Contemporary Updates on the Physiology of Glucagon like Peptide-1 and Its Agonist to Treat Type 2 Diabetes Mellitus

Pathogenesis of diabetes mellitus involves scores of different factors, out of which Glucagon like factor-1 (GLP-1) plays a foremost role. GLP-1 is a pepti     

Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth

The reproducible pattern of organismal growth during metazoan development is the product of genetically controlled signaling pathways. Patterned activation of these pathways shapes developing organs and dictates overall organismal shape and size. Here, we show that patches of tissue that are mutant for the Drosophila Tsg101 ortholog, erupted, cause dramatic overproliferation of adjacent wild-type tissue. Tsg101 proteins function in endosomal sorting and are required to incorporate late endosomes into multivesicular bodies. Drosophila cells with impaired Tsg101 function show accumulation of the Notch receptor in intracellular compartments marked by the endosomal protein Hrs. This causes increased Notch-mediated signaling and ectopic expression of the Notch target gene unpaired (upd), which encodes the secreted ligand of the JAK-STAT pathway. Activation of JAK-STAT signaling in surrounding wild-type cells correlates with their overgrowth. These findings define a pathway by which changes in endocytic trafficking can regulate tissue growth in a non-cell-autonomous manner.     

Enriched Environment Prevents Hypobaric Hypoxia Induced Neurodegeneration and is Independent of Antioxidant Signaling

Hypobaric hypoxia (HH) induced neurodegeneration has been attributed to several factors including increased oxidative stress, glutamate excitotoxicity, decreased growth factors, apoptosis, etc. Though enriched environment (EE) has been known to have beneficial effects in various neurological disorders, its effect on HH mediated neurodegeneration remains to be studied. Therefore, the present study was conducted to explore the effect of EE on HH induced neurodegeneration. Male Sprague-Dawley rats were placed in enriched and standard conditions during exposure to HH (7 days) equivalent to an altitude of 25,000 ft. The effect of EE on oxidative stress markers, apoptosis, and corticosterone level in hippocampus was investigated. EE during exposure to HH was found to decrease neurodegeneration as evident from decreased caspase 3 expression and LDH leakage. However, no significant changes were observed in ROS, MDA, and antioxidant status of hippocampus. HH elevates corticosterone level and affected the diurnal corticoid rhythm which may contribute to neurodegeneration, whereas EE ameliorate this effect. Because of the association of neurotrophins and stress and/or corticosterone the BDNF and NGF levels were also examined and it was found that HH decreases their level but concurrent exposure to EE maintains their level. Moreover, inhibition of Tyrosine kinase receptor (Trk) with K252a nullifies the protective effect of EE, whereas Trk activation with agonist, amitriptyline showed protective effect similar to EE. Taken together, we conclude that EE has a potential to ameliorate HH mediated neuronal degeneration which may act through antioxidant independent pathway by modulation of neurotrophins.     

Growth regulation: a beginning for the hippo pathway

A signaling pathway involving two protein kinases, Hippo and Warts, restricts the growth of imaginal discs in Drosophila. Four recent studies taken together show that the protocadherin Fat can regulate Warts in two different ways.     

The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling

Mutations that inactivate either merlin (mer) or expanded (ex) result in increased cell growth and proliferation in Drosophila. Both Mer and Ex are members of the Band 4.1 protein superfamily, and, based on analyses of mer ex double mutants, they are proposed to function together in at least a partially redundant manner upstream of the Hippo (Hpo) and Warts (Wts) proteins to regulate cell growth and division. By individually analyzing ex and mer mutant phenotypes, we have found important qualitative and quantitative differences in the ways Mer and Ex function to regulate cell proliferation and cell survival. Though both mer and ex restrict cell and tissue growth, ex clones exhibit delayed cell cycle exit in the developing eye, while mer clones do not. Conversely, loss of mer substantially compromises normal developmental apoptosis in the pupal retina, while loss of ex has only mild effects. Finally, ex has a role in regulating Wingless protein levels in the eye that is not obviously shared by either mer or hpo. Taken together, our data suggest that Mer and Ex differentially regulate multiple downstream pathways.     

Kitam Bird Sanctuary,the only low elevation protected area of Sikkim: A conservation hotspot for butterflies in the Eastern Himalaya

The lowland areas of the Himalayan region are subjected to immense anthropogenic pressure because of least representation in the protected area network. Kitam Bird Sanctuary is the only representative protected area that occurs below 1000 m in Sikkim state of India (a part of globally significant biodiversity hotspot of Himalayas) and serves as the refuge for various species of flora and fauna. Here we studied butterfly diversity and community composition in Kitam Bird Sanctuary (a small protected area of 6 km² geographical area) following point count method spread across predetermined transects. Altogether 1674 butterflies belonging to 111 species and six families were recorded after completion of 240 point counts. Among these, 18 species are federally protected under the Wildlife (Protection) Act (1972) of India. Most of the butterflies were forest specialist in terms of habitat preference, whereas based on host plant specificity, the butterfly community was mostly dominated by generalist feeder (Oligophagous II and Polyphagous). Butterfly community parameters showed a strong correlation with habitat variables. While Kitam Bird Sanctuary is primarily designated for conservation of lowland birds, the high diversity of butterflies both in terms of taxonomic richness and trait composition suggests that the sanctuary harbors an ideal habitat for butterflies of the tropical region and invites conservation attention.     

Differences in levels of the transmembrane protein Crumbs can influence cell survival at clonal boundaries

The survival and growth of individual cells in a tissue can be nonautonomously regulated by the properties of adjacent cells. In mosaic Drosophila imaginal discs, for example, wild-type cells induce the elimination of adjacent slow-growing Minute cells by apoptosis, while, conversely, certain types of faster-growing cells are able to eliminate adjacent wild-type cells. This process, known as cell competition, represents one example of a diverse group of phenomena in which short-range heterotypic interactions result in the selective elimination of one type of cell by another. The mechanisms that designate "winner" and "loser" genotypes in these processes are not known. Here we show that apoptosis is observed preferentially at boundaries that separate populations of cells that express different levels of the transmembrane protein Crumbs (Crb). Cells that express higher levels of Crb tend to be eliminated when they are near cells that express lower levels of Crb. We also observe distortions in the structure of epithelia on either side of boundaries between populations of cells that differ in Crb expression. Thus, while previous studies have focused mostly on the cell autonomous functions of Crb, we show that Crb can regulate cell survival and tissue morphology nonautonomously. Moreover, we find that the extracellular domain (ECD) of Crb, which seems to be dispensable for some of the other characterised functions of Crb, is required to elicit the nonautonomous effects on cell survival. The ECD can also regulate the subcellular localisation of Hippo pathway components, and possibly other proteins, in adjacent cells and may therefore directly mediate these effects. Several genetic lesions alter Crb levels, including loss-of-function mutations in hyperplastic tumour suppressors in the Hippo-Salvador-Warts pathway and in neoplastic tumour suppressor genes, such as scribble. Thus, Crb may be part of a "surveillance mechanism" that is responsible for the cell death that is observed at the boundaries of mutant clones in these cases.