Moritz Armbruster, Chris G Dulla, Jeffrey S Diamond
Fluorescent glutamate indicators distort the time course of neurotransmitter diffusion and uptake by competing with transporters, an important caveat to consider when using iGluSnFR and its analogs.
SKAP2 is critical for hematopoietic cell protection against Klebsiella infection in mouse lungs, for full phosphorylation of Src Family Kinases, Syk, and Pyk2, and for Klebsiella-induced reactive oxygen species production.
The development of an advanced cell cycle tag toolbox will enable a wide variety of cell cycle studies and shows post-replicative function of nucleases resolving replication/recombination structures.
The forces that multicellular tumor aggregates exert on their environment lead to non-linear, scale-invariant tissue deformations far away from the tumor, which can be exploited to quantify its collective contractility.
Transient cell-cell contact of eukaryotic cells, called contact following locomotion, causes cell density segregation, and its high-density region traveled as a band within the disordered background.
A new user-intervention-free classification, using single-fluorescent markers, measures conventionally unmeasureable phenotypes in early stages during clathrin-mediated endocytosis.
David J Herzfeld, Nathan J Hall ... Stephen G Lisberger
Quantitative analysis of behavior coupled with computational modeling reveal the set of circuit-level principles that underlie cerebellar-dependent motor learning in smooth pursuit eye movements of monkeys across timescales.
Mohamed Mahgoub, Jacob Paiano ... Todd S Macfarlan
The meiotic recombination landscape in vertebrates was re-engineered via the co-evolution of a dual histone H3K4/H3K36 methylation 'writer' PRDM9 and its 'reader' ZCWPW1 that facilitates efficient double strand break repair.
Maternal spindle transfer is a feasible approach to enhance embryonic developmental of compromised oocytes, which can represent a new strategy for patients with forms of infertility refractory to current treatments.
Eliminating the calcium-binding protein Doc2b does not alter transmission at a mature synapse under physiological conditions, counter to the prevailing view of Doc2b based on cultured neurons.
Isabella V Soluri, Lauren M Zumerling ... Shelby A Blythe
Mechanisms for shaping the chromatin accessibility landscape operate during development to regulate how embryonic patterning information is interpreted at the level of gene regulatory networks.
Ponto-spinal CRH neurons in Barrington’s nucleus are a core component of an inferential circuit that regulates autonomous micturition and generates voids when the bladder is full.
Nicolaas C Baudoin, Joshua M Nicholson ... Daniela Cimini
Newly formed tetraploid cells rapidly lose extra centrosomes acquired upon tetraploidization via asymmetric centrosome clustering during cell division and selective advantage of tetraploid daughter cells that inherit a single centrosome.
Tucked within a well-known story of diverging gene function is a single enhancer encoding two inseparable specificities that regulates two adjacent genes, each with different spatiotemporal expression patterns.
Disease-associated mutants of the TRPM3 ion channel are overactive, and they are inhibited by the antiepileptic medication primidone, offering a potential therapeutic intervention to treat this channelopathy.
Jonathan Y An, Kristopher A Kerns ... Matt Kaeberlein
Short-term treatment with rapamycin reverses periodontal bone loss, attenuates inflammation, and remodels the oral microbiome toward a more youthful state.
Zhuo Guan, Monica C Quiñones-Frías ... J Troy Littleton
Drosophila synaptotagmin 7 functions to restrict SV availability and release, but does not act as the Ca2+ sensor mediating the asynchronous release and facilitation remaining in synaptotagmin 1 mutants.
Combined simulations and electrophysiological experiments show that the CLC channels and exchangers form physically distinct and evolutionarily conserved pathways through which Cl- and H+ ions move when crossing biological membranes.
James M Mossner, Renata Batista-Brito ... Jessica A Cardin
Loss of function of the Rett syndrome gene MeCP2 in a small but powerful interneuron population, the VIP cells, causes a unique combination of impairments in neural function and behavior.
Competition between minor and major splice sites in SRSF10 controls cell type-dependent expression of all SR-proteins and reveals a global impact of the minor spliceosome on major intron splicing.
The Aire-dependent genes show a preference for short 3’UTR transcript isoforms resulting in the escape from the post-transcriptional repression mediated by miRNAs in medullary thymic epithelial cells.
Unexpected structural diversity of nematode small molecules, as revealed by high-resolution phylogenetic analysis, suggests recurrent biochemical innovation, a pattern that is probably typical across animals.
Aisling Y Coughlan, Lisa Lombardi ... Kenneth H Wolfe
A family of homing genetic elements that look like inteins but work differently is the progenitor of the endonuclease that enables Saccharomyces cerevisiae to change its mating type.
Histone variant H2A.Z is deposited near transcription start sites by the chromatin remodeler SWR1 and seems to be removed by RNA polymerase II at an early stage of transcription elongation.
Anneke Dixie Kakebeen, Alexander Daniel Chitsazan ... Andrea Elizabeth Wills
Regenerating neural progenitors of the Xenopus tropicalis tail prioritize differentiation to motor neuron types earlier than proliferation, a decision partly regulated by the transcription factors Pbx3 and Meis1.
Sarah Jacquelyn Smith, Lance A Davidson, Mark Rebeiz
A new morphological structure evolved through extreme changes in cell height requires novel connections to an extracellular matrix network, which predates the origin of structure.
Cristina Olivieri, Yingjie Wang ... Gianluigi Veglia
A combination of NMR, fluorescence, and molecular dynamics simulations reveals the recognition mechanism for the intrinsically disordered regulator of protein kinase A, highlighting the enzyme's nuclear export process.
Gabriel M Stine, Ariel Zylberberg ... Michael N Shadlen
The determination that a decision-maker integrated evidence to form perceptual decisions is shown to be much more difficult than previously appreciated.
Kevin I Manage, Alicia K Rogers ... Carolyn Marie Phillips
SIMR-1 acts downstream of the piRNA pathway to promote siRNA amplification by the Mutator complex and localizes to perinuclear foci distinct from Mutator foci, P granules and Z granules.
Glycolysis is locally enhanced and redirected in zebrafish to generate lactate, which functions as a signaling molecule to fully activate Fgf target genes required for proper sensory and neural development.
Genetic analyses illustrate the novel requirement of Ftz-f1 and Sim in adult Drosophila ovaries for regulating follicle cell differentiation and ovulation that is likely conserved in mammals.
Tim DD Somerville, Giulia Biffi ... Christopher R Vakoc
A major consequence of ductal-to-squamous lineage transition in pancreatic cancer cells is to augment inflammation, which may explain the exceptionally poor clinical outcomes of squamous-subtype tumors.
Beatriz Alvarez-Castelao, Susanne tom Dieck ... Erin M Schuman
In neurons, inhibition of the proteasome results in feedback inhibition of protein synthesis, mediated by heme-regulated kinase 1, which is optimized to act as both a sensor and an effector.
Genetic and molecular analyses identify and characterize an evolutionary battle over lysis timing wherein a bacteriophage delays lysis through lysis inhibition while a defensive phage satellite accelerates lysis.
Neuronal serotonin release tunes transcription response times of Caenorhabditis elegans germ cells to promote the survival and stress resistance of future offspring.
Valerie PI Vidal, Fariba Jian-Motamedi ... Andreas Schedl
In the developing kidney, secreted molecules of the R-spondin family control progenitor cell proliferation and nephron formation by permitting WNT/β-catenin signalling.
Direct and indirect pathways in the basal ganglia have opposing effects not only on action performance but also on internal timing of expected reward delivery.
Orthogonal to traditional paradigms that manipulate neuroligin expression level, optogenetic stimulation of tyrosine phosphorylation highlights a role of the intracellular domain of endogenous neuroligin-1 in excitatory synaptic differentiation and potentiation.
Nodal signaling regulates gastrulation cell behaviors largely in parallel with planar cell polarity signaling and is sufficient for ex vivo extension of embryonic explants.
Brian D DeAngelis, Jacob A Zavatone-Veth ... Damon A Clark
A simple, computationally efficient method provides spatiotemporally precise optogenetic perturbations in freely walking Drosophila, revealing the asymmetries and region-specificity of behavioral programs evoked by activating mechanosensory and chemosensory neurons.
Laura L Arnold, Alessandra Cecchini ... DDW Cornelison
The juxtacrine signaling molecule EphA7, when expressed on terminally-differentiated myocytes, non-cell-autonomously induces adjacent myoblasts to also commit to terminal differentiation leading to rapid coordinated differentiation across the entire population.
Ross O Smith, Takeshi Ninchoji ... Lena Claesson-Welsh
Pathological vessel leakage in mouse retinopathy models depends on VE-cadherin Y685 phosphorylation status, which in turn is regulated by a signaling cascade originating with VEGFR2 Y949 phosphorylation.
Networks simulations and in vivo imaging suggest a stable backbone of stimulus representation formed by neurons with low population coupling, alongside a flexible substrate of neurons with high population coupling.
Male-type aggressive and courtship behaviors of the fruit flies are differentially specified by two sex-determining genes, providing a substrate for the evolution to sculpt these two behaviors independently.
Kira Delmore, Juan Carlos Illera ... Miriam Liedvogel
Variation in migration can evolve rapidly and traits that comprise this behaviour may be determined by standing variation at a few regulatory regions that are not common across taxonomic groups.
Paul J Wichgers Schreur, Sandra van de Water ... Jeroen Kortekaas
Llama-derived single-domain antibodies, formatted as bispecific antibodies with human Fc domains, reduce and prevent bunyavirus-induced morbidity and mortality in mice upon prophylactic and therapeutic administration.
Single-turnover studies reveal quantitative insights into the inner mechanics and unfold hidden facets in the conformational coupling of ATP binding, hydrolysis, and substrate translocation by ABC transporters.
John Kerwin, Israr Khan, Reproducibility Project: Cancer Biology
Editors' Summary: This Replication Study has reproduced some parts of the original paper but it also contains results that are not consistent with other parts of the original paper.
Helena Bilandžija, Breanna Hollifield ... William Jeffery
Astyanax mexicanus surface-dwelling fish exposed to complete darkness develop many traits resembling cavefish adaptations by phenotypic plasticity in a single generation.
A library of the paired peptide/HLA multimers and artificial APCs allows for construction of a large database of class I-restricted peptides and cognate tumor-reactive TCR genes at an unprecedented scale.
Sonic hedgehog signaling is crucial for the self-renewal of outer radial glial cells and gyrus formation of the cerebral cortex in gyrencephalic mammals.
Adela Constantinescu-Bercu, Luigi Grassi ... James TB Crawley
The interaction between activated αIIbβ3 on platelets and SLC44A2 on circulating neutrophils facilitates neutrophil capture and drives flow-dependent NETosis.
New transgenic mice, which can be ablated both orexin neurons and MCH neurons, showed new brain state and revealed functional interaction that MCH neurons have protective role in narcolepsy symptoms.
Sex-specific characteristics of the fruit fly courtship behavior are not specified by a single binary switch, but as a combination of traits that are modularly specified by separable genetic switches.
Nucleation, elasticity theory, and simulations were combined to construct a general phase diagram that elucidates the conditions for successful viral assembly and the key factors to prevent it.
Novel mechanisms for cellular centering and symmetry breaking involving persistent contractile actomyosin flows and their hydrodynamic interactions with the fluid cytosol are presented and studied using a minimal, reconstituted system.
Group III metabotropic glutamate receptor inhibition facilitates synaptic plasticity in the plasticity-resistant synapses of hippocampal area CA2, a brain region critical for social memory.
Combining psychophysics and functional MRI reveals a qualitative asymmetry in neural engagement when reflecting on whether a stimulus is seen (detection) compared to reflecting on what a stimulus is (discrimination).
Centromere deletion in Cryptococcus deuterogattii results in neocentromeres, which span actively expressed genes and at elevated temperatures cen10∆ mutants are unstable leading to chromosome fusion and silencing of the neocentromere.
Neuroimaging reveals that the brain response to spoken language can be better explained by rule-based models than statistical models recently developed in artificial intelligence research.
Crystallography together with electron-resonance spectroscopy, molecular-dynamics simulations, and transport measurements reveal the molecular details of protein conformational change, and how this change contributes to function in a CLC-type chloride/proton exchanger.
A combination of genetic fate-mapping and parabiotic experiments reveals the chronological expansion of yolk-sac-derived renal tissue-resident macrophages with age by cellular proliferation and recruitment from circulating progenitors.
Ana Rita Amândio, Lucille Lopez-Delisle ... Denis Duboule
In vertebrates, large regulatory landscapes sometimes behave as coherent regulatory units, which may explain the lack of effect sometimes observed when single enhancer sequences are deleted in isolation.
In vitro and in cellulo characterization of oligomerization by the cytoplasmic Wnt effector dishevelled and its partner Axin provide new mechanistic principles for Wnt/β-catenin signaling.
Nils Stührwohldt, Stefan Scholl ... Andreas Schaller
Step-wise processing of plant peptide hormone precursors by subtilisin-like proteinases in consecutive compartments of the secretory pathway is required for formation and secretion of the bioactive peptides.
Under hypoxic stress, when cellular demand for energy relies entirely on glycolysis, the machinery for glycolysis binds RNA and phase separates into G bodies, leading to enhanced glycolysis rates.
RecO efficiently displaces SSB from ssDNA without consuming ATPs using its two DNA-binding sites, even though SSB binds to ssDNA approximately 300 times more strongly than RecO does.
Joshua Henk Balsters, Valerio Zerbi ... Rogier B Mars
Connectivity fingerprint matching bridges the gap between mouse and primate neuroanatomy, addressing crucial questions surrounding brain evolution that likely impact translation across species.
Cell lineage tracing and biochemical analysis of cell fate during murine stem cell differentiation demonstrates a specific cooperativity between perturbations in histone methylation and eroded telomeres that destabilize cell differentiation.
Sara Marelli, James C Williamson ... Nicholas J Matheson
Systematic screen of HIV-1 Vif mutants identifies synthetic and naturally occurring amino acid polymorphisms separating PPP2R5 and APOBEC3 family protein depletion and uncovers the mechanism of Vif-dependent cell cycle arrest.
Zinc metalloproteinase Papp-aa-mediated Igfbp5 proteolysis functions as a [Ca2+]-regulated molecular switch linking IGF signaling to epithelial cell proliferation and bone calcification.
The impact of mass intervention campaigns is determined by the interaction between implementation logistics, patterns of human mobility and how transmission risk is distributed over space.
Elucidating the contribution of augmented artificial skin-stretch stimulation to the fingertips to the immediate illusion of a higher stiffness and to an increased predictive grip force control.
Michelle S Reid, David M Kern, Stephen Graf Brohawn
The structure of the potassium-chloride cotransporter KCC4 provides insight into the basis of ion specificity, transport stoichiometry, and activity regulation for a broadly physiologically and clinically important transporter family.
Stefan Brückner, Rajib Schubert ... Hans-Ulrich Mösch
Structural, biophysical and physiological analysis reveals how yeast cell surface adhesins evolved to confer self-nonself discrimination in single cells and whole populations.
Alexander Shakeel Bates, James D Manton ... Gregory SXE Jefferis
Open source software enables neuroscientists to integrate single neuron or synaptic-resolution datasets from different imaging modalities to analyse morphology and connectivity at the scale of whole brains and connectomes.
Oliver W Bayfield, Alasdair C Steven, Alfred A Antson
Structure of the portal protein of a thermostable virus, determined in its capsid-bound state, reveals a molecular mechanism that prevents DNA slippage during genome packaging.
Haojiang Luan, Alexander Kuzin ... Benjamin H White
A genetic method allows neurons to be individually identified and characterized by combining information about both their developmental origins and their mature patterns of gene expression.
Vps29 promotes retromer localization in the adult Drosophila brain, engaging Rab7 and TBC1D5, and its loss triggers age-dependent neuronal impairments in endolysosomal trafficking and synaptic transmission.
The chloride channel Ano1/Tmem16a plays an essential and non-redundant role in the developing airway by inhibiting mucus cell hyperplasia and promoting proper immune function of the airway mucosal barrier.
Confidence-dependent reinforcement learning is active and produces trial-to-trial choice updating even in well-learned perceptual decisions without explicit reward biases, across species and sensory modalities.
The superior colliculus reveals hallmarks of sophisticated visual computation, including selectivity, invariance, and stimulus-specific habituation to behaviorally relevant stimuli.
A high-phytate-low Ca2+ diet causes crystal nephropathies, renal phosphate wasting, and bone disease in rats, whereas high Ca2+ intake ameliorates the detrimental effects of a high-phytate diet.
Viktor V Feketa, Yury A Nikolaev ... Elena O Gracheva
CNGA3 is a cold-potentiated ion channel that confers cold sensitivity to mouse hypothalamic neurons, whereas CNGA3 from hibernating ground squirrels is cold-insensitive.
An unrecognized regulation on MAGEA protein stability promotes pancreatic cancer progression via manipulating autophagy and may impact the clinical utility of MAGEA-targeted immunotherapy.
Rats are highly social animals that show complex social skills, which has not been acknowledged enough when controlling them in the wild and conducting research in the laboratory.
David S White, Marcel P Goldschen-Ohm ... Baron Chanda
A new analysis algorithm (DISC) enables accurate analysis of data from high-throughput single-molecule paradigms and reveals a non-cooperative binding mechanism of cyclic nucleotide-binding domains from HCN ion channels.
A linear array of spectrin tetramers imparts mechanical stability to axons by allowing spectrin domains to unfold reversibly when an axon is stretched, thereby acting as tension buffers.
Single-molecule immunoprecipitation method reveals that the high catalytic rate and multi-tasking capability make a concerted contribution to the strong signaling potency of the HER2-HER3 heterodimers.
Janine D Brunner, Roman P Jakob ... Stephan Schenck
Structural and functional analysis of a recently discovered non-canonical potassium channel family reveals a unique selectivity filter that is exposed to permeating ions only in the conductive state.
André Kuhn, Sigurd Ramans Harborough ... Lars Østergaard
Auxin binding to the ETTIN transcription factor disrupts the interaction between ETT and a TPL/TPR co-repressor and subsequently affects chromatin dynamics to ensure proper gynoecium development.
Eli M Carrami, Sahand Sharifzadeh ... Ahmed A Ahmed
A robust library preparation and variant calling strategy (DigiPico/MutLX) eliminates false positive single nucleotide variants from picogram quantities of DNA following whole genome amplification.
Patric M Vaelli, Kevin R Theis ... Heather L Eisthen
Skin-associated bacteria underlie the production of a potent defensive neurotoxin in newts, impacting host physiology, molecular evolution, and predator-prey interactions in a coevolutionary arms race.
Artificial selection on wing color and CRISPR/Cas9 knockout of the optix gene both alter scale lamina thickness in Junonia coenia, which shifts structural color wavelength and mimics macroevolutionary butterfly diversity.
The work uncovers a muscle-epidermis-glia signaling axis, modulated by protease mig-17 and the basement membrane, that regulates synaptic allometry during growth in Caenorhabditis elegans.
(O-Acyl)-ω-hydroxy fatty acids and their derivatives, produced by the fatty acid ω-hydroxylase Cyp4f39, form a lipid polarity gradient in the lipid layer of the tear film and prevent dry eye.
Amira Hassan, Pablo Araguas Rodriguez ... Tony D Southall
The condensin I subunit Cap-G is expressed in post-mitotic neurons and its removal, especially from less mature neurons, results in gene expression changes, reduced survival and behavioural defects in Drosophila.
A gain-of-function in a new chemical defense resulted in no trade-offs and and independent evolution between novel and ancestral defenses, suggesting low redundancy among different defensive chemicals.
Danielle C DeVille, Rayus Kuplicki ... Sahib S Khalsa
People who have attempted suicide exhibit blunted sensory processing during breathing and pain perturbations, as well as lower heartbeat perception accuracy and reduced mid/posterior insula activity during interoceptive attention.
Comprehensive, high-resolution lineage mapping of the fly brain reveals straightforward rules that drive neuronal complexity and probable evidence of brain evolution.
Aconitate decarboxylase 1-derived itaconate reduces mitochondrial respiration via inhibition of succinate dehydrogenase but does not regulate inflammatory response or NRF2 expression in response to particulate matter.
Joseph L Harman, Andrea N Loes ... Michael J Harms
In the ancestor of mammals, a multifunctional innate immune protein evolved when a mutation enhanced the protein’s pro-inflammatory activity and proteolytic regulation without disrupting the protein’s antimicrobial activity.
Anna Plana-Bonamaisó, Santiago López-Begines ... Ana Méndez
The nucleotide sensing ability of IMPDH1 at the Bateman domain is regulated by light-dependent phosphorylation in the retina, to adjust GTP synthesis to illumination conditions.
John ME Nichols, Vlatka Antolović ... Jonathan R Chubb
Efficient dedifferentiation is characterized by robustness to mutation, flexibility in ordering of cellular events and reversal of developmental changes along a single gene expression trajectory.
Edward J Banigan, Aafke A van den Berg ... Leonid A Mirny
Seemingly contradictory findings of single-molecule and in vivo experiments on a major mechanism of chromosome organization are reconciled by computationally investigating mechanisms of loop extrusion that are consistent with both.
Collective responses of animals are generally controlled by complex biological mechanisms and in Caenorhabditis eleganscollective dynamics are purely controlled by physical parameters such as oxygen penetration and bacterial diffusion.
Alexandra Schauer, Diana Pinheiro ... Carl-Philipp Heisenberg
Blastoderm tissue organization and patterning in zebrafish explants is driven by a genetically encoded and controlled self-assembly mechanism, rather than a bonafide self-organization mechanism.
Current evidence does not suggest adverse effects of ACE inhibitors or ARBs in COVID-19 patients and, to the contrary, discontinuing these drugs in these patients may potentially be harmful.
A combination of in vitro and in vivo experiments demonstrate a cell-autonomous role of the KIT ligand/KIT signaling pathway in protecting retinal photoreceptor cells from environmentally or genetically caused degeneration.
Aline Ricarda Dörrbaum, Beatriz Alvarez-Castelao ... Erin M Schuman
Dynamic SILAC labeling in combination with mass spectrometry revealed substantial regulation of protein synthesis, degradation, turnover, and abundance during homeostatic scaling in neurons.
HLA class I-disease associations have been studied for decades; a new approach for investigating the underlying mechanism can overcome past problems with interpretation and help to understand the etiology of human diseases.
Branden R Nelson, Rebecca D Hodge ... Robert F Hevner
Multiphoton live-imaging illuminates the dynamic underpinnings of how different types of progenitor cells migrate and interact to robustly build the mammalian Dentate Gyrus neural circuitry and new outer neurogenic niche.
David J Forsthoefel, Nicholas I Cejda ... Phillip A Newmark
Application of laser-capture microdissection to planarian intestinal tissue provides a new tool for analysis of tissue-specific gene expression in flatworms, and a new resource to advance investigations of gastrointestinal regeneration.
Emilie Barruet, Steven M Garcia ... Jason H Pomerantz
Single cell RNA sequencing leads to identification and separation of transcriptionally and functionally heterogeneous, natural human satellite cells, including a subpopulation marked by CAV1 harboring quiescence phenotypes and engraftment potential.
In mouse brain slices, native delta glutamate receptors carry ionic current and underlie the α1-adrenergic receptor-mediated depolarization of dorsal raphe neurons that drives action potential firing in vivo.
Human neural tube closure defects associated mutations in planar cell polarity (PCP) genes are causative of the disease, as revealed in the intricate Drosophila PCP model.
Deep mining of GT-A fold sequences provides an evolutionary framework for investigating complex relationships connecting GT-A fold sequence, structure, function and regulation.
Vascular degeneration of the choroid and RPE disorganization were associated with pharmacological macrophage ablation, indicating that insufficiency of macrophage function may be a mechanism underlying age- and AMD-associated pathology.
Calcium influx stimulates formation of ER/plasma membrane contacts adjacent to focal adhesions, and lipid transfer at these sites is required for adhesion disassembly during cell migration.
