RESUMEN
BACKGROUND: American Indians and Alaskan Natives (AI/AN) are a highly diverse group in terms of culture and language, but share a history of oppression and attempted extermination that has left many with a legacy of poverty and poor health. Cultural and biological survival are important issues for many AI/AN groups. METHODS: Using US criteria, AI/AN groups are more likely to be poor. The US National Center for Health Statistics reports that US AI/ANs have higher mortality and morbidity rates than the US population. While all groups racially defined by the US National Center for Health Statistics have been experiencing a decline in fertility since 1983, AI/ANs seem to be suffering a substantially greater and earlier decline in fertility. Given the importance of fertility in the survival of AI/AN communities, it is important to identify the source of this decline. RESULTS: A recent study of one AI/AN group living along the St. Lawrence River found that obesity and exposure to a particular group of polychlorinated biphenyls were the factors most highly associated with indicators of impaired fertility. Economic factors are often cited as reasons for fertility declines, however in this situation these other factors may have either primary or contributing roles. CONCLUSIONS: If the associations with obesity and toxicant exposure are confirmed, intervening on these factors might be important steps in stemming continued declines in fertility.
Asunto(s)
Exposición a Riesgos Ambientales , Contaminantes Ambientales/toxicidad , Estado de Salud , Pobreza , Clase Social , /estadística & datos numéricos , Humanos , Indígenas Norteamericanos/estadística & datos numéricos , Estados UnidosRESUMEN
The generation time of HIV Type 1 (HIV-1) in vivo has previously been estimated using a mathematical model of viral dynamics and was found to be on the order of one to two days per generation. Here, we describe a new method based on coalescence theory that allows the estimate of generation times to be derived by using nucleotide sequence data and a reconstructed genealogy of sequences obtained over time. The method is applied to sequences obtained from a long-term nonprogressing individual at five sampling occasions. The estimate of viral generation time using the coalescent method is 1.2 days per generation and is close to that obtained by mathematical modeling (1.8 days per generation), thus strengthening confidence in estimates of a short viral generation time. Apart from the estimation of relevant parameters relating to viral dynamics, coalescent modeling also allows us to simulate the evolutionary behavior of samples of sequences obtained over time.
Asunto(s)
Evolución Molecular , Genes env , VIH-1/fisiología , Filogenia , Replicación Viral , ADN Viral/genética , Seropositividad para VIH/virología , VIH-1/genética , Homosexualidad Masculina , Humanos , Masculino , Modelos Genéticos , Modelos Estadísticos , Datos de Secuencia Molecular , Factores de TiempoRESUMEN
The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes are governed by the repertoire of expressed genes, and the levels and timing of expression, it is important to have experimental tools for the direct monitoring of large numbers of mRNAs in parallel. We have developed an approach that is based on hybridization to small, high-density arrays containing tens of thousands of synthetic oligonucleotides. The arrays are designed based on sequence information alone and are synthesized in situ using a combination of photolithography and oligonucleotide chemistry. RNAs present at a frequency of 1:300,000 are unambiguously detected, and detection is quantitative over more than three orders of magnitude. This approach provides a way to use directly the growing body of sequence information for highly parallel experimental investigations. Because of the combinatorial nature of the chemistry and the ability to synthesize small arrays containing hundreds of thousands of specifically chosen oligonucleotides, the method is readily scalable to the simultaneous monitoring of tens of thousands of genes.
Asunto(s)
Cartilla de ADN/genética , Regulación de la Expresión Génica/genética , Genoma Humano , Animales , Linfocitos B/metabolismo , Línea Celular , Mapeo Cromosómico , Citocinas/genética , Cartilla de ADN/síntesis química , ADN Complementario/análisis , Humanos , Hibridación Fluorescente in Situ , Ionóforos , Ratones , Hibridación de Ácido Nucleico , Sondas de Oligonucleótidos , Poli A , Empalme del ARN , ARN Mensajero/análisis , Linfocitos T Colaboradores-Inductores/metabolismo , Acetato de TetradecanoilforbolRESUMEN
Nested-primer polymerase chain reaction (PCR) has been applied to the molecular cloning of 4.6-kb half-genome fragments of human immunodeficiency virus type 1 (HIV-1) taken directly from the peripheral blood mononuclear cells (PBMC) of an individual with neurological symptoms of HIV-1 infection. In a similar manner, gp120-coding portions of the envelope gene were cloned after PBMC from the same blood sample were cocultivated with uninfected PBMC for 28 days. The complete 1.6-kb nucleotide sequence of the gp120 gene was determined from each of 35 clones examined. Two of 13 (15%) PBMC-derived gp120 genes and 3 of 22 (14%) coculture-derived gp120 genes were defective as a result of frameshifts and an in-frame stop codon(s). Mean diversity between individual gp120-coding sequences in PBMC was fivefold greater (3.24%) than after coculture (0.65%). A predominant sequence of "strain" was found after coculture that was distinct from the diverse viral genotypes detected in vivo and therefore was selectively amplified during in vitro propagation. Multiple distinct third variable (V3) regions encoding the principal neutralizing domain of the envelope protein were detected in PBMC-derived genes, suggesting the presence of immunologic diversity of HIV env genes in vivo not reflected in the cocultured virus sample. The large size of the HIV fragments generated in this study will permit analysis of the diversity of immunologic reactivity, gene function, and pathogenicity of HIV genomes present within infected individuals, including the functional significance of the loss of diversity that occurs upon coculture.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/microbiología , Genes Virales , Variación Genética , VIH-1/genética , Proteínas del Envoltorio Viral/genética , Proteínas Estructurales Virales/genética , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Células Cultivadas , Clonación Molecular , ADN Viral/genética , ADN Viral/aislamiento & purificación , Genoma Viral , VIH-1/aislamiento & purificación , VIH-1/fisiología , Humanos , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa/métodos , Mapeo Restrictivo , Homología de Secuencia de Ácido NucleicoRESUMEN
Within the fatal immunodeficiency disease-inducing strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to acutely pathogenic, most of the latter of which are also replication defective (clone 61C is the prototype). Mixtures of 61E and 61C virus and chimeras generated between them, but not 61E alone, killed feline T cells. T-cell killing depended on changes within a 7-amino-acid region near the C terminus of the gp70 env gene or was achieved independently by changes within a 109-amino-acid region encompassing the N terminus of gp70. The carboxy-terminal change was also sufficient for induction of fatal immunodeficiency disease in cats. Other changes within the 61C gp70 gene enhanced T-cell killing, as did changes in the long terminal repeat, the latter of which also enhanced virus replication. T-cell killing correlated with high levels of intracellular unintegrated and proviral DNA, all of which were blocked by treatment of infected cells with sera from 61C-immune cats or with a neutralizing monoclonal antibody. These findings indicate that T-cell killing is a consequence of superinfection and that the mutations in env critical to pathogenicity of the immunosuppressive variant result in a failure to establish superinfection interference in infected cells.