bluuebunny/crossref_metadata_2025_split huggingface dataset:
H3K36&nbsp;Methylation Reprograms Gene Expression to Drive Early Gametocyte Development in Plasmodium Falciparum
Authors: Connacher Jessica , Josling Gabrielle A , Orchard Lindsey M , Reader Janette , Llinas Manuel , Birkholtz Lyn-Marie 
Published: January 2021

Abstract
Background: The Plasmodium sexual gametocyte stages are the only transmissible form of the malaria parasite and are thus responsible for the continued transmission of the disease. Gametocytes undergo extensive functional and morphological changes from commitment to maturity, directed by an equally extensive control program. Several interconnected mechanisms governing sexual commitment have been described. However, the processes that drive the subsequent differentiation and development of the gametocyte remain largely unexplored. Using chromatin immunoprecipitation followed by high-throughput sequencing we describe an association between H3K36 di- and tri-methylation (H3K36me2&3) and the global changes in the transcriptional program driving gametocyte development post-commitment. Results: Here, we show that in stage II gametocytes, H3K36me2&3 are associated with an active repression of genes involved in asexual proliferation and sexual commitment, linking H3K36me2&3 to the transition from early gametocyte differentiation to intermediate development. Specifically, we establish a link between H3K36me2&3 and the repression of genes that are upregulated during commitment once terminal differentiation renders their protein products obsolete in developing gametocytes, thereby securing an appropriate transcriptional environment for intermediate gametocyte development. Lastly, we associate the enhanced potency of JIB-04 in gametocytes with the inhibition of H3K36me2&3 demethylation and a disruption of normal transcriptional programs.Conclusions: Taken together, our results provide the first description of an association between global gene expression reprogramming and histone post-translational modifications during P. falciparum sexual development. In addition to fulfilling the same role in virulence gene regulation as in asexual parasites, the stage II gametocyte-specific abundance of H3K36me2/3 manifests as a largely interdependent enrichment of the two modifications targeted towards genes whose functions become obsolete in post-commitment gametocytes. This contrasts with the broad repression associated with wide-spread H3K36me2 occupancy in asexual parasites, highlighting H3K36me2/3 enrichment as a marker of directed transcriptional repression specific to early gametocytes. The importance of such histone methylation during gametocyte development is underscored by the transcriptional disruption associated with histone demethylase inhibition in P. falciparum gametocytes. By demonstrating the participation of H3K36me2&3 in gametocyte development, we provide a more thorough understanding of the link between epigenetic mechanisms and gene expression in the transmissible stages of the malaria parasite.
Identification of Aberrantly Methylated-differentially Expressed Genes and Potential Agents for Ewing’s Sarcoma
Authors: Gao Shijie , Li Guowang , Yu Hao , Yuan Shiyang , Li Wenxiang , Xiang Ziqian , Zhao Yajie , Ruan Wendong , Xu Baoshan , Ning Guangzhi 
Published: January 2021

Abstract
Background: DNA methylation is a common epigenetic regulatory way, and it plays a critical role in various human diseases. However, the potential role of how DNA methylation impacts Ewing’s sarcoma (ES) is not clear. This study aimed to explore the regulatory role of DNA methylation in ES.Methods: The microarray data of gene expression and methylation were downloaded from Gene Expression Omnibus (GEO) database, and analyzed via GEO2R. Venn analysis was then applied to identify aberrantly methylated differentially expressed genes (DEGs). Subsequently, Function and pathway enrichment analysis was conducted. Protein-protein interaction (PPI) network was constructed. Hub genes were determined. Besides, a connectivity map (CMap) analysis was performed to screen bioactive compounds for ES treatment.Results: A total of 135 hypomethylated high expression genes and 523 hypermethylated low expression genes were identified. The hypomethylated high expression genes were enriched in signal transduction and the apoptosis process. Meanwhile, hypermethylated low expression genes were related to DNA replication and transcription regulation. We next determined 10 hub genes through PPI analysis, among them, C3, TF, and TCEB1 might serve as diagnostic and therapeutic targets. Furthermore, CMap analysis revealed 6 chemicals as potential options for ES treatment. Conclusions: For the first time, we jointly analyzed gene profiling and methylation data about ES. The introduction of DNA methylation characteristics over DEGs is helpful to understand the pathogenesis of ES. The identified hub aberrantly methylated DEGs and chemicals might provide some novel insights on ES treatment.
Risk Factors for Nonischemic St-segment Elevation in Patients With Electrocardiographic Left Ventricular Hypertrophy
Authors: Guo Haisen , Zhang Weidai , Zhang Jiawei , Ni Chumin , Cai Zhixiong , Chen Songming , Huang Xiansheng 
Published: January 2021

Abstract
Background ST-segment elevation (STE) is not a specific change for ST-segment elevation myocardial infarction (STEMI). This may lead to a mistaken diagnosis of STEMI and false-positive cardiac catheterization laboratory activation. We aimed to investigate risk factors for STE secondary to electrocardiographic LVH in order to provide more information for differential diagnosis.Methods A total of 1,590 inpatients with electrocardiographic LVH without confounding factors (such as myocardial infarction) were enrolled in this study. Data on potential risk factors and patient characteristics were collected. Logistic regression analysis and receiver operating characteristic curve (ROC) were used to identify the risk of STE in patients with LVH.Results After reviewing the ECGs, 1590 cases of electrocardiographic LVH were divided into an ST-segment elevation group (STE group, 81 cases) and non-ST segment elevation group (1509 cases). Eighty-seven cases were randomly selected from the non-ST segment elevation group to form a new non-ST segment elevation group (non-STE group, 87 cases) for further analysis. The mean age of the 168 participants (119 men, 70.83%) was 62.33 ± 16.27. Multivariate analysis showed that stroke, infection, and the value of SV1+RV5 were significantly associated with STE secondary to LVH. The area under the receiver operating characteristic curve showed that the optimal value of SV1+RV5 cut-off for predicting STE was 4.805 (sensitivity: 40.74%; specificity: 80.46%; AUC: 0.634; 95% CI: 0.550–0.719; P < 0.05).Conclusions A value of SV1+RV5 larger than 4.8 mV, stroke, and infection are independent risk factors for STE in patients with electrocardiographic LVH.
Investigating the Prevalence of Unsafe Behaviors and the Factors Affecting It Using a Cross-sectional Study in a Steel Company in Iran
Authors: Rabiei Hadiseh , Malakoutikhah Mahdi , Karimi Ali , Zare Asma , Saberi Hamidreza 
Published: January 2021

Abstract
Background: Unsafe behaviors (UBs) are the most important cause of accidents (98 %). Therefore, identifying the cause of UBs is also significant. The aim of this study was to investigate the prevalence of UBs among the workers of a steel company in Iran and also to identify the factors affecting these behaviors.Method: This cross-sectional study was conducted on 270 people from the employees of a steel company in Iran in 2016. The present study consists of two parts. 1) investigate the prevalence of UBs of workers using safety behavior sampling method, 2) identify the factors affecting UBs using a questionnaire (demographic sections, general health questionnaire, work-family conflict questionnaire, and UK's HSE job stress questionnaire). The data from the questionnaires were analyzed by SPSS 16. Results: The frequency of observed UBs showed that out of 1310 observed behaviors, 531 cases (40.5%) were unsafe. Also, UB among the sample group was significantly higher than the control group (P < .05). The correlation between general health, work-family conflict, job stress, and UBs showed that general health had a significant relationship with UBs (P < .05).Conclusions: The relationship between support scale in job stress and accident showed that organizational factors such as organizational climate, safety culture, management and cooperation between people are among the factors affecting the accident and with optimal management of these factors can play a significant role in future accidents.
Differential Brain Tissue Proteins in Ovariectomized Hyperlipemia Rats After Intervention Using Erxian Extract
Authors: Wu Hongjin , Dai Weiwei , Zhang Jie , Wang Chenglong , Wang Libo 
Published: January 2021

Abstract
Background: Erxiantang (EXT) is a popular traditional Chinese medicine formula that has phytoestrogens with protective effects on the nervous system, hypertension, menopausal syndrome. We aimed to explore the effects of EXT on differential brain tissue proteins in ovariectomized (OVX) hyperlipemia rats using label-free high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).Methods: We randomly divided 40 eight-week-old female Sprague-Dawley rats into four groups: (1) SHAM (sham-operation, equal volume ddH2O); (2) OVX (ovariectomized, equal volume ddH2O); (3) EXT (ovariectomized, Erxian extract: 5.46 g/kg body weight); and (4) EV groups (ovariectomized, estradiol valerate: 0.1 mg/kg body weight). After administration for 6 weeks, we measured body weight, serum lipid, and estrogen. Rat brain tissues were analyzed using HPLC-MS/MS. Subsequently, we performed bioinformatics analysis and screened differential proteins for detection and verification through western blot analysis.Results: We identified 4678 proteins. There were 87 differential proteins in the SHAM and OVX group; 50 were up-regulated and 37 were down-regulated. There were 242 differential proteins in the EXT and OVX groups; 95 were up-regulated and 147 were down-regulated. Proteins in the EXT, EV, and SHAM groups that showed a similar trend to the OVX group were ApoE, slc6a1, gpd1, eno3, hmgcs1, u2af2, march5, mcam, actl6b, tmc2, coq3, dctn5, seleno, tmem109, derl1, syvn1, rbm39, cnpy2, bcl-2, acsf2, dc42ep4, and mapk8. These proteins were mainly involved in lipid metabolism, biological oxidation, signal transduction, cholesterol metabolism, immune response, stress response, and cell apoptosis. Western blot analysis of ApoE, GAT1, JNK, and p-JNK proteins showed that their expression in the EXT group was lower than in the OVX group, which was consistent with the proteomics analysis results.Conclusions: EXT may protect the OVX hyperlipemia rats by exerting an effect on lipid metabolism, immune response, stress response, and apoptosis. Moreover, the identified differential proteins may be related to the occurrence and development of hyperlipemia-related diseases.
Directional Decremental Abundance of (GA)9 and (GA)11 Blocks in Primate Speciation
Authors: Khamse Safoura , Arabfard Masoud , Salesi M , Behmard E , Khazaei Mona , Najafipour Reza , Jafarian Zahra , Afshar Hossein , Delbari Ahmad , Ohadi Mina 
Published: January 2021

Abstract
Background: Recent evidence indicates that expansion of a number of short tandem repeats (STRs) may be a result of natural selection. The human neuron-specific genes, RIT2 and GPM6B, contain two of the longest GA-STRs at 11 and 9-repeats, respectively, the length ranges of which are functional, and exceedingly rare repeats at the extreme end of those STRs occur with major human disorders. To examine the evolutionary trend of (GA)11 and (GA)9 blocks, two sets of chromosomal regions (each spanning 10 Mb of genomic DNA) across all chromosomes, were searched for those blocks across rodent and primate orders. We also sequenced the RIT2 and GPM6B STRs in 600 human subjects, consisting of late-onset neurocognitive disorder (n=200), multiple sclerosis (n=100), and controls (n=200). Results: We detected a directional decremental abundance of (GA)11 and (GA)9 blocks, matching the phylogenetic distance of the selected species as follows: mouse>macaque>great apes (p=0.000006). The RIT2 and GPM6B GA-repeats were at strict lengths of 11 and 9-repeats in human, respectively, and were predominantly human-specific in formula. Exception included a 9/11 genotype of the RIT2 GA-STR in an isolate case of multiple sclerosis. Conclusion: We report the first evidence of massive directional trend of STRs linking to speciation. Genes such as RIT2 and GPM6B may be suitable candidates to explore the evolutionary impact of STR blocks.
Hepatic Progenitor Cells Promote the Repair of Schistosomiasis Liver Injury Through Inhibiting IL-33 Secretion&nbsp;
Authors: Zhang Beibei , Wu Xiaoying , Li Jing , Ning An , Zhang Bo , Liu Jiahua , Song Langui , Yan Chao , Sun Xi , Zheng Kuiyang , Wu Zhongdao 
Published: January 2021

Abstract
Background: Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent and quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remained unknown.Methods: In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in S. japonicum infection mice model at different infection stages. For validating the role of HPCs in hepatic injury, TNF­related weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs. Histologic pathology and the expression of IL-33 were examined. Results: We found that the proliferation of HPCs paralleled with inflammatory granulomas and fibrosis formation. Promoting HPCs expansion promote the liver regeneration and inhibit the hepatocytes injury, the inflammatory eggs granulomas and the deposition of fibrotic collagen. Interestingly, the expression of IL-33 decreased when HPCs were manipulated to proliferate. Thus, IL-33 might be involved in the liver repair dominated by HPCs. Conclusions: Collectively, our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33 related manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.
The Relationship Between Physical Activity and the Presence of Sarcopenia in Older Adults: A Taiwanese Cross-sectional Study
Authors: Ko Yun-Chen , Chie Wei-Chu , Wu Tai-Yin , Ho Chin-Yu , Yu Wen-Ruey 
Published: January 2021

Abstract
To the best of our knowledge, none of Taiwanese studies on the relationship between physical activity (PA) and sarcopenia by the latest 2019 Asian Working Group for Sarcopenia (AWGS) cutoff points of sarcopenia has been published. We used the Taiwan version of international physical activity questionnaire-short version and the 2019 AWGS diagnostic criteria of sarcopenia to examine the relationship between PA and sarcopenia in older adults. Volunteers in this cross-sectional study were recruited from those attending senior health checkup program held at a regional hospital in Taipei City from May 2019 to Sep 2019. Muscle strength was assessed by grip strength, physical performance was assessed by usual gait speed on a 6-meter course, and muscle mass was measured by bioelectrical impedance analysis. Multiple logistic regression was used to analyze the relationship between PA and sarcopenia. 565 participants were recruited and data from 500 participants were used. 138 (27.6%) participants were classified as having sarcopenia, which included 87 women and 51 men. Among women, compared with those with low PA, moderate to high PA protected against the risk of sarcopenia with the adjusted odds ratio (aOR)=0.52 (95% CI: 0.27-0.98, p-value=0.043). As for men, the aOR was 0.34 (95% CI: 0.12-0.95, p-value=0.039). A significant protective effect of PA on sarcopenia was found among the older adults after adjusting for confounders, especially for the male participants.
Arbuscular Mycorrhizal Fungi Alleviate Arsenic Toxicity in Sophora Viciifolia Hance. by Improving The Growth, Photosynthesis, Reactive Oxygen Species and Gene Expression of Phytochelatin Synthase
Authors: Zhang QiaoMing , Gong Minggui , Xu Shanshan , Zhang Angran , Yuan Jiangfeng , Chang Qingshan 
Published: January 2021

Abstract
Arbuscular mycorrhizal fungi (AMF) can protect host plants against arsenic (As) toxicity. However, knowledge on the response of woody leguminous under As stress is limited so far. In this study, Sophora viciifolia seedlings were inoculated with/without AMF Rhizophagus intraradices, and S. viciifolia were grown in three levels (0, 50, and 100 mg As kg−1 soil) of As-polluted soil though the potted experiments. The objective of this study was to investigate the influences of AMF symbiosis on woody leguminous under As stress. Some physiological and biochemical parameters of S. viciifolia, which included the plant growth, photosynthesis, oxidative damage, antioxidant enzyme activities and gene expression of phytochelatins (PCs), were analyzed. The results showed that As toxicity in soils inhibited the AM colonization rate, plant growth, photosynthesis, increased the oxidative damage and antioxidant enzyme activities, and up-regulated the gene expression of SvPCS1 in the leaves and roots of S. viciifolia seedlings. However, compared with non-inoculated S. viciifolia at the same As level, R. intraradices-inoculated S. viciifolia had higher shoot and root dry weight, plant height, root length, photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (E), maximal photochemical efficiency of PSII photochemistry (Fv/Fm), actual quantum yield (ΦPSII), and photochemical quenching values (qP), as well as lower intercellular CO2 concentration (Ci) and non-photochemical quenching values (NPQ). R. intraradices inoculation inhibited the malondialdehyde (MDA), H2O2, and O2•– concentrations, but improved the activities of antioxidative enzymes (SOD, POD, and CAT) in S. viciifolia leaves and roots. The gene expression of SvPCS1 in the leaves and roots was obviously up-regulated by R. intraradices inoculation. These results demonstrated that R. intraradices inoculation enhanced the As tolerance of S. viciifolia seedlings, owing to the beneficial effects of AMF symbiosis on improving the plant growth, gas exchange, chlorophyll fluorescence, antioxidant enzymes, reactive oxygen species and gene expression of SvPCS1 in S. viciifolia seedlings. R. intraradices is possible to get involved in the defence response of S. viciifolia seedlings against. As toxicity stress. This investigation got more profound insights into As tolerance mechanisms of woody leguminous associated with AMF symbiosis.
Number of parity/live birth(s) and cardiovascular disease among Iranian women and men: Results of over 15 years of follow-up.
Authors: Moazzeni Seyyed Saeed , Toreyhi Hossein , Asgari Samaneh , Azizi Fereidoun , Tehrani Fahimeh Ramezani , Hadaegh Farzad 
Published: January 2021

Abstract
Background: Most previous studies conducted in non-Middle Eastern populations have suggested that an increase in the number of parity/live birth(s) leads to cardiovascular disease (CVD) development, although their findings were inconclusive on this issue for both sexes. Biologic and socioeconomic pathways were suggested to explain this association. We studied this issue among urban Iranian men and women.Methods: In this population-based cohort study, which included 3929 women and 2571 men aged ≥ 30 years, data for the number of parity/live birth(s) were obtained by a standard questionnaire. Participants were then annually followed for CVD events. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the number of parity/live birth(s) and other traditional CVD risk factors.Results: During more than 15 years of follow-up, 456 and 524 CVD events have occurred among women and men, respectively. Among women, a J-shaped association was found between the number of live births and incident CVD with the lowest risk for women with two live births. Among women in multivariate analyses, each unit increase in parity had a HR of 1.05 (CI: 1.01-1.10), and having ≥4 parity was associated with a HR of 1.86 (0.97-3.56, p-value=0.061). Among men, in comparison with participants who had 1 child, multivariate HRs of having 2, 3, and ≥4 children were 1.97 (1.24-3.12), 2.08 (1.31-3.31), and 2.08 (1.30-3.34), respectively.Conclusion: To the best of our knowledge, the current study is the first report on this issue in the Middle East and North Africa region, a region with a high burden of CVD. It can now be suggested that the number of parity/live birth(s) is linked to CVD among the Iranian population, with this issue being more prominent among men. Further research is needed to support our results and clarify the pathways between the number of parity/live birth(s) and CVD development among Iranian populations by considering potential risk factors, especially psycho-socio-economic risk factors.
Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes
Authors: Okuyama Tomoko , Shirakawa Jun , Nakamura Takashi , Murase Takayo , Miyashita Daisuke , Inoue Ryota , Kyohara Mayu , Togashi Yu , Terauchi Yasuo 
Published: January 2021

Abstract
Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM). The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlated with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease. Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM. Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.