Nicola Manfrini, Michela Clerici ... Maria Pia Longhese
The conversion of the ends of a double-strand break from double-stranded to single-stranded DNA, which is necessary to initiate homologous recombination, is responsible for loss of transcription and RNA polymerase occupancy around the double-strand break in Saccharomyces cerevisiae.
Prefrontal dopamine regulates inhibition of fear extinction circuits in the infralimbic cortex and disinhibition of fear expression circuits in the amygdala, leading to fear reinstatement.
Shi-Hui Dong, Weixin Tang ... Wilfred A van der Donk
The bacterial cytolysin synthetase CylM has a eukaryotic lipid kinase fold despite the absence of any clear sequence similarity, and contains adjacent phosphorylation and phosphate elimination active sites and an ordered activation loop in the absence of peptide substrate or regulatory proteins.
Guangliang Wang, Surendra K Rajpurohit ... Jeff S Mumm
A novel high-throughput, whole organism chemical screening platform was used to identify existing drugs that increase pancreatic beta-cell mass in zebrafish, implicating unique roles for the NF-κB and serotonergic signaling pathways in regulating pancreatic biology.
A hormone released after mating acts directly on adult intestinal progenitors and differentiated epithelial cells in Drosophila to change their homeostatic setpoint and maximise fecundity.
A gene regulatory network model provides a simplified explanation of the molecular interactions that orchestrate muscle development in the sea urchin embryo.
Experiments examining the actions of morphine on single neurons from one of the brain's reward centers, the VTA, reveal the mechanism by which the drug exerts its hedonic effects.
Starvation upregulates activity in certain sensory channels and downregulates it in others in what appears to be an optimization strategy that serves to increase the hedonic value of food odors.
Individual neurons can adjust the strength of their synapses by using spontaneous calcium influx through NMDA receptors to trigger the release of additional calcium from intracellular stores, which can in turn be used to regulate protein synthesis.
Mutations in four members of the mevalonate pathway have been identified from 134 index porokeratosis patients, including some that correlate with specific clinical manifestations of the disease.
Simon Roux, Steven J Hallam ... Matthew B Sullivan
From public microbial genomes, VirSorter revealed 12,498 viral genome sequences that expand the map of the global virosphere and whose analyses improve understanding of viral taxonomy, evolution and virus-host interactions.
Phosphate starvation in rice induces widespread, but transient, modulation of DNA methylation near stress responsive genes that is independent from the RNA-directed DNA methylation pathway.
Nathaniel Calloway, Géraldine Gouzer ... Timothy A Ryan
Munc13, a protein that is essential for exocytosis, controls the behavior of voltage gated calcium channels and shapes synaptic plasticity on fast time scales.
Michael J Steinbaugh, Sri Devi Narasimhan ... T Keith Blackwell
Germ cell ablation delays C. elegans aging, in part, because unconsumed fat triggers activation of the detoxification factor SKN-1/Nrf, which is regulated by lipid signals and maintains lipid homeostasis.
Kunitoshi Chiba, Joshua Z Johnson ... Dirk Hockemeyer
TERT promoter mutations impair TERT silencing upon cellular differentiation and are sufficient to facilitate cellular immortalization without additional tumor selected changes, explaining why they are associated with a very specific tumor spectrum.
The number of contacts at the interface of a protein–protein complex, together with the properties of the surface, provides a simple, but well-performing predictor of binding affinity.
Benjamin Brandt, Shintaro Munemasa ... Julian I Schroeder
The calcium-dependent signaling pathway during ABA-dependent stomatal closure requires the calcium-independent pathway, and calcium signaling specificity is mediated by PP2C protein phosphatases.
Jasmine C Wong, Kelley M Weinfurtner ... Kevin Shannon
Immature hematopoietic cells from mice with a large segmental deletion found in human myeloid malignancies exhibit cardinal features of myelodysplastic syndrome.
Robin M Harris, Barret D Pfeiffer ... James W Truman
Hemilineages link neuronal stem cells to behavioral functions by providing a conserved ground plan of neuronal types that evolution then uses to sculpt different types of walking and flight behaviors.
Christian Arquint, Anna-Maria Gabryjonczyk ... Timm Maier
Binding of STIL to PLK4's characteristic Polo-box 3 links PLK4 kinase activation to STIL self-association and is a crucial regulatory step for the localized recruitment of downstream factors in centriole duplication.
The mechanism of signaling receptor delivery to primary cilia involves a specific cellular role of a Rab protein that is critical for vertebrate development.
Viktoria Désirée Paul, Ulrich Mühlenhoff ... Roland Lill
Two newly identified assembly factors for the ribosome-associated iron-sulfur protein Rli1 reveal a general mechanism for how the cytosolic iron-sulfur protein assembly (CIA) machinery recruits apoproteins.
Yoong Wearn Lim, Lionel A Sanz ... Frédéric Chédin
Global epigenetic perturbations and accumulation of RNA:DNA hybrids are two novel hallmarks of the lupus-like inflammatory disorder Aicardi-Goutières syndrome.
Analysis of chromerid algal genomes reveals how apicomplexans have evolved from free-living algae into successful eukaryotic parasites via massive losses and re-inventing functional roles of genes.
Neha R Deshpande, Heather L Parrish, Michael S Kuhns
Higher affinity for self-pMHC complexes and broader promiscuity for foreign-pMHC complexes imparts a fitness advantage within the CD4+ T cell compartment in older mice.
Paul A Sigala, Jan R Crowley ... Daniel E Goldberg
Insights into the basic metabolic architecture and adaptations of malaria parasites for growth within human erythrocytes exemplify how incisive knowledge of biochemical pathways and mechanisms may be leveraged to develop new therapies.
Amandine Di-Cicco, Valérie Petit ... Marie-Ange Deugnier
Mammary progenitors identified by a new marker, ICAM-1, undergo epithelial-mesenchymal transition and luminal-to-basal switch in response to paracrine Met activation.
The AAA-ATPase VCP sustains sarcoplasmic proteostasis, in part, by controlling autophagosome-lysosome fusion and the integrity of a dynamic tubular lysosomal network.
Jeremy S Logue, Alexander X Cartagena-Rivera ... Clare M Waterman
Eps8, a specific effector of oncogenic signaling, organizes the cortical actin cytoskeleton of cancer cells to promote mechanical properties that favor a newly identified mode of confined, adhesion-independent cell migration.
María Belén Pardi, Mora Belén Ogando ... Antonia Marin-Burgin
Immature and mature granule cells in the hippocampal dentate gyrus show differing responses to physiologically relevant stimuli, with immature cells better at encoding stimulus frequency and mature cells better at encoding stimulus onset.
An individual-based model estimates exogenous boosting of immunity following re-exposure to chickenpox is limited to 2 years after re-exposure, but an increase in herpes zoster incidence is still expected to occur following universal varicella vaccination.
Sunbin Liu, Sina Mozaffari-Jovin ... Markus C Wahl
Structural and functional analyses show how the spliceosomal Prp3 protein concomitantly binds double- and single- stranded regions in U4/U6 di-snRNAs and serves to stabilize the U4/U6•U5 tri-snRNP for splicing.
Yael Mandelblat-Cerf, Rohan N Ramesh ... Mark L Andermann
Gradual changes in the firing of specific hypothalamic neurons over many hours signal falling energy levels, while short-lived changes over seconds and minutes signal the availability of food.
Structures of the signal recognition particle before and after it captures a transmembrane domain suggest how it chooses, engages, and shields its clients during membrane protein targeting to the endoplasmic reticulum.
Alexander D Kloth, Aleksandra Badura ... Samuel S-H Wang
Five mouse models of autism show deficits in delay eyeblink conditioning, a form of split-second sensory learning that involves the cerebellum, a frequent site of disruption in autistic brains.
The crystal structure of Norrie Disease Protein in complex with the extracellular cysteine-rich domain of Frizzled4 receptor and sucrose octasulfate reveals binding sites for Frizzled4, low density lipoprotein receptor related protein 5/6, and proteoglycan.
A community-based international effort generates standardized HLA allele-specific peptide assay libraries and enables the analysis of the human immunopeptidome by SWATH mass spectrometry.
Mai Nguyen-Chi, Béryl Laplace-Builhe ... Farida Djouad
The discovery of evolutionarily conserved macrophage subsets in zebrafish paves the way for a comprehensive study of macrophage behaviour and function.
Spontaneous, irregular spiking in single cortical pyramidal neurons assembles as neuronal avalanches at the group level identifying a robust scale-invariant organization of resting activity in the awake state.
Mia T Levine, Helen M Vander Wende, Harmit S Malik
Analysis of a spermiogenesis protein reveals a new chromatin requirement for synchrony between maternal DNA packaged in the egg and sperm-packaged paternal DNA in the first embryonic mitosis in Drosophila melanogaster.
A recent claim that humans can discriminate 1 trillion odors is found to be unwarranted, and further analysis offers insights into the dimensionality of olfactory perception.
Lukas Solanka, Mark CW van Rossum, Matthew F Nolan
Random fluctuations in neuronal firing may enable a single brain region, the medial entorhinal cortex, to perform distinct roles in cognition (by generating gamma waves) and spatial navigation (by producing a grid cell map).
Romaric Bouveret, Ashley J Waardenberg ... Richard P Harvey
Some NKX2-5 mutations that cause congenital heart disease retain transcriptional activity and can bind to many off-target genes, in part through their interactions with cofactors.
Cortical interneurons inhibit pyramidal cells to a greater degree when they form synapses with the pyramidal cell body than when they form synapses with dendrites.
Jonathan P Newman, Ming-fai Fong ... Steve M Potter
The 'Optoclamp' is a feedback control technology that enables precise, continuously updated, closed-loop optical control of neural firing both in vitro and in vivo.
Patterning of dendrites by protocadherin-dependent self-avoidance and self/non-self discrimination is required for proper function of a retinal circuit that computes the direction of motion.
Julio D Perez, Nimrod D Rubinstein ... Catherine Dulac
A subset of genes in the mouse brain show dynamically regulated and unequal expression of maternally and paternally derived variants, with implications for brain development and function.
Jyothsna Visweswaraiah, Yvette Pittman ... Alan G Hinnebusch
A structural element of mRNA exit channel protein Rps5 performs a critical role in start codon recognition during translation initiation by stabilizing initiator tRNA binding to the pre-initiation complex.
Floral scent and nectar are highly variable in natural populations and both traits can influence outcrossing rates differently for different pollinators and increase future herbivory.
Diana J Cha, Jeffrey L Franklin ... James G Patton
In isogenically matched colorectal cancer (CRC) cell lines, mutant KRAS alters the composition of secreted miRNAs in extracellular vesicles that can then transfer repressive activity to wild type cells.