SH3 domains: modules of protein–protein interactions

Src homology 3 (SH3) domains are involved in the regulation of important cellular pathways, such as cell proliferation, migration and cytoskeletal modifications. Recognition of polyproline and a number of noncanonical sequences by SH3 domains has been extensively studied by crystallography, nuclear magnetic resonance and other methods. High-affinity peptides that bind SH3 domains are used in drug development as candidates for anticancer treatment. This review summarizes the latest achievements in deciphering structural determinants of SH3 function.     

Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: results from the WHO World Health Survey

This study explored whether physical health problems are related to psychotic symptoms independently of a mental disorder diagnosis. A total of 224,254 subjects recruited for the World Health Organization World Health Survey were subdivided into those with both a lifetime diagnosis of psychosis and at least one psychotic symptom in the 12 months prior to the evaluation, those with at least one psychotic symptom in the past 12 months but no lifetime diagnosis of psychosis, and those without psychotic symptoms in the past 12 months and without a lifetime diagnosis of psychosis. The three groups were compared for the presence of medical conditions, health problems, and access to health care. Medical conditions and health problems (angina, asthma, arthritis, tuberculosis, vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking, and accidents), medication consumption, and hospital admissions (but not regular health care visits) were more frequent in individuals with psychotic symptoms but no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The number of medical conditions increased with the number of psychotic symptoms. Given the sample analyzed, this trend seems to be independent from the socio‐economic development of the country or the specific health care system.     

Disability Mediates the Impact of Common Conditions on Perceived Health

Background

We examined the extent to which disability mediates the observed associations of common mental and physical conditions with perceived health.

Methods and Findings

WHO World Mental Health (WMH) Surveys carried out in 22 countries worldwide (n = 51,344 respondents, 72.0% response rate). We assessed nine common mental conditions with the WHO Composite International Diagnostic Interview (CIDI), and ten chronic physical with a checklist. A visual analog scale (VAS) score (0, worst to 100, best) measured perceived health in the previous 30 days. Disability was assessed using a modified WHO Disability Assessment Schedule (WHODAS), including: cognition, mobility, self-care, getting along, role functioning (life activities), family burden, stigma, and discrimination. Path analysis was used to estimate total effects of conditions on perceived health VAS and their separate direct and indirect (through the WHODAS dimensions) effects.Twelve-month prevalence was 14.4% for any mental and 51.4% for any physical condition. 31.7% of respondents reported difficulties in role functioning, 11.4% in mobility, 8.3% in stigma, 8.1% in family burden and 6.9% in cognition. Other difficulties were much less common. Mean VAS score was 81.0 (SD = 0.1). Decrements in VAS scores were highest for neurological conditions (9.8), depression (8.2) and bipolar disorder (8.1). Across conditions, 36.8% (IQR: 31.2–51.5%) of the total decrement in perceived health associated with the condition were mediated by WHODAS disabilities (significant for 17 of 19 conditions). Role functioning was the dominant mediator for both mental and physical conditions. Stigma and family burden were also important mediators for mental conditions, and mobility for physical conditions.

Conclusions

More than a third of the decrement in perceived health associated with common conditions is mediated by disability. Although the decrement is similar for physical and mental conditions, the pattern of mediation is different. Research is needed on the benefits for perceived health of targeted interventions aimed at particular disability dimensions.     

Calreticulin transacetylase mediated upregulation of thioredoxin by 7,8-diacetoxy-4-methylcoumarin enhances the antioxidant potential and the expression of vascular endothelial growth factor in peripheral blood mononuclear cells

Extensive research carried out in our group on polyphenolic acetates (PAs) substantiated the potential role of PAs in causing diverse biological and pharmacological actions. Our earlier investigations firmly established the calreticulin transacetylase (CRTAase) catalyzed activation of nitric oxide synthase (NOS) by PAs. In this report, we have studied the effect of 7,8-diacetoxy-4-methylcoumarin (DAMC, a model PA) and other acetoxy coumarins on the thioredoxin and VEGF expression in human peripheral blood mononuclear cells (PBMCs), with a view to substantiate our earlier observation that DAMC was a superb inducer of angiogenesis. Real time RT-PCR analysis revealed the enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to the increased expression and activity of thioredoxin (TRX) in PBMCs due to the the action of DAMC. The fact that TRX activity of PBMCs was enhanced by various acetoxy coumarins in tune with their affinity to CRTAase as substrate, suggested the possible activation of TRX due to acetylation. The overexpression of thioredoxin was found to correlate with that of VEGF as proved by real time RT-PCR and VEGF -ELISA results, apart from the DAMC-caused enhanced production of NO acting as an inducer of VEGF. Moreover, the intracellular ROS levels were also found to be reduced drastically, by DAMC thus reducing the oxidative stress in cells. These observations strongly evidenced the crucial role of TRX in DAMC-induced tissue angiogenesis with the involvement of VEGF.     

Synthesis, biological studies of linear and branched arabinofuranoside-containing glycolipids and their interaction with surfactant protein A

Oligoarabinofuranoside-containing glycolipids relevant to mycobacterial cell wall components were synthesized in order to understand the functional roles of such glycolipids. A series of linear tetra-, hexa-, octa- and a branched heptasaccharide oligoarabinofuranosides, with 1?→?2 and 1?→?5 α-linkages between the furanoside residues, were synthesized by chemical methods from readily available monomer building blocks. Upon the synthesis of glycolipids, constituted with a double alkyl chain-substituted sn-glycerol core and oligosaccharide fragments, biological studies were performed to identify the effect of synthetic glycolipids on the biofilm formation and sliding motilities of Mycobacterium smegmatis. Synthetic glycolipids and arabinofuranosides displayed an inhibitory effect on the growth profile, but mostly on the biofilm formation and maturation. Similarly, synthetic compounds also influenced the sliding motility of the bacteria. Further, biophysical studies were undertaken, so as to identify the interactions of the glycolipids with a pulmonary surfactant protein, namely surfactant protein A (SP-A), with the aid of the surface plasmon resonance technique. Specificities of each glycolipid interacting with SP-A were thus evaluated. From this study, glycolipids were found to exhibit higher apparent association constants than the corresponding oligosaccharide portion alone, without the double alkyl group-substituted glycerol core.     

Chronic Conditions and Sleep Problems among Adults Aged 50 years or over in Nine Countries: A Multi-Country Study

BackgroundData on the association between chronic conditions or the number of chronic conditions and sleep problems in low- or middle-income countries is scarce, and global comparisons of these associations with high-income countries have not been conducted.MethodsData on 42116 individuals 50 years and older from nationally-representative samples of the Collaborative Research on Ageing in Europe (Finland, Poland, Spain) and the World Health Organization''s Study on Global Ageing and Adult Health (China, Ghana, India, Mexico, Russia, South Africa) conducted between 2011–2012 and 2007–2010 respectively were analyzed.ResultsThe association between nine chronic conditions (angina, arthritis, asthma, chronic lung disease, depression, diabetes, hypertension, obesity, and stroke) and self-reported severe/extreme sleep problems in the past 30 days was estimated by logistic regression with multiple variables. The age-adjusted prevalence of sleep problems ranged from 2.8% (China) to 17.0% (Poland). After adjustment for confounders, angina (OR 1.75–2.78), arthritis (OR 1.39–2.46), and depression (OR 1.75–5.12) were significantly associated with sleep problems in the majority or all of the countries. Sleep problems were also significantly associated with: asthma in Finland, Spain, and India; chronic lung disease in Poland, Spain, Ghana, and South Africa; diabetes in India; and stroke in China, Ghana, and India. A linear dose-dependent relationship between the number of chronic conditions and sleep problems was observed in all countries. Compared to no chronic conditions, the OR (95%CI) for 1,2,3, and≥4 chronic conditions was 1.41 (1.09–1.82), 2.55 (1.99–3.27), 3.22 (2.52–4.11), and 7.62 (5.88–9.87) respectively in the overall sample.ConclusionsIdentifying co-existing sleep problems among patients with chronic conditions and treating them simultaneously may lead to better treatment outcome. Clinicians should be aware of the high risk for sleep problems among patients with multimorbidity. Future studies are needed to elucidate the best treatment options for comorbid sleep problems especially in developing country settings.     

Sources and methods of manufacturing xanthan by fermentation of various carbon sources

Xanthan gum, an anionic polysaccharide with an exceptionally high molecular weight, is produced by the bacterium Xanthomonas sp. It is a versatile compound that has been utilized in various industries for decades. Xanthan gum was the second exopolysaccharide to be commercially produced, following dextran. In 1969, the US Food and Drug Administration (FDA) approved xanthan gum for use in the food and pharmaceutical industries. The food industry values xanthan gum for its exceptional rheological properties, which make it a popular thickening agent in many products. Meanwhile, the cosmetics industry capitalizes on xanthan gum's ability to form stable emulsions. The industrial production process of xanthan gum involves fermenting Xanthomonas in a medium that contains glucose, sucrose, starch, etc. as a substrate and other necessary nutrients to facilitate growth. This is achieved through batch fermentation under optimal conditions. However, the increasing costs of glucose in recent years have made the production of xanthan economically unviable. Therefore, many researchers have investigated alternative, cost-effective substrates for xanthan production, using various modified and unmodified raw materials. The objective of this analysis is to investigate how utilizing different raw materials can improve the cost-efficient production of xanthan gum.     

Socioeconomic inequality in smoking in low-income and middle-income countries: results from the world health survey

Objectives

To assess the magnitude and pattern of socioeconomic inequality in current smoking in low and middle income countries.

Methods

We used data from the World Health Survey [WHS] in 48 low-income and middle-income countries to estimate the crude prevalence of current smoking according to household wealth quintile. A Poisson regression model with a robust variance was used to generate the Relative Index of Inequality [RII] according to wealth within each of the countries studied.

Results

In males, smoking was disproportionately prevalent in the poor in the majority of countries. In numerous countries the poorest men were over 2.5 times more likely to smoke than the richest men. Socioeconomic inequality in women was more varied showing patterns of both pro-rich and pro-poor inequality. In 20 countries pro-rich relative socioeconomic inequality was statistically significant: the poorest women had a higher prevalence of smoking compared to the richest women. Conversely, in 9 countries women in the richest population groups had a statistically significant greater risk of smoking compared to the poorest groups.

Conclusion

Both the pattern and magnitude of relative inequality may vary greatly between countries. Prevention measures should address the specific pattern of smoking inequality observed within a population.     

Glycopeptidolipids: immuno-modulators in greasy mycobacterial cell envelope

Species of opportunistic mycobacteria are the major causative agent for disseminating pulmonary infections in immuno-compromised individuals. These naturally resistant strains recruit a unique type of glycolipid known as glycopeptidolipids (GPLs), noncovalently attached to the outer surface of their thick lipid rich cell envelope. Species specific GPLs constitute the chemical determinants of most nontuberculous mycobacterial serotypes, and their absence from the cell surface confers altered colony morphology, hydrophobicity, and inability to grow as biofilms. The objective of this review is to present a comprehensive account and highlight the renewed interest on this much neglected group of pleiotropic molecules with respect to their structural diversity and biosynthesis. In addition, the role of GPLs in mycobacterial survival, both intracellular and in the environment is also discussed. It also explores the possibility of identifying new targets for intervening Mycobacterium avium complex-related infections. These antigenic molecules have been considered to play a pivotal role in immune suppression and can also induce various cytokine mediated innate immune responses, the molecular mechanism of which remains obscure.