Bayesian models for DNA microarray data analysis

Selection of signi?cant genes via expression patterns is important in a microarray problem. Owing to small sample size and large number of variables (genes), the selection process can be unstable. This research proposes a hierarchical Bayesian model for gene (variable) selection. We employ latent variables in a regression setting and use a Bayesian mixture prior to perform the variable selection. Due to the binary nature of the data, the posterior distributions of the parameters are not in explicit form, and we need to use a combination of truncated sampling and Markov Chain Monte Carlo (MCMC) based computation techniques to simulate the posterior distributions. The Bayesian model is ?exible enough to identify the signi?cant genes as well as to perform future predictions. The method is applied to cancer classi?cation via cDNA microarrays. In particular, the genes BRCA1 and BRCA2 are associated with a hereditary disposition to breast cancer, and the method is used to identify the set of signi?cant genes to classify BRCA1 and others. Microarray data can also be applied to survival models. We address the issue of how to reduce the dimension in building model by selecting signi?cant genes as well as assessing the estimated survival curves. Additionally, we consider the wellknown Weibull regression and semiparametric proportional hazards (PH) models for survival analysis. With microarray data, we need to consider the case where the number of covariates p exceeds the number of samples n. Speci?cally, for a given vector of response values, which are times to event (death or censored times) and p gene expressions (covariates), we address the issue of how to reduce the dimension by selecting the responsible genes, which are controlling the survival time. This approach enables us to estimate the survival curve when n << p. In our approach, rather than ?xing the number of selected genes, we will assign a prior distribution to this number. The approach creates additional ?exibility by allowing the imposition of constraints, such as bounding the dimension via a prior, which in e?ect works as a penalty. To implement our methodology, we use a Markov Chain Monte Carlo (MCMC) method. We demonstrate the use of the methodology with (a) di?use large B??cell lymphoma (DLBCL) complementary DNA (cDNA) data and (b) Breast Carcinoma data. Lastly, we propose a mixture of Dirichlet process models using discrete wavelet transform for a curve clustering. In order to characterize these time??course gene expresssions, we consider them as trajectory functions of time and gene??speci?c parameters and obtain their wavelet coe?cients by a discrete wavelet transform. We then build cluster curves using a mixture of Dirichlet process priors

CD4+ T cells from MHC II-dependent thymocyte–thymocyte interaction provide efficient help for B cells

Recently, a novel CD4+ T-cell developmental pathway was reported that generates thymocyte–thymocyte (T–T) CD4+ T cells. We established a mouse system (CIITAtgCIITApIV−/−) where thymic positive selection occurred only by major histocompatibility complex (MHC) class II+ thymocytes. T–T CD4+ T cells selected via MHC class II-dependent T–T interaction are comprised of PLZF-negative and innate PLZF-positive populations. Until recently, the functional role of the PLZF-negative population was unclear. In this study, we demonstrate that naïve T–T CD4+ T cells provide B-cell help to a level comparable with that of naïve conventional CD4+ T cells. Considering the absence of PLZF expression in naïve T–T CD4+ T cells, these results suggest that PLZF-negative naïve T–T CD4+ T cells are functionally equivalent to conventional naïve CD4+ T cells in terms of B-cell help

COVID-19 Perception, Knowledge, and Preventive Practice: Comparison between South Korea, Ethiopia, and Democratic Republic of Congo

In Africa, the first confirmed case of COVID-19 was reported in Egypt on February 14, 2020. Since then, the number of cases has continued to&nbsp; increase with Ethiopia, the Democratic Republic of Congo (DRC), Nigeria, Sudan, Angola, Tanzania, Ghana, and Kenya identified as vulnerable&nbsp; countries. The present study aimed to: 1) identify differences in trust level of COVID-19 diagnosis, recent healthcare utilization experiences, and COVID-19-related knowledge, information, and prevention practices in South Korea, Ethiopia, and DRC; and 2) identify factors influencing trust level in healthcare facilities regarding COVID-19 diagnosis. The present study was cross-sectional. The questionnaire survey was conducted between May 1–14, 2020 using Google forms, and 748 respondents were included in the final analysis. The data collected were analyzed using ANOVA, post - hoc test, and binary logistic regression analysis. South Korea showed higher rate of practice for COVID-19 prevention such as hand washing, mask wearing, and etc. than Ethiopia and DRC. The results showed significant differences with the trust level being 3.129 times higher in respondents from DRC than those from Ethiopia (aOR=3.129, 95% CI: [1.884-5.196], p&lt;.000) and 29.137 times higher in respondents from South Korean than those from Ethiopia (aOR=29.137, 95% CI: [13.869-61.210], p&lt;.000). Gender, age, number of family members, healthcare utilization experience, information, and practice were significant variables. Health education expansion for information and practice about COVID-19 in Ethiopia and DRC is necessary. Keywords: COVID-19, Pandemic, Ethiopia, DRC, South Korea, Online Survey En Afrique, le premier cas confirmé de COVID-19 a été signalé en Égypte le 14 février 2020. Depuis, le nombre de cas n'a cessé d'augmenter avec l'Éthiopie, la République démocratique du Congo (RDC), le Nigéria, le Soudan, l'Angola, La Tanzanie, le Ghana et le Kenya ont été identifiés comme pays vulnérables. La présente étude visait à: 1) identifier les différences de niveau de confiance dans le diagnostic du COVID-19, les expériences récentes d'utilisation des soins de santé et les connaissances, informations et pratiques de prévention liées au COVID-19 en Corée du Sud, en Éthiopie et en RDC; et 2) identifier les facteurs influençant le niveau de confiance dans les établissements de santé concernant le diagnostic du COVID-19. La présente étude était transversale. L'enquête par questionnaire a été menée du 1er au 14 mai 2020 à l'aide de formulaires Google, et 748 répondants ont été inclus dans l'analyse finale. Les données collectées ont été analysées en utilisant une analyse ANOVA, un test post-hoc et une analyse de régression logistique binaire. La Corée du Sud a montré un taux de pratique plus élevé pour la prévention du COVID-19, comme le lavage des mains, le port d'un masque, etc. que l'Éthiopie et la RDC. Les résultats ont montré des différences significatives, le niveau de confiance étant 3,129 fois plus élevé chez les répondants de RDC que chez ceux d'Éthiopie (aOR = 3,129, IC à 95%: [1,884-5,196], p &lt;.000) et 29,137 fois plus élevé chez les répondants sud-coréens que ceux d'Éthiopie (aOR = 29,137, IC à 95%: [13,869-61,210], p &lt;.000). Le sexe, l'âge, le nombre de membres de la famille, l'expérience d'utilisation des soins de santé, l'information et la pratique étaient des variables importantes. L'élargissement de l'éducation sanitaire pour l'information et la pratique du COVID-19 en Éthiopie et en RDC est nécessaire. Mots-clés: COVID-19, Pandémie, Éthiopie, RDC, Corée du Sud, Enquête en lign

Cooperative roles of the suprachiasmatic nucleus central clock and the adrenal clock in controlling circadian glucocorticoid rhythm

The mammalian circadian timing system consists of the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and subsidiary peripheral clocks in other tissues. Glucocorticoids (GCs) are adrenal steroid hormones with widespread physiological effects that undergo daily oscillations. We previously demonstrated that the adrenal peripheral clock plays a pivotal role in circadian GC rhythm by driving cyclic GC biosynthesis. Here, we show that the daily rhythm in circulating GC levels is controlled by bimodal actions of central and adrenal clockwork. When mice were subjected to daytime restricted feeding to uncouple central and peripheral rhythms, adrenal GC contents and steroidogenic acute regulatory protein expression peaked around zeitgeber time 00 (ZT00), consistent with shifted adrenal clock gene expression. However, restricted feeding produced two distinct peaks in plasma GC levels: one related to adrenal GC content and the other around ZT12, which required an intact SCN. Light pulse-evoked activation of the SCN increased circulating GC levels in both wild-type and adrenal clock-disrupted mutant mice without marked induction of GC biosynthesis. In conclusion, we demonstrate that adrenal clock-dependent steroidogenesis and a SCN-driven central mechanism regulating GC release cooperate to produce daily circulatory GC rhythm. © The Author(s) 2017.1

Disease Prevalence and Mortality among Agricultural Workers in Korea

The aim of this paper was to provide an overview of mortality and disease prevalence related to occupational diseases among agricultural workers in Korea. We evaluated the age-standardized mortality rates and the prevalence of chronic diseases and compared them with those of other populations using death registration data from 2004 through 2008 and the 2005 Korean National Health and Nutrition Examination Survey. In addition, we conducted a literature review on published articles examining the health status of farmers in Korea. Agricultural workers have a significantly higher mortality of cancer, tuberculosis, chronic respiratory diseases, liver diseases, suicide, motor and non-motor vehicle accidents. Compared to other populations, farmers have higher prevalence rates of arthritis and intervertebral disc disorders. The literature review revealed a number of work-related diseases among farmers, such as musculoskeletal diseases, pesticide poisoning, infections, and respiratory and neurologic diseases. Korean farmers demonstrate a distinct pattern of mortality and disease prevalence compared to other populations. Although lifestyle factors remain important contributors to those deaths and diseases, our study suggests that occupation is a major determinant as well. Intensive programs such as surveillance systems, therefore, should be developed in order to identify and prevent work-related diseases among agricultural workers in Korea

Reactive oxygen species and p47phox activation are essential for the Mycobacterium tuberculosis-induced pro-inflammatory response in murine microglia

<p>Abstract</p> <p>Background</p> <p>Activated microglia elicits a robust amount of pro-inflammatory cytokines, which are implicated in the pathogenesis of tuberculosis in the central nervous system (CNS). However, little is known about the intracellular signaling mechanisms governing these inflammatory responses in microglia in response to <it>Mycobacterium tuberculosis </it>(Mtb).</p> <p>Methods</p> <p>Murine microglial BV-2 cells and primary mixed glial cells were stimulated with sonicated Mtb (s-Mtb). Intracellular ROS levels were measured by staining with oxidative fluorescent dyes [2',7'-Dichlorodihydrofluorescein diacetate (H₂DCFDA) and dihydroethidium (DHE)]. NADPH oxidase activities were measured by lucigenin chemiluminescence assay. S-Mtb-induced MAPK activation and pro-inflammatory cytokine release in microglial cells were measured using by Western blot analysis and enzyme-linked immunosorbent assay, respectively.</p> <p>Results</p> <p>We demonstrate that s-Mtb promotes the up-regulation of reactive oxygen species (ROS) and the rapid activation of mitogen-activated protein kinases (MAPKs), including p38 and extracellular signal-regulated kinase (ERK) 1/2, as well as the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12p40 in murine microglial BV-2 cells and primary mixed glial cells. Both NADPH oxidase and mitochondrial electron transfer chain subunit I play an indispensable role in s-Mtb-induced MAPK activation and pro-inflammatory cytokine production in BV-2 cells and mixed glial cells. Furthermore, the activation of cytosolic NADPH oxidase p47phox and MAPKs (p38 and ERK1/2) is mutually dependent on s-Mtb-induced inflammatory signaling in murine microglia. Neither TLR2 nor dectin-1 was involved in s-Mtb-induced inflammatory responses in murine microglia.</p> <p>Conclusion</p> <p>These data collectively demonstrate that s-Mtb actively induces the pro-inflammatory response in microglia through NADPH oxidase-dependent ROS generation, although the specific pattern-recognition receptors involved in these responses remain to be identified.</p