 70% of breast cancers in women need one or both of the female hormones ( estrogen and progesterone ) to grow . To treat these 'hormone-dependent' cancers , patients receive drugs that either block the production of estrogen or directly target a receptor protein that senses estrogen in the cancer cells . Unfortun...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2017	Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers
One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions . We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon ( GBT ) protein trap to simultaneously report and reversibly knockdown the tagged genes . Protein...	The human genome counts over 20 , 000 genes , which can be turned on and off to create the proteins required for most of life processes . Once produced , proteins need move to specific locations in the cell , where they are able to perform their jobs . Despite striking scientific advances , 90% of human genes are still...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "tools", "and", "resources" ]	2020	Building the vertebrate codex using the gene breaking protein trap library
Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time , which may restrict a cell’s ability to adapt to unanticipated environmental challenges . To bypass this limitation , cells have evolved mechanisms whereby exposure to mild stress increases their...	Harmful external conditions , such as extreme heat or radiation , can cause stress to cells that may lead to permanent damage and even death . Cell stress is responsible for some cancers and degenerative diseases , and is involved in the process of aging . Cells respond to stress by modifying their activities in order ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "computational", "and", "systems", "biology" ]	2017	Nonlinear feedback drives homeostatic plasticity in H2O2 stress response
Neurotransmitter release is mediated by the fast , calcium-triggered fusion of synaptic vesicles with the presynaptic plasma membrane , followed by endocytosis and recycling of the membrane of synaptic vesicles . While many of the proteins governing these processes are known , their regulation is only beginning to be u...	The human nervous system contains more than a hundred billion neurons that are connected with each other via junctions called synapses . When an electrical impulse travelling along a neuron arrives at a synapse , it triggers bubble-like packages called synaptic vesicles within the neuron to merge with the neuron’s surf...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Analysis of protein phosphorylation in nerve terminal reveals extensive changes in active zone proteins upon exocytosis
Ribosome stalling during translation can potentially be harmful , and is surveyed by a conserved quality control pathway that targets the associated mRNA and nascent polypeptide chain ( NC ) . In this pathway , the ribosome-associated quality control ( RQC ) complex promotes the ubiquitylation and degradation of NCs re...	Cells use molecular machines called ribosomes to build proteins by connecting amino acids – the building blocks of proteins – together in a particular sequence . The chain of amino acids gradually lengthens as the protein forms , yet remains attached to the ribosome until the protein is complete . While this process is...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2016	The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation

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