bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thalamic encoding of complex sensory patterns and its possible role in cognition
Authors: Castejon Carlos , Martin-Cortecero Jesus , Nuñez Angel 
Published: August 2020

AbstractThe function of the higher-order sensory thalamus remains unresolved. Here, POm nucleus was examined byin vivoextracellular recordings across a range of complex sensory patterns. We found that POm was highly sensitive to multiwhisker stimuli involving complex spatiotemporal interactions. The dynamical spatiotemporal structure of sensory patterns and the different complexity of their parts were accurately reflected in precise POm activity changes. Importantly, POm was also able to respond to ipsilateral stimulation and was implicated in the representation of bilateral tactile events by integrating simultaneous signals arising from both whisker pads. We found that POm nuclei are mutually connected through the cortex forming a functional POm-POm loop. We unravelled the nature and content of the messages travelling through this loop showing that they were ‘structured patterns of sustained activity’. These structured messages were transmitted preserving their integrated structure. The implication of different cortical areas was investigated revealing that S1 plays a protagonist role in this functional loop. Our results also demonstrated different laminar implication in the processing of sustained activity in this cortical area and its transmission between hemispheres. We propose a theoretical model in which these ‘structured patterns of sustained activity’ generated by POm may play important roles in perceptual, motor and cognitive functions. From a functional perspective, this proposal, supported by the results described here, provides a novel theoretical framework to understand the implication of the thalamus in cognition. In addition, a profound difference was found between VPM and POm functioning. The hypothesis of Complementary Components is proposed here to explain it.HighlightsPOm is implicated in the representation of complex sensory patterns.POm is implicated in the encoding of bilateral tactile events.POm nuclei are mutually connected through the cortex forming a functional POm-POm loop.‘Structured patterns of sustained activity’ travelling through the loopAbstract Figure
White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD
Authors: Graziano Paulo A. , Garic Dea , Dick Anthony S. 
Published: August 2020

AbstractBackgroundCallous-unemotional (CU) behaviors are important for identifying severe patterns of conduct problems (CP). One major fiber tract implicated in the development of CP is the uncinate fasciculus (UF), which connects amygdala and orbitofrontal cortex (OFC). The goals of the current study were to 1) explore differences in the white matter microstructure in the UF and other major fiber tracks (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], cingulum, and corticospinal tract [CST]) betweenyoungtypically developing (TD) children and those with Attention-Deficit/Hyperactivity Disorder (ADHD), and 2) explore, within the ADHD group, whether individual differences in these white matter microstructures relate to co-occurring CP and CU behaviors, respectively.MethodsParticipants included 198 young children (78% boys,Mage= 4.95 years; 80% Latinx; 49% TD). CU behaviors and CP were measured via a combination of teacher/parent ratings. Non-invasive diffusion-weighted imaging (DWI) was used to measure fractional anisotropy (FA), an indirect indicator of white matter properties.ResultsRelative to TD children, children with ADHD had reduced FA on four out of the five fiber tracks we examined (except for cingulum). Within the ADHD group, no associations were found between CP and reduced white matter integrity across any of the fiber tracks examined. However, we found that even after accounting for CP and a host of covariates including whole brain FA, CU behaviors were independently related to reduced FA in bilateral UF and left IFOF.ConclusionsThe bilateral UF and IFOF may be a biomarker of CU behaviors, even in very young children.
The nanoscale anatomy of exocytic dense-core vesicles in neuroendocrine cells
Authors: Prasai Bijeta , Haber Gideon J. , Strub Marie-Paule , Ciemniecki John A. , Sochacki Kem A. , Taraska Justin W. 
Published: August 2020

AbstractRab-GTPases and their interacting partners are key regulators of secretory vesicle trafficking, docking, and fusion to the plasma membrane in neurons and neuroendocrine cells. Where and how these proteins are positioned and organized with respect to the vesicle and plasma membrane are unknown. Here, we use correlative super-resolution light and platinum replica electron microscopy to map Rab-GTPases (Rab27a and Rab3a) and their effectors (Granuphilin-a, Rabphilin3a, and Rim2) at the nanoscale in 2D. Next, we develop a targetable genetically-encoded electron microscopy labeling method that uses histidine based affinity-tags and metal-binding gold-nanoparticles to determine the axial location of exocytic proteins using electron tomography. Our data show that Rab-GTPases and their effectors are distributed across the entire surface of individual docked vesicles. This circumferential distribution likely aids in the efficient transport, capture, docking, and rapid fusion of vesicles in excitable cells. The nanoscale molecular model of dense core vesicles generated from our methods reveals how key proteins assemble at the plasma membrane to regulate membrane trafficking and exocytosis.
InhA inhibitors have activity against non-replicatingMycobacterium tuberculosis
Authors: Flint Lindsay , Korkegian Aaron , Parish Tanya 
Published: August 2020

AbstractWe previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activityin vitroandin vivoand targets cell wall biosynthesis via inhibition of InhA. We tested the ability of two molecules of the diazaborine series to kill non-replicatingMycobacterium tuberculosisin the nutrient starvation model; both molecules were bactericidal, reducing viability by >3 logs in 21 days. Activity was not inoculum-dependent and showed similar kill rates to other InhA inhibitors (isoniazid and NITD-916). We conclude that inhibition of InhA is bactericidal against nutrient-starved non-replicatingM. tuberculosis.
Impaired miRNA degradation by post-transcriptional addition of 3’ cytosine and adenine in T cell activation
Authors: Rodríguez-Galán Ana , Dosil Sara G , Gómez Manuel José , Fernández-Delgado Irene , Sánchez-Cabo Fátima , Sánchez-Madrid Francisco 
Published: August 2020

ABSTRACTMiRNA repertoire of T cells undergoes extensive changes in response to activation. Whereas global miRNA downregulation occurs few hours after activation, some individual miRNAs are specifically up- or down-regulated. In this study, we have assessed miRNA expression and post-transcriptional modification kinetics in human primary CD4+ T cells upon short-term stimulation with αCD3αCD28 or IFN I using Next Generation Sequencing. Multiple miRNAs not related before with T cell activation profile have been identified as differentially expressed. Downregulated miRNAs presented higher 3’ uridylation. Dis3L2 and Eri1 (3’ to 5’ exoribonucleases that prefer uridylated RNA as substrates) increased their expression upon TCR stimulation, probably generating an adverse environment for miRNAs. Remarkably, non-templated cytosine additions to 3’ end, previously unknown to be a relevant post-transcriptional modification mechanism, were overrepresented in upregulated miRNAs, together with high levels of adenylation. In the midst of an increasing presence of exoribonucleases, miRNAs multiplying their levels may successfully escape degradation due to 3’ cytosine and adenine addition. These protective signals open a new avenue to improve miRNA stability for therapy in T cells.
Distinct aging-vulnerable trajectories of motor circuit functions in oxidation- and temperature-stressedDrosophila
Authors: Ram Iyengar Atulya Srisudarshan , Ruan Hongyu , Wu Chun-Fang 
Published: August 2020

AbstractWe examined several sensory-motor processing circuits inDrosophilaacross the lifespan and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. We observed relatively little deterioration toward the end of lifespan in the giant-fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex. In contrast, we found substantial age-dependent modifications in the performance of GF inputs and other circuits driving flight motoneuron activities. Importantly, in high temperature (HT)-reared flies (29 °C), the characteristic age-dependent progression of these properties was largely maintained, albeit over a compressed time scale, lending support for the common practice of expeditingDrosophilaaging studies by HT rearing. We discovered shortened lifespans inCu2+/Zn2+Superoxide Dismutase 1(Sod) mutant flies were accompanied by alterations distinct from HT-reared flies, highlighting differential effects of oxidative vs temperature stressors. This work also establishes several age-vulnerable parameters that may serve as quantitative neurophysiological landmarks for aging inDrosophila.
The genetic architecture and genomic context of glyphosate resistance inAmaranthus tuberculatus
Authors: Kreiner J.M. , Tranel P.J. , Weigel D. , Stinchcombe J.R. , Wright S.I. 
Published: August 2020

AbstractMuch of what we know about the genetic basis of herbicide resistance has come from detailed investigations of monogenic adaptation at known target-sites, despite the increasingly recognized importance of polygenic resistance. Little work has been done to characterize the broader genomic basis of herbicide resistance, including the number and distribution of genes involved, their effect sizes, allele frequencies, and signatures of selection. In this work, we implemented genome-wide association (GWA) and population genomic approaches to examine the genetic architecture of glyphosate resistance in the problematic agricultural weed,Amaranthus tuberculatus. A GWA was able to correctly identify the gene targeted by glyphosate, but when we statistically controlled for two target-site genetic mechanisms, we found an additional 250 genes across all 16 chromosomes associated with non-target site resistance (NTSR). The encoded proteins had functions that have been linked to non-target site resistance (NTSR), the most significant of which is response to chemicals, but also showed pleiotropic roles in reproduction and growth. The architecture of NTSR was enriched for large effect sizes and low allele frequencies, suggesting the role of pleiotropic constraints on its evolution. The enrichment of rare alleles also suggested that the genetic architecture of NTSR may be population-specific and heterogeneous across the range. Despite their rarity, we found signals of recent positive selection on NTSR-alleles by both window- and haplotype-based statistics, and an enrichment of amino-acid changing variants. In our samples, genome-wide SNPs explain a comparable amount of the total variation in glyphosate resistance to monogenic mechanisms, even in a collection of individuals where 80% of resistant individuals have large-effect TSR mutations, indicating an underappreciated polygenic contribution to the evolution of herbicide resistance in weed populations.
Larval zebrafish use olfactory detection of sodium and chloride to avoid salt-water
Authors: Herrera Kristian J. , Panier Thomas , Guggiana-Nilo Drago , Engert Florian 
Published: August 2020

AbstractSalinity levels constrain the habitable environment of all aquatic organisms. Zebrafish are freshwater fish that cannot tolerate high salt environments and would, therefore, benefit from neural mechanisms that enable the navigation of salt gradients to avoid high salinity. Yet, zebrafish lack epithelial sodium channels, the primary conduit land animals use to taste sodium. This suggests fish may possess novel, undescribed mechanisms for salt detection. In the present study, we show that zebrafish, indeed, respond to small temporal increases in salt by reorienting more frequently. Further, we use calcium imaging techniques to identify the olfactory system as the primary sense used for salt detection, and we find that a specific subset of olfactory receptor neurons encodes absolute salinity concentrations by detecting monovalent anions and cations. In summary, our study establishes that zebrafish larvae have the ability to navigate, and thus detect salinity gradients, and that this is achieved through previously undescribed sensory mechanisms for salt detection.
CRISPR-Cas9-mediated depletion ofO-GlcNAc hydrolase and transferase for functional dissection ofO-GlcNAcylation in human cells
Authors: Gorelik Andrii , Ferenbach Andrew T. 
Published: August 2020

AbstractO-GlcNAcylation is an abundant post-translational modification (PTM) on serine and threonine residues of nuclear and cytoplasmic proteins. Although this PTM has been reported on thousands of proteins,O-GlcNAc transferase (OGT) and hydrolase (OGA) are the only two enzymes that perform the respective addition and removal ofO-GlcNAc on protein substrates. To examine the consequences of deregulatedO-GlcNAcylation, theO-GlcNAc field has mostly relied on the use of RNA interference to knockdown OGT/OGA and inhibitors to block their activities in cells. Here, we describe the first complete CRISPR-Cas9 knockouts of OGA and a knockdown of OGT (with a maximal decrease in expression of over 80%) in two human cell lines. Notably, constitutive depletion of oneO-GlcNAc cycling enzyme not only led to a respective increase or decrease in totalO-GlcNAcylation levels but also resulted in diminished expression of the opposing enzyme, as a compensatory mechanism, observed in previous short-term pharmacological studies. The OGA knockout system presents a convenient platform to dissect OGA mutations and was used to further characterise the single Ser405O-GlcNAc site of human OGA using theS-GlcNAc genetic recoding approach, helping to identify anS-GlcNAc-specific antibody which was previously thought to primarily detectO-GlcNAc.
BART3D: Inferring transcriptional regulators associated with differential chromatin interactions from Hi-C data
Authors: Wang Zhenjia , Zhang Yifan , Zang Chongzhi 
Published: August 2020

ABSTRACTSummaryIdentification of functional transcriptional regulators associated with chromatin interactions is an important problem in studies of 3-dimensional genome organization and gene regulation. Direct inference of TR binding has been limited by the resolution of Hi-C data. Here, we present BART3D, a computational method for inferring TRs associated with genome-wide differential chromatin interactions by comparing Hi-C maps from two states, leveraging public ChIP-seq data for human and mouse. We demonstrate that BART3D can detect relevant TRs from dynamic Hi-C profiles with TR perturbation or cell differentiation. BART3D can be a useful tool in 3D genome data analysis and functional genomics research.Availability and ImplementationImplemented in Python, source code freely available athttps://github.com/zanglab/bart3dContactzang@virginia.eduSupplementary InformationSupplementary data are available.
Neural and subjective effects of inhaled DMT in natural settings
Authors: Pallavicini Carla , Cavanna Federico , Zamberlan Federico , de la Fuente Laura Alethia , Perl Yonatan Sanz , Arias Mauricio , Romero Celeste , Carhart-Harris Robin , Timmermann Christopher , Tagliazucchi Enzo 
Published: August 2020

AbstractBackgroundN,N-Dimethyltryptamine (DMT) is a short acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date addressed the neural and psychological effects of DMT alone, either administered intravenously or inhaled in freebase form, and none conducted in natural settings.AimsOur primary aim was to study the acute effects of inhaled DMT in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. “set” and “setting”), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming DMT in familiar and comfortable settings.MethodsWe combined state-of-the-art wireless electroencephalography (EEG) with psychometric questionnaires to study the neural and subjective effects of naturalistic DMT use in 35 healthy and experienced participants.ResultsWe observed that DMT significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of mystical-type experiences. DMT also increased/decreased global synchrony and metastability in the gamma/alpha band, and resulted in widespread increases in signal complexity.ConclusionsOur results are consistent with previous studies of psychedelic action in the human brain, while at the same time suggesting potential EEG markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.
Vector manipulation by a semi-persistent plant virus through disease symptom expression
Authors: Vasquez Diego F. , Borrero-Echeverry Felipe , Rincon Diego F. 
Published: August 2020

AbstractThe greenhouse whitefly (GWF),Trialeurodes vaporariorum(Westwood) (Hemiptera: Aleyrodidae) is rarely associated with potato plants yet is the only known vector of thePotato yellow vein virus(PYVV). A host shift related with vector’s cognition often requires neural alterations by the virus. However, PYVV, being semi-persistent, is not supposed to directly affect vector physiology. As such, we propose that changes in potato plants caused by PYVV infection should manipulate insect behaviour to increase transmission. Here, we studied the effect of PYVV infection and symptom expression on GWF biological parameters, and attraction towards infected and uninfected potato plants. We compared survival and development rates of GWF nymphs fed with PYVV-infected plants (symptomatic and asymptomatic) and healthy plants under controlled conditions. We also carried out free-choice tests to determine host preference of GWF adults as a function of PYVV infection and disease symptom expression. We found that PYVV infection (both symptomatic and asymptomatic) reduce GWF survival while increasing development time (in symptomatic plants). Combined, a prolonged development time and reduced survival should favour viral uptake and trigger migration of vectors from symptomatic plants short after acquiring the virus. We also found that symptom expression (yellowing) causes significantly greater GWF attraction and establishment compared to healthy or asymptomatic plants. Interestingly, we found that GWF adults that have previously fed on infected plants switch their host preference choosing and establishing on healthy potato plants, which clearly increases horizontal transmission rates. The mechanism through which this behavioural manipulation takes place is not yet well understood. Our results show that symptoms associated with PYVV infection may account for a set of behavioural modifications that make an improbable vector, such as the GWF, into an efficient agent that increases horizontal transmission rates of PYVV.HighlightsPYVD reduces the survival of GWF and increases development time when symptoms occurPYVD symptom makes potato, a non-host plant, attractive to GWFAfter feeding on infected plants, GWF preference changes to prefer uninfected plantsPYVV modulates GWF behaviour to enhance horizontal transmission between plants
Mechanistic Picture for Monomeric Human Fibroblast Growth Factor 1 Stabilization by Heparin Binding
Authors: Kumar Vivek Govind , Agrawal Shilpi , Kumar Thallapuranam Krishnaswamy Suresh , Moradi Mahmoud 
Published: August 2020

ABSTRACTHuman fibroblast growth factor (FGF) 1 or hFGF1 is a member of the FGF family that is involved in various vital processes such as cell proliferation, cell differentiation, angiogenesis and wound healing. hFGF1, which is associated with low stabilityin vivo, is known to be stabilized by binding heparin sulfate, a glycosaminoglycan that aids the protein in the activation of its cell surface receptor. The poor thermal and proteolytic stability of hFGF1 and the stabilizing role of heparin have long been observed experimentally; however, the mechanistic details of these phenomena are not well understood. Here, we have used a combination of microsecond-level equilibrium molecular dynamics (MD) simulations, and state-of-the-art enhanced sampling MD simulations to quantitatively characterize the structural dynamics of monomeric hFGF1 in the presence and absence of heparin hexasaccharide. We have observed a conformational change in the heparin-binding pocket of hFGF1 that occurs only in the absence of heparin. Several intramolecular hydrogen bonds were also identified within the heparin-binding pocket, that form only when hFGF1 interacts with heparin. The loss of both intermolecular and intramolecular electrostatic interactions in the absence of heparin plausibly leads to the observed conformational change. This conformational transition results in increased flexibility of the heparin-binding pocket and provides an explanation for the susceptibility ofapohFGF1 to proteolytic degradation and thermal instability. The hFGF1-heparin interaction has also been quantified using absolute binding free energy calculations. Binding affinity (Kd) estimates determined computationally using our novel MD approach are in good quantitative agreement with experimental Kdvalues from isothermal titration calorimetry experiments. The successful application of a combination of microsecond-level MD and accurate free energy calculations to explain the heparin-mediated stabilization of hFGF1 at a quantitative level, represents a promising approach for studying complex biomolecular interactions between proteins and their binding partners at a detailed molecular level using rigorous physics-based simulation techniques.