bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of acute lying and sleep deprivation on the behavior of lactating dairy cows
Authors: Kull Jessie A. , Proudfoot Katy L. , Pighetti Gina M. , Bewley Jeffery M. , O’Hara Bruce F. , Donohue Kevin D. , Krawczel Peter D. 
Published: February 2019

ABSTRACTThe objective was to determine the effects of sleep or lying deprivation on the behavior of dairy cows. Data were collected from 8 multi- and 4 primiparous cows (DIM = 199 ± 44 (mean ± SD); days pregnant = 77 ± 30). Using a crossover design, each cow experienced: 1) sleep deprivation implemented by noise or physical contact when their posture suggested sleep, and 2) lying deprivation imposed by a grid placed on the pen floor. One day before treatment (baseline), and treatment day (treatment) were followed by a 12-d washout period. Study days were organized from 2100 to 2059. During habituation (d −3 and −2 before treatment), baseline (d −1), and trt (d 0), housing was individual boxstalls (mattress with no bedding). After treatment, cows returned to sand-bedded freestalls for a 7-d recovery period (d 1 to 7) where data on lying behaviors were collected. Daily lying time, number lying bouts, bout duration, and number of steps were recorded by dataloggers attached to the hind leg of cows throughout the study period. Data were analyzed using a mixed model in SAS including fixed effects of treatment (sleep deprivation vs. sleep and lying deprivation), day, and their interaction with significant main effects separated using a PDIFF statement (P ≤ 0.05). Interactions between treatment and day were detected for daily lying time and the number of bouts. Lying time was lower for both treatments during the treatment period compared to baseline. Lying time increased during the recovery period for both lying and sleep deprived cows. However, it took 4 d for the lying deprived cows to fully recover their lying time after treatment, whereas it took the sleep deprived cows 2 d for their lying time to return to baseline levels. Results suggest that both sleep and lying deprivation can have impact cow behavior. Management factors that limit freestall access likely reduce lying time and sleep, causing negative welfare implications for dairy cows.
SCFAs-induced GLP-1 Secretion Links the Regulation of Gut Microbiome on Hepatic Lipogenesis in Chickens
Authors: Zhang Jianmei , Sun Yin shuang , Zhao Liqin , Chen Tiantian , Fan Meina , Jiao Hongchao , Zhao Jingpeng , Wang Xiaojuan , Li Fuchang , Li Haifang , Lin Hai 
Published: February 2019

ABSTRACTChickens represent a specific case in lipid metabolism that liver is the main site of lipid synthesis. As ovipara, their gut microbiota could be strongly influenced by environment and diets after hatching. The aim of this study is to elucidate the linkage of gut microbiota and fat synthesis in broilers. The broilers were subjected to dietary treatments of combined probiotics (Clostridium butyrate4×108cfu/kg,Bifidobacterium2×108cfu/kg,Lactobacillus plantarum2×108cfu/kg andLactococcus faecalis2×108cfu/kg, PB) and guar gum (1 g/kg, GG). The result showed that dietary supplementation of PB and GG changed the cecal microbiota diversity, altered short chain fatty acids (SCFAs) contents, and suppressed lipogenesis in liver and abdominal fat tissues. In intestinal epithelial cells (IECs), acetate, propionate, and butyrate upregulated the expression of glucagon-like peptide-1 (GLP-1) via MAPK pathways, especially via the ERK and p38 MAPK pathways. GLP-1 suppressed lipid accumulation in primary hepatocytes with the involvement of AMPK/ACC signaling. In conclusion, the result suggests that SCFAs-induced GLP-1 secretion links the regulation of gut microbiome on hepatic lipogenesis in chickens.IMPORTANCEIntestinal microbes metabolize SCFAs and stimulate intestinal epithelium L cells to produce GLP-1. Recent evidence showed that GLP-1 reduced fat deposition by reducing appetite and increasing satiety. However, how SCFAs stimulate the secretion of GLP-1 and whether GLP-1 directly affects fat metabolism is not clear. Poultry adipocytes have limited ability to produce fat, and 90% of carcass fat is synthesized in the liver. In addition, large intake of feeds easily leads to fatty liver diseases in chickens. The aim of this study is to investigate how SCFAs mediate secretion of GLP-1 and whether GLP-1 could directly affect hepatic deposition in broiler chickens. The hepatic lipogenesis regulated by the intestinal microbiota of chickens is of great significance to the study of intestinal microbiota and fat deposition in poultry, and this work could provide reference for intestinal microorganism and fat metabolism in mammals and humans.
Resilience trinity: safeguarding ecosystem services across three different time horizons and decision contexts
Authors: Weise H , Auge H , Baessler C , Bärlund I , Bennett E.M. , Berger U , Bohn F , Bonn A , Borchardt D , Brand F , Chatzinotas A , Corstanje R , De Laender F , Dietrich P , Dunker S , Durka W , Fazey I , Groeneveld J , Guilbaud CSE , Harms H , Harpole S , Harris J , Jax K , Jeltsch F , Johst K , Joshi J , Klotz S , Kühn I , Kuhlicke C , Müller B , Radchuk V , Reuter H , Rinke K , Schmitt-Jansen M , Seppelt R , Singer A , Standish RJ , Thulke HH , Tietjen B , Weitere M , Wirth C , Wolf C , Grimm V 
Published: February 2019

AbstractEnsuring ecosystem resilience is an intuitive approach to safeguard future provisioning of ecosystem services (ES). However, resilience is an ambiguous concept and difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough because the usefulness of a mechanism is context-dependent. We suggest a conceptual framework, resilience trinity, to facilitate management of resilience mechanisms in three distinctive decision contexts and time-horizons. i) reactive, when there is an imminent threat to ES resilience and a high pressure to act, ii) adjustive, when the threat is known in general but there is still time to adapt management, and iii) provident when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. This emphasizes that resilience has different interpretations and implications at different time horizons which however need to be reconciled. The inclusion of time into resilience thinking ensures that longer-term management actions are not missed while urgent threats to ES are given priority.
Paternal age affects offspring’s behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST
Authors: Yoshizaki Kaichi , Koike Tasuku , Kimura Ryuichi , Kikkawa Takako , Oki Shinya , Koike Kohei , Mochizuki Kentaro , Inada Hitoshi , Kobayashi Hisato , Matsui Yasuhisa , Kono Tomohiro , Osumi Noriko 
Published: February 2019

AbstractAdvanced paternal age has deleterious effects on mental health of next generation. Using a mouse model, we have confirmed that offspring derived from aged fathers showed impairments in behavior and abnormalities in the brain structure and activity. Comprehensive target DNA methylome analyses revealed in aged sperm more hypo-methylated genomic regions, in which REST/NRSF binding motif was enriched. Gene set enrichment analyses also identified enrichment of “REST/NRSF target genes”, in addition to “Late-fetal genes” and autism spectrum disorder-related “SFARI genes”, in up-regulated genes of developing brains from aged father. Indeed, gene sets near hypo-methylated genomic regions with REST/NRSF binding motif were also enriched in up-regulated genes of developing brains. Taken altogether, DNA hypo-methylation due to paternal aging in sperm will induce leaky expression of REST/NRSF target genes in the developing brain, thereby causing neuronal abnormalities and subsequent behavioral alteration in offspring.
Using time causal quantifiers to characterize sleep stages
Authors: Mateos Diego M. , Gómez-Ramírez Jaime , Rosso Osvaldo A. 
Published: February 2019

AbstractSleep plays substantial role in daily cognitive performance, mood and memory. The study of sleep has attracted the interest of neuroscientists, clinicans and the overall population, with increasing number of adults suffering from insufficient amounts of sleep. Sleep is an activity composed of different stages whose temporal dynamics, cycles and inter dependencies are not fully understood. Healthy body function and personal well being, however, depends on proper unfolding and continuance of the sleep cycles. The characterization of the different sleep stages can be undertaken with the development of biomarkers derived from sleep recording. For this purpose, in this work we analyzed single-channel EEG signals from 106 healthy subjects. The signals were quantified using the permutation vector approach using five different information theoretic measures: i) Shannon’s entropy, ii) MPR statistical complexity, iii) Fisher information, iv) Renyí Min-entropy and v) Lempel-Ziv complexity. The results show that all five information theory-based measures make possible to quantify and classify the underlying dynamics of the different sleep stages. In addition to this, we combine these measures to show that planes containing pairs of measures, such as the plane composed of Lempel-Ziv and Shannon, have a better performance for differentiating sleep states than measures used individually for the same purpose.
Noisy Perturbation Models Distinguish Network Specific from Embedding Variability
Authors: Piehler A. 
Published: February 2019

AbstractRecently, measurement technologies allowing to determine the abundance of tens signaling proteins in thousands of single cells became available. The interpretation of this high dimensional end-point time course data is often difficult, because sources of cell-to-cell abundance variation in measured species are hard to determine. Here I present an analytic tool to tackle this problem. By using a recently developed chemical signal generator to manipulate input noise of biochemical networks, measurement of state variables and modeling of input noise propagation, pathway-specific variability can be distinguished from environmental variability caused by network embedding. By employing different sources of natural input noise, changes in the output variability were quantified, indicating that also synthetic noisy perturbations are biologically feasible. The presented analytic tool shows how signal generators can improve our understanding of the origin of cellular variability and help to interpret multiplexed single cell information.
A Differentially Methylated CpG Site in theIL4Gene Associated with Anti-FVIII Inhibitor Antibody Development in Hemophilia A
Authors: de Souza Thiago Barbosa , de Souza Thais Louvain , Santos Ferreira Cristina dos , da Silva Cleiton Figueiredo Osório , Rossetti Liliana Carmen , Marchione Vanina Daniela , De Brasi Carlos Daniel , Medina-Acosta Enrique 
Published: February 2019

AbstractHemophilia A is the most common clotting disorder in humans. It affects one in five thousand live-born children. Mutations in the X-chromosome linkedF8gene lead to the deficiency of circulating factor VIII (FVIII). The defect is characterized by severe bleeding. The standard therapy is to replace the deficient factor intravenously. The main adverse event of the therapy is the development of anti-FVIII inhibitor antibodies that impair coagulation and result in increased complications and risk of death. Several risk factors have been described for the development of inhibitor antibodies, among them age, type of FVIII administered, ethnicity, and variant alleles in immune response genes. Epigenetic risks factors have not yet been explored. This work aimed to evaluate the methylation statuses at thirteen CpG sites (5meCpG) in regulatory regions of theIL1B, IL2, IL4, IL6, IL10, TNF, IFNG, CTLA4, CD28, andCST7immune regulation genes in hemophilia A affected males on replacement therapy who develop or do not develop inhibitor antibodies. At each of the thirteen specific CpG sites, we observed one of three possible statuses: hypermethylated, hypomethylated or intermediate methylated. We found a statistically significant (p= 0.04) decrease in the methylation level at one CpG site in theIL4intron 1 (CpG-3) in the affected group of patients presenting with anti-FVIII inhibitors as compared with the group of patients without inhibitors. The differential 5meCpG-3 maps within a predicted enhancer region inIL4intron 1 that overlaps DNase I hypersensitive chromatin region of the Th2IL5, IL13, andIL4cytokine gene cluster and, therefore, permissive for gene expression. Six-bp upstream of the differentially 5meCpG-3 is the rs2227282cisexpression quantitative trait locus that influences the transcript levels of thePDLIM4, SLC22A4, SLC22A5, RAD50, IL4, KIF3A, SEPT8genes. We consider theIL4(CpG-3) site a promising lead epigenetic mark, the potential value of which must be appraised in a larger group of patients. The methodology employed also allowed to evaluate the distribution of theIL6rs35081782 insertion/deletion variant, associated with white blood cell count traits in genome-wide association studies, and which showed no difference in distribution between the groups of patients.
Loss of TET proteins in regulatory T cells unleashes effector function
Authors: Yue Xiaojing , Lio Chan-Wang J. , Samaniego-Castruita Daniela , Li Xiang , Rao Anjana 
Published: February 2019

AbstractTET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and other oxidized methylcytosines, mediating DNA demethylation and serving as new epigenetic marks. Here we examine the role of TET proteins in Foxp3+ regulatory T (Treg) cells, a distinct lineage of CD4+ T cells that prevent autoimmunity and maintain immune homeostasis. We report that Tet2/3fl/flFoxp3Cre mice that lack Tet2 and Tet3 specifically in Treg cells develop splenomegaly, leukocyte infiltration into tissues and inflammatory disease. Treg cells from these mice showed altered expression of Treg signature genes, with upregulation of genes involved in cell cycle regulation, DNA damage repair and cancer. In littermate mice with more severe inflammation, both CD4+ Foxp3+ and CD4+ Foxp3- cells showed strong skewing towards Tfh and/or Th17 phenotypes. Notably, the presence of wild type Treg cells in mixed bone marrow chimeras and Tet2/3fl/flFoxp3WT/Cre heterozygous female mice did not suppress the aberrant phenotype and function of Tet2/3fl/flFoxp3Cre Treg cells. Fate-mapping experiments indicated that Treg cells from Tet2/3fl/flFoxp3Cre mice were more prone to lose Foxp3 expression; moreover, transfer of total CD4+ T cells isolated from Tet2/3fl/flFoxp3Cre mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis in mice.
Alpaca: a kmer-based approach for investigating mosaic structures in microbial genomes
Authors: Salazar Alex N. , Abeel Thomas 
Published: February 2019

AbstractSummaryMicrobial genomes are often mosaic: different regions can possess different evolutionary origins due to genetic recombination. The recent feasibility to assemble microbial genomes completely and the availability of sequencing data for complete microbial populations, means that researchers can now investigate the potentially rich evolutionary history of a microbe at a much higher resolution. Here, we present Alpaca: a method to investigate mosaicism in microbial genomes based on kmer similarity of large sequencing datasets. Alpaca partitions a given assembly into various sub-regions and compares their similarity across a population of genomes. The result is a high-resolution map of an entire genome and the most similar scoring clades across the given population.Availabilityhttps://github.com/AbeelLab/AlpacaContactt.abeel@tudelft.nl
AligNet: Alignment of Protein-Protein Interaction Networks
Authors: Alberich R. , Alcalá A. , Llabrés M. , Rosselló F. , Valiente G. 
Published: February 2019

AbstractOne of the most difficult problems difficult problem in systems biology is to discover protein-protein interactions as well as their associated functions. The analysis and alignment of protein-protein interaction networks (PPIN), which are the standard model to describe protein-protein interactions, has become a key ingredient to obtain functional orthologs as well as evolutionary conserved pathways and protein complexes. Several methods have been proposed to solve the PPIN alignment problem, aimed to match conserved subnetworks or functionally related proteins. However, the right balance between considering network topology and biological information is one of the most difficult and key points in any PPIN alignment algorithm which, unfortunately, remains unsolved. Therefore, in this work, we propose AligNet, a new method and software tool for the pairwise global alignment of PPIN that produces biologically meaningful alignments and more efficient computations than state-of-the-art methods and tools, by achieving a good balance between structural matching and protein function conservation as well as reasonable running times.
Extracellular matrix mineralization in the mouse osteoblast-like cell line MC3T3-E1 is regulated by actin cytoskeleton reorganization and non-protein molecules secreted from the cells themselves
Authors: Suzuki Hiraku , Tatei Kazuaki , Ohshima Noriyasu , Sato Seiichi , Izumi Takashi 
Published: February 2019

AbstractBone tissue constantly undergoes turnover via bone formation by osteoblasts and bone resorption by osteoclasts. This process enables bone to maintain its overall shape while altering its local structure. However, the detailed mechanism of how osteoblast cell-signaling systems induce various structural changes in bone tissue have not yet been completely elucidated. In this study, we focused on the actin cytoskeleton as a regulatory system for bone formation and constructed anin vitroexperimental system using the mouse osteoblast-like cell line MC3T3-E1. We found that, in MC3T3-E1 cells, the actin cytoskeleton had an important role in matrix mineralization via activation of specific developmental pathways and it was regulated by non-protein molecules secreted from MC3T3-E1 cells themselves. In MC3T3-E1 cells, we observed changes of actin cytoskeleton reorganization and accumulation of PIP2related to actin filament convergences during cell differentiation, in the undifferentiated, early, middle and late stage. Actin cytoskeleton disruption with Cyto D, polymerization inhibitor of actin filament, in early and middle stage cells induced significant increase of osteocalcin mRNA expression normally expressed only in late stage, decrease of Alkaline phosphatase mRNA expression after 24h and abnormal matrix mineralization in MC3T3-E1 cells. Inhibition of Giα with PTX known to regulate actin cytoskeleton in middle stage induced changes in the actin cytoskeleton and PIP2accumulation and suppression of matrix mineralization after 5 days. Furthermore, addition of non-protein molecules from culture medium of cells at various differentiation stage induced difference of PIP2accumulation after 5 min, actin cytoskeleton in 20 min, and matrix mineralization after 5 days. These results not only provide new knowledge about the actin cytoskeleton function in bone-forming cells, but also suggest that cell signaling via non-protein molecules such as lipids plays important roles in bone formation.
Network-wide abnormalities explain memory variability in hippocampal amnesia
Authors: Argyropoulos Georgios P. D. , Loane Clare , Roca-Fernandez Adriana , Lage-Martinez Carmen , Gurau Oana , Irani Sarosh R , Butler Christopher R 
Published: February 2019

AbstractPatients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n=38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Such network abnormalities may explain the variability across studies of amnesia and speak to theoretical debates in memory neuroscience.
Evaluations of short telomere risk-associated single nucleotide polymorphisms in telomerase reverse transcriptase gene on telomere length maintenance
Authors: Xu Jialin , Trudeau Matthew A. , Sandford Andrew J. , Wong Judy M.Y. 
Published: February 2019

ABSTRACTTelomere biology disorders (TBDs) refer to a spectrum of tissue degenerative disorders caused by genetic mutations in telomere biology genes. Most patients with TBDs suffer from telomere maintenance defects secondary to telomerase deficiency. While the highly penetrant mutations in the telomerase reverse transcriptase (TERT) gene that drive disease onset and progression of TBDs are relatively rare, there exist several single nucleotide polymorphisms (SNPs) in TERT that have been linked to various diseases in the TBD spectrum. In this study, we investigated the biochemical properties of five TERT variants. In an ex vivo cell model, we found that primary human fibroblasts expressing nonsynonymous TERT SNPs had comparable cell growth kinetics to primary cells expressing WT-TERT, while a parallel vector control expressing-cell line entered replicative senescence. At the molecular level, primary cells expressing the minor alleles of two of the five TERT variants (A279T, ΔE441) had replication-dependent loss of telomere length. In an in vitro primer extension assay, these two variants showed reduced telomerase nucleotide addition processivity. Together, our data suggested that selective, common TERT variants could be revealed to harbour telomere maintenance defects, leading to a plausible explanation for their observed associations to telomere biology disorders.