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Autophagy defects are implicated in multiple late-onset neurodegenerative diseases including Amyotrophic Lateral Sclerosis ( ALS ) and Alzheimer’s , Huntington’s , and Parkinson’s diseases . Since aging is the most common shared risk factor in neurodegeneration , we assessed rates of autophagy in mammalian neurons duri...
Unlike most of the cells in our body , our neurons are as old as we are: while other cell types are replaced as they wear out , our neurons must last our entire lifetime . The symptoms of disorders such as Alzheimer's disease and ALS result from neurons in the brain or spinal cord degenerating or dying . But why do neu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "neuroscience" ]
2019
Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons
T cell receptor ( TCR ) engagement opens Ca2+ release-activated Ca2+ ( CRAC ) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells . At the synapse , actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and d...
An effective immune response requires the immune system to rapidly recognize and respond to foreign invaders . Immune cells known as T cells recognize infection through a protein on their surface known as the T cell receptor . The T cell receptor binds to foreign proteins displayed on the surface of other cells . This ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "immunology", "and", "inflammation" ]
2016
Calcium influx through CRAC channels controls actin organization and dynamics at the immune synapse
Previous reports have shown that individual neurons of the brain can display somatic genomic mosaicism of unknown function . In this study , we report altered genomic mosaicism in single , sporadic Alzheimer's disease ( AD ) neurons characterized by increases in DNA content and amyloid precursor protein ( APP ) gene co...
The instructions for living cells are contained in certain stretches of DNA , called genes , and these instructions have been largely considered to be invariant , such that every cell in the body has the same DNA . However , research has revealed that many neurons in the human brain can contain different amounts of DNA...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Genomic mosaicism with increased amyloid precursor protein (APP) gene copy number in single neurons from sporadic Alzheimer's disease brains
Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles . In populations of African ancestry , two apolipoprotein-L1 ( APOL1 ) variants with a recessive kidney disease risk , named G1 and G2 , occur at high frequency . APOL1 is a trypanolytic protein that confers innate ...
African-Americans have a greater risk of developing chronic kidney disease than Americans with European ancestry . Much of this increased risk is explained by two versions of a gene called APOL1 that are common in people with African ancestry . These two versions of the gene , known as G1 and G2 , suddenly became much ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]
2017
APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis
Aging is a major risk factor in many forms of late-onset neurodegenerative disorders . The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging . Here , we show that using a recently demonstrate...
As we age , so do our cells . When cells are used in the laboratory to study the biology of diseases , it is important that the age of the cells reflects the age at which the disease develops . This is particularly important for illnesses with symptoms that develop during old age , and where younger cells may appear to...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "short", "report", "neuroscience" ]
2016
Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts
Under high light , oxygenic photosynthetic organisms avoid photodamage by thermally dissipating absorbed energy , which is called nonphotochemical quenching . In green algae , a chlorophyll and carotenoid-binding protein , light-harvesting complex stress-related ( LHCSR3 ) , detects excess energy via a pH drop and serv...
Green plants and algae rely on sunlight to transform light energy into chemical energy in a process known as photosynthesis . However , too much light can damage plants . Green plants prevent this by converting the extra absorbed light into heat . Both the absorption and the dissipation of sunlight into heat occur with...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "plant", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2021
Identification of distinct pH- and zeaxanthin-dependent quenching in LHCSR3 from Chlamydomonas reinhardtii
In this study , we report a new protein involved in the homeostatic regulation of sleep in Drosophila . We conducted a forward genetic screen of chemically mutagenized flies to identify short-sleeping mutants and found one , redeye ( rye ) that shows a severe reduction of sleep length . Cloning of rye reveals that it e...
Almost all animals need to sleep , including most insects . In experiments in the 1980s , a group of rats that were completely deprived of sleep died within only a few weeks . Sleep has been implicated in processes including tissue repair , memory consolidation and , more recently , the removal of waste materials from ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2014
Identification of Redeye, a new sleep-regulating protein whose expression is modulated by sleep amount
Postsynaptic cells can induce synaptic plasticity through the release of activity-dependent retrograde signals . We previously described a Ca2+-dependent retrograde signaling pathway mediated by postsynaptic Synaptotagmin 4 ( Syt4 ) . To identify proteins involved in postsynaptic exocytosis , we conducted a screen for ...
Synapses are connections that allow a neuron to communicate with a neighboring cell ( often another neuron ) . When an electrical impulse traveling down the “presynaptic” neuron reaches the synapse , it causes the neuron to release molecules called neurotransmitters . These molecules then bind to receptors on the surfa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "neuroscience" ]
2016
The postsynaptic t-SNARE Syntaxin 4 controls traffic of Neuroligin 1 and Synaptotagmin 4 to regulate retrograde signaling
Little is known about the capacity of lower vertebrates to experience itch . A screen of itch-inducing compounds ( pruritogens ) in zebrafish larvae yielded a single pruritogen , the TLR7 agonist imiquimod , that elicited a somatosensory neuron response . Imiquimod induced itch-like behaviors in zebrafish distinct from...
Itch is a common and uncomfortable sensation that creates a strong desire to scratch . This mechanism may have evolved so animals can remove harmful parasites or substances from themselves . Feelings like touch , pain , and itch arise when stimuli such as mechanical pressure , temperature , or chemicals activate groups...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
A zebrafish and mouse model for selective pruritus via direct activation of TRPA1
As neural circuits form , growing processes select the correct synaptic partners through interactions between cell surface proteins . The presence of such proteins on two neuronal processes may lead to either adhesion or repulsion; however , the consequences of mismatched expression have rarely been explored . Here , w...
New nerve cells in a developing organism face a difficult challenge: finding the right partners to connect with in order to form the complex neural networks characteristic of a fully formed brain . Each cell encounters many potential matches but it chooses to connect to only a few , partly based on the proteins that de...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "neuroscience" ]
2021
R7 photoreceptor axon targeting depends on the relative levels of lost and found expression in R7 and its synaptic partners
Molecular bistables are strong candidates for long-term information storage , for example , in synaptic plasticity . Calcium/calmodulin-dependent protein Kinase II ( CaMKII ) is a highly expressed synaptic protein which has been proposed to form a molecular bistable switch capable of maintaining its state for years des...
The brain stores memories by changing the strength of synapses , the connections between neurons . Synapses that change their strength easily can quickly encode new information . But such synapses are also unstable . They tend to revert back to their original state and so struggle to retain information . By contrast , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "computational", "and", "systems", "biology", "neuroscience" ]
2018
Subunit exchange enhances information retention by CaMKII in dendritic spines
Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment . Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and deve...
Endometriosis is a common disease in women caused by tissue that lines the uterus growing outside the uterine cavity on to other organs in the pelvis . This can cause a variety of symptoms including chronic pelvic pain , infertility , and pain during menstruation or sexual intercourse . These symptoms may contribute to...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "short", "report", "medicine", "neuroscience" ]
2020
Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain
Many learned motor behaviors are acquired by comparing ongoing behavior with an internal representation of correct performance , rather than using an explicit external reward . For example , juvenile songbirds learn to sing by comparing their song with the memory of a tutor song . At present , the brain regions subserv...
Most new skills , from playing a sport to learning a language , are acquired through a gradual process of trial and error . While some of this learning is driven by direct external rewards , such as praise , much of it occurs when the individual compares their current performance with their own impression of what a ‘co...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2014
A role for descending auditory cortical projections in songbird vocal learning
Pollen apertures , the characteristic gaps in pollen wall exine , have emerged as a model for studying the formation of distinct plasma membrane domains . In each species , aperture number , position , and morphology are typically fixed; across species they vary widely . During pollen development , certain plasma membr...
Zooming in on cells reveals patterns on their outer surfaces . These patterns are actually a collection of distinct areas of the cell surface , each containing specific combinations of molecules . The outer layers of pollen grains consist of a cell wall , and a softer cell membrane that sits underneath . As a pollen gr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "plant", "biology", "cell", "biology" ]
2021
Members of the ELMOD protein family specify formation of distinct aperture domains on the Arabidopsis pollen surface
Tauopathies feature progressive accumulation of tau amyloids . Pathology may begin when these amplify from a protein template , or seed , whose structure is unknown . We have purified and characterized distinct forms of tau monomer—inert ( Mi ) and seed-competent ( Ms ) . Recombinant Ms triggered intracellular tau aggr...
When doctors perform autopsies to look at the brain tissue of people with Alzheimer’s disease , they find toxic buildups of certain proteins – in particular , a protein called tau – in structures called ‘aggregates’ . People with more severe dementia have more tau aggregates in their brain . Aggregates form when indivi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "neuroscience" ]
2018
Inert and seed-competent tau monomers suggest structural origins of aggregation
LINE-1/L1 retrotransposon sequences comprise 17% of the human genome . Among the many classes of mobile genetic elements , L1 is the only autonomous retrotransposon that still drives human genomic plasticity today . Through its co-evolution with the human genome , L1 has intertwined itself with host cell biology . Howe...
Only two percent of our genetic material or genome are occupied by genes , while between 60-70 percent are made up of hundreds of thousands of copies of very similar DNA sequences . These repetitive sequences evolved from genetic elements called transposons . Transposons are often referred to as ‘jumping genes’ , as th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2018
LINE-1 protein localization and functional dynamics during the cell cycle
Resident microbes play important roles in the development of the gastrointestinal tract , but their influence on other digestive organs is less well explored . Using the gnotobiotic zebrafish , we discovered that the normal expansion of the pancreatic β cell population during early larval development requires the intes...
For a long time , genes and carefully orchestrated chemical signals from the mother’s body have been known to shape the earliest phases of an embryo’s development . More recently , researchers have started to appreciate that environmental cues – such as signals from nearby bacteria – also shape animal development . The...
[ "Abstract", "Introduction", "Results", "Discussion", "Material", "and", "methods" ]
[ "developmental", "biology", "microbiology", "and", "infectious", "disease" ]
2016
A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development
Glioblastomas ( GBM ) are aggressive and therapy-resistant brain tumours , which contain a subpopulation of tumour-propagating glioblastoma stem-like cells ( GSC ) thought to drive progression and recurrence . Diffuse invasion of the brain parenchyma , including along preexisting blood vessels , is a leading cause of t...
Glioblastoma is the most common and deadly type of brain cancer . On average , patients with glioblastoma only survive 15 months even with aggressive treatment . One of the main reasons that therapy fails is the strong tendency of the tumor cells in this form of cancer to spread into the normal brain tissue . This make...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2016
EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells
Practically all studies of gene expression in humans to date have been performed in a relatively small number of adult tissues . Gene regulation is highly dynamic and context-dependent . In order to better understand the connection between gene regulation and complex phenotypes , including disease , we need to be able ...
One major goal of human genetics is to understand how changes in the way genes are regulated affect human traits , including disease susceptibility . To date , most studies of gene regulation have been performed in adult tissues , such as liver or kidney tissue , that were collected at a single time point . Yet , gene ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "genetics", "and", "genomics" ]
2022
Human embryoid bodies as a novel system for genomic studies of functionally diverse cell types
Flows generated by ensembles of flagella are crucial to development , motility and sensing , but the mechanisms behind this striking coordination remain unclear . We present novel experiments in which two micropipette-held somatic cells of Volvox carteri , with distinct intrinsic beating frequencies , are studied by hi...
Sperm cells , as well as many bacteria and algae , propel themselves using whip-like appendages called flagella . Similar , shorter structures called cilia are also found on the surface of many cells , where they perform roles such as moving liquids over the cell . Each cilium or flagellum beats at its own characterist...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "physics", "of", "living", "systems" ]
2014
Flagellar synchronization through direct hydrodynamic interactions
Cells use phagocytosis and macropinocytosis to internalise bulk material , which in phagotrophic organisms supplies the nutrients necessary for growth . Wildtype Dictyostelium amoebae feed on bacteria , but for decades laboratory work has relied on axenic mutants that can also grow on liquid media . We used forward gen...
Dictyostelium amoebae are microbes that feed on bacteria living in the soil . They are unusual in that the amoebae can survive and grow in a single-celled form , but when food is scarce , many individual cells can gather together to form a simple multicellular organism . To feed on bacteria , the amoebae use a process ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology" ]
2015
Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium
Insect cuticular hydrocarbons ( CHCs ) prevent desiccation and serve as chemical signals that mediate social interactions . Drosophila melanogaster CHCs have been studied extensively , but the genetic basis for individual variation in CHC composition is largely unknown . We quantified variation in CHC profiles in the D...
The outermost layer of an insect’s body is called the epicuticle and is made of a blend of fat molecules . “Cuticular hydrocarbons” ( or CHCs ) are the most common fat molecules in the epicuticle , and play an important role in protecting the insect’s body from harsh , dry habitats . CHCs also have other roles in insec...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "genetics", "and", "genomics" ]
2015
Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster
The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS . Uniquely , our 2 . 5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer . One protomer is in the outside-facing state . Two are in different inside-facing states ....
Cells have specialized proteins known as transporters in their surface membranes that move molecules into or out of the cell . Transporters pass their cargo through the membrane by changing shape . This process requires energy and is sometimes driven by simultaneously transporting a charged ion such as sodium . There a...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2015
Mechanism of Na+-dependent citrate transport from the structure of an asymmetrical CitS dimer
The ring-shaped MCM helicase is essential to all phases of DNA replication . The complex loads at replication origins as an inactive double-hexamer encircling duplex DNA . Helicase activation converts this species to two active single hexamers that encircle single-stranded DNA ( ssDNA ) . The molecular details of MCM D...
When DNA was first recognised to be a double helix , it was clear that this structure could easily explain how DNA could be replicated . Each strand was made of bases—represented by the letters ‘A’ , ‘C’ , ‘G’ and ‘T’—and the two strands were held together by bonds between pairs of bases , one from each strand . Moreov...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2014
A conserved MCM single-stranded DNA binding element is essential for replication initiation
Protein biomarkers have been identified across many age-related morbidities . However , characterising epigenetic influences could further inform disease predictions . Here , we leverage epigenome-wide data to study links between the DNA methylation ( DNAm ) signatures of the circulating proteome and incident diseases ...
Although our genetic code does not change throughout our lives , our genes can be turned on and off as a result of epigenetics . Epigenetics can track how the environment and even certain behaviors add or remove small chemical markers to the DNA that makes up the genome . The type and location of these markers may affe...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "epidemiology", "and", "global", "health", "genetics", "and", "genomics" ]
2022
Epigenetic scores for the circulating proteome as tools for disease prediction
Neurons communicate through neurotransmitter release at specialized synaptic regions known as active zones ( AZs ) . Using biosensors to visualize single synaptic vesicle fusion events at Drosophila neuromuscular junctions , we analyzed the developmental and molecular determinants of release probability ( Pr ) for a de...
To send a message to its neighbor , a neuron releases chemicals called neurotransmitters into the gap – or synapse – between them . The neurotransmitter molecules bind to proteins on the receiver neuron called receptors . But what causes the sender neuron to release neurotransmitter in the first place ? The process sta...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2018
Characterization of developmental and molecular factors underlying release heterogeneity at Drosophila synapses
Fast spiking , parvalbumin ( PV ) expressing hippocampal interneurons are classified into basket , axo-axonic ( chandelier ) , and bistratified cells . These cell classes play key roles in regulating local circuit operations and rhythmogenesis by releasing GABA in precise temporal patterns onto distinct domains of prin...
The brain continuously processes information from outside and inside the body to cope with the challenges of everyday life . As the brain carries out these processes , networks of neurons produce patterns of electrical activities called oscillations . Fast-spiking PV cells are neurons that orchestrate the precise timin...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2014
Functional fission of parvalbumin interneuron classes during fast network events
Recent evidence suggests that autophagy facilitates the unconventional secretion of the pro-inflammatory cytokine interleukin 1β ( IL-1β ) . Here , we reconstituted an autophagy-regulated secretion of mature IL-1β ( m-IL-1β ) in non-macrophage cells . We found that cytoplasmic IL-1β associates with the autophagosome an...
Cells release a large number of proteins to the extracellular space . The majority of these ‘secreted’ proteins first pass through two structures inside cells called the endoplasmic reticulum and Golgi . However , a growing number of proteins have been identified that are released by an unconventional mechanism that by...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "cell", "biology" ]
2015
Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion
Binary fission has been well studied in rod-shaped bacteria , but the mechanisms underlying cell division in spherical bacteria are poorly understood . Rod-shaped bacteria harbor regulatory proteins that place and remodel the division machinery during cytokinesis . In the spherical human pathogen Staphylococcus aureus ...
A bacterium called Staphylococcus aureus causes many infections in humans , especially in hospital patients with weakened immune systems . These infections are generally treated with drugs known as antibiotics that interact with specific proteins in the bacteria to kill the cells , or stop them from growing . However ,...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2018
An essential Staphylococcus aureus cell division protein directly regulates FtsZ dynamics
Tissue mechanics is important for development; however , the spatio-temporal dynamics of in vivo tissue stiffness is still poorly understood . We here developed tiv-AFM , combining time-lapse in vivo atomic force microscopy with upright fluorescence imaging of embryonic tissue , to show that during development local ti...
Neurons in the brain form an intricate network that follows a precise template . For example , in a young frog embryo , the neurons from the eyes send out thin structures , called axons , which navigate along a well-defined path and eventually connect with the visual centres of the brain . This journey requires the axo...
[ "Abstract", "Materials", "and", "methods" ]
[ "developmental", "biology", "short", "report", "physics", "of", "living", "systems" ]
2019
Rapid changes in tissue mechanics regulate cell behaviour in the developing embryonic brain
Lamina-associated polypeptide 1 ( LAP1 ) resides at the nuclear envelope and interacts with Torsins , poorly understood endoplasmic reticulum ( ER ) -localized AAA+ ATPases , through a conserved , perinuclear domain . We determined the crystal structure of the perinuclear domain of human LAP1 . LAP1 possesses an atypic...
Cells are filled with activity—proteins must be folded into intricate shapes and unfolded , complex molecules must be built and taken apart—and all this activity requires energy . Cells use a molecule called ATP as a source of energy , with the energy being released when enzymes called ATPases remove a phosphate group ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2014
How lamina-associated polypeptide 1 (LAP1) activates Torsin
Transcription factors organize gene expression profiles by regulating promoter activity . However , the role of transcription factors after transcription initiation is poorly understood . Here , we show that the homeoprotein Nkx2-5 and the 5’-3’ exonuclease Xrn2 are involved in the regulation of alternative polyadenyla...
About one in every hundred babies is born with problems that either affect the structure of the heart or how it works . These problems are known as congenital heart disease , and result when the development of the heart is disrupted . How the heart develops is determined by thousands of genes whose activity or “express...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression" ]
2016
Regulation of alternative polyadenylation by Nkx2-5 and Xrn2 during mouse heart development
Folding of mammalian genomes into spatial domains is critical for gene regulation . The insulator protein CTCF and cohesin control domain location by folding domains into loop structures , which are widely thought to be stable . Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the sa...
A human cell contains about 2 meters of DNA tightly packed in a compartment called the nucleus . Within the space inside the nucleus , different parts of the DNA fold into distinct bundles known as domains . These domains are important for organising the genome and are crucial for regulating gene expression , by stimul...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "structural", "biology", "and", "molecular", "biophysics" ]
2017
CTCF and cohesin regulate chromatin loop stability with distinct dynamics
Exhaustion of stem cells is a hallmark of aging . In the Drosophila testis , dedifferentiated germline stem cells ( GSCs ) derived from spermatogonia increase during lifespan , leading to the model that dedifferentiation counteracts the decline of GSCs in aged males . To test this , we blocked dedifferentiation by mis-...
From the heart to the brain , our bodies are made of a collection of cells that are specialized to perform precise roles . Yet , certain organs host ‘stem cells’ , which can become any kind of tissue . For example , the testicles of the fruit fly contain germline stem cells; when one of these cells divides , a daughter...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology" ]
2018
JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis
Peripheral neural sensory mechanisms play a crucial role in metabolic regulation but less is known about the mechanisms underlying vagal sensing itself . Recently , we identified an enrichment of liver X receptor alpha and beta ( LXRα/β ) in the nodose ganglia of the vagus nerve . In this study , we show mice lacking L...
The vagus nerves run from the brainstem to the heart and the digestive system and help to control several processes including digestion and heart rate . Because of their role in regulating food intake , these nerves are attractive targets for scientists hoping to develop treatments for obesity . There are two types of ...
[ "Abstract", "Introduction", "Results", "Materials", "and", "methods" ]
[ "short", "report", "neuroscience" ]
2015
Loss of the liver X receptor LXRα/β in peripheral sensory neurons modifies energy expenditure
Protection against malaria in humans can be achieved by repeated exposure to infected mosquito bites during prophylactic chloroquine treatment ( chemoprophylaxis and sporozoites ( CPS ) ) . We established a new mouse model of CPS immunization to investigate the stage and strain-specificity of malaria immunity . Immuniz...
Malaria is a life-threatening infectious disease in humans that is caused by a single-celled parasite called Plasmodium . The parasite is carried between people by mosquitos; when an infected mosquito bites a human , the parasite is injected into the bloodstream with the mosquito's saliva . Plasmodium first infects liv...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease", "immunology", "and", "inflammation" ]
2015
Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization
Methods for measuring gut microbiota biochemical activities in vivo are needed to characterize its functional states in health and disease . To illustrate one approach , an arabinan-containing polysaccharide was isolated from pea fiber , its structure defined , and forward genetic and proteomic analyses used to compare...
Tens of trillions of microbes living in the gut help humans and other animals digest their food . In the process , the microbes provide necessary nutrients for themselves and the animal . Learning more about the interaction of food components and gut bacteria could help scientists to better understand how different die...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2021
Microbiota functional activity biosensors for characterizing nutrient metabolism in vivo
Social behavior in mammals is often studied in pairs under artificial conditions , yet groups may rely on more complicated social structures . Here , we use a novel system for tracking multiple animals in a rich environment to characterize the nature of group behavior and interactions , and show strongly correlated gro...
All animals need to interact with others of the same species , even if it is only to mate . To date , social behavior has been studied mainly at two extremes: detailed observation of pairs; and studies of the collective behavior of large groups , such as flocks of birds . However , to gain an understanding of social be...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2013
High-order social interactions in groups of mice
Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs . Genetic ancestry has been suggested as an alternative to this categorization . Herein , we typed over 450 , 000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who al...
Whether a person develops a particular disease can depend on both genetic and environmental factors . Many studies have found that people of different races and ethnicities have different likelihoods of acquiring certain diseases . Race and ethnicity are social constructs; that is , they are not necessarily defined bio...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression" ]
2017
Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures
Spatial learning requires the hippocampus , and the replay of spatial sequences during hippocampal sharp wave-ripple ( SPW-R ) events of quiet wakefulness and sleep is believed to play a crucial role . To test whether the coordination of VTA reward prediction error signals with these replayed spatial sequences could co...
Whether it’s meeting a friend for dinner at a new restaurant or hiking through a forest for the first time , new experiences lead to new memories . In order to create these memories , our brains do a lot of work behind the scenes . A region of the brain called the hippocampus ‘records’ experiences as they happen . It t...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
VTA neurons coordinate with the hippocampal reactivation of spatial experience
Activating mutations involving the PI3K pathway occur frequently in human cancers . However , PI3K inhibitors primarily induce cell cycle arrest , leaving a significant reservoir of tumor cells that may acquire or exhibit resistance . We searched for genes that are required for the survival of PI3K mutant cancer cells ...
When cells become cancerous , they accumulate mutations in their DNA that switch on some genes at the wrong time and to higher levels than normal . These over-active genes help cancer cells to survive , grow and evade death . One of the genes that is often mutated and over-active in breast cancer encodes an enzyme call...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cancer", "biology" ]
2017
Synergistic interactions with PI3K inhibition that induce apoptosis
Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices . However , there is relatively little evidence for such cortical reorganisation over the short-term . Using human somatosensory cortex as a model , we investigated the effects of a 24 hr glui...
The areas of the brain that receive inputs from our senses have a map-like structure . In an area called the visual cortex this map represents our field of vision; in the auditory cortex , it represents the range of different tones we can hear . The sense of touch is processed in the somatosensory cortex: an area of th...
[ "Abstract", "Introduction" ]
[ "short", "report", "neuroscience" ]
2016
Perceptually relevant remapping of human somatotopy in 24 hours
Cell proliferation and quiescence are intimately coordinated during metazoan development . Here , we adapt a cyclin-dependent kinase ( CDK ) sensor to uncouple these key events of the cell cycle in Caenorhabditis elegans and zebrafish through live-cell imaging . The CDK sensor consists of a fluorescently tagged CDK sub...
All living things are made up of cells that form the different tissues , organs and structures of an organism . The human body , for example , is thought to consist of some 37 trillion cells and harbor over 200 cell types . To maintain a working organism , cells divide to create new cells and replace the ones that have...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology", "tools", "and", "resources" ]
2020
Visualizing the metazoan proliferation-quiescence decision in vivo
Odorant binding proteins ( Obps ) are remarkable in their number , diversity , and abundance , yet their role in olfactory coding remains unclear . They are widely believed to be required for transporting hydrophobic odorants through an aqueous lymph to odorant receptors . We construct a map of the Drosophila antenna ,...
Insects use their sense of smell to find mates , to find food and – in the case of insects that transmit diseases such as malaria and Zika – to find us . If we can understand how insect scent detection works at the molecular and cellular level , we may be able to devise new ways of manipulating the insects’ sense of sm...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2016
Organization and function of Drosophila odorant binding proteins
Bacterial chemotaxis is a paradigm for how environmental signals modulate cellular behavior . Although the network underlying this process has been studied extensively , we do not yet have an end-to-end understanding of chemotaxis . Specifically , how the rotational states of a cell’s flagella cooperatively determine w...
Escherichia coli is a rod-shaped bacterium commonly found in the lower intestines of humans and other warm-blooded animals . While most strains of E . coli are harmless , including most of those found in the human gut , some can cause diseases such as food poisoning . Due to its close association with humans and the fa...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease" ]
2014
Escherichia coli swimming is robust against variations in flagellar number
We have examined the role of Fam60a , a gene highly expressed in embryonic stem cells , in mouse development . Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex , and most Fam60a–/– embryos manifest hypoplasia of visceral organs and die in utero . Fam60a is recruited to the promoter...
As an embryo develops , its cells continue to divide and transform from unspecialized embryonic stem cells into the specialized cells that form the tissues and organs of the adult body . This complex process is controlled by a network of genes . Although most adult cells carry the same genes , different cell types each...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology" ]
2018
Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters
The majority of adult hippocampal newborn cells die during early differentiation from intermediate progenitors ( IPCs ) to immature neurons . Neural stem cells in vivo are located in a relative hypoxic environment , and hypoxia enhances their survival , proliferation and stemness in vitro . Thus , we hypothesized that ...
The hippocampus is a region in the mammalian brain that has been implicated in the formation of new memories . This process involves the birth of new neurons , which are created at a rate of ∼4000 a day in the hippocampus of a young adult mouse . Yet only a fraction of these cells survive to form mature neurons . These...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
Localized hypoxia within the subgranular zone determines the early survival of newborn hippocampal granule cells
Heterochromatin formed by the SUV39 histone methyltransferases represses transcription from repetitive DNA sequences and ensures genomic stability . How SUV39 enzymes localize to their target genomic loci remains unclear . Here , we demonstrate that chromatin-associated RNA contributes to the stable association of SUV3...
Each cell in a human body contains the same DNA sequence , which serves as a set of instructions for how the body should develop and operate . However , only certain sections of DNA are “active” at any particular time and in any given type of cell . When a section of DNA is active , cells make many copies of it using a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "cell", "biology" ]
2017
RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin
Epstein-Barr virus ( EBV ) infection is associated with rheumatoid arthritis ( RA ) in adults , though the nature of the relationship remains unknown . Herein , we have examined the contribution of viral infection to the severity of arthritis in mice . We have provided the first evidence that latent gammaherpesvirus in...
Rheumatoid arthritis is one of the most common autoimmune diseases , leaving patients in pain as their immune system mistakenly attacks the lining of their joints . The precise cause is unknown , but research suggests a link to the Epstein-Barr virus , the agent responsible for mononucleosis ( also known as glandular f...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation" ]
2021
Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cells
The combined-immunotherapy of adoptive cell therapy ( ACT ) and cyclophosphamide ( CTX ) is one of the most efficient treatments for melanoma patients . However , no synergistic effects of CTX and ACT on the spatio-temporal dynamics of immunocytes in vivo have been described . Here , we visualized key cell events in im...
Melanoma is a form of skin cancer that is particularly difficult to treat . A new approach that has shown a lot of promise in treating many different cancers , including melanoma , is called “immunotherapy” . This technique harnesses the immune system – the body’s natural defences that help to protect against infection...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation", "cancer", "biology" ]
2016
Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy
Protein polarization underlies differentiation in metazoans and in bacteria . How symmetric polarization can instate functional asymmetry remains elusive . Here , we show by super-resolution photo-activated localization microscopy and edgetic mutations that the bitopic zinc-finger protein ZitP implements specialized de...
Living cells become asymmetric for many different reasons and how they do so has been a long-standing question in biology . In some cells , the asymmetry arises because a given protein accumulates at one side of the cell . In particular , this process happens before some cells divide to produce two non-identical daught...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "short", "report", "cell", "biology" ]
2016
Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator
The neuronal microtubule cytoskeleton underlies the polarization and proper functioning of neurons , amongst others by providing tracks for motor proteins that drive intracellular transport . Different subsets of neuronal microtubules , varying in composition , stability , and motor preference , are known to exist , bu...
Cells in the body need to control the position of the molecules and other components inside them . To do this , they use a system of proteins that work a bit like a road network . The ‘roads’ are tubular structures known as microtubules , while ‘vehicles’ are transporters , called motor proteins , that ‘walk’ along the...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2021
Quantitative mapping of dense microtubule arrays in mammalian neurons
Cytosine methylation regulates essential genome functions across eukaryotes , but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved . Here , we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler ...
Living cells add chemical tags to their DNA to regulate which genes are switched on or off at any given time . These tags include methyl groups added to one of the letters of the DNA code called cytosine . Both plants and mammals need cytosine methylation to develop properly . This methylation also keeps sections of fo...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "plant", "biology" ]
2017
DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
ISWI-family nucleosome remodeling enzymes need the histone H4 N-terminal tail to mobilize nucleosomes . Here we mapped the H4-tail binding pocket of ISWI . Surprisingly the binding site was adjacent to but not overlapping with the docking site of an auto-regulatory motif , AutoN , in the N-terminal region ( NTR ) of IS...
In the cells of animals , plants and other eukaryotes , DNA wraps tightly around proteins called histones to form structures known as nucleosomes that resemble beads on a string . When nucleosomes are sufficiently close to each other they interact and clump together , which compacts the DNA and prevents the genes in th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "biochemistry", "and", "chemical", "biology" ]
2017
Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail
The glymphatics system describes a CSF-mediated clearance pathway for the removal of potentially harmful molecules , such as amyloid beta , from the brain . As such , its components may represent new therapeutic targets to alleviate aberrant protein accumulation that defines the most prevalent neurodegenerative conditi...
Our brain is bathed in cerebrospinal fluid , a clear liquid that ‘cushions’ the fragile organ . This liquid travels into the brain along special channels – the perivascular space – that surround certain blood vessels . As the fluid washes in and out of the brain , it takes with it potentially harmful molecules , such a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "short", "report", "neuroscience" ]
2018
Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI
PPP-family phosphatases such as PP1 have little intrinsic specificity . Cofactors can target PP1 to substrates or subcellular locations , but it remains unclear how they might confer sequence-specificity on PP1 . The cytoskeletal regulator Phactr1 is a neuronally enriched PP1 cofactor that is controlled by G-actin . St...
Specific arrangements of atoms such as bulky phosphate groups can change the activity of a protein and how it interacts with other molecules . Enzymes called kinases are responsible for adding these groups onto a protein , while phosphatases remove them . Kinases are generally specific for a small number of proteins , ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2020
Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme
Defects in flagella growth are related to a number of human diseases . Central to flagellar growth is the organization of microtubules that polymerize from basal bodies to form the axoneme , which consists of hundreds of proteins . Flagella exist in all eukaryotic phyla , but neither the mechanism by which flagella gro...
Some cells have a whip-like appendage called a flagellum . This is most often used to propel the cell , notably in sperm cells , but it can also be involved in sensing cues in the surrounding environment . Flagella are found in all three domains of life—the eukaryotes ( which include the animals ) , bacteria and ancien...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "microbiology", "and", "infectious", "disease" ]
2014
Modes of flagellar assembly in Chlamydomonas reinhardtii and Trypanosoma brucei
Animals have developed mechanisms to reconstruct lost or damaged tissues . To regenerate those tissues the cells implicated have to undergo developmental reprogramming . The imaginal discs of Drosophila are subdivided into distinct compartments , which derive from different genetic programs . This feature makes them a ...
When cells or tissues are damaged , animals can often regenerate the affected tissues . In an effort to identify the genes and mechanisms that are involved in this regeneration process , researchers often perform experiments on relatively simple organisms or systems . These experiments frequently involve the amputation...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine" ]
2014
Transgressions of compartment boundaries and cell reprogramming during regeneration in Drosophila
Drosophila syncytial nuclear divisions limit transcription unit size of early zygotic genes . As mitosis inhibits not only transcription , but also pre-mRNA splicing , we reasoned that constraints on splicing were likely to exist in the early embryo , being splicing avoidance a possible explanation why most early zygot...
When a fertilized egg develops into an embryo , the expression of many genes must be carefully timed and coordinated . Researchers regularly use a type of fruit fly called Drosophila to study development because it is small , it has a short lifespan , and its whole genome sequence is already known . The development of ...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]
2014
Requirement for highly efficient pre-mRNA splicing during Drosophila early embryonic development
Many lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes . Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+/CD24− cell surface marker profil...
A single tumor can be made up of thousands of cancer cells that look and behave differently from one another . This observed diversity arises from changes in the DNA sequence of particular genes , changes in the activity of genes , and the ability of cells to transition between different states . As a result , individu...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2017
TGF-β reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+/CD24− cancer cells
Animals use spatial differences in environmental light levels for visual navigation; however , how light inputs are translated into coordinated motor outputs remains poorly understood . Here we reconstruct the neuronal connectome of a four-eye visual circuit in the larva of the annelid Platynereis using serial-section ...
Many animals show automatic responses to light , from moths , which are attracted to light sources , to cockroaches , which are repelled by them . This phenomenon , known as phototaxis , is thought to help animals navigate through their environment . It is an evolutionarily ancient behavior , as revealed by its widespr...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2014
Neuronal connectome of a sensory-motor circuit for visual navigation
Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells . They consist of arrays of sarcomeres , the smallest contractile unit of muscles . Within a muscle type , myofibril diameter is highly invariant and contributes to its physiological properties , yet little is known about the underlying...
Muscles are made up of many long muscle fibers , each containing thousands of cylindrical segments called sarcomeres . When animals move , proteins in the sarcomere move past each other , shortening the muscles . Inside each muscle , all sarcomeres have the same length and diameter . The protein titin controls the leng...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "cell", "biology" ]
2019
Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
Posttranslational modifications ( PTMs ) play a crucial role in a wide range of biological processes . Lysine crotonylation ( Kcr ) is a newly discovered histone PTM that is enriched at active gene promoters and potential enhancers in mammalian cell genomes . However , the cellular enzymes that regulate the addition an...
Most of the DNA in a cell is wound around histone proteins to form a compacted structure called chromatin . Enzymes can modify the histones by adding small chemical tags on to them , and these histone modifications can cause the chromatin to either become more tightly packed or more open . Opening up the chromatin make...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology" ]
2014
Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach
The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development . How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described . Using high-resolution live imagi...
The heart is the first organ to form and to begin working in an embryo during pregnancy . It must begin pumping early to supply oxygen and nutrients to the developing embryo . Coordinated contractions of specialised muscle cells in the heart , called cardiomyocytes , generate the force needed to pump blood . The flow o...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2016
Calcium handling precedes cardiac differentiation to initiate the first heartbeat
AMPA-type glutamate receptors ( AMPARs ) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength . A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites . The mechanisms underly...
Neurons send signals via electrical impulses that are transmitted between cells by small molecules known as neurotransmitters . The information is passed from neuron to neuron at specialized points of contact termed synapses . On release of neurotransmitters from the first neuron , the molecules attach to ‘docking stat...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2017
Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain
Reef-building corals depend on intracellular dinoflagellate symbionts that provide nutrients . Besides sugars , the transfer of sterols is essential for corals and other sterol-auxotrophic cnidarians . Sterols are important cell components , and variants of the conserved Niemann-Pick Type C2 ( NPC2 ) sterol transporter...
Coral reefs are the most biodiverse marine ecosystems on our planet . Their immense productivity is driven by friendly relationships , or symbioses , between microbes called algae and the corals . Related organisms , such as anemones , also rely on these close associations . The algae use energy from sunlight to make s...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "evolutionary", "biology", "cell", "biology" ]
2019
Sterol transfer by atypical cholesterol-binding NPC2 proteins in coral-algal symbiosis
Developmental signaling pathways often activate their own inhibitors . Such inhibitory feedback has been suggested to restrict the spatial and temporal extent of signaling or mitigate signaling fluctuations , but these models are difficult to rigorously test . Here , we determine whether the ability of the mesendoderm ...
During animal development , a single fertilized cell gives rise to different tissues and organs . This ‘patterning’ process depends on signaling molecules that instruct cells in different positions in the embryo to acquire different identities . To avoid mistakes during patterning , each cell must receive the correct a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2017
Nodal patterning without Lefty inhibitory feedback is functional but fragile
Unraveling the genetic susceptibility of complex diseases such as chronic kidney disease remains challenging . Here , we used inbred rat models of kidney damage associated with elevated blood pressure for the comprehensive analysis of a major albuminuria susceptibility locus detected in these models . We characterized ...
The human kidneys filter the entire volume of the blood about 300 times each day . This ability depends on specialized cells , known as podocytes , which wrap around some of the blood vessels in the kidney . These cells control which molecules leave the blood based on their size . Normally large molecules like proteins...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "genetics", "and", "genomics" ]
2019
Analysis of the genomic architecture of a complex trait locus in hypertensive rat models links Tmem63c to kidney damage
Malaria inflicts an enormous burden on global human health . The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies . Antibiotics that inhibit protein translation are promising candidates for reposition...
Each year , malaria kills more than 600 , 000 people , mostly children younger than 5 years old . Humans who have been bitten by mosquitoes infected with malaria-causing parasites become ill as the parasites rapidly multiply in blood cells . Although there are several drugs that are currently used to treat malaria , th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2014
Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine
Adult-born granule cells ( ABGCs ) are involved in certain forms of hippocampus-dependent learning and memory . It has been proposed that young but functionally integrated ABGCs ( 4-weeks-old ) specifically contribute to pattern separation functions of the dentate gyrus due to their heightened excitability , whereas ol...
Remembering what happened on different occasions involves a process in the brain called pattern separation , which allows us to separate and distinguish our memories . One part of the brain where pattern separation occurs is called the dentate gyrus , which sits in the hippocampus—the brain region that is in charge of ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "short", "report", "neuroscience" ]
2014
Adult-born granule cells mature through two functionally distinct states
Integrin activation is crucial for the regulation of leukocyte rolling , adhesion and trans-vessel migration during inflammation and occurs by engagement of myeloid cells through factors presented by inflamed vessels . However , endothelial-dependent mechanisms of myeloid cell recruitment are not fully understood . Her...
When tissues are damaged or infected , the body produces an inflammatory response . Neutrophils – a type of white blood cell – play an important part in this response . These cells normally circulate through the bloodstream , and are recruited to the inflamed site by chemical signals sent out by immune cells in the dam...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation" ]
2016
Endothelial cell-derived CD95 ligand serves as a chemokine in induction of neutrophil slow rolling and adhesion
The presynaptic protein complexin ( CPX ) is a critical regulator of synaptic vesicle fusion , but the mechanisms underlying its regulatory effects are not well understood . Its highly conserved central helix ( CH ) directly binds the ternary SNARE complex and is required for all known CPX functions . The adjacent acce...
The nervous system sends information around the body in the form of electrical signals that travel through cells called neurons . These signals cannot pass across the small gaps—called synapses—that separate neighboring neurons . Instead , when electrical signals reach the synapse , chemicals called neurotransmitters a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "neuroscience" ]
2014
The accessory helix of complexin functions by stabilizing central helix secondary structure
As a first-line vertebrate immune defense , the polymeric immunoglobulin receptor ( pIgR ) transports polymeric IgA and IgM across epithelia to mucosal secretions , where the cleaved ectodomain ( secretory component; SC ) becomes a component of secretory antibodies , or when unliganded , binds and excludes bacteria . H...
A sticky substance called mucus lines our airways and gut , where it acts as a physical barrier to prevent bacteria and other microbes from entering the body . Mucus also contains proteins called antibodies that can bind to and neutralize molecules from microbes ( known as antigens ) . The primary antibody found in muc...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "immunology", "and", "inflammation" ]
2016
The structure and dynamics of secretory component and its interactions with polymeric immunoglobulins
How metabolism is reprogrammed during neuronal differentiation is unknown . We found that the loss of hexokinase ( HK2 ) and lactate dehydrogenase ( LDHA ) expression , together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1 , marks the transition from aerobic glycolysis in neural progenitor cells ( N...
Structures called mitochondria act like the batteries of cells , and use several different metabolic processes to release energy . For example , neurons rely on a metabolic process called oxidative phosphorylation , while neural progenitor cells ( which develop , or differentiate , into neurons ) use a process called a...
[ "Abstract", "Introduction", "Result", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology" ]
2016
Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation
Medial and lateral hypothalamic loci are known to suppress and enhance appetite , respectively , but the dynamics and functional significance of their interaction have yet to be explored . Here we report that , in larval zebrafish , primarily serotonergic neurons of the ventromedial caudal hypothalamus ( cH ) become in...
How soon after a meal do you start feeling hungry again ? The answer depends on a complex set of processes within the brain that regulate appetite . A key player in these processes is the hypothalamus , a small structure at the base of the brain . The hypothalamus consists of many different subregions , some of which a...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2019
A bidirectional network for appetite control in larval zebrafish
Synaptic transmission between midbrain dopamine neurons and target neurons in the striatum is essential for the selection and reinforcement of movements . Recent evidence indicates that nigrostriatal dopamine neurons inhibit striatal projection neurons by releasing a neurotransmitter that activates GABAA receptors . He...
The electrical signals that are fired along neurons cannot be transmitted across the small gaps , called synapses that are found between neurons . Instead , the neuron sending the signal releases chemicals called neurotransmitters into the synapse . These neurotransmitters bind to receptor proteins on the surface of th...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2014
Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis
Botryllus schlosseri is a colonial urochordate that follows the chordate plan of development following sexual reproduction , but invokes a stem cell-mediated budding program during subsequent rounds of asexual reproduction . As urochordates are considered to be the closest living invertebrate relatives of vertebrates ,...
The tunicates are an evolutionary group that includes species such as sea squirts and sea tulips . Their name comes from the structure known as a ‘tunic’ that surrounds their sac-like bodies . As marine filter feeders , tunicates obtain nutrients by straining food particles from water , and they can live either alone o...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "genetics", "and", "genomics" ]
2013
The genome sequence of the colonial chordate, Botryllus schlosseri
How mammalian tissues maintain their architecture and tissue-specificity is poorly understood . Previously , we documented both the indispensable role of the extracellular matrix ( ECM ) protein , laminin-111 ( LN1 ) , in the formation of normal breast acini , and the phenotypic reversion of cancer cells to acini-like ...
Most animal cells can secrete molecules into their surroundings to form a supportive meshwork of large proteins , called the extracellular matrix . This matrix is connected to the cell membrane through receptors that can transmit signals to the cell nucleus to change the levels of small RNA molecules called microRNAs ....
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2018
Laminin signals initiate the reciprocal loop that informs breast-specific gene expression and homeostasis by activating NO, p53 and microRNAs
Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for structural biology . Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A ( CypA ) has been previously linked to its catalytic function , but the extent to which the different confo...
Proteins are the workhorses of the cell . The shape that a protein molecule adopts enables it to carry out its role . However , a protein’s shape , or 'conformation' , is not static . Instead , a protein can shift between different conformations . This is particularly true for enzymes – the proteins that catalyze chemi...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics" ]
2015
Mapping the conformational landscape of a dynamic enzyme by multitemperature and XFEL crystallography
Human papillomaviruses ( HPVs ) are the most common sexually transmitted infectious agents . Because of the species specificity of HPVs , study of their natural transmission in laboratory animals is not possible . The papillomavirus , MmuPV1 , which infects laboratory mice ( Mus musculus ) , can cause infections in the...
Human papillomaviruses are responsible for about 5% of all cancers: infections with high-risk strains of the virus lead to the vast majority of cervical cancers , other cancers of the anus and genital area , as well as a growing fraction of head and neck cancers . In humans , these viruses are transmitted through sexua...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "short", "report", "microbiology", "and", "infectious", "disease" ]
2019
Sexual transmission of murine papillomavirus (MmuPV1) in Mus musculus
To move the body , the brain must precisely coordinate patterns of activity among diverse populations of motor neurons . Here , we use in vivo calcium imaging , electrophysiology , and behavior to understand how genetically-identified motor neurons control flexion of the fruit fly tibia . We find that leg motor neurons...
In the body , spindly nerve cells called motor neurons connect the brain to the muscles . Their role is to control movement , as they translate the electrical signals from the brain into instructions to the muscles . In humans , it takes over 150 , 000 motor neurons to control the movement of one leg; in contrast , fru...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2020
A size principle for recruitment of Drosophila leg motor neurons
T follicular helper cells ( Tfh ) are crucial for the initiation and maintenance of germinal center ( GC ) reactions and high affinity , isotype-switched antibody responses . In this study , we demonstrate that direct TGF-β signaling to CD4 T cells is important for the formation of influenza-specific Tfh cells , GC rea...
The influenza virus is thought to cause illness in up to 10% of adults and 30% of children each year worldwide . Most of these cases resolve on their own and don’t require treatment , but three to five million people are hospitalized and up to half a million people die each year . Unfortunately , the vaccines currently...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation" ]
2015
The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa
Do we expect periodic grid cells to emerge in bats , or perhaps dolphins , exploring a three-dimensional environment ? How long will it take ? Our self-organizing model , based on ring-rate adaptation , points at a complex answer . The mathematical analysis leads to asymptotic states resembling face centered cubic ( FC...
Our ability to navigate through our environment depends on a region of the brain called the hippocampus . In the 1990s it was shown that this structure , which takes its name from the Greek word for ‘seahorse’ owing to its shape , was larger in London taxi drivers than it was in the general population . However , as ea...
[ "Abstract", "Introduction", "Model", "Results", "Discussion", "Materials", "and", "methods" ]
[ "neuroscience" ]
2015
The self-organization of grid cells in 3D
Brian 2 allows scientists to simply and efficiently simulate spiking neural network models . These models can feature novel dynamical equations , their interactions with the environment , and experimental protocols . To preserve high performance when defining new models , most simulators offer two options: low-level pr...
Simulating the brain starts with understanding the activity of a single neuron . From there , it quickly gets very complicated . To reconstruct the brain with computers , neuroscientists have to first understand how one brain cell communicates with another using electrical and chemical signals , and then describe these...
[ "Abstract", "Introduction", "Materials", "and", "methods", "Discussion" ]
[ "tools", "and", "resources", "neuroscience" ]
2019
Brian 2, an intuitive and efficient neural simulator
The dynamic assembly of multi-protein complexes underlies fundamental processes in cell biology . A mechanistic understanding of assemblies requires accurate measurement of their stoichiometry , affinity and cooperativity , and frequently consideration of multiple co-existing complexes . Sedimentation velocity analytic...
Many proteins in cells combine to form molecular machines or complexes that carry out specific processes inside cells . Analytical ultracentrifugation is a technique commonly used to explore the physical properties of proteins and their complexes and in this way to gain insights into the biological roles of these molec...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "tools", "and", "resources" ]
2016
Monochromatic multicomponent fluorescence sedimentation velocity for the study of high-affinity protein interactions
The epigenetic inheritance of DNA methylation requires UHRF1 , a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites of newly replicated DNA through ubiquitylation of histone H3 . UHRF1 binds DNA with selectivity towards hemi-methylated CpGs ( HeDNA ) ; however , the contribution of HeDNA sen...
Cells are able to regulate the activity of their genes in response to different cues . Genetic information is encoded in DNA and one way to regulate gene activity is to modify the DNA by attaching chemical “epigenetic” markers to it . When a cell divides , these epigenetic markers can be inherited by the daughter cells...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2016
Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1
A well-established cascade of transcription factor ( TF ) activity orchestrates adipogenesis in response to chemical cues , yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic . Here , we uncover a novel mechanism licensin...
Human body fat consists mostly of fat-storing cells called adipocytes . These cells develop in two main steps . First , mesenchymal stem cells—which can potentially become one of many different types of cell—commit to becoming pre-adipocyte cells . These pre-adipocytes then develop into mature adipocytes . Proteins cal...
[ "Abstract", "Introduction", "Results", "Discussion" ]
[ "chromosomes", "and", "gene", "expression", "developmental", "biology" ]
2015
ATF4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis
Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell . Mechanistic understanding of this process is hampered by limited structural information on these macromolecular complexes . A-kinase anch...
It was once thought that proteins needed to have structures that were both ordered and stable , but this view was changed by the discovery that certain proteins contain regions that are disordered and flexible . In some cases these regions of intrinsic disorder help the protein to function by linking more stable region...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "biochemistry", "and", "chemical", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2013
Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation
The NR5A-family nuclear receptors are highly conserved and function within the somatic follicle cells of the ovary to regulate folliculogenesis and ovulation in mammals; however , their roles in Drosophila ovaries are largely unknown . Here , we discover that Ftz-f1 , one of the NR5A nuclear receptors in Drosophila , i...
When animals reproduce , females release eggs from their ovaries which then get fertilized by sperm from males . Each egg needs to properly mature within a collection of cells known as follicle cells before it can be let go . As the egg matures , so do the follicle cells surrounding it , until both are primed and ready...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "genetics", "and", "genomics" ]
2020
Nuclear receptor Ftz-f1 promotes follicle maturation and ovulation partly via bHLH/PAS transcription factor Sim
Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood . In this study , we demonstrate that T cell-specific deletion of the IL-6 receptor α chain ( IL-6Rα ) results in impaired Th1 and Th17 T cell responses in vivo , and a ...
The human body's ability to defend itself against pathogens relies on two distinct but connected systems: the innate and the adaptive immune systems . Innate immune cells survey their environment and use receptors located on their surface to distinguish between molecules that are harmless and molecules that stem from p...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation" ]
2014
T cell-intrinsic role of IL-6 signaling in primary and memory responses
The biological properties of pancreatic cancer stem cells ( PCSCs ) remain incompletely defined and the central regulators are unknown . By bioinformatic analysis of a human PCSC-enriched gene signature , we identified the transcription factor HNF1A as a putative central regulator of PCSC function . Levels of HNF1A and...
Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer . It is also one of the deadliest types of cancer: fewer than one in ten patients live for five years after being diagnosed with the disease . Several reasons can explain this poor outcome including that the cancer is often diagnosed late , w...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine", "cancer", "biology" ]
2018
HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties
Wnt signaling is essential for tissue homeostasis and its dysregulation causes cancer . Wnt ligands trigger signaling by activating Frizzled receptors ( FZDRs ) , which belong to the G-protein coupled receptor superfamily . However , the mechanisms of G protein activation in Wnt signaling remain controversial . In this...
Our cells need to be able to communicate with each other to coordinate many processes in the body , including the formation and maintenance of our organs . A system called Wnt signaling allows cells in different tissues to communicate . During Wnt signaling , one cell releases a protein called Wnt that then binds to a ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "structural", "biology", "and", "molecular", "biophysics" ]
2015
Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling
The ability to isolate rare live cells within a heterogeneous population based solely on visual criteria remains technically challenging , due largely to limitations imposed by existing sorting technologies . Here , we present a new method that permits labeling cells of interest by attaching streptavidin-coated magneti...
When scientists use microscopes to look at cells , they often want to then isolate certain cells based on how these look like . For example , researchers may want to select cells with specific shapes , movements or division rates , because these visual clues give important information about how the cells may be behavin...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "tools", "and", "resources", "cancer", "biology" ]
2019
Opto-magnetic capture of individual cells based on visual phenotypes
α-Xenorhabdolysins ( Xax ) are α-pore-forming toxins ( α-PFT ) that form 1–1 . 3 MDa large pore complexes to perforate the host cell membrane . PFTs are used by a variety of bacterial pathogens to attack host cells . Due to the lack of structural information , the molecular mechanism of action of Xax toxins is poorly u...
Some bacteria make toxins that punch large holes into the membranes of host cells , destroying them like a puncture destroys a football . These “pore-forming toxins” allow many bacterial species to infect a variety of organisms , from insects to humans . Some sophisticated pore-forming toxins , such as the anthrax toxi...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "structural", "biology", "and", "molecular", "biophysics", "microbiology", "and", "infectious", "disease" ]
2018
Membrane insertion of α-xenorhabdolysin in near-atomic detail
Antiviral development is plagued by drug resistance and genetic barriers to resistance are needed . For HIV and hepatitis C virus ( HCV ) , combination therapy has proved life-saving . The targets of direct-acting antivirals for HCV infection are NS3/4A protease , NS5A phosphoprotein and NS5B polymerase . Differential ...
Viruses are simple organisms that consist of genetic information and a few types of proteins . They cannot replicate on their own , and instead hijack the molecular machinery of a host cell to produce more of themselves . Inside an infected cell , the genetic information of the virus is replicated and ‘read’ to create ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "microbiology", "and", "infectious", "disease", "genetics", "and", "genomics" ]
2018
Transmission genetics of drug-resistant hepatitis C virus
Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies . To this end we present an approach termed PRIME for generating cell-specific genome-scale metabolic models ( GSMMs ) based on molecular and phenotypic data . ...
Cancer is not just one disease , but a collection of disorders; as such there is no single general treatment that is effective against all cancers . Different tissues and organs—including the lungs , skin , and kidneys—can get cancer , and each need different treatments . Even two patients with the same type of cancer ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "cell", "biology", "cancer", "biology" ]
2014
Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer
To identify new approaches to enhance innate immunity to bacterial pneumonia , we investigated the natural experiment of gender differences in resistance to infections . Female and estrogen-treated male mice show greater resistance to pneumococcal pneumonia , seen as greater bacterial clearance , diminished lung inflam...
Pneumonia is a disease that is commonly caused by a bacterial infection and results in the lungs becoming inflamed . Pneumonia is a serious condition and can lead to hospitalization and sometimes death . However , women—and other female animals—are less likely than males to get pneumonia and are more likely to survive ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "immunology", "and", "inflammation" ]
2014
Female resistance to pneumonia identifies lung macrophage nitric oxide synthase-3 as a therapeutic target
Heterogeneity broadly exists in various cell types both during development and at homeostasis . Investigating heterogeneity is crucial for comprehensively understanding the complexity of ontogeny , dynamics , and function of specific cell types . Traditional bulk-labeling techniques are incompetent to dissect heterogen...
Animals begin life as a single cell that then divides to become a complex organism with many different types of cells . Every time a cell divides , each of its two daughter cells can either stay the same type as their parent or adopt a different identity . Once a cell acquires an identity , it usually cannot ‘go back’ ...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "stem", "cells", "and", "regenerative", "medicine", "developmental", "biology", "tools", "and", "resources" ]
2020
In vivo single-cell lineage tracing in zebrafish using high-resolution infrared laser-mediated gene induction microscopy
Crude oil spills are a worldwide ocean conservation threat . Fish are particularly vulnerable to the oiling of spawning habitats , and crude oil causes severe abnormalities in embryos and larvae . However , the underlying mechanisms for these developmental defects are not well understood . Here , we explore the transcr...
Accidental oil spills are a worldwide threat to ocean life . Fish eggs and larvae are especially vulnerable; therefore oil spills in areas where fish spawn are of great concern . Fish embryos exposed to crude oil grow slower than normal as larvae and juveniles and often show defects in the heart , face and jaw . Howeve...
[ "Abstract", "Introduction", "Results", "Discussion", "Materials", "and", "methods" ]
[ "ecology", "genetics", "and", "genomics" ]
2017
Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish
Morphogen gradients induce sharply defined domains of gene expression in a concentration-dependent manner , yet how cells interpret these signals in the face of spatial and temporal noise remains unclear . Using fluorescence lifetime imaging microscopy ( FLIM ) and phasor analysis to measure endogenous retinoic acid ( ...
Animal cells need to be able to communicate with each other so that they can work together in tissues and organs . To do so , cells release signaling molecules that can move around within a tissue and be detected by receptors on other cells . We tend to assume that the signaling molecules are evenly distributed across ...
[ "Abstract", "Introduction", "Results", "and", "discussion", "Materials", "and", "methods" ]
[ "developmental", "biology", "short", "report", "computational", "and", "systems", "biology" ]
2016
Noise modulation in retinoic acid signaling sharpens segmental boundaries of gene expression in the embryonic zebrafish hindbrain