Dilip Shah - Academia.edu (original) (raw)
Papers by Dilip Shah
Paint Coatings Industry, 2003
Paint Coatings Industry, Apr 1, 2004
Molecular Microbiology 2014 92 1357 74, Apr 1, 2014
MsDef1 and MtDef4 from Medicago spp. are small cysteine-rich defensins with potent antifungal act... more MsDef1 and MtDef4 from Medicago spp. are small cysteine-rich defensins with potent antifungal activity against a broad range of filamentous fungi. Each defensin has a hallmark γ-core motif (GXCX(3-9) C), which contains major determinants of its antifungal activity. In this study, the antifungal activities of MsDef1, MtDef4, and peptides derived from their γ-core motifs, were characterized during colony initiation in the fungal model, Neurospora crassa. These defensins and their cognate peptides inhibited conidial germination and accompanying cell fusion with different potencies. The inhibitory effects of MsDef1 were strongly mediated by the plasma membrane localized sphingolipid glucosylceramide. Cell fusion was selectively inhibited by the hexapeptide RGFRRR derived from the γ-core motif of MtDef4. Fluorescent labelling of this hexapeptide showed that it strongly bound to the germ tube plasma membrane/cell wall. Using N. crassa expressing the Ca(2+) reporter aequorin, MsDef1, MtDef4 and their cognate peptides were each shown to perturb Ca(2+) homeostasis in specific and distinct ways, and the disruptive effects of MsDef1 on Ca(2+) were mediated by glucosylceramide. Together, our results demonstrate that MsDef1 and MtDef4 differ markedly in their antifungal properties and specific domains within their γ-core motifs play important roles in their different modes of antifungal action.
The Embo Journal, May 1, 1987
A chimeric gene encoding the alfalfa mosaic virus (AlMV) coat protein was constructed and introdu... more A chimeric gene encoding the alfalfa mosaic virus (AlMV) coat protein was constructed and introduced into tobacco and tomato plants using Ti plasmid-derived plant transformation vectors. The progeny of the self-fertilized transgenic plants were significantly delayed in symptom development and in some cases completely escaped infection after inoculated with AlMV. The inoculated leaves of the transgenic plants had significantly reduced numbers of lesions and accumulated substantially lower amounts of coat protein due to virus replication than the control plants. These results show that high level expression of the chimeric viral coat protein gene confers protection against AlMV, which differs from other plant viruses in morphology, genome structure, gene expression strategy and early steps in viral replication. Based on our results with AlMV and those reported earlier for tobacco mosaic virus, it appears that genetically engineered cross-protection may be a general method for preventing viral disease in plants.
American Journal of Respiratory Cell and Molecular Biology, Jun 18, 2014
Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung dise... more Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. While alcoholism has been shown to alter hepatic metabolism leading to lipid accumulation, hepatitis, and eventually cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II (AEII) cells and alveolar macrophages in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMPactivated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids. Further, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triacylglycerides and free fatty acids within distal airspaces, alveolar macrophages, and to a lesser extent, AEII cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in fatty acids alter alveolar macrophage phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and/or treating alcoholrelated pulmonary disorders.
The Journal of Immunology, May 1, 2012
ABSTRACT Skin has been considered an attractive site for vaccine delivery for more than 3000 year... more ABSTRACT Skin has been considered an attractive site for vaccine delivery for more than 3000 years, but it is still not commonly used today, because of technical difficulties and a lack of inflammation-free adjuvant. Considerable progress made in generating convenient intradermal (i.d.) injection devices in the past decade raises an urgent need of developing potent vaccine adjuvants that introduce little skin inflammation. Many current vaccine adjuvants cause severe skin inflammation that jeopardizes the integrity of the skin and thus cannot be accepted for cutaneous vaccination. We develop a laser-based vaccine adjuvant (LVA) capable of boosting immune responses without incurring inflammation. LVA was induced by brief (2 min) illumination of a small area of the skin with a safe laser prior to i.d. administration of vaccines at the site of laser illumination. The pre-illumination augmented the hemagglutination inhibition (HAI) titers against seasonal or 2009-pandemic influenza vaccine by 10~20-folds when compared to i.m. immunization. And, while i.d. immunization blocked viral production in the lung by 2-fold over i.m. vaccination, i.d. immunization after laser illumination increased the blockade to 186-fold. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is a risk- and additive-free adjuvant and has distinct advantages over traditional vaccine adjuvants for cutaneous vaccination.
Nature Biotechnology, 2000
Defensins are small cysteine-rich peptides with antimicrobial activity. We demonstrate that the a... more Defensins are small cysteine-rich peptides with antimicrobial activity. We demonstrate that the alfalfa antifungal peptide (alfAFP) defensin isolated from seeds of Medicago sativa displays strong activity against the agronomically important fungal pathogen Verticillium dahliae. Expression of the alfAFP peptide in transgenic potato plants provides robust resistance in the greenhouse. Importantly, this resistance is maintained under field conditions. There have been no previous demonstrations of a single transgene imparting a disease resistance phenotype that is at least equivalent to those achieved through current practices using fumigants.
Reactive Oxygen Species in Biology and Human Health, 2016
Plast Reconstr Surg, 1979
Paint Coatings Industry, 2003
Paint Coatings Industry, Apr 1, 2004
Molecular Microbiology 2014 92 1357 74, Apr 1, 2014
MsDef1 and MtDef4 from Medicago spp. are small cysteine-rich defensins with potent antifungal act... more MsDef1 and MtDef4 from Medicago spp. are small cysteine-rich defensins with potent antifungal activity against a broad range of filamentous fungi. Each defensin has a hallmark γ-core motif (GXCX(3-9) C), which contains major determinants of its antifungal activity. In this study, the antifungal activities of MsDef1, MtDef4, and peptides derived from their γ-core motifs, were characterized during colony initiation in the fungal model, Neurospora crassa. These defensins and their cognate peptides inhibited conidial germination and accompanying cell fusion with different potencies. The inhibitory effects of MsDef1 were strongly mediated by the plasma membrane localized sphingolipid glucosylceramide. Cell fusion was selectively inhibited by the hexapeptide RGFRRR derived from the γ-core motif of MtDef4. Fluorescent labelling of this hexapeptide showed that it strongly bound to the germ tube plasma membrane/cell wall. Using N. crassa expressing the Ca(2+) reporter aequorin, MsDef1, MtDef4 and their cognate peptides were each shown to perturb Ca(2+) homeostasis in specific and distinct ways, and the disruptive effects of MsDef1 on Ca(2+) were mediated by glucosylceramide. Together, our results demonstrate that MsDef1 and MtDef4 differ markedly in their antifungal properties and specific domains within their γ-core motifs play important roles in their different modes of antifungal action.
The Embo Journal, May 1, 1987
A chimeric gene encoding the alfalfa mosaic virus (AlMV) coat protein was constructed and introdu... more A chimeric gene encoding the alfalfa mosaic virus (AlMV) coat protein was constructed and introduced into tobacco and tomato plants using Ti plasmid-derived plant transformation vectors. The progeny of the self-fertilized transgenic plants were significantly delayed in symptom development and in some cases completely escaped infection after inoculated with AlMV. The inoculated leaves of the transgenic plants had significantly reduced numbers of lesions and accumulated substantially lower amounts of coat protein due to virus replication than the control plants. These results show that high level expression of the chimeric viral coat protein gene confers protection against AlMV, which differs from other plant viruses in morphology, genome structure, gene expression strategy and early steps in viral replication. Based on our results with AlMV and those reported earlier for tobacco mosaic virus, it appears that genetically engineered cross-protection may be a general method for preventing viral disease in plants.
American Journal of Respiratory Cell and Molecular Biology, Jun 18, 2014
Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung dise... more Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. While alcoholism has been shown to alter hepatic metabolism leading to lipid accumulation, hepatitis, and eventually cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II (AEII) cells and alveolar macrophages in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMPactivated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids. Further, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triacylglycerides and free fatty acids within distal airspaces, alveolar macrophages, and to a lesser extent, AEII cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in fatty acids alter alveolar macrophage phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and/or treating alcoholrelated pulmonary disorders.
The Journal of Immunology, May 1, 2012
ABSTRACT Skin has been considered an attractive site for vaccine delivery for more than 3000 year... more ABSTRACT Skin has been considered an attractive site for vaccine delivery for more than 3000 years, but it is still not commonly used today, because of technical difficulties and a lack of inflammation-free adjuvant. Considerable progress made in generating convenient intradermal (i.d.) injection devices in the past decade raises an urgent need of developing potent vaccine adjuvants that introduce little skin inflammation. Many current vaccine adjuvants cause severe skin inflammation that jeopardizes the integrity of the skin and thus cannot be accepted for cutaneous vaccination. We develop a laser-based vaccine adjuvant (LVA) capable of boosting immune responses without incurring inflammation. LVA was induced by brief (2 min) illumination of a small area of the skin with a safe laser prior to i.d. administration of vaccines at the site of laser illumination. The pre-illumination augmented the hemagglutination inhibition (HAI) titers against seasonal or 2009-pandemic influenza vaccine by 10~20-folds when compared to i.m. immunization. And, while i.d. immunization blocked viral production in the lung by 2-fold over i.m. vaccination, i.d. immunization after laser illumination increased the blockade to 186-fold. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is a risk- and additive-free adjuvant and has distinct advantages over traditional vaccine adjuvants for cutaneous vaccination.
Nature Biotechnology, 2000
Defensins are small cysteine-rich peptides with antimicrobial activity. We demonstrate that the a... more Defensins are small cysteine-rich peptides with antimicrobial activity. We demonstrate that the alfalfa antifungal peptide (alfAFP) defensin isolated from seeds of Medicago sativa displays strong activity against the agronomically important fungal pathogen Verticillium dahliae. Expression of the alfAFP peptide in transgenic potato plants provides robust resistance in the greenhouse. Importantly, this resistance is maintained under field conditions. There have been no previous demonstrations of a single transgene imparting a disease resistance phenotype that is at least equivalent to those achieved through current practices using fumigants.
Reactive Oxygen Species in Biology and Human Health, 2016
Plast Reconstr Surg, 1979