bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-GlcNAcylation, oxidation and CaMKII contribute to atrial fibrillation in type 1 and type 2 diabetes by distinct mechanisms
Authors: Mesubi Olurotimi O. , Rokita Adam G. , Abrol Neha , Wu Yuejin , Chen Biyi , Wang Qinchuan , Granger Jonathan M. , Tucker-Bartley Anthony , Luczak Elizabeth D. , Murphy Kevin R. , Umapathi Priya , Banerjee Partha S. , Boronina Tatiana N. , Cole Robert N. , Maier Lars S. , Wehrens Xander H. , Pomerantz Joel L. , Song Long-Sheng , Ahima Rexford S. , Hart Gerald W. , Zachara Natasha E. , Anderson Mark E. 
Published: February 2020

AbstractDiabetes mellitus and atrial fibrillation (AF) are major unsolved public health problems, and diabetes is an independent risk factor for AF in patients. However, the mechanism(s) underlying this clinical association is unknown. Elevated proteinO-GlcNAcylation (OGN) and reactive oxygen species (ROS) are increased in diabetic hearts, and calmodulin kinase II (CaMKII) is a proarrhythmic signal that may be activated by OGN (OGN-CaMKII) and ROS (ox-CaMKII). We induced type 1 (T1D) and type 2 diabetes (T2D) in a portfolio of genetic mouse models capable of dissecting the role of OGN and ROS at CaMKII and the type 2 ryanodine receptor (RyR2), an intracellular Ca2+channel implicated as an important downstream mechanism of CaMKII- mediated arrhythmias. Here we show that T1D and T2D significantly increased AF, similar to observations in patients, and this increase required CaMKII. While T1D and T2D both require ox-CaMKII to increase AF, they respond differently to loss of OGN-CaMKII or OGN inhibition. Collectively, our data affirm CaMKII as a critical proarrhythmic signal in diabetic AF, and suggest ROS primarily promotes AF by ox-CaMKII, while OGN promotes AF by diverse mechanisms and targets, including CaMKII and RyR2. The proarrhythmic consequences of OGN- and ox-CaMKII differ between T1D and T2D. These results provide new and unanticipated insights into the mechanisms for increased AF in diabetes mellitus, and suggest successful future therapies will need to be different for AF in T1D and T2D.
Keratins and Plakin family cytolinker proteins control the length of epithelial microridge protrusions
Authors: Inaba Yasuko , Chauhan Vasudha , van Loon Aaron Paul , Choudhury Lamia Saiyara , Sagasti Alvaro 
Published: February 2020

ABSTRACTActin filaments and microtubules create diverse cellular protrusions, but intermediate filaments, the strongest and most stable class of cytoskeletal elements, are not known to directly participate in the formation of protrusions. Here we show that Keratin intermediate filaments directly regulate the morphogenesis of microridges, elongated protrusions from mucosal epithelial cells arranged in elaborate fingerprint-like patterns. Developing microridges on zebrafish skin cells contained both Actin and Keratin filaments. Keratin filaments maintained microridges upon F-actin disruption, and overexpressing Keratins lengthened microridges. Envoplakin and Periplakin, Plakin family cytolinkers that bind to F-actin and Keratins, localized to microridges and were required for their morphogenesis. Strikingly, Plakin protein levels directly determined microridge length. An actin-binding domain of Periplakin was required to initiate microridge morphogenesis, whereas Periplakin-Keratin binding was required to stabilize and elongate microridges. Our results thus separate microridge morphogenesis into two steps with differential requirements for cytoskeletal elements, expand our understanding of intermediate filament functions, and identify microridges as cellular protrusions that integrate actin and intermediate filaments.
Similar visual perception in GCaMP6 transgenic mice despite differences in learning and motivation
Authors: Groblewski Peter A. , Ollerenshaw Douglas R. , Kiggins Justin , Garrett Marina , Mochizuki Chris , Casal Linzy , Cross Sissy , Mace Kyla , Swapp Jackie , Manavi Sahar , Williams Derric , Mihalas Stefan , Olsen Shawn R. 
Published: February 2020

AbstractTo study mechanisms of perception and cognition, neural measurements must be made during behavior. A goal of theAllen Brain Observatoryis to map activity in distinct cortical cell classes during visual processing and behavior. Here we characterize learning and performance of five GCaMP6-expressing transgenic lines trained on a visual change detection task. We used automated training procedures to facilitate comparisons across mice. Training times varied, but most transgenic mice learned the task. Motivation levels also varied across mice. To compare mice in similar motivational states we subdivided sessions into over-, under-, and optimally motivated periods. When motivated, the pattern of perceptual decisions were highly correlated across transgenic lines, although overall d-prime was lower in one line labeling somatostatin inhibitory cells. These results provide important context for using these mice to map neural activity underlying perception and behavior.
Spatiotemporal Dynamics of Orthographic and Lexical Processing in the Ventral Visual Pathway
Authors: Woolnough Oscar , Donos Cristian , Rollo Patrick S. , Forseth Kiefer J. , Lakretz Yair , Crone Nathan E. , Fischer-Baum Simon , Dehaene Stanislas , Tandon Nitin 
Published: February 2020

AbstractReading is a rapid, distributed process that engages multiple components of the ventral visual stream. However, the neural constituents and their interactions that allow us to identify written words are not well understood. Using direct intracranial recordings in a large cohort of humans, we comprehensively isolated the spatiotemporal dynamics of visual word recognition across the entire left ventral occipitotemporal cortex. The mid-fusiform cortex is the first region that is sensitive to word identity and to both sub-lexical and lexical frequencies. Its activation, response latency and amplitude, are highly dependent on the statistics of natural language. Information about lexicality and word frequency propagates posteriorly from this region to traditional visual word form regions and to earlier visual cortex. This unique sensitivity of mid-fusiform cortex to the lexical characteristics of written words points to its central role as an orthographic lexicon, which accesses the long-term memory representations of visual word forms.
Kaposi’s sarcoma-associated herpesvirus fine-tunes the temporal expression of late genes by manipulating a host RNA quality control pathway
Authors: Ruiz Julio C. , Devlin Anne , Kim Jiwoong , Conrad Nicholas K. 
Published: February 2020

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncogenic nuclear DNA virus that expresses its genes using the host cell transcription and RNA processing machinery. As a result, KSHV transcripts are subject to degradation by at least two host-mediated nuclear RNA decay pathways, PABPN1 and PAPα/γ-mediated RNA decay (PPD) and an ARS2-dependent decay pathway. Here, we present global analyses of viral transcript levels to further understand the roles of these decay pathways in KSHV gene expression. Consistent with our recent report that the KSHV ORF57 protein increases viral transcript stability by impeding ARS2-dependent decay, ARS2 knockdown has little effect on viral gene expression 24 hours after lytic reactivation of wild-type virus. In contrast, inactivation of PPD results in premature accumulation of late transcripts. The up-regulation of late transcripts does not require the primary late gene-specific viral transactivation factor, suggesting that cryptic transcription produces the transcripts that then succumb to PPD. Remarkably, PPD inactivation has no effect on late transcripts at their proper time of expression. We show that this time-dependent PPD evasion by late transcripts requires the host factor NRDE2, which has previously been reported to protect cellular RNAs by sequestering decay factors. From these studies, we conclude that KSHV uses PPD to fine-tune the temporal expression of its genes by preventing their premature accumulation.ImportanceKaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that causes Kaposi’s sarcoma and other lymphoproliferative disorders. Nuclear expression of KSHV genes results in exposure to at least two host-mediated nuclear RNA decay pathways, PABPN1 and PAPα/γ-mediated RNA decay (PPD) and an ARS2-mediated decay pathway. Perhaps unsurprisingly, we previously found that KSHV uses specific mechanisms to protect its transcripts from ARS2-mediated decay. In contrast, here we show that PPD is required to dampen the expression of viral late transcripts that are prematurely transcribed, presumably due to cryptic transcription early in infection. At the proper time for their expression, KSHV late transcripts evade PPD through the activity of the host factor NRDE2. We conclude that KSHV fine-tunes the temporal expression of its genes by modulating PPD activity. Thus, the virus both protects from and exploits the host nuclear RNA decay machinery for proper expression of its genes.
Development of a knowledge translation platform for ataxia: Impact on readers and volunteer contributors
Authors: Suart Celeste , Graham Katherine , Suart Theresa Nowlan , Truant Ray 
Published: February 2020

AbstractBackgroundDissemination of accurate health research information to patients and families has become increasingly important with the rise of the internet as a means of finding health information. However, the public faces several barriers to accessing research information; including paywalls and technical jargon. One method to bridge this gap between patients, families, and research is using lay summaries. SCAsource is an online knowledge translation platform where peer-reviewed research papers on ataxia are translated into lay summaries. This online platform was launched in September 2018, with the goal of making ataxia research more accessible and understandable to patients and families. A secondary goal is to provide opportunities for ataxia researchers to develop and hone their knowledge translation skills, altogether improving the quality of patient communication in the ataxia community.AimThe aim of this study was to measure the impact of SCAsource on its readers and volunteer contributors after one year of activity. This is to ensure SCAsource is meeting its goals of (1) improving access and understanding of ataxia research to lay audiences, and (2) improving knowledge translation skills of volunteer contributors.MethodsTwo online surveys were launched, one for readers and one for volunteers. Each survey had a combination of multiple-choice, Likert-scale type, and open-ended short-answer questions. Descriptive quantitative analysis was used for respondent characteristics and Likert-type data. A grounded theory coding approach was used to analyze narrative feedback data.ResultsWe found that SCAsource has mutually beneficial outcomes for both lay person readers and volunteer contributors. Readers have an increased understanding of ataxia research and access to up-to-date information on recent publications. Volunteers develop knowledge translation skills and have increased confidence in communicating results to lay audiences. Areas of improvement were identified to be incorporated into the platform.ConclusionWe demonstrated that SCAsource improves access to information and understanding of research to lay audiences, while providing opportunities for researchers to develop knowledge translation skills. This framework can potentially be used by other rare disease organizations to launch and evaluate their own knowledge translation websites.
Analysis of MRC-supported early career researcher success in obtaining follow-on research funding
Authors: Viney Ian , Samarasinghe Buddhini , Dolby Kevin 
Published: February 2020

AbstractThis study examined the progress of MRC-funded researchers, with a focus on their success in securing subsequent research income. We report here results from compiling details of the research income of researchers that completed an MRC early career award between 2011 and 2015. Depending on the funding scheme 50-59 per cent of researchers spent on average more than 100,000 GBP per year from new grants secured within three years of finishing their MRC award. In each scheme around 30 per cent of researchers secured less than 50,000 GBP per year research funding in the three years following their MRC award. We apply the same approach to an analysis of progression for the MRC cadre of intramurally-supported Programme Leader Track researchers, and a sample of MRC research grant holders. We also supplement our results with a small number of interviews with researchers that held MRC New Investigator Research Grants. We suggest that these data confirm reasonably good progression rates, with MRC early career schemes demonstrably effective in supporting research careers. They confirm there is a bottleneck with some researchers taking several years to establish their research career, and that expansion of the research base will need balanced new investment across schemes and stages and cannot be driven through growth in early career schemes alone.
Integrated analysis of the aging brain transcriptome and proteome in tauopathy
Authors: Mangleburg Carl Grant , Wu Timothy , Yalamanchili Hari K. , Guo Caiwei , Hsieh Yi-Chen , Duong Duc M. , Dammer Eric B. , De Jager Philip L. , Seyfried Nicholas T. , Liu Zhandong , Shulman Joshua M. 
Published: February 2020

AbstractBackgroundTau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes.MethodsPaired, longitudinal RNA-sequencing and mass-spectrometry were performed in aDrosophilamodel of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutation causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy.ResultsTauWTinduced 1,514 and 213 differentially expressed transcripts and proteins, respectively. TauR406Whad a substantially greater impact, causing changes in 5,494 transcripts and 697 proteins. There was a ~70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation, despite the absence of microglia in flies. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes.ConclusionsOur results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.
Survey of Australian STEMM Early Career Researchers: job insecurity and questionable research practices are major structural concerns
Authors: Christian Katherine , Johnstone Carolyn , Larkins Jo-ann , Wright Wendy , Doran Michael R. 
Published: February 2020

AbstractWe sought to understand the pressures on Early Career Researchers (ECR) in the Science, Technology, Engineering, Mathematics, & Medicine (STEMM) disciplines, collecting data from 658 ECRs working in Australia. Respondents indicated a “love of science”, but most also indicated an intention to leave their position. Decisions were primarily motivated by job insecurity (52%), while grievances included poor supervision (60%), bullying or harassment (34%), inequitable hiring practices (39%) and poor support for families (9.6%). A concerning rate of “questionable research practices” by colleagues (34.1% to 41.1%) was reported to have impacted ECR career advancement. Our study links recent reports that characterise the health of the research industry, providing direct insight from ECRs on job insecurity, workplace culture challenges, and the logical rise of questionable research practices. Internationally, nationally and institutionally the research community needs to improve job security (care for our people) and the quality of research data (our product).
Tracing the origin of a new organ by inferring the genetic basis of rumen evolution
Authors: Pan Xiangyu , Wang Yu , Li Zongjun , Chen Xianqing , Heller Rasmus , Wang Nini , Zhao Chen , Cai Yudong , Xu Han , Li Songhai , Li Ming , Li Cunyuan , Hu Shengwei , Li Hui , Wang Kun , Chen Lei , Wei Bin , Zheng Zhuqing , Fu Weiwei , Yang Yue , Zhang Tingting , Hou Zhuoting , Yan Yueyang , Lv Xiaoyang , Sun Wei , Li Xinyu , Huang Shisheng , Liu Lixiang , Mao Shengyong , Liu Wenqing , Hua Jinlian , Li Zhipeng , Zhang Guojie , Chen Yulin , Wang Xihong , Qiu Qiang , Dalrymple Brian P. , Wang Wen , Jiang Yu 
Published: February 2020

AbstractThe rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers. We used 897 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen origin and evolution. Comparative analyses reveal that the rumen and the first-chamber stomachs of camels and cetaceans shared a common tissue origin from the esophagus. The rumen recruited genes from other tissues/organs and up-regulated many esophagus genes to aquire functional innovations involving epithelium absorption, improvement of the ketone body metabolism and regulation of microbial community. These innovations involve such genetic changes as ruminant-specific conserved elements, newly evolved genes and positively selected genes. Our in vitro experiements validate the functions of one enhancer, one positively selected gene and two newly evolved antibacterial genes. Our study provides novel insights into the origin and evolution of a complex organ.
Customizable Live-Cell Imaging Chambers for Multimodal and Multiplex Fluorescence Microscopy
Authors: Tepperman Adam , Zheng David Jiao , Abou Taka Maria , Vrieze Angela , Lam Austin Le , Heit Bryan 
Published: February 2020

AbstractUsing multiple imaging modalities while performing independent experiments in parallel can greatly enhance the throughput of microscopy-based research, but requires provision of appropriate experimental conditions in a format that meets the microscopy’s optical requirements. Although customized imaging chambers can meet these challenges, the difficulty of manufacturing custom chambers and the relatively high cost and design inflexibility of commercial chambers has limited the adoption of this approach. Herein, we demonstrate the use of 3D printing to produce inexpensive, customized live-cell imaging chambers that are compatible with a range of imaging modalities including super-resolution microscopy. In this approach, biocompatible plastics are used to print imaging chambers designed to meet the specific needs of an experiment, followed by adhesion of the printed chamber to a glass coverslip, producing a chamber that is impermeant to liquids and which supports the growth and imaging of cells over multiple days. This approach can also be used to produce moulds for casting PDMS microfluidic devices. The utility of these chambers is demonstrated using designs for multiplex microscopy, imaging under shear, chemotaxis, and general cellular imaging. Together, this approach represents an inexpensive yet highly customizable approach to produce imaging chambers that are compatible with modern microscopy techniques.
Impacts of climate change on agro-climatic suitability of major food crops and crop diversification potential in Ghana
Authors: Chemura Abel , Schauberger Bernhard , Gornott Christoph 
Published: February 2020

AbstractCrop diversification is a promising climate change adaptation strategy for food production stability. However, without quantitative assessments of where, with which crop mixes and to what extent diversification is possible now and under future climatic conditions, efforts to expand crop diversification under Nationally Determined Contributions (NDCs) and National Action Plans (NAP) are unsystematic. In this study, we used extreme gradient boosting, a machine learning approach to model the current climatic suitability for maize, sorghum, cassava and groundnut in Ghana using yield data and agronomically important variables. We then used multi-model future climate projections for the 2050s and two greenhouse gas emissions scenarios (RCP 2.6 and RCP 8.5) to predict changes in the suitability range of these crops. We achieved a good model fit in determining suitability classes for all crops (AUC=0.81-0.87). Precipitation-based factors are suggested as most important in determining crop suitability, though the importance is crop-specific. Under projected climatic conditions, optimal suitability areas will decrease for all crops except for groundnuts under RCP8.5 (no change: 0%), with greatest losses for maize (12% under RCP2.6 and 14% under RCP8.5). Under current climatic conditions, 18% of Ghana has optimal suitability for two crops, 2% for three crops with no area having optimal suitability for all the four crops. Under projected climatic conditions, areas with optimal suitability for producing two and three crops will decrease by 12% as areas having moderate and marginal conditions for multiple crops increase. We also found that although diversification opportunities are spatially distinct, cassava and groundnut will be more simultaneously suitable for the south while groundnut and sorghum will be more suitable for the northern parts of Ghana under projected climatic conditions.
Effects of carbon-based additive and ventilation rate on nitrogen loss and microbial community during chicken manure composting
Authors: Chang Ruixue , Li Yanming , Chen Qing , Gong Xiaoyan , Qi Zicheng 
Published: February 2020

AbstractAerobic composting is a sustainable method for recycling of chicken manure, while its unsuitable porosity and carbon to nitrogen ratio limit the oxygen supply, which must result in high nitrogen loss because of anaerobic micro-zones in the materials. Treatments with five carbon-based additives and two ventilation rates (0.18 and 0.36 L·min-1·kg-1 DM) were set in chicken manure composting, to investigate their effects on biodegradation process, ammonia (NH3) emission, nitrogen loss, physiochemical properties and microbial community. The additives and ventilation rates influenced the CO2 production from the 2nd week, meanwhile varied the physiochemical parameters all the process. No inhibitory effect on the maturity were observed in all treatments. With woody peat as additive, the NH3 emission amount and nitrogen loss rate were shown as 15.86 mg and 4.02 %, when compared with 31.08-80.13 mg and 24.26-34.24 % in other treatments. The high aeration rate increased the NH3 emission and nitrogen loss, which were varied with different additives. The T-RFLP results showed that the additives and the ventilation rates changed the microbial community, while the prominent microbial clones belonged to the class of Bacilli and Clostridia (in the phylum of Firmicutes), and Alphaproteobacteria, Deltaproteobacteria and Gammaproteobacteria (in the phylum of Proteobacteria). Bacillus spp. was observed to be the most dominant bacteria in all the composting stages and treatments. We concluded that woody peat could improve chicken manure composting more than other additives, especially on controlling nitrogen loss. 0.18 L·min-1·kg-1 DM was suitable for chicken manure composting with different additives.