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Changes in temperature affect biochemical reaction rates and , consequently , neural processing . The nervous systems of poikilothermic animals must have evolved mechanisms enabling them to retain their functionality under varying temperatures . Auditory receptor neurons of grasshoppers respond to sound in a surprising...	Warm-blooded animals—including mammals and birds—expend large amounts of energy in keeping their body temperature constant regardless of how hot or cold their environment is . By contrast , the body temperature of cold-blooded animals—including amphibians , reptiles , and insects—follows that of their surroundings . Co...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Cell-intrinsic mechanisms of temperature compensation in a grasshopper sensory receptor neuron
Results from genome-wide association studies ( GWAS ) can be used to infer causal relationships between phenotypes , using a strategy known as 2-sample Mendelian randomization ( 2SMR ) and bypassing the need for individual-level data . However , 2SMR methods are evolving rapidly and GWAS results are often insufficientl...	Our health is affected by many exposures and risk factors , including aspects of our lifestyles , our environments , and our biology . It can , however , be hard to work out the causes of health outcomes because ill-health can influence risk factors and risk factors tend to influence each other . To work out whether pa...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "tools", "and", "resources" ]	2018	The MR-Base platform supports systematic causal inference across the human phenome
The dynamic organization of signaling cascades inside primary cilia is key to signal propagation . Yet little is known about the dynamics of ciliary membrane proteins besides a possible role for motor-driven Intraflagellar Transport ( IFT ) . To characterize these dynamics , we imaged single molecules of Somatostatin R...	Primary cilia are tiny protrusions from the cell surface , which have a central role in processing sensory stimuli , such as light or odorants . Cilia are also involved in mediating the response to developmental signaling molecules , including Sonic Hedgehog , and may help to convert mechanical signals into electrical ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2013	Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors
In neuronal processes , microtubules ( MTs ) provide structural support and serve as tracks for molecular motors . While it is known that neuronal MTs are more stable than MTs in non-neuronal cells , the molecular mechanisms underlying this stability are not fully understood . In this study , we used live fluorescence ...	Microtubules are tiny tubular structures made from many copies of proteins called tubulins . Microtubules have a number of important roles inside cells: they are part of the cytoskeleton that provides structural support for the cell; they help to pull chromosomes apart during cell division; and they guide the trafficki...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2014	PTRN-1, a microtubule minus end-binding CAMSAP homolog, promotes microtubule function in Caenorhabditis elegans neurons
Proteins are necessary for cellular growth . Concurrently , however , protein production has high energetic demands associated with transcription and translation . Here , we propose that activity of molecular chaperones shape protein burden , that is the fitness costs associated with expression of unneeded proteins . T...	Proteins are vital for almost every process that keeps cells alive . They are made from chains of small molecules called amino acids , which need to fold into three-dimensional structures for the protein to become active . Specific molecules called chaperones help the proteins to fold properly . However , to produce pr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "genetics", "and", "genomics" ]	2018	Hsp70-associated chaperones have a critical role in buffering protein production costs
Zinc is widely recognized as essential for growth and proliferation , yet the mechanisms of how zinc deficiency arrests these processes remain enigmatic . Here we induce subtle zinc perturbations and track asynchronously cycling cells throughout division using fluorescent reporters , high throughput microscopy , and qu...	For an animal to grow , its cells have to divide . Cell division can only take place if the cell meets certain conditions: for example , the cell’s DNA must not be damaged . To ensure that cells only divide when these conditions are met , the cell goes through a series of stages or phases with checkpoints known as the ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2020	Single cell analysis reveals multiple requirements for zinc in the mammalian cell cycle
It is well documented that transposable elements ( TEs ) can regulate the expression of neighbouring genes . However , their ability to act in trans and influence ectopic loci has been reported rarely . We searched in rice transcriptomes for tissue-specific expression of TEs and found them to be regulated developmental...	An organism’s genome contains all of the DNA the individual needs to survive and grow . Transposons are pieces of DNA that can move around the genome . They make up almost half of human DNA and over 85% of the DNA of major crop plants like maize , barley and wheat . When transposons move they can cause harmful changes ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2017	Regulation of rice root development by a retrotransposon acting as a microRNA sponge
Diatoms are photosynthetic microorganisms of great ecological and biogeochemical importance , forming vast blooms in aquatic ecosystems . However , we are still lacking fundamental understanding of how individual cells sense and respond to diverse stress conditions , and what acclimation strategies are employed during ...	Microscopic algae , such as diatoms , are widely spread throughout the oceans , and are responsible for half of the oxygen we breathe . At certain times of the year these algae grow very rapidly to form large “blooms” that can be detected by satellites in space . These blooms are generally short-lived because the algae...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "microbiology", "and", "infectious", "disease" ]	2019	Light-dependent single-cell heterogeneity in the chloroplast redox state regulates cell fate in a marine diatom
Prions are self-propagating protein aggregates that are characteristically transmissible . In mammals , the PrP protein can form a prion that causes the fatal transmissible spongiform encephalopathies . Prions have also been uncovered in fungi , where they act as heritable , protein-based genetic elements . We previous...	Unlike most infectious agents—such as viruses or bacteria—that contain genetic material in the form of DNA or RNA , a prion is simply an aggregate of misfolded proteins . Although they are not living organisms , these prion aggregates can self-propagate; when they enter a healthy organism , they cause existing , correc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "microbiology", "and", "infectious", "disease" ]	2014	Prion propagation can occur in a prokaryote and requires the ClpB chaperone
In budding yeast , if the spindle becomes mispositioned , cells prevent exit from mitosis by inhibiting the mitotic exit network ( MEN ) . The MEN is a signaling cascade that localizes to spindle pole bodies ( SPBs ) and activates the phosphatase Cdc14 . There are two competing models that explain MEN regulation by spi...	Most cells duplicate their genetic material and then separate the two copies before they divide . This is true for budding yeast cells , which divide in an unusual manner . New daughter cells grow as a bud on the side of a larger mother cell and are eventually pinched off . To make healthy daughter cells , yeast must s...	[ "Abstract", "Introduction", "Results", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2016	Spatial signals link exit from mitosis to spindle position
Small fly eyes should not see fine image details . Because flies exhibit saccadic visual behaviors and their compound eyes have relatively few ommatidia ( sampling points ) , their photoreceptors would be expected to generate blurry and coarse retinal images of the world . Here we demonstrate that Drosophila see the wo...	Fruit flies have five eyes: two large compound eyes which support vision , plus three smaller single lens eyes which are used for navigation . Each compound eye monitors 180° of space and consists of roughly 750 units , each containing eight light-sensitive cells called photoreceptors . This relatively wide spacing of ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2017	Microsaccadic sampling of moving image information provides Drosophila hyperacute vision
In vivo two-photon calcium imaging currently allows us to observe the activity of multiple neurons up to ~900 µm below the cortical surface without cortical invasion . However , many important brain areas are located deeper than this . Here , we used an 1100 nm laser that underfilled the back aperture of the objective ...	Microscopes can now reveal what individual cells are doing inside a living brain . In a technique called two-photon microscopy , light-sensitive proteins are introduced into the brain cells . A laser then shines light of a specific wavelength into the brain . Whenever one of the proteins in an active brain cell absorbs...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2017	Two-photon calcium imaging of the medial prefrontal cortex and hippocampus without cortical invasion
Magneto- and electro-encephalography ( MEG/EEG ) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states . Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reve...	Neurons carry information in the form of electrical signals . Each of these signals is too weak to detect on its own . But the combined signals from large groups of neurons can be detected using techniques called EEG and MEG . Sensors on or near the scalp detect changes in the electrical activity of groups of neurons f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2020	Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data
Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue , and excessive storage is a feature of common metabolic disorders . CIDEA is a lipid droplet ( LD ) -protein enriched in brown adipocytes promoting the enlargement of LDs , which are dyn...	If other energy sources become unavailable , cells fall back on stores of fatty molecules called lipids . These are held in membrane-enclosed compartments in the cell called lipid droplets , which in mammals are particularly abundant in fat cells called adipocytes . There are two main types of adipocytes: white adipocy...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2015	The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix
Pheromones , chemical signals that convey social information , mediate many insect social behaviors , including navigation and aggregation . Several studies have suggested that behavior during the immature larval stages of Drosophila development is influenced by pheromones , but none of these compounds or the pheromone...	The release of chemical signals called pheromones is a common tactic used by animals in many social situations , such as to attract potential mates or to follow trails left by other members of their colony . Larvae of the fruit fly Drosophila melanogaster—a species commonly studied in the laboratory—gather together whe...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology", "neuroscience" ]	2014	Evolved differences in larval social behavior mediated by novel pheromones
Neuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits . Channelrhodopsin-based optogenetics shows the feasibility of stimulating neural repair but does not pin down specific signaling cascades . Here , we utilized optogenetic systems , optoRaf and optoAKT , to delinea...	Most cells have a built-in regeneration signaling program that allows them to divide and repair . But , in the cells of the central nervous system , which are called neurons , this program is ineffective . This is why accidents and illnesses affecting the brain and spinal cord can cause permanent damage . Reactivating ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2020	Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila
Individuals vary in their responses to stroke and trauma , hampering predictions of outcomes . One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury . We found that in the mollusc , Tritonia diomedea , subtle differences between an...	The outcome of a traumatic brain injury or a stroke can vary considerably from person to person , making it difficult to provide a reliable prognosis for any individual person . If clinicians were able to predict outcomes with better accuracy , patients would benefit from more tailored treatments . However , the sheer ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2014	Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury
bicoid mRNA localises to the Drosophila oocyte anterior from stage 9 of oogenesis onwards to provide a local source for Bicoid protein for embryonic patterning . Live imaging at stage 9 reveals that bicoid mRNA particles undergo rapid Dynein-dependent movements near the oocyte anterior , but with no directional bias . ...	Molecules of messenger RNA , or mRNA for short , contain the instructions needed to make proteins . Many mRNAs are only found in certain parts of the cell to ensure that the corresponding proteins are only produced where they are actually needed . The mRNAs are delivered to their final location in the cell by motor pro...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	bicoid mRNA localises to the Drosophila oocyte anterior by random Dynein-mediated transport and anchoring
RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons ( IFNs ) against RNA virus infection . In this study , we found that cyclophilin A ( CypA ) , a peptidyl-prolyl cis/trans isomerase , functioned as a critical positive regulator of RIG-I-mediated antiviral immune...	In mammals , an enzyme called Cyclophilin A ( CypA ) is found in almost all tissues and plays important roles in many biological processes including the production of proteins and inflammation . Recent work suggests that it also plays a role in fighting virus infections . CypA can interact directly with a protein from ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "immunology", "and", "inflammation" ]	2017	Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses
This study examined records of 2566 consecutive COVID-19 patients at five Massachusetts hospitals and sought to predict level-of-care requirements based on clinical and laboratory data . Several classification methods were applied and compared against standard pneumonia severity scores . The need for hospitalization , ...	The new coronavirus ( now named SARS-CoV-2 ) causing the disease pandemic in 2019 ( COVID-19 ) , has so far infected over 35 million people worldwide and killed more than 1 million . Most people with COVID-19 have no symptoms or only mild symptoms . But some become seriously ill and need hospitalization . The sickest a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "microbiology", "and", "infectious", "disease" ]	2020	Early prediction of level-of-care requirements in patients with COVID-19
HIV-1 reverse transcriptase utilizes a metamorphic polymerase domain that is able to adopt two alternate structures that fulfill catalytic and structural roles , thereby minimizing its coding requirements . This ambiguity introduces folding challenges that are met by a complex maturation process . We have investigated ...	Proteins are made up of long chains of building blocks called amino acids . These chains can twist and fold in numerous ways to adopt the specific three-dimensional shapes that enable each protein to perform its role . In recent years , researchers have identified several proteins that can adopt different shapes from t...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2015	Asymmetric conformational maturation of HIV-1 reverse transcriptase
The ability to revise one’s certainty or confidence in a preceding choice is a critical feature of adaptive decision-making but the neural mechanisms underpinning this metacognitive process have yet to be characterized . In the present study , we demonstrate that the same build-to-threshold decision variable signal tha...	Reflecting on our previous choices and accurately representing our confidence in their accuracy allows us to detect , correct and learn from our errors . Yet , it remains poorly understood how such “metacognition” , or thoughts about thoughts , occurs in the human brain . In particular , a long-standing debate in this ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Neural evidence accumulation persists after choice to inform metacognitive judgments
To anticipate potential seedling damage , plants block seed germination under unfavorable conditions . Previous studies investigated how seed germination is controlled in response to abiotic stresses through gibberellic and abscisic acid signaling . However , little is known about whether seeds respond to rhizosphere b...	The plant embryo within a seed is well protected . While it cannot stay within the seed forever , the embryo can often wait for the right conditions before it develops into a seedling and continues its life cycle . Indeed , plants have evolved several ways to time this process – which is known as germination – to maxim...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2018	The plant pathogen Pseudomonas aeruginosa triggers a DELLA-dependent seed germination arrest in Arabidopsis
Light-gated chloride channels are emerging as promising optogenetic tools for inhibition of neural activity . However , their effects depend on the transmembrane chloride electrochemical gradient and may be complex due to the heterogeneity of this gradient in different developmental stages , neuronal types , and subcel...	One way to study the role of a specific neuron is to activate or inhibit the cell and then observe the consequences . This can be achieved by using optogenetics , a technique that involves introducing ‘light-gated’ ion channels in the outer membrane of a target neuron . When light is shone on the cell , these pore-like...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2018	Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon
Cyclin D1 is a critical regulator of cell cycle progression and works at the G1 to S-phase transition . Here , we report the isolation and characterization of the novel c-Myc-regulated lncRNA LAST ( LncRNA-Assisted Stabilization of Transcripts ) , which acts as a CCND1 mRNA stabilizer . Mechanistically , LAST was shown...	Cell division involves a series of steps in which the cell grows , duplicates its contents , and then divides into two . Together these steps are called the cell cycle , and the transition between each step must be controlled to make sure that events take place in the right order . Any loss of control can cause cells t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "cancer", "biology" ]	2017	LAST, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote CCND1 mRNA stability in human cells
Recent functional , proteomic and ribosome profiling studies in eukaryotes have concurrently demonstrated the translation of alternative open-reading frames ( altORFs ) in addition to annotated protein coding sequences ( CDSs ) . We show that a large number of small proteins could in fact be coded by these altORFs . Th...	Proteins are often referred to as the workhorses of the cell , and these molecules affect all aspects of human health and disease . Thus , deciphering the entire set of proteins made by an organism is often an important challenge for biologists . Genes contain the instructions to make a protein , but first they must be...	[ "Abstract", "Introduction", "Results", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "computational", "and", "systems", "biology" ]	2017	Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins
High-content phenotypic screening has become the approach of choice for drug discovery due to its ability to extract drug-specific multi-layered data . In the field of epigenetics , such screening methods have suffered from a lack of tools sensitive to selective epigenetic perturbations . Here we describe a novel appro...	Each cell contains a complete copy of a person’s genes coded in their DNA . However , for a cell to perform its specific role , it only needs a small fraction of this genetic information . The mechanisms that control which genes a cell is using fall under the umbrella of ‘epigenetics’ ( meaning beyond genetics ) . Thes...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine", "cancer", "biology" ]	2019	Improving drug discovery using image-based multiparametric analysis of the epigenetic landscape
Dopamine is thought to regulate learning from appetitive and aversive events . Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions . In low reward contexts , most dopamine neurons were exclusively inhibited by ...	There are many types of learning; one type of learning means that rewards and punishments can shape future behavior . Dopamine is a molecule that allows neurons in the brain to communicate with one another , and it is released in response to unexpected rewards . Most neuroscientists believe that dopamine is important t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Midbrain dopamine neurons signal aversion in a reward-context-dependent manner
Stem cells are maintained in a specialized microenvironment called niche but the nature of stem cell niche remains poorly defined in many systems . Here we demonstrate that intestinal epithelium-derived BMP serves as a niche signal for intestinal stem cell ( ISC ) self-renewal in Drosophila adult midgut . We find that ...	Keeping an organ in top condition requires a steady supply of fresh cells to replace those that are dead or damaged . This is particularly critical for the epithelial cells lining the intestines , which only live for a few days , but are necessary for digesting food . These cells cannot simply reproduce by cell divisio...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2014	Intestinal epithelium-derived BMP controls stem cell self-renewal in Drosophila adult midgut
HNF4α has been implicated in colitis and colon cancer in humans but the role of the different HNF4α isoforms expressed from the two different promoters ( P1 and P2 ) active in the colon is not clear . Here , we show that P1-HNF4α is expressed primarily in the differentiated compartment of the mouse colonic crypt and P2...	The digestive system in animals consists of a network of organs – including the liver , stomach , pancreas and intestines – that work together to break down food and deliver energy to the rest of the body . Many proteins called transcription factors help to guide the development of these organs and keep them healthy th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]	2016	Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer
Genomic amplification of the androgen receptor ( AR ) is an established mechanism of antiandrogen resistance in prostate cancer . Here , we show that the magnitude of AR signaling output , independent of AR genomic alteration or expression level , also contributes to antiandrogen resistance , through upregulation of th...	The prostate is a roughly walnut-sized gland that makes up part of the reproductive system in men . The normal development of this gland depends on a protein known as the androgen receptor . This protein also plays an important role in driving the growth of prostate cancers , and doctors routinely treat such cancers wi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cancer", "biology" ]	2019	GREB1 amplifies androgen receptor output in human prostate cancer and contributes to antiandrogen resistance
Pediatric neural tumors are often initiated during early development and can undergo very rapid transformation . However , the molecular basis of this early malignant susceptibility remains unknown . During Drosophila development , neural stem cells ( NSCs ) divide asymmetrically and generate intermediate progenitors t...	Some aggressive brain tumors that affect children start to form before the child is even born . These tumors often develop much more rapidly than tumors found in adults , and require fewer genetic mutations to become dangerous and invasive . However , it is not known why this happens . Fruit flies are often used as ani...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cancer", "biology" ]	2016	Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila
Murine studies have linked TGF-β signaling to emphysema , and human genome-wide association studies ( GWAS ) studies of lung function and COPD have identified associated regions near genes in the TGF-β superfamily . However , the functional regulatory mechanisms at these loci have not been identified . We performed the...	It is well known that smoking is bad for the lungs . Not only can smoking cause lung cancer , it can also lead to conditions such as emphysema . This is the gradual damage to lung tissue that occurs when the walls of the tiny air-sacs in the lungs where the blood takes up oxygen , called the alveoli , weaken and break ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "genetics", "and", "genomics" ]	2019	Identification of an emphysema-associated genetic variant near TGFB2 with regulatory effects in lung fibroblasts
Generating mammalian cells with specific mitochondrial DNA ( mtDNA ) –nuclear DNA ( nDNA ) combinations is desirable but difficult to achieve and would be enabling for studies of mitochondrial-nuclear communication and coordination in controlling cell fates and functions . We developed ‘MitoPunch’ , a pressure-driven m...	Mitochondria are specialized structures within cells that generate vital energy and biological building blocks . Mitochondria have a double membrane and contain many copies of their own circular DNA ( mitochondrial DNA ) , which include the blueprints to create just thirteen essential mitochondrial proteins . Like all ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "tools", "and", "resources" ]	2021	Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery
Although individuals of many species inexorably age , a number of observations established that the rate of aging is modulated in response to a variety of mild stresses . Here , we investigated how heat stress promotes longevity in yeast . We show that upon growth at higher temperature , yeast cells relax the retention...	Aging is often an inevitable part of life . Yet , it seems like the aging process can be sped up or slowed down in organisms as distinct as fruit flies , mice and budding yeast in response to changes in the environment . Yeast , for example , lives 40% longer when grown at the elevated – and mildly stressful – temperat...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2017	Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell
Sleep is necessary for the optimal consolidation of newly acquired procedural memories . However , the mechanisms by which motor memory traces develop during sleep remain controversial in humans , as this process has been mainly investigated indirectly by comparing pre- and post-sleep conditions . Here , we used functi...	The idea that , while you sleep , you could be honing skills such as the ability to play a musical instrument may sound like science fiction . But studies have shown that sleep , in addition to being beneficial for physical and mental health , also enhances memories laid down during the day . The process by which the b...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Network-wide reorganization of procedural memory during NREM sleep revealed by fMRI
The ultimate overexpression of a protein could cause growth defects , which are known as the protein burden . However , the expression limit at which the protein-burden effect is triggered is still unclear . To estimate this limit , we systematically measured the overexpression limits of glycolytic proteins in Saccharo...	If a cell makes too much of a given protein , it can sometimes cause problems and impair the cell’s growth . Overproducing some proteins may deplete the cell’s limited resources , meaning it does not have enough to make other more essential proteins . This phenomenon is known as the protein burden effect . Theoreticall...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2018	Estimating the protein burden limit of yeast cells by measuring the expression limits of glycolytic proteins
The emergence of cooperation is a central question in evolutionary biology . Microorganisms often cooperate by producing a chemical resource ( a public good ) that benefits other cells . The sharing of public goods depends on their diffusion through space . Previous theory suggests that spatial structure can promote ev...	The natural world is often thought of as a cruel place , with most living things ruthlessly competing for space or resources as they struggle to survive . However , from two chimps picking the fleas off each other to thousands of worker ants toiling for the good of the colony , cooperation is fairly widespread in natur...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "ecology", "physics", "of", "living", "systems" ]	2013	Spatial dilemmas of diffusible public goods
Presenilin 1 ( PS1 ) is an essential γ-secretase component , the enzyme responsible for amyloid precursor protein ( APP ) intramembraneous cleavage . Mutations in PS1 lead to dominant-inheritance of early-onset familial Alzheimer’s disease ( FAD ) . Although expression of FAD-linked PS1 mutations enhances toxic Aβ prod...	One of the hallmarks of Alzheimer’s disease is the accumulation within the brain of sticky deposits called plaques . These plaques form from clumps of molecules called amyloid-beta peptide . An enzyme called gamma-secretase generates the amyloid-beta peptide , by cutting it from a membrane-associated protein called APP...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Loss of presenilin function is associated with a selective gain of APP function
Cellular actin assembly is controlled at the barbed ends of actin filaments , where capping protein ( CP ) limits polymerization . Twinfilin is a conserved in vivo binding partner of CP , yet the significance of this interaction has remained a mystery . Here , we discover that the C-terminal tail of Twinfilin harbors a...	Plant and animal cells are supported by skeleton-like structures that can grow and shrink beneath the cell membrane , pushing and pulling on the edges of the cell . This scaffolding network – known as the cytoskeleton – contains long strands , or filaments , made from many identical copies of a protein called actin . T...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2018	A novel mode of capping protein-regulation by twinfilin
CRISPR-Cas9 genome engineering has revolutionised high-throughput functional genomic screens . However , recent work has raised concerns regarding the performance of CRISPR-Cas9 screens using TP53 wild-type human cells due to a p53-mediated DNA damage response ( DDR ) limiting the efficiency of generating viable edited...	The invention of CRISPR-Cas9 genome editing has unlocked a greater understanding of the human genome . Researchers can use this system to make targeted cuts in any gene in the genome , forcing the cell to perform a rapid repair at the cut site . These repairs often introduce mutations into the damaged area , adding or ...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "genetics", "and", "genomics" ]	2020	Parallel CRISPR-Cas9 screens clarify impacts of p53 on screen performance
Many eukaryotic protein kinases are activated by phosphorylation on a specific conserved residue in the regulatory activation loop , a post-translational modification thought to stabilize the active DFG-In state of the catalytic domain . Here we use a battery of spectroscopic methods that track different catalytic elem...	The transfer of phosphate groups onto proteins ( protein phosphorylation ) is one of the most important methods used to send signals inside cells . The enzymes that catalyze this process , called protein kinases , are themselves controlled by the phosphorylation of a flexible region called the activation loop . For man...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "computational", "and", "systems", "biology" ]	2018	A dynamic mechanism for allosteric activation of Aurora kinase A by activation loop phosphorylation
We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs , via a microscopy-based Cell Painting assay . Indeed , 50% of the 220 tested genes yielded detectable morphological profiles , which grouped into biologically ...	Many human diseases are caused by particular changes , called mutations , in patients’ DNA . A genome is the complete DNA set of an organism , which contains all the information to build the body and keep it working . This information is stored as a code made up of four chemicals called bases . Humans have about 30 , 0...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "tools", "and", "resources" ]	2017	Systematic morphological profiling of human gene and allele function via Cell Painting
Deciphering how signaling enzymes operate within discrete microenvironments is fundamental to understanding biological processes . A-kinase anchoring proteins ( AKAPs ) restrict the range of action of protein kinases within intracellular compartments . We exploited the AKAP targeting concept to create genetically encod...	In order for an animal cell to divide it needs to duplicate its DNA and split this genetic material equally between its daughter cells . This process , also known as mitosis , requires a number of different proteins that work together to coordinate this vital aspect of the cell’s lifecycle . For example , two enzymes k...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]	2019	Subcellular drug targeting illuminates local kinase action
Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral infection . Improper access to the genome leads to translocations and mutations in B cells and contributes to the mutation landscape in cancer , such as kataegis . It remains unclear how deaminases access double stranded ...	In cells , genetic information is stored within molecules of DNA , which contain sequences of four ‘bases’ arranged in different orders . Replacing one of these bases with a different base results in a mutation , which can have a positive or negative influence on the cell . Mammals use a group of enzymes called cytidin...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "immunology", "and", "inflammation" ]	2014	Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes
Insertion of helix-forming segments into the membrane and their association determines the structure , function , and expression levels of all plasma membrane proteins . However , systematic and reliable quantification of membrane-protein energetics has been challenging . We developed a deep mutational scanning method ...	Cells are defined by a thin membrane that separates the inside of the cell from the outside . The core of this membrane is hydrophobic , meaning that it repels water . Many signals and nutrients cannot pass through the membrane itself , but can pass through the proteins that span the membrane . Membrane proteins are th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2016	Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane
While the human brain is clearly large relative to body size , less is known about the timing of brain and brain component expansion within primates and the relative magnitude of volumetric increases . Using Bayesian phylogenetic comparative methods and data for both extant and fossil species , we identified that a dis...	Humans have much larger brains than other primates , but it is not clear exactly when and how this difference emerged during evolution . Some scientists believe that the expansion of a part of the brain called the neocortex – which handles sight , hearing , conscious decision-making and language – drove the increase in...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "evolutionary", "biology", "neuroscience" ]	2019	Quantitative uniqueness of human brain evolution revealed through phylogenetic comparative analysis
The cerebellum plays a crucial role in the regulation of locomotion , but how movement is represented at the synaptic level is not known . Here , we use in vivo patch-clamp recordings to show that locomotion can be directly read out from mossy fiber synaptic input and spike output in single granule cells . The increase...	Our voluntary movements , such as shaking hands and walking , are controlled by a region of the brain called the cerebellum . Inside this region is a layer of cells called granule cells , which are the smallest and also the most numerous type of neuron in the brains of mammals . Granule cells receive information from m...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	Synaptic representation of locomotion in single cerebellar granule cells
The spatial organization of synaptic inputs on the dendritic tree of cortical neurons plays a major role for dendritic integration and neural computations , yet , remarkably little is known about it . We mapped the spatial organization of glutamatergic synapses between layer 5 pyramidal cells by combining optogenetics ...	Neurons in the brain exchange information through points of contact called synapses . If electrical activity arriving at a number of synapses exceeds a certain threshold , it can trigger an electrical impulse , which is transmitted to the next neuron . Synapses generally connect with branch-like structures called dendr...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2016	Clusters of synaptic inputs on dendrites of layer 5 pyramidal cells in mouse visual cortex
Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence . However , a clear effect of sleep deprivation on aggressive behaviors remains unclear . We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly , while other social behavior...	We know from personal experience that sleepless nights can change the way we behave , sometimes making us more irritable and less adept at social interactions . However , it can be difficult to establish cause and effect: does a lack of sleep lead to altered behavior , or vice versa ? The fruit fly , Drosophila melanog...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Sleep deprivation suppresses aggression in Drosophila
Neurons lose intrinsic axon regenerative ability with maturation , but the mechanism remains unclear . Using an in-vitro laser axotomy model , we show a progressive decline in the ability of cut CNS axons to form a new growth cone and then elongate . Failure of regeneration was associated with increased retraction afte...	The nerves in the brain and spinal cord can be damaged by trauma , stroke and other conditions . Damage to these nerve fibres can destroy the connections they form with each other , which may lead to paralysis , loss of sensation and loss of body control . If we could stimulate the regeneration and reconnection of the ...	[ "Abstract", "Introduction", "Results", "Discussion" ]	[ "neuroscience" ]	2017	Selective rab11 transport and the intrinsic regenerative ability of CNS axons
The nicotinic acetylcholine receptor ( nAChR ) is a major target of autoantibodies in myasthenia gravis ( MG ) , an autoimmune disease that causes neuromuscular transmission dysfunction . Despite decades of research , the molecular mechanisms underlying MG have not been fully elucidated . Here , we present the crystal ...	Myasthenia gravis is a disease that causes chronic weakness in muscles . It affects more than 20 in every 100 , 000 people and diagnosis is becoming more common due to increased awareness of the disease . However , most current treatments only temporarily relieve symptoms so there is a need to develop more effective th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2017	Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications
Avian influenza outbreaks have been occurring on smallholder poultry farms in Asia for two decades . Farmer responses to these outbreaks can slow down or accelerate virus transmission . We used a longitudinal survey of 53 small-scale chicken farms in southern Vietnam to investigate the impact of outbreaks with disease-...	The past few decades have seen the circulation of avian influenza viruses increase in domesticated poultry , regularly creating outbreaks associated with heavy economic loss . In addition , these viruses can sometimes ‘jump’ into humans , potentially allowing new diseases – including pandemics – to emerge . The Mekong ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "epidemiology", "and", "global", "health", "microbiology", "and", "infectious", "disease" ]	2020	Poultry farmer response to disease outbreaks in smallholder farming systems in southern Vietnam
Mammalian HMG-CoA reductase ( HMGCR ) , the rate-limiting enzyme of the cholesterol biosynthetic pathway and the therapeutic target of statins , is post-transcriptionally regulated by sterol-accelerated degradation . Under cholesterol-replete conditions , HMGCR is ubiquitinated and degraded , but the identity of the E3...	Cholesterol is a fatty molecule that is essential for our health; for example , it is a component of the outer membrane that surrounds every cell in our body . Yet , it also has a reputation for clogging arteries and causing heart attacks and strokes . Our organism can adjust the amount of cholesterol it creates throug...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "research", "communication", "cell", "biology" ]	2018	The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1
Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases . To determine how TREM2 variants contribute to these diseases , we performed structural and functional studies of wild-type and variant proteins . Our 3 . 1 Å TREM2 crystal structure revealed that mutations found i...	Alzheimer’s disease is a neurodegenerative disease and the most common cause of dementia – characterized by memory loss and difficulties with thinking , problem solving and language – in the elderly . Individuals with rare mutations in the gene that encodes a protein called TREM2 have a substantial risk of developing A...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2016	Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms
Trypanosomes are important disease agents of humans , livestock and cold-blooded species , including fish . The cellular morphology of trypanosomes is central to their motility , adaptation to the host’s environments and pathogenesis . However , visualizing the behaviour of trypanosomes resident in a live vertebrate ho...	Trypanosomes are one-celled parasites that cause the disease trypanosomiasis , which is also known as sleeping sickness . Trypanosomiasis is transmitted to humans and animals by a type of fly , known as tse-tse , which is commonly found in sub-Saharan Africa . A bite from the tse-tse fly transfers the trypanosome cells...	[ "Abstract", "Introduction", "Materials", "and", "methods", "Results", "Discussion" ]	[ "microbiology", "and", "infectious", "disease" ]	2019	Visualizing trypanosomes in a vertebrate host reveals novel swimming behaviours, adaptations and attachment mechanisms
Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter . To elucidate the behavioral role of the cotransmission , we targeted the glutamate-recycling enzyme glutaminase ( gene Gls1 ) . In mice with a dopamine transporter ( Slc6a3 ) -driven conditional heterozygous ( cHET ) reduction of Gls1 in ...	A small cluster of neurons found in the midbrain use dopamine to send signals to neurons involved in many processes including motivation and attention . Drugs of abuse such as amphetamine co-opt motivation by increasing dopamine signaling . When used excessively , the drugs can engender delusional thinking , as is seen...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Dopamine neuron dependent behaviors mediated by glutamate cotransmission
The SWI/SNF complex is a critical regulator of pluripotency in human embryonic stem cells ( hESCs ) , and individual subunits have varied and specific roles during development and in diseases . The core subunit SMARCB1 is required for early embryonic survival , and mutations can give rise to atypical teratoid/rhabdoid ...	Our bodies contain trillions of cells that play a wide variety of roles . Despite looking and behaving very differently to one another , all of these ‘mature’ cells somehow descend from a single fertilized egg that contains just one set of genes . This process is partially controlled by how ‘accessible’ genetic materia...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression" ]	2019	Tumor suppressor SMARCB1 suppresses super-enhancers to govern hESC lineage determination
Systems vaccinology approaches have been used successfully to define early signatures of the vaccine-induced immune response . However , the possibility that transcriptomics can also identify a correlate or surrogate for vaccine inflammation has not been fully explored . We have compared four licensed vaccines with kno...	Measles , whooping cough and other diseases can cause serious illness and death in humans , especially in young children and other vulnerable individuals . Giving people vaccines ‘trains’ their immune system to recognize and fight the microbes that cause the conditions . During an infection , the immune system triggers...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "immunology", "and", "inflammation" ]	2019	Identification of potential biomarkers of vaccine inflammation in mice
Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans . This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development . Here , we have searched for such differences by analysing cerebral organoi...	The human brain is about three times as big as the brain of our closest living relative , the chimpanzee . Moreover , a part of the brain called the cerebral cortex – which plays a key role in memory , attention , awareness and thought – contains twice as many cells in humans as the same region in chimpanzees . Network...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2016	Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development
A 5 . 3 Å resolution , cryo-electron microscopy ( cryoEM ) map of Chikungunya virus-like particles ( VLPs ) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer . The heterodimer structure was divided into domains to obtain a good fit to the cryoEM dens...	The Chikungunya virus is carried by mosquitos and can cause a number of diseases in humans including encephalitis , which can be fatal in some cases , and severe arthritis . A recent mutation in the E1 protein of the virus has allowed it to efficiently reproduce in a different species of mosquitos , leading to a Chikun...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2013	Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization
Transcranial magnetic stimulation ( TMS ) is a widely used non-invasive tool to study and modulate human brain functions . However , TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields . Here , we present a general method providing direct in vi...	Being able to tap into someone’s brain activity by holding loops of wires above their head sounds a little like the stuff of science fiction . And yet this technique , known as transcranial magnetic stimulation or TMS , is used in research and to treat many brain disorders . TMS emits a pulsed magnetic field that induc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "tools", "and", "resources", "neuroscience" ]	2017	Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation
Encoding of behavioral episodes as spike sequences during hippocampal theta oscillations provides a neural substrate for computations on events extended across time and space . However , the mechanisms underlying the numerous and diverse experimentally observed properties of theta sequences remain poorly understood . H...	Nerve cells in the brain exchange information via electrical impulses . In a given brain area , the electrical impulses at any particular moment can be thought of as forming a code that represents an aspect of the outside world . For example , groups of nerve cells in the hippocampus generate a type of code called a th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "neuroscience" ]	2016	Flexible theta sequence compression mediated via phase precessing interneurons
The rodent hippocampus represents different spatial environments distinctly via changes in the pattern of “place cell” firing . It remains unclear , though , how spatial remapping in rodents relates more generally to human memory . Here participants retrieved four virtual reality environments with repeating or novel la...	How do we remember the different places that we have visited during our day ? Studies of brain activity in rats suggest that each place a rat visits is represented by a different pattern of activity in a region of the brain called hippocampus . However , it is not clear what role this “spatial remapping” plays in the f...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Successful retrieval of competing spatial environments in humans involves hippocampal pattern separation mechanisms
Regeneration responses in animals are widespread across phyla . To identify molecular players that confer regenerative capacities to non-regenerative species is of key relevance for basic research and translational approaches . Here , we report a differential response in retinal regeneration between medaka ( Oryzias la...	All animals have at least some ability to repair their bodies after injury . But certain species can regenerate entire body parts and even internal organs . Salamanders , for example , can regrow their tail and limbs , as well as their eyes and heart . Many species of fish can also regenerate organs and tissues . In co...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine" ]	2018	Activating the regenerative potential of Müller glia cells in a regeneration-deficient retina
Joubert syndrome ( JBTS ) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems . Mutations in known JBTS genes account for approximately half of the cases . By homozygosity mapping and whole-exome sequencing , we identified a novel locus , JBTS23 , with a homozygous splice site mut...	Joubert syndrome is a rare and severe neurodevelopmental disease in which two parts of the brain called the cerebellar vermis and brainstem do not develop properly . The disease is caused by defects in the formation of small projections from the surface of cells , called cilia , which are essential for signalling proce...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology" ]	2015	TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23)
Non-additive interaction between genetic variants , or epistasis , is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci . Interactions give rise to genotype dependent variance , and therefore the identification of variance quantitative trait...	Every person has two copies of each gene: one is inherited from their mother and the other from their father . These two copies are often not identical because there can be many different variants of the same gene in the human population . Traits ( such as height , body mass and risk of disease ) vary from one person t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "chromosomes", "and", "gene", "expression", "genetics", "and", "genomics" ]	2014	Genetic interactions affecting human gene expression identified by variance association mapping
The transition from the juvenile to adult phase in plants is controlled by diverse exogenous and endogenous cues such as age , day length , light , nutrients , and temperature . Previous studies have shown that the gradual decline in microRNA156 ( miR156 ) with age promotes the expression of adult traits . However , ho...	Like animals , plants go through several stages of development before they reach maturity , and it has long been thought that some of the transitions between these stages are triggered by changes in the nutritional status of the plant . Now , based on experiments with the plant Arabidopsis thaliana , Yu et al . and , i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "developmental", "biology" ]	2013	Sugar is an endogenous cue for juvenile-to-adult phase transition in plants
Osteoclasts are bone-resorbing cells essential for skeletal remodeling . However , over-active osteoclasts can cause bone-degenerative disorders . Therefore , the level of NFATc1 , the master transcription factor of osteoclast , must be tightly controlled . Although the activation and amplification of NFATc1 have been ...	Bones are constantly remodeled in response to the stresses of everyday life . Cells called osteoclasts break down old or damaged bone and cells called osteoblasts make new bone . In healthy bones , the work of these two types of cells is well balanced . But in bone-weakening diseases like osteoporosis and certain bone ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2015	Nur77 prevents excessive osteoclastogenesis by inducing ubiquitin ligase Cbl-b to mediate NFATc1 self-limitation
Human γ-secretase is an intra-membrane protease that cleaves many different substrates . Aberrant cleavage of Notch is implicated in cancer , while abnormalities in cutting amyloid precursor protein lead to Alzheimer's disease . Our previous cryo-EM structure of γ-secretase revealed considerable disorder in its catalyt...	An enzyme called gamma-secretase cuts other proteins in cells into smaller pieces . Like most enzymes , gamma-secretase is expected to move through several different three-dimensional shapes to perform its role , and identifying these structures could help us to understand how the enzyme works . One of the proteins tha...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics" ]	2015	Sampling the conformational space of the catalytic subunit of human γ-secretase
Social norms can promote cooperation by assigning reputations to individuals based on their past actions . A good reputation indicates that an individual is likely to reciprocate . A large body of research has established norms of moral assessment that promote cooperation , assuming reputations are objective . But with...	When meerkats have pups , they employ an individual to stand guard and warn the others of potential dangers and predators , putting their own life at risk . What seems like a selfless act is actually a common behavior found throughout the animal kingdom . But rather than acting out of concern for another ones wellbeing...	[ "Abstract", "Introduction", "Model", "Results", "Discussion", "Materials", "and", "methods" ]	[ "evolutionary", "biology" ]	2019	Evolution of empathetic moral evaluation
The prolyl-3 , 4-dihydroxylase Ofd1 and nuclear import adaptor Nro1 regulate the hypoxic response in fission yeast by controlling activity of the sterol regulatory element-binding protein transcription factor Sre1 . Here , we identify an extra-ribosomal function for uS12/Rps23 central to this regulatory system . Nro1 b...	Animals , plants , and fungi need oxygen to release energy within their cells and for other chemical reactions . Enzymes that use oxygen typically become less active when less oxygen is available , and this makes them well suited to help cells sense oxygen . These enzymes include oxygenases , some of which modify prote...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2017	Prolyl dihydroxylation of unassembled uS12/Rps23 regulates fungal hypoxic adaptation
Parkinson’s disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies , in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons . Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites . We here report the struc...	People with Parkinson’s disease have damaged cells in a part of the brain involved in movement , learning and reward-seeking behaviors . These cells contain blob-like aggregates that contain abnormally high amounts of a protein called alpha-synuclein . It is generally believed that , within these blobs , this protein c...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]	2018	Cryo-EM structure of alpha-synuclein fibrils
Amyloid plaques , consisting of deposited beta-amyloid ( Aβ ) , are a neuropathological hallmark of Alzheimer’s Disease ( AD ) . Cerebral vessels play a major role in AD , as Aβ is cleared from the brain by pathways involving the cerebrovasculature , most AD patients have cerebrovascular amyloid ( cerebral amyloid angi...	Alzheimer’s disease causes gradual loss of memory and difficulties in learning . The brains of patients with the disease show several abnormalities including deposits of a peptide molecule called beta-amyloid that is known to be toxic to nerve cells . This peptide can also cause damage to the brain by accumulating with...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels
Reactive oxygen species ( ROS ) -dependent signaling pathways from chloroplasts and mitochondria merge at the nuclear protein RADICAL-INDUCED CELL DEATH1 ( RCD1 ) . RCD1 interacts in vivo and suppresses the activity of the transcription factors ANAC013 and ANAC017 , which mediate a ROS-related retrograde signal origina...	Most plant cells contain two types of compartments , the mitochondria and the chloroplasts , which work together to supply the chemical energy required by life processes . Genes located in another part of the cell , the nucleus , encode for the majority of the proteins found in these compartments . At any given time , ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology" ]	2019	Arabidopsis RCD1 coordinates chloroplast and mitochondrial functions through interaction with ANAC transcription factors
Although it is well known that long-term synaptic plasticity can be expressed both pre- and postsynaptically , the functional consequences of this arrangement have remained elusive . We show that spike-timing-dependent plasticity with both pre- and postsynaptic expression develops receptive fields with reduced variabil...	Throughout life , animals must learn how to respond accurately to new sensations and environments , while retaining knowledge of previous experiences . Learning is widely believed to modify the connections ( called synapses ) between neurons of the cerebral cortex and other brain areas . This process is known as synapt...	[ "Abstract", "Materials", "and", "methods" ]	[ "short", "report", "computational", "and", "systems", "biology", "neuroscience" ]	2015	Unified pre- and postsynaptic long-term plasticity enables reliable and flexible learning
Ribonucleotide reductases ( RNRs ) are key enzymes in DNA metabolism , with allosteric mechanisms controlling substrate specificity and overall activity . In RNRs , the activity master-switch , the ATP-cone , has been found exclusively in the catalytic subunit . In two class I RNR subclasses whose catalytic subunit lac...	When a cell copies its DNA , it uses four different building blocks called deoxyribonucleotides ( dNTPs ) . These consist of one of the four ‘bases’ ( A , T , C and G ) , which pair up to link the two strands of DNA in the double helix , bound to a sugar and a phosphate group . If the cell contains too little or too mu...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit
Plant leaves constitute a huge microbial habitat of global importance . How microorganisms survive the dry daytime on leaves and avoid desiccation is not well understood . There is evidence that microscopic surface wetness in the form of thin films and micrometer-sized droplets , invisible to the naked eye , persists o...	A single plant leaf can be home to about 10 million bacteria and other microbes . These microscopic organisms are part of a larger community of microbes – the microbiome – that plays an important role in the life and health of their plant host . Like all other organisms , bacteria need water to survive , but the surfac...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology", "microbiology", "and", "infectious", "disease" ]	2019	Bacterial survival in microscopic surface wetness
During embryonic development signalling pathways act repeatedly in different contexts to pattern the emerging germ layers . Understanding how these different responses are regulated is a central question for developmental biology . In this study , we used mouse embryonic stem cell ( mESC ) differentiation to uncover a ...	From conception to birth , a single fertilised egg will multiply into trillions of cells , with each cell becoming one of the 200 or so different types of cell that are found in the human body . The development of an embryo is complex and dynamic , with cells giving up their ability to become any cell type and committi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "developmental", "biology", "cell", "biology" ]	2013	PI3K/Akt1 signalling specifies foregut precursors by generating regionalized extra-cellular matrix
In response to an osmotic challenge , the synthesis of the antidiuretic hormone arginine vasopressin ( AVP ) increases in the hypothalamus , and this is accompanied by extension of the 3′ poly ( A ) tail of the AVP mRNA , and the up-regulation of the expression of RNA binding protein Caprin-2 . Here we show that Caprin...	Cells are only able to work properly if they maintain a more or less constant balance of water and salts . In mammals , a hormone called arginine vasopressin regulates water and salt levels in the whole body . This hormone is made by cells in a region of the brain called the hypothalamus , and is then transported to th...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2015	RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response
Witnessing another person’s suffering elicits vicarious brain activity in areas that are active when we ourselves are in pain . Whether this activity influences prosocial behavior remains the subject of debate . Here participants witnessed a confederate express pain through a reaction of the swatted hand or through a f...	When we experience physical pain , certain areas in our brain that process bodily sensation and emotions switch on . If we see someone else in pain , many of the same regions also get activated . In contrast , convicted criminals with psychopathic traits have less activation in these areas of the brain when witnessing ...	[ "Abstract", "Introduction", "Results", "Discussion", "Methods", "and", "material" ]	[ "neuroscience" ]	2018	The causal role of the somatosensory cortex in prosocial behaviour
Urodynamic status must interact with arousal and attentional processes so that voiding occurs under appropriate conditions . To elucidate the central encoding of this visceral demand , multisite recordings were made within a putative pontine-cortical micturition circuit from the pontine micturition center ( PMC ) , loc...	How do we know when we need to find a bathroom ? As the bladder fills up , it sends signals to the brain to say that it needs emptying . But before the brain sends a message back to the bladder muscles telling them to contract to release urine , it first triggers a change in behavior . By increasing our alertness and a...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2017	Brainstem network dynamics underlying the encoding of bladder information
Heterochromatin Protein 1 ( HP1 ) is a conserved chromosomal protein in eukaryotic cells that has a major role in directing heterochromatin formation , a process that requires co-transcriptional gene silencing mediated by small RNAs and their associated argonaute proteins . Heterochromatin formation requires erasing th...	The complete set of genetic material within a cell is known as a genome . The genomes of human and other animal cells have regions of active genes interspersed with ‘dark’ regions known as heterochromatin , which contain genes and other types of genetic material that have been inactivated . Heterochromatin commonly con...	[ "Abstract", "Introduction", "Materials", "and", "methods" ]	[ "stem", "cells", "and", "regenerative", "medicine", "research", "communication" ]	2019	Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing
Events in early life contribute to subsequent risk of asthma; however , the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma . Similarly , not all atopic individuals develop wheeze , and vice versa . The reasons for these differences are unclear . Using unsupervised model...	Asthma causes wheezy and troubled breathing , and can be life-threatening . Scientists and doctors understand that asthma begins in early childhood . Chest infections , exposure to bacteria , viruses , and allergies may cause or trigger asthma . One person with asthma may not have the same origins as another . But it i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "computational", "and", "systems", "biology" ]	2018	Trajectories of childhood immune development and respiratory health relevant to asthma and allergy
While the aging process is central to the pathogenesis of age-dependent diseases , it is poorly understood at the molecular level . We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases , suggesting that the responsible gene regulates retinal...	Older people have an increased risk of developing many diseases , such as diabetes and age-related macular degeneration ( which is often shortened to AMD ) . This suggests that changes that occur during normal aging may some how be linked to how such diseases develop . However , the molecular mechanisms responsible for...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "neuroscience" ]	2016	Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies
Abscisic acid ( ABA ) is a plant hormone that regulates plant growth and development and mediates abiotic stress responses . Direct cellular monitoring of dynamic ABA concentration changes in response to environmental cues is essential for understanding ABA action . We have developed ABAleons: ABA-specific optogenetic ...	Plants are able to respond to detrimental changes in their environment—when , for example , water becomes scarce or the soil becomes too salty—in ways that minimize stress and damage caused by these changes . Hormones are chemicals that trigger the plant’s response under these circumstances . Abscisic acid is the hormo...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "plant", "biology", "cell", "biology" ]	2014	FRET-based reporters for the direct visualization of abscisic acid concentration changes and distribution in Arabidopsis
The cytosolic antiviral innate immune sensor RIG-I distinguishes 5′ tri- or diphosphate containing viral double-stranded ( ds ) RNA from self-RNA by an incompletely understood mechanism that involves ATP hydrolysis by RIG-I's RNA translocase domain . Recently discovered mutations in ATPase motifs can lead to the multi-...	Living cells produce long , strand-like molecules of RNA that carry the instructions needed to make proteins . Viruses also make use of RNA molecules to hijack an infected cell’s protein-production machinery and create new copies of the virus . RNA molecules from viruses have a number of features that distinguish them ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "immunology", "and", "inflammation" ]	2015	ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA
In abstinent drug addicts , cues formerly associated with drug-taking experiences gain relapse-inducing potency ( ‘incubate’ ) over time . Animal models of incubation may help develop treatments to prevent relapse , but these models have ubiquitously focused on the role of conditioned stimuli ( CSs ) signaling drug del...	More than 85% of people who give up an addictive drug begin using it again within a year . Relapse rates have changed little over the past five decades . Situations , places and objects associated with drug-taking can trigger relapse long after a person’s last exposure to a drug . We can study relapse by training anima...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2019	Discriminative stimuli are sufficient for incubation of cocaine craving
Lecithin:cholesterol acyltransferase ( LCAT ) and LCAT-activating compounds are being investigated as treatments for coronary heart disease ( CHD ) and familial LCAT deficiency ( FLD ) . Herein we report the crystal structure of human LCAT in complex with a potent piperidinylpyrazolopyridine activator and an acyl inter...	Cholesterol is a fatty substance found throughout the body that is essential to our health . However , if too much cholesterol builds up in our blood vessels , it can cause blockages that lead to heart and kidney problems . The body removes excess cholesterol by sending out high-density lipoproteins ( HDL ) that captur...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2018	Molecular basis for activation of lecithin:cholesterol acyltransferase by a compound that increases HDL cholesterol
Primary Ovarian Insufficiency ( POI ) affects ~1% of women under forty . Exome sequencing of two Finnish sisters with non-syndromic POI revealed a homozygous mutation in FANCM , leading to a truncated protein ( p . Gln1701* ) . FANCM is a DNA-damage response gene whose heterozygous mutations predispose to breast cancer...	About one in 100 women under the age of 40 experience a condition known as primary ovarian insufficiency , which is sometimes known as premature menopause . Women with this condition may have fewer egg cells and are usually infertile . Women with primary ovarian insufficiency are also more at risk of other diseases , i...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "medicine" ]	2017	A homozygous FANCM mutation underlies a familial case of non-syndromic primary ovarian insufficiency
Information in a computer is quantified by the number of bits that can be stored and recovered . An important question about the brain is how much information can be stored at a synapse through synaptic plasticity , which depends on the history of probabilistic synaptic activity . The strong correlation between size an...	What is the memory capacity of a human brain ? The storage capacity in a computer memory is measured in bits , each of which can have a value of 0 or 1 . In the brain , information is stored in the form of synaptic strength , a measure of how strongly activity in one neuron influences another neuron to which it is conn...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Nanoconnectomic upper bound on the variability of synaptic plasticity
Motor neurons of the crustacean cardiac ganglion generate virtually identical , synchronized output despite the fact that each neuron uses distinct conductance magnitudes . As a result of this variability , manipulations that target ionic conductances have distinct effects on neurons within the same ganglion , disrupti...	Neurons can communicate with each other by releasing chemicals called neurotransmitters , or by forming direct connections with each other known as gap junctions . These direct connections allow electrical impulses to flow from one neuron to another via pores in the membranes between the cells . Unlike communication vi...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2016	Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network
In multicellular organisms , proteins of the extracellular matrix ( ECM ) play structural and functional roles in essentially all organs , so understanding ECM protein organization in health and disease remains an important goal . Here , we used sub-diffraction resolution stochastic optical reconstruction microscopy ( ...	The blood that flows through the body must be continually filtered to remove waste products and to ensure that it contains optimal levels of water and salts . Filtration is performed inside the kidneys by tufts of small blood vessels called glomeruli . These glomerular capillaries allow water and waste products to pass...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2013	Nanoscale protein architecture of the kidney glomerular basement membrane
Blood is arguably the most important bodily fluid and its analysis provides crucial health status information . A first routine measure to narrow down diagnosis in clinical practice is the differential blood count , determining the frequency of all major blood cells . What is lacking to advance initial blood diagnostic...	When you are sick and go to the doctor , it is often not obvious what exactly is wrong — what is causing fever , nausea , shortness of breath or other symptoms . It is important to find this out quickly so that the right action can be taken . One of the first steps is to obtain a blood sample and to count how many of t...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "structural", "biology", "and", "molecular", "biophysics", "tools", "and", "resources" ]	2018	Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood
Most reinforcement learning models assume that the reward signal arrives after the activity that led to the reward , placing constraints on the possible underlying cellular mechanisms . Here we show that dopamine , a positive reinforcement signal , can retroactively convert hippocampal timing-dependent synaptic depress...	To help someone learn a new task , we might give them a reward after they have performed well . However , these rewards tend to be given several seconds or minutes after the behavior they are supposed to promote . Therefore , it is unclear how the rewards affect the brain and help accelerate the learning process . Info...	[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	Retroactive modulation of spike timing-dependent plasticity by dopamine
Synaptic target specificity , whereby neurons make distinct types of synapses with different target cells , is critical for brain function , yet the mechanisms driving it are poorly understood . In this study , we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber ( MF ) synapses...	Nerve cells in the brain connect to each other via junctions called synapses to form vast networks that process information . Much like streets can be joined with stop signs , traffic lights , or exit ramps depending on the flow of traffic , different types of synapses control the flow of information along nerves in di...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "short", "report", "neuroscience" ]	2015	The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus
Gene regulation relies on transcription factors ( TFs ) exploring the nucleus searching their targets . So far , most studies have focused on how fast TFs diffuse , underestimating the role of nuclear architecture . We implemented a single-molecule tracking assay to determine TFs dynamics . We found that c-Myc is a glo...	Transcription factors are proteins that control the expression of genes in the nucleus , and they do this by binding to other proteins or DNA . First , however , these regulatory proteins need to overcome the challenge of finding their targets in the nucleus , which is crowded with other proteins and DNA . Much researc...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus
All animals use olfactory information to perform tasks essential to their survival . Odors typically activate multiple olfactory receptor neuron ( ORN ) classes and are therefore represented by the patterns of active ORNs . How the patterns of active ORN classes are decoded to drive behavior is under intense investigat...	Humans rely chiefly on vision to understand and navigate the world around them . But for many organisms , the world is dominated by their sense of smell . For these animals , everyday activities , like finding food , depend on being able to change behavior based on odor-based cues . To meet the challenges of detecting ...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "neuroscience" ]	2015	Odor-identity dependent motor programs underlie behavioral responses to odors
Spermatogenesis , the complex process of male germ cell proliferation , differentiation , and maturation , is the basis of male fertility . In the seminiferous tubules of the testes , spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions . Th...	As sperm develop in the testis , the immature cells must make their way through a maze of small tubes known as seminiferous tubules . However , at this stage , the cells do not yet move the long tails that normally allow them to ‘swim’; it is therefore unclear how they are able to move through the tubules . Now , Fleck...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology" ]	2021	ATP activation of peritubular cells drives testicular sperm transport
Kinetochores , multi-subunit complexes that assemble at the interface with centromeres , bind spindle microtubules to ensure faithful delivery of chromosomes during cell division . The configuration and function of the kinetochore–centromere interface is poorly understood . We report that a protein at this interface , ...	When a human cell divides to make new cells , its 46 chromosomes must be replicated and then separated evenly between the two daughter cells . The process of separation is performed by the spindle—a network of fibres that form inside the cell , attach to the chromosomes and pull the copies to the opposite ends of the c...	[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]	[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]	2014	The pseudo GTPase CENP-M drives human kinetochore assembly

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