Of Mice and ‘Convicts’: Origin of the Australian House Mouse, Mus musculus

The house mouse, Mus musculus, is one of the most ubiquitous invasive species worldwide and in Australia is particularly common and widespread, but where it originally came from is still unknown. Here we investigated this origin through a phylogeographic analysis of mitochondrial DNA sequences (D-loop) comparing mouse populations from Australia with those from the likely regional source area in Western Europe. Our results agree with human historical associations, showing a strong link between Australia and the British Isles. This outcome is of intrinsic and applied interest and helps to validate the colonization history of mice as a proxy for human settlement history

Prevalence of psychosis in black ethnic minorities in Britain: analysis based on three national surveys

Purpose A considerable excess of psychosis in black ethnic minorities is apparent from clinical studies, in Britain, as in other developed economies with white majority populations. This excess is not so marked in population surveys. Equitable health service provision should be informed by the best estimates of the excess. We used national survey data to establish the difference in the prevalence of psychosis between black ethnic groups and the white majority in the British general population. Methods Analysis of the combined datasets (N = 26,091) from the British national mental health surveys of 1993, 2000 and 2007. Cases of psychosis were determined either by the use of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), or from a combination of screening items. We controlled for sex, age, social class, unemployment, design features and other putative confounders, using a Disease Risk Score. Results People from black ethnic minorities had an excess prevalence rate of psychosis compared with the white majority population. The OR, weighted for study design and response rate, was 2.72 (95 % CI 1.3–5.6, p = 0.002). This was marginally increased after controlling for potential confounders (OR = 2.90, 95 % CI 1.4–6.2, p = 0.006). Conclusions The excess of psychosis in black ethnic minority groups was similar to that in two previous British community surveys, and less than that based on clinical studies. Even so it confirms a considerable need for increased mental health service resources in areas with high proportions of black ethnic minority inhabitants

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Antioxidant compounds recovery from Juçara residue by thermal assisted extraction

This study aimed to recover bioactive compounds by solid-liquid extraction from the agro-industrial residue obtained during juçara fruits processing into pulp. A preliminary study using different solvents (methanol, ethanol and water) indicated ethanol in aqueous solution as the best solvent for antioxidants recovery. Then, a Box-Behnken design was applied considering as independent variables the solvent composition (3070% ethanol in water), temperature (3070 °C) and time (3060 min), in order to evaluate the effects of these factors on antioxidant activity in juçara extract. Results showed that the extracts with higher antioxidant activity were obtained using 30% ethanol at 70 °C for 60 min; measurements included ABTS and DPPH assays, determination of total phenolic content and total monomeric anthocyanins. Furthermore, the effect of pH in antioxidants recovery was evaluated. For this purpose, the 30% ethanol solution was acidified to pH 1 and 2 with HCl. Principal component analysis showed the formation of three distinct groups: one characterized by high bioactive compounds content (pH 1.0), another with superior antioxidant activity (pH 5.75, non-acidified), and finally the group at pH 2 presenting the worst concentrations in the evaluated responses. HPLC analysis showed the presence of cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside in the extracts. Therefore, the conventional solid-liquid extraction using renewable solvent can be successfully applied to recover bioactive compounds from juçara residue, which can be used by different food industries.The authors gratefully acknowledge the institutions: Coordenação de Aperfeiçoamento Pessoal deEnsinoSuperior (CAPES), Universidade Federal do Rio de Janeiro, Embrapa Agroindústria de Alimentos and University of Minho by the financial support of the research work and Juçaí Alimentos for the juçara residue. Ricardo N. Pereira gratefully acknowledge to Portuguese Foundation for Science and Technology (FCT) the financial grant with reference SFRH/BPD/ 81887/2011.info:eu-repo/semantics/publishedVersio

The effect of seasoning with herbs on the nutritional, safety and sensory properties of reduced-sodium fermented Cobrançosa cv. table olives

This study aimed at evaluating the effectiveness of seasoning Cobrancosa table olives in a brine with aromatic ingredients, in order to mask the bitter taste given by KCl when added to reduced-sodium fermentation brines. Olives were fermented in two different salt combinations: Brine A, containing 8% NaCl and, Brine B, a reduced-sodium brine, containing 4% NaCl + 4% KCl. After the fermentation the olives were immersed in seasoning brines with NaCl (2%) and the aromatic herbs (thyme, oregano and calamintha), garlic and lemon. At the end of the fermentation and two weeks after seasoning, the physicochemical, nutritional, organoleptic, and microbiological parameters, were determined. The olives fermented in the reduced-sodium brines had half the sodium concentration, higher potassium and calcium content, a lower caloric level, but were considered, by a sensorial panel, more bitter than olives fermented in NaCl brine. Seasoned table olives, previously fermented in Brine A and Brine B, had no significant differences in the amounts of protein (1.23% or 1.11%), carbohydrates (1.0% or 0.66%), fat (20.0% or 20.5%) and dietary fiber (3.4% or 3.6%). Regarding mineral contents, the sodium-reduced fermented olives, presented one third of sodium, seven times more potassium and three times more calcium than the traditional olives fermented in 8% NaCl. Additionally, according to the panelists' evaluation, seasoning the olives fermented in 4% NaCl + 4% KCl, resulted in a decrease in bitterness and an improvement in the overall evaluation and flavor. Escherichia coli and Salmonella were not found in the olives produced.info:eu-repo/semantics/publishedVersio

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

A tiered-layered-staged model for informed consent in personal genome testing

In recent years, developments in genomics technologies have led to the rise of commercial personal genome testing (PGT): broad genome-wide testing for multiple diseases simultaneously. While some commercial providers require physicians to order a personal genome test, others can be accessed directly. All providers advertise directly to consumers and offer genetic risk information about dozens of diseases in one single purchase. The quantity and the complexity of risk information pose challenges to adequate pre-test and post-test information provision and informed consent. There are currently no guidelines for what should constitute informed consent in PGT or how adequate informed consent can be achieved. In this paper, we propose a tiered-layered-staged model for informed consent. First, the proposed model is tiered as it offers choices between categories of diseases that are associated with distinct ethical, personal or societal issues. Second, the model distinguishes layers of information with a first layer offering minimal, indispensable information that is material to all consumers, and additional layers offering more detailed information made available upon request. Finally, the model stages informed consent as a process by feeding information to consumers in each subsequent stage of the process of undergoing a test, and by accommodating renewed consent for test result updates, resulting from the ongoing development of the science underlying PGT. A tiered-layered-staged model for informed consent with a focus on the consumer perspective can help overcome the ethical problems of information provision and informed consent in direct-to-consumer PGT.European Journal of Human Genetics advance online publication, 21 November 2012; doi:10.1038/ejhg.2012.237

Capric Acid Secreted by S. boulardii Inhibits C. albicans Filamentous Growth, Adhesion and Biofilm Formation

Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and biofilm formation

Analysis of Nigerians with Apparently Sporadic Parkinson Disease for Mutations in LRRK2, PRKN and ATXN3

Several genetic variations have been associated with Parkinson disease in different populations over the past few years. Although a considerable number of worldwide populations have been screened for these variants, results from Sub-Saharan populations are very scarce in the literature. In the present report we have screened a cohort of Parkinson disease patients (n = 57) and healthy controls (n = 51) from Nigeria for mutations in the genes PRKN, LRRK2 and ATXN3. No pathogenic mutations were found in any of the genes. Hence, common pathogenic mutations in these genes, observed in several different populations, are not a frequent cause of Parkinson disease in Nigeria

Targeted kinase inhibition relieves slowness and tremor in a Drosophila model of LRRK2 Parkinson’s disease

Disease models: A reflex reaction A simple reflex in flies can be used to test the effectiveness of therapies that slow neurodegeneration in Parkinson’s disease (PD). Christopher Elliott and colleagues at the University of York in the United Kingdom investigated the contraction of the proboscis muscle which mediates a taste behavior response and is regulated by a single dopaminergic neuron. Flies bearing particular mutations in the PD-associated gene leucine-rich repeat kinase 2 (LRRK2) in dopaminergic neurons lost their ability to feed on a sweet solution. This was due to the movement of the proboscis muscle becoming slower and stiffer, hallmark features of PD. The authors rescued the impaired reflex reaction by feeding the flies l-DOPA or LRRK2 inhibitors. These findings highlight the proboscis extension response as a useful tool to identify other PD-associated mutations and test potential therapeutic compounds