Browsing by Author "Dhania, Narender K."

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FTIR based approach to study EnaC mechanosensory functions
(Elsevier Ltd, 2021-07-19T00:00:00) Govindan, Rekha; Banerjee, Pratibha; Dhania, Narender K.; Senapati, Sabyasachi
The pulmonary epithelial sodium ion channel (ENaC) is gaining importance for its sodium gating and mechanosensitive roles. The mechano functional studies on ENaC suggest direct molecular interactions between the ENaC protein with cytoskeleton microtubules and other extracellular matrix components. Also, in few mechanotransduction studies, ENaC was shown to respond both to membrane stretch as well as cell volume changes. However, the conformational characteristic of ENaC during sodium and mechano gating are yet to be fully elucidated. Thus obtaining ENaC protein conformational spectrum based on Fourier Transform Infrared Radiation (FTIR) spectroscopy in solution will be useful in predicting the nature of conformational changes occurring during any cell volume changes in an epithelial cell. The conformational spectrum looks promising in studying the disease biology of cystic fibrosis (CF) and CF like conditions that arise due to abnormal ion conductance membrane proteins and subsequent frequent fluid retentions. This review article presents the basics of epithelial ENaC protein as a gated mechanosensor and FTIR for developing fluid dynamics of ENaC protein. This can be applied to develop an ENaC based quantum mechanosensor for the prognosis as well as diagnosis of cystic fibrosis (CF) and allied lung diseases. � 2021 Elsevier Ltd
Gene-editing, immunological and iPSCs based therapeutics for muscular dystrophy
(Elsevier B.V., 2021-10-15T00:00:00) Singh, Shagun; Singh, Tejpal; Kunja, Chaitanya; Dhoat, Navdeep S.; Dhania, Narender K.
Muscular dystrophy is a well-known genetically heterogeneous group of rare muscle disorders. This progressive disease causes the breakdown of skeletal muscles over time and leads to grave weakness. This breakdown is caused by a diverse pattern of mutations in dystrophin and dystrophin associated protein complex. These mutations lead to the production of altered proteins in response to which, the body stimulates production of various cytokines and immune cells, particularly reactive oxygen species and NF?B. Immune cells display/exhibit a dual role by inducing muscle damage and muscle repair. Various anti-oxidants, anti-inflammatory and glucocorticoid drugs serve as potent therapeutics for muscular dystrophy. Along with the above mentioned therapeutics, induced pluripotent stem cells also serve as a novel approach paving a way for personalized treatment. These pluripotent stem cells allow regeneration of large numbers of regenerative myogenic progenitors that can be administered in muscular dystrophy patients which assist in the recovery of lost muscle fibers. In this review, we have summarized gene-editing, immunological and induced pluripotent stem cell based therapeutics for muscular dystrophy treatment. � 2021 Elsevier B.V.
Gut-specific arylphorin mediates midgut regenerative response against Cry-induced damage in Achaea janata
(Elsevier Inc., 2021-04-13T00:00:00) Dhania, Narender K.; Chauhan, Vinod K.; Abhilash, Dasari; Thakur, Vivek; Chaitanya, R.K.; Dutta-Gupta, Shourya; Dutta-Gupta, Aparna
Development of insect resistance to biopesticides is a current and pertinent global issue. Earlier, it was established that lepidopteran larvae can recover from Bt intoxication via a midgut regenerative response and subsequently generate resistance. Molecular aspects of restoration of the midgut integrity following toxin exposure are emerging recently. In the present study, we bring out the pivotal role of gut arylphorin in mediating the midgut regenerative response following sublethal Bt exposure in Achaea janata. Bt-induced midgut damage was characterized by microscopic analysis using differential interference contrast (DIC) and immunofluorescence (IF). Extensive disruption of brush-border membrane, associated with the underlying cytoskeletal alterations including F-actin, ?-actin and ?-tubulin was observed. Single-photon fluorescence microscopy combined with fluorescence lifetime imaging (FLIM) established the metabolic state associated with enhanced stem cell proliferation and migration from the basal side towards the luminal side following the damage. In-silico analysis revealed the phylogenetic relationship of gut arylphorin with closely related insect species and indicated the presence of two different subunits. Transient RNAi knockdown of the arylphorin resulted in diminished expression of mitotic Cyclin B mRNA levels. Human monoclonal Cyclin B antibody cross-reactivity with the Cyclin B located in the stem cells further validate the role of arylphorin as the mitogenic factor responsible for stem cell proliferation and epithelial regeneration. An in-depth understanding of resistance mechanisms will aid in the design of new strategies for the long-term usage and efficacy of Bt technology against pest control. � 2021
Midgut aminopeptidase N expression profile in castor semilooper (Achaea janata) during sublethal Cry toxin exposure
(Springer, 2021-03-19T00:00:00) Chauhan, Vinod K.; Dhania, Narender K.; Lokya, Vadthya; Bhuvanachandra, Bhoopal; Padmasree, Kollipara; Dutta-Gupta, Aparna
The midgut of lepidopteran larvae is a multifunctional tissue that performs roles in digestion, absorption, immunity, transmission of pathogens and interaction with ingested various molecules. The proteins localized at the inner apical brush border membrane are primarily digestive proteases, but some of them, like aminopeptidase N, alkaline phosphatase, cadherins, ABC transporter C2, etc., interact with Crystal (Cry) toxins produced by Bacillus thuringiensis (Bt). In the present study, aminopeptidase N (APN) was characterized as Cry-toxin-interacting protein in the larval midgut of castor semilooper, Achaea janata. Transcriptomic and proteomic analyses revealed the presence of multiple isoforms of APNs (APN1, 2, 4, 6 and 9) which have less than 40% sequence similarity but show the presence of characteristic �GAMENEG� and zinc-binding motifs. Feeding a sublethal dose of Cry toxin caused differential expression of various APN isoform. Further, 6th-generation Cry-toxin-exposed larvae showed reduced expression of APN2. This report suggests that A. janata larvae exploit altered expression of APNs to overcome the deleterious effects of Cry toxicity, which might facilitate toxin tolerance in the long run. � 2021, Indian Academy of Sciences.