bluuebunny/crossref_metadata_2025_split huggingface dataset:
Warming in the land of the midnight sun: breeding birds may suffer greater heat stress at high- vs low-Arctic sites
Authors: O’Connor Ryan S. , Pogam Audrey Le , Young Kevin G. , Love Oliver P. , Cox Christopher J. , Roy Gabrielle , Robitaille Francis , Elliott Kyle H. , Hargreaves Anna L. , Choy Emily S. , Gilchrist H. Grant , Berteaux Dominique , Tam Andrew , Vézina François 
Published: October 2021

AbstractRising global temperatures are expected to increase reproductive costs for wildlife as greater thermoregulatory demands interfere with essential breeding activities such as parental care. However, predicting the temperature threshold where reproductive performance is negatively impacted remains a significant hurdle. Using a novel thermoregulatory polygon approach, we predicted the threshold temperature at which an Arctic songbird–the snow bunting (Plectrophenax nivalis)–would need to reduce activity and perform below the 4-times basal metabolic rate (BMR) required to sustain nestling provisioning to avoid overheating. We then compared this threshold to operative temperatures recorded at high (82°N) and low (64°N) Arctic sites to estimate how heat constraints translate into site-specific impacts on sustained activity level. We predict buntings would become behaviourally constrained at operative temperatures above 11.7°C, whereupon they must reduce provisioning rates to maintain thermal balance. Low Arctic sites had larger fluctuations in solar radiation, producing consistent daily periods when operative temperatures exceeded 11.7°C. However, high-latitude birds faced entire, consecutive days where parents would not be able to sustain required provisioning rates. These data indicate that Arctic warming is likely already disrupting the breeding performance of cold-specialist birds, but also suggests counterintuitive and severe negative impacts of warming at high-latitude breeding locations.
A simple strategy for sample annotation error detection in cytometry datasets
Authors: Smithmyer Megan E , Wiedeman Alice E , Skibinski David A.G. , Savage Adam K. , Acosta-Vega Carolina , Scheiding Sheila , Gersuk Vivian H. , Long S. Alice , Buckner Jane H. , Speake Cate 
Published: October 2021

ABSTRACTMislabeling samples or data with the wrong participant information can impact study integrity and lead investigators to draw inaccurate conclusions. Quality control to prevent these types of errors is commonly embedded into the analysis of genomic datasets, but a similar identification strategy is not standard for cytometric data. Here, we present a method for detecting sample identification errors in cytometric data using expression of HLA class I alleles. We measured HLA-A*02 and HLA-B*07 expression in 3 longitudinal samples from 41 participants using a 33-marker CyTOF panel designed to identify major immune cell types. 3/123 samples (2.4%) showed HLA allele expression that did not match their longitudinal pairs. Furthermore, these same three samples’ cytometric signature did not match qPCR HLA class I allele data, suggesting that they were accurately identified as mismatches. We conclude that this technique is useful for detecting sample labeling errors in cytometric analyses of longitudinal data. This technique could also be used in conjunction with another method, like GWAS or PCR, to detect errors in cross-sectional data. We suggest widespread adoption of this or similar techniques will improve the quality of clinical studies that utilize cytometry.
LungCancer3D: A Comprehensive Database for Integrating Lung Cancer Chromatin Architecture with Other Multi-omics
Authors: Wu Xinyu , Jiang Anlan , Wang Jixin , Song Shiyang , Xu Yaping , Tang Qian , Zhang Shirong , Xia Bing , Chen Xueqin , Ma Shenglin , Liu Jian 
Published: October 2021

ABSTRACTWith the breakthrough of chromatin conformation capture technologies in recent years, the importance of three-dimensional (3D) genome structure in gene expression, cell function regulation, disease occurrence, and development has been gradually recognized. To provide a comprehensive visualization of chromatin architecture and other multi-omics data for lung cancer research, we have constructed a comprehensive database, LungCancer3D (http://www.lungcancer3d.net). This web-based tool focuses on displaying human lung cancer-related HiC data along with a variety of other publicly available data, such as RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, DNA methylation, DNA mutation, and copy number variations. Researchers can visualize these diverse multi-omics data directly through the genome browser and discover how the genes expression is regulated at diverse levels. For example, we have demonstrated that the high expression level of C-MYC in lung cancer may be caused by the distant enhancer introduced by the de novo chromatin loops in lung cancer cells to bind the C-MYC promoter. The integrated multi-omics analyses through the LungCancer3D website can reveal the mechanisms underlying lung cancer development and provide potential targets for lung cancer therapy.
Three water restriction schedules used in rodent behavioral tasks transiently impair growth and differentially evoke a stress hormone response without causing dehydration
Authors: Vasilev Dmitrii , Havel Daniel , Liebscher Simone , Slesiona-Kuenzel Silvia , Logothetis Nikos K. , Schenke-Layland Katja , Totah Nelson K. 
Published: October 2021

AbstractWater restriction is commonly used to motivate rodents to perform behavioral tasks; however, its on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using post-mortem histological evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Nominal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in corticosterone relative to the control group. Our results suggest that the water restriction schedules used here will maintain welfare in rats. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may only be achieved after one week of restriction.
Seizure Onset Zone Identification Using Phase-Amplitude Coupling and Multiple Machine Learning Approaches for Interictal Electrocorticogram
Authors: Miao Yao , Iimura Yasushi , Sugano Hidenori , Fukumori Kosuke , Tanaka Toshihisa 
Published: October 2021

AbstractAutomatic seizure onset zone (SOZ) localization using interictal electrocorticogram (ECoG) improves the diagnosis and treatment of patients with medically refractory epilepsy. This study aimed to investigate the characteristics of phase-amplitude coupling (PAC) extracted from interictal ECoG and the feasibility of PAC served as a promising biomarker for SOZ identification. We employed the mean vector length modulation index approach on the 20-s ECoG window to calculate PAC features between low-frequency rhythms (0.5–24 Hz) and high frequency oscillations (HFOs) (80–560 Hz). We used statistical measures to test the significant difference in PAC between SOZ and non-seizure onset zone (NSOZ). To overcome the drawback of handcraft feature engineering, we established novel machine learning models to automatically learn the characteristics of PAC features obtained and classify them to identify SOZ. Besides, to conquer the imbalance of datasets, we introduced novel feature-wise/class-wise re-weighting strategies in conjunction with classifiers. In addition, we proposed the time-series nest cross-validation to provide more accurate and unbiased evaluations for this model. Seven patients with focal cortical dysplasia were included in this study. The experiment results not only illustrate that the significant coupling at band pairs of slow waves and HFOs exists in the SOZ when compared with the NSOZ but also indicate the effectiveness of PAC features and the proposed models with better classification performance.
Loss of p16INK4a in neuroblastoma cells induces shift to an immature state with mesenchymal characteristics and increases sensitivity to EGFR inhibitors
Authors: Schubert Nil A. , van Hooff Sander R. , Schild Linda , Ober Kimberley , Hortensius Marjolein , van den Handel Kim , Essing Anke H.W. , Koopmans Bianca , Boeije Manon , Proost Natalie , van de Ven Marieke , Jansky Selina , Stainczyk Sabine A. , Toprak Umut H. , Westermann Frank , Eising Selma , Molenaar Jan J. , van den Boogaard Marlinde L. 
Published: October 2021

ABSTRACTHomozygous inactivation of the CDKN2A locus is one of the most common genomic aberrations in human cancer. The locus codes for two unrelated and distinctly regulated proteins: p14ARF and p16INK4a, which inhibit MDM2 and CDK4/6, respectively. Loss of CDKN2A is also a recurrent event in relapsed neuroblastoma, a childhood tumour that arises from neural crest cells. To examine the consequences of the loss of the two distinct gene transcripts in neuroblastoma, we used the CRISPR-Cas9 system to knockout p14, p16 and p14+p16 in SY5Y cells. RNA sequencing of the transcriptome revealed a striking shift towards an immature Schwann cell precursor-like phenotype with mesenchymal characteristics, specifically in the p16 and p14+p16 knockouts. High-throughput drug screening of p16 and p14+p16 knockout clones identified a large increase in sensitivity to EGFR inhibitors. On protein level, we were able to confirm that EGFR pathway activation is higher in p14+p16 knockout cells and that treatment with the EGFR inhibitor afatinib resulted in higher levels of apoptosis. Afatinib also reduced tumour growth in vivo in xenografts transplanted with p14+p16 knockout SY5Y cells. Overall, our study suggests that CDKN2A deletion in neuroblastoma relates to a phenotypic shift towards a more progenitor like state and increases sensitivity to EGFR inhibitors.
An iTSC-derived placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility in syncytiotrophoblasts
Authors: Chen J , Neil JA , Tan JP , Rudraraju R , Mohenska M , Sun YBY , Sun G , Zhou Y , Li Y , Drew D , Pymm P , Tham WH , Rossello FJ , Nie G , Liu X , Subbarao K , Polo JM 
Published: October 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has caused a global health crisis. The primary site of infection is in the respiratory tract but the virus has been associated with a variety of complications involving the gastrointestinal and cardiovascular systems. Since the virus affects a variety of tissue types, there has been interest in understanding SARS-CoV-2 infection in early development and the placenta. ACE2 and TMPRSS2, two genes that are critical for SARS-CoV-2 virus entry are expressed in placenta-specific cell types including extravillous trophoblasts (EVTs) and especially, syncytiotrophoblasts (STs). The potential of SARS-CoV-2 to infect these placental cells and its effect on placental development and function is still unclear. Furthermore, it is crucial to understand the possible mechanism of vertical transmission of SARS-CoV-2 through the placenta. Here, we developed an in vitro model of SARS-CoV-2 infection of placental cell types using induced trophoblast stem cells (iTSCs). This model allowed us to show that STs but not EVTs are infected. Importantly, infected STs lack the expression of key differentiation genes, lack typically observed differentiated morphology and produce significantly lower human chorionic gonadotropin (HCG) compared to non-infected controls. We also show that an anti-ACE2 antibody prevents SARS-CoV-2 infection and restores normal ST differentiation and function. We highlight the establishment of a platform to study SARS-CoV-2 infection in early placental cell types, which will facilitate investigation of antiviral therapy to protect the placenta during early pregnancy and development.
Tree-based Correlation Screen and Visualization for Exploring Phenotype-Cell Type Association in Multiple Sample Single-Cell RNA-Sequencing Experiments
Authors: Zhang Boyang , Ji Zhicheng , Ji Hongkai 
Published: October 2021

AbstractSingle-cell RNA-seq experiments with multiple samples are increasingly used to discover cell types and their molecular features that may influence samples’ phenotype (e.g. disease). However, analyzing and visualizing the complex cell type-phenotype association remains nontrivial. TreeCorTreat is an open source R package that tackles this problem by using a tree-based correlation screen to analyze and visualize the association between phenotype and transcriptomic features and cell types at multiple cell type resolution levels. With TreeCorTreat, one can conveniently explore and compare different feature types, phenotypic traits, analysis protocols and datasets, and evaluate the impacts of potential confounders.
In Vivo MRI of Endogenous Remyelination in a Nonhuman Primate Model of Multiple Sclerosis
Authors: Lee Nathanael J. , Sati Pascal , Ha Seung-Kwon , Luciano Nicholas J. , Roy Snehashis , Ineichen Benjamin , Leibovitch Emily C. , Yen Cecil C. , Pham Dzung L. , Silva Afonso C. , Johnson Mac , Jacobson Steven , Reich Daniel S. 
Published: October 2021

ABSTRACTRemyelination is crucial for recovery from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral MS lesions, we investigated whether remyelination can be detected and characterized noninvasively. In 6 animals followed with multisequence 7-tesla MRI, 36 focal lesions, classified as demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in 5 of 6 marmosets and 51% of lesions. Radiological-pathological comparison showed high sensitivity (88%) and specificity (90%) for detecting remyelination by in vivo MRI. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents and translation to clinical practice.
H3K9me1/2 methylation limits the lifespan ofC. elegans
Authors: Huang Meng , Hong Minjie , Zhu Chengming , Chen Di , Chen Xiangyang , Guang Shouhong , Feng Xuezhu 
Published: October 2021

AbstractHistone methylation plays crucial roles in the development, gene regulation and maintenance of stem cell pluripotency in mammals. Recent work shows that histone methylation is associated with aging, yet the underlying mechanism remains unclear. In this work, we identified a class of histone 3 lysine 9 mono-/dimethyltransferase genes (met-2, set-6, set-19, set-20, set-21, set-32andset-33), mutations in which induce synergistic lifespan extension in the long-lived DAF-2 (IGF-1 receptor) mutant inC. elegans. These histone methyltransferase plusdaf-2double mutants not only exhibited an average lifespan nearly three times that of wild-type animals and a maximal lifespan of approximately 100 days, but also significantly increased resistance to oxidative and heat stress. Synergistic lifespan extension depends on the transcription factor DAF-16 (FOXO). mRNA-seq experiments revealed that the mRNA levels of class I DAF-16 target genes, which are activated by DAF-16, were further elevated in the double mutants. Among these genes,F35E8.7, nhr-62, sod-3, asm-2andY39G8B.7are required for the lifespan extension of thedaf-2;set-21double mutant. In addition, treatingdaf-2animals with the H3K9me1/2 methyltransferase G9a inhibitor also extends lifespan and increases stress resistance. Therefore, investigation of DAF-2 and H3K9me1/2 methyltransferase deficiency-mediated synergistic longevity will contribute to a better understanding of the molecular mechanisms of aging and therapeutic applications.
MPDB: a unified multi-domain protein structure database integrating structural analogue detection
Authors: Peng Chun-Xiang , Zhou Xiao-Gen , Xia Yu-Hao , Zhang Yang , Zhang Gui-Jun 
Published: October 2021

AbstractWith the development of protein structure prediction methods and biological experimental determination techniques, the structure of single-domain proteins can be relatively easier to be modeled or experimentally solved. However, more than 80% of eukaryotic proteins and 67% of prokaryotic proteins contain multiple domains. Constructing a unified multi-domain protein structure database will promote the research of multi-domain proteins, especially in the modeling of multi-domain protein structures. In this work, we develop a unified multi-domain protein structure database (MPDB). Based on MPDB, we also develop a server with two functional modules: (1) the culling module, which filters the whole MPDB according to input criteria; (2) the detection module, which identifies structural analogues of the full-chain according to the structural similarity between input domain models and the protein in MPDB. The module can discover the potential analogue structures, which will contribute to high-quality multi-domain protein structure modeling.
Natural killer-like B cells promote Th17 cell differentiation and exacerbate rheumatoid arthritis
Authors: Wang Ping , Song Jing , Bai Mingxin , Zheng Xi , Xie Yang , Tang Yundi , Li Xin , Fang Xiangyu , Jia Yuan , Ren Limin , Ye Hua , Su Yin , Wang Shuo , Li Zhanguo , Hu Fanlei 
Published: October 2021

AbstractB cells are important participants in the pathogenesis of rheumatoid arthritis (RA). Besides classical B cells, novel B cell subsets are continually to be identified in recent years. Natural killer-like B (NKB) cells, a newly recognized B cell subset, are proved to be actively involved in the anti-infection immunity. However, their role in RA and the potential mechanism remain elusive. Here, we showed that NKB cells were expanded dramatically in collagen-induced arthritis (CIA) mice, demonstrating dynamic changes during the disease progression. These cells promoted CD4+ effector T cell proliferation and Th17 cell differentiation in vitro, while adoptive transfer of these cells exacerbated the arthritis severity of CIA mice. RNA Sequencing revealed that NKB cells displayed distinct differential gene expression profile under RA circumstance, potential perpetuating the disease progression. Moreover, the frequencies of NKB cells were significantly increased in RA patients, positively correlated with the clinical and immunological features. After effective therapy, these cells could be recovered to normal levels. Taken together, our results preliminarily revealed the pathogenic role of NKB cells in RA by promoting Th17 proinflammatory responses. Targeting these cells might provide potential therapeutic strategies for this persistent disease.
T Cell Receptor Non-Equilibrium Kinetics
Authors: Rollins Zachary A. , Faller R. , George Steven C. 
Published: October 2021

ABSTRACTAn atomic-scale mechanism describing the role of mechanosensing in T Cell Receptor (TCR) recognition of peptides in the binding groove of the peptide-major histocompatibility complex (pMHC) may inform the design of novel TCRs for immunotherapies. Using steered molecular dynamic simulations, our study demonstrates that mutations to peptides in the binding groove of the pMHC – which are known to discretely alter the T cell response to an antigen – influence MHC conformation and thus the overall strength of the TCR-pMHC bond including duration and length under constant load. Moreover, physiochemical features of the TCR-pMHC dynamic bond strength, such as hydrogen bonds and Lennard-Jones contacts, correlate with the immunogenic response elicited by the specific peptide in the MHC groove. Thus, formation of transient TCR-pMHC bonds is a characteristic of immunogenic peptides and is mediated by stabilized interactions.x
The Ribb-osome: Ribbon boosts ribosomal protein gene expression to coordinate organ form and function
Authors: Loganathan Rajprasad , Levings Daniel C. , Kim Ji Hoon , Wells Michael B. , Chiu Hannah , Wu Yifan , Slattery Matthew , Andrew Deborah J. 
Published: October 2021

ABSTRACTCell growth is well defined for the late (post-embryonic) stages of development, but evidence for early (embryonic) cell growth during post-mitotic morphogenesis is quite limited. Here, we identify early cell growth as a key characteristic of tubulogenesis in the Drosophila embryonic salivary gland (SG). A BTB/POZ domain nuclear factor, Ribbon (Rib), mediates this early cell growth. Rib binds the transcription start site of nearly every SG-expressed ribosomal protein gene (RPG) and is required for full expression of all RPGs tested. Rib binding to RPG promoters in vitro is weak and not sequence-specific, suggesting that specificity is achieved through co-factor interactions. Consistent with this hypothesis, we demonstrate Rib’s ability to physically interact with each of the three known contributors to RPG transcription. Surprisingly, Rib-dependent early cell growth in another tubular organ—the embryonic trachea—is not mediated by direct RPG transcription. These findings support a model of early cell growth sustained by transcriptional regulatory networks customized for organ form and function.
How far to build it before they come? Analyzing the use of the Field of Dreams hypothesis to bull kelp restoration
Authors: Arroyo-Esquivel Jorge , Baskett Marissa L. , McPherson Meredith , Hastings Alan 
Published: October 2021

AbstractIn restoration ecology, the Field of Dreams Hypothesis posits that restoration efforts that create a suitable environment could lead to eventual recovery of the remaining aspects of the ecosystem through natural processes. Natural processes following partial restoration has lead to ecosystem recovery in both terrestrial and aquatic systems. However, understanding the efficacy of a “field of dreams” approach requires comparison of different approaches to partial restoration in terms of spatial, temporal, and ecological scale to what would happen with more comprehensive restoration efforts. We explore the relative effect of partial restoration and ongoing recovery on restoration efficacy with a dynamical model based on temperate rocky reefs in Northern California. We analyze our model for both the ability and rate of bull kelp forest recovery under different restoration strategies. We compare the efficacy of a partial restoration approach with a more comprehensive restoration effort by exploring how kelp recovery likelihood and rate change with varying intensities of urchin removal and kelp outplanting over different time periods and spatial scales. We find that, for the case of bull kelp forests, setting more favorable initial conditions for kelp recovery through implementing both urchin harvesting and kelp outplanting at the start of the restoration project has a bigger impact on the kelp recovery rate than applying restoration efforts through a longer period of time. Therefore partial restoration efforts, in terms of spatial and temporal scale, can be significantly more effective when applied across multiple ecological scales in terms of both the capacity and rate of achieving the target outcomes.