The important role of serine biosynthesis in Müller cells may explain why the macula is so much more prone to developing disease than the rest of the retina.
Pharmacologic inhibition of DNA methylation restrains the growth of urothelial carcinoma by subtype conversion through heightened stromal Hedgehog pathway activity.
YQ Shirleen Soh, Louise H Moncla ... Jesse D Bloom
Complete mapping of human-adaptive mutations to the avian influenza PB2 protein shows how selection at key molecular interfaces combines with evolutionary accessibility to shape viral host adaptation.
A multiphase hydrodynamic theory reveals that the dynamics of colony expansion in microbial swarms and biofilms are limited by the constraints of water and nutrient availability.
Elizabeth ML Duxbury, Jonathan P Day ... Ben Longdon
A history of coevolution increases genetic variation in the susceptibility of Drosophila to viruses, largely by introducing major-effect resistance polymorphisms into populations.
Genetic studies reveal a role for Yap1 in lymphatic endothelial progenitor cell sprouting and proliferation during early zebrafish lymphatic vascular development.
Loes Koelewijn, Thomas M Lancaster ... Krish Singh
Electrophysiology pinpoints brain function abnormalities in young people genetically at risk of developing Alzheimer's disease much later in life, supporting theories of initial hyperconnectivity driving eventual profound disconnection.
David Trombley McSwiggen, Anders S Hansen ... Xavier Darzacq
Transient DNA interactions by DNA-binding proteins are utilized by herpes simple virus as an alternative route to generate membraneless compartments in the nucleus without invoking phase separation.
Kayle S Sawyer, Nasim Maleki ... Marlene Oscar-Berman
Neuroimaging shows brain responses to emotional pictures are more diminished in alcoholic men than in alcoholic women, implicating gender-related mechanisms of addiction.
Thomas SA Wallis, Christina M Funke ... Matthias Bethge
Peripheral appearance models emphasising pooling processes that depend on retinal eccentricity will instead need to explore input-dependent grouping and segmentation.
New intracellularly-expressed llama anti-EPS15 nanobodies reveal that pioneer clathrin-coat components function upstream of AP-2 clathrin adaptor deposition at the plasma membrane.
Madineh Sedigh-Sarvestani, Larry A Palmer, Diego Contreras
A characterization of LGN-V1 synaptic transmission properties demonstrates thalamocortical synapses in vivo are weak and unreliable, but biologically constrained models show they efficiently drive cortex.
Acetylcholine, a common modulator in the brain, controls spike-frequency adaptation by specifically attenuating Ether-a-go-go related K+ currents, thereby explaining many cortical network statistical changes often observed in vivo.
The heme and HRI-mediated eIF2aP–ATF4 integrated stress response in erythropoiesis has a major global impact, especially under the stress condition of iron deficiency.
The chromatin remodeler and tumor suppressor SMARCB1 acts to restrict superenhancer function to direct neural differentiation of embryonic stem cells while repressing bivalent gene activity in the pluripotent state.
The multi-stage model of carcinogenesis requires the incorporation of aging-dependent somatic selection and life history-dependent evolution of species-specific tumor suppressor mechanisms in order to generalize carcinogenesis across tissues and species.
The mammalian utricle can better regenerate hair cells compared to the cochlea because it maintains hair cell gene loci in a more transcriptionally accessible state.
During a sensorimotor perturbation, task outcome may serve as a gain on implicit adaptation or provide a distinct error signal for a second, independent implicit learning process.
Frederick Verbruggen, Adam R Aron ... C Nico Boehler
Clear guidelines and open-source software resources are provided for the stop-signal task, in order to streamline the use of this important tool, and to thereby increase its validity and reliability.
Greed personality trait is associated with behavioral loss aversion via the mediation of the neural loss aversion signal in the medial orbitofrontal cortex.
Salvador Dura-Bernal, Benjamin A Suter ... William W Lytton
The NetPyNE software tool provides a framework to efficiently develop, simulate, optimize and analyze experimentally grounded neural models spanning the molecular, cellular and circuit scales.
NR4A is a broadly conserved transcription factor that is required for concordance of patterning information and anatomy at both ends of the planarian anterior-posterior axis.
Expression of a Dravet syndrome-associated mutation in inhibitory neurons disrupts activity of brainstem respiratory neurons and diminishes respiratory behavior in conjunction with seizures and premature death.
An unbiased genetic screen in Drosophila provides evidence for a direct link between glial Ca2+ 25 signaling and classical functions of glia in buffering external K+ as a mechanism to regulate neuronal excitability.
Severe neurodevelopmental disorder risk gene functions are retained into adulthood and they contribute to disease phenotypes, indicating that these patients may respond to treatments throughout life.
Delayed inhibition precisely balances excitation from arbitrary combinations of CA3 neurons and controls the gain of CA1 output by reducing inhibitory delay with increasing excitation.
Siyu Serena Ding, Linus J Schumacher ... André EX Brown
Two seemingly distinct behaviors in social C. elegans worms, namely aggregating into groups and swarming over food, are driven by the same underlying mechanisms.
David William Kikuchi, Anna Dornhaus ... Thomas N Sherratt
In richer, more even communities, foragers form broad categories among their food resources that can select for convergence among signals, including mimetic resemblances.
Animal RanBP1 nuclear export and cargo dissociation mechanisms are surprisingly different from yeast, due to mutations of critical residues, leading to greater nuclear transport efficiency and higher energy cost.
During CRISPR adaptation, Cas4 forms a ternary complex with the Cas1-Cas2 spacer integration complex, an interaction that coordinates substrate hand-off following precise, PAM-dependent prespacer processing prior to integration.
Wanqing Shao, Sergio G-M Alcantara, Julia Zeitlinger
Reporter-ChIP-nexus captures paused Pol II on transfected plasmids and shows that pausing stability is influenced by core promoter sequences, especially by the initiator with a G at +2 position.
Biochemical studies revealed novel property of human tumor suppressor PALB2, which significantly contribute into DNA repair in cells and can be targeted for the development of novel anticancer treatment.
Luis Carrillo-Reid, Michelle Day ... D James Surmeier
In mouse models of Huntington's disease, striatal spiny projection neurons up-regulate dendritic potassium channels, which impairs their normal function, but a zinc finger gene therapy can reverse this deficit.
Caesar M Hernandez, Caitlin A Orsini ... Jennifer L Bizon
Optogenetic approaches in young and aged rats define multiple roles for basolateral amygdala in guiding intertemporal choice, and show that these roles change across the lifespan.
Shaun P Steele, Zach Chamberlain ... Thomas H Kawula
Francisella tularensis spreads from cell to cell when macrophages engulf small portions of infected cells upon cell contact, forming distinctive a double membraned endosome containing multiple bacteria per individual vacuole.
Christopher D Todd, Özgen Deniz ... Miguel R Branco
Genetic and epigenetic editing experiments establish causal links between transposon-derived enhancers and gene regulation in mouse embryonic and extraembryonic lineages.
Fusion of muscle progenitors drives continuous myonuclear accretion during exercise and impacts various adaptations in skeletal muscle including response to injury and hypertrophy.
Qiushuang Wu, Santiago Gerardo Medina ... Ariel Alejandro Bazzini
Genomic-profiles and reporters reveal that the three-nucleotide ‘words’ read by the ribosome, codons, have a strong effect on mRNA stability, impacting the homeostatic mRNA and protein levels in human cells.
Virginie Fresno, Shauna L Parkes ... Mathieu Wolff
Disconnection of the orbitofrontal cortex from the submedius nucleus but not the mediodorsal thalamus prevented rats to respond adaptively following action-outcome reversal, showing differential involvement of these thalamocortical circuits.
L. interrogans utilizes endocytic recycling and vesicular transport systems for transcytosis across endothelial or epithelial barrier in blood vessels or renal tubules, which contributes to spreading and transmission of leptospirosis.
Matthew J Kourakis, Cezar Borba ... William C Smith
The ascidian Ciona integrates visual information from two photoreceptor types through convergent excitatory and disinhibitory circuits, thereby evoking swim behaviors.
David Goyer, Marina A Silveira ... Michael T Roberts
VIP neurons are a novel class of inferior colliculus stellate neurons that project to long-range auditory and non-auditory targets and integrate inputs from the auditory brainstem and contralateral IC.
Polyglutamine expansion in mutant huntingtin disrupts a novel transcription-coupled DNA repair complex, providing an undescribed mechanism of neuronal toxicity and degeneration in Huntington's disease.
Restoration of molecular and morphological symmetry and mechanical integrity following epithelial fusion relies on adaptive changes that are mediated by cytoskeletal tension and Bazooka dependent modulation of fusing interface geometry.
Andrew K Lawton, Tyler Engstrom ... Alexandra L Joyner
A multi-phase wrinkling model accounts for the radial and circumferential tension and differential expansion between a uniformly proliferating outer fluid-like layer and an incompressible core that together drive cerebellar folding.
Three-dimensional chromatin architecture facilitates a promoter switch in order to ensure maintained expression of a gene involved in growth during embryonic stem cell differentiation.
NOD-like receptor NLRP12 is a critical regulator of hepatocyte proliferation and its activation could be therapeutically used to suppress hepatocellular carcinoma.
The nutrients available in some tumors and the factors that influence tumor nutrient availability are characterized, which provides insight into the metabolic constraints of the tumor microenvironment.
A 99-million year old beetle in amber was a myrmecophile—a social impostor of the earliest-known ant colonies—revealing the most ancient behavioral symbiosis yet discovered in the Metazoa.
Parvalbumin positive GABAergic neurons in the ventral zona incerta receive input from somatosensory cortex and enhance sound-induced flight behavior, which underlies a cross-modality facilitation of defensive behavior by somatosensory input.
Crystal structures of the mouse CMP-sialic acid transporter in complex with both CMP and CMP-sialic acid reveal the mechanisms of substrate selectivity and transport.
Meredith A Sommars, Krithika Ramachandran ... Grant D Barish
B cell lymphoma 6 (BCL6) represses fasting gene expression by opposing peroxisome proliferator-activated receptor alpha (PPARa) activity at enhancers, and its ablation protects against steatosis by enhancing fatty acid catabolism.
A transcriptome dataset of nearly 200 genetically identified mouse neuronal cell types revealed that short low-noise homeobox transcription factors and long neuronal effector genes best distinguish neuronal cell types.
Environmental heterogeneity can dramatically reduce the efficacy of selection and alter the neutral evolutionary dynamics in microbial range expansions.
Hirofumi Noguchi, Jesse Garcia Castillo ... Samuel J Pleasure
Sufu controls dentate gyrus stem cell quiescence by acting as a positive regulator of Shh signaling and loss of Sufu leads to dramatic failure to produce sufficient quiescent stem cells.
Structural and functional analysis of the OTOP3 channel from Xenopus tropicalis offers insights into the mechanism of ion transport and regulation in the otopetrin proton channel family.
Both exogenous and endogenous genes can be highly activated in cells by a new dCas9-based activator, CRISPR-assisted trans enhancer, that can be used to activate genes for biomedical applications.
Loïc Binan, François Bélanger ... Santiago Costantino
Single cells from a large heterogeneous population can be identified, isolated and clonally expanded using commonly available microscopy equipment and simple reagents, based solely on visual characteristics.
Dmitry Kobak, Jose L Pardo-Vazquez ... Alfonso Renart
Representation of sound lateralisation and intensity by neural population in the rat auditory cortex strongly depends on the brain state suggesting that the neural tuning to lateralisation is not hard-wired.
Neutrophil-dependent innate immune responses to the human pathogen, methicillin-resistant Staphylococcus aureus, are modulated by an interplay between interleukin-21 and type 1 interferons.
Valentina Arkhipova, Gianluca Trinco ... Albert Guskov
Glutamate transporter homologs can efficiently bind and transport both L- and D- enantiomeric substrates with only slight rearrangements in the binding site.
Zachary F Hallberg, Chi Ho Chan ... Ming C Hammond
A newfound signaling enzyme that diverged from a protein family ubiquitous in bacteria provides mechanistic insights into how new signaling activity emerges to control distinct cellular function and physiology.
Elena Gonzalo-Gil, Patrick B Rapuano ... Richard E Sutton
A subset of EC/VCs have CD4+T cells with resistance specific to R5-tropic HIV infection associated with transcriptional down-regulation of ccr5, a phenotype that appears to be heritable, across multiple generations.
Simeon Leupold, Georg Hubmann ... Matthias Heinemann
With replicative age, S. cerevisiae shifts from a fermentative towards an unusual respiratory metabolism, accompanied by a decrease in growth and glucose uptake rate.
Maria Pernemalm, AnnSofi Sandberg ... Janne Lehtiö
Comprehensive mass spectrometry analysis of human plasma proteome reveals tissue leakage proteins, describes variability between individual plasma proteomes and demonstrates protein transfer across the placenta during pregnancy.
The rhythmicity in upper-limb tracking movements and associated population dynamics in primary motor cortex is explained by a feedback controller incorporating optimal state estimation.
Sergio Menchero, Isabel Rollan ... Miguel Manzanares
The Notch signaling pathway drives transitions in differentiation capacities during the gradual loss of potency that occurs in the preimplantation mouse embryo before the onset of the first lineage decisions.
Epigenome and Mitochondrial Barcode of Lineage from Endogenous Mutations (EMBLEM) enable tracking cell lineage in combination with chromatin profile in ATAC-seq data.
At gastrulation, mesoderm arises as a migratory germ layer that will participate to both foetal and placental development through region-dependant adaptation of cytoskeleton composition, cell shape and migration mode.
Ruben M Atilho, Gayan Mirihana Arachchilage ... Ronald R Breaker
Many bacteria use a tiny riboswitch aptamer to sense the thiamin precursor HMP-PP to regulate the production of another thiamin precursor HET-P to efficiently biosynthesize this essential coenzyme.
The F-box and U-box E3 ubiquitin ligase decoy library is a powerful tool for the functional characterization of redundant E3 ubiquitin ligases, like MAC3A and MAC3B, novel circadian clock regulators.
Liquid-liquid phase separation of tau is demonstrated to be an equilibrium state, stable only within a narrow range near physiological conditions, and thus has the capacity to regulate biological processes.
Javier A Suarez, James D Howard ... Thorsten Kahnt
Activity in the midbrain responds to unexpected changes in outcome identity (i.e. sensory prediction error) but does not scale with perceptual distance between expected and receipt reward.
O Sascha Yousefi, Matthias Günther ... Wolfgang WA Schamel
Controlling the duration of ligand binding to the T cell receptor by light shows that T cells discriminate stimulatory from non-stimulatory ligands by measuring the dynamics of ligand binding.
Sarcoidosis, a granulomatous disease characterized by macrophage and T-cell activation, is found to be associated with increased HIF-1α transcriptional activity, and modulation of HIF-1α regulates inflammatory immune responses.
Kevin P Koster, Walter Francesconi ... Akira Yoshii
NMDA receptor function is regulated by protein depalmitoylation during visual cortical maturation and is dysfunctional in infantile neuronal ceroid lipofuscinosis.
Luhong Wang, Charlotte Vanacker ... Suzanne M Moenter
Estradiol regulates the pre-ovulatory luteinizing hormone surge through hypothalamic anteroventral periventricular kisspeptin neurons and maintains reproductive cyclicity through arcuate kisspeptin neurons in an activational manner.
Rebecca L Newcomer, Jason R Schrad ... Kristin N Parent
The structure of phage L's Dec demonstrates a new fold within this family of proteins, and shows modulation of capsid binding occurs through two sites, with site 1 being preferred.
The bed nucleus of the stria terminalis (BNST) is required for the expression of defensive behavior to uncertain threats, a function that is central to pathological anxiety.
Arabidopsis deploys the core signalling module that perceives distinct stress signals, such as DNA damage and heat stresses, and represses G2/M-specific genes, thereby causing cell cycle arrest.
SPARK2 allows a transcriptional readout of inter- and intracellular protein-protein interactions, with near-zero background, by employing proximity-dependent luciferase-LOV regulation.
Degradosome-associated nucleases PNPase and RNase J2 are required for type III CRISPR immunity against diverse nucleic acid invaders originating from plasmid and phage.
David J Thaller, Matteo Allegretti ... C Patrick Lusk
ESCRT-driven mechanisms that sense and seal holes in the nuclear membranes directly monitor the nuclear transport system and the exposure of the inner nuclear membrane.
Invertebrate TRPM2 channels have stable pores but act as chanzymes that hydrolyze their activating ligand ADP ribose (ADPR), whereas vertebrate TRPM2 channels are catalytically dead but undergo pore inactivation.
Human mobility drives malaria importation within countries and threatens elimination interventions, but can be measured using new approaches that combine parasite genetics, mobile phone data, travel surveys and models.
Combining parasite genetic and human mobility data can provide detailed information on local and cross-border connectivity, allowing programs to strengthen local and regional coordination for successful elimination of malaria.
Adelaida M Celaya, Isabel Sánchez-Pérez ... Isabel Varela-Nieto
Mitogen-activated protein kinase phosphatase 1 (DUSP1) deficiency causes early redox imbalance and increased inflammatory response in the cochlea, leading to cell loss and progressive neurosensory hearing loss.
Nick D Pokorzynski, Amanda J Brinkworth, Rey Carabeo
Analysis of the atypical tryptophan biosynthetic operon of Chlamydia trachomatis revealed the simultaneous regulation of transcriptional initiation and termination by an iron-dependent repressor, expanding known regulatory mechanisms of this pathway.
Fabienne Benz, Viraya Wichitnaowarat ... Stefan Liebner
Endothelial tightening by augmenting low level Wnt/β-catenin activity in vessels of the mouse subfornical organ, influences neuronal activation in water-deprived mice, linking endothelial barrier properties to neuro-vascular coupling.
Elevating beta-catenin signaling converts endothelial cells in typically fenestrated central nervous system vasculature to a blood-brain barrier (BBB) phenotype and promotes a BBB gene expression program and chromatin landscape.
