Metabolic analysis of the cutaneous fungi Malassezia globosa and M. restricta for insights on scalp condition and dandruff

Dandruff is a global consumer problem, characterized by flaking and scaling of the scalp, accompanied by itch and irritancy. However, the aetiology of the condition remains poorly understood, although there is a strong consensus that the cutaneous fungi Malassezia globosa and M. restricta are a major contributory factor. Although there is a paucity of understanding on how these commensal microorganisms adopt a pathogenic phenotype, a rich source of potential insights now exists in the shape of the recently published whole‐genome sequence of M. globosa, a functional annotation and metabolic reconstruction of which is freely accessible via the integrated microbial genomes (IMG) online community resource ( http://www.hmpdacc-resources.org/cgi-bin/imgm_hmp/main.cgi ). In these studies, we have taken a combined in‐silico and in‐vitro approach to investigate aspects of lipid and amino acid metabolism by M. globosa and M. restricta that have the potential to impact on scalp condition and dandruff. The IMG platform was employed to analyse the metabolism of triacylglycerols and fatty acids, as well as the aromatic amino acid tryptophan, by M. globosa, to investigate pro‐inflammatory pathways linked in the literature to dandruff and pityriasis versicolour, respectively. Results were equivocal, leaving question marks over the ability of M. globosa to fully degrade unsaturated fatty acids and metabolize tryptophan to indole‐3‐pyruvic acid. In‐vitro assay systems were then developed to study the biotransformation of these metabolites by both M. globosa and M. restricta, as well as their effect on human keratinocytes, and the results here indicated that neither unsaturated fatty acids nor indole derivatives are likely to be major aetiological factors in dandruff.     

Picture detection in rapid serial visual presentation: Features or identity?

A pictured object can be readily detected in a rapid serial visual presentation sequence when the target is specified by a superordinate category name such as animal or vehicle. Are category features the initial basis for detection, with identification of the specific object occurring in a second stage (Evans & Treisman, 2005), or is identification of the object the basis for detection? When 2 targets in the same superordinate category are presented successively (lag 1), only the identification-first hypothesis predicts lag 1 sparing of the second target. The results of 2 experiments with novel pictures and a wide range of categories supported the identification-first hypothesis and a transient-attention model of lag 1 sparing and the attentional blink (Wyble, Bowman, & Potter, 2009). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D‐Lactate production as a function of glucose metabolism in Saccharomyces cerevisiae

Methylglyoxal, a reactive, toxic dicarbonyl, is generated by the spontaneous degradation of glycolytic intermediates. Methylglyoxal can form covalent adducts with cellular macromolecules, potentially disrupting cellular function. We performed experiments using the model organism Saccharomyces cerevisiae, grown in media containing low, moderate and high glucose concentrations, to determine the relationship between glucose consumption and methylglyoxal metabolism. Normal growth experiments and glutathione depletion experiments showed that metabolism of methylglyoxal by log‐phase yeast cultured aerobically occurred primarily through the glyoxalase pathway. Growth in high‐glucose media resulted in increased generation of the methylglyoxal metabolite d ‐lactate and overall lower efficiency of glucose utilization as measured by growth rates. Cells grown in high‐glucose media maintained higher glucose uptake flux than cells grown in moderate‐glucose or low‐glucose media. Computational modelling showed that increased glucose consumption may impair catabolism of triose phosphates as a result of an altered NAD⁺:NADH ratio. Copyright © 2013 John Wiley & Sons, Ltd.     

Efficacy of relapse prevention: A meta-analytic review.

Although relapse prevention (RP) has become a widely adopted cognitive-behavioral treatment intervention for alcohol, smoking, and other substance use, outcome studies have yielded an inconsistent picture of the efficacy of this approach or conditions for maximal effectiveness. A meta-analysis was performed to evaluate the overall effectiveness of RP and the extent to which certain variables may relate to treatment outcome. Twenty-six published and unpublished studies with 70 hypothesis tests representing a sample of 9,504 participants were included in the analysis. Results indicated that RP was generally effective, particularly for alcohol problems. Additionally, outcome was moderated by several variables. Specifically, RP was most effective when applied to alcohol or polysubstance use disorders, combined with the adjunctive use of medication, and when evaluated immediately following treatment using uncontrolled pre–post tests. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early teacher perceptions and later student academic achievement.

The researchers explore relationships between preschool teachers' appraisals of intelligence, concurrent child characteristics, and future high school performance in a core sample of 110 4-year-olds. Children with higher socioeconomic status (SES) and those perceived as assertive and independent were judged by teachers more positively than IQ score predicted; conversely, low SES and perceived immaturity were associated with more negative teacher judgments than IQ score predicted. After controlling for SES, preschool teachers' over- and underestimates of intelligence relative to IQ score significantly predicted grade point average (GPA) and Scholastic Aptitude Test (SAT) test-taking 14 years later. The relationship between teacher ratings and GPA was strongest for children whose ability was underestimated. Teacher predictions were weakest in homes rated by observers as more orderly or with mothers who were more career or community active. Prescient versus influential interpretations of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Off‐Target Effects Related to the Phosphorothioate Modification of Nucleic Acids

Phosphorothioate antisense oligonucleotides have been widely used in clinical studies for rational sequence‐specific gene silencing. However, several sequence‐unspecific off‐target effects have been recently described for this compound class. In contrast to siRNA‐mediated knockdown of the same gene, the bcl‐2‐targeted oblimersen (Genasense, G3139) downregulates a number of proteins involved in apoptotic resistance and several glycolytic enzymes in 607B human melanoma cells. Regardless of their target, phosphorothioate‐modified antisense and siRNA compounds, but not oligonucleotides with a phosphodiester backbone, resulted in a similar impact on the proteome. Unspecifically downregulated proteins include cancer markers involved in apoptotic resistance and endoplasmatic reticulum (ER) stress such as the 78 kDa glucose regulated protein (GRP 78), protein disulfide isomerase A3 (PDIA3, GRP 58), calumenin, and galectin‐1, as well as the glycolytic enzymes triose phosphate isomerase, glyceraldehyde phosphodehydrogenase, and phosphoglycerate mutase. The depletion of the glycolytic enzymes is reflected by a decrease in L ‐lactate production, indicating a partial reversal of the Warburg effect. Compared with other phosphorothioate oligonucleotides, oblimersen generally led to a more pronounced effect both in terms of the number of influenced proteins and the extent of downregulation, suggesting a synergistic effect of Bcl‐2 downregulation.     

Human Prostatic Acid Phosphatase: Structure,Function and Regulation

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy.     

Plant Dependence on Rhizobia for Nitrogen Influences Induced Plant Defenses and Herbivore Performance

Symbiotic rhizobia induce many changes in legumes that could affect aboveground interactions with herbivores. We explored how changing the intensity of Bradyrhizobium japonicum, as modulated by soil nitrogen (N) levels, influenced the interaction between soybean (Glycine max) and herbivores of different feeding guilds. When we employed a range of fertilizer applications to manipulate soil N, plants primarily dependent on rhizobia for N exhibited increased root nodulation and higher levels of foliar ureides than plants given N fertilizer; yet all treatments maintained similar total N levels. Soybean podworm (Helicoverpa zea) larvae grew best on plants with the highest levels of rhizobia but, somewhat surprisingly, preferred to feed on high-N-fertilized plants when given a choice. Induction of the defense signaling compound jasmonic acid (JA) by H. zea feeding damage was highest in plants primarily dependent on rhizobia. Differences in rhizobial dependency on soybean did not appear to affect interactions with the phloem-feeding soybean aphid (Aphis glycines). Overall, our results suggest that rhizobia association can affect plant nutritional quality and the induction of defense signaling pathways and that these effects may influence herbivore feeding preferences and performance—though such effects may vary considerably for different classes of herbivores.