bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obstructive sleep apnea is associated with depressive symptoms in pregnancy
Authors: Redhead Karen , Walsh Jennifer , Galbally Megan , Newnham John P , Watson Stuart J , Eastwood Peter 
Published: November 2019

Abstract

Study Objectives
In pregnancy, the prevalence of both obstructive sleep apnea (OSA) and depression increases. Research reveals an association in the general population with up to 45% of patients diagnosed with OSA having depressive symptoms. Therefore, this study aimed to investigate the relationship between OSA and depression in pregnant women.

Methods
One hundred and eighty-nine women ≥26 weeks pregnant were recruited from a tertiary perinatal hospital. This cross-sectional study measured OSA (Apnea Hypopnea Index, AHI, using an ApneaLink device) and symptoms of depression (Edinburgh Postnatal Depression Scale, EPDS). Data were collected from medical records including participant age, ethnicity, parity, BMI, smoking status, history of depression, and use of antidepressants.

Results
Of the consenting women, data from 124 were suitable for analysis. Twenty women (16.1%) had OSA (AHI ≥ 5 events/h) and 11 (8.8%) had depressive symptoms (EPDS &gt; 12). Women with OSA were more likely to have depressive symptoms after adjusting for covariates, odds ratio = 8.36, 95% CI [1.57, 44.46]. OSA was also related to higher EPDS scores and these were greater in women with a history of depression.

Conclusions
During late pregnancy women with OSA had eight times the odds of having depressive symptoms. Furthermore, an interaction was found between OSA and history of depression. Specifically, in women with no history of depression, OSA increases depressive symptoms. In women with a history of depression, OSA has an even stronger effect on depressive symptomology. This suggests screening for OSA in pregnancy may identify women prone to future depressive episodes and allow for targeted interventions.
Phellem versus xylem: genome-wide transcriptomic analysis reveals novel regulators of cork formation in cork oak
Authors: Lopes Susana T , Sobral Daniel , Costa Bruno , Perdiguero Pedro , Chaves Inês , Costa Augusta , Miguel Célia M 
Published: November 2019

Abstract
Cork cambium (or phellogen) is a secondary meristem responsible for the formation of phelloderm and phellem/cork, which together compose the periderm. In Quercus suber L., the phellogen is active throughout the entire life of the tree, producing a continuous and renewable outer bark of cork. To identify specific candidate genes associated with cork cambium activity and phellem differentiation, we performed a comparative transcriptomic study of Q. suber secondary growth tissues (xylem and phellogen/phellem) using RNA-seq. The present work provides a high-resolution map of all the transcripts identified in the phellogen/phellem tissues. A total of 6013 differentially expressed genes were identified, with 2875 of the transcripts being specifically enriched during the cork formation process versus secondary xylem formation. Furthermore, cork samples originating from the original phellogen (`virgin’ cork) and from a traumatic phellogen (`amadia’ cork) were also compared. Our results point to a shortlist of potentially relevant candidate genes regulating phellogen activity and phellem differentiation, including novel genes involved in the suberization process, as well as genes associated to ethylene and jasmonate signaling and to meristem function. The future functional characterization of some of the identified candidate genes will help to elucidate the molecular mechanisms underlying cork cambium activity and phellem differentiation.
Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p‐STAT3 in Helicobacter pylori‐associated gastritis
Authors: Teng Yong‐Sheng , Zhao Yong‐Liang , Li Mao‐Shi , Liu Yu‐Gang , Cheng Ping , Lv Yi‐Pin , Mao Fang‐Yuan , Chen Weisan , Yang Shi‐Ming , Hao Chuan‐Jie , Peng Liu‐Sheng , Zhang Jin‐Yu , Zhang Wei‐Jun , Zou Quan‐Ming , Zhuang Yuan 
Published: November 2019

AbstractBHLHE40, a member of the basic helix‐loop‐helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)‐associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori‐infected GECs express BHLHE40 via cagA‐ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein‐activated p‐STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA‐BHLHE40‐CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.
Glucocorticoid receptors signaling impairment potentiates amyloid‐β oligomers‐induced pathology in an acute model of Alzheimer’s disease
Authors: Canet Geoffrey , Pineau Fanny , Zussy Charleine , Hernandez Célia , Hunt Hazel , Chevallier Nathalie , Perrier Véronique , Torrent Joan , Belanoff Joseph K. , Meijer Onno C. , Desrumaux Catherine , Givalois Laurent 
Published: November 2019

AbstractDysregulation of the hypothalamic‐pituitary‐adrenal (HPA) axis occurs early in Alzheimer's disease (AD), associated with elevated circulating glucocorticoids (GC) and glucocorticoid receptors (GR) signaling impairment. However, the precise role of GR in the pathophysiology of AD remains unclear. Using an acute model of AD induced by the intracerebroventricular injection of amyloid‐β oligomers (oAβ), we analyzed cellular and behavioral hallmarks of AD, GR signaling pathways, processing of amyloid precursor protein, and enzymes involved in Tau phosphorylation. We focused on the prefrontal cortex (PFC), particularly rich in GR, early altered in AD and involved in HPA axis control and cognitive functions. We found that oAβ impaired cognitive and emotional behaviors, increased plasma GC levels, synaptic deficits, apoptosis and neuroinflammatory processes. Moreover, oAβ potentiated the amyloidogenic pathway and enzymes involved both in Tau hyperphosphorylation and GR activation. Treatment with a selective GR modulator (sGRm) normalized plasma GC levels and all behavioral and biochemical parameters analyzed. GR seems to occupy a central position in the pathophysiology of AD. Deregulation of the HPA axis and a feed‐forward effect on PFC GR sensitivity could participate in the etiology of AD, in perturbing Aβ and Tau homeostasis. These results also reinforce the therapeutic potential of sGRm in AD.
PTEN deletion drives aberrations of DNA methylome and transcriptome in different stages of prostate cancer
Authors: Wang Chao , Feng Yaping , Zhang Chengyue , Cheng David , Wu Renyi , Yang Yuqing , Sargsyan Davit , Kumar Dibyendu , Kong Ah‐Ng 
Published: November 2019

AbstractPhosphatase and tensin homolog located on chromosome 10 (PTEN) is a tumor suppressor gene and one of the most frequently mutated/deleted genes in human prostate cancer (PCa). However, how PTEN deletion would impact the epigenome and transcriptome alterations remain unknown. This hypothesis was tested in a prostate‐specific PTEN−/− (KO) mouse prostatic adenocarcinoma model through DNA methyl‐Seq and RNA‐Seq analyses. Examination of cancer genomic datasets revealed that PTEN is expressed at lower levels in PTEN‐deleted tumor samples than in normal solid tissue samples. Methylome and transcriptome profiling identified several inflammatory responses and immune response signaling pathways, including NF‐kB signaling, IL‐6 signaling, LPS/IL‐1‐mediated inhibition of RXR Function, PI3K in B lymphocytes, iCOS‐iCOSL in T helper cells, and the role of NFAT in regulating the immune response, were affected by PTEN deletion. Importantly, a small subset of genes that showed DNA hypermethylation or hypomethylation was correlated with decreased or increased gene expression including CXCL1. quantitative polymerase chain reaction analyses of representative genes validated the RNA‐Seq results. Histopathological examinations showed that the severity of prostatic intraepithelial neoplasia and inflammation development gradually increased as PTEN null mice aged. Collectively, these findings suggest that loss of PTEN drives global changes in DNA CpG methylation and transcriptomic gene expression and highly associated with several inflammatory and immune molecular pathways during PCa development. These biomarkers could be valuable molecular targets for cancer drug discovery and development against PCa.
Fasciola helminth defense molecule‐1 protects against experimental arthritis by inhibiting osteoclast formation and function without modulating the systemic immune response
Authors: Khan Yasir Akhtar , Maurya Shailendra Kumar , Kulkarni Chirag , Tiwari Mahesh Chandra , Nagar Geet Kumar , Chattopadhyay Naibedya 
Published: November 2019

AbstractAn inverse correlation between helminth infection and the autoimmune disease appears to be contributed by the anti‐inflammatory factors produced by these organisms. Suppressing osteoclast function without affecting the systemic immunological response is an emerging therapeutic strategy for rheumatoid arthritis (RA). We observed that a synthetic peptide corresponding to 34 amino acids of C‐terminal sequence of Fasciola helminth defense molecule‐1 (C‐FhHDM‐1) inhibited RANKL‐induced osteoclast formation and lysosomal acidification with an attendant upregulation of sequestome1/p62, a negative regulator of NF‐κB expression. C‐FhHDM‐1 also suppressed RANKL production from osteoblasts. Macrophages are the major inflammatory cells in the joints of RA and C‐FhHDM‐1 suppressed ICAM‐1 (an inflammatory surrogate) expression in these cells. In a murine model of collagen II‐induced arthritis (CIA), C‐FhHDM‐1 improved clinical score, protected against cartilage destruction, and maintained bone mass and bone architecture of joints compared with the CIA group. C‐FhHDM‐1 suppressed the CIA‐induced expression of TNF, IL‐17, and IFN‐γ in joints but not their serum levels. The peptide also had no effect on the CIA‐induced suppression of T regulatory response. We conclude that C‐FhHDM‐1 has a joint‐specific protective effect in experimental arthritis without mitigating systemic inflammation, and thus could become an adjuvant anti‐arthritis therapy to prevent RA‐induced osteopenia.
Structure and kinetic properties of human d‐aspartate oxidase, the enzyme‐controlling d‐aspartate levels in brain
Authors: Molla Gianluca , Chaves‐Sanjuan Antonio , Savinelli Antonio , Nardini Marco , Pollegioni Loredano 
Published: November 2019

Abstractd‐Amino acids are the “wrong” enantiomers of amino acids as they are not used in proteins synthesis but evolved in selected functions. On this side, d‐aspartate (d‐Asp) plays several significant roles in mammals, especially as an agonist of N‐methyl‐d‐aspartate receptors (NMDAR), and is involved in relevant diseases, such as schizophrenia and Alzheimer's disease. In vivo modulation of d‐Asp levels represents an intriguing task to cope with such pathological states. As little is known about d‐Asp synthesis, the only option for modulating the levels is via degradation, which is due to the flavoenzyme d‐aspartate oxidase (DASPO). Here we present the first three‐dimensional structure of a DASPO enzyme (from human) which belongs to the d‐amino acid oxidase family. Notably, human DASPO differs from human d‐amino acid oxidase (attributed to d‐serine degradation, the main coagonist of NMDAR) showing peculiar structural features (a specific active site charge distribution), oligomeric state and kinetic mechanism, and a higher FAD affinity and activity. These results provide useful insights into the structure‐function relationships of human DASPO: modulating its activity represents now a feasible novel therapeutic target.
DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2‐DMR0 as a DNA methylation‐dependent, P0 promoter‐specific enhancer
Authors: Watanabe Hidetaka , Higashimoto Ken , Miyake Noriko , Morita Sumiyo , Horii Takuro , Kimura Mika , Suzuki Takayuki , Maeda Toshiyuki , Hidaka Hidenori , Aoki Saori , Yatsuki Hitomi , Okamoto Nobuhiko , Uemura Tetsuji , Hatada Izuho , Matsumoto Naomichi , Soejima Hidenobu 
Published: November 2019

AbstractHaploinsufficiency of NSD1, which dimethylates histone H3 lysine 36 (H3K36), causes Sotos syndrome (SoS), an overgrowth syndrome. DNMT3A and DNMT3B recognizes H3K36 trimethylation (H3K36me3) through PWWP domain to exert de novo DNA methyltransferase activity and establish imprinted differentially methylated regions (DMRs). Since decrease of H3K36me3 and genome‐wide DNA hypomethylation in SoS were observed, hypomethylation of imprinted DMRs in SoS was suggested. We explored DNA methylation status of 28 imprinted DMRs in 31 SoS patients with NSD1 defect and found that hypomethylation of IGF2‐DMR0 and IG‐DMR in a substantial proportion of SoS patients. Luciferase assay revealed that IGF2‐DMR0 enhanced transcription from the IGF2 P0 promoter but not the P3 and P4 promoters. Chromatin immunoprecipitation‐quantitative PCR (ChIP‐qPCR) revealed active enhancer histone modifications at IGF2‐DMR0, with high enrichment of H3K4me1 and H3 lysine 27 acetylation (H3K27ac). CRISPR‐Cas9 epigenome editing revealed that specifically induced hypomethylation at IGF2‐DMR0 increased transcription from the P0 promoter but not the P3 and P4 promoters. NSD1 knockdown suggested that NSD1 targeted IGF2‐DMR0; however, IGF2‐DMR0 DNA methylation and IGF2 expression were unaltered. This study could elucidate the function of IGF2‐DMR0 as a DNA methylation dependent, P0 promoter‐specific enhancer. NSD1 may play a role in the establishment or maintenance of IGF2‐DMR0 methylation during the postimplantation period.
Phellinus linteus polysaccharide extract improves insulin resistance by regulating gut microbiota composition
Authors: Liu Yangyang , Wang Chaorui , Li Jinshan , Li Tiantian , Zhang Yong , Liang Yunxiang , Mei Yuxia 
Published: November 2019

AbstractThe hypoglycemic effect of Phellinus linteus polysaccharide extract (PLPE) has been documented in several previous studies, but the functional interactions among PLPE, gut microbiota, and the hypoglycemic effect remain unclear. We examined the regulatory effect of PLPE on gut microbiota, and the molecular mechanism underlying improvement of insulin resistance, using a type 2 diabetic rat model. Here, 24 male Sprague‐Dawley rats were randomly divided into four groups that were subjected to intervention of saline (normal and model control group), metformin (120 mg/kg.bw), and PLPE (600 mg/kg.bw) by oral administration. After 8 weeks of treatment, PLPE increased levels of short‐chain fatty acids (SCFAs) by enhancing abundance of SCFA‐producing bacteria. SCFAs maintained intestinal barrier function and reduced lipopolysaccharides content in blood, thereby helping to reduce systemic inflammation and reverse insulin resistance. Our findings suggest that PLPE (in which polysaccharides are the major component) has potential application as a prebiotic for regulating gut microbiota composition in diabetic patients.
Nucleolar control by a non‐apoptotic p53‐caspases‐deubiquitinylase axis promotes resistance to bacterial infection
Authors: Chen Po‐Hsiang , Chen Yi‐Tung , Chu Tai‐Ying , Ma Tian‐Hsiang , Wu Mei‐Hsuan , Lin Hsi‐Hsien , Chang Yu‐Sun , Tan Bertrand Chin‐Ming , Lo Szecheng J. 
Published: November 2019

AbstractThe nucleolus is best known for its cellular role in regulating ribosome production and growth. More recently, an unanticipated role for the nucleolus in innate immunity has recently emerged whereby downregulation of fibrillarin and nucleolar contraction confers pathogen resistance across taxa. The mechanism of this downregulation, however, remains obscure. Here we report that rather than fibrillarin itself being the proximal factor in this pathway, the key player is a fibrillarin‐stabilizing deubiquitinylase USP‐33. This was discovered by a candidate‐gene search of Caenorhabditis elegans in which CED‐3 caspase was revealed to execute targeted cleavage of USP‐33, thus destabilizing fibrillarin. We also showed that cep‐1 and ced‐3 mutant worms altered nucleolar size and decreased antimicrobial peptide gene, spp‐1, expression rendering susceptibility to bacterial infection. These phenotypes were reversed by usp‐33 knockdown, thus linking the CEP‐1‐CED‐3‐USP‐33 pathway with nucleolar control and resistance to bacterial infection in worms. Parallel experiments with the human analogs of caspases and USP36 revealed similar roles in coordinating these two processes. In summary, our work outlined a conserved cascade that connects cell death signaling to nucleolar control and innate immune response.
Glycolysis regulated transglutaminase 2 activation in cardiopulmonary fibrogenic remodeling
Authors: Bhedi Chinmayee D. , Nasirova Sabina , Toksoz Deniz , Warburton Rod R. , Morine Kevin J. , Kapur Navin K. , Galper Jonas B. , Preston Ioana R. , Hill Nicholas S. , Fanburg Barry L. , Penumatsa Krishna C. 
Published: November 2019

AbstractThe pathophysiology of pulmonary hypertension (PH) and heart failure (HF) includes fibrogenic remodeling associated with the loss of pulmonary arterial (PA) and cardiac compliance. We and others have previously identified transglutaminase 2 (TG2) as a participant in adverse fibrogenic remodeling. However, little is known about the biologic mechanisms that regulate TG2 function. We examined physiological mouse models of experimental PH, HF, and type 1 diabetes that are associated with altered glucose metabolism/glycolysis and report here that TG2 expression and activity are elevated in pulmonary and cardiac tissues under all these conditions. We additionally used PA adventitial fibroblasts to test the hypothesis that TG2 is an intermediary between enhanced tissue glycolysis and fibrogenesis. Our in vitro results show that glycolytic enzymes and TG2 are upregulated in fibroblasts exposed to high glucose, which stimulates cellular glycolysis as measured by Seahorse analysis. We examined the relationship of TG2 to a terminal glycolytic enzyme, pyruvate kinase M2 (PKM2), and found that PKM2 regulates glucose‐induced TG2 expression and activity as well as fibrogenesis. Our studies further show that TG2 inhibition blocks glucose‐induced fibrogenesis and cell proliferation. Our findings support a novel role for glycolysis‐mediated TG2 induction and tissue fibrosis associated with experimental PH, HF, and hyperglycemia.
A new workflow combining R packages for statistical analysis of metabolites
Authors: Ferrario Paola G. 
Published: November 2019

AbstractIn metabolomics, the investigation of an association between many metabolites and one trait (such as age in humans or cultivar in foods) is a central research question. On this topic, we present a complete statistical analysis, combining selected R packages in a new workflow, which we are sharing completely, according to modern standards and research reproducibility requirements. We demonstrate the workflow using a large-scale study with public data, available on repositories. Hence, the workflow can directly be re-used on quite different metabolomics data, when searching for association with one covariate of interest.
Gamma coherence mediates interhemispheric integration during multiple object tracking
Authors: Bland Nicholas S. , Mattingley Jason B. , Sale Martin V. 
Published: November 2019

ABSTRACTOur ability to track the paths of multiple visual objects moving between the hemifields requires effective integration of information between the two cerebral hemispheres. Coherent neural oscillations in the gamma band (35–70 Hz) are hypothesised to drive this information transfer. Here we manipulated the need for interhemispheric integration using a novel multiple object tracking (MOT) task in which stimuli either moved between the two visual hemifields—requiring interhemispheric integration—or moved within separate visual hemifields. We used electroencephalography (EEG) to measure interhemispheric coherence during the task. Human observers (21 female; 20 male) were poorer at tracking objects between-versus within-hemifields, reflecting a cost of interhemispheric integration. Critically, gamma coherence was greater in trials requiring interhemispheric integration, particularly between sensors over parieto-occipital areas. In approximately half of the participants, the observed cost of integration was associated with a failure of the cerebral hemispheres to become coherent in the gamma band. Moreover, individual differences in this integration cost correlated with endogenous gamma coherence at these same sensors, though with generally opposing relationships for the real and imaginary part of coherence. The real part (capturing synchronisation with a near-zero phase-lag) benefited between-hemifield tracking; imaginary coherence was detrimental. Finally, instantaneous phase-coherence over the tracking period uniquely predicted between-hemifield tracking performance, suggesting that effective integration benefits from sustained interhemispheric synchronisation. Our results show that gamma coherence mediates interhemispheric integration during MOT, and add to a growing body of work demonstrating that coherence drives communication across cortically distributed neural networks.
Disconnect between signalling potency and in vivo efficacy of pharmacokinetically optimised biased glucagon-like peptide-1 receptor agonists
Authors: Lucey Maria , Pickford Philip , Minnion James , Ungewiss Jan , Schoeneberg Katja , Rutter Guy A , Bloom Stephen R , Tomas Alejandra , Jones Ben 
Published: November 2019

AbstractObjectiveTo determine how pharmacokinetically advantageous acylation impacts on glucagon-like peptide-1 receptor (GLP-1R) signal bias, trafficking, anti-hyperglycaemic efficacy and appetite suppression.MethodsIn vitro signalling responses were measured using biochemical and biosensor assays. GLP-1 receptor trafficking was determined by confocal microscopy and diffusion-enhanced resonance energy transfer. Pharmacokinetics, glucoregulatory effects and appetite suppression were measured in acute, sub-chronic and chronic settings in mice.ResultsA C-terminally acylated ligand, exendin-phe1-C16, was identified with undetectable β-arrestin recruitment and GLP-1R internalisation. Depending on the cellular system used, this molecule was up to 1000-fold less potent than the comparator exendin-asp-3-C16 for cyclic AMP signalling, yet was considerably more effective in vivo, particularly for glucose regulation.ConclusionsC-terminal acylation of biased GLP-1R agonists increases their degree of signal bias in favour of cAMP production and improves their therapeutic potential.