bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic liability to bipolar disorder and body mass index: A bidirectional two-sample mendelian randomization study
Authors: Byg Lars Meinertz , Speed Maria , Speed Doug , Østergaard Søren Dinesen 
Published: February 2022

AbstractObjectivesBipolar disorder is associated with increased body mass index (BMI), but it remains undetermined if this association is causal and, if so, in which direction it goes. Here, we sought to answer these questions using bidirectional two-sample Mendelian Randomization, a method from genetic epidemiology that uses data from genome-wide association studies (GWAS) to examine whether a risk factor is causal for an outcome.MethodsWe used summary statistics from GWAS of bipolar disorder and BMI conducted using data collected by the Psychiatric Genomics Consortium and the UK Biobank, respectively. The genetic instrument for bipolar disorder contained 53 SNPs and explained 0.5% of phenotypic variance, while the genetic instrument for BMI contained 517 SNPs and explained 7.1% of phenotypic variance.ResultsWe found that a two-fold increase in the genetic liability to bipolar disorder causes a 0.6 (kg/m2) reduction in BMI, which is statistically significant (P=0.009), and predominantly driven by reduced fat mass. Conversely, we found no evidence that BMI causes changes in the risk of developing bipolar disorder (P=0.59).ConclusionThe findings of this study indicate that the increased BMI observed among individuals with bipolar disorder is not a direct consequence of genetic liability to bipolar disorder, but more likely represents the sum of downstream correlates of manifest bipolar disorder, such as side effects of pharmacological treatment, poor diet and sedentary lifestyle, that are all modifiable and could potentially be targeted as part of clinical management.
Neuronal RNA granules are ribosome complexes stalled at the pre-translocation state
Authors: Kipper Kalle , Mansour Abbas , Pulk Arto 
Published: February 2022

AbstractThe polarized cell morphology of neurons dictates many neuronal processes, including the axodendridic transport of specific mRNAs and subsequent translation. mRNAs together with ribosomes and RNA-binding proteins form RNA granules that are targeted to axodendrites for localized translation in neurons. It has been established that localized protein synthesis in neurons is essential for long-term memory formation, synaptic plasticity, and neurodegeneration. We have used proteomics and electron microscopy to characterize neuronal RNA granules (nRNAg) isolated from rat brain tissues or human neuroblastoma. We show that ribosome containing RNA granules are morula-like structures when visualized by electron microscopy. Crosslinking-coupled mass-spectrometry identified potential G3BP2 binding site on the ribosome near the eIF3d-binding site on the 40S ribosomal subunit. We used cryo-EM to resolve the structure of the ribosome-component of nRNAg. The cryo-EM reveals that ribosomes in the nRNAg are stalled at the elongation state where tRNA’s are in the hybrid A/P and P/E site, and resemble the pre-translocation state ribosomes. We also describe a new kind of principal motion of the ribosome, which we call the rocking motion.
Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer
Authors: Pariollaud Marie , Ibrahim Lara H. , Irizarry Emanuel , Mello Rebecca M. , Chan Alanna B. , Altman Brian J. , Shaw Reuben J. , Bollong Michael J. , Wiseman R. Luke , Lamia Katja A. 
Published: February 2022

AbstractDisrupted circadian rhythmicity is a prominent feature of modern society and has been designated as a probable carcinogen by the World Health Organization. However, the biological mechanisms that connect circadian disruption and cancer risk remain largely undefined. We demonstrate that exposure to chronic circadian disruption (chronic jetlag, CJL) increases tumor burden in a mouse model of KRAS-driven lung cancer. Molecular characterization of tumors and tumor-bearing lung tissues revealed that CJL enhances the expression of heat shock factor 1 (HSF1) target genes. Consistently, exposure to CJL disrupted the highly rhythmic nuclear trafficking of HSF1 in the lung, resulting in an enhanced accumulation of HSF1 in the nucleus. HSF1 has been shown to promote tumorigenesis in other systems, and we find that pharmacological inhibition of HSF1 reduces the growth of KRAS-mutant human lung cancer cells. These findings implicate HSF1 as a molecular link between circadian disruption and enhanced tumorigenesis.
Pseudotime analysis reveals novel regulatory factors for multigenic onset and monogenic transition of odorant receptor expression
Authors: Hussainy Mohammad , Korsching Sigrun I. , Tresch Achim 
Published: February 2022

AbstractDuring their maturation from horizontal basal stem cells, olfactory sensory neurons (OSNs) are known to select exactly one out of hundreds of olfactory receptors (ORs) and express it on their surface, a process called monogenic selection. Monogenic expression is preceded by a multigenic phase during which several OR genes are expressed in a single OSN. Here, we perform pseudotime analysis of a single cell RNA-Seq dataset of murine olfactory epithelium to precisely align the multigenic and monogenic expression phases with the cell types occurring during OSN differentiation. In combination with motif analysis of OR gene cluster-associated enhancer regions, we identify known and novel transcription (co-)factors (Ebf1, Lhx2, Ldb1, Fos and Sspp2) and chromatin remodelers (Kdm1a, Eed and Zmynd8) associated with OR expression. The inferred temporal order of their activity suggests novel mechanisms contributing to multigenic OR expression and monogenic selection.
Acyl-ghrelin attenuates neurochemical and motor deficits in the 6-OHDA model of Parkinson’s disease
Authors: Rees Daniel , Johnson Amy L. , Lelos Mariah , Smith Gaynor , Roberts Luke D. , Phelps Lindsay , Dunnett Stephen B. , Morgan Alwena H , Brown Rowan M , Wells Timothy , Davies Jeffrey S. 
Published: February 2022

AbstractThe feeding-related hormone, acyl-ghrelin, protects dopamine neurons in murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-based models of experimental Parkinson’s disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7-days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine–induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival. While acyl-ghrelin treatment was insufficient to elevate food intake or body weight, it attenuated amphetamine-induced circling behaviour and SNpc dopamine neurone loss induced by 6-OHDA. These data support the notion that elevating circulating acyl-ghrelin may be a valuable approach to slow or impair progression of neurone loss in PD.HighlightsAcyl-ghrelin attenuates SNpc dopamine cell loss in rat 6-OHDA-lesion model of PDAcyl-ghrelin attenuates motor deficits in rat 6-OHDA-lesion model of PD
Single-cell atlas of epithelial and stromal cell heterogeneity by lobe and strain in the mouse prostate
Authors: Graham Mindy K , Chikarmane Roshan , Wang Rulin , Vaghasia Ajay , Gupta Anuj , Zheng Qizhi , Wodu Bulouere , Pan Xin , Castagna Nicole , Liu Jianyong , Meyers Jennifer , Skaist Alyza , Wheelan Sarah , Simons Brian W , Bieberich Charles , Nelson William G , DeWeese Theodore L , De Marzo Angelo M , Yegnasubramanian Srinivasan 
Published: February 2022

ABSTRACTEvaluating the complex interplay of cell types in the tissue microenvironment is critical to understanding the origin and progression of diseases in the prostate and potential opportunities for intervention. Mouse models are an essential tool to investigate the molecular and cell-type-specific contributions of prostate disease at an organismal level. While there are well-documented differences in the extent, timing, and nature of disease development in various genetically engineered mouse models in different mouse strains and prostate lobes within each mouse strain, yet, the underlying molecular phenotypic differences in cell types across mouse strains and prostate lobes are incompletely understood. To address this, we examined the single-cell transcriptomes of individual mouse prostate lobes from two commonly used mouse strains, FVB/NJ and C57BL/6J. Data dimensionality reduction and clustering analysis revealed that basal and luminal cells possessed strain-specific transcriptomic differences, with luminal cells also displaying marked lobe-specific differences. Additionally, three rare populations of epithelial cells clustered independently of strain and lobe: one population of luminal cells expressing Foxi1 and components of the vacuolar ATPase proton pump (Atp6v0d2andAtp6v1g3), another population expressing Psca and other stem cell-associated genes (Ly6a/Sca-1, Tacstd2/Trop-2), and a neuroendocrine population expressingChga, Chgb, andSyp. In contrast, stromal cell clusters, including fibroblasts, smooth muscle cells, endothelial cells, pericytes, and immune cell types, were conserved across strain and lobe, clustering largely by cell type and not by strain or lobe. One notable exception to this was the identification of two distinct fibroblast populations that we term subglandular fibroblasts and interstitial fibroblasts based on their strikingly distinct spatial distribution in the mouse prostate. Altogether, these data provide a practical reference of the transcriptional profiles of mouse prostate from two commonly used mouse strains and across all four prostate lobes.
Common signatures of differential microRNA expression in Parkinson’s and Alzheimer’s disease brains
Authors: Dobricic Valerija , Schilling Marcel , Farkas Ildiko , Gveric Djordje O , Schulz Jessica , Middleton Lefkos , Gentleman Steve , Parkkinen Laura , Bertram Lars , Lill Christina M. 
Published: February 2022

AbstractBackgroundDysregulation of microRNA (miRNA)-mediated gene expression has been implicated in the pathogenesis and course of many neurodegenerative diseases including Parkinson’s disease (PD). However, the functionally relevant miRNAs remain largely unknown. Previous meta-analyses on differential miRNA expression data inpost-mortemPD brains have highlighted several miRNAs showing consistent and statistically significant effects. However, these meta-analyses were based on exceedingly small sample sizes.MethodsIn this study, we quantified the expression of the four most compelling PD candidate miRNAs from these meta-analyses in the superior temporal gyrus (STG) of one of the largest case-controlpost-mortembrain datasets available (261 samples), thereby quadruplicating previously investigated sample sizes. Furthermore, we probed for common differential miRNA expression signatures with Alzheimer’s disease (AD) by also analyzing these miRNAs inpost-mortemSTG of 190 AD patients and controls and by testing six top AD miRNAs in the PD brains.ResultsOf all ten analyzed miRNAs, PD candidate miRNA homo sapiens (hsa-) miR-132-3p showed evidence for differential expression in both PD (p=4.89E-06) and AD (p=3.20E-24), and AD miRNAs hsa-miR-132-5p (p=4.52E-06) and hsa-miR-129-5p (p=0.0379) showed evidence for differential expression in PD. Combining these novel data with previously published data substantially improved the statistical support (α=3.85E-03 using Bonferroni correction) of the corresponding meta-analyses clearly and compellingly implicating these miRNAs in both PD and AD. Furthermore, hsa-miR-132-3p/-5p (but not hsa-miR-129-5p) showed association with neuropathological Braak PD staging (p=3.51E-03/p=0.0117), suggesting that these miRNAs may play a role in α-synuclein aggregation beyond the early disease phase.ConclusionsOur study represents the largest independent assessment of recently highlighted candidate brain miRNAs in PD and ADpost-mortembrain samples, to date. Our results implicate hsa-miR-132-3p/-5p and hsa-miR-129-5p to be differentially expressed in both PD and AD brains, potentially pinpointing shared pathogenic mechanisms across these neurodegenerative diseases.
Single-cell transcriptomics of dynamic cell behaviors
Authors: Kwok Sheldon J.J. , Montoro Daniel T. , Haber Adam L. , Yun Seok-Hyun , Vinarsky Vladimir 
Published: February 2022

AbstractDespite advances in spatial transcriptomics, the molecular profiling of dynamic behaviors of cells in their native environment remains a major challenge. We present a method, termed behavioral transcriptomics, that allows us to couple physiological behaviors of single cells in an intact tissue to deep molecular profiling of individual cells. This method enabled us to establish a novel molecular signature for a striking migratory cellular behavior following tissue injury.
A second DNA binding site on RFC facilitates clamp loading at gapped or nicked DNA
Authors: Liu Xingchen , Gaubitz Christl , Pajak Joshua , Kelch Brian A 
Published: February 2022

SUMMARYClamp loaders place circular sliding clamp proteins onto DNA so that clamp-binding partner proteins can synthesize, scan, and repair the genome. DNA with nicks or small single-stranded gaps are common clamp-loading targets in DNA repair, yet these substrates would be sterically blocked given the known mechanism for binding of primer-template DNA. Here, we report the discovery of a second DNA binding site in the yeast clamp loader Replication Factor C (RFC) that aids in binding to nicked or gapped DNA. This DNA binding site is on the external surface and is only accessible in the open conformation of RFC. Initial DNA binding at this site thus provides access to the primary DNA binding site in the central chamber. Furthermore, we identify that this site can partially unwind DNA to create an extended single-stranded gap for DNA binding in RFC’s central chamber and subsequent ATPase activation. Finally, we show that deletion of the BRCT domain, a major component of the external DNA binding site, results in defective yeast growth in the presence of DNA damage where nicked or gapped DNA intermediates occur. We propose that RFC’s external DNA binding site acts to enhance DNA binding and clamp loading, particularly at DNA architectures typically found in DNA repair.
CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells
Authors: Liang Shang , Silva Joana Clara , Suska Olga , Lukoszek Radoslaw , Almohammed Rajaei , Cowling Victoria H 
Published: February 2022

ABSTRACTCMTR1 (cap methyltransferase 1) catalyses methylation of the first transcribed nucleotide of RNAPII transcripts (N1 2’-O-Me), creating part of the mammalian RNA cap structure. In addition to marking RNA as self, N1 2’-O-Me has ill-defined roles in RNA expression and translation. Here we investigated the gene specificity of CMTR1 and its impact on RNA expression in embryonic stem cells. Using chromatin immunoprecipitation, CMTR1 was found to bind to transcription start sites (TSS) correlating with RNAPII levels, predominantly binding at histone genes and ribosomal protein (RP) genes. Repression of CMTR1 expression resulted in repression of RNAPII binding at the TSS and repression of RNA expression, particularly of histone and RP genes. In correlation with regulation of histones and RP genes, CMTR1 repression resulted in repression of translation and induction of DNA replication stress and damage. Indicating a direct role for CMTR1 in transcription, addition of recombinant CMTR1 to purified nuclei increased transcription of the histone and RP genes. CMTR1 was found to be upregulated during neural differentiation and there was an enhanced requirement for CMTR1 for gene expression and proliferation during this process. We highlight the distinct roles of the cap methyltransferases RNMT and CMTR1 in target gene expression and differentiation.
CDK11 Promotes Centromeric Transcription to Maintain Centromeric Cohesion during Mitosis
Authors: Zhang Qian , Chen Yujue , Teng Zhen , Lin Zhen , Liu Hong 
Published: February 2022

AbstractActively-transcribing RNA polymerase (RNAP)II is remained on centromeres to maintain centromeric cohesion during mitosis although it is largely released from chromosome arms. This pool of RNAPII plays an important role in centromere functions. However, the mechanism of RNAPII retention on mitotic centromeres is poorly understood. We here demonstrate that Cdk11 depletion-induced centromeric cohesion defects are largely independent of Bub1. We further show that Cdk11 depletion and expression of its kinase-dead version significantly reduce both RNAPII and elongating RNAPII (pSer2) levels on centromeres, and also decrease centromeric transcription without altering the protein expression of cohesin and cohesion-regulators. Interestingly, enhanced centromeric transcription by THZ1 treatment or overexpression of CENP-B DNA-binding domain completely rescues Cdk11-depletion defects. These results suggest that Cdk11 promotes centromeric cohesion through facilitating centromeric transcription. Mechanistically, Cdk11 binds and phosphorylates RNAPII to promote transcription. Furthermore, mitosis-specific degradation of G2/M Cdk11-p58 recapitulates Cdk11-depletion defects. Altogether, our findings establish Cdk11 as an important regulator of centromeric transcription and as part of the mechanism for retaining RNAPII on centromeres during mitosis.
Exploring the effectiveness of word embedding based deep learning model for improving email classification
Authors: Asudani Deepak Suresh , Nagwani Naresh Kumar , Singh Pradeep 
Published: February 2022

PurposeClassifying emails as ham or spam based on their content is essential. Determining the semantic and syntactic meaning of words and putting them in a high-dimensional feature vector form for processing is the most difficult challenge in email categorization. The purpose of this paper is to examine the effectiveness of the pre-trained embedding model for the classification of emails using deep learning classifiers such as the long short-term memory (LSTM) model and convolutional neural network (CNN) model.Design/methodology/approachIn this paper, global vectors (GloVe) and Bidirectional Encoder Representations Transformers (BERT) pre-trained word embedding are used to identify relationships between words, which helps to classify emails into their relevant categories using machine learning and deep learning models. Two benchmark datasets, SpamAssassin and Enron, are used in the experimentation.FindingsIn the first set of experiments, machine learning classifiers, the support vector machine (SVM) model, perform better than other machine learning methodologies. The second set of experiments compares the deep learning model performance without embedding, GloVe and BERT embedding. The experiments show that GloVe embedding can be helpful for faster execution with better performance on large-sized datasets.Originality/valueThe experiment reveals that the CNN model with GloVe embedding gives slightly better accuracy than the model with BERT embedding and traditional machine learning algorithms to classify an email as ham or spam. It is concluded that the word embedding models improve email classifiers accuracy.
Evaluating the demographic scenario of gated communities in Dammam metropolitan area, kingdom of Saudi Arabia
Authors: AlQahtany Ali 
Published: February 2022

Purpose
The purpose of this paper is to assess the nature of gated communities in the Kingdom of Saudi Arabia (KSA) focusing on the experiences of residents from different gated communities in the Dammam Metropolitan Area (DMA). It seeks to assess the socio-economic background of such communities and find out why people choose to live in gated communities and their perceptions of such housing patterns.

Design/methodology/approach
The questionnaire survey technique was used in this study to achieve the main purpose. The study used the triangulation method, which includes both qualitative and quantitative techniques as the most appropriate approach to be adopted. Qualitative data was analyzed using content analysis, while statistical analysis was performed to analyze quantitative data.

Findings
The findings of the study highlight that although gated communities are physically closed by walls and gates, it is distinguished by good social relations not only among their residents but even with the external surroundings, which makes these communities more attractive. Of course, this contrasts to some extent with the prevailing thinking that such communities live in a state of social isolation.

Research limitations/implications
The ideas of people who live outside gated communities are very important, however, it was not explored in this study due to time limitations. So, future research could focus on citizens’ perceptions of this type of urban settlement.

Originality/value
To the best of the author’s knowledge, this is the first study assessing the nature of gated communities in KSA by focusing on the experiences of residents of different gated communities in DMA. Only a few studies have been done in this regard, so this research paper was conducted to bridge this research gap and build upon the literature.
Online teaching during COVID-19 crisis: the role of technostress and emotional dissonance on online teaching exhaustion and teaching staff productivity
Authors: Dahabiyeh Laila , Najjar Mohammad S. , Wang Gongtai 
Published: February 2022

PurposeAmid the coronavirus disease 2019 (COVID-19) pandemic, higher education institutions (HEI) all over the world have transitioned to online teaching. The purpose of this study is to examine the impact of technostress and negative emotional dissonance on online teaching exhaustion and teaching staff productivity.Design/methodology/approachSurvey methodology was used to collect data from faculty members in Jordanian universities. A total of 217 responses were analyzed to test the research model.FindingsThe research findings reveal that technostress creators have various impact on online teaching exhaustion and teaching staff productivity. Negative emotional dissonance has positive impact on both online teaching exhaustion and teaching staff productivity. Further, online teaching exhaustion is negatively associated with teaching staff productivity.Research limitations/implicationsThis research extends prior literature on technostress by examining the phenomenon in abnormal conditions (during a crisis). It further integrates technostress theory with emotional dissonance theory to better understand the impact of technostress creators on individual teaching staff productivity while catering for the interactional nature of teaching which is captured through emotional dissonance theory.Practical implicationsThe research offers valuable insights for HEI and policymakers on how to support teaching staff and identifies strategies that should facilitate a smooth delivery of online education.Originality/valueUnlike prior research that have examined technostress under normal operational conditions, this research examines the impact of technostress during a crisis. This study shows that technostress creators vary in their impact. Moreover, this study integrates technostress theory with emotional dissonance theory. While technostress theory captures the impact of technostress creators on individual teaching staff productivity, emotional dissonance theory captures the dynamic nature of the teaching process that involves interactions among teachers and students.