Role of charge in the radioprotection of E. coli by thiols.

The role of net charge (Z) of thiols in their ability to radioprotect cells has been investigated in a glutathione (GSH)-deficient strain of E. coli. This strain, 7, is deficient in the enzyme gamma-glutamylcysteine synthetase and allows the effects of added low molecular weight thiols to be studied. Using the gas explosion system it is possible to measure the chemical repair of the free-radical precursors of lethal lesions by thiols in intact cells. The first-order chemical repair rate in strain 7 is 280s(-1) in comparison with 1100s(-1) in the wild-type strain 1157. From the measured difference in the intracellular concentration of GSH between the wild-type and the mutant, this gives a second-order repair rate, k(r)'s of 1.23 +/- 0.3 X 10(5) dm(3)mol(-1)s(-1). Measurement of intracellular thiol levels after addition of various low molecular weight thiols showed that uptake was rapid, leading to stable thiol levels within 1 min. The ratios of the intracellular to extracellular concentrations (C-in/C-out) were 0.74 for 3-mercaptopropionic acid (Z=-1), 0.56 for 2-mercaptoethanol (Z=0), 1.47 for cysteamine (Z=+1) and 1.04 for WR1065 (Z=+2). The k(r)'s for these thiols were 1.3 +/- 0.5 X 10(5) dm(3)mol(-1)s(-1) for 30-mercaptopropionic acid, 3.3 +/- 1.6 x 10(5) dm(3)mol(-1)s(-1) for 2-mercaptoethanol, 3.9 +/- 1.1 X 10(5) dm(3)mol(-1)s(-1) for cysteamine and 2.7 +/- 1.1 X 10(6) dm(3)mol(-1)s(-1) for WR1065. These are lower and increase less with charge than previously published values for chemical repair in isolated pBR322 DNA, probably because of the association of nucleoproteins and polyamines with the cellular DNA of E. coli. However, the approximate three-fold increase in k(r) per unit increase in Z shows that the counter-ion condensation and co-ion depletion are important in determining the effectiveness of charged thiols in the radioprotection of E. coli.

Job Strain and Alcohol Intake:A Collaborative Meta-Analysis of Individual-Participant Data from 140 000 Men and Women

BACKGROUND: The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake. METHODOLOGY AND PRINCIPAL FINDINGS: We analysed cross-sectional data from 12 European studies (n?=?142 140) and longitudinal data from four studies (n?=?48 646). Job strain and alcohol intake were self-reported. Job strain was analysed as a binary variable (strain vs. no strain). Alcohol intake was harmonised into the following categories: none, moderate (women: 1-14, men: 1-21 drinks/week), intermediate (women: 15-20, men: 22-27 drinks/week) and heavy (women: >20, men: >27 drinks/week). Cross-sectional associations were modelled using logistic regression and the results pooled in random effects meta-analyses. Longitudinal associations were examined using mixed effects logistic and modified Poisson regression. Compared to moderate drinkers, non-drinkers and (random effects odds ratio (OR): 1.10, 95% CI: 1.05, 1.14) and heavy drinkers (OR: 1.12, 95% CI: 1.00, 1.26) had higher odds of job strain. Intermediate drinkers, on the other hand, had lower odds of job strain (OR: 0.92, 95% CI: 0.86, 0.99). We found no clear evidence for longitudinal associations between job strain and alcohol intake. CONCLUSIONS: Our findings suggest that compared to moderate drinkers, non-drinkers and heavy drinkers are more likely and intermediate drinkers less likely to report work-related stress.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage ( European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009

The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-beta-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common 'thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5, 10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individuals.

Waterpower: Politics and the Geography of Water Provision

Access to potable water is frequently said to be the defining world crisis of the twenty-first century. The argument is usually framed in terms of either direct environmental constraints or various totalistic views of how the political determines outcomes. There is little or no scope for the agency of practical politics. Both physical and human geographers tend to be dismissive of the possibilities of democratic politics ever resolving crises such as those of the geography of water provision, in part because of views of scientific expertise that devalue popular participation in decisions about technical matters such as water quality and distribution. Such dismissal also has much to do with a more generalized denigration of politics. Politics (the art of political deliberation, negotiation, and compromise) needs defending against its critics and many of its practitioners. Showing how politics is at work around the world in managing water problems and identifying the challenges that water problems pose for politics provides a retort to those who can only envisage inevitable destruction or a totalistic political panacea as the outcomes of the crisis of the century.

Interventions for prevention of giant retinal tear in the fellow eye

Background: A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees ormore in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. Objectives: To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear and/or a retinal detachment. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2008, Issue 4), MEDLINE (January 1950 to December 2008), EMBASE (January 1980 to December 2008) and Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2008). In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 15 December 2008. Selection criteria: Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. Data collection and analysis: We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. Main results: No studies met the inclusion criteria for this review. Authors' conclusions: No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Interventions for prevention of giant retinal tear in the fellow eye.

BACKGROUND: A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees or more in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. OBJECTIVES: To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear and/or a retinal detachment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2008, Issue 4), MEDLINE (January 1950 to December 2008), EMBASE (January 1980 to December 2008) and Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2008). In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 15 December 2008. SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. DATA COLLECTION AND ANALYSIS: We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. MAIN RESULTS: No studies met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears.

Interventions for prevention of giant retinal tear in the fellow eye.

A giant retinal tear is a full-thickness retinal break that extends circumferentially around the retina for 90 degrees or more in the presence of a posteriorly detached vitreous. It causes significant visual morbidity from retinal detachment and proliferative vitreoretinopathy. The fellow eye of patients who have had a spontaneous giant retinal tear has an increased risk of developing a giant retinal tear, a retinal detachment or both. Interventions such as 360-degree encircling scleral buckling, 360-degree cryotherapy and 360-degree laser photocoagulation have been advocated by some ophthalmologists as prophylaxis for the fellow eye against the development of a giant retinal tear and/or a retinal detachment, or to prevent its extension. To evaluate the effectiveness of prophylactic 360-degree interventions in the fellow eye of patients with unilateral giant retinal tear to prevent the occurrence of a giant retinal tear, a retinal detachment or both. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to December 2011), EMBASE (January 1980 to December 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 December 2011. In addition, we searched the proceedings of the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) up to 2008 for information about other relevant studies. Prospective randomised controlled trials (RCTs) comparing one prophylactic treatment for fellow eyes of patients with giant retinal tear against observation (no treatment) or another form of prophylactic treatment. In the absence of RCTs, we planned to discuss case-control studies that met the inclusion criteria but we would not conduct a meta-analysis using these studies. We did not find any studies that met the inclusion criteria for the review and therefore no assessment of methodological quality or meta-analysis could be performed. No studies met the inclusion criteria for this review. No strong evidence in the literature was found to support or refute prophylactic 360-degree treatments to prevent a giant retinal tear or a retinal detachment in the fellow eye of patients with unilateral giant retinal tears.

The C-Terminal Variable Region Specifies the Dynamic Properties of Arabidopsis Microtubule-Associated Protein MAP65 Isotypes

The microtubule-associated protein, MAP65, is a member of a family of divergent microtubule-associated proteins from different organisms generally involved in maintaining the integrity of the central spindle in mitosis. The dicotyledon Arabidopsis thaliana and the monocotyledon rice (Oryza sativa) genomes contain 9 and 11 MAP65 genes, respectively. In this work, we show that the majority of these proteins fall into five phylogenetic clades, with the greatest variation between clades being in the C-terminal random coil domain. At least one Arabidopsis and one rice isotype is within each clade, indicating a functional specification for the C terminus. In At MAP65-1, the C-terminal domain is a microtubule binding region (MTB2) harboring the phosphorylation sites that control its activity. The At MAP65 isotypes show differential localization to microtubule arrays and promote microtubule polymerization with variable efficiency in a MTB2-dependent manner. In vivo studies demonstrate that the dynamics of the association and dissociation of different MAP65 isotypes with microtubules can vary up to 10-fold and that this correlates with their ability to promote microtubule polymerization. Our data demonstrate that the C-terminal variable region, MTB2, determines the dynamic properties of individual isotypes and suggest that slower turnover is conditional for more efficient microtubule polymerization.

An exploration of the relationship between social support and depressive symptoms in schizophrenia

Objective: Depressive symptoms in schizophrenia have previously been associated with a perceived lack of social support. The aim of this study was to explore the relationship between perceived social support and depressive symptoms in schizophrenia; to assess the psychological wellbeing of their carers; and to examine the quality of the relationship between the patients and their carers. Method: Individuals with schizophrenia (n = 17) were assessed on the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), a measure of perceived social support, the Significant Others Scale (SOS) and the Quality of Relationship Inventory (QRI). Results: The mean score on the BDI for patients fell within the moderate-severe range and the mean range on the BHS fell within the moderate range. Family and friends were perceived as supportive resources by patients. There was no significant relationship between patient epressive symptoms or hopelessness and perceived social support. Carers of patients did not report high rates of depressive symptoms or hopelessness. Conclusions: These findings do not support the previous finding of an association between depressive symptoms and a perceived lack of social support in schizophrenia.

Clinical and technical factors associated with skin intrinsic fluorescence in subjects with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications(EDIC) studies have established multiyear mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in persons with type 1 diabetes. However, multiyear mean HbA1c is not always available in the clinical setting. Skin advanced glycation end products (AGEs) are thought to partially reflect effects of hyperglycemia over time, and measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate with the concentration of skin AGEs, noninvasive measurement by skin intrinsic fluorescence(SIF) facilitates the exploration of the association of mean HbA1c and other clinical/technical factors with SIF using the detailed phenotypic database available in DCCT/EDIC.