Artificial neural network to predict the effect of obesity on the risk of tuberculosis infection

Background: Body weight has been implicated as a risk factor for latent tuberculosis infection (LTBI) and the active disease.Design and Methods: This study aimed to develop artificial neural network (ANN) models for predicting LTBI from body weight and other host-related disease risk factors. We used datasets from participants of the US-National Health and Nutrition Examination Survey (NHANES; 2012; n=5,156; 514 with LTBI and 4,642 controls) to develop three ANNs employing body mass index (BMI, Network I), BMI and HbA1C (as a proxy for diabetes; Network II) and BMI, HbA1C and education (as a proxy for socioeconomic status; Network III). The models were trained on n=1018 age- and sex-matched subjects equally distributed between the control and LTBI groups. The endpoint was the prediction of LTBI.Results: When data was adjusted for age, sex, diabetes and level of education, odds ratio (OR) and 95% confidence intervals (CI) for risk of LTBI with increased BMI was 0.85 (95%CI: 0.77 – 0.96, p=0.01). The three ANNs had a predictive accuracy varied from 75 to 80% with sensitivities ranged from 85% to 94% and specificities of approximately 70%. Areas under the receiver operating characteristic curve (AUC) were between 0.82 and 0.87. Optimal ANN performance was noted using BMI as a risk indicator.Conclusion: Body weight can be employed in developing artificial intelligence-based tool to predict LTBI. This can be useful in precise decision making in clinical and public health practices aiming to curb the burden of tuberculosis, e.g., in the management and monitoring of the tuberculosis prevention programs and to evaluate the impact of healthy weight on tuberculosis risk and burden

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1-9. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression

Recurrent deletions of ULK4 in schizophrenia : a gene crucial for neuritogenesis and neuronal motility

Peer reviewedPublisher PD

Pectin chemistry and cellulose crystallinity govern pavement cell morphogenesis in a multi-step mechanism

Author Posting. ©American Society of Plant Biologists, 2019. This article is posted here by permission of [publisher] for personal use, not for redistribution. The definitive version was published in Altartouri, B., Bidhendi, A. J., Tani, T., Suzuki, J., Conrad, C., Chebli, Y., Liu, N., Karunakaran, C., Scarcelli, G., & Geitmann, A. Pectin chemistry and cellulose crystallinity govern pavement cell morphogenesis in a multi-step mechanism. Plant Physiology, 181(1), (2019): 127-141, doi:10.1104/pp.19.00303.Simple plant cell morphologies, such as cylindrical shoot cells, are determined by the extensibility pattern of the primary cell wall, which is thought to be largely dominated by cellulose microfibrils, but the mechanism leading to more complex shapes, such as the interdigitated patterns in the epidermis of many eudicotyledon leaves, is much less well understood. Details about the manner in which cell wall polymers at the periclinal wall regulate the morphogenetic process in epidermal pavement cells and mechanistic information about the initial steps leading to the characteristic undulations in the cell borders are elusive. Here, we used genetics and recently developed cell mechanical and imaging methods to study the impact of the spatio-temporal dynamics of cellulose and homogalacturonan pectin distribution during lobe formation in the epidermal pavement cells of Arabidopsis (Arabidopsis thaliana) cotyledons. We show that nonuniform distribution of cellulose microfibrils and demethylated pectin coincides with spatial differences in cell wall stiffness but may intervene at different developmental stages. We also show that lobe period can be reduced when demethyl-esterification of pectins increases under conditions of reduced cellulose crystallinity. Our data suggest that lobe initiation involves a modulation of cell wall stiffness through local enrichment in demethylated pectin, whereas subsequent increase in lobe amplitude is mediated by the stress-induced deposition of aligned cellulose microfibrils. Our results reveal a key role of noncellulosic polymers in the biomechanical regulation of cell morphogenesis.Natural Sciences and Engineering Research Council of Canada Canada Research Chair Program Marine Biological Laboratory NIH R01GM100160 Canada Foundation for Innovation University of Saskatchewan Government of Saskatchewan Western Economic Diversification Canada National Research Council (Canada) Canadian Institutes of Health Researc

Public Health Nutrition: page 1 of 10 doi:10.1017/S1368980012000754 Review Article The science on front-of-package food labels

Objective: The US Food and Drug Administration and Institute of Medicine are currently investigating front-of-package (FOP) food labelling systems to provide sciencebased guidance to the food industry. The present paper reviews the literature on FOP labelling and supermarket shelf-labelling systems published or under review by February 2011 to inform current investigations and identify areas of future research. Design: A structured search was undertaken of research studies on consumer use, understanding of, preference for, perception of and behaviours relating to FOP/ shelf labelling published between January 2004 and February 2011. Results: Twenty-eight studies from a structured search met inclusion criteria. Reviewed studies examined consumer preferences, understanding and use of different labelling systems as well as label impact on purchasing patterns and industry product reformulation. Conclusions: The findings indicate that the Multiple Traffic Light system has most consistently helped consumers identify healthier products; however, additional research on different labelling systems ’ abilities to influence consumer behaviour is needed. In May 2010 the White House Childhood Obesity Task Force highlighted the need to ‘empower parents and caregivers to make healthy choices ’ with simple, practical information, including improved front-of-package (FOP) food labels (1). Currently the US Food and Drug Administration (FDA) has undertaken a Front-of-Package Labeling Initiative (2) with the goal of reviewing available evidence on FOP labelling systems to determine whether one approach can be recommended over others. Congress also requested that the Institute of Medicine (IOM) examine this issue and in October 2010 the Committee o

A Randomized Controlled Trial of a Faith-Placed, Lay Health Advisor Delivered Smoking Cessation Intervention for Rural Residents

Introduction. Rural US residents smoke at higher rates than urban or suburban residents. We report results from a community-based smoking cessation intervention in Appalachian Kentucky. Study design. Single-blind, group-randomized trial with outcome measurements at baseline, 17 weeks and 43 weeks. Setting/participants. This faith-placed CBPR project was located in six counties of rural Appalachian Kentucky. A total of 590 individual participants clustered in 28 churches were enrolled in the study. Intervention. Local lay health advisors delivered the 12-week Cooper/Clayton Method to Stop Smoking program, leveraging sociocultural factors to improve the cultural salience of the program for Appalachian smokers. Participants met with an interventionist for one 90 min group session once per week incorporating didactic information, group discussion, and nicotine replacement therapy. Main outcome measures. The primary outcome was self-reported smoking status. Secondary outcomes included Fagerström nicotine dependence, self-efficacy, and decisional balance. Results. With post-intervention data from 92% of participants, those in intervention group churches (N = 383) had 13.6 times higher odds of reporting quitting smoking one month post-intervention than participants in attention control group churches (N = 154, p \u3c 0.0001). In addition, although only 3.2% of attention control group participants reported quitting during the control period, 15.4% of attention control participants reported quitting smoking after receiving the intervention. A significant dose effect of the 12-session Cooper/Clayton Method was detected: for each additional session completed, the odds of quitting smoking increased by 26%. Conclusions. The Cooper/Clayton Method, delivered in rural Appalachian churches by lay health advisors, has strong potential to reduce smoking rates and improve individuals\u27 health

Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains

Background miRNAs are short single-stranded non-coding RNAs involved in post-transcriptional gene regulation that play a major role in normal biological functions and diseases. Little is currently known about how expression of miRNAs is regulated. We surveyed variation in miRNA abundance in the hippocampus of mouse inbred strains, allowing us to take a genetic approach to the study of miRNA regulation, which is novel for miRNAs. The BXD recombinant inbred panel is a very well characterized genetic reference panel which allows quantitative trait locus (QTL) analysis of miRNA abundance and detection of correlates in a large store of brain and behavioural phenotypes. Results We found five suggestive trans QTLs for the regulation of miRNAs investigated. Further analysis of these QTLs revealed two genes, Tnik and Phf17, under the miR-212 regulatory QTLs, whose expression levels were significantly correlated with miR-212 expression. We found that miR-212 expression is correlated with cocaine-related behaviour, consistent with a reported role for this miRNA in the control of cocaine consumption. miR-31 is correlated with anxiety and alcohol related behaviours. KEGG pathway analysis of each miRNA’s expression correlates revealed enrichment of pathways including MAP kinase, cancer, long-term potentiation, axonal guidance and WNT signalling. Conclusions The BXD reference panel allowed us to establish genetic regulation and characterize biological function of specific miRNAs. QTL analysis enabled detection of genetic loci that regulate the expression of these miRNAs. eQTLs that regulate miRNA abundance are a new mechanism by which genetic variation influences brain and behaviour. Analysis of one of these QTLs revealed a gene, Tnik, which may regulate the expression of a miRNA, a molecular pathway and a behavioural phenotype. Evidence of genetic covariation of miR-212 abundance and cocaine related behaviours is strongly supported by previous functional studies, demonstrating the value of this approach for discovery of new functional roles and downstream processes regulated by miRNA