RESUMEN
Environmental factors can promote phenotypic variation through alterations in the epigenome and facilitate adaptation of an organism to the environment. Although hydrogen sulfide is toxic to most organisms, the fish Poecilia mexicana has adapted to survive in environments with high levels that exceed toxicity thresholds by orders of magnitude. Epigenetic changes in response to this environmental stressor were examined by assessing DNA methylation alterations in red blood cells, which are nucleated in fish. Males and females were sampled from sulfidic and nonsulfidic natural environments; individuals were also propagated for two generations in a nonsulfidic laboratory environment. We compared epimutations between the sexes as well as field and laboratory populations. For both the wild-caught (F0) and the laboratory-reared (F2) fish, comparing the sulfidic and nonsulfidic populations revealed evidence for significant differential DNA methylation regions (DMRs). More importantly, there was over 80% overlap in DMRs across generations, suggesting that the DMRs have stable generational inheritance in the absence of the sulfidic environment. This is an example of epigenetic generational stability after the removal of an environmental stressor. The DMR-associated genes were related to sulfur toxicity and metabolic processes. These findings suggest that adaptation of P. mexicana to sulfidic environments in southern Mexico may, in part, be promoted through epigenetic DNA methylation alterations that become stable and are inherited by subsequent generations independent of the environment.
Asunto(s)
Metilación de ADN/genética , Epigénesis Genética , Sulfuro de Hidrógeno/análisis , Manantiales Naturales/química , Poecilia/genética , Animales , Femenino , Geografía , Masculino , México , Análisis de Componente PrincipalRESUMEN
BACKGROUND: The molecular basis of evolutionary change is assumed to be genetic variation. However, growing evidence suggests that epigenetic mechanisms, such as DNA methylation, may also be involved in rapid adaptation to new environments. An important first step in evaluating this hypothesis is to test for the presence of epigenetic variation between natural populations living under different environmental conditions. RESULTS: In the current study we explored variation between populations of Darwin's finches, which comprise one of the best-studied examples of adaptive radiation. We tested for morphological, genetic, and epigenetic differences between adjacent "urban" and "rural" populations of each of two species of ground finches, Geospiza fortis and G. fuliginosa, on Santa Cruz Island in the Galápagos. Using data collected from more than 1000 birds, we found significant morphological differences between populations of G. fortis, but not G. fuliginosa. We did not find large size copy number variation (CNV) genetic differences between populations of either species. However, other genetic variants were not investigated. In contrast, we did find dramatic epigenetic differences between the urban and rural populations of both species, based on DNA methylation analysis. We explored genomic features and gene associations of the differentially DNA methylated regions (DMR), as well as their possible functional significance. CONCLUSIONS: In summary, our study documents local population epigenetic variation within each of two species of Darwin's finches.
Asunto(s)
Ciudades , Epigénesis Genética , Pinzones/genética , Variación Genética , Animales , Cromosomas/genética , Islas de CpG/genética , Variaciones en el Número de Copia de ADN/genética , Metilación de ADN/genética , Ecuador , Geografía , Masculino , Transducción de Señal/genética , Especificidad de la Especie , Espermatozoides/metabolismoRESUMEN
Thrombocytopenia with life-threatening hemorrhage in childhood immune thrombocytopenic purpura is rare, but effective therapeutic options are limited for the patient with bleeding. We report the efficacy of humanized anti-CD20 monoclonal antibody (rituximab, Rituxan) therapy for an infant with severe, refractory life-threatening immune thrombocytopenic purpura.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino , Humanos , Lactante , Masculino , Rituximab , Resultado del TratamientoRESUMEN
Recombinant avipoxvirus vectors are attractive candidates for use in vaccination strategies for infections such as human immunodeficiency virus type 1 (HIV-1), where induction of a CD8+ T cell response is thought to be an important component of protective immunity. Here, we report the expression of a multiepitope polypeptide (TAB9) composed of the central 15 amino acids of the V3 loop from six different isolates of HIV-1 in a fowlpox virus (FWPV) vector, and the use of this vector (FPTAB9LZ) to induce strong HIV-specific CD8+ T cell responses in mice. In animals immunized twice intravenously with FPTAB9LZ, almost 2% of the CD8+ T cells in the spleen were shown to produce IFN-gamma in response to stimulation with HIV-1 peptides 1 week after the second immunization. The most dominant response was to the HIV-1 IIIB peptide. A strong HIV-specific response was also induced by intraperitoneal immunization of mice with FPTAB9LZ, whilst subcutaneous immunization elicited a weaker response. Intraperitoneal immunization with FPTAB9LZ was also shown to provide protection against challenge with a recombinant vaccinia virus expressing antigens, including those in TAB9. These results confirm the potential of FWPV vectors for use in HIV vaccination strategies.