bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of FMRFamide on voltage-dependent currents in identified centrifugal neurons of the optic lobe of the cuttlefish,Sepia officinalis
Authors: Chrachri Abdesslam 
Published: October 2020

AbstractWhole-cell patch-clamp recordings from identified centrifugal neurons of the optic lobe in a slice preparation allowed the characterization of five voltage-dependent currents; two outward and three inward currents. The outward currents were; the 4-aminopyridine-sensitive transient potassium or A-current (IA), the TEA-sensitive sustained current or delayed rectifier (IK). The inward currents were; the tetrodotoxin-sensitive transient current or sodium current (INa). The second is the cobalt- and cadmium-sensitive sustained current which is enhanced by barium and blocked by the dihydropyridine antagonist, nifedipine suggesting that it could be the L-type calcium current (ICaL). Finally, another transient inward current, also carried by calcium, but unlike the L-type, this current is activated at more negative potentials and resembles the low-voltage-activated or T-type calcium current (ICaT) of other preparations.Application of the neuropeptide FMRFamide caused a significant attenuation to the peak amplitude of both sodium and sustained calcium currents without any apparent effect on the transient calcium current. Furthermore, FMRFamide also caused a reduction of both outward currents in these centrifugal neurons. The fact that FMRFamide reduced the magnitude of four of five characterized currents could suggest that this neuropeptide may act as a strong inhibitory agent on these neurons.SummaryFMRFamide modulate the ionic currents in identified centrifugal neurons in the optic lobe of cuttlefish: thus, FMRFamide could play a key role in visual processing of these animals.
Cardiac Sex Differences are Established Prior to Gonad Formation
Authors: Shi Wei , Sheng Xinlei , Dorr Kerry M. , Hutton Josiah E. , Davies Haley A. , Andrade Tia D. , Greco Todd M. , Hashimoto Yutaka , Federspiel Joel D. , Robbe Zachary L. , Chen Xuqi , Arnold Arthur P. , Cristea Ileana M. , Conlon Frank L. 
Published: October 2020

ABSTRACTMale and female disease states differ in their prevalence, treatment responses, and survival rates. In cardiac disease, women almost uniformly fare far worse than men. Though sex plays a critical role in cardiac disease, the mechanisms underlying sex differences in cardiac homeostasis and disease remain unexplained. Here, in adult and embryonic hearts we reveal sex-specific transcriptomes and proteomes and show that cardiac sex differences are predominately accounted for by post-transcriptional mechanisms. We found differential expression of male-female proteins in the cardiomyocytes. Using a quantitative proteomics-based approach, we characterized differential sex-specific enriched cardiac proteins, protein complexes, and biological sex processes in the context of global genetic diversity of the Collaborative Cross, an established surrogate for human diversity. We also found that sex differences in cardiac protein expression are established by both hormonal and sex chromosomal mechanisms. We have demonstrated the onset of sex-biased protein expression and discovered that sex disparities in heart tissue occur at the earliest stages of heart development at a period that preceeds mammalian gonadal development. Collectively, these findings may explain why congenital heart disease, a leading cause of death whose origin is often developmental, is sex biased. Our results reveal molecular foundations for differences in cardiac tissue that underlie sex disparities in health, disease, and treatment outcomes.
Reversal of visual feedback modulates somatosensory plasticity
Authors: Goldenkoff Elana R. , McGregor Heather R. , Mergos Joshua , Gholizadeh Puyan , Bridenstine John , Brown Matt J.N. , Vesia Michael 
Published: October 2020

AbstractReversed visual feedback during unimanual training increases transfer of skills to the opposite untrained hand and modulates plasticity in motor areas of the brain. However, it is unclear if unimanual training with reversed visual feedback also affects somatosensory areas. Here we manipulated visual input during unimanual training using left-right optical reversing spectacles and tested whether unimanual training with reversed vision modulates somatosensory cortical excitability to facilitate motor performance. Thirty participants practiced a unimanual ball-rotation task using the right hand with either left-right reversed vision (incongruent visual and somatosensory feedback) or direct vision (congruent feedback) of the moving hand. We estimated cortical excitability in primary somatosensory cortex (S1) before and after unimanual training by measuring somatosensory evoked potentials (SEPs). This was done by electrically stimulating the median nerve in the wrist while participants rested, and recording potentials over both hemispheres using electroencephalography. Performance of the ball-rotation task improved for both the right (trained) and left (untrained) hand after training across both direct and reversed vision conditions. Participants with direct vision of the right hand during training showed SEPs amplitudes increased bilaterally. In contrast, participants in the reversed visual condition showed attenuated SEPs following training. The results suggest that cortical suppression of S1 activity supports skilled motor performance after unimanual training with reversed vision, presumably by sensory gating of afferent signals from the movement. This finding provides insight into the mechanisms by which visual input interacts with the sensorimotor system and induces neuroplastic changes in S1 to support skilled motor performance.
Predator diversity and thermal niche complementarity attenuate indirect effects of warming on prey survival
Authors: Pepi Adam , McMunn Marshall 
Published: October 2020

AbstractClimate warming has broad-reaching effects on communities, and although much research has focused on direct abiotic effects, indirect effects of warming meditated through biotic interactions can be of equal or greater magnitude. A body of theoretical and empirical work has developed examining the effects of climate warming on predator-prey interactions, but most studies have focused on single predator and prey species. We develop a model with multiple predator species using simulated and measured predator thermal niches from a community of ants, to examine the influence of predator diversity and other aspects of community thermal niche on the indirect effects of climate warming on prey survival probability. We find that predator diversity attenuates the indirect effect of climate warming on prey survival probability, and that sufficient variation of predator thermal optima, closer prey and mean predator thermal optima, and higher predator niche complementarity increases the attenuation effect of predator diversity. We predict therefore that more diverse and complementary communities are likely more affected by direct versus indirect effects of climate warming, and vice versa for less diverse and complementary communities. If general, these predictions could lessen the difficulty of predicting the effects of climate warming on a focal species of interest.
LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection
Authors: Jones Bryan E. , Brown-Augsburger Patricia L. , Corbett Kizzmekia S. , Westendorf Kathryn , Davies Julian , Cujec Thomas P. , Wiethoff Christopher M. , Blackbourne Jamie L. , Heinz Beverly A. , Foster Denisa , Higgs Richard E. , Balasubramaniam Deepa , Wang Lingshu , Bidshahri Roza , Kraft Lucas , Hwang Yuri , Žentelis Stefanie , Jepson Kevin R. , Goya Rodrigo , Smith Maia A. , Collins David W. , Hinshaw Samuel J. , Tycho Sean A. , Pellacani Davide , Xiang Ping , Muthuraman Krithika , Sobhanifar Solmaz , Piper Marissa H. , Triana Franz J. , Hendle Jorg , Pustilnik Anna , Adams Andrew C. , Berens Shawn J. , Baric Ralph S. , Martinez David R. , Cross Robert W. , Geisbert Thomas W. , Borisevich Viktoriya , Abiona Olubukola , Belli Hayley M. , de Vries Maren , Mohamed Adil , Dittmann Meike , Samanovic Marie , Mulligan Mark J. , Goldsmith Jory A. , Hsieh Ching-Lin , Johnson Nicole V. , Wrapp Daniel , McLellan Jason S. , Barnhart Bryan C. , Graham Barney S. , Mascola John R. , Hansen Carl L. , Falconer Ester 
Published: October 2020

AbstractSARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection.One Sentence SummaryLY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.
Alternative splicing tunes sodium channels to support channel- and neuron-specific effects
Authors: Lignani Gabriele , Liavas Andrianos , Kullmann Dimitri M , Schorge Stephanie 
Published: October 2020

AbstractNeuronal excitability is tightly regulated, requiring rapidly activating and inactivating voltage-gated sodium channels to allow accurate temporal encoding of information. Alternative splicing greatly broadens the repertoire of channels, but the adaptive significance of this phenomenon is incompletely understood. An alternative splicing event that is conserved across vertebrates affects part of the first domain of sodium channels and modulates their availability after inactivation. Here we use this conserved splicing event to ask whether this modulation has consistent effects in different neuronal backgrounds, or whether a conserved splicing event can be exploited to produce distinct effects in different cell types. We show that the consequences of alternate splicing of human Nav1.1 and Nav1.2 for neuronal activity depend on whether they are expressed in the cell types where they normally predominate (interneurons or excitatory neurons, respectively). Splicing in the ‘adult’ isoform in both channels is sufficient to slow action potential rise times in all neurons. However, changes to both action potential half width and maximal firing rate are specific to cell type and channel, with each channel appearing tuned to mediate effects in its predominant neuronal background. Finally, we use dynamic clamp to demonstrate that alternative splicing in Nav1.1 changes how interneurons fire during epileptiform events. Our data show that, for sodium channels, despite conserved amino acid changes and similar effects on channel gating, alternative splicing has distinct impacts on neuronal properties, thus highlighting how closely sodium channels are tuned to distinct cellular backgrounds.
Keap1 binds cytokine promoters upon virus infection and moderates their induction by recruiting NFκB p50 and G9a-GLP
Authors: Burns Veronica Elizabeth , Kerppola Tom Klaus 
Published: October 2020

AbstractInnate immunity requires a balance of positive and negative regulators of cytokine transcription. Keap1 deletion in mice alters innate immunity and inflammation. We investigated the influence of Keap1 on cytokine gene induction by Sendai virus infection in mouse embryo fibroblasts (MEFs). Keap1 bound to theIfnb1, TnfandIl6promoters upon virus infection, and moderated viral induction of their transcription. Keap1 was required for viral induction of NFκB p50 and G9a-GLP lysine methyltransferase binding to these genes. Keap1 formed BiFC complexes with NFκB p50 that were localized to the nuclei in a subset of cells. Nrf2 counteracted viral induction of Keap1 binding to the promoters, and the effects of Keap1 on NFκB p50 and on G9a-GLP recruitment. Lysine methyltransferase inhibitors enhanced viral induction of transcription of the genes that were bound by Keap1 only in MEFs with intact Keap1, and not inKeap1-/-MEFs. They also enhanced NFκB p50 and NFκB p65 recruitment to these genes only in MEFs with intact Keap1, whereas they inhibited G9a-GLP recruitment. The reciprocal effects of Keap1 and of G9a-GLP lysine methyltransferase activity on chromatin binding by each other constitute a feedback circuit that moderates viral induction of cytokine transcription.SummaryVirus infection induces Keap1 binding to cytokine promoters, which recruits NFκB p50 and G9a-GLP and moderates their transcription.
Whole brain wiring diagram of oxytocin system in adult mice
Authors: Son Seoyoung , Manjila Steffy B. , Newmaster Kyra T. , Wu Yuan-ting , Vanselow Daniel J. , Ciarletta Matt , Anthony Todd E. , Cheng Keith C. , Kim Yongsoo 
Published: October 2020

AbstractOxytocin (OT) neurons regulate diverse physiological responses via direct connections with different neural circuits. However, the lack of comprehensive input-output wiring diagrams of OT neurons and their quantitative relationship with OT receptor (OTR) expression presents challenges to understanding circuit specific OT functions. Here, we establish a whole-brain distribution and anatomical connectivity map of OT neurons, and their relationship with OTR expression using cell type specific viral tools and high-resolution 3D mapping methods. We utilize a flatmap to describe OT neuronal expression in four hypothalamic domains including under-characterized OT neurons in the tuberal nucleus. OT neurons in the paraventricular hypothalamus (PVH) broadly project to nine functional circuits that control cognition, brain state, and somatic visceral response. In contrast, OT neurons in the supraoptic (SO) and accessory nuclei have limited central projection to a small subset of the nine circuits. Surprisingly, quantitative comparison between OT output and OTR expression showed no significant correlation across the whole brain, suggesting abundant indirect OT signaling in OTR expressing areas. Unlike output, OT neurons in both the PVH and SO receive similar mono-synaptic inputs from a subset of the nine circuits mainly in the thalamic, hypothalamic, and cerebral nuclei areas. Our results suggest that PVH-OT neurons serve as a central modulator to integrate external and internal information via largely reciprocal connection with the nine circuits while the SO-OT neurons act mainly as unidirectional OT hormonal output. In summary, our OT wiring diagram provides anatomical insights about distinct behavioral functions of OT signaling in the brain.Significance StatementOxytocin (OT) neurons regulate diverse physiological functions from pro-social behavior to pain sensation via central projection in the brain. Thus, understanding detailed anatomical connectivity of OT neurons can provide insight on circuit specific roles of OT signaling in regulating different physiological functions. Here, we utilize high resolution mapping methods to describe the 3D distribution, mono-synaptic input and long-range output of OT neurons, and their relationship with OT receptor (OTR) expression across the entire mouse brain. We found OT connections with nine functional circuits controlling cognition, brain state, and somatic visceral response. Furthermore, we identified a quantitatively unmatched OT-OTR relationship, suggesting broad indirect OT signaling. Together, our comprehensive OT wiring diagram advances our understanding of circuit specific roles of OT neurons.
Chicken cGAS senses fowlpox virus infection and regulates macrophage effector functions
Authors: Oliveira Marisa , Rodrigues Damaris Ribeiro , Guillory Vanaique , Kut Emmanuel , Giotis Efstathios S. , Skinner Michael A. , Guabiraba Rodrigo , Bryant Clare E , Ferguson Brian J 
Published: October 2020

AbstractThe anti-viral immune response is dependent on the ability of infected cells to sense foreign nucleic acids. In multiple species, the pattern recognition receptor (PRR) cyclic GMP-AMP synthase (cGAS) senses viral DNA as an essential component of the innate response. cGAS initiates a range of signalling outputs that are dependent on generation of the second messenger cGAMP that binds to the adaptor protein stimulator of interferon genes (STING). Here we show that in chicken macrophages, the cGAS/STING pathway is essential not only for the production of type-I interferons in response to intracellular DNA stimulation, but also for regulation of macrophage effector functions including the expression of MHC-II and co-stimulatory molecules. In the context of fowlpox, an avian DNA virus infection, the cGAS/STING pathway was found to be responsible for type-I interferon production and MHC-II transcription. The sensing of fowlpox virus DNA is therefore essential for mounting an anti-viral response in chicken cells and for regulation of a specific set of macrophage effector functions.
The restricted nature of protein glycosylation in the mammalian brain
Authors: Williams Sarah E. , Noel Maxence , Lehoux Sylvain , Cetinbas Murat , Xavier Ramnik J. , Sadreyev Ruslan , Scolnick Edward M. , Smoller Jordan W. , Cummings Richard D. , Mealer Robert G. 
Published: October 2020

SummaryGlycosylation is essential to brain development and function, though prior studies have often been limited to a single analytical technique. Using several methodologies, we analyzed Asn-linked (N-glycans) and Ser/Thr/Tyr-linked (O-glycans) protein glycosylation between brain regions and sexes in mice. Brain N-glycans were surprisingly less complex in sequence and variety compared to other tissues, consisting predominantly of high-mannose precursors and fucosylated/bisected structures. Most brain O-glycans were unbranched, sialylated O-GalNAc and O-mannose structures. A consistent pattern was observed between regions, and sex differences were minimal compared to those observed in plasma. Brain glycans correlate with RNA expression of their synthetic enzymes, and analysis of all glycosylation genes in humans showed a global downregulation in the brain compared to other tissues. We hypothesize that the restricted repertoire of protein glycans arises from their tight regulation in the brain. These results provide a roadmap for future studies of glycosylation in neurodevelopment and disease.
Deletion ofGremlin-2alters estrous cyclicity and disrupts female fertility in mice
Authors: Rydze Robert T. , Patton Bethany , Salazar-Torralba Hannia , Briley Shawn , Gipson Gregory , James Rebecca , Rajkovic Aleksandar , Thompson Thomas , Pangas Stephanie A. 
Published: October 2020

AbstractMembers of the differential screening-selected gene aberrative in neuroblastoma (DAN) protein family are developmentally conserved extracellular binding proteins that antagonize bone morphogenetic protein (BMP) signaling. This protein family includes the Gremlin proteins, GREM1 and GREM2, which are known to have key functions during embryogenesis and adult physiology. While BMPs play essential roles in adult female reproductive physiology, the role of the DAN family in ovarian function is less understood. We generated mice null forGrem2to study its role in female fertility in addition to screening patients with primary ovarian insufficiency for variants in GREM2.Grem2-/-mice are viable and femaleGrem2-/-mice have diminished fecundity and irregular estrous cycles. This is accompanied by reduced serum levels of anti-Müllerian hormone, a marker of the ovarian reserve, in adult mice. Alterations in ovarian expression of inhibin and activin subunit genes, which are required for regulation of the hypothalamic-pituitary-ovarian (HPO) axis, were identified. WhileGrem2mRNA transcript was not detected in the pituitary,Grem2was expressed in the hypothalami of wild type female mice. Additionally, screening 106 women with primary ovarian insufficiency identified one individual with a heterozygous variant in GREM2 that lies within the predicted BMP-GREM2 interface. In total, these data suggest thatGrem2is necessary for female fecundity by playing a novel role in regulating the HPO axis and possibly contributing to female reproductive disease.
Megasphaerain the stool microbiota is negatively associated with diarrheal cryptosporidiosis
Authors: Carey Maureen A. , Medlock Gregory L. , Alam Masud , Kabir Mamun , Uddin Md Jashim , Nayak Uma , Papin Jason , Faruque A.S.G , Haque Rashidul , Petri William A. , Gilchrist Carol A. 
Published: October 2020

ABSTRACTBackgroundThe protozoan parasites in theCryptosporidiumgenus cause both acute diarrheal disease and subclinical (i.e. non-diarrheal) disease. It is unclear if the microbiota can influence the manifestation of diarrhea during aCryptosporidiuminfection.MethodsTo characterize the role of the gut microbiota in diarrheal cryptosporidiosis, the microbiome composition of both diarrheal and surveillanceCryptosporidium-positive fecal samples was evaluated using 16S rRNA gene sequencing. Additionally, the microbiome composition prior to infection was examined to test whether a preexisting microbiome profile could influence theCryptosporidiuminfection phenotype.ResultsFecal microbiome composition was associated with diarrheal symptoms at two timepoints.Megasphaerawas significantly less abundant in diarrheal samples when compared to subclinical samples at the time ofCryptosporidiumdetection (log2(fold change) = -4.3,p=10−10) and prior to infection (log2(fold change) = -2.0,p=10−4). Random forest classification also identifiedMegasphaeraabundance in the pre- and post-exposure microbiota.as predictive of a subclinical infection.ConclusionsMicrobiome composition broadly, and specifically lowMegasphaeraabundance, was associated with diarrheal symptoms prior to and at the time ofCryptosporidiumdetection. This observation suggests that the gut microenvironment may play a role in determining the severity of aCryptosporidiuminfection.SummaryMegasphaeraabundance in the stool of Bangladeshi infants is associated with the development of diarrhea upon infection with theCryptosporidiumparasite.
The impact of supply chain relationship quality on knowledge sharing and innovation performance: evidence from Chinese manufacturing industry
Authors: Li Gang 
Published: October 2020

Purpose
This study aims to investigate the impact mechanism of supply chain relationship quality on knowledge sharing and firms’ innovation performance during supply chain collaborative innovation.

Design/methodology/approach
A conceptual model linking supply chain relationship quality, knowledge sharing and firms’ innovation performance is developed, and the hypotheses of the relationships among them are proposed. To test these hypotheses with structural equation modeling, this study conducts a survey of 287 Chinese manufacturing firms that carried out collaborative innovation with supply chain partners.

Findings
Supply chain relationship quality has a significant positive effect on tacit knowledge sharing but its positive effect on explicit knowledge sharing is not significant. Both explicit and tacit knowledge sharing across supply chain enterprises positively influence firms’ innovation performance. Supply chain relationship quality influences firms’ innovation performance directly as well as indirectly through the mediating roles of explicit and tacit knowledge sharing.

Originality/value
This study provides empirical evidence of supply chain relationship quality’s direct and indirect effects through explicit and tacit knowledge sharing on firms’ innovation performance. This study also provides supply chain practitioners with better understanding of the importance of developing relationship quality and knowledge sharing across supply chain as they are positively associated with firms’ innovation performance.