When the neuropeptide orexin is peripherally administered in mice with septic shock, it penetrates the blood-brain barrier and acts in the brain to improve survival through multiple autonomic and neuroendocrine pathways.
Cooperation theory and a novel synthetic infection system provides a mechanistic understanding of why a seemingly successful disease management strategy can have devastating consequences for infected hosts.
The centromeric protein CENP-T assembles the microtubule-binding interface of kinetochores through direct recruitment of two Ndc80 complexes and indirect recruitment of a third one through the Mis12 complex.
Biochemical and cell-based analyses reveal how a non-enveloped virus exploits the chaperone activity of an ER transmembrane protein to penetrate the ER membrane required for successful virus infection.
Spontaneous theta oscillations and interneuron-specific phase preferences emerge spontaneously in a full-scale model of the isolated hippocampal CA1 subfield, corroborating and extending recent experimental findings.
Specialized fungal pathogen populations infect rice varieties with contrasting immune systems co-cultivated in a traditional agro-system, indicating the relevance of crop diversity to restricting epidemics in the landscape.
Hydrogen-Deuterium exchange experiments show that Ric-8A induces similar dynamic changes in the structure of Gα as G protein-coupled receptors, yet protects a larger surface of the nucleotide-binding Ras domain.
DNA-bound crystal structures of an essential Xer site-specific recombinase from the bacterium Helicobacter pylori reveal how large conformational changes initiate the untangling of chromosomes upon cell division.
Behavioral pharmacology and molecular biology reveal a translational control mechanism underlying auditory imprinting and structural plasticity that can be pharmacologically manipulated to reopen the critical period.
The hepatitis C virus IRES binds and remodels preassembled eukaryotic translation preinitiation complexes, using specific initiation factor protein within a "bacterial-like" mode of initiation that can function in both stressed and unstressed cells.
Common ancestries, activities and structural determinants of a modular (bi-)polarization control system encoded in free-living and obligate intracellular α-proteobacteria, including the rickettsial pathogens, are described.
Forward genetics and super-resolution microscopy identifies ZitP as a conserved multifunctional regulator that accumulates at both cell extremities in distinct macromolecular structures to perform different functions in the asymmetric model bacterium Caulobacter crescentus.
Analyses with genetically engineered mouse models in combination with biochemical approaches reveal a crucial role of the receptor tyrosine kinase Tie2 mediated signals in venogenesis via an Akt mediated regulation of COUP-TFII protein stabilization.
Building on previous work (Chatterjee et al., 2014), the mechanism of coincidence detection in bacterial second messenger signaling across membranes is revealed at a molecular level, providing insight into the regulation of a conserved transmembrane receptor.
Repression of the G protein-coupled chemokine receptor CCR5 enhances MAPK/CREB signaling, long-term potentiation, somatosensory cortical plasticity, and learning and memory, while CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits.
In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.
Building on previous work (Fu et al., 2016), we demonstrate the critical role of Sam68 in orchestrating genotoxic stress-initiated NF-κB signaling in the colon and the pathophysiological relevance of Sam68-dependent NF-κB activation in colonic cell survival/recovery from extrinsic DNA damage.
Mitophagy regulates mitochondrial quality and mediates extensive mitochondrial degradation in (patho-)physiological settings and is one of the key components of hypoxic preconditioning which protects the heart from ischemia/reperfusion injury.
De novo transcriptome assembly and comprehensive characterization of gene expression in proliferating cells of regeneration-capable flatworm Macrostomum lignano advance this organism as a powerful model for stem cell research.
IRBIT and the Bcl-2 homolog Bcl2l10 form a complex at the endoplasmic reticulum that controls Ca2+ signaling, however IRBIT turns into an apoptosis facilitator following stress and inhibits anti-apoptotic activity of Bcl2l10.
Structural, biophysical, and functional analyses reveal that mutations in TREM2 trigger either misfolding or reduced binding to cell-surface glycosaminoglycans, which segregate with neurodegenerative disease link and highlight a functional surface linked to the pathogenesis of Alzheimer's disease.
Mice deficient in the TRPM6 channel suffer from impaired prenatal development, shortened lifespan, growth deficit and disturbed energy balance due to a defect in epithelial Mg2+ uptake, thus highlighting a pivotal role of TRPM6 in organismal Mg2+ homeostasis.
Three-dimensional electron microscopy (3DEM) demonstrates the dependence on presynaptic mitochondria for vesicle mobilization as dendritic spines are silently added at P15 or synapses are silently enlarged in adults after long-term potentiation.
A catalytically dead paralog activates its cognate enzyme through an allosteric mechanism that combined structural and phylogenomic analysis indicates arose through acquisition of a dimerization domain, suggesting a general model for how complex allostery evolves.
Natural variation for an adaptively important life history trait is largely due to variation at a single, major-effect locus with multiple alleles, demonstrating that not all complex traits are massively polygenic.
Building on previous work (Huang et al., 2016), we show that translational control by p-eIF2α is a defense mechanism that prevents persistent cocaine-induced synaptic synaptic potentiation underlying compulsive drug seeking.
A C-type lectin domain protein is an anabolic growth factor that promotes mesenchymal progenitors in the bone marrow to differentiate into bone cells to maintain skeletal bone mass throughout adult life.
The molecular mechanism of switching between phosphotransferase- and phosphatase-competent states in histidine-kinases has been uncovered, through direct crystallographic observation of bona fide complexes between a histidine-kinase and its response regulator from Bacillus subtilise.
Akt mediated S14 phosphorylation of Id2 augments its protein stability and growth cone localization, promoting growth cone formation and axon growth in the developing neuron and contributing to axon regeneration in the damaged hippocampus slice.
Feedback mechanisms that contribute to the deactivation of the unfolded protein response lead to the dysregulation of mRNA expression during chronic stress in the liver, including that of the critical endoplasmic reticulum chaperone BiP.
Weak yet highly species-specific protein-protein interactions enhance the activity of metabolically related enzymes in bacteria at endogenous conditions, but also mean that overexpression of one partner leads to permanent non-physiological complexes and gene dosage toxicity.
Activity-regulated genes in Drosophila neurons differ from the well-characterized situation in mammals, and these genes provided a strategy to construct reporters for monitoring neuronal activity in fly brains.
A toxin is used to introduce an otherwise cell-impermeant fluorophore-antibody (or some thing which is equally specific) to bind to an intracellular protein which allows for super resolution imaging and single particle tracking inside the living cell.
Detailed molecular profiling investigations alongside antitumor testing and tolerability studies in animals suggest caution when considering the clinical development of inhibitors of CDK8 and CDK19, since a clear therapeutic window could not be demonstrated with two structurally distinct, potent and selective prototype drugs.
Herpes simplex virus evades the immune response by inhibiting the TAP transporter with a peptide inhibitor ICP47 that has an extensive interface at the peptide translocation cavity and locks the transporter in an inactive state.
Biochemical dissections show that the Guided Entry of Tail Anchored proteins (GET) pathway selects ER-destined tail-anchored proteins using at least two distinct molecular mechanisms, each recognizing a distinct physicochemical feature in the substrate.
Calcium influx during acute cell stimulation triggers a global actin reset in mammalian cells, which is linked to plasma membrane repair and transcription and has implications for our understanding of cell migration, cancer, inflammation and cell stress response.
Evolutionary bioinformatics and experimentation are applied to the components of the Tat protein transport system to elucidate the structure of the membrane-bound receptor complex and to deduce a molecular description for its substrate-triggered activation.
Fine mapping of transposable element presence/absence variation amongst 216 Arabidopsis strains uncovers widespread novel genetic diversity that underlies differences in transcription and DNA methylation patterns.