Mickey Sharma | National Institute of Advanced Studies (original) (raw)

Papers by Mickey Sharma

Experimental Biology and Medicine, 2009

Acute lung injury (ALI) has been documented clinically following several pathological states such... more Acute lung injury (ALI) has been documented clinically following several pathological states such as trauma, septic shock and pneumonia. The histopathological characteristics, paired with the production of a number of cellular pro-inflammatory mediators, play a crucial role in the progression of ALI. During ALI, polymorphonuclear neutrophil (PMN)-mediated apoptosis is delayed by macrophages, possibly via effects on the Fas/FasL mediated pathway, leading to the accumulation of these cells at the site of injury and inflammation. The transcriptional regulation of NFjB, CREB, and AP-1 also regulates the pathogenesis of ALI. During sepsis and septic shock, we found evidence of infiltrating leukocytes in the alveolar spaces along with an increased number of TUNEL-positive cells in the lung sections. We also observed an increased expression of TRADD and Bax/ Bcl 2 ratio at 7 days post-sepsis. In contrast, the NFjB/IjB ratio increased at 1 day post-sepsis. Together, these data provide evidence illustrating the induction of apoptosis in lung tissues subsequent to the onset of polymicrobial sepsis. The results support the concept that the upregulation of apoptosis following lung inflammation plays a crucial role in the development of acute lung injury and related disorders such as ARDS.

Transplantation, 1975

Contrary to previous reports, human granulocytes are capable of causing transformation of allogen... more Contrary to previous reports, human granulocytes are capable of causing transformation of allogeneic lymphocytes. Pretreatment of granulocytes with mitomycin C results in nonstimulation, but untreated granulocytes are capable of stimulating lymphocytes. Nonstimulation with mitomycin C-treated granulocytes may result from the reduced viability of the cells. It is concluded that granulocytes possess alloantigens that stimulate lymphocytes in vitro.

This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research p... more This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research partnership between IBM and the Lawrence Livermore National Laboratory as part of the United States Department of Energy ASCI Advanced Architecture Research Program. Application performance and scaling studies have recently been initiated with partners at a number of academic and government institutions, including the San Diego Supercomputer Center and the California Institute of Technology. This massively parallel system of 65,536 nodes is based on a new architecture that exploits system-on-a-chip technology to deliver target peak processing power of 360 teraFLOPS (trillion floating-point operations per second). The machine is scheduled to be operational in the 2004-2005 time frame, at price/performance and power consumption/performance targets unobtainable with conventional architectures.

Tissue Antigens, 1978

The frequencies of HLA antigens were determined in 32 black sarcoidosis patients and in 89 normal... more The frequencies of HLA antigens were determined in 32 black sarcoidosis patients and in 89 normal black controls. Aw23 was found in 23.6% of controls as compared with a lower frequency (6.2%) in patients (P= 0.06). No other associations were found.

This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research p... more This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research partnership between IBM and the Lawrence Livermore National Laboratory as part of the United States Department of Energy ASCI Advanced Architecture Research Program. Application performance and scaling studies have recently been initiated with partners at a number of academic and government institutions, including the San Diego Supercomputer Center and the California Institute of Technology. This massively parallel system of 65,536 nodes is based on a new architecture that exploits system-on-a-chip technology to deliver target peak processing power of 360 teraFLOPS (trillion floating-point operations per second). The machine is scheduled to be operational in the 2004-2005 time frame, at price/performance and power consumption/performance targets unobtainable with conventional architectures.

Plant Methods, 2010

Background TILLING (Targeting Induced Local Lesions in Genomes) is a reverse genetics procedure f... more Background TILLING (Targeting Induced Local Lesions in Genomes) is a reverse genetics procedure for identifying point mutations in selected gene(s) amplified from a mutagenized population using high-throughput detection platforms such as slab gel electrophoresis, capillary electrophoresis or dHPLC. One essential pre-requisite for TILLING is genomic DNA isolation from a large population for PCR amplification of selected target genes. It also requires multiplexing of genomic DNA isolated from different individuals (pooling) in typically 8-fold pools, for mutation scanning, and to minimize the number of PCR amplifications, which is a strenuous and long-drawn-out work. We describe here a simplified procedure of multiplexing, NEATTILL (Nucleic acid Extraction from Arrayed Tissue for TILLING), which is rapid and equally efficient in assisting mutation detection. Results The NEATTILL procedure was evaluated for the tomato TILLING platform and was found to be simpler and more efficient than previously available methods. The procedure consisted of pooling tissue samples, instead of nucleic acid, from individual plants in 96-well plates, followed by DNA isolation from the arrayed samples by a novel protocol. The three variants of the NEATTILL procedure (vast, in-depth and intermediate) can be applied across various genomes depending upon the population size of the TILLING platform. The 2-D pooling ensures the precise confirmation of the coordinates of the positive mutant line while scanning complementary plates. Choice of tissue for arraying and nucleic acid isolation is discussed in detail with reference to tomato. Conclusion NEATTILL is a convenient procedure that can be applied to all organisms, the genomes of which have been mutagenized and are being scanned for multiple alleles of various genes by TILLING for understanding gene-to-phenotype relationships. It is a time-saving, less labour intensive and reasonably cost-effective method. Tissue arraying can cut costs by up to 90% and minimizes the risk of exposing the DNA to nucleases. Before arraying, different tissues should be evaluated for DNA quality, as the case study in tomato showed that cotyledons rather than leaves are better suited for DNA isolation. The protocol described here for nucleic acid isolation can be generally adapted for large-scale projects such as insertional mutagenesis, transgenic confirmation, mapping and fingerprinting which require isolation of DNA from large populations.

Water bacteria" is a loose term used to describe bacteria which are frequently found in water. Th... more Water bacteria" is a loose term used to describe bacteria which are frequently found in water. There are several major categories:

Experimental Biology and Medicine, 2009

Acute lung injury (ALI) has been documented clinically following several pathological states such... more Acute lung injury (ALI) has been documented clinically following several pathological states such as trauma, septic shock and pneumonia. The histopathological characteristics, paired with the production of a number of cellular pro-inflammatory mediators, play a crucial role in the progression of ALI. During ALI, polymorphonuclear neutrophil (PMN)-mediated apoptosis is delayed by macrophages, possibly via effects on the Fas/FasL mediated pathway, leading to the accumulation of these cells at the site of injury and inflammation. The transcriptional regulation of NFjB, CREB, and AP-1 also regulates the pathogenesis of ALI. During sepsis and septic shock, we found evidence of infiltrating leukocytes in the alveolar spaces along with an increased number of TUNEL-positive cells in the lung sections. We also observed an increased expression of TRADD and Bax/ Bcl 2 ratio at 7 days post-sepsis. In contrast, the NFjB/IjB ratio increased at 1 day post-sepsis. Together, these data provide evidence illustrating the induction of apoptosis in lung tissues subsequent to the onset of polymicrobial sepsis. The results support the concept that the upregulation of apoptosis following lung inflammation plays a crucial role in the development of acute lung injury and related disorders such as ARDS.

Transplantation, 1975

Contrary to previous reports, human granulocytes are capable of causing transformation of allogen... more Contrary to previous reports, human granulocytes are capable of causing transformation of allogeneic lymphocytes. Pretreatment of granulocytes with mitomycin C results in nonstimulation, but untreated granulocytes are capable of stimulating lymphocytes. Nonstimulation with mitomycin C-treated granulocytes may result from the reduced viability of the cells. It is concluded that granulocytes possess alloantigens that stimulate lymphocytes in vitro.

This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research p... more This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research partnership between IBM and the Lawrence Livermore National Laboratory as part of the United States Department of Energy ASCI Advanced Architecture Research Program. Application performance and scaling studies have recently been initiated with partners at a number of academic and government institutions, including the San Diego Supercomputer Center and the California Institute of Technology. This massively parallel system of 65,536 nodes is based on a new architecture that exploits system-on-a-chip technology to deliver target peak processing power of 360 teraFLOPS (trillion floating-point operations per second). The machine is scheduled to be operational in the 2004-2005 time frame, at price/performance and power consumption/performance targets unobtainable with conventional architectures.

Tissue Antigens, 1978

The frequencies of HLA antigens were determined in 32 black sarcoidosis patients and in 89 normal... more The frequencies of HLA antigens were determined in 32 black sarcoidosis patients and in 89 normal black controls. Aw23 was found in 23.6% of controls as compared with a lower frequency (6.2%) in patients (P= 0.06). No other associations were found.

This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research p... more This paper gives an overview of the BlueGene/L Supercomputer. This is a jointly funded research partnership between IBM and the Lawrence Livermore National Laboratory as part of the United States Department of Energy ASCI Advanced Architecture Research Program. Application performance and scaling studies have recently been initiated with partners at a number of academic and government institutions, including the San Diego Supercomputer Center and the California Institute of Technology. This massively parallel system of 65,536 nodes is based on a new architecture that exploits system-on-a-chip technology to deliver target peak processing power of 360 teraFLOPS (trillion floating-point operations per second). The machine is scheduled to be operational in the 2004-2005 time frame, at price/performance and power consumption/performance targets unobtainable with conventional architectures.

Plant Methods, 2010

Background TILLING (Targeting Induced Local Lesions in Genomes) is a reverse genetics procedure f... more Background TILLING (Targeting Induced Local Lesions in Genomes) is a reverse genetics procedure for identifying point mutations in selected gene(s) amplified from a mutagenized population using high-throughput detection platforms such as slab gel electrophoresis, capillary electrophoresis or dHPLC. One essential pre-requisite for TILLING is genomic DNA isolation from a large population for PCR amplification of selected target genes. It also requires multiplexing of genomic DNA isolated from different individuals (pooling) in typically 8-fold pools, for mutation scanning, and to minimize the number of PCR amplifications, which is a strenuous and long-drawn-out work. We describe here a simplified procedure of multiplexing, NEATTILL (Nucleic acid Extraction from Arrayed Tissue for TILLING), which is rapid and equally efficient in assisting mutation detection. Results The NEATTILL procedure was evaluated for the tomato TILLING platform and was found to be simpler and more efficient than previously available methods. The procedure consisted of pooling tissue samples, instead of nucleic acid, from individual plants in 96-well plates, followed by DNA isolation from the arrayed samples by a novel protocol. The three variants of the NEATTILL procedure (vast, in-depth and intermediate) can be applied across various genomes depending upon the population size of the TILLING platform. The 2-D pooling ensures the precise confirmation of the coordinates of the positive mutant line while scanning complementary plates. Choice of tissue for arraying and nucleic acid isolation is discussed in detail with reference to tomato. Conclusion NEATTILL is a convenient procedure that can be applied to all organisms, the genomes of which have been mutagenized and are being scanned for multiple alleles of various genes by TILLING for understanding gene-to-phenotype relationships. It is a time-saving, less labour intensive and reasonably cost-effective method. Tissue arraying can cut costs by up to 90% and minimizes the risk of exposing the DNA to nucleases. Before arraying, different tissues should be evaluated for DNA quality, as the case study in tomato showed that cotyledons rather than leaves are better suited for DNA isolation. The protocol described here for nucleic acid isolation can be generally adapted for large-scale projects such as insertional mutagenesis, transgenic confirmation, mapping and fingerprinting which require isolation of DNA from large populations.

Water bacteria" is a loose term used to describe bacteria which are frequently found in water. Th... more Water bacteria" is a loose term used to describe bacteria which are frequently found in water. There are several major categories: