Transient suppression of activity in the macaque mediodorsal thalamus impairs adjustment of secondary reinforcer values and disrupts appropriate action selection in a reinforcer devaluation task; this profile is distinct from that of amygdala or subregions of orbitofrontal cortex.
The numerous reports in support of action-value representation in the striatum are based on statistical analyses that are subject to two critical confounds and, thus, this long-held belief of striatal action-value representation should be retested using different experiments and analyses.
Maria M Diehl, Christian Bravo-Rivera ... Gregory J Quirk
Avoiding danger requires inhibitory signaling in the prelimbic prefrontal cortex, as evidenced by optogenetic manipulations based on neuronal firing patterns.
The genomes of animal progenitors evolved as mosaics of old, new, rearranged, and repurposed protein domains, genes and pathways and paved the way for the origin and evolution of animals.
The symbiotic relationship between Hydra and Chlorella is driven by metabolic co-dependence and characterized by changes in the photobiont genome in terms of lack of genes essential in free-living algae.
Donna L Mallery, Chantal L Márquez ... Leo C James
The inositol phosphate IP6 is selectively packaged into HIV virions, where it coordinates electropositive pores in the capsid to prevent spontaneous collapse and promote encapsidated DNA synthesis.
Time resolved crystal structures reveal the binding of activated monomers to the template, followed by generation of the imidazolium-bridged dinucleotide intermediate, and finally formation of a phosphodiester bond between the primer and the adjacent monomer.
Maria L Spletter, Christiane Barz ... Frank Schnorrer
A developmental transcriptomics resource from Drosophila flight muscles quantifies the transcriptional dynamics during muscle morphogenesis and identifies three ordered phases of sarcomere morphogenesis.
Francois M Lambert, Laura Cardoit ... Didier Le Ray
Molecular labeling, electrophysiology and calcium imaging have revealed a novel switching of neurotransmitter at the frog neuromuscular junction where motoneurons transiently release glutamate before acetylcholine at synapses on developing hindlimb muscles at the onset of metamorphosis.
Compiling public datasets into a single, centralised repository and linking directly to analytical software completely transforms the scale and scope of causal inference across the phenome.
Anna R Moore, Sarah E Richards ... Suzanne Paradis
In vivo and ex vivo analysis of the activity-regulated gene Rem2 in the mouse visual system sheds new light on the contribution of intrinsic excitability in circuit plasticity.
Alex J Noble, Venkata P Dandey ... Bridget Carragher
Fiducial-less tomography on single particle cryoEM samples reveals that most particles are adsorbed to the air-water interface and allows for researchers to diagnose and solve sample, grid, ice thickness, collection, and processing issues.
A combined approach of unbiased proteomics, biochemistry, genetics, and transgenic animal models reveals that GPR56/ADGRG1 regulates myelin formation and repair by interacting with its microglial-derived ligand transglutaminase 2.
Matthew J Shurtleff, Daniel N Itzhak ... Jonathan S Weissman
The ER membrane protein complex promotes the biogenesis of a subset multipass membrane proteins enriched for transporters and other proteins with destabilizing features in transmembrane domains.
Regulatory success operates by goal-consistent increases and decreases of distinct attribute representations in generic neural hubs and in domain-specific brain regions, explaining when and why regulatory success generalizes across domains and contexts.
The Hippo signaling restricts the number of SHF cardiomyocytes in the venous pole by negatively regulating Bmp-Smad signaling in the cells of lateral plate mesoderm.
Jessica Winger, Ilana M Nodelman ... Gregory D Bowman
Based on its nucleotide-bound state, the Chd1 chromatin remodeler can locally alter DNA twist on the nucleosome, which either pulls in or expels ~1 bp of DNA at the internal SHL2 binding site.
Roman M Stilling, Gerard M Moloney ... John F Cryan
Social-interaction impairment in germ-free mice is associated with a markedly altered transcriptional response to social novelty in the amygdala, as characterised by replacement of upregulation of common stimulus-induced pathways with upregulation of the splicing machinery.
A cryo-electron microscopy study of the human CLC-1 chloride ion channel reveals the structural basis of why some CLC proteins function as passive chloride channels whereas others function as an active proton-chloride antiporters.
Microtubule nucleation from the nuclear envelope in fission yeast involves repurposing of nuclear export proteins for a non-export-related function, docking cytoplasmic proteins at nuclear pore complexes.
Emilia Dimitrova, Takashi Kondo ... Robert J Klose
The ZF-CxxC protein FBXL19 recruits kinase-associated Mediator to CpG islands of silent developmental genes in embryonic stem cells, which primes these genes for activation during differentiation and is required for embryonic development.
Cdc48-like protein of actinobacteria (Cpa) is a AAA+ proteasomal interactor involved in adaptation of mycobacteria to carbon limitation and potentially influencing ribosomal composition of the cell.
Jeroen B Smaers, Alan H Turner ... Chet C Sherwood
Multiple independent directional selection events on a neural substrate that underpins domain-general associative abilities partly explains independent occurrences of complex behavior in different lineages of mammals.
Nadine Dijkstra, Pim Mostert ... Marcel AJ van Gerven
In contrast to perception, during visual imagery, there are no clear time-locked processing stages and imagery specifically overlaps with perceptual processing around 160 ms after stimulus onset and from 300 ms onwards.
Ali Farshchian, Alessandra Sciutti ... Ferdinando A Mussa-Ivaldi
The brain obtains and preserves a consistent temporal alignment of multisensory and motor information flowing along staggered streams by maintaining an invariant estimate across modalities of the energy exchanged with the environment at discrete events.
Joana A Santos, Stephan Rempel ... Dirk J Slotboom
ECF-CbrT is a bacterial vitamin B12 transporter that is structurally different from the well-characterized transporter BtuCDF, yet has similar functional properties.
Sina Ibne Noor, Somayeh Jamali ... Holger M Becker
Carbonic anhydrase II features a surface proton antenna that exclusively mediates proton exchange with monocarboxylate transporters to facilitate proton-coupled lactate transport in cancer cells.
Stunning new scan data of an enigmatic fish from the Early Devonian of Australia, Ligulalepis, is identified as a stem osteichthyan, specifically, as the sister taxon to the 'psarolepids' plus crown osteichthyans.
Epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging, and stimulation of glycolysis promotes metabolic health and longevity.
A family of fluorescent biosensors for nicotinamide adenine dinucleotides allows quantification of these cofactors in live cells with spatio-temporal resolution.
Azadeh Yazdan-Shahmorad, Daniel B Silversmith ... Philip N Sabes
Focal optogenetic stimulation strengthens functional connectivity between primary somatosensory and motor cortices in macaques, in a manner consistent with a Hebbian model of stimulus-driven plasticity.
Profilin helps to maintain formin at the growing barbed end of an actin filament, while piconewton mechanical tension drastically enhances formin dissociation from the barbed end.
Iwan Zimmermann, Pascal Egloff ... Markus A Seeger
Synthetic single domain antibody libraries and a binder selection cascade encompassing ribosome and phage display enable the selection of conformation-specific binders against previously intractable membrane proteins within three weeks.
Structures of CysZ show a antiparallel membrane protein with an unanticipated fold and together with functional characterization provide insight into a bacterial sulfate translocating system.
Riley Perszyk, Brooke M Katzman ... Stephen F Traynelis
A series of novel compounds selective for N-methyl-D-aspartate-type glutamate receptor includes positive and negative allosteric modulators that act at the same site, show use-dependence, increase agonist potency, and have differential activity based on the agonist concentration.
Plant diversification can make an important contribution to ecological intensification and the sustainable use of associated ecosystem services in an urban ecosystem.
The subjective time of social interactions reflects one's autistic-like tendency and is critically mediated by oxytocin, indicating that time perception is ingrained with personality traits, which likely have neuroendocrine origins as per previous research.
Transgenic expression of glucanase, xylanase and phytase in pigs enhances growth performance and reduces nitrogen/phosphorus emission, and offers a very valuable biological strategy for sustainable resource utilization and environmental protection in the pork industry.
Fossilized feces (coprolites) of extinct bone-crushing dogs, Borophagus parvus, from late Miocene (6 million years ago) of California demonstrates consumption and preservation of bones in digestive tracts and potential social hunting behavior by these predators.
Poh Hui Chia, Franklin Lei Zhong ... Bruno Reversade
A biallelic missense mutation in the highly conserved, neuron-specific kinase CAMK2A abrogates holoenzyme assembly and causes a new inherited neurodevelopmental disease.
James Attwater, Aditya Raguram ... Philipp Holliger
Adopting RNA trinucleotides as substrates, ribozymes can catalyse the copying of structured RNA sequences, allowing self-synthesis by part of a newly evolved symbiotic ribozyme pair.
The preoptic area (POA) regulates distinct metabolic adaptations, via leptin-dependent (fasting-induced hypometabolism and high-fat-diet-induced hypermetabolism), or leptin-independent mechanisms (temperature induced metabolic changes) and thus significantly contributes to body weight homeostasis.
Almary Guerra, Raoul FV Germano ... Sven Reischauer
A discovery of two previously unknown, molecularly distinct fields of cardiac progenitors in zebrafish provides evidence for cardiac laterality prior to the emergence of cardiac septation and allows novel insights into cardiac development and disease.
Inducing presomitic mesoderm (PSM)-fated ES cells clarified that Ripply2 directly interacts with Tbx6 and degrades Tbx6 in proteasome-ubiquitin pathway by recruiting the 26S proteasome, which is a PSM-specific event to define the segment border during mouse somitogenesis.
Certain types of 3D chromatin loops are easy to predict from existing or easily obtainable 2D information, which benefits gene expression studies in tissues/cells/organisms without extensive pre-existing 3D information.
Genetic and biochemical analyses reveal a virulence mechanism employed by V. dahliae that involves inhibition of the transcription factor activity of CBP60g and SARD1.
Surface protein precursors traffic to lipoteichoic acid-rich septal membranes of Staphylococcus aureus for cleavage of their YSIRK-GXXS motif signal peptides and SecA-mediated translocation across the plasma membrane.
A broadly applicable method that faithfully preserves genetically labeled cellular structures for 3D electron microscopy (EM) and correlated light and electron microscopy (CLEM).
Rogier B Mars, Stamatios N Sotiropoulos ... Saad Jbabdi
White matter connectivity assessed using diffusion MRI allows one to compare whole-brain organization between different animal species in a quantitative fashion, identifying homologous areas and regions of unique specialization.
Comparative structural studies reveal how the cytoplasmic tails of Eph receptors can differentiate different downstream target proteins via highly specific SAM–SAM domain interactions.
Katharina Schlereth, Dieter Weichenhan ... Hellmut G Augustin
The acquisition of vascular quiescence during transition to adulthood is driven by distinct transcriptional and epigenetic programs of pro- and anti-angiogenic genes, with the most prominent effect on the suppression of TGFß family signaling.
Plant-unique RAB5 effector 2 (PUF2) is an effector of plant-unique ARA6, which plays a key role in plant endosomal transport, integrating functions of the two plant RAB5 groups by an unprecedented mechanism.
Identification of a transporter complex comprised of SLC37A3 and ATRAID is required for nitrogen-containing bisphosphonates to enter the cytosol from lysosomes and exert their therapeutic effects on bone.
Clonal heterozygosity for recessive disease alleles can elicit unexpected phenotypes in vivo, suggesting a new genetic concept relevant to understanding pathogenesis (deleterious heteromosaicism).
Loss of a maternally inherited epigenetic modifier leads to establishment of an aberrant regulatory network in preimplantation embryos, developmental delay and destabilisation of cell-fate choices.
Kevin F Chau, Morgan L Shannon ... Maria K Lehtinen
Unbiased transcriptome analyses reveal that neural progenitor cells downregulate protein biosynthetic machinery during early forebrain development, and this fundamental process matches proteomic changes in the adjacent cerebrospinal fluid and is regulated in part by MYC.
The 3Å structure and correlated functional analysis of the TRPM2 cation channel from Nematostella vectensis shed light on the molecular mechanisms of TRPM2 regulation by intra- and extracellular Ca2+, and of inactivation of human TRPM2.
Ben Krause-Kyora, Julian Susat ... Johannes Krause
Ancient hepatitis B virus (HBV) genomes were reconstructed from up to 7000-year-old Stone Age human skeletons, suggesting a long-time complex co-evolution with human populations.
HLA-B*35:01 molecules that are peptide-deficient are thermostable, bind CD8 with higher affinity than their peptide-filled versions, accumulate at immunological synapses and enhance antigen-specific CD8+ T cell immune responses.
Madara Ratnadiwakara, Stuart K Archer ... Minna-Liisa Anko
RNA-binding protein SRSF3 mediates critical changes in RNA processing of pluripotency genes, which reveals functional consequences of regulated RNA processing during stem cell self-renewal and early development.
Philipp K Zuber, Irina Artsimovitch ... Stefan H Knauer
Transcription factors can read out both the sequence and the structure of the non-template DNA strand in the transcription bubble, expanding the repertoire of mechanisms to control transcription.
Hiroshi Yamaguchi, Toshiyuki Oda ... Hiroyuki Takeda
Zebrafish genetics and cryo-electron tomography reveal distinct roles of all vertebrate PIH family proteins in axonemal dynein assembly and cilia/flagella motions, assigning specific dynein subtypes to each PIH protein.
ATM plays an important role in maintaining the fidelity of DNA repair through the regulation of ARP8 phosphorylation to prevent the chromosome abnormality.
A combination of human imaging and brain stimulation techniques show that the somatosensory cortex is essential to prosocial decision making, by transforming observed pain in accurate perception of others' distress.
David A Knowles, Courtney K Burrows ... Yoav Gilad
Genetic variants that modulate transcriptomic response to doxorubicin in human iPSC-derived cardiomyocytes are predictive of cardiac damage and in vivo sensitivity to anthracycline cardiotoxicity.
Individual differences in generalization of aversive value (but not safety information) during human active avoidance learning specifically predict experience of anxiety and intrusive thoughts.
Javier García-Nafría, Yang Lee ... Christopher G Tate
The adenosine A2a receptor couples to the heterotrimeric G protein Gs using both conserved contacts seen in other complexes and, in addition, novel contacts to the beta subunit of the G protein.
Hani Ebrahimi, Hirohisa Masuda ... Julia Promisel Cooper
The nuclear periphery houses compositionally and functionally distinct domains, one of which provides a 'safe zone' for replication and reassembly of heterochromatic genome regions.
Stefanos Stagkourakis, Carolina Thörn Pérez ... Christian Broberger
An unexpected species difference in electrical coupling of analogous neuroendocrine dopamine neurons in rats and mice reveals a role for gap junction connectivity as a band-pass filter for oscillation frequency in neural networks.
A general machine learning scheme for integrating time-series data from single-molecule experiments and molecular dynamics simulations is proposed and successfully demonstrated for the folding dynamics of the WW domain.
The clinically approved HER2 inhibitor lapatinib causes HER2 and HER3 kinase domains to dimerise in a non-canonical, symmetric orientation, providing a platform for oligomerisation and predisposing to receptor-driven cell proliferation.
Spatial and temporal cues intersect, likely via enhancer-promoter looping, to turn on a master identity switch that in turn dictates natural lineage reprogramming with high efficiency and temporospatial precision.
Tomohide Saio, Soichiro Kawagoe ... Charalampos G Kalodimos
A combined NMR and kinetic study demonstrates how the dynamic transition of a molecular chaperone between different oligomerization states can modulate its activity by altering the binding kinetics and energetics of non-native proteins.
Two SET-domain containing proteins regulate H3K4me3 by their binding to H3K4me3 through their PHD domain and directly regulate expression of a subset of genes.
Bronwen R Burton, Richard K Tennant ... Harry N White
Investigation of antibody responses to variant Dengue virus proteins demonstrate new mechanisms that could increase the potential for vaccines to protect against mutable pathogens such as Flu, Dengue and HIV.
A brain-wide mapping of the direct inputs to striatal cholinergic and parvalbumin interneurons reveals connectivity differences and implies their distinct roles in regulating striatal function.
Cellular carbon accumulation systems are a fundamental prerequisite for biomineralization to stabilize pH and to supply inorganic carbon for CaCO3 precipitation under changing environmental conditions.
Binding of multiple LC8 copies to the intrinsically disordered region of the transcription factor ASCIZ exemplifies a new and potentially widespread molecular mechanism for negative feedback regulation.
Emilie Battivelli, Matthew S Dahabieh ... Eric Verdin
Analysis of HIV integration sites from induced and non-induced latently infected populations reveals the role of genomic localization and chromatin context in the fate of HIV-1 infection and the reversal of viral latency.
The melanoma cell interaction with lymphatic endothelial cells promotes melanoma metastasis by inducing a reversible switch to invasively sprouting melanoma cells.
