Cryo-electron tomography, reconstitution, and electrophysiological data show that a fundamental function of Munc13-1 is to bridge synaptic vesicles to the presynaptic plasma membrane.
Kumi Harada, Tetsuya Kotani ... Hitoshi Nakatogawa
How the autophagy-related E3 complex localizes to pre-autophagosomal structures and a non-E3 function of the complex were revealed, significantly advancing our understanding of the nucleation step in autophagosome formation.
Single molecule DNA-binding trajectories and deterministic modeling analyses demonstrate a functional role for high energy partly folded states in Transcription Activator-Like Effectors that could improve future TALEN design.
The switch from mitotic cell cycles to the one meiotic cell cycle in each generation is triggered through dramatic upregulation of a broad gene expression program by transcriptional regulator STRA8.
Basalins are intrinsically disordered proteins with astonishingly high-sequence divergence that are essential for building the transition zone basal plate and for proper central pair nucleation.
Anna S Trigos, Richard B Pearson ... David L Goode
Cancer is a consequence of the release of basal cellular functions inherited from our unicellular ancestors from the control of regulatory networks that evolved during the emergence of multicellularity.
A combined systematic alanine scanning and molecular modelling approach reveals the molecular basis for an allosteric inhibition mechanism of K+-flux gating in K2P channels.
Mark Austin Hanson, Anna Dostálová ... Bruno Lemaitre
While antimicrobial cocktails are highly effective for defence against pathogenic microbes, the innate immune response may instead employ highly specific peptidic antibiotics to combat certain natural enemies.
Daniel Arthur Abrams, Aarthi Padmanabhan ... Vinod Menon
Children with autism often 'tune out' the voices in their environment and new results show that impaired processing of voices in the brain's reward system may underlie this social behavior.
A new computational framework provides a flexible and general approach for single and collective biological motion characterisation and phenotyping ideally suited for high-throughput timelapse screens.
Bigger bumblebee eyes have better vision, yet their field of view, sensitivity, and resolution do not all simply scale up with eye size, being improved locally instead.
The scaling of spindle elongation velocity with cell size is regulated by the amounts of Kinesin-6 molecules and the number of binding sites for the motor to the mitotic spindle.
RIM binding UNC-13L C2A domain releases UNC-13L from an autoinhibitory homodimeric complex to become fusion-competent, and regulates probability of synaptic vesicle release in the post-priming process.
Any effects of environmental 50/60 Hz magnetic fields on human biology due to a radical pair mechanism should be no more dangerous than those incurred by travelling a few kilometres.
Rajtarun Madangopal, Brendan J Tunstall ... Bruce T Hope
Stimuli signaling reward availability potentiate and control relapse for up to 300 days of abstinence following cocaine, but not food, self-administration in rats.
Newly forming descending pathways are arranged to function in parallel to existing ones and contribute to increasingly sophisticated locomotor behaviors that emerge postnatally with suitable connectivity patterns and biophysical properties.
Consolidation of long-term courtship memory in Drosophila is mediated by a novel class of sleep promoting neurons that reactivates dopaminergic neurons engaged earlier in memory acquisition during post-learning sleep.
Kerstin Klinkert, Nicolas Levernier ... Pierre Gönczy
Experiments reveal mechanisms through which Caenorhabditis elegans zygotes depleted of Aurora A or lacking centrosomes spontaneously establish two posterior PAR-2 domains, one at each pole, in a curvature-dependent manner.
Efraín E Rivera-Serrano, Olga González-López ... Stanley M Lemon
Quasi-enveloped hepatitis A virions undergo clathrin-mediated endocytosis, followed by ALIX-dependent trafficking to lysosomes where the quasi-envelope is degraded, triggering uncoating of the RNA genome in association with lysosomal membrane rupture.
Low-frequency correlations among neurons in monkey visual area V4 impair the animal's ability to perform an attention-demanding task, suggesting a causal role of these fluctuations in perception.
Bernadette C Young, Sarah G Earle ... Catrin E Moore
Genome-wide association studies have established staphylococcal pyomyositis as a disease whose pathogenesis depends critically on expression of a single toxin, Panton–Valentine leukocidin.
A novel framework for separating normal and pathological high-frequency oscillations in animals with epilepsy uncovers new mechanisms for impaired hippocampal network function.
David J Jörg, Elizabeth E Caygill ... Benjamin D Simons
A model of signalling pathways interacting with proneural gene expression explains the sequential patterning of the largest visual processing centre in the developing Drosophila brain.
Michael Puljung, Natascia Vedovato ... Frances Ashcroft
A combined FRET- and electrophysiology-based approach is used to study ATP/ADP ADP binding to the stimulatory nucleotide binding site of ATP-sensitive K+ channels and investigate their activation mechanism.
Sergio A Muñoz-Gómez, Sebastian Hess ... Andrew J Roger
Diverse sophisticated phylogenetic analyses update the phylogeny of the Alphaproteobacteria and show that the parasitic Holosporales is a derived group within the Rhodospirillales order which comprises primarily free-living alphaproteobacteria.
Nathan T Henderson, Sylvain J Le Marchand ... Matthew B Dalva
Competition between neurons for postsynaptic ephrin-B3 controls distribution of a limited pool of synapses and defines a novel trans-synaptic mechanism enabling neurons to set the number of synapses they receive.
Structural research, supplemented by biochemical experiments and enzymatic assays, unravels the sequence-dependent molecular mechanism by which SETD3 recognizes β-actin and methylates His73 of β-actin.
Youngah Jo, Jason S Hamilton ... Russell A DeBose-Boyd
UBIAD1 mediates a unique geranylgeranyl pyrophosphate-sensing mechanism that when disrupted, inhibits degradation of HMG CoA reductase and triggers overproduction of corneal cholesterol that characterizes the eye disease Schnyder Corneal Dystrophy.
Carolina Alvadia, Novandy K Lim ... Cristina Paulino
While activated by a common mechanism, both functions in TMEM16F - lipid scrambling and ion conduction - are likely mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.
cryo-EM reveals the properties of distinct conformations occupied during activation of the lipid scramblase nhTMEM16 and provides new insights into its interactions with the lipid environment.
M Görkem Patir-Nebioglu, Zaida Andrés ... Karin Schumacher
In vivo inhibition of SUMO activating E1-enzymes by pyrophosphate reveals a mode of integrating metabolism and stress tolerance that is conserved across kingdoms.
Isabel ML Saur, Saskia Bauer ... Paul Schulze-Lefert
Allelic MLA immune receptors have an exceptional propensity to directly detect sequence-unrelated pathogen effectors and this feature might have facilitated functional diversification of the receptor in the host population.
The basis for small-molecule block, insights into gating, and an unexpected architectural role for the lipid membrane are revealed in structures of the volume regulated anion channel LRRC8A.
Common nuclear genetic variants are associated with fundamental biological processes occurring in human mitochondria and potentially point to novel roles for nuclear genes in transcriptional regulation of the mitochondrial genome.
King Faisal Yambire, Lorena Fernandez-Mosquera ... Nuno Raimundo
Transcription factors KLF2 and ETV1 repress the transcriptional program of mitochondrial biogenesis, resulting in impaired mitochondrial function in lysosomal storage diseases.
Sven Schenk, Stephanie C Bannister ... Kristin Tessmar-Raible
A molecular profiling approach to quantify transcripts and proteins from identical samples allows study of molecular effects of maturation, sexual differentiation and the endogenous circalunar clock in a marine worm.
Reconstitution and cryo-EM reconstruction of the yeast Ctf19 complex (constitutive centromere associated network, or CCAN, in other organisms) shows how inner kinetochore proteins assemble.
L Bailey Lindenmaier, Nicolas Parmentier ... Kevin M Wright
Dystroglycan interacts with multiple partners, including the transmembrane receptor Celsr3, to regulate axon tract formation throughout the developing nervous system.
MT plus-end-mediated recruitment of a cortical pool of ECT2 trigger RhoA activation upon contact, which results in localized contractility during cytokinesis.
David AD Munro, Yishay Wineberg ... Jamie A Davies
Embryonic macrophages encourage early kidney development, interact with developing renal blood vessels, are enriched for mRNAs linked to vascular development, and promote endothelial cross-connections.
Consideration of signal detection theory shows how decision ecology relates to optimal collective decisions, helping explain the prevalence of quorum-sensing in even the simplest collective systems, such as bacterial communities.
Peter Ahorukomeye, Maria M Disotuar ... Helena Safavi-Hemami
The unique modus operandi of cone snail venom insulins provides new insight into insulin receptor activation and informs on the design of insulin analogs for the treatment of diabetes.
Thomas SB Schmidt, Matthew R Hayward ... Peer Bork
Microbial populations are continuous along the gastrointestinal tract, with increased transmission in colorectal cancer and rheumatoid arthritis patients.
Zhiling Li, Marlene M Hao ... Pieter Vanden Berghe
Calcium response profiling of large populations of enteric neurons reveals hard-wired neural circuits that reflect the motility program portfolio of the intestinal region they occupy.
A computational model of collective physical interaction reveals that individuals infer the collective's movement goal in order to enhance the group's overall performance and coordinate with several partners in seconds.
Nicolò Tosetti, Nicolas Dos Santos Pacheco ... Damien Jacot
Toxoplasma gondii formins have several non-overlapping roles including generating an apico-basal flux of F-actin that is controlled by phosphorylation and methylation and is essential for motility.
Wondwossen M Yeshaw, Marianne van der Zwaag ... Ody CM Sibon
VPS13A is associated with the endoplasmic reticulum, mitochondria and lipid droplets and is required for cellular processes that require interaction between these organells.
A detailed description of the structure of procentriole MT triplet by cryoET, along with its associated non-tubulin proteins and its assembly intermediates, reveals possible molecular mechanism for the procentriole assembly.
Inhibitory noninvasive stimulation to the precuneus disrupts theta and gamma oscillatory coupling between medial temporal lobes and neocortical regions during complex personal memory retrieval.
Madhav Jagannathan, Ryan Cummings, Yukiko M Yamashita
Cell biological study reveals the mechanism by which multiple satellite-DNA-binding proteins cooperate to form chromocenter to encapsulate the full complement of chromosomes.
Andrea Cosolo, Janhvi Jaiswal ... Anne-Kathrin Classen
Tissue damage induces a reversible cell cycle arrest in G2, which promotes survival and mitogenic signals to facilitate tissue regeneration but drives senescence-like phenotypes under chronic stress conditions.
Targeted recordings from subcortical projection neurons in the auditory cortex reveal two cell classes with distinct signatures of sensory processing and different patterns of local and long-range connectivity.
Evgeniya V Nazarova, Christine R Montague ... Brian C VanderVen
An unbiased forward genetic screen identified genes in Mycobacterium tuberculosis that are required for fatty acid import when the bacterium is residing within macrophages.
Autocrine activation of macrophages is modulated by Connexin-43-mediated ATP release in response to TLR-4 and -2 agonists in a P2Y1-dependent manner, ultimately determining sepsis survival.
Leave-One-Trial-Out (LOTO) is a general, efficient and easily implementable approach for inferring trial-by-trial measures of computational model parameters in order to link these measures to neural mechanisms.
Florian Kopp, Mahmoud M Elguindy ... Joshua T Mendell
Long noncoding RNA Norad performs an essential function in mammalian physiology by inhibiting the activity of PUMILIO RNA binding proteins, thereby suppressing a multi-system degenerative phenotype resembling premature aging.
Single-cell RNA sequencing resolves inter- and intra-population heterogeneity, identifies rare cell types, and reconstructs specification trajectories during early neurogenesis of the mouse cerebellum.
Valerie S Salazar, Luciane P Capelo ... Vicki Rosen
A periosteal Bmp2 signaling center couples bone length to bone width during development and must be reactivated by clinical bone anabolic therapies to reduce fracture risk and accelerate fracture repair.
Kathryn M Tabor, Gregory D Marquart ... Harold A Burgess
A new resource of transgenic zebrafish lines facilitates precise targeting of neuronal cell-types within the brain, supported by online software for visualizing transgene expression patterns.
Denise M Poltavski, Pauline Colombier ... Takako Makita
Second-order guidance, a novel mechanism by which an initial guidance cue controls expression of a second guidance receptor, is required for precise refinement of axon trajectories during PNS development.
The liver-specific miRNA microRNA-122 plays a previously unknown role in hepatocyte intrinsic innate immunity by targeting the RTKs/STAT3 signaling pathway.
Byounghoon Kim, Shobha Channabasappa Kenchappa ... Ari Rosenberg
The Real-Time Experimental Control with Graphical User Interface (REC-GUI) framework can facilitate cutting-edge neuroscience research by providing precise experimental control using high-level programming environments familiar to many experimentalists.
Maria C Marchetto, Branka Hrvoj-Mihic ... Fred H Gage
Using iPSCs as a model to study neurodevelopmental differences between human and nonhuman primates lays the groundwork for understanding aspects of human brain evolution and neurological disease susceptibility.
With the removal of confounding artifacts, ribosome profiling can yield insight into the mechanism of protein synthesis in bacteria at high resolution.
Niels A Kloosterman, Jan Willem de Gee ... Johannes Jacobus Fahrenfort
Decision-makers are able to intentionally control neural excitability to strategically bias sensory evidence accumulation towards the decision bound that maximizes reward within a given ecological context.
Sensory representation in the primary olfactory area is rapidly modulated when mice switch between easy and difficult discrimination tasks, optimising the sensory representation for the task at hand.
Construction of a first atomic model for an intact bacterial ATP synthase allows for a structural understanding of the roles of individual amino acids in the mechanism of ATP synthesis.
Single-molecule observations reveal a mechanism that may be used by multiple competing regulatory proteins to control ribosomal RNA production during rapid bacterial cell growth.
Photoswitchable ceramides containing an azobenzene photoswitch behave as light-controllable substrates for both sphingomyelin synthase and glucosylceramide synthase.
Wenjuan Zhang, Benjamin Falcon ... Sjors HW Scheres
Cryo-EM structures of heparin-induced tau filaments differ from those observed in neurodegenerative disease, illustrating their structural versatility, and prompting questions about the relevance of in vitro amyloid models.
Fabian E Ortega, Elena F Koslover, Julie A Theriot
The pathogenic bacterium Listeria monocytogenes spreads infection using a two-tiered strategy, where most bacteria spread locally but a few 'pioneers' move further, increasing the likelihood of a persistent infection.
A systematic high-throughput neurohistological and computational pipeline for marmoset which establishes a foundational setup in brain mapping and circuit tracing to support current and emerging research in primate studies.
Emily L Mackevicius, Andrew H Bahle ... Michale S Fee
Building on simple unsupervised matrix factorization techniques, the seqNMF algorithm successfully recovers neural sequences in a wide range of simulated and real datasets.
Evgeniya Lukinova, Yuyue Wang ... Jeffrey C Erlich
People have stable time-preferences regardless of whether they are measured using a non-verbal experiential task, as is typical in animal experiments, or using a more traditional verbal task.
Genetic change among enzyme orthologous with similar phenotypic properties can cause substantial differences in evolutionary response to a new enzyme function in terms of their molecular and fitness outcomes.
The MondoA transcription factor localizes to the outer mitochondrial membrane where it coordinates an adaptive transcriptional response to elevated cellular energy represented by high cytoplasmic glucose and high mitochondrial ATP.
Harshad Ghodke, Bishnu P Paudel ... Antoine M van Oijen
Phase separated DNA-free stored forms of RecA dissolve in response to DNA damage to make RecA available for repair and recombination reactions as part of the bacterial (Escherichia coli) SOS response.
Daan B Wesselink, Fiona MZ van den Heiligenberg ... Tamar R Makin
fMRI results show that despite arm amputation, and varying degrees of phantom sensations, canonical hand representation in primary somatosensory cortex is largely maintained.
By inhibiting the activation of NF-κB, HIV-1 Vpu exerts much broader immunosuppressive effects than previously anticipated and may be an important determinant of chronic inflammation in HIV-1 infected individuals.
Atypical intrinsic neural timescales in the sensory cortex and caudate were associated with local grey matter volume, and linked with the severity of autism.
Functional imaging and circuit mapping in the Drosophila brain identifies neuropils where sleep-promoting and arousal-promoting neuronal networks converge.
Nicholas R Ader, Patrick C Hoffmann ... Wanda Kukulski
Correlative microscopy and electron cryo-tomography on apoptotic HeLa cells reveal remodeling of outer and inner mitochondrial membranes, Bax cluster ultrastructure and ATP synthase reorganization in ruptured mitochondria.
Laura Hanson, Santhosh Sethuramanujam ... Gautam B Awatramani
Experimental and computational models reveal how parallel 'core' mechanisms shape direction selectivity at the dendrites of starburst amacrine cells and ganglion cells in the mouse retina.
James Ashley, Violet Sorrentino ... Robert A Carrillo
Synaptic partner recognition in the Drosophila neuromuscular circuit requires interactions between the Dpr and DIP subfamilies of immunoglobulin cell-surface proteins.
Arjun Narayanan, Anatoli Meriin ... Ibrahim I Cisse
Quantitative single molecule and super resolution imaging in mammalian cells reveal a population of precursor aggregates describable by first order phase transition theory.
Lalanti Venkatasubramanian, Zhenhao Guo ... Richard S Mann
Ig domain family members DIP-alpha and Dpr10 are required in a subset of Drosophila leg motor neurons and muscles, respectively, to establish their fine terminal branching pattern and synapses.
Aaron T Bozzi, Christina M Zimanyi ... Rachelle Gaudet
Nramp-family transporters adapt a common fold to a novel mechanism in which the spatial and temporal separation of like-charge transition metal and proton co-substrates circumvents the expected electrostatic repulsion.
Phototrophic growth laws are elucidated by combining computational modeling and experiments for quantitative evaluation of cellular physiology, morphology and proteome allocation across a wide range of light conditions.
Colored surfaces induce strong gamma-synchronization yet sparse firing in V1 when receptive field inputs are predicted from the surrounding spatial context.
A fatty acyl reductase gene family expansion in the Hymenoptera crown group led to recruitment of novel pheromone-biosynthetic enzymes and is linked to evolution of pheromone marking behavior.
The Eyeless/Pax6 temporal transcription factor generates neuronal identity, connectivity, and flight navigation behavior within the conserved adult brain structure called the central complex.
Paul M Berube, Anna Rasmussen ... Sallie W Chisholm
In the context of an organism's ecology, physiology, and macroevolutionary history, inheritance and gene loss can yield emergent patterns of trait variability that give the appearance of gene acquisition.
