REGULATION OF MACROAUTOPHAGY BY VITAMIN A/ RETINOIDS

Retinoic acids (RAs) have diverse biologic effects and regulate several cellular functions. Here, we investigated the role of RA on autophagy by studying its effects on autophagosome (AUT) maturation, as well as on upstream regulators of autophagosome biogenesis. Our studies, based on the use of pH-sensitive fluorescent reporter markers, suggest that RA promotes AUT acidification and maturation. By using competitive inhibitors and specific agonists, we demonstrated that this effect is not mediated by the classic Retinoic Acid Receptor (RAR) and Retinoid X Receptors (RXR). RA did not affect the protein expression levels of upstream regulators of autophagy, such as Beclin-1, phospho-mTOR, and phospho-Akt1, but induced redistribution of both endogenous cation-independent mannose-6-phosphate receptor CI-MPR and transiently transfected GFP and RFP full-length CI-MPR fusion proteins from the trans-Golgi region to acidified AUT structures. Those structures were found to be amphisomes (acidified AUTs) and not autophagolysosomes. The critical role of CI-MPR in AUT maturation was further demonstrated by siRNA-mediated silencing of endogenous CI-MPR. Transient CI-MPR knockdown resulted in remarkable accumulation of nonacidified AUTs, a process that could not be reversed with RA.These results suggest that RA induces AUT acidification and maturation by regulating CI-MPR subcellular location, a process critical in the cellular autophagic mechanism

In-Vivo Gene Therapy with Foamy Virus Vectors

Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as novel vectors (foamy virus vector, FVV) for stable gene transfer into different cells and tissues. FVVs have emerged as an alternative platform to contemporary viral vectors (e.g., adeno associated and lentiviral vectors) for experimental and therapeutic gene therapy of a variety of monogenetic diseases. Some of the important features of FVVs include the ability to efficiently transduce hematopoietic stem and progenitor cells (HSPCs) from humans, NHPs, canines and rodents. We have successfully used FVV for proof of concept studies to demonstrate safety and efficacy following in-vivo delivery in large animal models. In this review, we will comprehensively discuss FVV based in-vivo gene therapy approaches established in the X-linked severe combined immunodeficiency (SCID-X1) canine model

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Not AvailableSorghum anthracnose, caused by Colletotrichum graminicola, is a destructive disease, and increasing dependency on chemical fungicides for its control has serious environmental concerns since sorghum is fed to cattle. Thus there is a need to develop effective bio-pesticide for biological control of C. graminicola. Since Trichoderma is a proven biocontrol agent against plant pathogens, exploring the greater diversity that exists in Trichoderma, could be of notable economic significance in terms of disease control. To harness the hidden potential of Trichoderma strains against C. graminicola, a study was undertaken with 20 Trichoderma spp. isolated from 40 rhizospheric soil samples. Dual plate antagonism assay indicated the potential of T3, T4, T6, T15, and T19 isolates of Trichoderma against C. graminicola, with T3 isolate showing maximum (76.47%) mycelial growth inhibition. Molecular characterization based on the sequence analysis of ITS-rRNA and tef-1α genes identified these isolates as Trichoderma asperellum and Trichoderma harzianum. Under the glasshouse condition, biopriming of seed with Trichoderma spp. had significantly decreased the percent disease index to 32.92% and helped improve plant growthpromoting attributes compared to untreated control. Seed biopriming with T3 isolate exhibited higher antioxidant enzyme activities in terms of superoxide dismutase (36.63%), peroxidase (43.59%), and polyphenol oxidaseNot Availabl