Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea

Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates

Cost-effectiveness of financial incentives to promote adherence to depot antipsychotic medication: economic evaluation of a cluster-randomised controlled trial

Background: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5%at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration: ISRCTN.com 7776928

Weakened magnetic braking as the origin of anomalously rapid rotation in old field stars

A knowledge of stellar ages is crucial for our understanding of many astrophysical phenomena, and yet ages can be difficult to determine. As they become older, stars lose mass and angular momentum, resulting in an observed slowdown in surface rotation. The technique of 'gyrochronology' uses the rotation period of a star to calculate its age. However, stars of known age must be used for calibration, and, until recently, the approach was untested for old stars (older than 1 gigayear, Gyr). Rotation periods are now known for stars in an open cluster of intermediate age (NGC 6819; 2.5 Gyr old), and for old field stars whose ages have been determined with asteroseismology. The data for the cluster agree with previous period-age relations, but these relations fail to describe the asteroseismic sample. Here we report stellar evolutionary modelling, and confirm the presence of unexpectedly rapid rotation in stars that are more evolved than the Sun. We demonstrate that models that incorporate dramatically weakened magnetic braking for old stars can---unlike existing models---reproduce both the asteroseismic and the cluster data. Our findings might suggest a fundamental change in the nature of ageing stellar dynamos, with the Sun being close to the critical transition to much weaker magnetized winds. This weakened braking limits the diagnostic power of gyrochronology for those stars that are more than halfway through their main-sequence lifetimes.Comment: 25 pages, 3 figures in main paper, 6 extended data figures, 1 table. Published in Nature, January 2016. Please see https://youtu.be/O6HzYgP5uyc for a video description of the resul

The capacity of short-chain fructo-oligosaccharides to stimulate faecal bifidobacteria: a dose-response relationship study in healthy humans

BACKGROUND: Short-chain fructo-oligosaccharides (scFOS) are well-known for their bifidogenicity. In a large study comprising 200 healthy volunteers, we determined the bifidogenic properties of 7 non-digestible carbohydrates administered at a dose of 10 g/d in the diet; we analysed dose-response relationships of the bifidogenic substrates at doses ranging from 2.5 to 10 g/d in comparison with a placebo. The aim of this presentation is to give more details about the dose-response effects of short-chain fructo-oligosaccharides (scFOS). METHODS: Forty healthy volunteers (18 males, 22 females) eating their usual diets were randomly divided into 5 groups of 8 subjects and received scFOS at a dose of 2.5, 5.0, 7.5 and 10 g/d or a placebo for 7 d. Stools were collected before (day (d) 8) and at the end (day (d) 15) of sugar consumption, and tolerance was evaluated using a daily chart. RESULTS (M ± SEM): Bifidobacteria counts increase was higher in scFOS than in placebo group for all doses tested [2.5 g/d (from 9.15 ± 0.59 to 9.39 ± 0.70; P = 0.02); 5 g/d (from 10.21 ± 0.21 to 10.67 ± 0.22; P = 0.03); 7.5 g/d (from 9.28 ± 0.49 to 9.85 ± 0.35;P = 0.01); 10 g/d (from 9.00 ± 0.81 to 10.18 ± 0.60; P = 0.003)]. A significant correlation between the ingested dose of scFOS and faecal bifidobacteria counts was observed at d15 (r(2 )= 0.307, P < 0.001). Total anaerobes increased at the dose of 10 g/d. No significant differences were found for Bacteroides, Lactobacillus, enterobacteria or pH in any group. The frequency of digestive symptoms was not different between scFOS at any of the doses tested and placebo. Bloating was significantly more intense during scFOS ingestion at doses of 2.5 and 5 g/d, but not at doses of 7.5 and 10 g/d. Excess flatus, borborygmi and abdominal pain did not differ from the placebo at any of the doses tested. CONCLUSION: This study showed that scFOS is bifidogenic and well tolerated at doses ranging from 2.5 to 10 g/d, and that there is a dose-response relationship in healthy volunteers

Transcriptome pathways unique to dehydration tolerant relatives of modern wheat

Among abiotic stressors, drought is a major factor responsible for dramatic yield loss in agriculture. In order to reveal differences in global expression profiles of drought tolerant and sensitive wild emmer wheat genotypes, a previously deployed shock-like dehydration process was utilized to compare transcriptomes at two time points in root and leaf tissues using the Affymetrix GeneChip(R) Wheat Genome Array hybridization. The comparison of transcriptomes reveal several unique genes or expression patterns such as differential usage of IP(3)-dependent signal transduction pathways, ethylene- and abscisic acid (ABA)-dependent signaling, and preferential or faster induction of ABA-dependent transcription factors by the tolerant genotype that distinguish contrasting genotypes indicative of distinctive stress response pathways. The data also show that wild emmer wheat is capable of engaging known drought stress responsive mechanisms. The global comparison of transcriptomes in the absence of and after dehydration underlined the gene networks especially in root tissues that may have been lost in the selection processes generating modern bread wheats

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins

Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model

<p>Abstract</p> <p>Background</p> <p>Hematopoietic stem cell transplantation is increasingly performed for hematologic diseases. As a major side effect, acute graft versus host disease (GvHD) with serious gastrointestinal symptoms including diarrhea, gastrointestinal bleeding and high mortality can be observed. Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models.</p> <p>Methods</p> <p>To investigate the effects of GvHD on the intestinal barrier of the small intestine we utilized an established acute semi allogenic GvHD in C57BL/6 and B6D2F1 mice.</p> <p>Results</p> <p>By assessing the differential uptake of lactulose and mannitol in the jejunum, we observed an increased paracellular permeability as a likely mechanism for disturbed intestinal barrier function. Electron microscopy, immunohistochemistry and PCR analysis indicated profound changes of the tight-junction complex, characterized by downregulation of the tight junction protein occludin without any changes in ZO-1. Furthermore TNF-α expression was significantly upregulated.</p> <p>Conclusions</p> <p>This analysis in a murine model of GvHD of the small intestine demonstrates serious impairment of intestinal barrier function in the jejunum, with an increased permeability and morphological changes through downregulation and localization shift of the tight junction protein occludin.</p

The Adolescent Depression Rating Scale (ADRS): a validation study

BACKGROUND: To examine the psychometric properties of the Adolescent Depression Rating Scale (ADRS), a new measure was specifically designed to evaluate adolescent depression. METHODS: The 11-item clinician-report and 44-item self-report versions of the ADRS were developed from a qualitative phase involving interviews of experts and adolescents. These two instruments were then administered to 402 French speaking adolescents with and without depressive disorders. Item distribution, internal consistency, convergent validity, discriminant validity and factorial structure were assessed. RESULTS: After reduction procedures, a 10-item clinician version and a 10-item self-report version were obtained. The ADRS demonstrated good internal consistency (alpha Cronbach coefficient >.70). It also discriminated better between adolescents with and without depression than the Hamilton Depressive Rating Scale and the Beck Depression Inventory (BDI-13). CONCLUSION: The ADRS is a useful, short, clinician-report and self-report scale to evaluate adolescent depression. Further studies to replicate our findings and evaluate ADRS sensitivity to effects of treatment and psychometric properties in populations of adolescents with several psychiatric disorders are warranted

Genome screen in familial intracranial aneurysm

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