bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation age is accelerated in alcohol dependence
Authors: Rosen Allison D. , Robertson Keith D. , Hlady Ryan A. , Muench Christine , Lee Jisoo , Philibert Robert , Horvath Steve , Kaminsky Zachary A. , Lohoff Falk W. 
Published: September 2018

AbstractAlcohol dependence (ALC) is a chronic, relapsing disorder that increases the burden of chronic disease and significantly contributes to numerous premature deaths each year. Previous research suggests that chronic, heavy alcohol consumption is associated with differential DNA methylation patterns. In addition, DNA methylation levels at certain CpG sites have been correlated with age. We used an epigenetic clock to investigate the potential role of excessive alcohol consumption in epigenetic aging. We explored this question in five independent cohorts, including DNA methylation data derived from datasets from blood (n = 129, n = 329), liver (n = 92, n = 49), and postmortem prefrontal cortex (n = 46). One blood dataset and one liver tissue dataset of individuals with ALC exhibited positive age acceleration (p < 0.0001 and p = 0.0069, respectively), whereas the other blood and liver tissue datasets both exhibited trends of positive age acceleration that were not significant (p = 0.83 and p = 0.57, respectively). Prefrontal cortex tissue exhibited a trend of negative age acceleration (p = 0.19). These results suggest that excessive alcohol consumption may be associated with epigenetic aging in a tissue-specific manner and warrants further investigation using multiple tissue samples from the same individuals.
A gene co-expression module implicating the mitochondrial electron transport chain is associated with long-term response to lithium treatment in bipolar affective disorder
Authors: Stacey David , Schubert K. Oliver , Clark Scott R. , Amare Azmeraw T. , Milanesi Elena , Maj Carlo , Leckband Susan G. , Shekhtman Tatyana , Kelsoe John R. , Gurwitz David , Baune Bernhard T. 
Published: September 2018

AbstractLithium is the first-line treatment for bipolar affective disorder (BPAD) but two-thirds of patients respond only partially or not at all. The reasons for this high variability in lithium response are not well understood. Transcriptome-wide profiling, which tests the interface between genes and the environment, represents a viable means of exploring the molecular mechanisms underlying lithium response variability. Thus, in the present study we performed co-expression network analyses of whole-blood-derived RNA-seq data from n = 50 lithium-treated BPAD patients. Lithium response was assessed using the well-validated ALDA scale, which we used to define both a continuous and a dichotomous measure. We identified a nominally significant correlation between a co-expression module comprising 46 genes and lithium response represented as a continuous (i.e., scale ranging 0–10) phenotype (cor = −0.299, p = 0.035). Forty-three of these 46 genes had reduced mRNA expression levels in better lithium responders relative to poorer responders, and the central regulators of this module were all mitochondrially-encoded (MT-ND1, MT-ATP6, MT-CYB). Accordingly, enrichment analyses indicated that genes involved in mitochondrial functioning were heavily over-represented in this module, specifically highlighting the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) as affected processes. Disrupted ETC and OXPHOS activity have previously been implicated in the pathophysiology of BPAD. Our data adds to previous evidence suggesting that a normalisation of these processes could be central to lithium’s mode of action, and could underlie a favourable therapeutic response.
TRIM52 plays an oncogenic role in ovarian cancer associated with NF-kB pathway
Authors: Yang Weihong , Liu Li , Li Caixia , Luo Ning , Chen Rong , Li Li , Yu Fudong , Cheng Zhongping 
Published: September 2018

AbstractEmerging evidence suggests that the members of the tripartite motif (TRIM) family play a crucial role in cancer development and progression. The purpose of the study was to explore TRIM52's role in tumorigenesis and its potential molecular mechanism in ovarian cancer. The study demonstrated that knockdown of TRIM52 in SKOV3 and CAOV3 cells inhibited ovarian cancer cell invasion, migration, and proliferation, and induced cell apoptosis. On the contrary, overexpression of TRIM52 in HO8910 cells showed contrary results. Further, overexpression of TRIM52 enhanced the expression of phosphorylated IKKβ and IKBα proteins and nuclear protein P65, which implied the activation of NF-kB signal pathway. Knockdown of TRIM52 downregulated the mRNA and protein levels of NF-kB signal downstream effectors of the NF-kB pathway, including MMP9, Bcl2, IL8, and TNFα, but upregulated caspase-3 expression. These results suggested that activation of the NF-kB pathway is involved in TRIM52-mediated regulation in ovarian cancer. The nude mice study further confirmed that knockdown of TRIM52 blocked tumor growth, inhibited cell proliferation, and promoted cell apoptosis. Our data strongly suggested that TRIM52 plays an oncogenic role in ovarian cancer development associated with the NF-kB signal pathway and may be a potential target for cancer therapy.
SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death
Authors: Yue Yuan , Nabar Neel R. , Shi Chong-Shan , Kamenyeva Olena , Xiao Xun , Hwang Il-Young , Wang Min , Kehrl John H. 
Published: September 2018

AbstractThe molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation—all likely contributing to the clinical manifestations of SARS-CoV infection.
Four putative SWI2/SNF2 chromatin remodelers have dual roles in regulating DNA methylation in Arabidopsis
Authors: Yang Dong-Lei , Zhang Guiping , Wang Lili , Li Jingwen , Xu Dachao , Di Cuiru , Tang Kai , Yang Lan , Zeng Liang , Miki Daisuke , Duan Cheng-Guo , Zhang Huiming , Zhu Jian-Kang 
Published: September 2018

AbstractDNA methylation is a conserved epigenetic mark that is critical for many biological processes in plants and mammals. In Arabidopsis, the antagonistic activities of RNA-directed DNA methylation (RdDM) and ROS1-dependent active DNA demethylation are key for the dynamic regulation of locus-specific DNA methylation. However, the molecular factors that coordinate RdDM and active demethylation are largely unknown. Here we report that CLSY4 and its three paralogous SWI2/SNF2-type chromatin-remodeling proteins function in both RdDM and DNA demethylation in Arabidopsis. We initially identified CLSY4 in a genetic screen for DNA demethylation factors and subsequently demonstrated that it also is important in RdDM. Comprehensive genetic analyses using single and high order mutants of CLSY family proteins revealed their roles as double agents in the balance between methylation and demethylation reactions. The four CLSY proteins collectively are necessary for the canonical RdDM pathway; at the same time, each CLSY likely mediates DNA demethylation at specific loci where DNA methylation depends on RdDM. These results indicate that the four chromatin-remodeling proteins have dual functions in regulating genomic DNA methylation, and thus provide new insights into the dynamic regulation of DNA methylation in a model multicellular eukaryotic organism.
A flexible high speed pulse chopper system for an inverted neutron time-of-flight option on backscattering spectrometers
Authors: Appel Markus , Frick Bernhard , Magerl Andreas 
Published: September 2018

AbstractWe present the design and simulation of a high resolution inverted time-of-flight option for a neutron spectrometer with crystal analysers in backscattering, with specific reference to the IN16B spectrometer at the Institut Laue-Langevin, Grenoble. While the conventional configuration with Si 111 crystals provides sub-μeV resolution in an energy range limited to ±30 μeV, the novel BATS option (BATS: Backscattering and Time-of-flight Spectrometer) extends the energy window to 340 μeV with only a slightly increased resolution of 1.2 μeV. Moreover, the observation window can be shifted to inelastic energy transfers. To bring this about, a novel fast chopper system with disks of large diameter and complex slit pattern is used, offering high flexibility in resolution and repetition rate. The chopper system consists out of two counter rotating disk chopper pairs. It provides 7 different pulse lengths, three pulse repetition rates up to 237 Hz and can operate with Si 111 or Si 311 crystal analysers. The latter option is a unique feature which covers a Q-range up to 3.7 Å−1 with a resolution of 6.8 μeV. Extensive ray-tracing simulations have been used to validate the design of the pulse chopper system, set limits on the sample size, and assess the achievable energy resolutions of the different chopper configurations.
Macrofungal species distributions depend on habitat partitioning of topography, light, and vegetation in a temperate mountain forest
Authors: Chen Yun , Yuan Zhiliang , Bi Shuai , Wang Xueying , Ye Yongzhong , Svenning Jens-Christian 
Published: September 2018

AbstractThe habitat partitioning hypothesis provides a conceptual framework for explaining the maintenance of plant and animal diversity. Its central tenet assumes environmental conditions are spatially structured, and that this structure is reflected in species distributions through associations with different habitats. Studies confirming habitat partitioning effects have focused primarily on spatial distributions of plants and animals, with habitat partitioning hypothesis under explored for macrofungi. Here, we examined the sporocarps of macrofungi in a 5-ha forest dynamics plot in China. We used four different methods to define microhabitats for habitat partitioning analyses based on topography, understory light availability, plant community, or a combination of these factors, and analyzed the effect of microhabitat partitioning on epigeous macrofungal community. Our results showed that the characteristics of the macrofungal assemblages varied among the habitats. A total of 85 species examined were associated with one or more of the habitat types (85/125, 68%). The factors related to the sporocarp composition differed among the various microhabitats. Our findings suggest that different microhabitats favor occurrence of different macrofungal species, and sporocarps -environment relation varied among the different microhabitats at this temperate mountain forest locality. These findings shed new light to the biodiversity conservation in macrofungi in temperate deciduous broad-leaved forest and point to the potential importance of microhabitat partitioning for sporocarp formation.
Modeling clock-related metabolic syndrome due to conflicting light and food cues
Authors: Woller Aurore , Gonze Didier 
Published: September 2018

AbstractMost organisms possess a light- and food- entrainable circadian clock system enabling their adaptation to daily environmental changes in sunlight and food availability. The mammalian circadian system is composed of multiple clocks throughout the body. These local clocks are entrained by nutrient, neural, endocrine and temperature cues and drive diverse physiological functions including metabolism. In particular, the clock of the pancreatic β cell rhythmically regulates the transcription of genes involved in glucose-stimulated insulin secretion. Perturbations of this fine-tuned oscillatory network increase the susceptibility to diseases. Besides chronic jet lag and shift work, common perturbations are ill-timed eating patterns which can lead to metabolic troubles (such as hypoinsulinemia). We have built a mathematical model describing the clock-dependent pancreatic regulation of glucose homeostasis in rodents. After calibrating the model using experimental data, we have investigated the effect of restricting food access to the normal rest phase. Our simulations show that the conflict between the light-dark cycle and the feeding-fasting cycle creates a differential phase shift in the expression of core clock genes (consistent with experimental observations). Our model further predicts that this induces a non-concomitance between nutrient cues and clock-controlled cues driving metabolic outputs which results in hypoinsulinemia, hyperglycemia as well as in a loss of food anticipation.
Identification of differentially methylated region (DMR) networks associated with progression of nonalcoholic fatty liver disease
Authors: Hotta Kikuko , Kitamoto Aya , Kitamoto Takuya , Ogawa Yuji , Honda Yasushi , Kessoku Takaomi , Yoneda Masato , Imajo Kento , Tomeno Wataru , Saito Satoru , Nakajima Atsushi 
Published: September 2018

AbstractThe progression of nonalcoholic fatty liver disease (NAFLD) is affected by epigenetics. We performed differentially methylated region (DMR) and co-methylation analyses to identify DMR networks associated with the progression of NAFLD. DMRs displaying differences in multiple consecutive differentially methylated CpGs between mild and advanced NAFLD were extracted. The average values of topological overlap measures for the CpG matrix combining two different DMRs were calculated and two DMR networks that strongly correlated with the stages of fibrosis were identified. The annotated genes of one network included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation. The annotated genes of the second network were primarily associated with metabolic pathways. The CpG methylation levels in these networks were strongly affected by age and fasting plasma glucose levels, which may be important co-regulatory factors. The methylation status of five DMRs in the second network was reversible following weight loss. Our results suggest that CpG methylation in DMR networks is regulated concomitantly via aging and hyperglycemia and plays important roles in hepatic metabolic dysfunction, fibrosis, and potential tumorigenesis, which occur during the progression of NAFLD. By controlling weight and blood glucose levels, the methylation of DMRs in the second network may be reduced.
Changes in the midgut diverticula epithelial cells of the European cave spider, Meta menardi, under controlled winter starvation
Authors: Lipovšek Saška , Novak Tone , Janžekovič Franc , Brdelak Nina , Leitinger Gerd 
Published: September 2018

AbstractThe European cave spider, Meta menardi, is among the most common troglophile species inhabiting the cave entrance zone in Europe, where prey is scarce in winter. Spiders feed only if prey is available; otherwise, they are subjected to long-term winter starvation. We carried out a four-month winter starvation of M. menardi under controlled conditions to analyze ultrastructural changes in the midgut diverticula epithelial cells at the beginning, in the middle and at the end of the starvation period. We used light microscopy, TEM and quantified reserve lipids and glycogen. The midgut diverticula epithelium consisted of secretory cells, digestive cells and adipocytes. During starvation, gradual vacuolization of some digestive cells, and some necrotic digestive cells and adipocytes appeared. Autophagic structures, autophagosomes, autolysosomes and residual bodies were found in all three cell types. Spherites and the energy-reserve compounds were gradually exploited, until in some spherites only the membrane remained. Comparison between spring, autumn and winter starvation reveals that, during the growth period, M. menardi accumulate reserve compounds in spherites and protein granules, and energy-supplying lipids and glycogen, like many epigean, overwintering arthropods. In M. menardi, otherwise active all over the year, this is an adaptive response to the potential absence of prey in winter.
Glucosylceramide modifies the LPS-induced inflammatory response in macrophages and the orientation of the LPS/TLR4 complex in silico
Authors: Mobarak Edouard , Håversen Liliana , Manna Moutusi , Rutberg Mikael , Levin Malin , Perkins Rosie , Rog Tomasz , Vattulainen Ilpo , Borén Jan 
Published: September 2018

AbstractToll-like receptor 4 (TLR4) is activated by bacterial lipopolysaccharide (LPS), which drives the production of proinflammatory cytokines. Earlier studies have indicated that cholesterol- and glycosphingolipid-rich subregions of the plasma membrane (lipid domains) are important for TLR4-mediated signaling. We report that inhibition of glucosylceramide (GluCer) synthase, which resulted in decreased concentrations of the glycosphingolipid GluCer in lipid domains, reduced the LPS-induced inflammatory response in both mouse and human macrophages. Atomistic molecular dynamics simulations of the TLR4 dimer complex (with and without LPS in its MD-2 binding pockets) in membranes (in the presence and absence of GluCer) showed that: (1) LPS induced a tilted orientation of TLR4 and increased dimer integrity; (2) GluCer did not affect the integrity of the LPS/TLR4 dimer but reduced the LPS-induced tilt; and (3) GluCer increased electrostatic interactions between the membrane and the TLR4 extracellular domain, which could potentially modulate the tilt. We also showed that GCS inhibition reduced the interaction between TLR4 and the intracellular adaptor protein Mal. We conclude that the GluCer-induced effects on LPS/TLR4 orientation may influence the signaling capabilities of the LPS/TLR4 complex by affecting its interaction with downstream signaling proteins.
Transcriptomic analyses of cacao cell suspensions in light and dark provide target genes for controlled flavonoid production
Authors: Gallego Adriana M. , Rojas Luisa F. , Parra Oriana , Rodriguez Héctor A. , Mazo Rivas Juan C. , Urrea Aura Inés , Atehortúa Lucía , Fister Andrew S. , Guiltinan Mark J. , Maximova Siela N. , Pabón-Mora Natalia 
Published: September 2018

AbstractCatechins, including catechin (C) and epicatechin (E), are the main type of flavonoids in cacao seeds. They play important roles in plant defense and have been associated with human health benefits. Although flavonoid biosynthesis has been extensively studied using in vitro and in vivo models, the regulatory mechanisms controlling their accumulation under light/dark conditions remain poorly understood. To identify differences in flavonoid biosynthesis (particularly catechins) under different light treatments, we used cacao cell suspensions exposed to white-blue light and darkness during 14 days. RNA-Seq was applied to evaluate differential gene expression. Our results indicate that light can effectively regulate flavonoid profiles, inducing a faster accumulation of phenolic compounds and shifting E/C ratios, in particular as a response to switching from white to blue light. The results demonstrated that HY5, MYB12, ANR and LAR were differentially regulated under light/dark conditions and could be targeted by overexpression aiming to improve catechin synthesis in cell cultures. In conclusion, our RNA-Seq analysis of cacao cells cultured under different light conditions provides a platform to dissect key aspects into the genetic regulatory network of flavonoids. These light-responsive candidate genes can be used further to modulate the flavonoid production in in vitro systems with value-added characteristics.
Subtropical adaptation of a temperate plant (Brassica oleracea var. italica) utilizes non-vernalization-responsive QTLs
Authors: Lin Yann-rong , Lee Jou-yi , Tseng Meng-chun , Lee Chieh-ying , Shen Chian-he , Wang Chun-shan , Liou Chia-ching , Shuang Lan-shuan , Paterson Andrew H. , Hwu Kae-kang 
Published: September 2018

AbstractWhile many tropical plants have been adapted to temperate cultivation, few temperate plants have been adapted to the tropics. Originating in Western Europe,Brassica oleraceavernalization requires a period of low temperature andBoFLC2 regulates the transition to floral development. InB. oleraceagermplasm selected in Taiwan, a non-vernalization pathway involvingBoFLC3rather thanBoFLC2 regulates curd induction. In 112 subtropical breeding lines, specific haplotype combinations ofBoFLC3andPAN(involved in floral organ identity and a positional candidate for additional curd induction variation) adaptB. oleraceato high ambient temperature and short daylength. Duplicated genes permitted evolution of alternative pathways for control of flowering in temperate and tropical environments, a principle that might be utilized via natural or engineered approaches in other plants. New insight into regulation of Brassica flowering exemplifies translational agriculture, tapping knowledge of botanical models to improve food security under projected climate change scenarios.
Circuit‐based flux linkage measurement method with the automated resistance correction for SRM sensorless position control
Authors: Liang Yan , Chen Hao 
Published: September 2018

The accuracy of flux linkage measurement is significantly important for a number of sensorless control methods for switched reluctance motor (SRM). This study proposes a novel flux linkage measurement circuit with the automated resistance correction, which comprises only circuit components. During the SRM sensorless operation, the dependence of resistance on temperature leads to the errors in flux linkage measurement and position estimation. The developed scheme is based on the zero‐crossing property which asserts that the flux linkage and current pass through zero simultaneously. Hence, the flux linkage error captured at the time when the current falls to zero represents the resistance error and is used for resistance correction. The proposed circuit has been successfully implemented and tested on a sensorless SRM system. Experiment results indicate that the proposed system in sensorless control can be operated stably at different load torques and at the condition of given speed mutation and load mutation, and the speed range in steady state with rated load torque is 0–160 r/min. The overall estimated position error remains within an acceptable margin of 2%. Hence, it significantly improves the sensorless position estimation and thus SRM performance.