Microbial regulation of the L cell transcriptome.

L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in Lpos cells from ileum. This finding was corroborated by electron microscopy of Lpos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Alcohol Outlet Density and Young Women’s Perpetration of Violence Toward Male Intimate Partners

This paper examines the relationships between alcohol outlet density, alcohol use, and perpetration of intimate partner violence (IPV) among young adult women in the US. Data were from Wave III of the National Longitudinal Study of Adolescent Health (Add Health; N = 4,430 in present analyses). Multinomial logistic regression was used to examine occurrence of past year IPV perpetration toward a male partner based on tract-level on-premise and off-premise alcohol outlet density, controlling for individuals’ demographic, alcohol use, and childhood abuse characteristics and neighborhood socio-demographic factors. Higher off-premise alcohol outlet density was found to be associated with young women’s perpetration of physical only IPV, controlling for individual-level and ecological factors. Alcohol use had an independent association with IPV perpetration but was not a mediator of the outlet density-IPV relationship. Findings suggest that considering alcohol-related environmental factors may help efforts aimed at preventing young women’s use of physical violence toward partners

Stem cells and breast cancer: A field in transit

Evidence that supports the existence of a tumour stem cell for breast cancer has given fresh impetus to the search for an adult mammary epithelial stem cell in the normal breast. Such a cell might be responsible for routine tissue renewal and the massive expansion in epithelial tissue that the breast undergoes during pregnancy, and might be the cell of origin of most, if not all, breast tumours. So, what evidence is there that an adult mammary epithelial stem cell exists, what is its possible identity and what opportunities might the identification of such a cell present for the development of novel therapeutic and prophylactic strategies for treating breast cancer