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Métodos Terapéuticos y Terapias MTCI
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1.
Am J Trop Med Hyg ; 94(6): 1266-75, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27001761

RESUMEN

Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.


Asunto(s)
Ácido Abscísico/administración & dosificación , Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Ácido Abscísico/sangre , Animales , Anopheles/parasitología , Suplementos Dietéticos , Femenino , Malaria/parasitología , Ratones , Parasitemia/tratamiento farmacológico , Plasmodium yoelii
2.
Plant J ; 67(6): 1018-28, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21615570

RESUMEN

To identify the underlying molecular basis of carbon partitioning between starch and oil we conducted 454 pyrosequencing, followed by custom microarrays to profile gene expression throughout endosperm development, of two closely related oat cultivars that differ in oil content at the expense of starch as determined by several approaches including non-invasive magnetic resonance imaging. Comparative transcriptome analysis in conjunction with metabolic profiling displays a close coordination between energy metabolism and carbon partitioning pathways, with increased demands for energy and reducing equivalents in kernels with a higher oil content. These studies further expand the repertoire of networks regulating carbon partitioning to those involved in metabolism of cofactors, suggesting that an elevated supply of cofactors, here called cofactomes, contribute to the allocation of higher carbon pools for production of oils and storage proteins. These data highlight a close association between cofactomes and carbon partitioning, thereby providing a biotechnological target for conversion of starch to oil.


Asunto(s)
Avena/genética , Avena/metabolismo , Biocombustibles , Carbono/metabolismo , Coenzimas/metabolismo , Aceites de Plantas/metabolismo , Metabolismo Energético , Perfilación de la Expresión Génica , Metabolismo de los Lípidos , Espectroscopía de Resonancia Magnética , Análisis de Secuencia por Matrices de Oligonucleótidos , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Almidón/metabolismo , Transcriptoma
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