After developing a force-gliding assay with nanometer and piconewton precision, it is concluded that multiple kinesins driving a single cargo induces tension, resulting in smooth cargo transport, even with roadblocks.
Phenotypic evolution can originate from variations in very precocious developmental events, starting even before fecundation, during the fabrication of the egg in the mother's gonad.
Danielle J Clark, Laura E McMillan ... Christoph Wülfing
A membrane-associated, supramolecular protein complex with dynamically changing components, the central supramolecular activation cluster, regulates the generation of the T cell effector cytokine IL-2 depending on its composition.
In motor cortex pyramidal neurons, diverse task-related signals are distributed throughout the dendritic arbor and compartmentalized by dendritic distance and branching.
Luis F Sifuentes-Dominguez, Haiying Li ... Ezra Burstein
A novel mutation in SCGN is associated with risk for inflammatory bowel disease and implicates the intestinal neuroendocrine compartment in the pathogenesis of this disorder.
Elliot Imler, Jin Sang Pyon ... Konrad E Zinsmaier
Genetic analysis of a CLN4 Drosophila model suggests that the disease-causing alleles act as dominant gain of function mutations that cause CSPα oligomerization and impair secretory and prelysosomal trafficking.
Xiao Min Zhang, Urielle François ... Etienne Herzog
In mammals, the vesicular glutamate transporter 1 acquired a proline-rich sequence that negatively regulates the spontaneous release of glutamate by reducing the exchange of synaptic vesicles along the axon.
Nicholas C Vierra, Michael Kirmiz ... James S Trimmer
A potassium channel, as a nonconducting function, organizes compartmentalized neuronal calcium signaling microdomains via structural and functional coupling of plasma membrane and endoplasmic reticulum calcium channels.
Conditional gene knockout in combination with fluorescent labeling of different alleles can be achieved with high efficiency in zebrafish through NHEJ-mediated targeted insertion using a CRISPR/Cas system.
Pengxing Cao, Katharine A Collins ... James M McCaw
A mathematical model of blood-stage infection with Plasmodium falciparum malaria capturing the sexual stage of the parasite life-cycle is validated against human data, providing new insight into human-to-mosquito transmission.
The archaeal MCM helicase can load in multiple orientations on DNA but translocation proceeds with a leading N-terminal domain, which affects double hexamer activation at origins of replication.
David Massa López, Melanie Thelen ... Markus Damme
The so far uncharacterized lysosomal transporter protein MFSD1 is essential for liver homeostasis and needs the highly glycosylated GLMP protein as an accessory subunit for stability.
Other than its function in mechanotransduction, TMC1 is indispensable for action potential firing of auditory hair cells by mediating a leak conductance that alters tonotopically along the cochlea coil.
The universal bacteria cell wall component peptidoglycan impacts the egg-laying behavior of infected Drosophila females by directly modulating the activity of few brain octopaminergic neurons.
Evolutionary trade-offs enhance efficacy of antibiotic therapy by constraining bacterial adaptation in dependence of drug order and trade-off effect size.
Clara Sidor, Nerea Borreguero-Munoz ... Barry J Thompson
The MASK family of proteins regulate the action of the YAP/TAZ family of transcriptional coactivators, key regulators of stem cell proliferation and cancer.
Electrophysiological recordings in monkeys reveal that cerebellar complex spikes encode future reward size when reward information is first made available, but not during reward delivery or smooth pursuit eye movement.
Jonathan H Cornford, Marion S Mercier ... Dimitri M Kullmann
NMDA receptors on PV+ interneurons mediate supralinear integration at feedback synapses from local pyramidal neurons, enabling competing networks to ‘lock’ onto salient inputs.
Antonio Michelucci, Simona Boncompagni ... Feliciano Protasi
Structural and functional analyses show that transverse tubule association with stacks of sarcoplasmic reticulum enhances Orai1-dependent Ca2+ entry to replenish Ca2+ stores, maintain Ca2+ release, and maximize force during exercise.
Mark S Ladinsky, Wannisa Khamaikawin ... Collin Kieffer
Large-volume light microscopy combined with higher-resolution electron tomography revealed the spatial distribution of virus-producing cells and highlighted mechanisms of HIV-1 dissemination in bone marrow from a small animal model.
The patched hedgehog receptor inhibits the transmembrane transducer smoothened by reducing the accessibility of cholesterol locally at the membrane of the primary cilium.
Matthew Swire, Yuri Kotelevtsev ... Charles ffrench-Constant
Endothelin signalling, regulated by changes in neuronal activity associated with experience, influences the number of myelin sheaths formed by individual oligodendrocytes.
Mykola Pinkevych, Christine M Fennessey ... Miles P Davenport
The frequency of SIV reactivation from latency after treatment interruption is not directly related to measures of SIV DNA, RNA, immune activation or immune response in peripheral blood.
The HCoV-229E coronavirus S-protein accommodates extensive mutational change and possesses hydrophilic subunit interfaces in the S2 region, features that provide new insights into immune evasion, cross-species transmission and membrane fusion.
A temperate bacteriophage reprograms the oxygen response of a bacterial signaling system by replacing a host-encoded promoter with a phage-encoded promoter.
Although odorant binding proteins are widely believed to be required for transport of odorants to receptors, six types of sensilla of Drosophila respond robustly in their absence to many odor stimuli.
Omaya Dudin, Andrej Ondracka ... Iñaki Ruiz-Trillo
Cellularization in Sphaeroforma arctica generates a self-organized structure that morphologically resembles an epithelium, and is associated with tightly regulated expression of cell adhesion pathways.
Téo Fournier, Omar Abou Saada ... Joseph Schacherer
Genome-wide association studies on a diallel yeast panel revealed the relevance of low-frequency variants on the phenotypic diversity and consequently on the missing heritability at a population-scale.
Adriana E Golding, Ilaria Visco ... William M Bement
Through visualization of directly-labeled RhoGTPase both in vitro and in vivo, RhoGDI is found to spatiotemporally regulate RhoGTPase activity through the extraction of active RhoGTPase.
Taylor ET Hughes, John Smith Del Rosario ... Vera Y Moiseenkova-Bell
Structure-based virtual screening reveals multiple novel TRPV5 inhibitors that bind and exert their effect from previously unidentified binding sites as characterized by cryo-electron microscopy and electrophysiology.
The combination of single-cell transcriptomics and whole-brain mapping of bulk and single-cell projections reveals the relationship between the molecular architecture, cell body distribution, and axonal arborization of serotonin neurons.
Rare, evolutionarily recent variants have larger effect sizes and are more likely to decrease fitness, providing evidence that quantitative traits in yeast have evolved under purifying selection.
Hemoglobin affinity and cooperativity reveal mechanistic insights in how the relation between physiology and evolutionary variations shape a protein's molecular property.
Rachel A Liberatore, Emily J Mastrocola ... Paul D Bieniasz
A new animal model permits the in vivo study of HIV-1 entry, as well as the elicitation and antiviral activity of antibodies, in a genetically manipulatable host.
Prashant Rajbhandari, Douglas Arneson ... Peter Tontonoz
Crosstalk between IL10-producing immune cells and adipocytes within adipose tissue is an important determinant of thermogenesis and systemic energy balance.
The readiness potential—a long-established neural precursor of voluntary action claimed to precede the onset of the conscious decision to move—is absent, or at least significantly reduced, for deliberate decisions.
Miklos Argyelan, Leif Oltedal ... Christopher Abbott
The electroconvulsive therapy induced electric field magnitude and laterality is related to volumetric increases in cortical and subcortical structures, but the association with clinical outcomes remains elusive.
Chen Farhy, Santosh Hariharan ... Alexey V Terskikh
A novel phenotypic screening platform based on immunofluorescent imaging of histone modifications enables accurate identification of cell fates and environmental perturbations.
Kate A Rawlinson, Francois Lapraz ... Maximilian J Telford
A new opsin receptor is light-sensitive and expressed in a unique type of photoreceptor in a flatworm that encloses over 400 sensory cilia within its cell membrane.
Conservative mutations within a secondary active transport protein influenced the conformational equilibrium probed using NMR spectroscopy which correlated to the functional output in vivo.
Post-translational modifications regulate transient protein-protein interactions to disrupt Ubiquitin enzyme/ligase complexes, a strategy used by Shigella to inactivate the host immune response.
Lydia V Luncz, Mike Gill ... Suchinda Malaivijitnond
Tool behaviour of long-tailed macaques leaves archaeological signatures that differ between populations despite similar ecological conditions, highlighting the potential for diversity in material culture.
Kimberly M Fornace, Neal Alexander ... Chris Drakeley
Local human movement into mosquito habitats around forest edges intensifies interactions between pathogens, insects and people, increasing exposure risks to the zoonotic malaria Plasmodium knowlesi in Malaysian Borneo.
Herpes simplex ICP4 preferentially binds to and delineates the viral genome, ultimately resulting in robust viral transcription at the expense of the host.
Softer sound appears closer to midline than louder sound, conflicting with a labelled-line representation of auditory space and supporting the idea that humans use rate coding when calculating sound directionality.
Daniel P Murphy, Andrew EO Hughes ... Joseph C Corbo
While photoreceptor and bipolar cells exhibit very similar cis-regulatory grammars, subtle differences in homeodomain motif enrichment represent a key distinction driving the divergence in their transcriptomes.
Neutrophils are essential for itch in a mouse model of atopic dermatitis, and promote the transition from acute to chronic itch via induction of CXCL10/CXCR3 signaling.
Maria R Stupnikov, Ying Yang ... Wellington V Cardoso
Notch ligands from the Delta and Jagged families have distinct roles in epithelial progenitor cell fate of extrapulmonary and intrapulmonary airways and differentially restrict expansion of the neuroendocrine microenvironment.
Brain imaging and behavioral analysis reveal two opposing states of hunger, represented by anti-correlated lateral and caudal hypothalamic dynamics that are important for the homeostatic control of feeding in zebrafish.
An ancestral apical brain center contributed to the evolution of the insect central complex requiring foxQ2, which is essential for the development of midline structures of the insect brain.
Yuansheng Cao, Elisabeth Ghabache, Wouter-Jan Rappel
Computational and experimental studies show that different migration modes of eukaryotic cells are the result of the interplay between signaling waves and cell mechanics.
Using different sets of input sequences to evolutionary reconstruction algorithms results in the exploration of many possible models, the intergration over which produces significantly more accurate models.
Virus infection in mosquitoes initiates a highly discriminatory process in which fragments of viral RNA are reverse transcribed to create DNA copies that serve as templates of small antiviral RNAs.
Youna Vandaele, Nagaraj R Mahajan ... Patricia H Janak
Dorsomedial and dorsolateral striatal neural activity differ during early learning of action sequences but do not change with performance improvement across sessions, and become similar after extended training.
Benjamin R Thomson, Isabel A Carota ... Susan E Quaggin
Genetic deletion of one Ptprb allele leads to increased phosphorylation of the TEK receptor, increasing Schlemm's canal area and protecting retinal ganglion cells in a mouse model of glaucoma.
Paola Bardetti, Sónia Marisa Castanheira ... José Pérez-Martín
Degradation of a mitotic inducer coordinates the transition of two successive cell cycle arrests during the infective process of a plant pathogenic fungus.
Shannon N Mostyn, Katie A Wilson ... Robert J Vandenberg
Identification of how bioactive lipids bind and inhibit glycine transporters has the potential to be exploited in the development of a new class of analgesics for chronic pain.
Grid cells lose their hexagonality during hippocampal inactivation, but maintain temporal and spatial synchrony between pairs of cells, implying that hippocampus does not determine phase relations between grid cells.
MmuPV1, a papillomavirus that infects laboratory mice (Mus musculus), is discovered to be sexually transmitted, providing a new animal virus model to study sexually transmitted human papillomaviruses (HPVs).
Jessica K Nadalin, Louis-Emmanuel Martinet ... Mark A Kramer
A new measure for cross-frequency coupling assesses phase-amplitude coupling and amplitude-amplitude coupling, and accounts for confounding factors such as low-frequency amplitude fluctuations, using a flexible statistical modeling approach.
A genetic screen in a unicellular photosynthetic organism uncovers the first essential signaling component in the chloroplast unfolded protein response that relays information from the chloroplast to the nuclear compartment.
Atiqur Rahman, Katherine M Henry ... Lynne R Prince
Targeting ErbB receptor tyrosine kinases modifies neutrophil survival and inflammation across multiple species, and reveals a new use for ErbB therapeutics in resolving inflammatory disease.
Evolutionary loss of foot muscle in a bipedal rodent shares similarities with skeletal muscle atrophy, which is typically considered a pathological response to injury or disease.
A spatial analysis of auditory and non-auditory properties of excitatory and inhibitory neurons in the mouse dorsal inferior colliculus defines the border between the lateral and the dorsal cortex.
A new intricate reciprocity between microbiology and physics results in collective protection from desiccation through differential formation of stable microdroplets around bacterial aggregates on surfaces drying under moderate humidity.
Sarah L Griner, Paul Seidler ... David S Eisenberg
Aβ inhibitors effectively block its aggregation, while also reducing seeding of tau aggregation from Aβ, tau, and AD derived fibrils, suggesting the two share a structurally related disease relevant interface.
An insulin-Myc feed-forward loop triggered by transient JNK boosts transcription of genes essential for mitochondrial respiration and biogenesis during early oogenesis to support massive mtDNA replication and inheritance in Drosophila.
Cassandra L Stowe, Thomas A Burley ... Martin A Pule
Two cellular populations can be tracked in the same small animal model using near-infrared bioluminescence imaging, for the first time opening up the window for multi-coloured bioluminescence.
Probability of upcoming actions modulates subclasses of neurons in frontoparietal motor-planning areas in a complementary fashion and frontal-lobe processing takes the leading role when primates commit to a decision.
The fruit fly estimates visual motion by incorporating ON-OFF asymmetric processing that only improves performance when stimuli have light-dark asymmetries matched to natural scenes.
Metabolic defects following expression of Aβ1-42 in nematode neurons are partially caused by inactivation of alpha-ketoglutarate dehydrogenase and can be rescued by Metformin.
Rebecca Delventhal, Reed M O'Connor ... Mimi Shirasu-Hiza
Through novel, cell-specific CRISPR tools to disrupt molecular clock genes, it was revealed that circadian rhythms are coordinated through a network, rather than by the clock of 'master regulatory' neurons.
Matthias Schlichting, Madelen M Díaz ... Michael Rosbash
Network silencing experiments and cell-specific CRISPR/Cas9 knockouts suggest that network communication is necessary for generating robust rhythms within the clock neuron network.
Studying the impact of natural variation on a key immune gene highlights how focusing on a single wild-type sequence overlooks that rare variants cause the most disease.
FRET biosensor-based measurement of cAMP signaling and single-channel recording reveal that β-blockers trigger local activation of adrenergic receptors and calcium channels in primary neurons.
Gabriela Krejčová, Adéla Danielová ... Adam Bajgar
Activated Drosophila macrophages undergo transient metabolic remodeling towards Hypoxia inducible factor 1 α-driven aerobic glycolysis, a program that induces systemic metabolic changes and is crucial for resistance to infection.
Zoé Christenson Wick, Madison R Tetzlaff, Esther Krook-Magnuson
An intersectional genetic vector approach allows the identification and characterization of novel hippocampal inhibitory neurons with both broad local connectivity within CA1 and long-range projections to several extrahippocampal areas.
José Muñoz-Dorado, Aurelio Moraleda-Muñoz ... Juana Pérez
Investigation of global gene expression profiles during formation of the Myxococcus xanthus specialized biofilm reveals a genetic regulatory network that coordinates cell motility, differentiation, and secondary metabolite production.
Koshika Yadava, Carlos Obed Medina ... Paul L Bollyky
Natural Tr1-like cells do not form a functionally stable memory response to allergens, and this instability may limit efforts to re-establish tolerance by expanding Tr1.
Genetic and cell biological analyses reveal a new role of Drp1 in postsynaptic endocytosis during brain development beyond mitochondrial division GTPase.
Nick Owens, Thaleia Papadopoulou ... Pablo Navarro
In contrast to other transcription factors, CTCF and Esrrb rapidly regain binding after replication and remain bound to their targets during mitosis, preserving local nucleosome organization throughout the cell cycle.
Motor and non-motor functions are represented in spatially segregated and temporally organized climbing fiber signals to distinct cerebellar zones during goal-directed behavior.
In the microbe Chlamydomonas reinhardtii, a disassembly rate which depends on flagellar length provides an effective method to regulate the length of its two flagella.
Kathryn S Carpentier, Bennett J Davenport ... Thomas E Morrison
The scavenger receptor MARCO and liver phagocytes are required for clearance of circulating alphavirus particles and thereby limit viremia and viral dissemination.
In scene-selective occipital cortex and within 200 ms of processing, visual inputs are sorted according to their typical spatial position within a scene.
Neurons in motor cortex contain information about each arm, but these signals are separated into different dimensions, allowing separate control of each arm.
Yoki Nakamura, Dilyan I Dryanovski ... Carl R Lupica
Non-synaptic extracellular vesicles may be involved in the release of endogenous cannabinoids in the central nervous system thereby representing a novel mechanism to mediate their effects on synaptic transmission.
Direct cortical recordings in humans link the spectral structure of local field potentials to inhibition/disinhibition mechanisms coordinating sensorimotor neuronal populations during movement imagery.
Functional definition of NrtR and the discovery of its acetylation represents a first paradigm for linking protein acetylation to bacterial central NAD+ metabolism.
Ayhan Atmanli, Dongjian Hu ... Ibrahim John Domian
A novel live-cell mRNA imaging technology identifies individual living cells based on their gene expression and enables the concurrent study of their physiology.
Matthew D Hall, Matthew TG Holden ... Christophe Fraser
Reconstruction of transmission pathways of methicillin-resistant Staphylococcus aureus using multiple genomes per host reveals great variation in the size of the transmission bottleneck and limited evidence for body site/phylogeny association.
Drug resistance in HIV is the result of mutations, which affect fitness depending on epistatic interactions with the entire sequence background that varies within and between patient populations.
Zebrafish use their sense of gravity and their cerebellum to coordinate the fin and body movements that, as they develop, allow them to better maintain balance as they climb.
Inhibitory interneuron activity is dynamically modulated in new environments while individual interneurons show consistent levels of activity modulation across multiple environments, suggesting functional specialization of inhibitory subnetworks.
Peripheral injury induces a programmed but reversible transformation of gene expression in somatosensory neurons providing a mechanism to regulate sensory input during wound healing.
Michael J Skelly, James J Furniss ... Steven H Spoel
Expression of plant immune genes is controlled by the opposing actions of ubiquitin ligases and deubiquitinases that modify the master coactivator NPR1, thereby regulating its intrinsic transcriptional activity.
Seksiri Arttamangkul, Andrew Plazek ... John T Williams
Opioid sensitive neurons were identified using a traceless affinity labeling strategy to covalently label endogenous mu-opioid receptors with fluorescent compounds in living brain slices from wild type animals.
DeepFly3D, a deep learning-based software, measures limb and appendage movements in tethered, behaving Drosophila and enables precise behavioral measurements during neural recordings, stimulation, and other biological experiments.
Andrea Cuentas-Condori, Ben Mulcahy ... David M Miller III
Caenorhabditis elegans has bona fide dendritic spines, suggesting that the advantages of small model organisms, such as genetic manipulations and live-cell imaging, can be exploited to study dendritic spines.
Xiaocheng Zhao, Pavel Nedvetsky ... Holger Gerhardt
The cAMP-dependent protein kinase A controls the switch from actively sprouting new blood vessel formation to vessel quiescence by reducing endothelial autophagy through phosphorylation-mediated destabilisation of ATG16L1.
Cryo-EM structures of unliganded SLC1A5 and its complex with glutamine in outward-facing state provide insights into the substrate specificity and transport mechanism and will be helpful for developing selective inhibitors.
Leslie A McCauliff, Annette Langan ... Judith Storch
Sterol kinetics and cell-based assays reveal a heretofore unknown step in cholesterol trafficking through the endolysosomal compartment, involving a direct functional interaction between NPC2 and lysosbisphosphatidic acid.
Tracheal-derived matrix metalloproteinase 1 activity sustains tracheal branch invasion into myotubes by modulating ECM properties and dynamic behavior of sprouting tip cells.
Alex Hunt, Matthew Robert Geoffrey Russell ... Moritz Treeck
Partially overlapping functions of a limited subset of actin binding proteins allow the parasite Toxoplasma gondii to achieve actin regulation required for complex cellular processes.
Jakub Witold Bubnicki, Marcin Churski ... Dries PJ Kuijper
The spatial interactions between humans, large carnivores and herbivores cascade down in a complex but predictable way to lower trophic levels affecting regeneration of tree species in a temperate forest.
People compete by trying to outsmart their opponents as long as they win, but show random behavior, and neural signs of suppressing knowledge about opponents’ strategies, when they lose.
FGFRs regulate multipolar cortical neuron orientation and the morphological change into bipolar cells in vivo under the control of N-Cadherin and the extracellular matrix protein Reelin.
Míriam Javier-Torrent, Sergi Marco ... Carlos A Saura
EphA signaling plays dual opposite roles on axon dynamics in neurons, so it inhibits and promotes axon growth through ligand binding and receptor processing, respectively.
A new deep-learning software toolkit with general-purpose methods for quickly and reliably measuring the full body posture of animals directly from images or videos without physical markers.
Oocyte maturation and ovulation in the sister group of vertebrates, Ciona intestinalis Type A, are triggered by Ci-VP, the Ciona homolog of a typical neruopeptide, vasopressin.
Impairment of the autocrine S1PR1-Gi signaling on HEVs results in high-endothelial cell apoptosis, reduced CCL21-secretion from HEVs, and cessation of HEV-DC interactions and lymphocyte immigration across the high-endothelial barrier.
Andrey Poleshko, Cheryl L Smith ... Jonathan A Epstein
The histone modification H3K9me2 marks peripheral heterochromatin and ensures positional information is safeguarded through cell division such that individual lamina-associated domains are re-established at the nuclear periphery in daughter nuclei.
When an essential metabolic gene in E. coli is mutationally inactivated, subsequent evolution rarely reverts the mutation to wild type but rather follows unexpected paths that rewire metabolic fluxes.
Axelle Calcus, Outi Tuomainen ... Lorna F Halliday
Mild-to-moderate sensorineural hearing loss causes changes in the neurophysiological functioning that emerge during adolescence, as suggested by both cross-sectional and longitudinal designs.
Ramakrishnan Vasudeva, Andreas Sutter ... Matthew JG Gage
Sperm and egg development are temperature sensitive, enabling males and females to significantly improve their reproductive success by matching gamete function to varying thermal environments for fertilisation and offspring development.
Environmental transmission is atypical of symbionts that have undergone genome degradation, yet genetically reduced deep-sea anglerfish symbionts likely persist in the deep sea biome in search of a new host.
Carolina Chavez, Grisel Cruz-Becerra ... James T Kadonaga
Dsup, a unique protein found only in tardigrades, is a nucleosome-binding protein that protects DNA from damage by hydroxyl radicals, such as those generated by ionizing radiation or oxidants.
Kishore R Mosaliganti, Ian A Swinburne ... Sean G Megason
Size regulation of the otic vesicle, the progenitor of the inner ear, is mediated by mechanical feedback involving fluid influx, hydraulic pressure, and tissue mechanics.
Amanda F Clouser, Hannah ER Baughman ... Rachel E Klevit
Multiple iso-energetic-specific interactions involving the intrinsically-disordered region of sHSP HSPB1 define a quasi-ordered state, providing insights into inherited disease-associated mutations within the region that are thought to be disordered.
Heme accumulation is toxic, but deficiency of the heme transporter HRG1/SLC48A1 causes heme sequestration and crystallization into hemozoin within enlarged lysosomes of macrophages, thereby conferring heme tolerance to mammals.
