bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the tea bag method as a potential tool for detecting the effects of added nutrients and their interactions with climate on litter decomposition
Authors: Mori Taiki , Hashimoto Toru , Sakai Yoshimi 
Published: January 2021

AbstractIt is acknowledged that exogenous nutrient addition often stimulates early-stage litter decomposition in forests and late-stage decomposition is generally suppressed by nitrogen addition, whereas the interactive effects of nutrient addition and abiotic environmental factors, such as climate, on decomposition remain unclear. The tea bag method, which was developed to provide the decomposition rate constantkof early-stage decomposition and stabilization factorSof labile materials in the late stage, is a potentially useful tool for examining the impacts of nutrient addition on both early- and late-stage litter decomposition and their interactions with climate. At a long-term (38-year) continuous fertilization experimental site (anAbies sachalinensisFr. Schmidt stand) in Hokkaido, Japan, we examined whether a standard tea bag method protocol was sufficiently sensitive to reveal any impacts of nutrient addition on early- and late-stage decomposition. In addition, we tested the interactive effects of nutrient addition and climate on litter decomposition. The short incubation period of the tea bag method (ca. 90 days) enabled us to obtain decomposition data from the same location at three different times in a year, i.e., early summer, midsummer, and winter, providing an opportunity to test interactive effects. We demonstrated that the decomposition rate of rooibos tea and the decomposition rate constantkof early-stage decomposition were clearly stimulated by fertilization in midsummer, but no impacts were detected in other seasons, probably because the relative importance of nutrient availability was elevated in midsummer, during which decomposition rates were less constrained by temperature and moisture. The green tea decomposition rate and stabilization factorS, an index related to late-stage decomposition, were unaffected by fertilization. This was probably because the tea bag method does not take into account lignin degradation, which is considered a key factor controlling late-stage litter decomposition. Overall, the present study (i) successfully determined the interactive effects of nutrient addition and climate factors on litter decomposition by making full use of the tea bag method, and (ii) the results suggest that the tea bag method can be a suitable tool for examining the direct effects of nutrient addition and their interactions with environmental factors on early-stage litter decomposition, but not those on late-stage decomposition.
Somatic mutational profiles and germline polygenic risk scores in human cancer
Authors: Liu Yuxi , Gusev Alexander , Heng Yujing J. , Alexandrov Ludmil B. , Kraft Peter 
Published: January 2021

ABSTRACTThe mutational profile of a cancer reflects the activity of the mutagenic processes which have been operative throughout the lineage of the cancer cell. These processes leave characteristic profiles of somatic mutations called mutational signatures. Mutational signatures, including single-based substitution (SBS) signatures, may reflect the effects of exogenous or endogenous exposures. Here, we used polygenic risk score (PRS) as proxies for exposures and examined the association between somatic mutational profiles and germline PRS in 12 cancer types from The Cancer Genome Atlas project. We found 17 statistically significant associations after Bonferroni correction (p < 3.15×10−5), including positive associations between germline inflammatory bowel disease PRS and number of somatic mutations of signature SBS1 in prostate cancer and APOBEC-related signatures in breast cancer. The age at menarche PRS was inversely associated with mutation counts of SBS1 in prostate cancer. Our analysis suggests that there are robust associations between tumor somatic mutational profiles and germline PRS. These may reflect mechanisms through hormone regulation and immunological responses that contribute to cancer etiology and drive cancer progression.
Inference of an integrative, executable network for Rheumatoid Arthritis combining data-driven machine learning approaches and a state-of-the-art mechanistic disease map
Authors: Miagoux Quentin , Singh Vidisha , de Mézquita Dereck , Chaudru Valerie , Elati Mohamed , Petit-Teixeira Elisabeth , Niarakis Anna 
Published: January 2021

AbstractRheumatoid arthritis (RA) is a multifactorial, complex autoimmune disease that involves various genetic, environmental and epigenetic factors. Systems biology approaches provide the means to study complex diseases through the integration of different layers of biological information. Combining multiple data types can help compensate for missing or conflicting information and limit the possibility of false positives. In this work, we aim to unravel mechanisms governing the regulation of key transcription factors in RA and derive patient-specific models to gain more insights into the disease heterogeneity and the response to treatment.We first make use of publicly available transcriptomic datasets (peripheral blood) relative to RA and machine learning to create an RA specific transcription factor (TF) co-regulatory network. The TF cooperativity network is subsequently enriched in signalling cascades and upstream regulators using a state-of-the-art, RA-specific molecular map. The integrative network is then used as a template to analyze patients’ data regarding their response to anti-TNF treatment and identify master regulators and upstream cascades affected by the treatment. We use the Boolean formalism to simulate in silico subparts of the integrated network and identify combinations and conditions that can switch on or off the identified TFs, mimicking the effects of single and combined perturbations.
ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity
Authors: Fougerat Anne , Schoiswohl Gabriele , Polizzi Arnaud , Régnier Marion , Wagner Carina , Smati Sarra , Fougeray Tiffany , Lippi Yannick , Lasserre Frederic , Melin Valentine , Tramunt Blandine , Alkhoury Chantal , Emile Anthony , Schupp Michael , Gourdy Pierre , Dubot Patricia , Levade Thierry , Ellero-Simatos Sandrine , Gamet-Payrastre Laurence , Panasyuk Ganna , Amri Ez-Zoubir , Postic Catherine , Wahli Walter , Loiseau Nicolas , Montagner Alexandra , Langin Dominique , Lass Achim , Guillou Hervé 
Published: January 2021

ABSTRACTObjectiveIn hepatocytes, peroxisome proliferator-activated receptor α (PPARα) acts as a lipid sensor that regulates hepatic lipid catabolism during fasting and orchestrates a genomic response required for whole-body homeostasis. This includes the biosynthesis of ketone bodies and the secretion of the starvation hormone fibroblast growth factor 21 (FGF21). Several lines of evidence suggest that adipose tissue lipolysis contributes to this specific process. However, whether adipose tissue lipolysis is a dominant signal for the extensive remodeling of liver gene expression dependent on PPARα has not been investigated.MethodsFirst, using mice lacking adipose tissue lipolysis through adipocyte-specific deletion of adipose triglyceride lipase (ATGL), we characterized the responses dependent on adipocyte ATGL during fasting. Next, we performed liver whole genome expression analysis in fasted mice upon deletion of adipocyte ATGL or hepatocyte PPARα. Finally, we tested the consequences of hepatocyte-specific PPARα deficiency during pharmacological induction of adipocyte lipolysis with a β3-adrenergic receptor agonist.ResultsIn the absence of ATGL in adipocytes, ketone body and FGF21 productions were impaired in response to starvation. Liver transcriptome analysis revealed that adipocyte ATGL is critical for regulation of hepatic gene expression during fasting and highlighted a strong enrichment in PPARα target genes in this condition. Genome expression analysis confirmed that a large set of fasting-induced genes are sensitive to both ATGL and PPARα. Adipose tissue lipolysis induced by acute activation of the β3-adrenergic receptor also triggered PPARα-dependent responses in the liver, supporting a role for adipocyte-derived fatty acids as dominant signals for hepatocyte PPARα activity. In addition, the absence of hepatocyte PPARα altered brown adipose tissue (BAT) morphology and reduced UCP1 expression upon stimulation of the β3-adrenergic receptor. In agreement with this finding, mice lacking hepatocyte PPARα showed decreased tolerance to acute cold exposure.ConclusionsThese results underscore the central role of hepatocyte PPARα in the sensing of adipocyte-derived fatty acids and reveal that its activity is essential for full activation of BAT. Intact PPARα activity in hepatocytes is required for cross-talk between adipose tissues and the liver during fat mobilization during fasting and cold exposure.
deepManReg: a deep manifold-regularized learning model for improving phenotype prediction from multi-modal data
Authors: Nguyen Nam D. , Huang Jiawei , Wang Daifeng 
Published: January 2021

AbstractThe biological processes from genotype to phenotype are complex involving multi-scale mechanisms. Increasing multi-modal data enables deeper understanding of underlying complex mechanisms in various phenotypes. However, integrating and interpreting such large-scale multi-modal data remains challenging, especially given highly heterogeneous, nonlinear relationships across modalities. To address this, we developed an interpretable regularized learning model, deepManReg to predict phenotypes from multi-modal data. First, deepManReg employs deep neural networks to learn cross-modal manifolds and then align multi-modal features onto a common latent space. This space aims to preserve both global consistency and local smoothness across modalities and reveal higher-order nonlinear cross-modal relationships. Second, deepManReg uses cross-modal manifolds as a feature graph to regularize the classifiers for improving phenotype predictions and also prioritizing the multi-modal features and cross-modal interactions for the phenotypes. We applied deepManReg to recent single cell multi-modal data such as Patch-seq data including transcriptomics and electrophysiology for neuronal cells in the mouse brain. We show that deepManReg significantly improves predicting cellular phenotypes and also prioritizing genes and electrophysiological features for the phenotypes. Finally, deepManReg is open-source and general for phenotype prediction from multi-modal data. deepManReg is open-source available athttps://github.com/daifengwanglab/deepManReg.
Talker discontinuity disrupts attention to speech: Evidence from EEG and pupillometry
Authors: Lim Sung-Joo , Carter Yaminah D. , Njoroge J. Michelle , Shinn-Cunningham Barbara G. , Perrachione Tyler K. 
Published: January 2021

AbstractSpeech is processed less efficiently from discontinuous, mixed talkers than one consistent talker, but little is known about the neural mechanisms for processing talker variability. Here, we measured psychophysiological responses to talker variability using electroencephalography (EEG) and pupillometry while listeners performed a delayed recall of digit span task. Listeners heard and recalled seven-digit sequences with both talker (single- vs. mixed-talker digits) and temporal (0- vs. 500-ms inter-digit intervals) discontinuities. Talker discontinuity reduced serial recall accuracy. Both talker and temporal discontinuities elicited P3a-like neural evoked response, while rapid processing of mixed-talkers’ speech led to increased phasic pupil dilation. Furthermore, mixed-talkers’ speech produced less alpha oscillatory power during working memory maintenance, but not during speech encoding. Overall, these results are consistent with an auditory attention and streaming framework in which talker discontinuity leads to involuntary, stimulus-driven attentional reorientation to novel speech sources, resulting in the processing interference classically associated with talker variability.
Resident Cardiac Macrophages Mediate Adaptive Myocardial Remodeling
Authors: Wong Nicole R. , Mohan Jay , Kopecky Benjamin J , Guo Shuchi , Du Lixia , Leid Jamison , Dmytrenko Oleksandr , Luehmann Hannah , Bajpai Geetika , Ewald Laura , Bell Lauren , Patel Nikhil , Lokshina Inessa , Bredemeyer Andrea , Weinheimer Carla J. , Nigro Jessica M. , Kovacs Attila , Morimoto Sachio , Bayguinov Peter O. , Fisher Max. R. , Fitzpatrick James A.J. , Epelman Slava , Kreisel Daniel , Sah Rajan , Liu Yongjian , Hu Hongzhen , Lavine Kory J. 
Published: January 2021

SummaryCardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2−) macrophages. Herein, we identify an essential role for CCR2− macrophages in the chronically failing heart. Depletion of CCR2− macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2− macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and introduce a new mechanism of cardiac macrophage activation.
A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19
Authors: Malherbe Delphine C. , Kurup Drishya , Wirblich Christoph , Ronk Adam J. , Mire Chad , Kuzmina Natalia , Shaik Noor , Periasamy Sivakumar , Hyde Matthew A. , Williams Julie M. , Shi Pei-Yong , Schnell Matthias J. , Bukreyev Alexander 
Published: January 2021

SUMMARYThe development of effective countermeasures against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal model of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.
Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for Atopic Dermatitis (AD) treatment
Authors: Baylet Audrey , Vyumvuhore Raoul , Laclaverie Marine , Marchand Laëtitia , Mainzer Carine , Bordes Sylvie , Closs-Gonthier Brigitte , Delpy Laurent 
Published: January 2021

SummaryBackgroundCurrently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis (PSO) or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin.ObjectivesThe aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4).MethodsTranscutaneous penetration was evaluated byex vivostudies on tape-stripped pig ear skin. Antibody visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied using two 2D models. First, embryonic alkaline phosphatase (SEAP) secretion by HEK-Blue™ IL-4/IL-13 cells, proportional to hIL-4 cells stimulation, was quantified by OD 620 nm measurement in presence or absence of an anti-hIL4 scFv or Ab. Then, normal human keratinocytes (NHKs) were stimulated with polyinosinic-polycytidylic acid (poly I:C) +/− hIL-4 and treated with anti-hIL4 scFv. Human Interleukin-8 (hIL-8) concentrations were determined in culture supernatants by ELISA.ResultsAfter 24h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on thestratum corneum. In addition, the anti-hIL4 scFv showed better efficiency compared to Ab, with a neutralization percentage at 200 nM of 68% and 47%, respectively, in the HEK-Blue™ IL-4/IL-13 model. hIL-8 dosage in stimulated NHKs supernatants revealed that addition of scFv induced a dose-dependent hIL-4 neutralization.ConclusionsscFv penetrates through to the upper papillary dermis while Ab remains on the surface. The anti-hIL4 scFv neutralizes its target effectively in two 2D models suggesting its potential use as topical therapy for AD.
STARCH SYNTHASE 4 is required for normal starch granule initiation in amyloplasts of wheat endosperm
Authors: Hawkins Erica , Chen Jiawen , Watson-Lazowski Alexander , Ahn-Jarvis Jennifer , Barclay J. Elaine , Fahy Brendan , Hartley Matthew , Warren Frederick J. , Seung David 
Published: January 2021

SUMMARYStarch granule initiation is poorly understood at the molecular level. The glucosyltransferase, STARCH SYNTHASE 4 (SS4), plays a central role in granule initiation in Arabidopsis leaves, but its function in cereal endosperms is unknown. We investigated the role of SS4 in wheat, which has a distinct spatiotemporal pattern of granule initiation during grain development.We generated TILLING mutants in tetraploid wheat (Triticum turgidum) that are defective in both SS4 homoeologs. The morphology of endosperm starch was examined in developing and mature grains.SS4 deficiency led to severe alterations in endosperm starch granule morphology. During early grain development, while the wild type initiated single ‘A-type’ granules per amyloplast, most amyloplasts in the mutant formed compound granules due to multiple initiations. This phenotype was similar to mutants deficient in B-GRANULE CONTENT 1 (BGC1). SS4 deficiency also reduced starch content in leaves and pollen grains.We propose that SS4 and BGC1 are required for the proper control of granule initiation during early grain development that leads to a single A-type granule per amyloplast. The absence of either protein results in a variable number of initiations per amyloplast and compound granule formation.
MicroRNA775 and targetGalactosyltransferase(GALT9) module regulates recovery from submergence induced senescence by modulatingSAGsinArabidopsis thaliana
Authors: Mishra Vishnu , Singh Archita , Gandhi Nidhi , Sarkar Das Shabari , Yadav Sandeep , Kumar Ashutosh , Sarkar Ananda K. 
Published: January 2021

SummarySubmergence induced hypoxic condition is one of the abiotic stresses which negatively affects the plant growth and development, and causes early onset of senescence. Hypoxic conditions ateres the expression of a number of non-coding microRNAs (miRNAs), besides protein-coding genes. However, the molecular function of stress-induced miRNA in submergence induced physiological or developmental changes and recovery remains to be understood. The expression of miR775 is highly induced under hypoxic stress conditions. Here, we show that miR775 is a potential post-transcriptional regulator number of targets, includingGalactosyltransferase(GALT9). The expression of miR775 and targetGALT9was significantly induced and reduced respectively at 24 hours of submergence. The overexpression of miR775 (miR775-Oe) confers enhanced recovery from submergence stress and reduced accumulation of ROS, in contrast to wild type and endogenous target mimic of miR775 (MIM775) Arabidopsisplants. We observed a similar recovery phenotype in case of targetgalt9mutant plants, indicating the role of miR775-GALT9module in recovery from submergence. Further, we showed that the expression ofSENESCENCE ASSOCIATED GENES(SAGs), such asSAG12, SAG29, andORE1. was increased inMIM775and reduced in miR775-Oe andgalt9plants. Thus, our results suggest that miR775-GALT9module plays a crucial role in the recovery from submergence by modulating the expression ofSAGsthrough differential accumulation of ROS.
Comprehensive molecular features of polycystic ovary syndrome revealed by transcriptome analysis of oocytes and cumulus cells
Authors: Li Jie , Chen Haixia , Gou Mo , Tian Chenglei , Wang Huasong , Song Xueru , Keefe David. L. , Bai Xiaohong , Liu Lin 
Published: January 2021

AbstractPCOS is typically characterized by polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes, however, poor quality of oocytes lead to lower fertilization and implantation rates, decreased pregnancy and increased miscarriage rates. Our study suggests that global gene expression and cell to cell interactions of oocytes and CCs are significantly altered in women with PCOS. Noticeably, genes related to microtubules such as TUBB8 and TUBA1C are abnormally highly expressed in PCOS oocytes, reducing oocyte quality. The pattern of transposable element expression distinguishes PCOS from Control oocytes, implying the role of transposable elements in the occurrence of PCOS.
Multiscale mechanics and temporal evolution of vimentin intermediate filament networks
Authors: Schepers Anna V. , Lorenz Charlotta , Nietmann Peter , Janshoff Andreas , Klumpp Stefan , Köster Sarah 
Published: January 2021

AbstractThe cytoskeleton, an intricate network of protein filaments, motor proteins, and crosslinkers, largely determines the mechanical properties of cells. Among the three filamentous components, F-actin, microtubules, and intermediate filaments (IFs), the IF network is by far the most extensible and resilient to stress. We present a multiscale approach to disentangle the three main contributions to vimentin IF network mechanics – single filament mechanics, filament length, and interactions between filaments – including their temporal evolution. Combining particle tracking, quadruple optical trapping and computational modeling, we derive quantitative information on the strength and kinetics of filament interactions. Specifically, we find that hydrophobic contributions to network mechanics enter mostly via filament elongation kinetics, whereas electrostatics have a direct influence on filament–filament interactions. These results indicate that cells might need to explicitly suppress attractive interactions to re-organize the extremely stable cellular vimentin network.