A replicon trans-packaging system reveals the requirement of nonstructural proteins for the assembly of bovine viral diarrhea virus (BVDV) virion

A selective trans-packaging system was developed to produce and isolate bovine viral diarrhea virus (BVDV) pseudo-particles with complementing reporter replicons and their packaging proteins expressed in trans with recombinant vaccinia virus. The encapsidation of replicon rNS3-5B was dependent not only on the in trans expression of structural proteins C, E^rns, E1 and E2, but also the nonstructural proteins, p7 and contiguous precursor NS2-3-4A. Nonstructural p7, NS4B, NS5A or NS5B could be expressed in cis and in trans with precursor NS2-3-4A without significantly affecting virion assembly efficiency. NS2-3-4A was identified as an in trans functional precursor in virion assembly. BVDV genomes with mutant NS5B, which did not undergo active replication, were packaged 5-fold less efficiently than the intact genomes demonstrating the importance of replication in virion packaging. These results suggest that genome replication and assembly are closely associated, consistent with a model in which these two steps are coupled for maximum efficiency.     

Partnerships,community participation and intersectoral collaboration in South Africa

Five community partnerships (CP) were initiated in South Africa as demonstration projects aimed at the re-orientation of health professionals' education (HPE) to be more community responsive and interprofessional. A cluster evaluation of these partnerships has demonstrated that, in addition to motivating all stakeholders to forge closer working relationships, it is necessary for partnerships to pay close attention to a variety of structural and operational dimensions, the lack of which could prove to be major constraints to effective partnership functioning. This study critically reviews the challenges to collaborative working as experienced by the South African cluster. Within the context of the post-apartheid restructuring and development, the discussion highlights the insights that partnerships offer to clarify the extent to which potential barriers could affect the stakeholder groups. The paper identifies potential impediments, and makes explicit how they impact on partnership fostering. Evidence is also presented for their early detection and possible solutions are identified. The lessons learnt from these South African cases are that wide representation, commitment and a sense of ownership, sound leadership skills, regular and effective communication, reliable member expertise and capabilities and attention to power issues are crucial elements in the partnership equation. The paper concludes with an invitation to health administrators and partnership executives to devote attention to the array of interacting components that, collectively, could impinge on the effectiveness of the multifaceted nature of interprofessional joint working arrangements.     

Age-related changes in mitochondrial respiration and oxidative damage in the cerebral cortex of the Fischer 344 rat

This study probed possible age-related changes in mitochondrial bioenergetics in naïve Fischer 344 rats. Synaptic and extrasynaptic mitochondria were isolated from the cortex of one hemisphere of young (3-5 months), middle (12-14 months), or aged (22-24 months) rats. Respiration parameters were obtained using a Clarke-type electrode. Aged rats displayed no significant alterations in respiration, indicating mitochondria must be more resilient to the aging process than previously thought. Synaptic mitochondria displayed lower respiration capacities than the extrasynaptic fraction. Aged F344 rats appear capable of normal electron transport chain function without declines in ability to produce ATP. Markers of cortical oxidative damage (3-nitrotyrosine [3-NT], 4-hydroxynonenal [4-HNE], and protein carbonyls [PC]) were collected from the post-mitochondrial supernatant (PMS) from the contralateral hemisphere, and from mitochondrial samples following respiration analysis. Age-related increases in PC and 3-NT levels were found in synaptic mitochondria, whereas significant extrasynaptic elevations were only found in middle aged rats. These findings support an age-related increase in oxidative damage in the cortex, while proposing the two fractions of mitochondria are differentially affected by the aging process. Levels of oxidative damage that accumulates in the cortex with age does not appear to significantly impair cortical mitochondrial respiration of F344 rats.     

Induction of autoimmune cholangitis in non‐obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC‐E2) leads to an anti‐mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our work has also highlighted the importance of genetic susceptibility. Using the non‐obese diabetic (NOD) congenic strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3 regions from B6 introgressed onto a NOD background, we exposed animals to 2‐octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been demonstrated previously by a quantitative structural activity relationship to react as well as or better than lipoic acid to anti‐mitochondrial antibodies. We demonstrate herein that NOD.1101 mice immunized with 2OA‐BSA, but not with BSA alone, develop high titre anti‐mitochondrial antibodies and histological features, including portal infiltrates enriched in CD8⁺ cells and liver granulomas, similar to human PBC. We believe this model will allow the rigorous dissection of early immunogenetic cause of biliary damage.     

Operational feasibility and efficacy of deltamethrin impregnated hessian curtains in comparison to HCH indoor residual spraying to control malaria in selected villages of District Ghaziabad (U.P.), India

A study was carried out in selected villages of District Ghaziabad to evaluate the operational feasibility and efficacy of hessian curtains impregnated with deltamethrin@100 mg/m2 in comparison to indoor residual spraying of HCH@0.2 g/m2. The impregnation was carried out before onset of transmission and observations were continued up to two transmission periods. District Health Authorities have carried out HCH indoor residual spraying (IRS) as per schedule in the control village. Entomological evaluation revealed 87 per cent reduction of An. culicifacies up to six months in comparison to HCH indoor residual spraying. However, the reduction in densities of total mosquitoes was only 61.6 per cent. Follow-up studies revealed that the impact of deltamethrin impregnated curtains was diluted after 6-7 months. The results of bioassay tests revealed 100 per cent mortality up to 6-7 months. Epidemiological evaluation revealed 81.9 per cent reduction in total malaria cases as against 88.5 per cent with P. falciparum cases. Similar reduction was also observed when slide positivity rate (SPR), slide falciparum rate (SfR), cases/000 and Pf/000 were compared to corresponding village. Pilot studies are indicated to evaluate the relative efficacy of impregnated curtains, which is quite cheaper than conventional residual insecticide spraying (IRS).     

Ectopic prostate: An unusual bladder tumor

A 25-year-old man presented with gross painless hematuria. Cystoscopy revealed a smooth surfaced mass in the supratrigonal region. Complete transurethral resection of the mass was done. Histopathological examination revealed benign prostatic tissue situated ectopically.     

Glaucoma: squaring the psychophysics and neurobiology

Advances in our understanding of the pathophysiology of retinal ganglion cell death in glaucoma are providing important insights into the functional changes occurring in retinal ganglion cells in the early stages of the disease. These exciting new findings may help us develop psychophysical tests to monitor early retinal ganglion cell damage, possibly before neurons are committed to the process of cell death.