Current use of smokeless tobacco among adolescents in the Republic of Congo

<p>Abstract</p> <p>Background</p> <p>Tobacco use is a leading cause of global morbidity and mortality. Much of the epidemiologic research on tobacco focuses on smoking, especially cigarette smoking, but little attention on smokeless tobacco (SLT).</p> <p>Methods</p> <p>Using data from the Republic of Congo Global Youth Tobacco Survey (GYTS) of 2006, we estimated the prevalence of SLT use among in-school adolescents. We also assessed the association between SLT use and cigarette smoking as well as the traditional factors which are associated with cigarette smoking among adolescents (e.g. age, sex, parental or peer smoking). Unadjusted odds ratios (OR) and adjusted odds ratios (AOR) together with their 95% confidence intervals (CI) were used to measure magnitudes of associations.</p> <p>Results</p> <p>Of the 3,034 respondents, 18.0% (18.0% males and 18.1% females) reported having used smokeless tobacco (chewing tobacco, sniff or dip) in the last 30 days. In multivariate analysis, no significant associations were observed between age and sex on one hand and current smokeless tobacco use on the other. Cigarette smokers were more than six times likely to report current use of smokeless tobacco (AOR = 6.65; 95% CI [4.84, 9.14]). Having parents or friends smokers was positively associated with using smokeless tobacco (AOR = 1.98; 95% CI [1.51, 2.59] for parents who smoked cigarettes, AOR = 1.82; 95% CI [1.41, 2.69] for some friends who smoked cigarettes, and AOR = 2.02; 95% CI [1.49, 2.47] for most or all friends who smoked cigarettes). Respondents who reported have seen tobacco advertisement on TV, billboards and in newspapers/magazines were 1.95 times more likely to report current use of smokeless tobacco (AOR = 1.95; 95% CI [1.34, 3.08]). Perception that smoking was harmful to health was negatively associated with current use of smokeless tobacco (AOR = 0.60; 95% CI [0.46, 0.78]).</p> <p>Conclusions</p> <p>Prevention programs aimed to reduce teen [cigarette] smoking must also be designed to reduce other forms of tobacco use. The teenagers environment at home, at school and at leisure must also be factored in order to prevent their uptake or maintenance of tobacco use.</p

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

A miRNA-Target Prediction Case Study

Giansanti, V., Castelli, M., Beretta, S., & Merelli, I. (2019). Comparing Deep and Machine Learning Approaches in Bioinformatics: A miRNA-Target Prediction Case Study. In V. V. Krzhizhanovskaya, M. H. Lees, P. M. A. Sloot, J. J. Dongarra, J. M. F. Rodrigues, P. J. S. Cardoso, J. Monteiro, ... R. Lam (Eds.), Computational Science – ICCS 2019: 19th International Conference, Faro, Portugal, June 12–14, 2019, Proceedings, Part III (pp. 31-44). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 11538 LNCS). Springer Verlag. https://doi.org/10.1007/978-3-030-22744-9_3MicroRNAs (miRNAs) are small non-coding RNAs with a key role in the post-transcriptional gene expression regularization, thanks to their ability to link with the target mRNA through the complementary base pairing mechanism. Given their role, it is important to identify their targets and, to this purpose, different tools were proposed to solve this problem. However, their results can be very different, so the community is now moving toward the deployment of integration tools, which should be able to perform better than the single ones. As Machine and Deep Learning algorithms are now in their popular years, we developed different classifiers from both areas to verify their ability to recognize possible miRNA-mRNA interactions and evaluated their performance, showing the potentialities and the limits that those algorithms have in this field. Here, we apply two deep learning classifiers and three different machine learning models to two different miRNA-mRNA datasets, of predictions from 3 different tools: TargetScan, miRanda, and RNAhybrid. Although an experimental validation of the results is needed to better confirm the predictions, deep learning techniques achieved the best performance when the evaluation scores are taken into account.authorsversionpublishe

CHD7 Targets Active Gene Enhancer Elements to Modulate ES Cell-Specific Gene Expression

CHD7 is one of nine members of the chromodomain helicase DNA–binding domain family of ATP–dependent chromatin remodeling enzymes found in mammalian cells. De novo mutation of CHD7 is a major cause of CHARGE syndrome, a genetic condition characterized by multiple congenital anomalies. To gain insights to the function of CHD7, we used the technique of chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP–Seq) to map CHD7 sites in mouse ES cells. We identified 10,483 sites on chromatin bound by CHD7 at high confidence. Most of the CHD7 sites show features of gene enhancer elements. Specifically, CHD7 sites are predominantly located distal to transcription start sites, contain high levels of H3K4 mono-methylation, found within open chromatin that is hypersensitive to DNase I digestion, and correlate with ES cell-specific gene expression. Moreover, CHD7 co-localizes with P300, a known enhancer-binding protein and strong predictor of enhancer activity. Correlations with 18 other factors mapped by ChIP–seq in mouse ES cells indicate that CHD7 also co-localizes with ES cell master regulators OCT4, SOX2, and NANOG. Correlations between CHD7 sites and global gene expression profiles obtained from Chd7+/+, Chd7+/−, and Chd7−/− ES cells indicate that CHD7 functions at enhancers as a transcriptional rheostat to modulate, or fine-tune the expression levels of ES–specific genes. CHD7 can modulate genes in either the positive or negative direction, although negative regulation appears to be the more direct effect of CHD7 binding. These data indicate that enhancer-binding proteins can limit gene expression and are not necessarily co-activators. Although ES cells are not likely to be affected in CHARGE syndrome, we propose that enhancer-mediated gene dysregulation contributes to disease pathogenesis and that the critical CHD7 target genes may be subject to positive or negative regulation

Evidence for Involvement of Th17 Type Responses in Post Kala Azar Dermal Leishmaniasis (PKDL)

Post kala azar dermal leishamniasis (PKDL), an unusual dermatosis, develops in 5–15% of apparently cured visceral leishmaniasis cases in India and in about 60% of cases in Sudan. PKDL cases assume importance since they constitute an important human reservoir for the parasite. Host immunological responses, considered as major factors in PKDL development, are poorly understood. Limited studies have been performed to explore the host immune responses and that too, restricted to a few immune parameters. The present study employed cDNA array technique that identified various host immuno-determinants including cytokines, chemokines, apoptotic and signaling molecules which were not reported previously in PKDL. In addition, we showed for the first time that Th17 responses are present during L. donovani infection in PKDL which possibly contributes significantly to disease pathogenesis by inducing TNF-α and nitric oxide production. Our findings lead to improved understanding of the host parasite interaction in terms of immune responses and pathology in tissue lesions of PKDL

Radiotherapy Suppresses Angiogenesis in Mice through TGF-βRI/ALK5-Dependent Inhibition of Endothelial Cell Sprouting

BACKGROUND: Radiotherapy is widely used to treat cancer. While rapidly dividing cancer cells are naturally considered the main target of radiotherapy, emerging evidence indicates that radiotherapy also affects endothelial cell functions, and possibly also their angiogenic capacity. In spite of its clinical relevance, such putative anti-angiogenic effect of radiotherapy has not been thoroughly characterized. We have investigated the effect of ionizing radiation on angiogenesis using in vivo, ex vivo and in vitro experimental models in combination with genetic and pharmacological interventions. PRINCIPAL FINDINGS: Here we show that high doses ionizing radiation locally suppressed VEGF- and FGF-2-induced Matrigel plug angiogenesis in mice in vivo and prevented endothelial cell sprouting from mouse aortic rings following in vivo or ex vivo irradiation. Quiescent human endothelial cells exposed to ionizing radiation in vitro resisted apoptosis, demonstrated reduced sprouting, migration and proliferation capacities, showed enhanced adhesion to matrix proteins, and underwent premature senescence. Irradiation induced the expression of P53 and P21 proteins in endothelial cells, but p53 or p21 deficiency and P21 silencing did not prevent radiation-induced inhibition of sprouting or proliferation. Radiation induced Smad-2 phosphorylation in skin in vivo and in endothelial cells in vitro. Inhibition of the TGF-beta type I receptor ALK5 rescued deficient endothelial cell sprouting and migration but not proliferation in vitro and restored defective Matrigel plug angiogenesis in irradiated mice in vivo. ALK5 inhibition, however, did not rescue deficient proliferation. Notch signaling, known to hinder angiogenesis, was activated by radiation but its inhibition, alone or in combination with ALK5 inhibition, did not rescue suppressed proliferation. CONCLUSIONS: These results demonstrate that irradiation of quiescent endothelial cells suppresses subsequent angiogenesis and that ALK5 is a critical mediator of this suppression. These results extend our understanding of radiotherapy-induced endothelial dysfunctions, relevant to both therapeutic and unwanted effects of radiotherapy

GABA Expression and Regulation by Sensory Experience in the Developing Visual System

The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA) has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Prospect and potential of Burkholderia sp. against Phytophthora capsici Leonian: a causative agent for foot rot disease of black pepper

Foot rot disease is a very destructive disease in black pepper in Malaysia. It is caused by Phytophthora capsici Leonian, which is a soilborne pathogenic protist (phylum, Oomycota) that infects aerial and subterranean structures of many host plants. This pathogen is a polycyclic, such that multiple cycles of infection and inoculum production occur in a single growing season. It is more prevalent in the tropics because of the favourable environmental conditions. The utilization of plant growth-promoting rhizobacteria (PGPR) as a biological control agent has been successfully implemented in controlling many plant pathogens. Many studies on the exploration of beneficial organisms have been carried out such as Pseudomonas fluorescens, which is one of the best examples used for the control of Fusarium wilt in tomato. Similarly, P. fluorescens is found to be an effective biocontrol agent against the foot rot disease in black pepper. Nowadays there is tremendous novel increase in the species of Burkholderia with either mutualistic or antagonistic interactions in the environment. Burkholderia sp. is an indigenous PGPR capable of producing a large number of commercially important hydrolytic enzymes and bioactive substances that promote plant growth and health; are eco-friendly, biodegradable and specific in their actions; and have a broad spectrum of antimicrobial activity in keeping down the population of phytopathogens, thus playing a great role in promoting sustainable agriculture today. Hence, in this book chapter, the potential applications of Burkholderia sp. to control foot rot disease of black pepper in Malaysia, their control mechanisms, plant growth promotion, commercial potentials and the future prospects as indigenous PGPR were discussed in relation to sustainable agriculture