Sonal Nagarkar-Jaiswal, Sathiya N Manivannan ... Hugo J Bellen
A conditional gene inactivation system that permits the tracking of protein expression, and creates fluorescently-labelled mutant cells in both developing and adult Drosophila tissues.
Jenna L Wingfield, Ilaria Mengoni ... Karl Lechtreck
Multimegadalton intraflagellar transport (IFT) trains assemble by sequential recruitment of IFT subcomplexes from the cell body to the ciliary basal bodies and tubulin, the main IFT cargo, is loaded briefly before trains depart.
Neurons in the lateral habenula are activated by pain, bitterness and social defeat, and their responses are dynamically shaped by learning, suggesting a role in experience-dependent selection of behavioral actions to stressors.
Single-particle cryo-EM and electrophysiology studies of the chloride channel TMEM16A reveals the structural basis for anion conduction and uncover its relationship to lipid scramblases of the same family.
A geneome-scale shRNA screen identifies five genes whose suppression promotes cell death upon PI3K inhibition both in vitro and in vivo, thus suggesting potential combination therapies involving PI3K inhibition.
In response to tissue damage, reactive oxygen species can be sensed by cation channels TRPA1/RyR to cause increases of cytosolic Ca2+ in intestinal stem cells, activating Ras/MAPK activity and stimulating stem cell proliferation in Drosophila.
The structure of the VemP-stalled ribosome reveals a helix-double turn-helix conformation of the nascent chain within the ribosomal tunnel, illustrating how secondary structure formation directly at the peptidyltransferase center of the ribosome can induce translational arrest.
Masatoshi Hara, Boryana Petrova, Terry L Orr-Weaver
The kinase that controls maternal mRNA translation is regulated by phosphorylation of its activating subunit to restrict kinase activity to the developmental window between meiosis completion and early embryogenesis.
Nicholas L Balderston, Elizabeth Hale ... Christian Grillon
Multimodal neuroimaging was used to study the effect of threat on spontaneous brain activity and functional connectivity, and demonstrated that threat increases both activity and connectivity of the intraparietal sulcus, a key node in the frontoparietal attention network.
Sarah Elizabeth Albritton, Anna-Lena Kranz ... Sevinc Ercan
Gene regulatory elements can target a chromatin regulatory complex to a single chromosome in the genome through hierarchical specification and long distance cooperation.
Mohammed Mostafizur Rahman, Sonal Kedia ... Sumantra Chattarji
Activation of the same glutamate receptor in the lateral amygdala gives rise to distinct effects on specific versus indiscriminate fear by modulating intrinsic excitability and synaptic plasticity.
EPO/JAK2/PKA signaling cascade via AKAP10 relocalization to the outer mitochondrial membrane results in the phosphorylation of the terminal heme synthesis enzyme ferrochelatase, which contributes to heme production in red cells.
A new paradigm of DNA methylation mediated gene activation and chromatin remodeling provides a general framework to dissect the biological functions of DNA methylation readers and effectors.
Intrinsic tolerance of Mycobacterium tuberculosis toward the world's most successful antibacterials, β-lactams, is dependent on cytoplasmic redox potential and an intracellular redox-sensor WhiB4.
Halving dosage of the Smith-Magenis syndrome responsible gene Rai1 in the mouse greatly amplifies the direct, suppressing effects of light on active-wake behavior through increased activation of the ventral-subparaventricular zone.
Eukaryotic chemotaxis to live bacteria was quantified at a high throughput level, for the first time, and mechanistically examined for the interrelationship between chemotaxis and phagocytosis.
Discrete classes of cerebellar Purkinje neurons show distinct changes in synaptic and spiking activity during motor learning, with simple spikes playing a shifting role during acquisition, expression, and maintenance of learned responses.
In budding yeast cells, slow monomeric septin GTPase activity and the cytosolic GTP:GDP ratio dictate the relative incorporation of alternative subunits during septin hetero-oligomer assembly, which proceeds by discrete, ordered steps dependent on allostery between interaction interfaces.
Hannah Steinert, Florian Sochor ... Harald Schwalbe
The discontinuous speed of transcription enables riboswitch molecules to adopt meta-stable structures in response to the presence of their cognate ligand, thereby gene-regulation by means of structure induced transcription termination can occur.
Eunice HoYee Chan, Pruthvi Chavadimane Shivakumar ... Pierre-François Lenne
N-cadherin at heterotypic contacts controls the level and asymmetric localisation of Myosin-II motor, thereby influencing cell shapes and cell packing.
Sofia Battaglia, Michael Lidschreiber ... Patrick Cramer
In vivo and in vitro elongation factor-RNA interaction data provide a missing link in understanding how processive elongation complexes are formed on active genes and disassembled at the end of genes.
Quantitative 4D image analysis identifies a group of cells which enter into the otic primordium during morphogenesis and instructs neuronal specification.
Matthew A Churgin, Sang-Kyu Jung ... Christopher Fang-Yen
The WorMotel, a novel microfabricated device for automated longitudinal imaging of aging in large numbers of Caenorhabditis elegans, reveals that long and short lived strains vary in their behavioral decline during aging in a similar way to the long and short lived individuals in a wild type population.
Oct1 replaces Oct4 at critical targets shortly after ESC differentiation to promote expression of lineage-specific genes and repress lineage-inappropriate genes.
The beneficial contribution of a language network for a specific function depends on the level of functional disruption and may reflect the differential compensatory potential of distinct language networks.
A novel mechanism for gating nociceptive sensory-motor behavior is identified in freely behaving rats using high-speed videography that is controlled by posture and modulated by opioid and non-opioid receptor-dependent processes.
Yuki Tanimoto, Akiko Yamazoe-Umemoto ... Koutarou D Kimura
A series of quantitative behavioural and opto-physiological analyses using a novel robot microscope system reveals that C. elegans computes the time-differential and time-integral of sensory information for decision-making during olfactory navigation.
The Srs2 helicase functions in Synthesis-Dependent Strand Annealing to avoid crossover formation during homologous recombination by disrupting D-loops that are extended by DNA polymerase delta in an ATP-dependent and direction-specific manner.
Timothy Erickson, Clive P Morgan ... Teresa Nicolson
A zebrafish model for a particular form of human deafness (DFNB63) changes our view of this disease by revealing a defect in the localization of Transmembrane channel-like proteins that are essential for mechanotransduction in sensory cells.
Viktoria Klippenstein, Christian Hoppmann ... Pierre Paoletti
Introduction of single photoswitchable unnatural amino acid into a neuronal receptor provides reversible, rapid and robust control of its activity by light, representing an important contribution to the fast expanding field of optopharmacology.
AGRP neurons integrate environmental food-related cues with internal metabolic signals to modulate interscapular brown adipose tissue thermogenesis and energy expenditure, at least in part, via mTORC1 signalling.
William F Tobin, Rachel I Wilson, Wei-Chung Allen Lee
Systematic and coordinated variations in morphology and connectivity can structurally tune a microcircuit's computation but non-systematic variably also exists, imparting "connection noise" that potentially limits processing performance.
Daniel Turner-Evans, Stephanie Wegener ... Vivek Jayaraman
A distinctive recurrent network motif in the Drosophila central brain enables neurons that encode angular velocity to shift population activity in compass neurons, thereby updating their heading representation whenever the fly turns.
Adam C Miller, Alex C Whitebirch ... Cecilia B Moens
Electrical synapses are neuronal, gap-junction-based connections found throughout the nervous system that, in the escape circuit of zebrafish, are composed of molecularly distinct pre- and postsynaptic junction forming proteins that are required for behavioral performance.
Niels Bradshaw, Vladimir M Levdikov ... Richard Losick
Structures of active and inactive conformations of a PP2C family phosphatase reveal a conserved switch that controls enzymatic activity and point to an unexpected relationship between phosphatases and proteasomal proteases.
A novel auto-inhibitory mechanism regulates the functional activity of the cellular prion protein, PrPC, providing for the first time a coherent molecular model for both its pathological and physiological effects.
The structure of a human antibody in which the variable loops position a human protein LAIR1 for antigen recognition, reveals a novel and indirect mode of antibody function.
SNARE proteins are delivered as complexes already from the endoplasmic reticulum along the secretory pathway to the cell division plane to mediate the formation of the partitioning membrane by vesicle fusion.
Daniëlle Rianne José Verboogen, Natalia González Mancha ... Geert van den Bogaart
A novel microscopy-based assay shows that dendritic cells encountering pathogenic stimuli form increased complexes of specific SNARE proteins, driving release of large amounts of inflammatory cytokines.
Chronic pain distorts intensity coding in the anterior cingulate cortex to give rise to generalized anatomically nonspecific enhancement in pain aversion.
A damaging form of positive feedback linking elevated calcium levels and metabotropic glutamate receptor function in Purkinje neurons plays a critical role in the pathology in spinocerebellar ataxias.
Marco Lepore, Artem Kalinichenko ... Gennaro De Libero
MR1T cells are human polyclonal T cells endowed with diverse effector functions in response to endogenous antigens presented by MHC-class 1-related molecule, MR1.
Dhivya Kumar, Daniela Strenkert ... Betty A Eipper
Analysis of Chlamydomonas, planaria and mice reveals a novel and unanticipated role for a peptide amidating enzyme in primary and motile ciliary assembly through effects on post-Golgi trafficking.
Bioinformatics and experimental approaches identify families of membrane proteins requiring the co-ordinated action of the Sec pathway and Tat pathways for their integration and define features of the polypeptides that mediate interaction with these pathways.
A versatile invertible gene trap vector is generated and inserted into a defined genomic locus in zebrafish via homologous recombination, demonstrating an efficient genetic approach to performing conditional knockout analysis.
Alejandro A Granados, Matthew M Crane ... Peter S Swain
Single-cell experiments and mathematical modelling show that cellular signalling networks are vulnerable to trade-offs in speed versus accuracy, but that these vulnerabilities can be overcome by distributing the two tasks to different, although interacting, subnetworks.
Daniel R Machado, Dinis JS Afonso ... Kyunghee Koh
The balance between sleep and sex drives determines whether male flies sleep or court, and a subset of octopaminergic neurons interact with the Fruitless-expressing courtship circuit to suppress sleep for sustained courtship.
Human sensory neurons may not only bridge a critical gap between drug discovery and clinical trials, but force a re-evaluation of basic assumptions about the mechanisms controlling primary afferent excitability.
Two major subtypes of cortical interneurons, the PV and the SST positive cells, causally contribute to the regulation of large-scale state transitions in the cortex.
Host CD81 and Scavenger Receptor BI operate independently to mediate invasion of hepatocytes by different species of Plasmodium sporozoites, which use the parasite protein P36 as a key determinant of the entry route.
Connectomic reconstruction combined with activity imaging uncovered a rhythmically active neuronal circuit for the coordination of ciliary activity across the whole body of a marine larva.
Building on previous work (Plumb et al., 2015), it is shown that the Sec61 translocon controls the oligomerization, activation and inactivation of Ire1α during endoplasmic reticulum stress.
Jennifer C Swart, Monja I Froböse ... Hanneke EM den Ouden
Motivational coupling of action to reward and inhibition to punishment is subserved by dissociable learning and choice processes, and is modulated by dopamine/noradrenaline transporter blockade.
A novel algorithm is used to solve the first 3D reconstruction of a stepping kinesin dimer on microtubules, directly visualizing the conformational effects of inter-head strain and giving novel insights into the motility mechanism.
Marina Diskowski, Ahmad Reza Mehdipour ... Inga Hänelt
The K(+) uptake system KtrAB is controlled by an allosteric mechanism entirely new for membrane channels, which operates the channel gate over a 35 Å distance.
Nadinath B Nillegoda, Antonia Stank ... Bernd Bukau
The emergence of complementary electrostatic potentials after the prokaryotic-to-eukaryotic split drives physical and functional cooperation between canonical class A and class B J-proteins to boost protein disaggregation.
Association of curvature generating proteins to the Golgi membranes by sphingomyelin metabolism essentially controls the flatness of a Golgi cisterna that is necessary for efficient sorting and export.
In concert phosphorylation site modification of both XRCC4 and XLF C-terminal disordered tails promotes disassembly of XRCC4/XLF DNA tethers during c-NHEJ.
Ting-ting Zhang, David G Gonzalez ... Ann M Haberman
CD40 signaling is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.
Max van Lessen, Shannon Shibata-Germanos ... Stefan Schulte-Merker
The discovery of a unique brain lymphatic cell type in the zebrafish model will facilitate the study of embryonic development and physiology, an essential mission to understand how clearance of macromolecules impact neurological diseases.
Integration of complementary computational approaches reveals an evolutionarily conserved interaction interface between molecular chaperones Hsp70 and Hsp40, rationalizing previous observations.
An in silico reconstruction of a chloroplast that existed hundreds of millions of years ago casts new insights in the evolutionary processes, endosymbioses and chimerism events that shape the origin of plastids.
Non-specific sodium entry inhibits T cell receptor induced gene expression and differentiation of T cells by depleting intracellular ATP and disrupting mTORC2 dependent signalling axis.
Maintenance of ubiquitin homeostasis is essential for proper control of the size of postsynaptic density and the growth of specialized membrane structure.
The neurotransmitter noradrenaline selectively modulates metacognition, the conscious insight into one's performance, but does not alter perceptual decision making, revealing that different neuromodulators affect different stages of a decision making process.
Isaac Cervantes-Sandoval, Anna Phan ... Ronald L Davis
Structural and functional analysis of axonal-axonal reciprocal connections between dopamine neurons and Kenyon cells provides insight into the brain computations for normal associative olfactory learning.
The phosphate starvation response network in a commensal yeast evolved to expand its downstream targets via changes in the main transcription factor's dependence on its co-activator, potentially altering the physiological response.
Elin Näsström, Christopher M Parry ... Stephen Baker
Mass spectrometry on plasma from patients with typhoid fever and other febrile disease identified and validated 24 metabolites that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.
The discovery of new skeletal remains of Homo naledi in the Lesedi Chamber, South Africa, adds more evidence to our understanding of the morphology and behavior of this recently discovered species.
Independent dating techniques have established that the H. naledi fossils are between 236 and 335 thousand years old, indicating that small-brained hominins with relatively primitive body shapes co-existed with our early ancestors in Africa.
MCTP is a novel presynaptic calcium sensor, resident within the endoplasmic reticulum, that is required for normal baseline neurotransmission, short-term synaptic plasticity and presynaptic homeostatic plasticity.
A late Middle Pleistocene age for Homo naledi demonstrates a diversity of hominin species in Africa at this critical time in the archaeological record.
Molecular beacon based FISH shows the capability of visualizing a 2.5 kb non-repetitive genomic DNA sequence in situ in human or mouse nuclear genome at super resolution.
Agnès H Michel, Riko Hatakeyama ... Benoît Kornmann
A new method maps functional and structural features of yeast genomes with unprecedented ease and throughput, which allows identification of protein domains at the genome scale.
Inspired by the sparse, sequential neural activity patterns observed in striatum, a new circuit model implements variable-speed activity, the encoding of multiple sequences, and a tutor/student relationship between cortex and striatum.
Emilie-Fleur Neubauer, Angela Z Poole ... Virginia M Weis
The colonization of corals and their relatives by intracellular microalgae is facilitated by immunity proteins in the animal that contain thrombospondin-type-1 repeats, elucidating the inter-partner recognition processes required for the establishment of this ecologically important symbiosis.
CDPK4 is a pleiotropic regulator controlling initiation of DNA replication, mitotic spindle assembly and flagellar activation during the early stages of Plasmodium transmission.
Biophysical and functional data strongly support the notion that Munc18-1 acts as a template to assemble the neuronal SNARE complex, and that inhibition of this activity underlies diverse forms of regulation of neurotransmitter release.
Ewa Piskadlo, Alexandra Tavares, Raquel A Oliveira
Condensin I maintains chromosome organization throughout metaphase by preventing erroneous topoisomerase II-dependent sister chromatid re-entanglements.
Changes in Shank gene dosage alter voltage-activated calcium current and calcium-activated gene expression in a manner that parallels the effects of human Shank copy number variation on psychiatric disease risk.
Kerstin Seidel, Pauline Marangoni ... Ophir D Klein
Gene co-expression analysis identifies coherent transcriptional patterns driven by distinct cell types in the mouse incisor, and functional studies of candidate genes reveal how the tissues are maintained through stem cell-fueled renewal.
Thibaud Taillefumier, Anna Posfai ... Ned S Wingreen
In a consumer-resource model obeying the physical requirement of flux conservation, metabolic competition between microbes yields consortia of cell types that collectively resist invasion via optimal use of resources.
Sandra Kleinecke, Sarah Richert ... Celia Michèle Kassmann
Dysfunctions of myelin peroxisomes cause a lysosomal storage-like disorder associated with alterations in glial and axonal membranes, which is the likely cause of nerve impairment in peroxisomal disorders.
Overexpression of TCF7L1 overrides oncogenic Ras-induced senescence, induces cell migration, and promotes growth of skin squamous cell carcinoma independently of its interaction with β-catenin.
Jonci Nikolai Wolff, Neil J Gemmell ... Damian K Dowling
Mitochondrial genomes harbor male-fertility-reducing mutations that can be harnessed to control population viability as a novel approach to control economic and environmental pests.
Using a sequential neurofeedback-arm reaching task, a new link is established among population neural activity patterns, generation of beta oscillations, and motor behavior changes.
Cellular and genetic approaches reveal that exposure of a normally buried nuclear export signal (NES)-like sequence mediates export of ALS-linked mutant and misfolded wild-type SOD1 to the cytoplasm by CRM1.
A novel ALS-associated variant in UBQLN4 impairs proteasome function and beta-catenin degradation to drive aberrant axon morphogenesis in motor neurons.
The guide RNA and donor DNA of the CRISPR/Cas system tolerate large chemical modifications and can be engineered for enhanced delivery and gene editing.
In Drosophila, key neurons controlling sleep play an important role in adjusting the temperature set-point before dawn via time-dependent neuronal plasticity within the clock circuits.
Neural computations necessary for efficient control of saccades capture the phenomenon of saccadic suppression, which suggests that neural resources are shared for perception and control.
The endosymbiosis between an alga and the spotted salamander shows several parallels to invertebrate-algal symbioses as well as to pathogen associations in vertebrate animals.
Joscha Griger, Robin Schneider ... Carmen Birchmeier
The stem cells of the postnatal muscle allow postnatal muscle growth and repair and withdraw from the cell cycle when the tyrosine phosphatase Ptpn11 (Shp2) is inhibited or mutated in mice.
Patrick J O'Hern, Inês do Carmo G. Gonçalves ... Anne C Hart
In invertebrate and vertebrate models of Spinal Muscular Atrophy, diminished SMN protein causes Gemin3-dependent decreases in microRNA function, leading to upregulated M2 muscarinic receptor and deleterious consequences.
Inactivation of the master mitotic checkpoint regulator Mps1 by protein phosphatase 1 is required for timely segregation of the genetic material during cell division.
Sec14l3/SEC14L2 respond to upstream Wnt/Frizzled/Dvl stimulation to recruit and activate phospholipase Cδ4a (Plcδ4a) to further initiate calcium release.
Population mutation rates are highly flexible and evolvable under extreme stress conditions, matching changes in selective pressure to avoid extinction of the entire population.
Stefania Monterisi, Miguel J Lobo ... Manuela Zaccolo
The enzyme phosphodiesterase 2A2 localises at the mitochondrial membrane and its inhibition results in a local increase in cAMP concentration, mitochondrial elongation and resistance to apoptosis.
Sven Kenjiro Vogel, Ferdinand Greiss ... Petra Schwille
Building on previous work (Vogel et al., 2013b), it is shown that myosin-driven actin filament rearrangements actively move, split or fuse individual lipid domains and change their overall shape.
