Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle.Medical Research Council (MRC); Biotechnology and Biological Sciences Research Council (BBSRC); European Union; Academy of Finland (to H.M.C.). Funding for open access charge: MRC

Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication

Mammalian mitochondria operate multiple mechanisms of DNA replication. In many cells and tissues a strand-asynchronous mechanism predominates over coupled leading and lagging-strand DNA synthesis. However, little is known of the factors that control or influence the different mechanisms of replication, and the idea that strand-asynchronous replication entails transient incorporation of transcripts (aka bootlaces) is controversial. A firm prediction of the bootlace model is that it depends on mitochondrial transcripts. Here, we show that elevated expression of Twinkle DNA helicase in human mitochondria induces bidirectional, coupled leading and lagging-strand DNA synthesis, at the expense of strand-asynchronous replication; and this switch is accompanied by decreases in the steady-state level of some mitochondrial transcripts. However, in the so-called minor arc of mitochondrial DNA where transcript levels remain high, the strand-asynchronous replication mechanism is instated. Hence, replication switches to a strand-coupled mechanism only where transcripts are scarce, thereby establishing a direct correlation between transcript availability and the mechanism of replication. Thus, these findings support a critical role of mitochondrial transcripts in the strand-asynchronous mechanism of mitochondrial DNA replication; and, as a corollary, mitochondrial RNA availability and RNA/DNA hybrid formation offer means of regulating the mechanisms of DNA replication in the organelle

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings

Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple error–correction procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons

Sentiment Analysis in Social Streams

In this chapter we review and discuss the state of the art on sentiment analysis in social streams –such as web forums, micro-blogging systems, and so- cial networks–, aiming to clarify how user opinions, affective states, and intended emotional effects are extracted from user generated content, how they are modeled, and how they could be finally exploited. We explain why sentiment analysis tasks are more difficult for social streams than for other textual sources, and entail going beyond classic text-based opinion mining techniques. We show, for example, that social streams may use vocabularies and expressions that exist outside the main- stream of standard, formal languages, and may reflect complex dynamics in the opinions and sentiments expressed by individuals and communities

Predictors of gastrointestinal lesions on endoscopy in iron deficiency anemia without gastrointestinal symptoms

<p>Abstract</p> <p>Background</p> <p>Iron deficiency anaemia (IDA) due to occult gastrointestinal (GI) blood loss usually remains unnoticed until patient become symptomatic. There is sparse data in IDA patients without gastrointestinal symptoms. This study was designed to find out the frequency and predictors of endoscopic lesions in IDA without gastrointestinal symptoms. Cross-sectional study performed on a convenience sample of consecutive subjects.</p> <p>Methods</p> <p>Ninety five consecutive patients with laboratory based diagnosis of IDA having no gastrointestinal symptoms were interviewed and their clinical and biochemical variables were recorded. All the study patients underwent esophago-gastroduodenoscopy (EGD) and colonoscopy. Endoscopic findings were documented as presence/absence of bleeding related lesion and presence/absence of cause of IDA. Multiple logistic regressions were performed to identify variables significantly related to outcome variables.</p> <p>Results</p> <p>Possible cause of anaemia was found in 71% and bleeding related lesions were found in 53% of patients. Upper gastrointestinal tract lesions were found in 41% of patients with bleeding related lesions. On multivariable logistic regression; advancing age, low mean corpuscular volume (MCV ≤ 60 fl), and positive fecal occult blood test were predictive factors for bleeding related GI lesions and cause of IDA</p> <p>Conclusion</p> <p>Clinical and Biochemical markers can predict gastrointestinal lesions on endoscopy in IDA patients without gastrointestinal symptoms. High proportion of upper gastrointestinal involvement warrants EGD as initial endoscopic procedure however, this needs validation by further studies.</p

Demographic, risk behaviour and personal network variables associated with prevalent hepatitis C, hepatitis B, and HIV infection in injection drug users in Winnipeg, Canada

BACKGROUND: Previous studies have used social network variables to improve our understanding of HIV transmission. Similar analytic approaches have not been undertaken for hepatitis C (HCV) or B (HBV), nor used to conduct comparative studies on these pathogens within a single setting. METHODS: A cross-sectional survey consisting of a questionnaire and blood sample was conducted on injection drug users in Winnipeg between December 2003 and September 2004. Logistic regression analyses were used to correlate respondent and personal network data with HCV, HBV and HIV prevalence. RESULTS: At the multivariate level, pathogen prevalence was correlated with both respondent and IDU risk network variables. Pathogen transmission was associated with several distinct types of high-risk networks formed around specific venues (shooting galleries, hotels) or within users who are linked by their drug use preferences. Smaller, isolated pockets of IDUs also appear to exist within the larger population where behavioural patterns pose a lesser risk, unless or until, a given pathogen enters those networks. CONCLUSION: The findings suggest that consideration of both respondent and personal network variables can assist in understanding the transmission patterns of HCV, HBV, and HIV. It is important to assess these effects for multiple pathogens within one setting as the associations identified and the direction of those associations can differ between pathogens

Production properties of K*(892) vector mesons and their spin alignment as measured in the NOMAD experiment

First measurements of K*(892) mesons production properties and their spin alignment in nu_mu charged current (CC) and neutral current (NC) interactions are presented. The analysis of the full data sample of the NOMAD experiment is performed in different kinematic regions. For K*+ and K*- mesons produced in nu_mu CC interactions and decaying into K0 pi+/- we have found the following yields per event: (2.6 +/- 0.2 (stat.) +/- 0.2 (syst.))% and (1.6 +/- 0.1 (stat.) +/- 0.1 (syst.))% respectively, while for the K*+ and K*- mesons produced in nu NC interactions the corresponding yields per event are: (2.5 +/- 0.3 (stat.) +/- 0.3 (syst.))% and (1.0 +/- 0.3 (stat.) +/- 0.2 (syst.))%. The results obtained for the rho00 parameter, 0.40 +/- 0.06 (stat) +/- 0.03 (syst) and 0.28 +/- 0.07 (stat) +/- 0.03 (syst) for K*+ and K*- produced in nu_mu CC interactions, are compared to theoretical predictions tuned on LEP measurements in e+e- annihilation at the Z0 pole. For K*+ mesons produced in nu NC interactions the measured rho00 parameter is 0.66 +/- 0.10 (stat) +/- 0.05 (syst).Comment: 20 p