Common mitochondrial polymorphisms as risk factor for endometrial cancer

Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility factors. To investigate the presence of mtDNA somatic mutations and distribution of inherited polymorphisms in endometrial adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and their corresponding normal tissues and moreover performed mitochondrial haplogroup analysis. We detected 2 somatic mutation and increased incidence of mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%, p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analysis revealed that endometrial carcinoma population haplogroup distribution differs from the Polish population and that haplogroup H (with its defining polymorphism - C7028T) is strongly underrepresented (p = 0.003), therefore might be a cancer-protective factor. Our report supports the notion that mtDNA polymorphisms establish a specific genetic background for endometrial adenocarcinoma development and that mtDNA analysis may result in the development of new molecular tool for cancer detection

Prediction of the structure of the common perimitochondrial localization signal of nuclear transcripts in yeast

Many nuclear genes encoding mitochondrial proteins require specific localization of their mRNAs to the vicinity of mitochondria for proper expression. Studies in Saccharomyces cerevisiae have shown that the cis-acting signal responsible for subcellular localization of mRNAs is localized in the 3' UTR of the transcript. In this paper we present an in silico approach for prediction of a common perimitochondrial localization signal of nuclear transcripts encoding mitochondrial proteins. We computed a consensus structure for this signal by comparison of 3' UTR models for about 3000 yeast transcripts with known localization. Our studies show a short stem-loop structure which appears in most mRNAs localized to the vicinity of mitochondria. The degree of similarity of a given 3' UTR to our consensus structure strongly correlates with experimentally determined perimitochondrial localization of the mRNA, therefore we believe that the structure we predicted acts as a subcellular localization signal. Since our algorithm operates on structures, it seems to be more reliable than sequence-based algorithms. The good predictive value of our model is supported by statistical analysis

Balance between Transcription and RNA Degradation Is Vital for Saccharomyces cerevisiae Mitochondria: Reduced Transcription Rescues the Phenotype of Deficient RNA Degradation

The Saccharomyces cerevisiae SUV3 gene encodes the helicase component of the mitochondrial degradosome (mtEXO), the principal 3′-to-5′ exoribonuclease of yeast mitochondria responsible for RNA turnover and surveillance. Inactivation of SUV3 (suv3Δ) causes multiple defects related to overaccumulation of aberrant transcripts and precursors, leading to a disruption of mitochondrial gene expression and loss of respiratory function. We isolated spontaneous suppressors that partially restore mitochondrial function in suv3Δ strains devoid of mitochondrial introns and found that they correspond to partial loss-of-function mutations in genes encoding the two subunits of the mitochondrial RNA polymerase (Rpo41p and Mtf1p) that severely reduce the transcription rate in mitochondria. These results show that reducing the transcription rate rescues defects in RNA turnover and demonstrates directly the vital importance of maintaining the balance between RNA synthesis and degradation

Pedagogy as possibility: Health interventions as digital openness

In this article we propose an approach to digital health tracking technologies that draws on design anthropology. This entails re-thinking the pedagogical importance of personal data as lying in how they participate in the constitution of new possibilities that enable people to learn about, and configure, their everyday health in new ways. There have been two dominant strands in traditional debates in the field of pedagogy: one that refers to processes of teaching people to do things in particular ways; and another that seeks to enable learning. The first of these corresponds with existing understandings of self-tracking technologies as either unsuccessful behavioural change devices, or as providing solutions to problems that do not necessarily exist. When seen as such, self-tracking technologies inevitably fail as forms of intervention towards better health. In this article we investigate what happens when we take the second strand-the notion of enabling learning as an incremental and emergent process-seriously as a mode of intervention towards health through self-tracking technologies. We show how such a shift in pedagogical understanding of the routes to knowing these technologies offer creates opportunities to move beyond simplistic ideas of behavioural change as the main application of digital body monitoring in everyday life. In what follows, we first demonstrate how the disjunctures that arise from this context emerge. We then outline a critical response to how learning through life-tracking has been conceptualised in research in health and human-computer interaction research. We offer an alternative response by drawing on a processual theory of learning and recent and emerging research in sociology, media studies, anthropology, and cognate disciplines. Then, drawing on ethnographic research, we argue for understanding learning through the production of personal data as involving emplaced and non-representational routes to knowing. Thi

Additional file 6: Table S6. of The transcriptome of Candida albicans mitochondria and the evolution of organellar transcription units in yeasts

Mitochondrial genome sequences used in the evolutionary comparisons. Genome size, accession numbers, number of introns, and references are provided. (XLSX 14 kb

Additional file 2: Table S2. of The transcriptome of Candida albicans mitochondria and the evolution of organellar transcription units in yeasts

Promoters and promoter-like sequences in C. albicans mtDNA. Promoters of the primary transcription units are highlighted. In the “support” column “none” means that a consensus nonanucleotide is present, but no transcriptional activity can be reliably attributed to the promoter, “reads” means that there is an increased number of reads mapping downstream of the promoter, “reads and 5’-RACE” means promoters confirmed independently (Fig. 4). The second copy of inverted repeat (IRb) is omitted, as in Fig. 2b. (XLSX 9 kb