Nuclear respiratory factor 2 induces SIRT3 expression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113760/1/acel12360-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113760/2/acel12360.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113760/3/acel12360-sup-0002-FigS2.pd

Activated c-SRC in ductal carcinoma in situ correlates with high tumour grade, high proliferation and HER2 positivity

Overexpression and/or activity of c-Src non-receptor tyrosine kinase is associated with progression of several human epithelial cancers including breast cancer. c-Src activity in ‘pure' ductal carcinoma in situ (DCIS) was measured to assess whether this predicts recurrence and/or correlates with HER2 expression and other clinical parameters. Activated c-Src levels were evaluated in DCIS biopsies from 129 women, with median follow-up at 60 months. High levels of activated c-Src correlated with HER2 positivity, high tumour grade, comedo necrosis and elevated epithelial proliferation. In univariate analysis, high activated c-Src level associated with lower recurrence-free survival at 5 years (P=0.011). Thus, high c-Src activity may identify a subset of DCIS with high risk of recurrence or progression to invasive cancer where therapeutics targeting c-Src may benefit this patient subset

Education and older adults at the University of the Third Age

This article reports a critical analysis of older adult education in Malta. In educational gerontology, a critical perspective demands the exposure of how relations of power and inequality, in their myriad forms, combinations, and complexities, are manifest in late-life learning initiatives. Fieldwork conducted at the University of the Third Age (UTA) in Malta uncovered the political nature of elder-learning, especially with respect to three intersecting lines of inequality - namely, positive aging, elitism, and gender. A cautionary note is, therefore, warranted at the dominant positive interpretations of UTAs since late-life learning, as any other education activity, is not politically neutral.peer-reviewe

Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era

Abstract Background Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings. Methods We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding. Results Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4. Conclusions These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci.http://deepblue.lib.umich.edu/bitstream/2027.42/109537/1/12920_2013_Article_485.pd

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

African farmer-led irrigation development: re-framing agricultural policy and investment?

The past decade has witnessed an intensifying focus on the development of irrigation in sub-Saharan Africa. It follows a 20-year hiatus in the wake of disappointing irrigation performance during the 1970s and 1980s. Persistent low productivity in African agriculture and vulnerability of African food supplies to increasing instability in international commodity markets are driving pan-African agricultural investment initiatives, such as the Comprehensive Africa Agricultural Development Programme (CAADP), that identify as a priority the improvement in reliability of water control for agriculture. The paper argues that, for such initiatives to be effective, there needs to be a re-appraisal of current dynamics of irrigation development in sub-Saharan Africa, particularly with respect to the role of small-scale producers’ initiatives in expanding irrigation. The paper reviews the principal forms such initiatives take and argues that official narratives and statistics on African irrigation often underestimate the extent of such activities. The paper identifies five key characteristics which, it argues, contradict widely held assumptions that inform irrigation policy in Africa. The paper concludes by offering a definition of ‘farmer-led irrigation’ that embraces a range of interaction between producers and commercial, government and non-government agencies, and identifies priority areas for research on the growth potential and impact of such interactions and strategies for their future development

Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR