High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. the results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of ( pro) renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. the increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. the consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.UNIFESP, Div Renal, BR-04023900 São Paulo, BrazilUNIFESP, Div Renal, BR-04023900 São Paulo, BrazilWeb of Scienc

Smoke gets in your eyes:what is sociological about cigarettes?

Contemporary public health approaches increasingly draw attention to the unequal social distribution of cigarette smoking. In contrast, critical accounts emphasize the importance of smokers’ situated agency, the relevance of embodiment and how public health measures against smoking potentially play upon and exacerbate social divisions and inequality. Nevertheless, if the social context of cigarettes is worthy of such attention, and sociology lays a distinct claim to understanding the social, we need to articulate a distinct, positive and systematic claim for smoking as an object of sociological enquiry. This article attempts to address this by situating smoking across three main dimensions of sociological thinking: history and social change; individual agency and experience; and social structures and power. It locates the emergence and development of cigarettes in everyday life within the project of modernity of the nineteenth and twentieth centuries. It goes on to assess the habituated, temporal and experiential aspects of individual smoking practices in everyday lifeworlds. Finally, it argues that smoking, while distributed in important ways by social class, also works relationally to render and inscribe it

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population

ABSTRACT. We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53*11 Glu/Gln or Lys (GAG->CAG or AAG), TP53*72 Arg/Pro (CCG->CCC), and TP53*248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53*11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. The genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/ Lys); the homozygous variant genotype was not identified (P = 0.02). TP53*72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). The genotypic distribution in the endometriosis group was 16.15% homozygous wildtype (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53*248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53*72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Job Creation and Trade in Manufactures: Industry-Level Analysis Across Countries

This paper examines industry-level responses of manufacturing employment in the context of globalization using a large sample of developed, developing, and transition economies. We find that developing countries need atypically high rates of value-added growth (about 10 %) to increase manufacturing employment appreciably (about 4 %). The employment benefits of export orientation are also modest even in “comparative advantage” industries of developing countries. However, diversifying the export basket contributes significantly to employment growth, particularly in the medium- and high-technology industries. Import competition does not undermine employment growth in low-technology industries of developing countries while it displaces jobs in the same industries in Organisation for Economic Co-operation and Development (OECD) and transition economies. For developing countries, import-induced job losses are higher in the more capital-intensive medium-technology industries. Jobs in high-technology industries are less sensitive to imports with positive relationships observed in the OECD. Investment also complements job creation in low-technology industries of developing countries that have yet to industrialize

Cultural attitudes are stronger predictors of bushmeat consumption and preference than economic factors among urban Amazonians from Brazil and Colombia

ABSTRACT. Bushmeat consumption persists in urban areas in the Neotropics, yet knowledge of its scale and the relative importance of cultural and economic factors in determining consumption and preference remain elusive. Moreover, the roles of cultural beliefs, social norms, and attitudes in driving urban bushmeat consumption are rarely evaluated. Therefore, we explored in this article the factors that influence consumption and preference for bushmeat in Amazonian towns. Given the availability of other sources of animal protein and the cultural and social importance of bushmeat in the region, we hypothesized that cultural attributes should be better predictors than economic factors of bushmeat consumption and preference. Data analysis involved fitting two-level mixed-effects regressions (random intercepts) to a structured sample of 227 individuals (99 households) from four towns in the Brazilian (Tabatinga and Atalaia do Norte) and Colombian (Leticia and Puerto Nariño) Amazon. The results indicate that a third of the interviewees had consumed bushmeat in the past month, which had primarily been harvested by the family or received as a gift rather than obtained through trade. In general, both economic and cultural factors predicted bushmeat consumption and preference, but the objective proxy for culture, individual origin, was unimportant. Among the tested indicators, the strongest predictor was the importance of bushmeat to social relations. Moreover, informal social norms, such as the greater importance attributed to taboos, tended to decrease the average number of wild species that a person would eat, whereas attitudes toward the illegality of hunting were less important. The two economic indicators, increased income and wealth, tended to decrease preference for bushmeat and the likelihood of consumption. Our findings highlight the importance of human beliefs, attitudes, and social norms to the understanding of bushmeat consumption and preference and may contribute to the design of more effective and locally appropriate conservation and management strategies

Work-time underemployment and financial hardship: class inequalities and recession in the UK

The economic crisis that led to recession in the UK in 2008–9 impacted in multiple ways on work and economic life. This article examines changes to the work-time of employees. The UK stood out for its recessionary expansion of work-time underemployment. Working in a job that provides ‘too few’ hours can have serious ramifications for the economic livelihood of workers. Working-class workers are central here. Drawing on analysis of large-scale survey data, the article identifies that workers in lower level occupations experienced the most substantial post-recessionary growth in the proportions working ‘too few’ hours. Did these work-time changes narrow or widen class inequalities in feelings of financial hardship? The article concludes that although middle-class workers also saw their financial positions damaged, this so-called ‘first middle-class recession’ did not erode class inequalities in financial hardship among UK workers

Subjective well-being and engagement in arts, culture and sport

This paper explores the relationship between engagement in arts, culture and sport, and subjective well-being, contributing to our understanding of the leisure experience, and cultural value, of these activities. Ordered probit analysis of UK data from wave 2 (2010-11) of Understanding Society , provides evidence in support of a wide range of cultural goods generating positive leisure experience, reflected in overall (life, general happiness) and domain (leisure) satisfaction. Frequency of engagement is central to certain activities: only regular participation in arts activities and sport generates positive effects. In contrast, arts events are positive irrespective of frequency. The findings also indicate even less frequent engagement in activities exhibiting cultural characteristics, e.g. museums/historical sites, has positive association with satisfaction. Finally, although employment has a negative association with leisure satisfaction, engagement in leisure activities is not found to spillover into job satisfaction (with the exception of certain sports). This suggests individuals consider work and leisure (including quality of leisure time) separately

Revolution from above in English schools: neoliberalism, the democratic commons and education

The ideas of the New Left and the recently emerged alter-globalisation movements are marginal within current policy debates concerning the English education system. Here I seek to demonstrate the interconnections between the New Left and the alter-globalisation movement and suggest that these ideas contain a powerful corrective to the increasingly authoritarian present. The next part of the article considers the development of neoliberalism both in a theoretical context and since the arrival of the new Conservative–Liberal government in the UK. Here I outline the rapid transformation of English schools under the academies programme and look at how it has been explicitly linked to ideas of ‘moral collapse’ evident in the popular discourse of ‘Broken Britain’. Especially significant in this respect has been the labelling of comprehensive schools as ‘failures’ and the explicit imposition of more authoritarian understandings of pedagogy. I seek to explore both the rapidity of this transformation in the context of the dissatisfaction with the idea of comprehensive schools shown by the political Right and the Third Way’s reworking of socialism. Finally I briefly consider more progressive alternatives for schools and education by returning to the idea of the democratic commons. In this respect, the cultural Left needs to explore more radical alternatives beyond the defence of comprehensive schooling which sounds both nostalgic and misplaced within our global times