Construction of integrated microRNA and mRNA immune cell signatures to predict survival of patients with breast and ovarian cancer.

In the tumor microenvironment, immune cells have emerged as key regulators of cancer progression. While much work has focused on characterizing tumor-related immune cells through gene expression profiling, microRNAs (miRNAs) have also been reported to regulate immune cells in the tumor microenvironment. Using regression-based computational methods, we have constructed for the first time, immune cell signatures based on miRNA expression from The Cancer Genome Atlas breast and ovarian cancer datasets. Combined with existing mRNA immune cell signatures, the integrated mRNA-miRNA leukocyte signatures are better able to delineate prognostic immune cell subsets within both cancers compared to the mRNA or miRNA signatures alone. Moreover, using the miRNA signatures, the anti-inflammatory M2 macrophages emerged as the most significantly prognostic cell type in the breast cancer data (HR [hazard ratio]: 12.9; CI [confidence interval]: 3.09-52.9; P = 4.22E-4), whereas the pro-inflammatory M1 macrophages emerged as the most prognostic immune cell type in the ovarian cancer data (HR: 0.2; CI: 0.04-0.56, P = 5.02E-3). These results suggest that our integrated miRNA and mRNA leukocyte signatures could be used to better delineate prognostic leukocyte subsets within cancers, whereas continued investigation may further support the regulatory relationships predicted between the miRNAs and immune cells found within our signature matrices.

Hypertension Treatment Rates and Health Care Worker Density.

Elevated blood pressure is the leading cause of death worldwide; however, treatment and control rates for hypertension are low. Here, we analyze the relationship between physician and nurse density and hypertension treatment rates worldwide. Data on hypertension treatment rates were collected from the STEPwise approach to Surveillance country reports, individual studies resulting from a PubMed search for articles published between 1990 and 2010, and manual search of the reference lists of extracted studies. Data on health care worker density were obtained from the Global Atlas of the Health Workforce. We controlled for a variety of variables related to population characteristics and access to health care, data obtained from the World Bank, World Development Indicators, United Nations, and World Health Organization. We used clustering of SEs at the country level. Full data were available for 154 hypertension treatment rate values representing 68 countries between 1990 and 2010. Hypertension treatment rate ranged from 3.4% to 82.5%, with higher treatment rates associated with higher income classification. Physician and nurse/midwife generally increased with income classification. Total healthcare worker density was significantly associated with hypertension treatment rate in the unadjusted model ( P<0.001); however, only nurse density remained significant in the fully adjusted model ( P=0.050). These analyses suggest that nurse density, not physician density, explains most of the relationship with hypertension treatment rate and remains significant even after adjusting for other independent variables. These results have important implications for health policy, health system design, and program implementation.

Genomic DNA transposition induced by human PGBD5.

Transposons are mobile genetic elements that are found in nearly all organisms, including humans. Mobilization of DNA transposons by transposase enzymes can cause genomic rearrangements, but our knowledge of human genes derived from transposases is limited. In this study, we find that the protein encoded by human PGBD5, the most evolutionarily conserved transposable element-derived gene in vertebrates, can induce stereotypical cut-and-paste DNA transposition in human cells. Genomic integration activity of PGBD5 requires distinct aspartic acid residues in its transposase domain, and specific DNA sequences containing inverted terminal repeats with similarity to piggyBac transposons. DNA transposition catalyzed by PGBD5 in human cells occurs genome-wide, with precise transposon excision and preference for insertion at TTAA sites. The apparent conservation of DNA transposition activity by PGBD5 suggests that genomic remodeling contributes to its biological function.

Mycobacteriophages BPs, Angel and Halo: comparative genomics reveals a novel class of ultra-small mobile genetic elements.

Mycobacteriophages BPs, Angel and Halo are closely related viruses isolated from Mycobacterium smegmatis, and possess the smallest known mycobacteriophage genomes, 41,901 bp, 42,289 bp and 41,441 bp, respectively. Comparative genome analysis reveals a novel class of ultra-small mobile genetic elements; BPs and Halo each contain an insertion of the proposed mobile elements MPME1 and MPME2, respectively, at different locations, while Angel contains neither. The close similarity of the genomes provides a comparison of the pre- and post-integration sequences, revealing an unusual 6 bp insertion at one end of the element and no target duplication. Nine additional copies of these mobile elements are identified in a variety of different contexts in other mycobacteriophage genomes. In addition, BPs, Angel and Halo have an unusual lysogeny module in which the repressor and integrase genes are closely linked. The attP site is located within the repressor-coding region, such that prophage formation results in expression of a C-terminally truncated, but active, form of the repressor.