Prevalence of Amphetamine-Type Stimulant Use and Related Factors among Methadone Maintenance Patients in Ho Chi Minh City Vietnam: A Cross-Sectional Study.

The objective of this study was to determine the prevalence of amphetamine-type stimulant use and associated factors among methadone maintenance treatment (MMT) patients. In 2018, a cross-sectional study was conducted on 967 MMT patients at two methadone clinics in Ho Chi Minh City that serve Vietnamese patients. Amphetamine-type stimulant use was assessed by rapid urine test and face-to-face interview using the Alcohol, Smoking, Substance Involvement Screening Test (ASSIST) tool. The prevalence of amphetamine-type stimulant use assessed by urine test was 25.4%. According to ASSIST, the prevalence of moderate and high risk amphetamine-type stimulant use was 15.5% and 1.1%, respectively. Amphetamine-type stimulant use and hazardous use were more prevalent in younger patients, having a part-time job, drug injection, having a lower score of self-health assessment, treated with a higher dose of methadone and missing methadone dose in the past 3 months. By contrast, patients who were HIV positive were less likely to use amphetamine-type stimulants. Cannabis and heroin use were significantly associated with amphetamine-type stimulant use (OR = 1.46; 95% CI: 1.38-8.67; and OR = 1.50; CI: 1.04-2.18, respectively) and hazardous use (OR = 4.07; CI: 1.67-9.92; and OR = 2.38; CI: 1.56-3.63, respectively). Screening and interventions are needed to cope with this issue on time, particularly in young patients, having drug injection and concurrent drugs user groups.

Epigenetic regulation of spurious transcription initiation in Arabidopsis.

In plants, epigenetic regulation is critical for silencing transposons and maintaining proper gene expression. However, its impact on the genome-wide transcription initiation landscape remains elusive. By conducting a genome-wide analysis of transcription start sites (TSSs) using cap analysis of gene expression (CAGE) sequencing, we show that thousands of TSSs are exclusively activated in various epigenetic mutants of Arabidopsis thaliana and referred to as cryptic TSSs. Many have not been identified in previous studies, of which up to 65% are contributed by transposons. They possess similar genetic features to regular TSSs and their activation is strongly associated with the ectopic recruitment of RNAPII machinery. The activation of cryptic TSSs significantly alters transcription of nearby TSSs, including those of genes important for development and stress responses. Our study, therefore, sheds light on the role of epigenetic regulation in maintaining proper gene functions in plants by suppressing transcription from cryptic TSSs.

miR2118-dependent U-rich phasiRNA production in rice anther wall development.

Reproduction-specific small RNAs are vital regulators of germline development in animals and plants. MicroRNA2118 (miR2118) is conserved in plants and induces the production of phased small interfering RNAs (phasiRNAs). To reveal the biological functions of miR2118, we describe here rice mutants with large deletions of the miR2118 cluster. Our results demonstrate that the loss of miR2118 causes severe male and female sterility in rice, associated with marked morphological and developmental abnormalities in somatic anther wall cells. Small RNA profiling reveals that miR2118-dependent 21-nucleotide (nt) phasiRNAs in the anther wall are U-rich, distinct from the phasiRNAs in germ cells. Furthermore, the miR2118-dependent biogenesis of 21-nt phasiRNAs may involve the Argonaute proteins OsAGO1b/OsAGO1d, which are abundant in anther wall cell layers. Our study highlights the site-specific differences of phasiRNAs between somatic anther wall and germ cells, and demonstrates the significance of miR2118/U-phasiRNA functions in anther wall development and rice reproduction.

Clinical prognostic models for severe dengue: a systematic review protocol.

Background: Dengue is a common mosquito-borne, with high morbidity rates recorded in the annual. Dengue contributes to a major disease burden in many tropical countries. This demonstrates the urgent need in developing effective approaches to identify severe cases early. For this purpose, many multivariable prognostic models using multiple prognostic variables were developed to predict the risk of progression to severe outcomes. The aim of the planned systematic review is to identify and describe the existing clinical multivariable prognostic models for severe dengue as well as examine the possibility of combining them. These findings will suggest directions for further research of this field. Methods: This protocol has followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta - Analyses Protocol (PRISMA-P). We will conduct a comprehensive search of Pubmed, Embase, and Web of Science. Eligibility criteria include being published in peer-review journals, focusing on human subjects and developing the multivariable prognostic model for severe dengue, without any restriction on language, location and period of publication, and study design. The reference list will be captured and removed from duplications. We will use the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to extract data and Prediction study risk of bias assessment tool (PROBAST) to assess the study quality. Discussion: This systematic review will describe the existing prediction models, summarize the current status of prognostic research on dengue, and report the possibility to combine the models to optimize the power of each paradigm. PROSPERO registration: CRD42018102907.

Computational reconstruction of transcriptional relationships from ChIP-chip data.

UNLABELLED: Eukaryotic gene transcription is a complex process, which requires the orchestrated recruitment of a large number of proteins, such as sequence-specific DNA binding factors, chromatin remodelers and modifiers, and general transcription machinery, to regulatory regions. Previous works have shown that these regulatory proteins favor specific organizational theme along promoters. Details about how they cooperatively regulate transcriptional process, however, remain unclear. We developed a method to reconstruct a Bayesian network (BN) model representing functional relationships among various transcriptional components. The positive/negative influence between these components was measured from protein binding and nucleosome occupancy data and embedded into the model. Application on S.cerevisiae ChIP-Chip data showed that the proposed method can recover confirmed relationships, such as Isw1-Pol II, TFIIH-Pol II, TFIIB-TBP, Pol II-H3K36Me3, H3K4Me3-H3K14Ac, etc. Moreover, it can distinguish colocating components from functionally related ones. Novel relationships, e.g., ones between Mediator and chromatin remodeling complexes (CRCs), and the combinatorial regulation of Pol II recruitment and activity by CRCs and general transcription factors (GTFs), were also suggested. CONCLUSION: protein binding events during transcription positively influence each other. Among contributing components, GTFs and CRCs play pivotal roles in transcriptional regulation. These findings provide insights into the regulatory mechanism.

Sequence-dependent histone variant positioning signatures.

BACKGROUND: Nucleosome, the fundamental unit of chromatin, is formed by wrapping nearly 147bp of DNA around an octamer of histone proteins. This histone core has many variants that are different from each other by their biochemical compositions as well as biological functions. Although the deposition of histone variants onto chromatin has been implicated in many important biological processes, such as transcription and replication, the mechanisms of how they are deposited on target sites are still obscure. RESULTS: By analyzing genomic sequences of nucleosomes bearing different histone variants from human, including H2A.Z, H3.3 and both (H3.3/H2A.Z, so-called double variant histones), we found that genomic sequence contributes in part to determining target sites for different histone variants. Moreover, dinucleotides CA/TG are remarkably important in distinguishing target sites of H2A.Z-only nucleosomes with those of H3.3-containing (both H3.3-only and double variant) nucleosomes. CONCLUSIONS: There exists a DNA-related mechanism regulating the deposition of different histone variants onto chromatin and biological outcomes thereof. This provides additional insights into epigenetic regulatory mechanisms of many important cellular processes.

Characterizing nucleosome dynamics from genomic and epigenetic information using rule induction learning.

BACKGROUND: Eukaryotic genomes are packaged into chromatin, a compact structure containing fundamental repeating units, the nucleosomes. The mobility of nucleosomes plays important roles in many DNA-related processes by regulating the accessibility of regulatory elements to biological machineries. Although it has been known that various factors, such as DNA sequences, histone modifications, and chromatin remodelling complexes, could affect nucleosome stability, the mechanisms of how they regulate this stability are still unclear. RESULTS: In this paper, we propose a novel computational method based on rule induction learning to characterize nucleosome dynamics using both genomic and histone modification information. When applied on S. cerevisiae data, our method produced totally 98 rules characterizing nucleosome dynamics on chromosome III and promoter regions. Analyzing these rules we discovered that, some DNA motifs and post-translational modifications of histone proteins play significant roles in regulating nucleosome stability. Notably, these DNA motifs are strong determinants for nucleosome forming and inhibiting potential; and these histone modifications have strong relation with transcriptional activities, i.e. activation and repression. We also found some new patterns which may reflect the cooperation between these two factors in regulating the stability of nucleosomes. CONCLUSION: DNA motifs and histone modifications can individually and, in some cases, cooperatively regulate nucleosome stability. This suggests additional insights into mechanisms by which cells control important biological processes, such as transcription, replication, and DNA repair.