Several reports have cells might involve a population of Ngn3-expressing cells small changes

To determine whether recapitulation of the embryonic developmental pathway by reactivating Ngn3-positive progenitors contributed to the increase in b-cell numbers during pregnancy, we used a transgenic mouse that has previously been used to determine whether b-cell regeneration in injured adult pancreas involves reactivation of Ngn3. Ngn3 is an early transcription factor that directs progenitors towards the endocrine cell fate. Since EGFP expression is reported to be stable for at least 48 hours, it allows us to detect even a very transient expression of Ngn3. The presence of EGFP also offers us another marker to detect Ngn3, as Ngn3 protein detection in adult pancreas tissue by immunofluorescence can be difficult. The source of new b-cells during pregnancy has not been clearly identified. While some studies have attributed the increase in bcells numbers during pregnancy solely to b-cell duplication, others have postulated that a progenitor cell source may contribute to the increase in b-cell mass during pregnancy. When we examined downstream targets of Ngn3, small changes in expression of Tle3, NeuroD, and Nkx2.2 were detected. Tle3 has been shown to promote b-cell differentiation. NeuroD is crucial for pancreas development and it is a transactivator of the insulin gene, while Nkx2.2 acts as both a transcription activator for b-cell maturation and function as well as a repressor for alpha- and b-cell formation. Rfx6 regulates islet formation downstream of Ngn3 in both mice and human, and IA1 has also been shown to regulate development and differentiation of both pancreatic b-cells and intestinal cells. It is possible that these small reductions in gene expression confer little biological impact, though definitive conclusion requires using gene knockout models that allow titration of gene dosage. Nevertheless, these results are consistent with known functions of genes that regulate b-cell differentiation, and to our knowledge, this is the first study that examined their expression in adult pancreatic islets during pregnancy. These changes in expression of Ngn3 and its regulatory network may hint at genes required for islet adaptations during pregnancy. A clear understanding of the mechanisms engaged during pregnancy to mobilize non-bcells to take on a mature b-cell phenotype will likely lead to development of therapeutic strategies in conditions of b-cell failure such as diabetes. The H5N1 influenza virus is a global threat to birds and humans, and by January 2014, there had been 650 cases of infections in people, with 386 deaths. The disease in humans is epidemic in Asian and African countries such as Vietnam, Indonesia, Cambodia, and Egypt. Infections by H5N1 in people are limited to those who had close contact with infected animals, although the range and severity of symptoms in humans is not clear. For example, meta-analysis of serological studies on human H5N1 infections indicates a large number of missed infections.

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