bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cowboy effect: robot gaze influences human decisions
Authors: Belkaid Marwen , Kompatsiari Kyveli , de Tommaso Davide , Zablith Ingrid , Wykowska Agnieszka 
Published: October 2020

AbstractIn most everyday life situations, the brain needs to engage not only in making decisions, but also in anticipating and predicting the behavior of others. In such contexts, gaze can be highly informative about others’ intentions, goals and upcoming decisions. Here, we investigated whether a humanoid robot’s gaze (mutual or averted) influences the way people strategically reason in a social decisionmaking context. Specifically, participants played a strategic game with the robot iCub while we measured their behavior and neural (EEG) activity. Participants were slower to respond when iCub established mutual gaze prior to their decision, relative to averted gaze. This was associated with a higher decision threshold in the drift diffusion model and accompanied by more synchronized EEG alpha activity. In addition, we found that participants reasoned about the robot’s actions in both conditions. However, those who mostly experienced the averted gaze were more likely to adopt a self-oriented strategy and their neural activity showed higher sensitivity to outcome. Altogether, these findings suggest that robot gaze acts as a strong social signal for humans, modulating response times, decision threshold, neural synchronization, as well as choice strategies and sensitivity outcomes. This has strong implications for all contexts involving human-robot interaction, from robotics to clinical applications.
The molecular coupling between substrate recognition and ATP turnover in a AAA+ hexameric helicase loader
Authors: Puri Neha , Fernandez Amy J. , Murray Valerie L. O’Shea , McMillan Sarah , Keck James L. , Berger James M. 
Published: October 2020

ABSTRACTIn many bacteria and in eukaryotes, replication fork establishment requires the controlled loading of hexameric, ring-shaped helicases around DNA by AAA+ ATPases. How loading factors use ATP to control helicase deposition is poorly understood. Here, we dissect how specific ATPase elements ofE. coliDnaC, an archetypal loader for the bacterial DnaB helicase, play distinct roles in helicase loading and the activation of DNA unwinding. We identify a new element, the arginine-coupler, which regulates the switch-like behavior of DnaC to prevent futile ATPase cycling and maintains loader responsiveness to replication restart systems. Our data help explain how the ATPase cycle of a AAA+-family helicase loader is channeled into productive action on its target; comparative studies indicate elements analogous to the Arg-coupler are present in related, switch-like AAA+ proteins that control replicative helicase loading in eukaryotes, as well as polymerase clamp loading and certain classes of DNA transposases.
Robust Mendelian randomization in the presence of residual population stratification, batch effects and horizontal pleiotropy
Authors: Cinelli Carlos , LaPierre Nathan , Hill Brian L. , Sankararaman Sriram , Eskin Eleazar 
Published: October 2020

ABSTRACTMendelian Randomization (MR) exploits genetic variants as instrumental variables to estimate the causal effect of an “exposure” trait on an “outcome” trait from observational data. However, the validity of such studies is threatened by population stratification, batch effects, and horizontal pleiotropy. Although a variety of methods have been proposed to partially mitigate those problems, residual biases may still remain, leading to highly statistically significant false positives in large genetic databases. Here, we describe a suite of sensitivity analysis tools for MR that enables investigators to properly quantify the robustness of their findings against these (and other) unobserved validity threats. Specifically, we propose the routine reporting of sensitivity statistics that can be used to readily quantify the robustness of a MR result: (i) the partialR2of the genetic instrument with the exposure and the outcome traits; and, (ii) therobustness valueof both genetic associations. These statistics quantify theminimal strengthof violations of the MR assumptions that would be necessary to explain away the MR causal effect estimate. We also provide intuitive displays to visualize the sensitivity of the MR estimate to any degree of violation, and formal methods tobound the worst-case biascaused by violations in terms of multiples of the observed strength of principal components, batch effects, as well as putative pleiotropic pathways. We demonstrate how these tools can aid researchers in distinguishing robust from fragile findings, by showing that the MR estimate of the causal effect of body mass index (BMI) on diastolic blood pressure is relatively robust, whereas the MR estimate of the causal effect of BMI on Townsend deprivation index is relatively fragile.
Plant Scaffolds Support Motor Recovery and Regeneration in Rats after Traumatic Spinal Cord Injury
Authors: Modulevsky Daniel J. , Cuerrier Charles M. , Leblanc-Latour Maxime , Hickey Ryan J. , Obhi Ras-Jeevan K. , Shore Isabel , Galuta Ahmad , Walker Krystal L. A. , Tsai Eve C. , Pelling Andrew E. 
Published: October 2020

ABSTRACTAs of yet, no standard of care incorporates biomaterials to treat traumatic spinal cord injury (SCI). However, intense development of biomaterials for treating SCI has focused on fabricating microscale channels to support the regrowth of axons while minimizing scar formation. We previously demonstrated that plant tissues could be decellularized and processed to form sterile, biocompatible and implantable biomaterials that support cell infiltration and vascularizationin vivo. Vascularized plant tissues contain continuous microscale channels with geometries relevant for supporting neural regeneration. We hypothesized that decellularized vascular bundles would support neural regeneration and motor recovery in SCI. Sprague Dawley rats received a complete T8-T9 spinal cord transection and were implanted with acellular plant-derived scaffolds and allowed to recover over 28 weeks. Animals that received the scaffolds alone, with no other therapeutic compounds, demonstrated a significant and stable partial improvement in motor function compared to control animals as early as week 4 post-injury. Hind-limb motor function did not deteriorate over the remaining 28 weeks. Histological analysis revealed minimal astrocyte scarring at the spinal cord - scaffold interface, aligned axonal projection through the scaffolds, populations of serotonergic neurons and Schwann cells, laminin and collagen deposition and the presence of blood vessels. Axonal reconnection via the scaffold was also confirmed by Fluro-gold retrograde tracing. Taken together, our work defines a novel route for building upon naturally occurring plant microarchitectures to support the repair of the spinal cord post-injury. Notably, these results were achieved without the use of growth factors, stem/progenitor cells, or any other interventions.
Integrated Single Cell Atlas of Endothelial Cells of the Human Lung
Authors: Schupp Jonas C. , Adams Taylor S. , Cosme Carlos , Raredon Micha Sam Brickman , Omote Norihito , De Frias Sergio Poli , Rose Kadi-Ann , Manning Edward , Sauler Maor , DeIuliis Giuseppe , Ahangari Farida , Neumark Nir , Yuan Yifan , Habermann Arun C. , Gutierrez Austin J. , Bui Linh T. , Meyer Kerstin B. , Nawijn Martijn C. , Teichmann Sarah A. , Banovich Nicholas E. , Kropski Jonathan A. , Niklason Laura E. , Pe’er Dana , Yan Xiting , Homer Robert , Rosas Ivan O. , Kaminski Naftali 
Published: October 2020

AbstractBackgroundDespite its importance in health and disease, the cellular diversity of the lung endothelium has not been systematically characterized in humans. Here we provide a reference atlas of human lung endothelial cells (ECs), to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium, both in health and disease.MethodsWe reprocessed control single cell RNA sequencing (scRNAseq) data from five datasets of whole lungs that were used for the analysis of pan-endothelial markers, we later included a sixth dataset of sorted control EC for the vascular subpopulation analysis. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by immunohistochemistry andin situhybridization. Signaling network between different lung cell types was studied using connectomic analysis. For cross species analysis we applied the same methods to scRNAseq data obtained from mouse lungs.ResultsThe six lung scRNAseq datasets were reanalyzed and annotated to identify over 15,000 vascular EC cells from 73 individuals. Differential expression analysis of EC revealed signatures corresponding to endothelial lineage, including pan-endothelial, pan-vascular and subpopulation-specific marker gene sets. Beyond the broad cellular categories of lymphatic, capillary, arterial and venous ECs we found previously indistinguishable subpopulations; among venous EC we identified two previously indistinguishable populations, pulmonary-venous ECs (COL15A1neg) localized to the lung parenchyma and systemic-venous ECs (COL15A1pos) localized to the airways and the visceral pleura; among capillary EC we confirmed their subclassification into recently discovered aerocytes characterized by EDNRB, SOSTDC1 and TBX2 and general capillary EC. We confirmed that all six endothelial cell types, including the systemic-venous EC and aerocytes are present in mice and identified endothelial marker genes conserved in humans and mice. Ligand-Receptor connectome analysis revealed important homeostatic crosstalk of EC with other lung resident cell types. Our manuscript is accompanied by an online data mining tool (www.LungEndothelialCellAtlas.com).ConclusionOur integrated analysis provides the comprehensive and well-crafted reference atlas of lung endothelial cells in the normal lung and confirms and describes in detail previously unrecognized endothelial populations across a large number of humans and mice.
The RNA-binding protein HuR promotes nonalcoholic steatohepatitis (NASH) progression by enhancing death signaling pathway
Authors: Li Xinzhi , Yuan Bingchuan , Yao Zhicheng , Sun Xu , Guo Weixiang , Chen Zheng 
Published: October 2020

AbstractHepatocyte death triggers liver inflammation, liver injury, and fibrosis, which contributes to non-alcoholic steatohepatitis (NASH) pathogenesis. However, whether RNA processing regulates death signaling pathway during NASH progression is not investigated. In this study, we show that HuR, a widely expressed RNA-binding protein, promotes NASH progression by increasing DR5/caspase8/caspase3-mediated hepatocyte death. Cytosolic HuR levels are abnormally elevated in human patients with NASH. Hepatocyte-specific deletion ofHuRprotects against MCD-induced NASH by decreasing liver steatosis, inflammation and cell death, whereas hepatic overexpression of HuR induces liver injury by increasing DR5-induced hepatocyte death. Furthermore, in primary hepatocytes, HuR deficiency ameliorates PA&TNFα-induced hepatocyte death due to decreased DR5/caspase8/caspase 3 signaling pathway while overexpression of HuR induces hepatocyte death by increasing DR5/caspase8/caspase 3 signaling pathway. Mechanistically, HuR directly binds to 3′-UTR of DR5 transcript and promotes its mRNA stability, contributing to the hepatocyte death during NASH progression. Our data reveal a novel mechanism by which HuR promotes mRNA stability of DR5, which contributes to NASH progression.
Inhibitory interneurons show early dysfunction in a SOD1 mouse model of amyotrophic lateral sclerosis
Authors: Cavarsan C. F. , Steele P. R. , Genry L. T. , Reedich E.J. , McCane L. M. , LaPre K. J. , Puritz A. C. , Manuel M. , Katenka N. , Quinlan K. A. 
Published: October 2020

AbstractFew studies in amyotrophic lateral sclerosis (ALS) measure effects of the disease on inhibitory interneurons synapsing onto motoneurons (MNs). However, inhibitory interneurons could contribute to dysfunction, particularly if altered before MN neuropathology, and establish a long-term imbalance of inhibition / excitation. We directly assessed excitability and morphology of glycinergic (GlyT2 expressing) ventral lumbar interneurons from SOD1G93AGlyT2eGFP (SOD1) and wildtype GlyT2eGFP (WT) mice on postnatal days 6-10. Patch clamp revealed dampened excitability in SOD1 interneurons, including depolarized persistent inward currents (PICs), increased voltage and current threshold for firing action potentials, along with a marginal decrease in afterhyperpolarization (AHP) duration. Primary neurites of ventral SOD1 inhibitory interneurons were larger in volume and surface area than WT. GlyT2 interneurons were then divided into 3 subgroups based on location: (1) interneurons within 100 μm of the ventral white matter, where Renshaw cells (RCs) are located, (2) interneurons interspersed with MNs in lamina IX, and (3) interneurons in the intermediate ventral area including laminae VII and VIII. Ventral interneurons in the RC area were the most profoundly affected, exhibiting more depolarized PICs and larger primary neurites. Interneurons in lamina IX had depolarized PIC onset. In lamina VII-VIII, interneurons were least affected. In summary, inhibitory interneurons show very early region-specific perturbations poised to impact excitatory / inhibitory balance of MNs, modify motor output, and provide early biomarkers of ALS. Therapeutics like riluzole which universally reduce CNS excitability could exacerbate the inhibitory dysfunction described here.Abstract FigureAbstract Figure:SOD1 glycinergic interneurons in the ventral horn show altered morphology and excitability, including depolarization of PICs, depolarized threshold, shorter AHPs, smaller somata and larger primary neurites. Ventrally located interneurons are the most prominently affected.Key Points SummarySpinal inhibitory interneurons could contribute to amyotrophic lateral sclerosis (ALS) pathology, but their excitability has never been directly measured.We studied the excitability and morphology of glycinergic interneurons in early postnatal transgenic mice (SOD1G93AGlyT2eGFP).Interneurons were less excitable and had marginally smaller somas but larger primary neurites in SOD1 mice.GlyT2 interneurons were analyzed according to their localization within the ventral spinal cord. Interestingly, the greatest differences were observed in the most ventrally-located interneurons.We conclude that inhibitory interneurons show presymptomatic changes that may contribute to excitatory / inhibitory imbalance in ALS.
Computational study of the effect of hypoxia on cancer response to radiation treatment
Authors: Korhonen T. , Lagerlöf J. H. , Muntean A. 
Published: October 2020

AbstractWe perform a computational study of the propagation of the oxygen concentration within a two-dimensional slice of a heterogeneous tumour region where the position and shape of the blood vessels are known. Exploiting the parameters space, we explore which effect is noticeable what concerns the formation of hypoxic zones. We use this information to anticipate a patient-specific radiation treatment with controlled response of the cancer growth.
Prediction andin vitrosilencing of two lipid biosynthetic genes viz.SCDandSREBP1in chicken using RNA interference
Authors: Sagar N. Govardhana , Prasad A. Rajendra , Chatterjee R.N. , Kumar Pushpendra , Bhushan Bharat , Vishnu P. Guru , Bhattacharya T. K. 
Published: October 2020

AbstractRNA interference is a widely used post transcriptional silencing mechanism for suppressing expression of the target gene. In the current study, five shRNA molecules each againstSCDandSREBP1genes were designed after considering the parameters like secondary structures of shRNA constructs, mRNA target regions, GC content and thermodynamic properties (ΔG overall, ΔG duplex and ΔG break-target) to knockdown their expression. After successful transfection of these shRNA molecules into the chicken embryonic hepatocyte culture, expression of the target genes were monitored by real time PCR. Significant reduction (P<0.05) in the expression ofSCDandSREBP1genes with minimal activation of immune response genes in hepatocytes was observed after transfecting the shRNA molecules into them. The shRNA constructs againstSCDgene showed the knock down efficiency ranged from 20.4% to 74.2%. In case of shRNA constructs againstSREBP1gene, they showed knock down efficiency ranging from 26.8% to 95.85%. These results clearly demonstrated the successful down regulation of the gene expression by designed shRNA molecules against both the target genes underin vitrocondition. The shRNA2 molecule forSCDgene and the shRNA1 molecule forSREBP1gene were found as the best among all the shRNA molecules used for silencing the target genes under cell culture system. It is concluded that the shRNA molecules designed against SCD and SREBP1 genes showed potential to silence the expression of these genes under in vitro chicken embryonic hepatocyte cell culture system.
MutatingPINK1gene by paired truncated sgRNA/Cas9-D10A in Cynomolgus Monkey
Authors: Chen Zhenzhen , Wang Jianying , Kang Yu , Yang Qiaoyan , Gu Xueying , Zhi Dalong , Yan Li , Shen Bin , Niu Yuyu 
Published: October 2020

AbstractMutations ofPINK1cause early-onset Parkinson’s disease (PD) with selective neurodegeneration in humans. However,currentPINK1knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients, indicating that it is essential to generatePINK1disease models in non-human primates (NHPs) that are highly close to humans, to investigate the unique function of PINK1 in primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9, both enabling the reduction of the off-target effect without apparently compromising the on-target editing, are two optimized strategies in applying the CRISPR/Cas9 system to establish disease animal models. Here, we combined the two strategies and injected Cas9-D10A mRNA and two truncated sgRNAs into one-cell-stage cynomolgus zygotes to targetPINK1gene. We show precise and efficient gene editing of the target site in the three new born cynomolgus monkeys. The frame shift mutations ofPINK1in mutant fibroblasts leaded to the reduction of the mRNA, However, western-blot and immunofluorescencestaining confirmed the PINK1 proteinlevels werecomparable to that in the wild-type fibroblasts. We further reprogramed mutant fibroblast into induced pluripotent stem cells (iPSCs) and they show similar ability of differentiation into dopamine (DA) neurons. Taken together, our results showed that coinjection of Cas9-D10A nickase mRNA and sgRNA into one-cell-stage cynomolgus embryos enable the generation of human disease models in NHPs and the target editing by paired truncated sgRNA/Cas9-D10A inPINK1gene exon 2 did not impact the protein expression.
Viral susceptibility across host species is largely independent of dietary protein to carbohydrate ratios
Authors: Roberts Katherine E , Longdon Ben 
Published: October 2020

AbstractThe likelihood of a successful host shift of a parasite to a novel host species can be influenced by environmental factors that can act on both the host and parasite. Changes in nutritional resource availability have been shown to alter pathogen susceptibility and the outcome of infection in a range of systems. Here we examined how dietary protein to carbohydrate altered susceptibility in a large cross infection experiment. We infected 27 species of Drosophilidae with an RNA virus on three food types of differing protein to carbohydrate ratios. We then measured how viral load and mortality across species was affected by changes in diet. We found that changes in the protein:carbohydrate in the diet did not alter the outcomes of infection, with strong positive inter-species correlations in both viral load and mortality across diets, suggesting no species by diet interaction. Mortality and viral load were strongly positively correlated, and this association was consistent across diets. This suggests changes in diet may give consistent outcomes across host species, and may not be universally important in determining host susceptibility to pathogens.Twitter summaryNo role of host diet in susceptibility to a novel viral pathogen across host speciesImpact StatementA successful host shift of a parasite from one susceptible species to a novel host can be influenced by many ecological factors. Changes in host diet can alter the immune response and outcomes of host–parasite interactions and could potentially alter the outcome of a virus host shift. To investigate, we infected 27 species of Drosophilidae with an RNA virus (DCV) across three food types with differing protein to carbohydrate ratios. We then looked at pathogen loads and survival of infected hosts compared to uninfected controls. Changes in the ratio of protein to carbohydrate did not alter susceptibility to DCV across host species.
Compensatory hepatic adaptation accompanies permanent absence of intrahepatic biliary network due to YAP1 loss in liver progenitors
Authors: Molina Laura M. , Zhu Junjie , Li Qin , Pradhan-Sundd Tirthadipa , Sayed Khaled , Jenkins Nathaniel , Vats Ravi , Ko Sungjin , Hu Shikai , Poddar Minakshi , Singh Sucha , Tao Junyan , Sundd Prithu , Singhi Aatur , Watkins Simon , Ma Xiaochao , Benos Panayiotis V. , Feranchak Andrew , Nejak-Bowen Kari , Watson Alan , Bell Aaron , Monga Satdarshan P. 
Published: October 2020

SummaryYAP1 regulates cell plasticity during liver injury, regeneration and cancer, but its role in liver development is unknown. YAP1 activity was detected in biliary cells and in cells at the hepato-biliary bifurcation in single-cell RNA-sequencing analysis of developing livers. Hepatoblast deletion ofYap1led to no impairment in Notch-driven SOX9+ ductal plate formation, but prevented the formation of the abutting second layer of SOX9+ ductal cells, blocking the formation of a patent intrahepatic biliary tree. Intriguingly, the mice survived for 8 months with severe cholestatic injury and without any hepatocyte-to-biliary transdifferentiation. Ductular reaction in the perihilar region suggested extrahepatic biliary proliferation likely seeking the missing intrahepatic biliary network. Long-term survival of these mice occurred through hepatocyte adaptation via reduced metabolic and synthetic function including altered bile acid metabolism and transport. Overall, we show YAP1 as a key regulator of bile duct development while highlighting a profound adaptive capability of hepatocytes.
Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878
Authors: Khatri Bhagwati , Keeble James , Dagg Belinda , Kaveh Daryan A. , Hogarth Philip J. , Ho Mei Mei 
Published: October 2020

AbstractIn this study, 2 strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3×105to 30 CFU/mouse, followed by either immunogenicity evaluation or aerosol infection withMycobacterium tuberculosis(a laboratory strain H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3×105– 3000 CFU (BALB/c) and 3×105-300 CFU (CB6F1). Whereas, both strains of mice when infected with H37Rv, significant protection was seen in BCG doses at 3×105- 300 CFU. Immunological evaluation revealed interesting results; i) both strains of mice demonstrated a significant increase in the frequencies of BCG-specific IFNγ+IL2+TNFα+CD4 T cells in the BCG doses at 3×105– 3000 CFU (BALB/c) and 3×105- 300 CFU (CB6F1); ii) secretion of IL2 and IFNγ were correlated with the bacterial burden in the lungs of HN878 infected CB6F1 mice. The study demonstrated a BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight index) is protective in both strains of mice and the use of a virulent clinical isolate in testing new tuberculosis vaccine/advancing research is recommended.