RESUMEN
Kasurdi Health and Demographic Surveillance System (Kasurdi HDSS) was established at Rural Health Training Center Kasurdi on February 16, 2018. Kasurdi HDSS has been established to increase the research potential of medical colleges and develop real-time data for research purposes to study the changes in population demography, health, and health-care utilization. Kasurdi HDSS currently follows 2755 individuals living in 549 households. The system collects the data from the population through annual rounds conducted by postgraduate residents of the department of community medicine. The data are collected in the digital format with the help of android-based tablets. HDSS has collected demographic data, reproductive data, data on diseases such as tuberculosis and noncommunicable diseases, and socioeconomic data. The HDSS is in the process to upgrade its data management system to a more integrated platform, coordinated and guided by national/international standards, and data sharing policy.
Asunto(s)
Vigilancia de la Población , Demografía , Encuestas Epidemiológicas , Humanos , India/epidemiología , Factores SocioeconómicosRESUMEN
Cells activate DNA repair pathways and cell cycle checkpoints when they suffer damage to their genome. They also activate tolerance pathways that facilitate survival. In Escherichia coli, a mechanism known as postreplication repair (PRR) is used to bypass lesions that would otherwise present a physical block to DNA polymerase. PRR has also been proposed to occur in eukaryotic cells, although the partitioning of DNA synthesis to a discrete S-phase would suggest that it is only operative within a defined period of the cell cycle. Eukaryotic PRR has been most extensively studied in the budding yeast Saccharomyces cerevisiae. Two important genes for components of this repair pathway are RAD6, which encodes an ubiquitin-conjugating enzyme, and RAD18, which encodes a RING-finger protein and forms a heterodimer with Rad6p. Rad18p can also bind to DNA. We report here the identification of the Schizosaccharomyces pombe homologue of RAD18, which we have denoted rhp18. rhp18 mutants are hypersensitive to DNA-damaging agents, but show this hypersensitivity throughout the cell cycle. rhp18 mutants are characterised by a longer than usual DNA damage checkpoint arrest that is required for their residual viability following irradiation. Genetic analyses show that rhp18 controls a unique DNA damage repair/tolerance pathway that extends beyond the requirement to tolerate damage during S-phase, suggesting a broader definition of the function of this eukaryotic PRR protein.
Asunto(s)
Reparación del ADN , Replicación del ADN , Proteínas de Unión al ADN/genética , Proteínas de Saccharomyces cerevisiae , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces/genética , Rayos Ultravioleta , Secuencia de Aminoácidos , Ciclo Celular , Clonación Molecular , Daño del ADN , Reparación del ADN/efectos de la radiación , Replicación del ADN/efectos de la radiación , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta en la Radiación , Escherichia coli/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Cinética , Datos de Secuencia Molecular , Mutagénesis , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Schizosaccharomyces/citología , Schizosaccharomyces/efectos de la radiación , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Factores de Tiempo , Dedos de ZincRESUMEN
Hematopoiesis is maintained by "fine-tuned" regulation among cytokines, neuropeptides, neurotransmitters, and neurotrophic factors. Neurotransmitters, derived from PPT-I exert immune and hematopoietic regulation. PPT-I is also expressed locally in bone marrow (BM) stromal cells. PPT-I peptides induce the production of cytokines in BM cells, resulting in regulation of both committed progenitors (CFU-GM) and primitive hematopoietic progenitors (CAFC). Both types of progenitors are regulated differently by the two major PPT-I peptides, SP and NK-A. Endopeptidases, present in BM cells, can digest SP to produce SP(1-4) and SP(4-11). In this study, we investigated the hematopoietic effects of these fragments on CFU-GM and CAFC. Similar to the two major intact PPT-I peptides (SP and NK-A), we observed different hematopoietic effects by SP(1-4) and SP(4-11). Whereas SP(1-4) exerted inhibitory effects on CFU-GM and CAFC, SP(4-11) mediated stimulatory effects. Similar to NK-A, the inhibitory effects of SP(1-4) can be partly explained by the induction of suppressive cytokines (TGF-beta, TNF-alpha, and INF-gamma). Use of antagonists and screening of a dodecapeptide expression library determined that the effects of SP(1-4) were mediated by NK-1. These results show that PPT-I peptides and their endopeptidase-derived fragments may add to the fine-tuned regulation on hematopoiesis. Furthermore, PPT-I may be exerting autoregulation to protect hematopoietic stem cells. These studies have relevance to stem cell protection and BM transplant.
