November 2019

Cover articles

    1. Evolutionary Biology

    Extra vertebra seen in giant caiman fossil

    Torsten M Scheyer, John R Hutchinson ... Marcelo R Sánchez-Villagra
    1. Immunology and Inflammation
    2. Neuroscience

    Pathogen avoidance in C. elegans

    Jogender Singh, Alejandro Aballay
    1. Physics of Living Systems

    Pattern formation from minimal motifs

    Philipp Glock, Fridtjof Brauns ... Petra Schwille
    1. Neuroscience

    Seasonal changes and circadian clocks

    Kayla E Rohr, Harshida Pancholi ... Jennifer Evans

Highlights controls:

Research articles

    1. Neuroscience

    Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls

    Swagata Ghatak, Nima Dolatabadi ... Stuart A Lipton
    Increased excitation and decreased inhibition associated with abnormal neuronal morphology, aberrant ion channel properties, and synaptic dysfunction contribute to hyperexcitability in Alzheimer’s disease hiPSC-derived neuronal cultures and cerebral organoids.
    1. Neuroscience

    Causal links between parietal alpha activity and spatial auditory attention

    Yuqi Deng, Robert MG Reinhart ... Barbara G Shinn-Cunningham
    Stimulating one side of parietal cortex using an appropriate frequency of alternating current interferes with attention to a sound stream from a location on the opposite side of a space.
    1. Neuroscience

    Alpha/beta power decreases track the fidelity of stimulus-specific information

    Benjamin James Griffiths, Stephen D Mayhew ... Simon Hanslmayr
    Neural representations of stimulus-specific information increase in fidelity as the power of alpha/beta activity decreases, suggesting that alpha/beta power decreases reflect a domain-general mechanism that supports information representation.
    1. Developmental Biology

    Endothelial EphB4 maintains vascular integrity and transport function in adult heart

    Guillermo Luxán, Jonas Stewen ... Ralf H Adams
    EphB4 maintains critical functional properties of the adult cardiac vasculature, namely mechanical resistance and fatty acid transport capability, and thereby prevents dilated cardiomyopathy-like defects.
    1. Cell Biology
    2. Genetics and Genomics

    Micronuclei-based model system reveals functional consequences of chromothripsis in human cells

    Maja Kneissig, Kristina Keuper ... Zuzana Storchova
    A method to generate human cells with massive chromosomal aberrations on a specific chromosome allows analysis of their consequences.
    1. Biochemistry and Chemical Biology

    Specific lid-base contacts in the 26s proteasome control the conformational switching required for substrate degradation

    Eric R Greene, Ellen A Goodall ... Andreas Martin
    The 26S proteasome lid subcomplex acts as an external scaffold whose interactions with the ATPase motor stabilize the substrate-engagement-competent state, and control conformational changes upon engagement for subsequent degradation steps.
    1. Evolutionary Biology

    Giant extinct caiman breaks constraint on the axial skeleton of extant crocodylians

    Torsten M Scheyer, John R Hutchinson ... Marcelo R Sánchez-Villagra
    The giant caiman Purussaurus from the Miocene of Venezuela is the first recorded member of crown Crocodylia having three sacrals, thus breaking the otherwise strict vertebral constraint of the group.
    1. Neuroscience

    Kv1.1 contributes to a rapid homeostatic plasticity of intrinsic excitability in CA1 pyramidal neurons in vivo

    Peter James Morgan, Romain Bourboulou ... Jérôme Epsztein
    Short, theta-bursts of action potential firing decrease the global excitability of CA1 pyramidal neurons, providing an internal mechanism which could regulate their allocation to memory engrams.
    1. Structural Biology and Molecular Biophysics

    Real time dynamics of Gating-Related conformational changes in CorA

    Martina Rangl, Nicolaus Schmandt ... Simon Scheuring
    High-speed atomic force microscopy reveals that the open state of the divalent ion channel CorA is highly dynamic and defined by the fast exchange between conformations.
    1. Developmental Biology
    2. Microbiology and Infectious Disease

    The Wolbachia cytoplasmic incompatibility enzyme CidB targets nuclear import and protamine-histone exchange factors

    John Frederick Beckmann, Gagan Deep Sharma ... Mark Hochstrasser
    Genetic and proteomic screening with Wolbachia's CidB enzyme reveal the mechanisms and targets of cytoplasmic incompatibility (CI).
    1. Plant Biology

    An N-terminal motif in NLR immune receptors is functionally conserved across distantly related plant species

    Hiroaki Adachi, Mauricio P Contreras ... Sophien Kamoun
    The MADA motif is functionally conserved across NLRs from distantly related plants and has degenerated in sensor NLRs over evolutionary time.
    1. Structural Biology and Molecular Biophysics

    Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating

    Marina A Kasimova, Debanjan Tewari ... Baron Chanda
    The gating polarity of a voltage-gated ion channel is primarily determined by turn propensity of residues at a critical position in the middle of the S4 voltage-sensing helix.
    1. Neuroscience

    The role of premature evidence accumulation in making difficult perceptual decisions under temporal uncertainty

    Ciara A Devine, Christine Gaffney ... Redmond G O'Connell
    Temporal uncertainty interferes with the timely onset of evidence accumulation in perceptual decision making prompting the brain to rely instead on statistical regularities in the temporal structure of the environment.
    1. Immunology and Inflammation

    Kinetics of cytokine receptor trafficking determine signaling and functional selectivity

    Jonathan Martinez-Fabregas, Stephan Wilmes ... Ignacio Moraga
    Engineering cytokines to exhibit different receptor binding dwell times is a useful strategy to decouple their functional pleiotropy and reduce their toxicity in the clinic.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Demographic reconstruction from ancient DNA supports rapid extinction of the great auk

    Jessica E Thomas, Gary R Carvalho ... Michael Knapp
    Reconstruction of great auk population dynamics suggests that hunting pressure alone could have been responsible for their extinction, demonstrating that even abundant, widespread species can be vulnerable to intense exploitation.
    1. Cell Biology

    Evolutionarily conserved long-chain Acyl-CoA synthetases regulate membrane composition and fluidity

    Mario Ruiz, Rakesh Bodhicharla ... Marc Pilon
    Silencing the acyl-coA synthethase ACSL1 protects against saturated fat lipotoxicity by preventing the degradation of polyunsaturated fatty acids, allowing them to be incorporated into phospholipids and improves membrane fluidity.
    1. Cancer Biology
    2. Genetics and Genomics

    Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction

    Shixiang Wang, Zaoke He ... Xue-Song Liu
    Tumor immunogenicity is quantified with a novel method, and the resulting tumor immunogenicity score is an effective tumor-inherent biomarker for prediction of response to immune checkpoint inhibitors.
    1. Neuroscience

    Punishment insensitivity emerges from impaired contingency detection, not aversion insensitivity or reward dominance

    Philip Jean-Richard-dit-Bressel, Cassandra Ma ... Gavan P McNally
    Behavioral analyses show that individuals insensitive to punishment are afraid of aversive events, they are simply unable to change their behaviour to avoid them.
    1. Neuroscience

    Ten simple rules for the computational modeling of behavioral data

    Robert C Wilson, Anne GE Collins
    Computational modeling of cognitive and neuroscience data is an insightful and powerful tool, but has many potential pitfalls that can be avoided by following simple guidelines.
    1. Microbiology and Infectious Disease

    Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL, and NCK1

    Hongbing Jiang, Christian Leung ... David Wang
    Genetic and biochemical analyses identify a pathway important for infection by many picornaviruses.
    1. Structural Biology and Molecular Biophysics

    The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels

    Alessandro Porro, Andrea Saponaro ... Anna Moroni
    Experimental and computational approaches reveal how ligand binding is coupled to voltage sensing in a HCN channels.
    1. Neuroscience
    2. Physics of Living Systems

    Elements of a stochastic 3D prediction engine in larval zebrafish prey capture

    Andrew D Bolton, Martin Haesemeyer ... Florian Engert
    Zebrafish implement a stochastic recursive algorithm during prey capture that reflects an implicit physical model of the world.
    1. Physics of Living Systems
    2. Structural Biology and Molecular Biophysics

    Nucleolar dynamics and interactions with nucleoplasm in living cells

    Christina M Caragine, Shannon C Haley, Alexandra Zidovska
    The nucleoplasm surrounding nucleoli in living cells plays a key role in nucleolar dynamics and shape fluctuations in vivo.
    1. Physics of Living Systems

    Design of biochemical pattern forming systems from minimal motifs

    Philipp Glock, Fridtjof Brauns ... Petra Schwille
    Theoretical analysis and in vitro reconstitution of a biological reaction-diffusion system identify key functional motifs as well as underlying principles and enable rebuilding pattern formation in a modular fashion.
    1. Genetics and Genomics

    Novel genetic loci affecting facial shape variation in humans

    Ziyi Xiong, Gabriela Dankova ... Manfred Kayser
    A comprehensive genome scan of 18,000 multi-ethnic individuals with 3-dimensional facial images highlighted multiple face-associated genetic loci for which regulatory activities in human neural cells were established.
    1. Neuroscience

    Novel charged sodium and calcium channel inhibitor active against neurogenic inflammation

    Seungkyu Lee, Sooyeon Jo ... Bruce P Bean
    A cationic molecule derived from an uncharged Cav2.2 calcium channel inhibitor powerfully inhibits both sodium and calcium channels with extracellular application and inhibits both pain and neurogenic inflammation.
    1. Neuroscience

    Apolipoprotein M-bound sphingosine-1-phosphate regulates blood–brain barrier paracellular permeability and transcytosis

    Mette Mathiesen Janiurek, Rana Soylu-Kucharz ... Martin Lauritzen
    Shortage of blood-borne apolipoprotein-M–bound sphingosine-1-phosphate, which accompanies various brain disorders, causes paracellular leak and increase in transcytosis at the blood–brain barrier, which can be reversed, thus is of clinical relevance.
    1. Evolutionary Biology
    2. Plant Biology

    Asymmetrical diversification of the receptor-ligand interaction controlling self-incompatibility in Arabidopsis

    Maxime Chantreau, Céline Poux ... Vincent Castric
    In-planta ancestral protein resurrection of the female determinant of self-incompatibility specificity in Arabidopsis halleri demonstrates that two allelic variants currently segregating as distinct receptor-ligand combinations diverged through an asymmetrical process.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the KvAP channel reveals a non-domain-swapped voltage sensor topology

    Xiao Tao, Roderick MacKinnon
    The structure of KvAP addresses a mechanism of voltage-dependent gating that has been debated for 16 years.
    1. Cell Biology
    2. Plant Biology

    From plasmodesma geometry to effective symplasmic permeability through biophysical modelling

    Eva E Deinum, Bela M Mulder, Yoselin Benitez-Alfonso
    A new biophysical model enables the reconciliation of ultrastructural and tissue level measurements on parameters affecting intercellular communication, and provides novel functional insight into experimental findings.
    1. Developmental Biology

    Prolonged ovarian storage of mature Drosophila oocytes dramatically increases meiotic spindle instability

    Ethan J Greenblatt, Rebecca Obniski ... Allan C Spradling
    Meiotic chromosome segregation in mature Drosophila oocytes is sensitive to prolonged quiescence, suggesting that human oocyte instability may result from storage of mature rather than primordial oocytes and be modifiable.
    1. Ecology

    Multistability and regime shifts in microbial communities explained by competition for essential nutrients

    Veronika Dubinkina, Yulia Fridman ... Sergei Maslov
    Multistability and regime shifts are common and species diversity is high in microbial communities when nutrient supplies are balanced and competing species have different stoichiometries of essential nutrients.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Chromatin-bound CRM1 recruits SET-Nup214 and NPM1c onto HOX clusters causing aberrant HOX expression in leukemia cells

    Masahiro Oka, Sonoko Mura ... Yasuyuki Ohkawa
    A key molecule that connects leukemogenic proteins to aberrant HOX gene regulation turned out to be a nuclear export factor, CRM1.
    1. Structural Biology and Molecular Biophysics

    Crystal structure of dopamine receptor D4 bound to the subtype selective ligand, L745870

    Ye Zhou, Can Cao ... Xuejun Cai Zhang
    The structure of receptor-ligand complex reveals the ligand binding selectivity among different dopamine receptor subtypes and also shows how this ligand class inhibits receptor activity.
    1. Microbiology and Infectious Disease

    Persistent Mycobacterium tuberculosis infection in mice requires PerM for successful cell division

    Ruojun Wang, Kaj Kreutzfeldt ... Sabine Ehrt
    PerM-mediated FtsB stabilization is essential for cell division of Mycobacterium tuberculosis during chronic but not acute mouse infections.
    1. Cell Biology
    2. Genetics and Genomics

    The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells

    Heather P Harding, Adriana Ordonez ... David Ron
    Genetic lesions that compromise the ribosome P-stalk implicate direct signalling from the ribosome to the translation initiation factor eIF2 kinase GCN2 in the cellular response to amino acid starvation.
    1. Neuroscience

    A projection specific logic to sampling visual inputs in mouse superior colliculus

    Katja Reinhard, Chen Li ... Karl Farrow
    Transsynaptic viral tracing reveals that neurons in the superior colliculus employ projection specific rules to the sampling of retinal inputs, directing distinct visual features to different downstream targets.
    1. Cell Biology
    2. Developmental Biology

    Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila

    Nicanor González-Morales, Yu Shu Xiao ... Frieder Schöck
    Myofibril diameter is set by the controlled oligomerization of the PDZ and LIM domain protein Zasp in Drosophila.
    1. Developmental Biology
    2. Neuroscience

    Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons

    Max Koppers, Roberta Cagnetta ... Christine E Holt
    Multiple axonal guidance receptors control the local and selective translation of mRNAs by binding to ribosomes, specific mRNAs and RNA-binding proteins.
    1. Developmental Biology
    2. Genetics and Genomics

    Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

    Claudia Racioppi, Keira A Wiechecki, Lionel Christiaen
    ATAC-seq, CRISPR/Cas9 mutagenesis, reporter and gene expression assays revealed dynamic chromatin accessibility profiles governing differential gene expression during heart vs. pharyngeal muscle fate choices in the powerful chordate model Ciona.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease

    Matteo D'Antonio, Joaquin Reyna ... Kelly A Frazer
    Analysis of the major histocompatibility complex using whole genome sequencing and RNA-seq data from hundreds of individuals provides novel insights into mechanisms underlying associations of this interval with disease.
    1. Neuroscience

    Seasonal plasticity in GABAA signaling is necessary for restoring phase synchrony in the master circadian clock network

    Kayla E Rohr, Harshida Pancholi ... Jennifer Evans
    A seasonal switch to excitatory GABAA signaling dictates how daily clock neurons interact to encode environmental change.
    1. Neuroscience

    Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex

    Rachida Yakoubi, Astrid Rollenhagen ... Joachim HR Lübke
    Neocortical synapses in layer 4 of the human temporal lobe neocortex were quantitatively characterized, at the subcellular level, using high-end, high-resolution electron microscopy and 3D-volume reconstructions.
    1. Neuroscience

    Single cell transcriptome atlas of the Drosophila larval brain

    Clarisse Brunet Avalos, G Larisa Maier ... Simon G Sprecher
    Single-cell transcriptomics identifies cellular composition of the first instar Drosophila brain and the response to starvation.
    1. Neuroscience

    Elevating acetyl-CoA levels reduces aspects of brain aging

    Antonio Currais, Ling Huang ... Pamela Maher
    A novel neuroprotective pathway that enhances acetyl-CoA metabolism via inhibition of acetyl-CoA carboxylase 1 may prevent the contribution of the aging process in the brain to Alzheimer's disease.
    1. Immunology and Inflammation

    Differential impact of self and environmental antigens on the ontogeny and maintenance of CD4+ T cell memory

    Thea Hogan, Maria Nowicka ... Benedict Seddon
    Comparing mice in clean and dirty environments reveals that environment drives initial establishment and size of T cell memory compartments, but not their maintenance in adults.
    1. Developmental Biology
    2. Neuroscience

    Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth

    Ryan T Willett, N Sumru Bayin ... Alexandra L Joyner
    The first born excitatory cerebellar nuclei neurons influence the survival of their Purkinje cell partners which stimulate the expansion of granule cells and interneurons to produce functional local circuits.
    1. Neuroscience

    High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp

    Yangfan Peng, Franz Xaver Mittermaier ... Jörg Rolf Paul Geiger
    Combining a multineuron patch-clamp system with an automated pipette pressure and cleaning device enables efficient screening of synaptic connectivity in human brain slices and allows inter-individual comparison.
    1. Cancer Biology
    2. Cell Biology

    Genome-wide CRISPR screening reveals genetic modifiers of mutant EGFR dependence in human NSCLC

    Hao Zeng, Johnny Castillo-Cabrera ... Feng Cong
    Functional genomic screening reveals new synthetic lethality with and modes of resistance to epidermal growth factor receptor (EGFR) targeted therapy in EGFR-mutant human lung cancer.
    1. Neuroscience

    Local axonal morphology guides the topography of interneuron myelination in mouse and human neocortex

    Jeffrey Stedehouder, Demi Brizee ... Steven A Kushner
    The joint combination of interbranch distance and local caliber is sufficient to predict with high accuracy the distribution of myelin internodes along individual axons of neocortical GABAergic interneurons.
    1. Cancer Biology
    2. Computational and Systems Biology

    A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

    Adam C Palmer, Christopher Chidley, Peter K Sorger
    Drugs in a curative chemotherapy regimen are independently effective and resisted by different mechanisms, so cancer cells have little chance of surviving all drugs, and this benefit occurs without synergistic interactions.
    1. Neuroscience

    Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn

    Kwan Yeop Lee, Stéphanie Ratté, Steven A Prescott
    The flow of somatosensory information through the spinal dorsal horn is regulated by synaptic inhibition, which acts upon excitatory and inhibitory interneurons, but the former are especially prone to disinhibition.
    1. Developmental Biology
    2. Neuroscience

    A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture

    Alfredo Llorca, Gabriele Ciceri ... Oscar Marin
    The specification of a very small number of progenitor cells with competence to adapt their neurogenic output to different probabilistic rules underlies the generation of distinct cortical cytoarchitectures.
    1. Neuroscience

    Brain clusterin protein isoforms and mitochondrial localization

    Sarah K Herring, Hee-Jung Moon ... Liqin Zhao
    Identification and characterization of multiple brain clusterin isoforms, including a mitochondrial matrix-targeted isoform, provides foundation to potentially clarify the link between these proteins and the development of late-onset Alzheimer’s disease.
    1. Neuroscience

    Rapid learning and unlearning of predicted sensory delays in self-generated touch

    Konstantina Kilteni, Christian Houborg, H Henrik Ehrsson
    The brain continuously updates the learned temporal relationship between motor commands and their associated somatosensory feedback, which determines the perceived intensity and ticklishness of self-touch.
    1. Neuroscience
    2. Physics of Living Systems

    Replay as wavefronts and theta sequences as bump oscillations in a grid cell attractor network

    Louis Kang, Michael R DeWeese
    An experimentally supported model of grid cells naturally enables them to participate in firing sequences that encode rapid trajectories in space.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation

    Daniel Andergassen, Zachary D Smith ... John L Rinn
    The X-linked loci Firre and Dxz4 are involved in autosomal gene regulation rather than XCI biology.
    1. Neuroscience

    Spatiotemporal constraints on optogenetic inactivation in cortical circuits

    Nuo Li, Susu Chen ... Karel Svoboda
    Electrophysiology measurements characterized eight optogenetic methods, including a new reporter mouse expressing soma-localized light-activated chloride channels, for inactivating small regions of mouse neocortex.
    1. Stem Cells and Regenerative Medicine

    Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction

    Shir Toubiana, Miriam Gagliardi ... Sara Selig
    Correction of the DNA methyltransferase 3B gene in ICF1 syndrome fails to rescue the abnormal DNA hypomethylation at subtelomeric regions due to accompanied epigenetic abnormalities in these regions.
    1. Neuroscience

    Neural representation of newly instructed rule identities during early implementation trials

    Hannes Ruge, Theo AJ Schäfer ... Uta Wolfensteller
    Ventro-lateral prefrontal cortex codes novel rules starting from their first-time implementation right after instruction while early consolidation is channeled through increasing cooperation with the anterior striatum.
    1. Developmental Biology

    Multifaceted roles of microRNAs: From motor neuron generation in embryos to degeneration in spinal muscular atrophy

    Tai-Heng Chen, Jun-An Chen
    Summary review of microRNA roles during motor neuron generation and degeneration.
    1. Evolutionary Biology
    2. Structural Biology and Molecular Biophysics

    Structure of a mitochondrial ATP synthase with bound native cardiolipin

    Alexander Mühleip, Sarah E McComas, Alexey Amunts
    The atomic model of a mitochondrial ATP synthase dimer underlies functions of its specific protein constituents and boundary cardiolipins.
    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation

    Soluble PD-L1 generated by endogenous retroelement exaptation is a receptor antagonist

    Kevin W Ng, Jan Attig ... George Kassiotis
    An ancient integration of an endogenous retroelement in the gene encoding PD-L1 is exapted to generate a soluble form that antagonises the suppressive function of the membrane-bound form.
    1. Epidemiology and Global Health
    2. Medicine

    Risk factors for asthma among schoolchildren who participated in a case-control study in urban Uganda

    Harriet Mpairwe, Milly Namutebi ... Alison M Elliott
    Asthma risk among schoolchildren increases depending on area of residence in early life, from rural to town to city, and this risk increases further with other known risk factors.
    1. Neuroscience

    Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics

    Yoshinori Aso, Robert P Ray ... Gerald M Rubin
    The interplay of nitric oxide and dopamine specialize one memory unit in a fly brain in predicting the value of odors based only on recent experience.
    1. Neuroscience

    Stimulating the hippocampal posterior-medial network enhances task-dependent connectivity and memory

    Kristen N Warren, Molly S Hermiller ... Joel L Voss
    Noninvasive stimulation of hippocampal networks increases connectivity in a functionally-specific manner that is highly relevant to effective episodic memory performance that depends on the targeted network.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Formation of a β-barrel membrane protein is catalyzed by the interior surface of the assembly machine protein BamA

    James Lee, David Tomasek ... Daniel Kahne
    Outer membrane β-barrel proteins in Gram-negative bacteria are assembled within the lumen of the BamA β-barrel.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex

    Tomoki Naito, Bilge Ercan ... Yasunori Saheki
    GRAMD1 proteins sense a transient expansion of the accessible pool of plasma membrane cholesterol and facilitate its transport to the endoplasmic reticulum at ER-PM contact sites.
    1. Developmental Biology
    2. Neuroscience

    Shifts in myeloarchitecture characterise adolescent development of cortical gradients

    Casey Paquola, Richard AI Bethlehem ... Edward T Bullmore
    Layer-specific microstructural changes contribute to the maturation of cortical organisation during adolescence.
    1. Structural Biology and Molecular Biophysics

    The ion selectivity filter is not an activation gate in TRPV1-3 channels

    Andrés Jara-Oseguera, Katherine E Huffer, Kenton J Swartz
    The TRPV1, TRPV2 and TRPV3 channels are gated on the cytosolic side of the pore, whereas structural changes in the ion selectivity filter associated with activation don't control cation access.
    1. Structural Biology and Molecular Biophysics

    Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel

    Ailing Tong, John T Petroff II ... Wayland WL Cheng
    Phosphatidylglycerol binding at multiple sites stabilizes the open state relative to the desensitized state of a pentameric ligand-gated ion channel.
    1. Cell Biology
    2. Developmental Biology

    Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex

    Yue Qu, Ines Hahn ... Andreas Prokop
    The cortical collapse factor Efa6 limits axon growth and branching and maintains axonal microtubule bundle integrity by inhibiting microtubule polymerisation at the cell cortex.
    1. Neuroscience

    Reliability of an interneuron response depends on an integrated sensory state

    May Dobosiewicz, Qiang Liu, Cornelia I Bargmann
    A pair of interneurons in C. elegans condenses information from multiple sensory neurons into a uniform response, using an AND-gate logic to represent a stimulus with positive valence.
    1. Structural Biology and Molecular Biophysics

    Auto-regulation of Rab5 GEF activity in Rabex5 by allosteric structural changes, catalytic core dynamics and ubiquitin binding

    Janelle Lauer, Sandra Segeletz ... Marino Zerial
    Understanding the complex auto-regulatory mechanisms for guanine nucleotide exchange factors is critically important for fully appreciating the layers of control for small GTPases.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Cycles of autoubiquitination and deubiquitination regulate the ERAD ubiquitin ligase Hrd1

    Brian G Peterson, Morgan L Glaser ... Ryan D Baldridge
    The Hrd1-centric endoplasmic reticulum associated degradation system is regulated by interplay between the system's components.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Exploring structural dynamics of a membrane protein by combining bioorthogonal chemistry and cysteine mutagenesis

    Kanchan Gupta, Gilman ES Toombes, Kenton J Swartz
    A facile method is implemented to modify membrane proteins with biophysical reporters using cysteine-independent approaches in live cells.
    1. Immunology and Inflammation

    Atypical memory B-cells are associated with Plasmodium falciparum anemia through anti-phosphatidylserine antibodies

    Juan Rivera-Correa, Maria Sophia Mackroth ... Ana Rodriguez
    The association of atypical memory B-cells and autoimmune antibodies (anti-phosphatidylserine) with hemoglobin levels in malaria patients uncovers a novel mechanism for the human malaria-induced anemia previously identified in mice.
    1. Neuroscience

    The effects of psychosocial stress on dopaminergic function and the acute stress response

    Michael AP Bloomfield, Robert A McCutcheon ... Oliver Howes
    Imaging and laboratory-induced psychosocial stress showed that exposure to psychosocial adversity was associated with dampened striatal dopaminergic function alongside blunted physiological yet potentiated subjective responses to acute stress.
    1. Microbiology and Infectious Disease

    Interspecies interactions induce exploratory motility in Pseudomonas aeruginosa

    Dominique H Limoli, Elizabeth A Warren ... George A O'Toole
    Pseudomonas aeruginosa coordinates invasion and destruction of Staphylococcus aureus communities by modulating single-cell and collective motility.
    1. Neuroscience

    Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn

    Kelly M Smith, Tyler J Browne ... Brett A Graham
    A signal amplifier network that transmits mechanical pain is delineated through characterising an excitatory interneuron population in the spinal cord dorsal horn and defining the postsynaptic populations they regulate.
    1. Cell Biology

    DNA damage checkpoint activation impairs chromatin homeostasis and promotes mitotic catastrophe during aging

    Matthew M Crane, Adam E Russell ... Matt Kaeberlein
    Activation of a DNA-damage cell cycle checkpoint during aging causes genome instability and senescence in yeast mother cells.
    1. Epidemiology and Global Health

    The mother’s risk of premature death after child loss across two centuries

    Unnur A Valdimarsdóttir, Donghao Lu ... Kári Stefánsson
    A large-scale, sibling-based analysis of the Icelandic population spanning two centuries demonstrates an increase in maternal mortality rates after child loss on both sides of a major demographic transition.
    1. Neuroscience

    Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat

    Fuyuki Karube, Susumu Takahashi ... Fumino Fujiyama
    Globus pallidus neurons projecting to the striatum are preferentially activated by direct glutamatergic innervation from the motor cortex.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Initiation of chromosome replication controls both division and replication cycles in E. coli through a double-adder mechanism

    Guillaume Witz, Erik van Nimwegen, Thomas Julou
    Single-cell measurements combined with a new statistical framework for discriminating between models of cell cycle regulation show that chromosome initiation controls the E. coli cell cycle via two adder mechanisms.
    1. Developmental Biology

    Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4

    Jianlin Liang, Nan Wang ... Kehkooi Kee
    In vitro reprogramming of human fibroblasts to Sertoli-like cells with immunosuppressive properties provides platforms for basic research and clinical application.
    1. Neuroscience

    One-shot learning and behavioral eligibility traces in sequential decision making

    Marco P Lehmann, He A Xu ... Kerstin Preuschoff
    Human learning relies on short-term memories (eligibility traces) which provide a mechanism to reinforce sequences of actions from a single reward (one-shot).
    1. Neuroscience

    Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

    Stephen J Smith, Uygar Sümbül ... Michael Hawrylycz
    Single-cell mRNA sequencing data from mouse neocortex expose evidence for peptidergic neuromodulation networks that locally interconnect every cortical neuron.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes

    Sridhar Selvaraj, Ricardo Mondragon-Gonzalez ... Rita CR Perlingeiro
    Treatment of human pluripotent stem cell-derived myotubes with a cocktail of small molecules induces their maturation, as shown by gene expression, biochemical and functional assays.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Cryo electron tomography with volta phase plate reveals novel structural foundations of the 96-nm axonemal repeat in the pathogen Trypanosoma brucei

    Simon Imhof, Jiayan Zhang ... Kent L Hill
    Cryo electron tomography provides the first high-resolution 3D axoneme structure from any pathogenic organism, revealing novel structures that support the unique motility of these pathogens through host tissues.
    1. Microbiology and Infectious Disease

    Perinatal hormones favor CC17 group B Streptococcus intestinal translocation through M cells and hypervirulence in neonates

    Constantin Hays, Gérald Touak ... Asmaa Tazi
    Hormonal concentrations found in over 7-day-old neonates favor CC17 GBS invasiveness in a process linked to intestinal M cells maturation and mediated by the CC17 GBS surface protein Srr2.
    1. Chromosomes and Gene Expression
    2. Evolutionary Biology

    The DNA-binding protein HTa from Thermoplasma acidophilum is an archaeal histone analog

    Antoine Hocher, Maria Rojec ... Tobias Warnecke
    In Thermoplasma acidophilum, an archaeon without histones, a DNA-binding protein acquired from bacteria via horizontal gene transfer mediates histone-like chromatin architecture.
    1. Neuroscience

    Thermosensitive alternative splicing senses and mediates temperature adaptation in Drosophila

    Ane Martin Anduaga, Naveh Evantal ... Sebastian Kadener
    Temperature controls the circadian clock by directly regulating the alternative splicing of timeless..
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration

    Dana Gancz, Brian C Raftrey ... Karina Yaniv
    Cardiac lymphatic vessels of heterogeneous origins and molecular signatures support cardiac growth and regeneration.
    1. Neuroscience

    An image-computable model for the stimulus selectivity of gamma oscillations

    Dora Hermes, Natalia Petridou ... Jonathan Winawer
    Gamma-band oscillations show striking differences in stimulus selectivity compared to fMRI and broadband field potentials in human visual cortex, and are explained by a novel, image-computable model.
    1. Biochemistry and Chemical Biology

    Non-enzymatic primer extension with strand displacement

    Lijun Zhou, Seohyun Chris Kim ... Jack W Szostak
    Relying on RNA fragments derived from degradation or partial template copying, non-enzymatic primer extension with strand displacement offers a novel and prebiotically plausible approach to RNA self-replication.
    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

    Michael RM Harrison, Xidi Feng ... Ching-Ling Lien
    Zebrafish develop cardiac lymphatic vessels along coronary arteries and this vasculature supports scar reduction following severe damage to the myocardium.
    1. Neuroscience

    Drosophila PSI controls circadian period and the phase of circadian behavior under temperature cycle via tim splicing

    Lauren E Foley, Jinli Ling ... Patrick Emery
    A screen targeting RNA-associated proteins reveals that PSI regulates timeless alternative splicing and thus controls the period of Drosophila circadian behavior and its phase under temperature cycles.
    1. Evolutionary Biology

    Selection on mutators is not frequency-dependent

    Yevgeniy Raynes, Daniel Weinreich
    Contrary to intuition that the evolutionary fate of mutation rate modifying alleles is frequency-dependent, neither the strength nor the sign of selection on modifiers depends on initial frequency.
    1. Cancer Biology
    2. Computational and Systems Biology

    Computational and cellular studies reveal structural destabilization and degradation of MLH1 variants in Lynch syndrome

    Amanda B Abildgaard, Amelie Stein ... Rasmus Hartmann-Petersen
    Biophysical modeling, performed in silico, can predict the abundance, metabolic stability, and function of MLH1 inside living cells.
    1. Neuroscience

    Differential contributions of the two human cerebral hemispheres to action timing

    Anja Pflug, Florian Gompf ... Christian Alexander Kell
    Brain imaging reveals frequency-dependent lateralized rhythmic finger tapping control by the auditory cortex with left-lateralized control of relative fast and right-lateralized control of relative slow rhythms.
    1. Cell Biology

    Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2 in Drosophila

    Johanna Lattner, Weihua Leng ... David Flores-Benitez
    The polarity protein crumbs controls apical secretion and the architecture of the apical domain by modulating PI(4,5)P2 levels and the organization of apical Rab6-, Rab11-, and Rab30-dependent trafficking.
    1. Cell Biology
    2. Neuroscience

    Free circular introns with an unusual branchpoint in neuronal projections

    Harleen Saini, Alicia A Bicknell ... Melissa J Moore
    A systematic study of RNA localization unexpectedly finds a set of free circular introns with a non-canonical C branchpoint enriched in neuronal projections.
    1. Chromosomes and Gene Expression
    2. Evolutionary Biology

    Chromatinization of Escherichia coli with archaeal histones

    Maria Rojec, Antoine Hocher ... Tobias Warnecke
    Escherichia coli is surprisingly tolerant to chromatinization by archaeal histones, suggesting that histones can become established as ubiquitous chromatin proteins without interfering critically with some key DNA-templated processes.
    1. Neuroscience

    Lateral orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases

    Christine M Constantinople, Alex T Piet ... Carlos D Brody
    The lateral orbitofrontal cortex promotes learning of abstract, task-specific biases, but not spatial ones.
    1. Cell Biology

    Negative regulation of autophagy by UBA6-BIRC6–mediated ubiquitination of LC3

    Rui Jia, Juan S Bonifacino
    An ensemble of the ubiquitin-activating enzyme UBA6 and ubiquitin-conjugating enzyme/ubiquitin-ligase BIRC6 mediates ubiquitination of LC3, targeting the latter for proteasomal degradation and thus attenuating autophagic degradation of cellular substrates.
    1. Neuroscience

    Interactions between Dpr11 and DIP-γ control selection of amacrine neurons in Drosophila color vision circuits

    Kaushiki P Menon, Vivek Kulkarni ... Kai Zinn
    The survival of Drosophila amacrine neurons is controlled by neurotrophic signaling mediated by interactions between the cell surface protein DIP-γ and its partner Dpr11, which is expressed on presynaptic photoreceptors.
    1. Medicine

    Loss of adaptive capacity in asthmatic patients revealed by biomarker fluctuation dynamics after rhinovirus challenge

    Anirban Sinha, René Lutter ... Edgar Delgado Eckert
    Fluctuation of biomarkers is a novel way of studying system stability during stable and unstable states of health and disease, revealing the systems' ability to cope with external perturbations.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    RNA from a simple-tandem repeat is required for sperm maturation and male fertility in Drosophila melanogaster

    Wilbur Kyle Mills, Yuh Chwen G Lee ... Gary H Karpen
    Sperm production and male fertility in Drosophila melanogaster depend on transcripts generated from the AAGAG(n) repeated satellite DNA within primary spermatocytes.
    1. Neuroscience

    Interhemispherically dynamic representation of an eye movement-related activity in mouse frontal cortex

    Takashi R Sato, Takahide Itokazu ... Tatsuo K Sato
    Optogenetically induced motor disruption can evoke plasticity in the mouse frontal cortex that compensates for the motor deficits, accompanying changes in inter-hemispheric motor representation.
    1. Genetics and Genomics
    2. Neuroscience

    Modular transcriptional programs separately define axon and dendrite connectivity

    Yerbol Z Kurmangaliyev, Juyoun Yoo ... S Lawrence Zipursky
    Diverse morphologies of Drosophila T4/T5 neuronal subtypes are defined by the modular assembly of transcriptional programs for distinct wiring features.
    1. Cell Biology

    The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating drosha activity

    Tsui Han Loo, Xiaoqian Ye ... Colin L Stewart
    The LINC complex, that couples the interphase cytoskeleton to the nucleus, regulates the processing of a cluster of miRNAs required for muscle regeneration by recruiting and interacting directly with Drosha.
    1. Cancer Biology
    2. Microbiology and Infectious Disease

    A single clonal lineage of transmissible cancer identified in two marine mussel species in South America and Europe

    Marisa A Yonemitsu, Rachael M Giersch ... Michael J Metzger
    A transmissible cancer that arose in a marine mussel spread from a single animal to become a global pathogen affecting two other mussel species in both Europe and South America.
    1. Neuroscience

    Dichotomous organization of amygdala/temporal-prefrontal bundles in both humans and monkeys

    Davide Folloni, Jerome Sallet ... Rogier B Mars
    Amygdala/temporal-prefrontal cortex fibers are organised in separate amygdalofugal and uncinate bundles in humans and macaques, shaping the anatomical foundation for decision-making and socio-emotional behaviour.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

    Andrea Brenna, Iwona Olejniczak ... Urs Albrecht
    Cyclin-dependent kinase 5 regulates the circadian clock involving phosphorylation of the PER2 protein.
    1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP

    Arunava Roy, Anandita Ghosh ... Bala Chandran
    The innate immune DNA sensor IFI16 is in association with H3K9 methyltransferases SUV39H1 and GLP under physiological conditions in the nucleus which facilitates the epigenetic silencing of foreign viral DNA.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Chromosome territory formation attenuates the translocation potential of cells

    Leah F Rosin, Olivia Crocker ... Eric F Joyce
    The translocation potential of cells can be modulated by Condensin II activity during interphase.
    1. Cell Biology

    Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome

    Yilin Kang, Alexander J Anderson ... Diana Stojanovski
    A neuronal specific function of the mitochondrial chaperone, hTim8a in Complex IV biology provides insight into the pathomechanisms underlying the mitochondrial disease, Mohr-Tranebjaerg syndrome.
    1. Cell Biology

    Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander disease severity

    Rachel A Battaglia, Adriana S Beltran ... Natasha T Snider
    GFAP protein carries a distinct post-translational modification signature that facilitates its pathogenic accumulation and aggregation in astrocytes of patients who succumb to Alexander Disease very early in life.
    1. Structural Biology and Molecular Biophysics
    2. Biochemistry and Chemical Biology

    Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ

    Alan Sulpizio, Marena E Minelli ... Yuxin Mao
    The pseudokinase-like Legionella effector SidJ catalyzes the glutamylation of bacterial ubiquitin ligases in a calmodulin-dependent manner.
    1. Cell Biology
    2. Developmental Biology

    Single-cell proteomics reveals changes in expression during hair-cell development

    Ying Zhu, Mirko Scheibinger ... Peter G Barr-Gillespie
    Protein mass spectrometry can be used to uncover developmental trajectories in small single cells of differentiating tissues.
    1. Physics of Living Systems
    2. Structural Biology and Molecular Biophysics

    High-throughput, single-particle tracking reveals nested membrane domains that dictate KRasG12D diffusion and trafficking

    Yerim Lee, Carey Phelps ... Xiaolin Nan
    The nanoscopic landscape of the membrane has a direct impact on the spatiotemporal, and likely also the signaling, dynamics of Ras proteins.
    1. Cell Biology
    2. Genetics and Genomics

    Retro-2 protects cells from ricin toxicity by inhibiting ASNA1-mediated ER targeting and insertion of tail-anchored proteins

    David W Morgens, Charlene Chan ... Michael C Bassik
    Using a suite of CRISPR technologies, unique chemical tools, and carefully designed biochemical and cell biological assays, we define the mechanism of action of Retro-2, an inhibitor of retrograde toxins.
    1. Ecology
    2. Neuroscience

    Optimal searching behaviour generated intrinsically by the central pattern generator for locomotion

    David W Sims, Nicolas E Humphries ... Jimena Berni
    The nervous system circuitry that controls locomotion has evolved to intrinsically generate an optimal search pattern for resources.
    1. Neuroscience

    Dopamine neuron ensembles signal the content of sensory prediction errors

    Thomas A Stalnaker, James D Howard ... Geoffrey Schoenbaum
    Dopamine neurons function as an ensemble to signal a multidimensional feature prediction error.
    1. Immunology and Inflammation
    2. Neuroscience

    Intestinal infection regulates behavior and learning via neuroendocrine signaling

    Jogender Singh, Alejandro Aballay
    Feedback from the intestine during infection can modulate the behavior, learning, and microbial perception of the host.
    1. Neuroscience

    The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier

    Stephen G Brohawn, Weiwei Wang ... Roderick MacKinnon
    The mechanosensitive potassium channel TRAAK is localized to nodes of Ranvier is mammalian axons where it hyperpolarizes the resting potential and may contribute to mechanical repolarization of neurons.
    1. Genetics and Genomics

    An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms

    Oguz Kanca, Jonathan Zirin ... Hugo J Bellen
    Optimization of homology donor DNA production and integration schemes facilitates homologous recombination in vivo and in cell culture in Drosophila melanogaster..

Magazine

    1. Cancer Biology

    Philosophy of Biology: Characterizing causality in cancer

    Elena Rondeau, Nicolas Larmonier ... Andreas Bikfalvi
    1. Immunology and Inflammation
    2. Neuroscience

    Autoimmunity: Bringing on the itch

    Daniel A Waizman, Sourav Ghosh, Carla V Rothlin
    1. Neuroscience

    Behavior: The cerebellum shows its stripes

    Ashley L Holloway, Talia N Lerner
    1. Neuroscience

    Brain Development: The impact of light during the night

    Sophia TC Leung, R Anne McKinney, Alanna J Watt
    1. Neuroscience

    Prefrontal Cortex: A tale of two pathways

    Jonathan A Oler, Julie L Fudge