Neural stem cell properties of Müller glia in the mammalian retina: Regulation by Notch and Wnt signaling

AbstractThe retina in adult mammals, unlike those in lower vertebrates such as fish and amphibians, is not known to support neurogenesis. However, when injured, the adult mammalian retina displays neurogenic changes, raising the possibility that neurogenic potential may be evolutionarily conserved and could be exploited for regenerative therapy. Here, we show that Müller cells, when retrospectively enriched from the normal retina, like their radial glial counterparts in the central nervous system (CNS), display cardinal features of neural stem cells (NSCs), i.e., they self-renew and generate all three basic cell types of the CNS. In addition, they possess the potential to generate retinal neurons, both in vitro and in vivo. We also provide direct evidence, by transplanting prospectively enriched injury-activated Müller cells into normal eye, that Müller cells have neurogenic potential and can generate retinal neurons, confirming a hypothesis, first proposed in lower vertebrates. This potential is likely due to the NSC nature of Müller cells that remains dormant under the constraint of non-neurogenic environment of the adult normal retina. Additionally, we demonstrate that the mechanism of activating the dormant stem cell properties in Müller cells involves Wnt and Notch pathways. Together, these results identify Müller cells as latent NSCs in the mammalian retina and hence, may serve as a potential target for cellular manipulation for treating retinal degeneration

Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic-Exposed Mothers

The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning–based two-class prediction algorithms, we identified expression signatures from babies born to arsenic-unexposed and -exposed mothers that were highly predictive of prenatal arsenic exposure in a subsequent test population. Furthermore, 11 transcripts were identified that captured the maximal predictive capacity to classify prenatal arsenic exposure. Network analysis of the arsenic-modulated transcripts identified the activation of extensive molecular networks that are indicative of stress, inflammation, metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important health hazard both in the United States and around the world, and is associated with increased risk for several types of cancer and other chronic diseases. These studies clearly demonstrate the robust impact of a mother's arsenic consumption on fetal gene expression as evidenced by transcript levels in newborn cord blood

Diagnostic Yield of Fiber Optic Bronchoscopy and CECT Thorax in Patients of Haemoptysis with Normal Chest X-Ray

Introduction: Contrast enhanced computed tomography (CECT) thorax & Fibre Optic Bronchoscopy (FOB) are main investigations in patients of hemoptysis with normal chest X-ray. But there are limited data on their diagnostic yield especially from South East Asia. Methods: An observational study on 60 patients with hemoptysis with normal chest X -ray was conducted from April 2012 to April 2014. CECT thorax and FOB were done in all of them. Results: Out of 60 patients 38 (63.3%) were male with even age distribution. Yield of CECT was 40% (24 patients) and main diagnosis were bronchiectesis (25%) and tuberculosis (11.6%). Diagnostic yield of FOB was 47% (28 patients) with predominant diagnosis of tuberculosis (18.33%), bronchitis (18.33%) and bronchogenic carcinoma (6.66%). Overall diagnostic yield was 76.6% (46 cases). Bronchogenic carcinoma cases were all male smokers and 3 of them were more than 40 years old. Conclusion: CECT thorax and FOB are complimentary to each other in evaluation of hemoptysis with normal chest x-ray. Bronchogenic carcinoma and tuberculosis cases require specific treatment and they were diagnosed in confirm way only by FOB. So, FOB have advantage over CT scan, especially among patients with increased risk of bronchogenic carcinoma (male-smokers with age > 40 years)