Ashutosh Pudasaini, Jae Sung Shim ... Brian D Zoltowski
In the plant circadian clock photoreceptor ZEITLUPE, evolutionarily selected residues distinguish photocycle kinetics and allosteric signal transduction pathways to permit proper circadian timing.
SREBP-2 directly regulates genes involved in cholesterol homeostasis and indirectly regulates fatty acid synthesis through the production of a ligand responsible for the activation of LXR and SREBP-1c.
Gisela Schimmack, Kenji Schorpp ... Daniel Krappmann
The deubiquitinating enzyme YOD1 binds to the E3 ligase TRAF6 to counteract p62/sequestosome1 mediated pro-inflammatory NF-κB signaling in response to interleukin-1.
Julieta E Lischinsky, Katie Sokolowski ... Joshua G Corbin
Studying the development of the medial amygdala in the mouse reveals how the brain may potentially process sex differences in innate behaviors such as mating.
James G Granneman, Vickie A Kimler ... Ryan Thummel
Phylogenetic, biochemical, and genetic techniques reveal a novel and ancient member of the Perilipin family, termed Plin6, that functions to concentrate and traffic lipophilic skin pigment in teleost fish.
The novel neural marker for the integration of top-down predictions and bottom-up signals in perception elucidates uncertainty in perceptual inference and provides evidence for the predictive coding account of perception.
Data-driven methods predict over 35 mosquitoes are potential vectors of Zika virus, suggesting a larger geographic area and a greater human population is at risk of infection.
A genetic analysis has identified the cholinergic SIA sublateral motor neurons, which innervate all four body wall muscles separately, as crucial regulators of turning around during sleep in Caenorhabditis elegans.
Martijn S Luijsterburg, Dimitris Typas ... Haico van Attikum
A new mechanism is uncovered by which the RNF168 ubiquitin ligase couples PALB2-dependent homologous recombination to H2A ubiquitylation to promote DNA repair and preserve genome integrity.
TD Barbara Nguyen-Vu, Grace Q Zhao ... Jennifer L Raymond
Learning capacity depends on a dynamic interplay between the brain’s ability to change the strength of its synapses and the history of activity at those synapses.
Xuemeng Zhang, Thomas Kampourakis ... Yin-Biao Sun
The Frank–Starling law of the heart and its underlying mechanism of length-dependent activation involve distinctive structural changes in both the thin and thick filaments of cardiac muscle cells.
Vidhyasankar Krishnamoorthy, Michael Weick, Tim Gollisch
The encoding of visual images by certain retinal ganglion cells is fundamentally altered in the context of eye-movement-like image transitions; the transitions trigger inhibitory interactions, which make these cells particularly sensitive to recurring images.
Structure specific nucleases that act in DNA replication, repair and recombination actively mold their DNA while transforming their own structure to achieve precise cleavage of their cognate DNA and avoid the deleterious cleavage of noncognate DNA.
A biologically plausible learning rule allows recurrent neural networks to learn nontrivial tasks, using only sparse, delayed rewards, and the neural dynamics of trained networks exhibit complex dynamics observed in animal frontal cortices.
Tomoya Hasegawa, Christopher J Hall ... Atsushi Kawakami
The Interleukin 1 beta signaling and tissue inflammation act as a double-edged sword: they are required for regeneration, but when in excess, they impair tissue regeneration and induce apoptosis.
A computational model reveals how response properties of category-selective regions in the visual cortex reflect both bottom-up stimulus-driven signals and top-down attentional signals from the parietal cortex.
Interaction of P. falciparum with the erythrocyte activates a phosphorylation cascade altering the viscoelastic properties of this area of the host membrane conditioning it for successful invasion.
A new component, CatSper zeta, is required for continuous alignment of the calcium channel along the sperm's tail and is crucial for normal sperm swimming behavior and fertility.
Eszter Posfai, Sophie Petropoulos ... Janet Rossant
Lineage specification and commitment are synchronized in the developing trophectoderm lineage of the mouse embryo, but are asynchronous events in the maturing inner cell mass, revealing a window of plasticity in this lineage.
Ameya A Mashruwala, Adriana van de Guchte, Jeffrey M Boyd
The absence of oxygen prompts Staphylococcus aureus cells to rupture resulting in increased formation of biofilms, which are the etiological agents of recurrent infections.
James E Gomez, Benjamin B Kaufmann-Malaga ... Deborah T Hung
Mutations in several components of a bacterial ribosome are shown to broadly decrease antibiotic and stress sensitivity, and readily accessible reversion mutations allow these ribosomal mutations to serve as stepping stones to high level antibiotic resistance.
Olga Martzoukou, Sotiris Amillis ... George Diallinas
In filamentous fungi the AP-2 complex, which in mammals is an adaptor of clathrin-mediated endocytosis, is recruited to specific clathrin-independent apical endocytosis necessary for proper lipid maintenance and polar growth.
Emma E Laing, Carla S Möller-Levet ... Derk-Jan Dijk
An unbiased modelling approach shows that only a few blood transcriptome samples are required to accurately assess the human circadian melatonin phase, even during altered sleep schedules.
The neuroanatomical and functional analysis of genetically-identified motoneurons controlling all major steps of Drosophila proboscis extension provides new insights into the architecture of a motor circuitry controlling a reaching-like behavior.
Building on previous work (Faull et al, 2016), it shown that the different connectivity profiles of the individual columns of the human periaqueductal gray support their proposed roles in human threat behaviours, such as freezing or fight/flight.
Yvette E Fisher, Helen H Yang ... Thomas R Clandinin
FlpStop is a generalizable tool for conditional gene disruption and rescue and enables critical experiments examining the interactions between genes, circuits, and computation.
Collin Kieffer, Mark S Ladinsky ... Pamela J Bjorkman
Combined tissue clearing, 3D-immunofluorescence, and electron tomography spatially revealed the dynamics of early HIV-1 spread within lymphoid tissues of humanized mice at the resolution of single cells and individual virions.
Iva Gudernova, Silvie Foldynova-Trantirkova ... Pavel Krejci
A new luciferase and fluorescent reporter system enables rapid and efficient in-cell profiling of the majority of protein kinase oncogenes known to date.
Matthew J Sternfeld, Christopher A Hinckley ... Samuel L Pfaff
Stem cell derived ventral-spinal cord excitatory neurons self-assemble into a rhythmically bursting neural network whose speed and intercellular coordination are both instructively modulated by cell-type specific interactions with inhibitory neurons.
Mark D Morrissey, Nathan Insel, Kaori Takehara-Nishiuchi
Neuron ensembles in the medial prefrontal cortex gradually develop codes for relevant, latent variables common across multiple experiences while – apparently independently – losing information about irrelevant, contextual variables unique to each experience.
A genetic approach documents that mitochondrial DNA moves from donor cells to recipient mtDNA-depleted cells in whole mitochondria and that this restores mitochondrial respiration and the capacity of the cells to form tumours.
Lukasz Kedzierski, Michelle D Tate ... Sandra E Nicholson
The intracellular SOCS5 protein has a unique and key role in restraining influenza A infection by regulating epidermal growth factor receptor signaling in airway epithelial cells.
The crystal structures of the key vaccine candidate CyRPA alone and in complex with antibody Fab fragment was solved and this will be important information for designing a vaccine.
An image-based multiplex autophagosome RNAi screen targeting all Rab GTPases as well as their GAPs and GEFs identifies the Rab GEF SMCR8 as multifaceted autophagy modulator, which regulates kinase activity and gene expression of ULK1.
The structure of the promising malaria blood-stage vaccine candidate antigen PfCyRPA and the characterization of a protective epitope are facilitating research on its essential role in parasite invasion, and will guide future epitope-focused vaccine design.
Patrícia A Correia, Eran Lottem ... Zachary F Mainen
Phasic activation of dorsal raphe serotonin neurons transiently inhibits locomotion without influencing anxiety or producing reinforcement, but when repeated over many days a long-term facilitation of locomotion is produced.
The cancer-associated human ubiquitin ligase HUWE1 can adopt an auto-inhibited dimeric state, whose occupancy is regulated by competing intra- and intermolecular interactions of the dimerization region and by the tumor suppressor p14ARF.
Prostate cancer resistance to androgen receptor antagonist therapy occurs by way of tumors impeding local glucocorticoid metabolism and inactivation and thereby permitting sustained glucocorticoids to stimulate up-regulated glucocorticoid receptor.
The ability of the Ndc80 complex to bind two Dam1 complex rings is important for chromosome attachment, and the distance between the two rings is vital for supporting growth.
Davide M Coda, Tessa Gaarenstroom ... Caroline S Hill
NODAL/Activin-induced SMAD2 binding directly drives remodeling of both open and closed chromatin and does not directly correlate with temporal patterns of gene expression upon prolonged signaling.
Folding and unfolding pathways are described for a ribosome-binding 3' cap-independent translation enhancer at the center of a conformational rearrangement that is implicated in the transition from translation to replication of an RNA virus.
Visual pigments with a longer peak-absorption wavelength or an open chromophore-binding pocket are generally noisier, being more prone to spontaneous activity.
Wenchang Zhou, Fabrizio Marinelli ... José D Faraldo-Gómez
The notion that the lumen of the ATP synthase membrane rotor is the long-sought megachannel that triggers the onset of the mitochondrial permeability transition is found to be inconsistent with its actual structural and functional properties.
Ceri A Fielding, Michael P Weekes ... Gavin W G Wilkinson
The human cytomegalovirus US12 gene family work co-operatively to degrade large numbers of immune ligands and prevent recognition by natural killer cells.
José A Rodríguez-Martínez, Aaron W Reinke ... Aseem Z Ansari
Cognate site identification uncovers the impact of combinatorial dimerization in specifying new DNA binding sites for human bZIP transcription factors and comprehensive specificity landscapes predict the impact of SNPs on bZIP binding at previously unannotated regulatory loci.
Myomaker is activated on muscle stem cells to promote their fusion with myofibers, which is essential for induction of pro-growth signaling pathways and physiological muscle hypertrophy.
Ana Tamarkin-Ben-Harush, Jean-Jacques Vasseur ... Rivka Dikstein
Differential eIF4E binding to transcription initiation nucleotides and alternative promoter usage of eIF1A, PABP and other genes are involved in the response of the translation machinery to energy stress.
The crystal structure of a large C-terminal fragment of Munc13-1 provides a key framework to understand how Munc13-1 mediates neurotransmitter release and presynaptic plasticity.
Jacqueline M Tabler, Maggie M Rigney ... John B Wallingford
Genetic studies in mice reveal the molecular and embryological mechanisms of vocal fold development and function, thereby informing our understanding of vocal communication and congenital voice defects.
Biochemical data demonstrate that the conformation of the target site DNA can dramatically modulate the kinetics and directionality of the otherwise isoenergetic transposition reaction of DDE transposases.
Stephanie L Leal, Susan M Landau ... William J Jagust
Cognitively normal older adults show a positive relationship between neural activity during memory encoding and brain β-amyloid deposition rate over the subsequent 3-4 years, supporting preclinical data that associates neural activity with β-amyloid deposition.
Direct in-vivo measurements in the human brain test validity of detailed computational models of trancranial electric stimulation and show that electric fields in the brain are weaker than currently assumed.
Rima S Chakrabarti, Sally A Ingham ... Helen H Hobbs
Accessible cholesterol levels in human red blood cells were found to be stable within individuals but vary >10-fold among individuals and this variability may contribute to differences in cholesterol trafficking among tissues.
The stability of metabolic autocatalytic cycles that are widespread in central metabolism limits the affinities of enzymes at flux branch points and explains excess expression of these enzymes.
Elisabeth Cassier, Nathalie Gallay ... Franck Vandermoere
Phosphoproteomics identifies β-arrestin 2 phosphorylation at Thr383 by MEK as a key step of GPCR-induced Erk½ activation, thus providing new insight into the molecular mechanism underlying β-arrestin-dependent GPCR-operated signaling.
The medial and lateral subdivisions of the entorhinal cortex are important for deciding "where to go from here" and "what to do to this object" in a visual context, respectively.
Stano Pekár, Lenka Petráková ... Marie E Herberstein
A mimetic complex composed of at least 140 species of ants, wasps, spiders, true bugs and treehoppers, all with conspicuous golden bodies, has been discovered.
An endoplasmic reticulum membrane protein regulates synaptic transmission, alcohol sensitivity, and gene expression by controlling the trafficking of a calcium-activated potassium channel.
Building on previous work (Entchev et al, 2015), computational analyses reveal that the choice between redundant versus synergistic encoding in a gene expression code for food abundance is controlled by cross-talk and auto-regulation among TGF-beta and serotonin pathways.
The small subunit ribosomal protein uS7/Rps5 interacts with translation initiation factor eIF2α to stabilize first the open, and then the closed conformation of the pre-initiation complex to promote accurate start codon selection in vivo.
Dimers of Bak assemble into clusters without using a distinct protein-protein interface, which may explain the apparent difficulties in obtaining high resolution structures of the pore complex and in targeting dimer-dimer interactions to regulate apoptosis.
Huaibin Chen, William M Marsiglia ... Moosa Mohammadi
A four-switch long-range allosteric network controls FGF receptor kinase conformational dynamics as well as activity and is applicable to other receptor tyrosine kinases.
Gustavo S Betini, Andrew G McAdam ... D Ryan Norris
Seasonal variation in resources causes opposing episodes of selection on body size, which interact with density dependence to influence population dynamics.
First two transmembrane segments of Tim17 are involved in interaction with the channel and the second two with the motor of the presequence translocase suggesting how proteins are handed over during their translocation into mitochondria.
Genetic analysis of how neuropeptides control C. elegans reproductive behavior shows how T-type calcium channels engage and disengage target neurons from these critical regulators of neural circuits and behavior.
Dongsheng Xiao, Matthieu P Vanni ... Timothy H Murphy
Mesoscale cortical calcium activity correlating with single cortical and thalamic cell spiking reveal rich dynamics and support a novel approach for investigating in vivo functional networks in the mammalian brain.
Codon optimization through biased synonymous substitutions is a characteristic feature of the genomes of generalist fungal parasites and is associated with the colonization of multiple hosts.
James Watson, Walter RJ Taylor ... Nicholas J White
In silico modelling of all available data shows that a twenty-day ascending-dose primaquine regimen could be safe to administer to G6PD deficient patients for the radical cure of vivax malaria.
Shu-Hsien Sheu, Juan Carlos Tapia ... Jeff W Lichtman
A similar pattern of developmental synaptic refinement leads two consecutive synaptic relays to have the same organization suggesting that some general principle of neural organization is at play.
Matthew B Stone, Sarah A Shelby ... Sarah L Veatch
Clustering the B cell receptor generates a membrane domain analogous to the liquid-ordered phase, localizing proteins involved in early receptor activation.
Sebastian Ocklenburg, Judith Schmitz ... Onur Güntürkün
Gene expression asymmetries in fetal spinal cord are triggered by epigenetic mechanisms suggesting that handedness has a spinal instead of a cortical origin.
Heather M Meyer, José Teles ... Adrienne H K Roeder
Fluctuations of a transcription factor that coincide with the G2 phase of the cell cycle pattern two interspersed cell fates in a multicellular system.
