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Search Results: 1 - 10 of 368 matches for " Aravind Asokan "
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Biology of Adeno-Associated Viral Vectors in the Central Nervous System
Giridhar Murlidharan,Aravind Asokan
Frontiers in Molecular Neuroscience , 2014, DOI: 10.3389/fnmol.2014.00076
Abstract: Gene therapy is a promising approach for treating a spectrum of neurological and neurodegenerative disorders by delivering corrective genes to the central nervous system (CNS). In particular, Adeno-Associated Viruses (AAV) have emerged as promising tools for clinical gene transfer in a broad range of genetic disorders with neurological manifestations. In the current review, we have attempted to bridge our understanding of the biology of different AAV strains with their transduction profiles, cellular tropisms and transport mechanisms within the CNS. Continued efforts to dissect AAV-host interactions within the brain are likely to aid in the development of improved vectors for CNS-directed gene transfer applications in the clinic.
Intra- and Inter-Subunit Disulfide Bond Formation Is Nonessential in Adeno-Associated Viral Capsids
Nagesh Pulicherla, Pradeep Kota, Nikolay V. Dokholyan, Aravind Asokan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032163
Abstract: The capsid proteins of adeno-associated viruses (AAV) have five conserved cysteine residues. Structural analysis of AAV serotype 2 reveals that Cys289 and Cys361 are located adjacent to each other within each monomer, while Cys230 and Cys394 are located on opposite edges of each subunit and juxtaposed at the pentamer interface. The Cys482 residue is located at the base of a surface loop within the trimer region. Although plausible based on molecular dynamics simulations, intra- or inter-subunit disulfides have not been observed in structural studies. In the current study, we generated a panel of Cys-to-Ser mutants to interrogate the potential for disulfide bond formation in AAV capsids. The C289S, C361S and C482S mutants were similar to wild type AAV with regard to titer and transduction efficiency. However, AAV capsid protein subunits with C230S or C394S mutations were prone to proteasomal degradation within the host cells. Proteasomal inhibition partially blocked degradation of mutant capsid proteins, but failed to rescue infectious virions. While these results suggest that the Cys230/394 pair is critical, a C394V mutant was found viable, but not the corresponding C230V mutant. Although the exact nature of the structural contribution(s) of Cys230 and Cys394 residues to AAV capsid formation remains to be determined, these results support the notion that disulfide bond formation within the Cys289/361 or Cys230/394 pair appears to be nonessential. These studies represent an important step towards understanding the role of inter-subunit interactions that drive AAV capsid assembly.
Bocavirus Episome in Infected Human Tissue Contains Non-Identical Termini
Amit Kapoor, Mady Hornig, Aravind Asokan, Brent Williams, Jose A. Henriquez, W. Ian Lipkin
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021362
Abstract: Human bocaviruses (HBoV) are highly prevalent human infections whose pathogenic potential remains unknown. Recent identification of the first non-human primate bocavirus [1] in captive gorillas raised the possibility of the persistent nature of bocavirus infection. To characterize bocavirus infection in humans, we tested intestinal biopsies from 22 children with gastrointestinal disease for the presence of HBoV DNA. Four HBoV-positive tissue samples were analyzed to determine whether viral DNA was present in the linear genomic, the episomal closed circular or the host genome-integrated form. Whereas one tissue sample positive for HBoV3 contained the episomal form (HBoV3-E1), none had the genome-integrated form. The complete genome sequence of HBoV3-E1 contains 5319 nucleotides of which 513 represent the non-coding terminal sequence. The secondary structure of HBoV3-E1 termini suggests several conserved and variable features among human and animal bocaviruses. Our observation that HBoV genome exists as head-to-tail monomer in infected tissue either reflects the likely evolution of alternative replication mechanism in primate bocaviruses or a mechanism of viral persistence in their host. Moreover, we identified the HBoV genomic terminal sequences that will be helpful in developing reverse genetic systems for these widely prevalent parvoviruses. Significance HBoV have been found in healthy human controls as well as individuals with respiratory or gastrointestinal disease. Our findings suggest that HBoV DNA can exist as episomes in infected human tissues and therefore can likely establish persistent infection in the host. Previous efforts to grow HBoV in cell culture and to develop reverse genetic systems have been unsuccessful. Complete genomic sequence of the HBoV3 episome and its genomic termini will improve our understanding of HBoV replication mechanism and its pathogenesis.
Genetic variability of Aspergillus terreus from dried grapes  [PDF]
Banu Narasimhan, Madhivathani Asokan
Advances in Bioscience and Biotechnology (ABB) , 2010, DOI: 10.4236/abb.2010.14046
Abstract: RAPD was used to examine the genetic variability among five isolates of Aspergillus terreus spp.. Two random primers were selected for the RAPD assay PG01–5’ CAGGTGTTGC 3’ and PG02–5’ CTGGACAGAC 3’ (Progen Technologies). The characterization of Aspergillus terreus species have been mostly applied on the basis of morphology, phenotype and physiology. DNA Polymorphisms are based on differences in DNA sequences and have advantages over protein polymorphisms. But morphological characterization besides molecular tools will remain a basic and powerful key in the identification of Aspergillus terreus species. The objective of the present study was to isolate the fungal contaminants from dried grapes and compare the genomic profile of the Aspergillus terreus speices isolated from the dried grapes, through RAPD analysis. In the present study with primer PG 01 four different discriminations was there among the A. terreus isolates. There was a homology of genotype between the isolates 1 & 3. And with primer PG 02 four different discriminations were there and there was a homology between 1 & 3. The predominant type was type I in primer I & II. The other isolates belonged to 2, 3 and 4. No similarity was detected for isolates 3, 4 and 5 indicating great genomic diversity of A. terreus.
An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses
Claire A. Schreiber?,Toshie Sakuma?,Yoshihiro Izumiya?,Sara J. Holditch?,Raymond D. Hickey?,Robert K. Bressin?,Upamanyu Basu?,Kazunori Koide?,Aravind Asokan,Yasuhiro Ikeda
PLOS Pathogens , 2015, DOI: 10.1371/journal.ppat.1005082
Abstract: Adeno-associated viruses (AAV) have evolved to exploit the dynamic reorganization of host cell machinery during co-infection by adenoviruses and other helper viruses. In the absence of helper viruses, host factors such as the proteasome and DNA damage response machinery have been shown to effectively inhibit AAV transduction by restricting processes ranging from nuclear entry to second-strand DNA synthesis. To identify host factors that might affect other key steps in AAV infection, we screened an siRNA library that revealed several candidate genes including the PHD finger-like domain protein 5A (PHF5A), a U2 snRNP-associated protein. Disruption of PHF5A expression selectively enhanced transgene expression from AAV by increasing transcript levels and appears to influence a step after second-strand synthesis in a serotype and cell type-independent manner. Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this host-mediated restriction. Notably, adenoviral co-infection and U2 snRNP inhibition appeared to target a common pathway in increasing expression from AAV vectors. Moreover, pharmacological inhibition of U2 snRNP by meayamycin B, a potent SF3B1 inhibitor, substantially enhanced AAV vector transduction of clinically relevant cell types. Further analysis suggested that U2 snRNP proteins suppress AAV vector transgene expression through direct recognition of intact AAV capsids. In summary, we identify U2 snRNP and associated splicing factors, which are known to be affected during adenoviral infection, as novel host restriction factors that effectively limit AAV transgene expression. Concurrently, we postulate that pharmacological/genetic manipulation of components of the spliceosomal machinery might enable more effective gene transfer modalities with recombinant AAV vectors.
Racial Affliction And Class Oppression In Toni Morrison's Sula
Amirthavalli Asokan
Golden Research Thoughts , 2012, DOI: 10.9780/22315063
Abstract: Toni Morrison seems to have realized this awful truth by the time she comes to write her second novel, Sula (1973). The major predicament that Morrison considers in this novel is, therefore, two-fold-the effect of racism upon black identity formation, and the effect of racism and sexism upon the identity formation of the black female. In an interview conducted by Colette Dowling, Morrison states that “blacks is they are to succeed in America society, must leave their native communities, and in so doing, cut themselves off from their old lives.” (New York Times Magazine, 58) This amounts to double isolation, since the doors to the white America mainstream generally remain closed to blacks.
Oil pulling therapy
Asokan Sharath
Indian Journal of Dental Research , 2008,
Abstract:
Towards an ideal paradigm
Asokan T
Indian Journal of Psychological Medicine , 2009,
Abstract:
Uta Fenske: Mannsbilder. Eine geschlechterhistorische Betrachtung von Hollywoodfilmen 1946–1960. Bielefeld: transcript Verlag 2008.
Asokan Nirmalarajah
querelles-net , 2009,
Abstract: Uta Fenske besch ftigt sich in ihrer Dissertation mit den M nnlichkeitsentwürfen des klassischen Hollywoodfilms der 1950er Jahre. Die Historikerin blickt damit zurück in eine ra US-amerikanischer Geschichte, in der soziokulturelle Umbrüche zu einer Erschütterung tradierter M nnlichkeitsbilder, zu einem Krisendiskurs über den modernen Mann führten. Fenskes kulturwissenschaftliche Studie kann sich dabei aus zweierlei Sicht profilieren. Zum einen erweitert sie mit der unorthodoxen Wahl ihres Untersuchungsgegenstandes das geschichtswissenschaftliche Quellenkorpus. Zum anderen kann sie durch ihren Rekurs auf eine Vielzahl von Genres zeigen, dass die Hollywoodfilme der 1950er eine gr ere Fülle an Antworten auf die Krise anbieten als gemeinhin angenommen. Uta Fenske’s dissertation examines concepts of masculinity in classic 1950s Hollywood films. The historian thus looks back to an era of US history in which sociocultural upheavals led to a disturbance of traditional images of masculinity and to a discourse of crisis of the modern man. Fenske’s examination, informed by cultural studies, distinguishes itself in two different ways. Firstly, through the unorthodox choice of its object of inquiry the study expands the corpus of historical sources. Secondly, through recourse to a variety of genres it can show that the Hollywood films of the 1950s offer a greater richness of answers to the crisis than heretofore assumed.
E-commerce websites with jQuery
Asokan M
International Journal on Computer Science and Engineering , 2013,
Abstract: The internet is one of the most innovative and revolutionary technologies. In recent times ECommerce emerged as one of the most important features of Internet. An e-commerce website, is an online shop, a virtual space for online sale or where the company can expose its catalog of products and/or services, and conduct commercial transaction safely and without limits. Online shopping is becoming increasingly popular because of speed and ease of use for customers. A one-second performance delay in e-commerce response time reduces conversions by 7 percent, according to a study conducted by the Aberdeen Group. Competition is just a click away!. Therefore there is a need to develop faster loading websites. Using jQuery we can create faster loading eye catching websites. This paper discuss about advantages of jQuery and advantages of e-commerce websites. Two of the famous e-commerce based plugins jMenu and jQzoom have been explained . They have been tested in our default browser and works well.
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