The triphenylmethane dye brilliant blue G is only moderately effective at inhibiting amyloid formation by human amylin or at disaggregating amylin amyloid fibrils, but interferes with amyloid assays; Implications for inhibitor design.

The development of inhibitors of islet amyloid formation is important as pancreatic amyloid deposition contributes to type-2 diabetes and islet transplant failure. The Alzheimer's Aβ peptide and human amylin (h-amylin), the polypeptide responsible for amyloid formation in type-2 diabetes, share common physio-chemical features and some inhibitors of Aβ also inhibit amyloid formation by h-amylin and vice versa. Thus, a popular and potentially useful strategy to find lead compounds for anti-amylin amyloid agents is to examine compounds that have effects on Aβ amyloid formation. The triphenylmethane dye, brilliant blue G (BBG, Sodium;3-[[4-[(E)-[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]-2-methylcyclohexa-2,5-dien-1-ylidene]methyl]-N-ethyl-3-methylanilino]methyl]benzenesulfonate) has been shown to modulate Aβ amyloid formation and inhibit Aβ induced toxicity. However, the effects of BBG on h-amylin have not been examined, although other triphenylmethane derivatives inhibit h-amylin amyloid formation. The compound has only a modest impact on h-amylin amyloid formation unless it is added in significant excess. BBG also remodels preformed h-amylin amyloid fibrils if added in excess, however BBG has no significant effect on h-amylin induced toxicity towards cultured β-cells or cultured CHO-T cells except at high concentrations. BBG is shown to interfere with standard thioflavin-T assays of h-amylin amyloid formation and disaggregation, highlighting the difficulty of interpreting such experiments in the absence of other measurements. BBG also interferes with ANS based assays of h-amylin amyloid formation. The work highlights the differences between inhibition of Aβ and h-amylin amyloid formation, illustrates the limitation of using Aβ inhibitors as leads for h-amylin amyloid inhibitors, and reinforces the difficulties in interpreting dye binding assays of amyloid formation

Livestock, vulnerability, and poverty dynamics in India

The focus of this study is to identify the livelihood activities that produce the major share of household income as well as to identify the livelihood pathways and strategies, and the role of livestock in these activities and strategies over a six year period. The paper is organized as follows. Section one is Introduction; Section 2 describes the methodology and data. Section 3 examines the extent of movements into and out of poverty amongst the sample households. Sections 4 and 5 describe the extent of destitution, vulnerability, viability and sustainability in connection with livelihood pathways. Section 6 examines the factors associated with economic/poverty status. Section 7 summarises the role of livestock in these livelihood connections. Finally, the paper draws some policy conclusions and recommendations and discusses the future direction of research

Livestock and poverty reduction in India: findings from the ODI Livelihood Options Project

This paper is based on data collected under the Livelihood Options Project, a three year DFID funded policy study located in the Indian States of Andhra Pradesh (AP) and Madhya Pradesh (MP). The purpose of this project is to identify factors promoting or impeding diversification out of low productivity livelihoods, and identify the policy changes necessary to support upward trajectories and prevent downward ones. It explores the role of livestock in rural livelihoods and its potential to assist people in escaping poverty using a combination of quantitative and qualitative methods. Main topics of discussion include economic importance of livestock; macro level trends in AP and MP; and variations in income and livestock keeping. Three study findings are presented. These are Broad patters-lists livestock and farmer category, and livestock types by caste categories; Who keeps what and why? This finding discusses overviews of Andhra Pradesh and Madhya Pradesh and discusses goats as an increasingly popular accumulative option. The last Study finding - Does livestock provide a useful coping mechanism to vulnerable households and individuals - outlines migration and livestock case studies, and village accounts of livestock keeping patterns. The paper ends with conclusion and policy implications

Drought and vulnerability of livestock in India

This study examines the dynamics of livestock keeping in recent years when occurrence of droughts was severe; the function of livestock in reducing the vulnerability to shocks and stresses to which the poor are exposed; and the relationship between migration and aspects of livestock keeping in the context of drought and vulnerability. The discussion paper is organized as follows: Following the executive summary, Section 2 introduces the paper giving its background. Section 3 describes the methodology. Section 4 presents an overview of livestock keeping and poverty. Section 5 describes the dynamics of livestock keeping in two subsections. Section 6 analyzes livestock sales due to major expenses in three years. The relationship between migration income and livestock keeping is examined in Section 7. The paper concludes with Section 8, where implications are discussed. Questionnaire for 2005 panel re-survey and qualitative assessment of the impact of commercial poultry farms on backyard poultry production and additional tabulation are included in the appendices. The report is primarily based on the 2005 re-survey data supplemented by data collected from 2001-02 survey as well as qualitative method

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

Impact of sequence variation in the ul128 locus on production of human cytomegalovirus in fibroblast and epithelial cells

The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism

Reaching the poor with health interventions: programme-incidence analysis of seven randomised trials of women's groups to reduce newborn mortality in Asia and Africa

Efforts to end preventable newborn deaths will fail if the poor are not reached with effective interventions. To understand what works to reach vulnerable groups, we describe and explain the uptake of a highly effective community-based newborn health intervention across social strata in Asia and Africa

The impact of type 2 diabetes on health related quality of life in Bangladesh: results from a matched study comparing treated cases with non-diabetic controls

Background Little is known about the association between diabetes and health related quality of life (HRQL) in lower-middle income countries. This study aimed to investigate HRQL among individuals with and without diabetes in Bangladesh. Methods The analysis is based on data of a case-control study, including 591 patients with type 2 diabetes (cases) who attended an outpatient unit of a hospital in Dhaka and 591 age -and sex-matched individuals without diabetes (controls). Information about socio-demographic characteristics, health conditions, and HRQL were assessed in a structured interview. HRQL was measured with the EuroQol (EQ) visual analogue scale (VAS) and the EQ five-dimensional (5D) descriptive system. The association between diabetes status and quality of life was examined using multiple linear and logistic regression models. Results Mean EQ-VAS score of patients with diabetes was 11.5 points lower (95 %-CI: −13.5, −9.6) compared to controls without diabetes. Patients with diabetes were more likely to report problems in all EQ-5D dimensions than controls, with the largest effect observed in the dimensions ‘self-care’ (OR = 5.9; 95 %-CI: 2.9, 11.8) and ‘mobility’ (OR = 4.5; 95 %-CI: 3.0, −6.6). In patients with diabetes, male gender, high education, and high-income were associated with higher VAS score and diabetes duration and foot ulcer associated with lower VAS scores. Other diabetes-related complications were not significantly associated with HRQL. Conclusions Our findings suggest that the impact of diabetes on HRQL in the Bangladeshi population is much higher than what is known from western populations and that unlike in western populations comorbidities/complications are not the driving factor for this effect