bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulus-dependent representational drift in primary visual cortex
Authors: Marks Tyler D. , Goard Michael J. 
Published: December 2020

ABSTRACTTo produce consistent sensory perception, neurons must maintain stable representations of sensory input. However, neurons in many regions exhibit progressive drift across days. Longitudinal studies have found stable responses to artificial stimuli across sessions in primary sensory areas, but it is unclear whether this stability extends to naturalistic stimuli. We performed chronic 2-photon imaging of mouse V1 populations to directly compare the representational stability of artificial versus naturalistic visual stimuli over weeks. Responses to gratings were highly stable across sessions. However, neural responses to naturalistic movies exhibited progressive representational drift across sessions. Differential drift was present across cortical layers, in inhibitory interneurons, and could not be explained by differential response strength or higher order stimulus statistics. However, representational drift was accompanied by similar differential changes in local population correlation structure. These results suggest representational stability in V1 is stimulus-dependent and related to differences in preexisting circuit architecture of co-tuned neurons.
The Role of Human Platelet-Rich Plasma to Enhance the Differentiation from Adipose derived Mesenchymal Stem Cells into Cardiomyocyte: An Experimental Study
Authors: Suryawan I Gde Rurus , Andrianto  , Anggaraeni Arifta Devi , Agita Arisya , Nugraha Ricardo Adrian 
Published: December 2020

BackgroundAdipose derived mesenchymal stem cells (AMSCs) offer great potential to differentiate into cardiomyocyte. However, the optimal method to maximize the proliferation and differentiation is challenging. Platelet rich plasma (PRP) which contains high levels of diverse growth factors that can stimulate stem cell proliferation and differentiation in the context of cardiac tissue regenerationObjectiveTo analyze the effect of PRP administration on the AMSCs differentiation into cardiomyocyte and compare to the group without PRP administration.MethodsThis study is a true experimental randomized post-test design study. AMSCs were isolated from adipose tissues and cultured until 4 passages. The samples were divided into 3 groups, i.e. negative control (α-MEM), positive control (differentiation medium), and treatment group (PRP). The assessment of GATA-4 marker expression was conducted using flowcytometry on the fifth day and cTnT was conducted using immunocytochemistry on the tenth day to determine the differentiation to cardiomyocyte. Data analysis was conducted using T-test and One-Way ANOVA on normally distributed data determined through Shapiro Wilk test.ResultsFlowcytometry on GATA-4 expression revealed significant improvement on PRP group compared to negative and positive controls (67.04 ± 4.49 vs 58.15 ± 1.23 p < 0.05; 67.04 ± 4.49 vs 52.96 ± 2.02 p < 0.05). This was supported by the results of immunocytochemistry on troponin expression which revealed significant improvement on PRP group compared to negative and positive controls (38.13 ± 5.2 vs 10.73 ± 2.39 p < 0.05; 38.13 ± 5.2 vs 26.00 ± 0.4 p < 0.05). This was concordant to the hypothesis which stated that there was an effect of PRP administration on AMSCs differentiation into cardiomyocyte.ConclusionPRP administration on AMSCs culture significantly improve the differentiation to cardiomyocyte measured by GATA-4 and cTnT expressions.
Plasma neutralizing antibodies in an infant with interclade HIV-1 superinfection preferentially neutralize superinfecting HIV-1 strains
Authors: Mishra Nitesh , Sharma Shaifali , Dobhal Ayushman , Kumar Sanjeev , Chawla Himanshi , Singh Swarandeep , Singh Ravinder , Das Bimal Kumar , Lodha Rakesh , Kabra Sushil Kumar , Luthra Kalpana 
Published: December 2020

AbstractHIV-1 superinfection is defined as infection by an unrelated second strain of HIV-1 after seroconversion due to primary infecting strain and has been associated with development of breadth in the neutralizing antibody (nAb) response, altered disease progression and efficacy of antiretrovirals; though conflicting observations have also been reported. Superinfection has been reported in HIV-1 infected adults. Recently we observed that multivariant infection in infants was associated with early induction of plasma broadly neutralizing antibodies (bnAbs) targeting diverse autologous viruses, however, there is paucity of information on infants with HIV-1 superinfection. Furthermore, the mechanisms by which superinfection in an infant, after priming by an initial infection, potentiate the evolution of a bnAb response have not been evaluated. Herein, we performed a longitudinal analysis and observed evolution of nAb responses in an antiretroviral naïve perinatally HIV-1 infected infant, with interclade superinfection (clade C followed by a unique A1C recombinant). The nAb responses broadened rapidly after superinfection targeted an undefined glycan-dependent epitope on the superinfecting variant, while no enrichment of nAb response against the primary infecting strain occurred. Defining virological features in infants with sequential infection with highly divergent circulating viruses that improve nAb responses will contribute information that could be leveraged for optimization of multicomponent candidate vaccines.ImportanceHIV-1 infected infants develop bnAbs rapidly suggesting factors governing bnAb induction in infants are distinct from adults. HIV-1 superinfection is more common in adults whereas the stringent genetic bottleneck for transmission in infants often leads to infection by a single transmitted/founder HIV-1 strain. Longitudinal studies in infants with HIV-1 superinfection can provide key information on the viral factors that induce a bnAb response towards development of a polyvalent vaccine. Herein, we show that in infant who was sequentially infected with two HIV-1 strains from different clades, antibody responses were primarily generated against the superinfecting, second strain of HIV-1.These antibody responses were dependent on glycans, and targeted an undefined epitope in the C3V4 region of HIV-1 Env. A better understanding of how neutralizing antibody responses develop during natural HIV-1 superinfection in infants will provide information relevant to HIV Env vaccine development and evaluation.
Role of two metacaspases in development and pathogenicity of the Rice Blast fungus,Magnaporthe oryzae
Authors: Fernandez Jessie , Lopez Victor , Kinch Lisa , Pfeifer Mariel A. , Gray Hillery , Garcia Nalleli , Grishin Nick V. , Khang Chang-Hyun , Orth Kim 
Published: December 2020

ABSTRACTRice blast disease caused byMagnaporthe oryzaeis a devastating disease of cultivated rice worldwide. Infections by this fungus lead to a significant reduction in rice yields and threats to food security. To gain better insight into growth and cell death inM. oryzaeduring infection, we characterized two predictedM. oryzaemetacaspase proteins, MoMca1 and MoMca2. These proteins appear to be functionally redundant and are able to complement the yeast Yca1 homologue. Biochemical analysis revealed thatM. oryzaemetacaspases exhibited Ca2+dependent caspase activityin vitro. Deletion of bothMoMca1andMoMca2inM. oryzaeresulted in reduced sporulation, delay in conidial germination and attenuation of disease severity. In addition, the double ΔMomca1mca2mutant strain showed increased radial growth in the presence of oxidative stress. Interestingly, the ΔMomca1mca2strain showed an increase accumulation of insoluble aggregates compared to the wild-type strain during vegetative growth. Our findings suggest that MoMca1 and MoMca2 promote the clearance of insoluble aggregates inM. oryzae, demonstrating the important role these metacaspases have in fungal protein homeostasis. Furthermore, these metacaspase proteins may play additional roles, like in regulating stress responses, that would help maintain the fitness of fungal cells required for host infection.IMPORTANCEMagnaporthe oryzaecauses rice blast disease that threatens global food security by resulting in the severe loss of rice production every year. A tightly regulated life cycle allowsM. oryzaeto disarm the host plant immune system during its biotrophic stage before triggering plant cell death in its necrotrophic stage. The waysM. oryzaenavigates its complex life cycle remains unclear. This work characterizes two metacaspase proteins with peptidase activity inM. oryzaethat are shown to be involved in the regulation of fungal growth and development prior to infection by potentially helping maintain fungal fitness. This study provides new insight into the role of metacaspase proteins in filamentous fungi by illustrating the delays inM. oryzaemorphogenesis in the absence of these proteins. Understanding the mechanisms by whichM. oryzaemorphology and development promote its devastating pathogenicity may lead to the emergence of proper methods for disease control.
Effective connectivity extracts clinically relevant prognostic information from resting state activity in stroke
Authors: Adhikari Mohit H , Griffis Joseph , Siegel Joshua S. , de Schotten Michel Thiebaut , Deco Gustavo , Instabato Andrea , Gilson Mathieu , Corbetta Maurizio 
Published: December 2020

ABSTRACTRecent resting-state fMRI studies in stroke patients have identified two robust biomarkers of acute brain dysfunction: a reduction of inter-hemispheric functional connectivity (FC) between homotopic regions of the same network, and an abnormal increase of ipsilesional FC between task-negative and task-positive resting-state networks (RSNs). Whole-brain computational modeling studies, at the individual subject level, using undirected effective connectivity (EC) derived from empirically measured FC, have shown a reduction of measures of integration and segregation in stroke as compared to healthy brains. Here we employ a novel method, first, to infer whole-brain directional EC from zero-lagged and lagged FC, then, to compare it to empirically measured FC for predicting stroke vs. healthy status, and patient performance (zero, one, multiple deficits) across neuropsychological tests. We also investigated the accuracy of FC vs. model EC in predicting the long-term outcome from acute measures.Both FC and EC predicted healthy from stroke individuals significantly better than the chance-level, however, EC accuracy was significantly higher than that of FC at 1-2 weeks, three months, and one year post-stroke. The predictive FC links mainly included those reported in previous studies (within-network inter-hemispheric, and between task-positive and -negative networks intra-hemispherically). Predictive EC links included additional between-network links. EC was a better predictor than FC of the number of behavioral domains in which patients suffered deficits, both at two weeks and one-year post onset of stroke. Interestingly, patient deficits at one-year time point were better predicted by EC values at two weeks rather than at one-year time point. Our results thus demonstrate that the second-order statistics of fMRI resting-state activity at an early stage of stroke, derived from a whole-brain EC, estimated in a model fitted to reproduce the propagation of BOLD activity, has pertinent information for clinical prognosis.
Therapeutic effects of Chlorzoxazone, a BKCa channel agonist, in a mouse model of Fragile X syndrome
Authors: Lemaire-Mayo Valerie , Piquemal Marion , Crusio Wim E. , Louette Eric , Pietropaolo Susanna 
Published: December 2020

ABSTRACTFragile X syndrome (FXS) is an X-linked developmental disorder characterized by several behavioral abnormalities, including hyperactivity, sensory hyper-responsiveness and cognitive deficits, as well as autistic symptoms, e.g., reduced social interaction. These behavioural alterations are recapitulated by the major animal model of FXS, i.e., the Fmr1-KO mouse, which has been extensively employed to identify therapeutic targets for FXS, though effective pharmacological treatments are still lacking. Here we focused on the therapeutic role of large-conductance Calcium-dependent potassium (BKCa) channels, playing a crucial role in neuronal excitability and neurotransmitter release. Reduced expression/functionality of these channels has been described in FXS patients and mice, so that molecules activating these channels have been proposed as promising treatments for this syndrome. Here we performed an extensive characterization of the therapeutic impact of a novel BKCa agonist on FXS-like symptoms in the Fmr1-KO mouse model, employing a drug repurposing setting. We evaluated the acute and chronic effects of chlorzoxazone, i.e., a classical drug used for non-developmental muscular pathologies, on the locomotor, social, cognitive and sensory-motor alterations of Fmr1-KO mice and compared them with other pharmacological treatments recently proposed for FXS that instead do not target BKCa channels. Our results clearly demonstrate for the first time the marked efficacy of chlorzoxazone in treating all the behavioral abnormalities of FXS mice, thus encouraging the preferential use of this molecule over others for clinical applications in the field of FXS, and potentially of other neurodevelopmental disorders.
Plant sedimentary ancient DNA from Far East Russia covering the last 28 ka reveals different assembly rules in cold and warm climates
Authors: Huang Sichao , Stoof-Leichsenring Kathleen R. , Liu Sisi , Courtin Jeremy , Andreev Andrej A. , Pestryakova Luidmila. A. , Herzschuh Ulrike 
Published: December 2020

AbstractWoody plants are expanding into the Arctic under a warming climate. The related impact on plant diversity is not well understood because we have only limited knowledge about plant assembly rules and because of a lack of time-series of plant diversity. Here, we applied sedimentary ancient DNA metabarcoding using the plant-specificgandhprimers of thetrnLgene to a sediment record from Lake Ilirney (central Chukotka Far Eastern Russia) covering the last 28 thousand years. Our results show that forb-dominated steppe-tundra and Saliceae-rich dwarf-shrub tundra communities dominated during the cold climate before 14 ka, while deciduous erect-shrub tundra was abundant during the warm period between 14 and 0 ka.Larixinvasion during the late Holocene substantially lagged behind the period of densest vegetation and likely warmest period between 10 and 6 ka. Overall, we discovered the highest richness during 28–23 ka and a second richness peak during 13–10 ka: both periods are characterised by low shrub abundance. The richest communities during the cold pre-14 ka period were phylogenetically clustered, which probably originates from environmental filtering along with niche differentiation under limited resources. In contrast, the richest post-14 ka community was phylogenetically overdispersed, likely originating from an erratic recruitment process in the course of warming. Despite differences in timescale, some of our evidence can be relevant to arctic plant diversity changes. By analogy to the past, we expect a lagged response of tree invasion. In the long-term, ongoing expansion of deciduous shrubs will eventually result in a phylogenetically more diverse community but will also cause reduced plant taxonomic richness; however, richness may overshoot in the short-term.
Feasibility and application of polygenic score analysis to the morphology of human induced pluripotent stem cells
Authors: Coleman Jonathan R. I. 
Published: December 2020

AbstractGenome-wide association studies have identified thousands of significant associations between genetic variants and complex traits. Inferring biological insights from these associations has been challenging. One approach attempted has been to examine the effects of individual variants in cellular models. Here, I demonstrate the feasibility of examining the aggregate effect of many variants on cellular phenotypes. I examine the effects of polygenic scores for cross-psychiatric disorder risk, schizophrenia, body mass index and height on cellular morphology, using 1.5 million induced pluripotent stem cells (iPSC) from 60 European-ancestry donors from the Human iPSC Initiative dataset. I show that measuring multiple cells per donor provides sufficient power for polygenic score analyses, and that cross-psychiatric disorder risk is associated with cell area (p = 0.004). Combined with emerging methods of high-throughput iPSC phenotyping, cellular polygenic scoring is a promising method for understanding potential biological effects of the polygenic component of complex traits.
Duplex formation between the template and the nascent strand in the transcription-regulating sequences determines the site of template switching in SARS – CoV-2
Authors: D’souza Aaron R. , Buckingham Amanda , Salasc Fanny , Ingemarsdotter Carin , Iaconis Gennaro , Jarvis Isobel , Groom Harriet C. T. , Kenyon Julia , Lever Andrew M. L. 
Published: December 2020

ABSTRACTRecently published transcriptomic data of the SARS-CoV-2 coronavirus show that there is a large variation in the frequency and steady state levels of subgenomic mRNA sequences. This variation is derived from discontinuous subgenomic RNA synthesis where the polymerase switches template from a 3’ proximal genome body sequence to a 5’ untranslated leader sequence. This leads to a fusion between the common 5’ leader sequence and a 3’ proximal body sequence in the RNA product. This process revolves around a common core sequence (CS) that is present at both the template sites that make up the fusion junction. Base-pairing between the leader CS and the nascent complementary minus strand body CS, and flanking regions (together called the transcription regulating sequence, TRS) is vital for this template switching event. However, various factors can influence the site of template switching within the same TRS duplex. Here, we model the duplexes formed between the leader and complementary body TRS regions, hypothesising the role of the stability of the TRS duplex in determining the major sites of template switching for the most abundant mRNAs. We indicate that the stability of secondary structures and the speed of transcription play key roles in determining the probability of template switching in the production of subgenomic RNAs.
Evolutionarily ancient role of cholecystokinin-type neuropeptide signalling as an inhibitory regulator of feeding-related processes revealed in an echinoderm
Authors: Tinoco Ana B. , Barreiro-Iglesias Antón , Yañez-Guerra Luis Alfonso , Delroisse Jérôme , Zhang Ya , Gunner Elizabeth F. , Zampronio Cleidiane , Jones Alexandra M. , Egertová Michaela , Elphick Maurice R. 
Published: December 2020

AbstractCholecystokinin (CCK) / sulfakinin (SK)-type neuropeptides regulate feeding and digestion in chordates and protostomes (e.g. insects). Here we characterised CCK/SK-type signalling for the first time in a non-chordate deuterostome - the starfishAsterias rubens(phylum Echinodermata). In this species, two neuropeptides (ArCCK1, ArCCK2) derived from the precursor protein ArCCKP act as ligands for a CCK/SK-type receptor (ArCCKR) and are expressed in the nervous system, digestive system, tube feet and body wall. Furthermore, ArCCK1 and ArCCK2 cause dose-dependent contraction of cardiac stomach, tube foot and body wall apical muscle preparationsin vitroand injection of these neuropeptidesin vivotriggers cardiac stomach retraction and inhibition of the onset of feeding inA. rubens. Thus, an evolutionarily ancient role of CCK/SK-type neuropeptides as inhibitory regulators of feeding-related processes in the Bilateria has been conserved in the unusual and unique context of the extra-oral feeding behaviour and pentaradial body plan of an echinoderm.
The Personalized Proteome: Comparing Proteogenomics and Open Variant Search Approaches for Single Amino Acid Variant Detection
Authors: Salz Renee , Bouwmeester Robbin , Gabriels Ralf , Degroeve Sven , Martens Lennart , Volders Pieter-Jan , ’t Hoen Peter A.C. 
Published: December 2020

AbstractDiscovery of variant peptides such as single amino acid variant (SAAV) in shotgun proteomics data is essential for personalized proteomics. Both the resolution of shotgun proteomics methods and the search engines have improved dramatically, allowing for confident identification of SAAV peptides. However, it is not yet known if these methods are truly successful in accurately identifying SAAV peptides without prior genomic information in the search database. We studied this in unprecedented detail by exploiting publicly available long-read RNA seq and shotgun proteomics data from the gold standard reference cell line NA12878. Searching spectra from this cell line with the state-of-the-art open modification search engineionbotagainst carefully curated search databases resulted in 96.7% false positive SAAVs and an 85% lower true positive rate than searching with peptide search databases that incorporate prior genetic information. While adding genetic variants to the search database remains indispensable for correct peptide identification, inclusion of long-read RNA sequences in the search database contributes only 0.3% new peptide identifications. These findings reveal the differences in SAAV detection that result from various approaches, providing guidance to researchers studying SAAV peptides and developers of peptide spectrum identification tools.
A Synthetic Transcription Platform for Programmable Gene Expression in Mammalian Cells
Authors: Chen William C.W. , Gaidukov Leonid , Lai Yong , Wu Ming-Ru , Cao Jicong , Gutbrod Michael J. , Choi Gigi C.G. , Utomo Rachel P. , Chen Ying-Chou , Wroblewska Liliana , Kellis Manolis , Zhang Lin , Weiss Ron , Lu Timothy K. 
Published: December 2020

AbstractPrecise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. We created a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements expressed mammalian genes in a highly predictable and tunable manner. We demonstrated the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more activity than seen with the EF1α promoter, in multiple cell types. We used these circuits to program the secretion of human monoclonal antibodies and to control T-cell effector function marked by interferon-γ production. Antibody titers and interferon-γ concentrations significantly correlated with synthetic promoter strengths, providing a platform for programming gene expression and cellular function in diverse applications.