Dichotomy of Nitric Oxide in Cancer Biology and its Therapeutic Implications

The role of Nitric oxide, which is an important signalling molecule, has become an active and controversial area of research in cancer. Nitric oxide has been designated as “Double-edged sword” in Cancer as it has exhibited both pro-apoptotic and anti-apoptotic effects. Nitric oxide synthase (NOS) levels have been associated with contrasting effects of tumor suppression tumor progression. The discovery of generation of NO in mammalian tissues and its biological role in cancer has thrown light into tumor biology research. Through various studies conducted, it has become clear that concentration and time dependent regulation of Nitric oxide lead to tumor growth, cytostasis and cell death .The regulation of tumor growth by Nitric oxide represents an important new dimension in cancer research and  understanding of mechanisms involved  behind this process at molecular and cellular level is a major area of concern which will open up new avenues in Cancer Research and may help to provide new and better therapeutic interventions in diagnosis, treatment and cure of Cancer

CONSTRAINTS FACED BY THE RESPONDENTS IN AVAILING THE BENEFITS OF DWCRA IN SRIKAKULAM DISTRICT OF ANDHRA PRADESH

Women and Children constitute 67.7 per cent of the country’s total population as per the census 2001. Women exclusively accounted for million constituting 48.3 percent of the country’s population. By virtue of these figures, they shall be considered as an important target group. Hence, it becomes an essentiality to empower women economically and socially for promoting national development. Development of Women and Children in Rural Areas (DWCRA) was launched as sub scheme of IRDP. It was initially started as pilot project in 50 selected districts in all states during 1982- 1983. During, the IX plan almost all state governments started implementing DWCRA activities in rural areas. The objectives of this programme are to organize women into socio-economic activity groups with the dual purpose of providing self- employment opportunities and social strength to them. Besides, providing financial support for income generating activities, DWCRA also increases women’s access to basic services of health, education, children’s nutrition, safe drinking water, sanitation and environment. Though there are many achievements to its credit, still there is wider space to accommodate many innovative ideas elicited through the participation of women over the years for improving the programme periphery. View Article DOI: 10.47856/ijaast.2021.v08i9.01

Next-Generation Sequencing of HIV-1 Single Genome Amplicons

The analysis of HIV-1 sequences has helped understand the viral molecular epidemiology, monitor the development of antiretroviral drug resistance, and design candidate vaccines. The introduction of single genome amplification (SGA) has been a major advancement in the field, allowing for the characterization of multiple sequences per patient while preserving linkage among polymorphisms in the same viral genome copy. Sequencing of SGA amplicons is performed by capillary Sanger sequencing, which presents low throughput, requires a high amount of template, and is highly sensitive to template/primer mismatching. In order to meet the increasing demand for HIV-1 SGA amplicon sequencing, we have developed a platform based on benchtop next-generation sequencing (NGS) (IonTorrent) accompanied by a bioinformatics pipeline capable of running on computer resources commonly available at research laboratories. During assay validation, the NGS-based sequencing of 10 HIV-1 env SGA amplicons was fully concordant with Sanger sequencing. The field test was conducted on plasma samples from 10 US Navy and Marine service members with recent HIV-1 infection (sampling interval: 2005-2010; plasma viral load: 5,884-194,984 copies/ml). The NGS analysis of 101 SGA amplicons (median: 10 amplicons/individual) showed within-individual viral sequence profiles expected in individuals at this disease stage, including individuals with highly homogeneous quasispecies, individuals with two highly homogeneous viral lineages, and individuals with heterogeneous viral populations. In a scalability assessment using the Ion Chef automated system, 41/43 tested env SGA amplicons (95%) multiplexed on a single Ion 318 chip showed consistent gene-wide coverage \u3e50×. With lower sample requirements and higher throughput, this approach is suitable to support the increasing demand for high-quality and cost-effective HIV-1 sequences in fields such as molecular epidemiology, and development of preventive and therapeutic strategies

HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania.

In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident strains revealed the emergence of CRF41_CD and many unique recombinants, as well as the presence of six local transmission networks most of which were confined to the rural subpopulation. In the context of vaccine cohort selection, these results suggest distinct infection transmission dynamics within these three geographically close subpopulations. The diversity and genetic sequences of the HIV-1 strains obtained during this study will greatly contribute to the planning, immunogen selection, and analysis of vaccine-induced immune responses observed during HIV-1 vaccine trials in Tanzania and neighboring countries

Humoral Response to the HIV-1 Envelope V2 Region in a Thai Early Acute Infection Cohort

Reduced risk of HIV-1 infection correlated with antibody responses to the envelope variable 1 and 2 regions in the RV144 vaccine trial. To understand the relationship between antibody responses, V2 sequence, and structure, plasma samples (n = 16) from an early acute HIV-1 infection cohort from Thailand infected with CRF01_AE strain were analyzed for binding to V2 peptides by surface plasmon resonance. Five participants with a range of V2 binding responses at week 24 post-infection were further analyzed against a set of four overlapping V2 peptides that were designed based on envelope single-genome amplification. Antibody responses that were relatively consistent over the four segments of the V2 region or a focused response to the C-strand (residues 165–186) of the V2 region were observed. Viral escape in the V2 region resulted in significantly reduced antibody binding. Structural modeling indicated that the C-strand and the sites of viral variation were highly accessible in the open conformation of the HIV-1 Env trimer. V2 residues, 165–186 are preferentially targeted during acute infection. Residues 169–184 were also preferentially targeted by the protective immune response in the RV144 trial, thus emphasizing the importance of these residues for vaccine design

HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART

HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM−) stage, that is ≤2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA