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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.