bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits
Authors: Tekriwal Anand , Lintz Mario J. , Thompson John A. , Felsen Gidon 
Published: June 2020

AbstractParkinsonian motor deficits are associated with elevated inhibitory output from the basal ganglia (BG). However, several features of Parkinson’s disease (PD) have not been accounted for by this simple “rate model” framework, including the observation in PD patients that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference in impairment due to divergent processing within the BG itself, or to the recruitment of extra-BG pathways by sensory processing? In addition, surprisingly little is known about precisely when, in the sequence from selecting to executing movements, BG output is altered by PD. Here, we address these questions by recording activity in the SNr, a key BG output nucleus, in hemiparkinsonian (hemi-PD) mice performing a well-controlled behavioral task requiring stimulus-guided and internally-specified directional movements. We found that hemi-PD mice exhibited a bias ipsilateral to the side of dopaminergic cell loss that was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in parkinsonian SNr activity during movement preparation could account for the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements, consistent with some aspects of the rate model. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified than stimulus-guided movements.
High resolution genome-wide occupancy inCandida spp. using ChEC-seq
Authors: Tebbji Faiza , Khemiri Inès , Sellam Adnane 
Published: June 2020

AbstractTo persist in their hostile and dynamic human host environments, fungal pathogens has to sense and adapt by modulating their gene expression to fulfil their cellular needs. Understanding transcriptional regulation on a global scale would uncover cellular processes linked to persistence and virulence mechanisms that could be targeted for antifungal therapeutics. Infections associated with the yeastCandida albicans, a highly prevalent fungal pathogen, and the multi-resistant related speciesC. aurisare becoming a serious public health threat. To define the set of a gene regulated by a transcriptional regulator inC. albicans, Chromatin Immuno-Precipitation (ChIP) based techniques including ChIP-chip or ChIP-seq has been widely used. Here, we describe a new set of PCR-based MNase-tagging plasmids forC. albicansand otherCandida spp. to determine genome-wide location of any transcriptional regulator of interest using Chromatin endogenous cleavage (ChEC) coupled to high-throughput sequencing (ChEC-seq). The ChEC procedure does not require protein-DNA crosslinking or sonication avoiding thus artefacts related to epitope masking or the hyper-ChIPable euchromatic phenomenon. In a proof-of-concept application of ChEC-seq, we provided a high-resolution binding map of the SWI/SNF chromatin remodeling complex, a master regulator of fungal fitness inC. albicansin addition to the transcription factor NsiI that is an ortholog of the DNA-binding protein Reb1 for which genome-wide occupancy were previously established inSaccharomyces cerevisiae. The ChEC-seq procedure described here will allow a high-resolution genomic location definition which will enable a better understanding of transcriptional regulatory circuits that govern fungal fitness and drug resistance in these medically important fungi.ImportanceSystemic fungal infections caused byCandida albicansand the ‘superbug’C. aurisare becoming a serious public health threat. The ability of these yeasts to cause disease is linked to their faculty to modulate the expression of genes that mediate their escape from the immune surveillance and their persistence in the different unfavourable niches within the host. Comprehensive knowledge on gene expression control of fungal fitness is consequently an interesting framework for the identification of essential infection processes that could be hindered by chemicals as potential therapeutics. Here, we expanded the use of ChEC-seq, a technique that was initially developed in the yeast modelSaccharomyces cerevisiaeto identify genes that are modulated by a transcriptional regulator, to the pathogenic yeastsC. albicansandC. auris. This robust technique will allow a better characterization of key gene expression regulators and their contribution to virulence and antifungal resistance in these pathogenic yeasts.
Photoperiodic induction without light-mediated circadian entrainment in a high arctic resident bird
Authors: Appenroth Daniel , Melum Vebjørn J. , West Alexander C. , Dardente Hugues , Hazlerigg David G. , Wagner Gabriela C. 
Published: June 2020

AbstractOrganisms use changes in photoperiod to anticipate and exploit favourable conditions in a seasonal environment. While species living at temperate latitudes receive day length information as a year-round input, species living in the Arctic may spend as much as two-thirds of the year without experiencing dawn or dusk. This suggests that specialised mechanisms may be required to maintain seasonal synchrony in polar regions.Svalbard ptarmigan (Lagopus muta hyperborea) are resident at 74-81° north latitude. They spend winter in constant darkness (DD) and summer in constant light (LL); extreme photoperiodic conditions under which they do not display overt circadian rhythms.Here we explored how arctic adaptation in circadian biology affects photoperiodic time measurement in captive Svalbard ptarmigan. For this purpose, DD-adapted birds, showing no circadian behaviour, either remained in prolonged DD, were transferred into a simulated natural photoperiod (SNP) or were transferred directly into LL. Birds transferred from DD to LL exhibited a strong photoperiodic response in terms of activation of the hypothalamic thyrotropin-mediated photoperiodic response pathway. This was assayed through expression of theEya3, Tshβ and deiodinase genes, as well as gonadal development. While transfer to SNP established synchronous diurnal activity patterns, activity in birds transferred from DD to LL showed no evidence of circadian rhythmicity.These data show that the Svalbard ptarmigan does not require circadian entrainment to develop a photoperiodic response involving conserved molecular elements found in temperate species. Further studies are required to define how exactly arctic adaptation modifies seasonal timer mechanisms.Summary statementSvalbard ptarmigan show photoperiodic responses when transferred from constant darkness to constant light without circadian entrainment.
Developmental pathways regulate cytokine-driven effector and feedback responses in the intestinal epithelium
Authors: Lindholm Håvard T. , Parmar Naveen , Drurey Claire , Ostrop Jenny , Díez-Sanchez Alberto , Maizels Rick M. , Oudhoff Menno J. 
Published: June 2020

AbstractThe intestinal tract is a common site for infection, and it relies on an appropriate immune response to defend against pathogens. The intestinal epithelium has an important role in effector responses, which is coordinated by immune-type specific cytokines. It is incompletely understood how cytokines drive epithelial responses. Here, using organoid-cytokine co-cultures, we provide a comprehensive analysis of how key cytokines affect the intestinal epithelium, and relate this toin vivoinfection models. We use imaging, based on a convolutional neural network, and transcriptomic analysis to reveal that cytokines use developmental pathways to define intestinal epithelial effector responses. For example, we find IL-22 and IL-13 dichotomously induce goblet cells, in which only IL-13 driven goblet cells are associated with NOTCH signaling. We further show that IL-13 induces BMP signalling to act as a negative feedback loop in IL-13 induced tuft cell hyperplasia, an important aspect of type 2 immunity. Together, we show that targeting developmental pathways may be a useful tool to tailor epithelial effector responses that are necessary for immunity to infection.
Genome-wide epigenomic stress response in the European sea bass (Dicentrarchus labrax, L.)
Authors: Krick M.V. , Desmarais E. , Samaras A. , Gueret E. , Dimitroglou A. , Pavlidis M. , Tsigenopoulos C.S. , Guinand B. 
Published: June 2020

AbstractBackgroundWhile the stress response inspired genome-wide epigenetic studies in vertebrate models, it remains mostly ignored in fish. We modified the epiGBS (epiGenotyping By sequencing) technique to explore changes in genome-wide cytosine methylation to a repeated acute stress challenge in the nucleated red blood cells (RBCs) of the European sea bass (Dicentrarchus labrax). This species is widely studied in both the natural and farmed environments, including issues regarding health and welfare.ResultsWe retrieved 501,108,033 sequencing reads after trimming, with a mean mapping efficiency of 73.0% (unique best hits). Fifty-seven differentially methylated cytosines (DMCs) close to 51 distinct stress-related genes distributed on 17 of 24 linkage groups (LGs) were detected between RBCs of pre- and post-stress individuals. Literature surveys indicated that thirty-eight of these genes were previously reported as differentially expressed in the brain of zebrafish, most of them involved in stress coping differences. DMC-related genes associated to the Brain Derived Neurotrophic Factor, a protein that favors stress adaptation and fear memory, are especially relevant.ConclusionWe provide an improved epiGBS protocol with increased multiplexing and sequencing capacities that offer new opportunities to improve data acquisition and to investigate important biological processes at a genome-wide level, such as the stress response. Minimally invasive RBCs deserve more attention to investigate the epigenetic response to stress without sacrificing fish.
Colletotrichumspp. from soybean cause disease on lupin but can also induce plant growth-promoting effects
Authors: Wirtz Louisa , Massola Júnior Nelson Sidnei , Rebellato Linhares de Castro Renata , Ruge-Wehling Brigitte , Schaffrath Ulrich , Loehrer Marco 
Published: June 2020

AbstractProtein crop plants such as soybean and lupin attract increasing attention because of their potential use as forage, green manure or for the production of oil and protein for human consumption. While soybean production only recently gained more importance in Germany and within the whole EU in frame of protein strategies, lupin production already is well established in Germany. The cultivation of lupins is impeded by the hemibiotrophic ascomyceteColletotrichum lupini, the causing agent of anthracnose disease. Worldwide, soybean is also a host for a variety ofColletotrichumspecies, but so far this seems not to be the case in Germany. Cross-virulence between lupin and soybean infecting isolates is a potential threat, especially taking into consideration the overlap of possible soybean and lupine growing areas in Germany. To address this question, we systematically investigated the interaction of differentColletotrichumspecies isolated from soybean in Brazil on actual German soybean and lupin plant cultivars. Conversely, we tested the interaction of a German field isolate ofC. lupiniwith soybean. Under controlled conditions,Colletotrichumspecies from soybean and lupin were able to cross-infect the other host plant with varying degrees of virulence, thus underpinning the potential risk of increased anthracnose diseases in the future. Interestingly, we observed a pronounced plant growth-promoting effect for some host-pathogen combinations which might open the route to the use of beneficial biological agents in lupine and soybean production.
Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins
Authors: Díez José-María , Romero Carolina , Vergara-Alert Júlia , Belló-Perez Melissa , Rodon Jordi , Honrubia José Manuel , Segalés Joaquim , Sola Isabel , Enjuanes Luis , Gajardo Rodrigo 
Published: June 2020

AbstractBackgroundThere is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy.MethodsThe neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10dilution which reduced the viral titer by 50%).ResultsAll IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV.ConclusionIn cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management.
Object and object-memory representations across the proximodistal axis of CA1
Authors: Vandrey Brianna , Ainge James A. 
Published: June 2020

AbstractEpisodic memory requires information about objects to be integrated into a spatial framework. Place cells in the hippocampus encode spatial representations of objects that could be generated through signalling from the entorhinal cortex. Projections from lateral and medial entorhinal cortex to the hippocampus terminate in distal and proximal CA1, respectively. We recorded place cells in distal and proximal CA1 as rats explored an environment that contained objects. Place cells in distal CA1 demonstrated higher measures of spatial tuning and expressed place fields closer to objects. Further, remapping to object displacement was modulated by place field proximity to objects in distal, but not proximal CA1. Finally, representations of previous object locations were more precise in distal CA1. Our data suggest that lateral entorhinal cortex inputs to the hippocampus support spatial representations that are more precise and responsive to objects in cue-rich environments. This is consistent with functional segregation in the entorhinal-hippocampal circuits underlying object-place memory.
Analysis of receptor-ligand pairings and distribution of myeloid subpopulations across the animal kingdom reveals neutrophil evolution was facilitated by colony-stimulating factors
Authors: Pinheiro Damilola , Mahwin Marie-Anne , Prendecki Maria , Woollard Kevin J 
Published: June 2020

AbstractNeutrophils or heterophils constitute the largest population of phagocytic granulocytes in the blood of mammals and birds. The development and function of neutrophils and monocytes is primarily governed by the granulocyte colony-stimulating factor receptor family (CSF3R/CSF3) and macrophage colony-stimulating factor receptor family (CSF1R/IL34/CSF1) respectively. Using various techniques this study considered how the emergence of receptor:ligand pairings shaped the distribution of blood myeloid cell populations. Comparative gene analysis supported the ancestral pairings of CSF1R/IL34 and CSF3R/CSF3, and the emergence of CSF1 later in tetrapod lineages after the advent of Jawed/Jawless fish. Further analysis suggested that the emergence of CSF3 lead to reorganisation of granulocyte distribution between amphibian and early reptiles. However, the advent of endothermy likely contributed to the dominance of the neutrophil/heterophil in modern-day mammals and birds. In summary, we show that the emergence of CSF3R/CSF3 was a key factor in the subsequent evolution of the modern-day mammalian neutrophil.Impact statementColony-stimulating factors (CSFs) are important for myeloid phagocyte development. The emergence of CSF3/CSF3R in tetrapod lineages has uniquely contributed to physical, functional and structural adaptions observed in mammalian neutrophils.
The SPIRE1 actin nucleator coordinates actin/myosin functions in the regulation of mitochondrial motility
Authors: Straub Felix , Welz Tobias , Alberico Hannah , Brandão Rafael Oliveira , Huber Anna , Samol-Wolf Annette , Brakebusch Cord , Woods Dori , Kollmar Martin , Martin-Gonzalez Javier , Kerkhoff Eugen 
Published: June 2020

AbstractSubcellular localisation of mitochondria provides a spatial and temporal organisation for cellular energy demands. Long-range mitochondrial transport is mediated by microtubule tracks and associated dynein and kinesin motor proteins. The actin cytoskeleton has a more versatile role and provides transport, tethering, and anchoring functions. SPIRE actin nucleators organise actin filament networks at vesicle membranes, which serve as tracks for myosin 5 motor protein-driven transport processes. Following alternative splicing, SPIRE1 is targeted to mitochondria. In analogy to vesicular SPIRE functions, we have analysed whether SPIRE1 regulates mitochondrial motility. By tracking mitochondria of living fibroblast cells fromSPIRE1mutant mice and splice-variant specific mitochondrial SPIRE1 knockout mice, we determined that the loss of SPIRE1 function increased mitochondrial motility. TheSPIRE1mutant phenotype was reversed by transient overexpression of mitochondrial SPIRE1, which almost completely inhibited motility. Conserved myosin 5 and formin interaction motifs contributed to this inhibition. Consistently, mitochondrial SPIRE1 targeted myosin 5 motors and formin actin filament generators to mitochondria. Our results indicate that SPIRE1 organises an actin/myosin network at mitochondria, which opposes mitochondrial motility.Summary statementThe mitochondrial SPIRE1 protein targets myosin 5 motor proteins and formin actin-filament nucleators/elongators towards mitochondria and negatively regulates mitochondrial motility.
Structure of the yeast Nup84-Nup133 complex details flexibility and reveals universal conservation of the membrane anchoring ALPS motif
Authors: Nordeen Sarah A. , Turman Daniel L. , Schwartz Thomas U. 
Published: June 2020

AbstractThe hallmark of the eukaryotic cell is the complex endomembrane system that compartmentalizes cellular functions. Transport into and out of the nucleus, occurs through the Nuclear Pore Complex (NPC). The heptameric Nup84 or Y complex is an essential scaffolding component of the NPC. Here we report two nanobody-bound structures: the full-length Nup84-Nup133 C-terminal domain complex and the Nup133 N-terminal domain, both fromS. cerevisiae. Together with previously published structures, this work enables the structural description of the entire 575 kDa Y complex, from one species. The structure of Nup84-Nup1 33CTDdetails the high flexibility of this dimeric unit of the Y complex. Further, the Nup133NTDcontains a structurally conserved amphipathic lipid packing sensor (ALPS) motif, confirmed by liposome interaction studies. The new structures reveal important details about the function of the Y complex that affect our understanding of NPC structure and assembly.
High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States
Authors: McNamara Ryan P. , Caro-Vegas Carolina , Landis Justin T. , Moorad Razia , Pluta Linda J. , Eason Anthony B. , Thompson Cecilia , Bailey Aubrey , Villamor Femi Cleola S. , Lange Philip T. , Wong Jason P. , Seltzer Tischan , Seltzer Jedediah , Zhou Yijun , Vahrson Wolfgang , Juarez Angelica , Meyo James O. , Calabre Tiphaine , Broussard Grant , Rivera-Soto Ricardo , Chappell Danielle L. , Baric Ralph S. , Damania Blossom , Miller Melissa B. , Dittmer Dirk P. 
Published: June 2020

AbstractSARS-CoV-2 is constantly evolving. Prior studies have focused on high case-density locations, such as the Northern and Western metropolitan areas in the U.S. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant. The presence of D614G was associated with a higher genome copy number and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3’ untranslated region. The data are consistent with community spread within the local population and the larger continental U.S. No strain had mutations in the target sites used in common diagnostic assays. The data instill confidence in the sensitivity of current tests and validate “testing by sequencing” as a new option to uncover cases, particularly those not conforming to the standard clinical presentation of COVID-19. This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S.
Are isokinetic leg torques and kick velocity reliable predictors for competitive success in taekwondo athletes?
Authors: Moreira Pedro Vieira Sarmet , Falco Coral , Menegaldo Luciano Luporini , Goethel Márcio Fagundes , de Paula Leandro Vinhas , Gonçalves Mauro 
Published: June 2020

AbstractThe aim of the study was to analyzed the relationship between isokinetic knee and hip peak torques and Roundhouse-kick velocities and expertise level (Elite vs. Subelite) of Taekwondo athletes. Seven elite and seven sub-elite athletes were tested for kick kinematic, power of impact and for isokinetic peak torque (PT) at slow (60°/s) and high (240°/s) concentric mode. PTs were compared between groups and correlated with the data of kick performance. It was found inter-group differences in hip flexors and extensors PT at the isokinetic fast speed. The hip flexion PT at 60°/s and 240°/s were negatively correlated with the kick time (R = −0.46, and R = −0.62, respectively). Hip flexion torque at 60°/s was also positively correlated (R = 0.52) with the peak of linear velocity of the foot (LVF) and the power of impact (R = 0.51). Peak torque of hip extension at 60°/s and hip abduction at 240°/s were correlated with the LVF (R= 0.56 and R = 0.46). Discriminant analysis presented an accuracy of 85.7% in predicting expertise level based on fast torques of hip flexion and extension and on the knee extension velocity during the kick. This study demonstrated that hip muscles strength is probably the dominant muscular factor for determining kick performance. Knee angular velocity combined with hip torques are the best discriminators for the competitive level in taekwondo athletes.