bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and replication of RNA-Seq gene network modules associated with depression severity
Authors: Le Trang T. , Savitz Jonathan , Suzuki Hideo , Misaki Masaya , Teague T. Kent , White Bill C. , Marino Julie H. , Wiley Graham , Gaffney Patrick M. , Drevets Wayne C. , McKinney Brett A. , Bodurka Jerzy 
Published: September 2018

AbstractGenomic variation underlying major depressive disorder (MDD) likely involves the interaction and regulation of multiple genes in a network. Data-driven co-expression network module inference has the potential to account for variation within regulatory networks, reduce the dimensionality of RNA-Seq data, and detect significant gene-expression modules associated with depression severity. We performed an RNA-Seq gene co-expression network analysis of mRNA data obtained from the peripheral blood mononuclear cells of unmedicated MDD (n = 78) and healthy control (n = 79) subjects. Across the combined MDD and HC groups, we assigned genes into modules using hierarchical clustering with a dynamic tree cut method and projected the expression data onto a lower-dimensional module space by computing the single-sample gene set enrichment score of each module. We tested the single-sample scores of each module for association with levels of depression severity measured by the Montgomery-Åsberg Depression Scale (MADRS). Independent of MDD status, we identified 23 gene modules from the co-expression network. Two modules were significantly associated with the MADRS score after multiple comparison adjustment (adjustedp = 0.009, 0.028 at 0.05 FDR threshold), and one of these modules replicated in a previous RNA-Seq study of MDD (p = 0.03). The two MADRS-associated modules contain genes previously implicated in mood disorders and show enrichment of apoptosis and B cell receptor signaling. The genes in these modules show a correlation between network centrality and univariate association with depression, suggesting that intramodular hub genes are more likely to be related to MDD compared to other genes in a module.
Inhibition of TRF2 accelerates telomere attrition and DNA damage in naïve CD4 T cells during HCV infection
Authors: Nguyen Lam Nhat , Zhao Juan , Cao Dechao , Dang Xindi , Wang Ling , Lian Jianqi , Zhang Ying , Jia Zhansheng , Wu Xiao Y. , Morrison Zheng , Xie Qian , Ji Yingjie , Zhang Zheng , El Gazzar Mohamed , Ning Shunbin , Moorman Jonathan P. , Yao Zhi Q. 
Published: September 2018

AbstractT cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF). Mechanistically, the telomere shelterin protein, in particular telomeric repeat binding factor 2 (TRF2) that functions to protect telomeres from DNA damage, was significantly inhibited posttranscriptionally via the p53-dependent Siah-1a ubiquitination. Importantly, knockdown of TRF2 in healthy T cells resulted in increases in telomeric DNA damage and T-cell apoptosis, whereas overexpression of TRF2 in HCV T cells alleviated telomeric DNA damage and T-cell apoptosis. To the best of our knowledge, this is the first report revealing that inhibition of TRF2 promotes T-cell telomere attrition and telomeric DNA damage that accelerates T-cell senescent and apoptotic programs, which contribute to naïve T-cell loss during viral infection. Thus, restoring the impaired T-cell telomeric shelterin machinery may offer a new strategy to improve immunotherapy and vaccine response against human viral diseases.
Polyphyllin I suppresses the formation of vasculogenic mimicry via Twist1/VE-cadherin pathway
Authors: Xiao Ting , Zhong Weilong , Zhao Jianmin , Qian Baoxin , Liu Huijuan , Chen Shuang , Qiao Kailiang , Lei Yueyang , Zong Shumin , Wang Hongzhi , Liang Yuan , Zhang Heng , Meng Jing , Zhou Honggang , Sun Tao , Liu Yanrong , Yang Cheng 
Published: September 2018

AbstractVasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells and is related to the metastasis and poor prognosis of many cancer types, including hepatocellular carcinoma (HCC). Thus far, no effective drugs have been developed to target VM. In this study, patients with liver cancer exhibited reduced VM in tumor tissues after treatment with Rhizoma Paridis. Polyphyllin I (PPI), which is the main component of Rhizoma Paridis, inhibited VM formation in HCC lines and transplanted hepatocellular carcinoma cells. Molecular mechanism analysis showed that PPI impaired VM formation by blocking the PI3k-Akt-Twist1-VE-cadherin pathway. PPI also displayed dual effects on Twist1 by inhibiting the transcriptional activation of the Twist1 promoter and interfering with the ability of Twist1 to bind to the promoter of VE-cadherin, resulting in VM blocking. This study is the first to report on the clinical application of the VM inhibitor. Results may contribute to the development of novel anti-VM drugs in clinical therapeutics.
BH3 mimetics induce apoptosis independent of DRP-1 in melanoma
Authors: Mukherjee Nabanita , Strosnider Andrew , Vagher Bay , Lambert Karoline A. , Slaven Sarah , Robinson William A. , Amato Carol M. , Couts Kasey L. , Bemis Judson G. T. , Turner Jacqueline A. , Norris David A. , Shellman Yiqun G. 
Published: September 2018

AbstractDespite the recent advancement in treating melanoma, options are still limited for patients without BRAF mutations or in relapse from current treatments. BH3 mimetics against members of the BCL-2 family have gained excitement with the recent success in hematological malignancies. However, single drug BH3 mimetic therapy in melanoma has limited effectiveness due to escape by the anti-apoptotic protein MCL-1 and/or survival of melanoma-initiating cells (MICs). We tested the efficacy of the BH3 mimetic combination of A-1210477 (an MCL-1 inhibitor) and ABT-263 (a BCL-2/BCL-XL/BCL-W inhibitor) in killing melanoma, especially MICs. We also sought to better define Dynamin-Related Protein 1 (DRP-1)’s role in melanoma; DRP-1 is known to interact with members of the BCL-2 family and is a possible therapeutic target for melanoma treatment. We used multiple assays (cell viability, apoptosis, bright field, immunoblot, and sphere formation), as well as the CRISPR/Cas9 genome-editing techniques. For clinical relevance, we employed patient samples of different mutation status, including some relapsed from current treatments such as anti-PD-1 immunotherapy. We found the BH3 mimetic combination kill both the MICs and non-MICs (bulk of melanoma) in all cell lines and patient samples irrespective of the mutation status or relapsed state (p < 0.05). Unexpectedly, the major pro-apoptotic proteins, NOXA and BIM, are not necessary for the combination-induced cell death. Furthermore, the combination impedes the activation of DRP-1, and inhibition of DRP-1 further enhances apoptosis (p < 0.05). DRP-1 effects in melanoma differ from those seen in other cancer cells. These results provide new insights into BCL-2 family’s regulation of the apoptotic pathway in melanoma, and suggest that inhibiting the major anti-apoptotic proteins is sufficient to induce cell death even without involvement from major pro-apoptotic proteins. Importantly, our study also indicates that DRP-1 inhibition is a promising adjuvant for BH3 mimetics in melanoma treatment.
Gravimetry through non-linear optomechanics
Authors: Qvarfort Sofia , Serafini Alessio , Barker P. F. , Bose Sougato 
Published: September 2018

AbstractPrecision gravimetry is key to a number of scientific and industrial applications, including climate change research, space exploration, geological surveys and fundamental investigations into the nature of gravity. A variety of quantum systems, such as atom interferometry and on-chip-Bose–Einstein condensates have thus far been investigated to this aim. Here, we propose a new method which involves using a quantum optomechanical system for measurements of gravitational acceleration. As a proof-of-concept, we investigate the fundamental sensitivity for gravitational accelerometry of a cavity optomechanical system with a trilinear radiation pressure light-matter interaction. The phase of the optical output encodes the gravitational acceleration g and is the only component which needs to be measured. We prove analytically that homodyne detection is the optimal readout method and we predict an ideal fundamental sensitivity of Δg = 10−15 ms−2 for state-of-the-art parameters of optomechanical systems, showing that they could, in principle, surpass the best atomic interferometers even for low optical intensities. Further, we show that the scheme is strikingly robust to the initial thermal state of the oscillator.
Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target
Authors: Yángüez Emilio , Hunziker Annika , Dobay Maria Pamela , Yildiz Soner , Schading Simon , Elshina Elizaveta , Karakus Umut , Gehrig Peter , Grossmann Jonas , Dijkman Ronald , Schmolke Mirco , Stertz Silke 
Published: September 2018

AbstractAlthough annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.
The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects
Authors: Srivatsan Anjana , Li Bin-Zhong , Szakal Barnabas , Branzei Dana , Putnam Christopher D. , Kolodner Richard D. 
Published: September 2018

AbstractGenome instability is associated with tumorigenesis. Here, we identify a role for the histone Htz1, which is deposited by the Swr1 chromatin-remodeling complex (SWR-C), in preventing genome instability in the absence of the replication fork/replication checkpoint proteins Mrc1, Csm3, or Tof1. When combined with deletion of SWR1 or HTZ1, deletion of MRC1, CSM3, or TOF1 or a replication-defective mrc1 mutation causes synergistic increases in gross chromosomal rearrangement (GCR) rates, accumulation of a broad spectrum of GCRs, and hypersensitivity to replication stress. The double mutants have severe replication defects and accumulate aberrant replication intermediates. None of the individual mutations cause large increases in GCR rates; however, defects in MRC1, CSM3 or TOF1 cause activation of the DNA damage checkpoint and replication defects. We propose a model in which Htz1 deposition and retention in chromatin prevents transiently stalled replication forks that occur in mrc1, tof1, or csm3 mutants from being converted to DNA double-strand breaks that trigger genome instability.
Materials structure genealogy and high-throughput topological classification of surfaces and 2D materials
Authors: Himanen Lauri , Rinke Patrick , Foster Adam Stuart 
Published: September 2018

AbstractAutomated and verifiable structural classification for atomistic structures is becoming necessary to cope with the vast amount of information stored in various computational materials databases. Here we present a general recursive scheme for the structural classification of atomistic systems and introduce a structural materials map that can be used to organize the materials structure genealogy. We also introduce our implementation for the automatic classification of two-dimensional structures, especially focusing on surfaces and 2D materials. This classification procedure can automatically determine the dimensionality of a structure, further categorize the structure as a surface or a 2D material, return the underlying unit cell and also identify the outlier atoms, such as adsorbates. The classification scheme does not require explicit search patterns and works even in the presence of defects and dislocations. The classification is tested on a wide variety of atomistic structures and provides a high-accuracy determination for all of the returned structural properties. A software implementation of the classification algorithm is freely available with an open-source license.
Rapid detection of tetracycline resistance in bovine Pasteurella multocida isolates by MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA)
Authors: Van Driessche Laura , Bokma Jade , Gille Linde , Ceyssens Pieter-Jan , Sparbier Katrin , Haesebrouck Freddy , Deprez Piet , Boyen Filip , Pardon Bart 
Published: September 2018

AbstractPasteurella multocida is notorious for its role as an opportunistic pathogen in infectious bronchopneumonia, the economically most important disease facing cattle industry and leading indication for antimicrobial therapy. To rationalize antimicrobial use, avoiding imprudent use of highly and critically important antimicrobials for human medicine, availability of a rapid antimicrobial susceptibility test is crucial. The objective of the present study was to design a MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA) procedure for tetracycline resistance detection in P. multocida. This procedure was validated on 100 clinical isolates with MIC-gradient strip test, and a comparison with disk diffusion was made. Sensitivity and specificity of the MBT-ASTRA procedure were 95.7% (95% confidence interval (CI) = 89.8–101.5) and 100% (95% CI = 100–100), respectively, classifying 98% of the isolates correctly after only three hours of incubation. Sensitivity and specificity of disk diffusion were 93.5% (95% CI = 86.3–100.6) and 96.3% (95% CI = 91.3–101.3) respectively, classifying 95% of the isolates correctly. In conclusion, this MBT-ASTRA procedure has all the potential to fulfil the need for a rapid and highly accurate tetracycline susceptibility testing in P. multocida to rationalize antimicrobial use in outbreaks of bronchopneumonia in cattle or other clinical presentations across species.
Interannual variability of leaf area index of an evergreen conifer stand was affected by carry-over effects from recent climate conditions
Authors: Sumida Akihiro , Watanabe Tsutomu , Miyaura Tomiyasu 
Published: September 2018

AbstractDespite the relevance of leaf area index (LAI) to forest productivity, few studies have focused on the interannual variability of LAI of an evergreen stand and its relationship with stand growth and meteorological factors. We estimated the change in LAI of an evergreen conifer (Chamaecyparis obtusa) stand over 19 years from a dataset using allometric methods. The LAI varied between 7.1 and 8.8 m2 m−2, with a 95% confidence interval of <1.1 m2 m−2over the 19 years. This LAI range was maintained such that the gradual increase in leaf area (LA) of the largest trees counterbalanced the gradual loss in LA of the smallest trees. Meanwhile, more trees showed a temporary decrease in LA in years with low summer precipitation. The LAI and current-year mean temperature for July and August (TJA) were weakly correlated, whereas the correlation coefficient increased (r = 0.93) when LAI was correlated with the moving averageTJAover the previous 6 years, which agreed with the estimated turnover time of canopy foliage. The annual stem biomass growth rate was significantly positively correlated with summer precipitation, but not with LAI. These results will be useful for refining models in studies on forest growth and global climate change.
Neurotransmitter identity and electrophysiological phenotype are genetically coupled in midbrain dopaminergic neurons
Authors: Tapia Mónica , Baudot Pierre , Formisano-Tréziny Christine , Dufour Martial A. , Temporal Simone , Lasserre Manon , Marquèze-Pouey Béatrice , Gabert Jean , Kobayashi Kazuto , Goaillard Jean-Marc 
Published: September 2018

AbstractMost neuronal types have a well-identified electrical phenotype. It is now admitted that a same phenotype can be produced using multiple biophysical solutions defined by ion channel expression levels. This argues that systems-level approaches are necessary to understand electrical phenotype genesis and stability. Midbrain dopaminergic (DA) neurons, although quite heterogeneous, exhibit a characteristic electrical phenotype. However, the quantitative genetic principles underlying this conserved phenotype remain unknown. Here we investigated the quantitative relationships between ion channels’ gene expression levels in midbrain DA neurons using single-cell microfluidic qPCR. Using multivariate mutual information analysis to decipher high-dimensional statistical dependences, we unravel co-varying gene modules that link neurotransmitter identity and electrical phenotype. We also identify new segregating gene modules underlying the diversity of this neuronal population. We propose that the newly identified genetic coupling between neurotransmitter identity and ion channels may play a homeostatic role in maintaining the electrophysiological phenotype of midbrain DA neurons.
ADAP1 limits neonatal cardiomyocyte hypertrophy by reducing integrin cell surface expression
Authors: Giguère Hugo , Dumont Audrey-Ann , Berthiaume Jonathan , Oliveira Vanessa , Laberge Gino , Auger-Messier Mannix 
Published: September 2018

AbstractThe ArfGAP with dual PH domains 1 (ADAP1) regulates the activation of the hypertrophic mitogen-activated protein kinase ERK1/2 pathway in non-cardiomyocytes. However, its role in cardiomyocytes is unknown. Our aim was to characterize the role of ADAP1 in the hypertrophic process of cardiomyocytes. We assessed the expression of ADAP1 in the hearts of adult and neonatal rats by RT-qPCR and Western blotting and showed that it is preferentially expressed in cardiomyocytes. Adenoviral-mediated ADAP1 overexpression in cultured rat neonatal ventricular cardiomyocytes limited their serum-induced hypertrophic response as measured by immunofluorescence microscopy. Furthermore, ADAP1 overexpression completely blocked phenylephrine- and Mek1 constitutively active (Mek1ca) mutant-induced hypertrophy in these cells. The anti-hypertrophic effect of ADAP1 was not caused by a reduction in protein synthesis, interference with the Erk1/2 pathway, or disruption of the fetal gene program activation, as assessed by nascent protein labeling, Western blotting, and RT-qPCR, respectively. An analysis of cultured cardiomyocytes by confocal microscopy revealed that ADAP1 partially re-organizes α-actinin into dense puncta, a phenomenon that is synergized by Mek1ca overexpression. Biotin labeling of cell surface proteins from cardiomyocytes overexpressing ADAP1 revealed that it reduces the surface expression of β1-integrin, an effect that is strongly potentiated by Mek1ca overexpression. Our findings provide insights into the anti-hypertrophic function of ADAP1 in cardiomyocytes.
Raman imaging as a new approach to identification of the mayenite group minerals
Authors: Środek D. , Dulski M. , Galuskina I. 
Published: September 2018

AbstractThe mayenite group includes minerals with common formula Ca12Al14O32−x(OH)3x[W6−3x], where W = F, Cl, OH, H2O and x = 0–2. This distinction in the composition is associated with W site which may remain unoccupied or be occupied by negatively charged ions: OH−, F−, Cl−, as well as neutral molecules like H2O. However, there is no experimental approach to easily detect or differentiate mineral species within the mayenite group. Electron micro-beam facilities with energy- or wavelength-dispersive X-ray detectors, as most common tools in mineralogy, appear to be insufficient and do not provide a definite identification, especially, of hydroxylated or hydrated phases. Some solution provides typical Raman analysis ensuring identification of minerals and 3D Raman imaging as an innovative approach to distinguish various co-existing minerals of the mayenite group within a small area of the rock sample. Raman spectroscopy has also been successfully used for a determination of water type incorporated into the mineral structure as well as for a spatial distribution of phases by cluster approach analysis and/or integrated intensity analysis of bands in the hydroxyl region. In this study, Raman technique was for the first time used to reconstruct a 3D model of mayenite group mineral zonation, as well as to determine a way of water incorporation in the structure of these minerals. Moreover, for the first time, Raman data were correlated with alterations during the mineral-forming processes and used for reconstruction of the thermal history of studied rock. As a result, the influence of combustion gases has been proposed as a crucial factor responsible for the transformation between fluormayenite and fluorkyuygenite.
Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival
Authors: Varghese Robin T. , Young Sarah , Pham Lily , Liang Yanping , Pridham Kevin J. , Guo Sujuan , Murphy Susan , Kelly Deborah F. , Sheng Zhi 
Published: September 2018

AbstractGlioblastoma is the most common malignant brain cancer with a dismal prognosis. The difficulty in treating glioblastoma is largely attributed to the lack of effective therapeutic targets. In our previous work, we identified casein kinase 1 ε (CK1ε, also known as CSNK1E) as a potential survival factor in glioblastoma. However, how CK1ε controls cell survival remains elusive and whether targeting CK1ε is a possible treatment for glioblastoma requires further investigation. Here we report that CK1ε was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma, but not glia cells. Depletion of CK1ε remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells, while having limited effect on astrocytes. CK1ε deprivation activated β-catenin and induced apoptosis, which was further counteracted by knockdown of β-catenin. The CK1ε inhibitor IC261, but not PF-4800567, activated β-catenin and blocked the growth of glioblastoma cells and glioblastoma stem cells. Congruently, IC261 elicited a robust growth inhibition of human glioblastoma xenografts in mice. Together, our results demonstrate that CK1ε regulates the survival of glioblastoma cells and glioblastoma stem cells through β-catenin signaling, underscoring the importance of targeting CK1ε as an effective treatment for glioblastoma.