miR-30 Family Controls Proliferation and Differentiation of Intestinal Epithelial Cell Models by Directing a Broad Gene Expression Program That Includes SOX9 and the Ubiquitin Ligase Pathway

Proliferation and differentiation of intestinal epithelial cells (IECs) occur in part through precise regulation of key transcription factors, such as SOX9. MicroRNAs (miRNAs) have emerged as prominent fine-tuners of transcription factor expression and activity. We hypothesized that miRNAs, in part through the regulation of SOX9, may mediate IEC homeostasis. Bioinformatic analyses of the SOX9 3′-UTR revealed highly conserved target sites for nine different miRNAs. Of these, only the miR-30 family members were both robustly and variably expressed across functionally distinct cell types of the murine jejunal epithelium. Inhibition of miR-30 using complementary locked nucleic acids (LNA30bcd) in both human IECs and human colorectal adenocarcinoma-derived Caco-2 cells resulted in significant up-regulation of SOX9 mRNA but, interestingly, significant down-regulation of SOX9 protein. To gain mechanistic insight into this non-intuitive finding, we performed RNA sequencing on LNA30bcd-treated human IECs and found 2440 significantly increased genes and 2651 significantly decreased genes across three time points. The up-regulated genes are highly enriched for both predicted miR-30 targets, as well as genes in the ubiquitin-proteasome pathway. Chemical suppression of the proteasome rescued the effect of LNA30bcd on SOX9 protein levels, indicating that the regulation of SOX9 protein by miR-30 is largely indirect through the proteasome pathway. Inhibition of the miR-30 family led to significantly reduced IEC proliferation and a dramatic increase in markers of enterocyte differentiation. This in-depth analysis of a complex miRNA regulatory program in intestinal epithelial cell models provides novel evidence that the miR-30 family likely plays an important role in IEC homeostasis

Health needs of Australian Indigenous young people entering detention

Aim: To determine whether there are different health needs associated with differences between Indigenous and non-Indigenous youth in detention in Brisbane, Queensland, Australia. Methods: All records of young people (aged 10 to 21 years) taken into detention in Brisbane Queensland over the period 1 July 2001 to 30 June 2009 were reviewed, and data were extracted documenting the mental health and related behaviours of those referred to the Mental Health, Alcohol, Tobacco and Other Drugs Service. International Statistical Classification of Diseases and Related Health Problems - Tenth Revision (ICD-10) criteria were applied to a clinical interview. ICD-10 diagnostic outcomes and reason for referral are presented by Indigenous status and age. Results: Young male (under 14 years of age) Indigenous respondents are substantially over-represented in youth in detention. Indigenous youth in detention are disproportionately referred and diagnosed with a substance use problem. Referral and diagnosis of substance use problems was not as commonly found for non-Indigenous youth. Conclusions: Young Indigenous persons are substantially over-represented in those taken into detention in Queensland. This study shows significant differences in relation to mental health and substance use assessment outcomes for Indigenous and non-Indigenous young people in youth detention in Queensland. Further research focusing on service delivery for Indigenous young people should focus on their specific needs

Disparities in physical activity resource availability in six US regions

We conducted an ecologic study to determine physical activity resource availability overall and by sociodemographic groups in parts of six states (CA, IL, MD, MN, NC, NY). Data on parks and recreational facilities were collected from 3 sources in 2009–2012. Three measures characterized park and recreational facility availability at the census tract level: presence of ≥1 resource, number of resources, and resource kernel density. Associations between resource availability and census tract characteristics (predominant racial/ethnic group, median income, and proportion of children and older adults) were estimated using linear, binomial, and zero-inflated negative binomial regression in 2014. Pooled and stratified analyses were conducted. The study included 7,139 census tracts, comprising 9.5% of the 2010 US population. Overall the availability of parks and recreational facilities was lower in predominantly minority relative to non-Hispanic white census tracts. Low-income census tracts and those with a higher proportion of children had an equal or greater availability of park resources but fewer recreational facilities. Stratification revealed substantial variation in resource availability by state. The availability of physical activity resources varied by sociodemographic characteristics and across regions. Improved knowledge of resource distribution can inform strategies to provide equitable access to parks and recreational facilities