anurag tiwari - Academia.edu (original) (raw)

Papers by anurag tiwari

Global Health Action, 2010

Background: The antiretroviral treatment (ART) scale-up service has been a recent development in ... more Background: The antiretroviral treatment (ART) scale-up service has been a recent development in Ethiopia, but its impact on mortality has not been well investigated. The aim of this study was to assess the early survival outcome of the scale-up service by utilizing routine hospital data. Methods: All adult HIV/AIDS patients who started on antiretroviral treatment in Shashemene and Assela hospitals from January 1, 2006 to May 31, 2006 were included and followed up for 2 years. Data were extracted from standard patient medical registrations. KaplanÁMeier curves were used to estimate survival probability and the Cox proportional hazard model was applied to determine predictors of mortality. Two alterative assumptions (real case and worst case) were made in determining predictors of mortality. Results: The median age of patients was 33 years and 57% were female. Eighty-five percent had CD4 B200 cells/mL with a median CD4 count of 103 cells/mL. The median survival time was 104.4 weeks. A total of 28 (10.3%) deaths were observed during the 2-year period and 48 patients (18%) were lost to follow up. The majority of deaths occurred in the first 4 months of treatment. In multivariate analysis, 2-year survival was significantly associated with the clinical stage of the disease, baseline hemoglobin, and cotrimoxazole prophylaxis therapy (CPT) at or before ART initiation in both assumptions. The median CD4 count and body weight showed a marked improvement during the first 6 months of treatment, followed by stagnation thereafter. Conclusion: The study has shown an overall low mortality but a high loss to follow-up rate of the cohort. Advanced clinical stage, anemia, low body weight, and lack of CPT initiation were independent predictors of mortality Á but not gender. CPT initiation should be encouraged in routine HIV care services, and patient retention mechanisms have to be strengthened. Stagnation in immunological and weight recovery after the first 6 months should be further investigated. The utilization of routine data should be encouraged in order to facilitate appropriate decision making.

Genetics, Jan 29, 2016

The retrograde response signals mitochondrial status to the nucleus compensating for accumulating... more The retrograde response signals mitochondrial status to the nucleus compensating for accumulating mitochondrial dysfunction during Saccharomyces cerevisiae aging and extending replicative lifespan. The histone acetylase Gcn5 is required for activation of nuclear genes and lifespan extension in the retrograde response. It is part of the transcriptional co-activators SAGA and SLIK, but it is not known which of these complexes is involved. Genetic manipulation showed that these complexes perform interchangeably in the retrograde response. These results, along with the finding that the histone deacetylase Sir2 was required for a robust retrograde response informed a bioinformatics screen that reduced to four the candidate genes causal for longevity out of the 410 retrograde response target genes. Of the four, only deletion of PHO84 suppressed lifespan extension. Retrograde-response activation of PHO84 displayed some preference for SAGA. Increased PHO84 mRNA levels from a second copy of ...

Frontiers in Genetics, 2012

In the budding yeast Saccharomyces cerevisiae, loss of mitochondrial DNA (rho 0) can induce the r... more In the budding yeast Saccharomyces cerevisiae, loss of mitochondrial DNA (rho 0) can induce the retrograde response under appropriate conditions, resulting in increased replicative lifespan (RLS). Although the retrograde pathway has been extensively elaborated, the nature of the mitochondrial signal triggering this response has not been clear. Mitochondrial membrane potential (MMP) was severely reduced in rho 0 compared to rho + cells, and RLS was concomitantly extended.To examine the role of MMP in the retrograde response, MMP was increased in the rho 0 strain by introducing a mutation in the ATP1 gene, and it was decreased in rho + cells by deletion of COX4. The ATP1-111 mutation in rho 0 cells partially restored the MMP and reduced mean RLS to that of rho + cells. COX4 deletion decreased MMP in rho + cells to a value intermediate between rho + and rho 0 cells and similarly increased RLS. The increase in expression of CIT2, the diagnostic gene for the retrograde response, seen in rho 0 cells, was substantially suppressed in the presence of the ATP1-111 mutation. In contrast, CIT2 expression increased in rho + cells on deletion of COX4. Activation of the retrograde response results in the translocation of the transcription factor Rtg3 from the cytoplasm to the nucleus. Rtg3-GFP translocation to the nucleus was directly observed in rho 0 and rho + cox4 0 Δ cells, but it was blunted in rho cells with the ATP1-111 mutation. We conclude that a decrease in MMP is the signal that initiates the retrograde response and leads to increased RLS.

Genome Research, 2012

The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of indi... more The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100–...

Global Health Action, 2010

Background: The antiretroviral treatment (ART) scale-up service has been a recent development in ... more Background: The antiretroviral treatment (ART) scale-up service has been a recent development in Ethiopia, but its impact on mortality has not been well investigated. The aim of this study was to assess the early survival outcome of the scale-up service by utilizing routine hospital data. Methods: All adult HIV/AIDS patients who started on antiretroviral treatment in Shashemene and Assela hospitals from January 1, 2006 to May 31, 2006 were included and followed up for 2 years. Data were extracted from standard patient medical registrations. KaplanÁMeier curves were used to estimate survival probability and the Cox proportional hazard model was applied to determine predictors of mortality. Two alterative assumptions (real case and worst case) were made in determining predictors of mortality. Results: The median age of patients was 33 years and 57% were female. Eighty-five percent had CD4 B200 cells/mL with a median CD4 count of 103 cells/mL. The median survival time was 104.4 weeks. A total of 28 (10.3%) deaths were observed during the 2-year period and 48 patients (18%) were lost to follow up. The majority of deaths occurred in the first 4 months of treatment. In multivariate analysis, 2-year survival was significantly associated with the clinical stage of the disease, baseline hemoglobin, and cotrimoxazole prophylaxis therapy (CPT) at or before ART initiation in both assumptions. The median CD4 count and body weight showed a marked improvement during the first 6 months of treatment, followed by stagnation thereafter. Conclusion: The study has shown an overall low mortality but a high loss to follow-up rate of the cohort. Advanced clinical stage, anemia, low body weight, and lack of CPT initiation were independent predictors of mortality Á but not gender. CPT initiation should be encouraged in routine HIV care services, and patient retention mechanisms have to be strengthened. Stagnation in immunological and weight recovery after the first 6 months should be further investigated. The utilization of routine data should be encouraged in order to facilitate appropriate decision making.

Genetics, Jan 29, 2016

The retrograde response signals mitochondrial status to the nucleus compensating for accumulating... more The retrograde response signals mitochondrial status to the nucleus compensating for accumulating mitochondrial dysfunction during Saccharomyces cerevisiae aging and extending replicative lifespan. The histone acetylase Gcn5 is required for activation of nuclear genes and lifespan extension in the retrograde response. It is part of the transcriptional co-activators SAGA and SLIK, but it is not known which of these complexes is involved. Genetic manipulation showed that these complexes perform interchangeably in the retrograde response. These results, along with the finding that the histone deacetylase Sir2 was required for a robust retrograde response informed a bioinformatics screen that reduced to four the candidate genes causal for longevity out of the 410 retrograde response target genes. Of the four, only deletion of PHO84 suppressed lifespan extension. Retrograde-response activation of PHO84 displayed some preference for SAGA. Increased PHO84 mRNA levels from a second copy of ...

Frontiers in Genetics, 2012

In the budding yeast Saccharomyces cerevisiae, loss of mitochondrial DNA (rho 0) can induce the r... more In the budding yeast Saccharomyces cerevisiae, loss of mitochondrial DNA (rho 0) can induce the retrograde response under appropriate conditions, resulting in increased replicative lifespan (RLS). Although the retrograde pathway has been extensively elaborated, the nature of the mitochondrial signal triggering this response has not been clear. Mitochondrial membrane potential (MMP) was severely reduced in rho 0 compared to rho + cells, and RLS was concomitantly extended.To examine the role of MMP in the retrograde response, MMP was increased in the rho 0 strain by introducing a mutation in the ATP1 gene, and it was decreased in rho + cells by deletion of COX4. The ATP1-111 mutation in rho 0 cells partially restored the MMP and reduced mean RLS to that of rho + cells. COX4 deletion decreased MMP in rho + cells to a value intermediate between rho + and rho 0 cells and similarly increased RLS. The increase in expression of CIT2, the diagnostic gene for the retrograde response, seen in rho 0 cells, was substantially suppressed in the presence of the ATP1-111 mutation. In contrast, CIT2 expression increased in rho + cells on deletion of COX4. Activation of the retrograde response results in the translocation of the transcription factor Rtg3 from the cytoplasm to the nucleus. Rtg3-GFP translocation to the nucleus was directly observed in rho 0 and rho + cox4 0 Δ cells, but it was blunted in rho cells with the ATP1-111 mutation. We conclude that a decrease in MMP is the signal that initiates the retrograde response and leads to increased RLS.

Genome Research, 2012

The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of indi... more The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100–...