The host response to influenza A infections is strongly influenced by host genetic factors. Anima... more The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection. We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional ...
Genetic differences in gene expression contribute significantly to phenotypic diversity and diffe... more Genetic differences in gene expression contribute significantly to phenotypic diversity and differences in disease susceptibility. In fact, the great majority of causal variants highlighted by genome-wide association are in non-coding regions that modulate expression. In order to quantify the extent of allelic differences in expression, we analyzed liver transcriptomes of isogenic F1 hybrid mice. Allele-specific expression (ASE) effects are pervasive and are detected in over 50% of assayed genes. Genes with strong ASE do not differ from those with no ASE with respect to their length or promoter complexity. However, they have a higher density of sequence variants, higher functional redundancy, and lower evolutionary conservation compared to genes with no ASE. Fifty percent of genes with no ASE are categorized as house-keeping genes. In contrast, the high ASE set may be critical in phenotype canalization. There is significant overlap between genes that exhibit ASE and those that exhib...
The focus of this paper is to locating the precise position of strain gauge on the sensor's s... more The focus of this paper is to locating the precise position of strain gauge on the sensor's substrate using geometrical parameters of the substrate. We used the program Autodesk Simulation Multiphysics 2012 student edition for modeling and finite element analysis. A specific cantilever sensor's substrate was selected and for optimization of position of strain gauge was studied. The von mises stress along centre line distance is compared against change in geometrical parameter of the substrate. The results show that the variation of stress due to geometrical change and suggesting the optimum position of strain gauge on the sensor's substrate for good sensitivity of the conversional sensors.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, Jan 2, 2015
The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug... more The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug delivery, food packaging and as anticancerous agents has increased the risk of human exposure to these NPs. Earlier in vitro and in vivo studies have demonstrated a cytotoxic and genotoxic potential of ZnO NPs. However, there is paucity of data regarding their immunomodulatory effects. Therefore, the present study was aimed to investigate the immunotoxic potential of ZnO NPs using human monocytic cell line (THP-1) as model to understand the underlying molecular mechanism. A significant (p < 0.01) increase in pro-inflammatory cytokines (TNF-α and IL-1β) and reactive oxygen species (ROS) was observed with a concomitant concentration dependent (0.5, 1, 5, 10, 15 and 20 μg/mL) decrease in the glutathione (GSH) levels as compared to control. The expression levels of mitogen activated protein kinase (MAPK) cascade proteins such as p-ERK1/2, p-p38 and p-JNK were also significantly (p < 0...
Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cos... more Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the performance of the MethylMiner was deemed poor. Given our positive experience with MethylMiner, we were surprised by this report. In an attempt to reproduce these findings we here have performed a direct comparison of MethylMiner with MethylCap (Diag...
West Pak[istan] dominated government’ (75). It further claimed that the American government had e... more West Pak[istan] dominated government’ (75). It further claimed that the American government had evidenced ‘moral bankruptcy, ironically at a time when the USSR sent President Yahya a message defending democracy’ (75). Nixon and Kissinger silenced Blood by calling him back to Washington and continued to neglect the killing, pretending to be ‘smart enough to stay the hell out of that’ (107). Bass reveals that the reason why Nixon and Kissinger ignored the bloodshed with a deafening silence, thus appeasing General Yahya Khan, was because the latter was working as their secret liaison to China. Disgusted by the hypocritical misuse of General Yahya’s vulnerability merely to accomplish their goal of fostering their relationship with China, Bass writes, ‘it is absolutely right that the normalization of the American relationship with China stands as an epochal event, but those who justifiably want to celebrate it should not overlook what it meant for the Bengalis and Indians’ (xv). Bass gives due credit to Indira Gandhi, the then Indian prime minister, for her efforts in providing shelter to the 10 million Bengali refugees, in training Bengali freedom fighters, and in midwifing the birth of Bangladesh by launching a military offensive against the Pakistani army. He also exposes how Nixon, who put a lot of effort into burnishing his image as a great statesman after a disgraceful exit from the White House, dealt with India during the conflict on the basis of his personal contempt for Indira Gandhi, whom he had called ‘the old bitch’ (252), rather than on political strategy. Focusing his research extensively on American sources and sparingly on Bangladeshi and Pakistani, the author is more interested in tarnishing the images of Nixon and Kissinger as villains and glorifying that of Archer Blood as a tragic hero of American foreign policy than with telling the horrific narrative of the birth of Bangladesh. Despite this, the book is an essential read for scholars and general readers interested in the 1971 conflict and the American diplomatic engagement in South Asia during the Cold War. The recent conviction of some of the former Pakistani army collaborators, after a four-decade long wait for justice, has heralded renewed interest in the 1971 conflict as a topic of academic and literary intervention by Bangladeshi as well as foreign scholars and writers. The Blood telegram stands out as one of the most riveting and accomplished of contemporary books on the topic.
Long-term exposure to dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP), an organophosp... more Long-term exposure to dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP), an organophosphate pesticide) is reported to exert neurotoxicity, i.e., generation of reactive oxygen species (ROS), oxidative damage, and neuronal cell death along with life- and health-span reduction in nontarget organisms including humans. However, studies on genetic modulation towards neuroprotection against prolonged DDVP exposure are elusive. Hsp27 (a small heat shock protein) is involved in various cellular processes and thus has attained emphasis as a therapeutic target. We aimed to examine the protective effect of hsp27 overexpression against prolonged DDVP exposure using an in vivo model Drosophila melanogaster. Flies were exposed to 15.0 ng/ml DDVP for a prolonged period to examine neuronal cell death, locomotor performance, and lifespan. After prolonged exposure, cell death, ROS level, glutathione depletion, nicotinamide adenine dinucleotide phosphate level (NADPH), glucose-6-phosphate dehydrogenase (G6PD), and thioredoxin reductase (TrxR) activities were examined in fly brain tissues at different days of age (days 10, 20, and 30). Flies with ubiquitous overexpression of hsp27 showed better resistance (improved lifespan and locomotor performance) in comparison to that targeted to motor neurons and nervous system. These flies also exhibited lesser intracellular ROS level and glutathione depletion by restoring G6PD activity, NADPH level, and TrxR activity in their brains thereby resisted neuronal cell death. Conversely, hsp27 knockdown flies exhibited reversal of the above endpoints. The study evidenced the neuroprotective efficacy of hsp27 overexpression against prolonged DDVP exposure and favored Hsp27 as a therapeutic target towards achieving better organismal (including human) health against long-term chemical exposure.
Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hep... more Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). Immunohistochemistry of archived HCC tumors showed abundant FBP1 expression in HCC tumors with CHC background. Oncomine data analysis of normal versus HCC tumors with CHC background indicated a 4-fold increase in FBP1 expression with a concomitant 2.5-fold decrease in the expression of p53. We found that FBP1 promotes HCV replication by inhibiting p53, and regulating BCCIP and TCTP, which, respectively, are positive and negative regulators of p53. The severe inhibition of HCV replication in FBP1-knockdown Huh7.5 cells was restored to a normal level by downregulation of either p53 or BCCIP. Although p53 in Huh7.5 cells is transcriptionally inactive as a result of Y220C mutation, we found that activation and DNA binding ability of Y220C p53 were strongly suppressed by FBP1, but significantly activated upon knockdown of FBP1. Transient expression of FBP1 in FBP1...
Apoptosis : an international journal on programmed cell death, Jan 10, 2015
Apoptosis causes elimination of more than 99 % of germ cells from cohort of ovary through follicu... more Apoptosis causes elimination of more than 99 % of germ cells from cohort of ovary through follicular atresia. Less than 1 % of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic…
Computational and structural biotechnology journal, 2015
Sumoylation is a reversible post-translational modification that involves the covalent attachment... more Sumoylation is a reversible post-translational modification that involves the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to their substrate proteins. Prior to their conjugation, SUMO proteins need to be proteolytically processed from its precursor form to mature or active form. SUMO specific proteases (SENPs) are cysteine proteases that cleave the pro or inactive form of SUMO at C-terminus using its hydrolase activity to expose two glycine residues. SENPs also catalyze the de-conjugation of SUMO proteins using their isopeptidase activity, which is crucial for recycling of SUMO from substrate proteins. SENPs are important for maintaining the balance between sumoylated and unsumoylated proteins required for normal cellular physiology. Several studies reported the overexpression of SENPs in disease conditions and highlighted their role in the development of various diseases, especially cancer. In this review, we will address the current biological understandin...
The host response to influenza A infections is strongly influenced by host genetic factors. Anima... more The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection. We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional ...
Genetic differences in gene expression contribute significantly to phenotypic diversity and diffe... more Genetic differences in gene expression contribute significantly to phenotypic diversity and differences in disease susceptibility. In fact, the great majority of causal variants highlighted by genome-wide association are in non-coding regions that modulate expression. In order to quantify the extent of allelic differences in expression, we analyzed liver transcriptomes of isogenic F1 hybrid mice. Allele-specific expression (ASE) effects are pervasive and are detected in over 50% of assayed genes. Genes with strong ASE do not differ from those with no ASE with respect to their length or promoter complexity. However, they have a higher density of sequence variants, higher functional redundancy, and lower evolutionary conservation compared to genes with no ASE. Fifty percent of genes with no ASE are categorized as house-keeping genes. In contrast, the high ASE set may be critical in phenotype canalization. There is significant overlap between genes that exhibit ASE and those that exhib...
The focus of this paper is to locating the precise position of strain gauge on the sensor's s... more The focus of this paper is to locating the precise position of strain gauge on the sensor's substrate using geometrical parameters of the substrate. We used the program Autodesk Simulation Multiphysics 2012 student edition for modeling and finite element analysis. A specific cantilever sensor's substrate was selected and for optimization of position of strain gauge was studied. The von mises stress along centre line distance is compared against change in geometrical parameter of the substrate. The results show that the variation of stress due to geometrical change and suggesting the optimum position of strain gauge on the sensor's substrate for good sensitivity of the conversional sensors.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, Jan 2, 2015
The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug... more The wide application of zinc oxide nanoparticles (ZnO NPs) in cosmetics, paints, biosensors, drug delivery, food packaging and as anticancerous agents has increased the risk of human exposure to these NPs. Earlier in vitro and in vivo studies have demonstrated a cytotoxic and genotoxic potential of ZnO NPs. However, there is paucity of data regarding their immunomodulatory effects. Therefore, the present study was aimed to investigate the immunotoxic potential of ZnO NPs using human monocytic cell line (THP-1) as model to understand the underlying molecular mechanism. A significant (p < 0.01) increase in pro-inflammatory cytokines (TNF-α and IL-1β) and reactive oxygen species (ROS) was observed with a concomitant concentration dependent (0.5, 1, 5, 10, 15 and 20 μg/mL) decrease in the glutathione (GSH) levels as compared to control. The expression levels of mitogen activated protein kinase (MAPK) cascade proteins such as p-ERK1/2, p-p38 and p-JNK were also significantly (p < 0...
Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cos... more Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the performance of the MethylMiner was deemed poor. Given our positive experience with MethylMiner, we were surprised by this report. In an attempt to reproduce these findings we here have performed a direct comparison of MethylMiner with MethylCap (Diag...
West Pak[istan] dominated government’ (75). It further claimed that the American government had e... more West Pak[istan] dominated government’ (75). It further claimed that the American government had evidenced ‘moral bankruptcy, ironically at a time when the USSR sent President Yahya a message defending democracy’ (75). Nixon and Kissinger silenced Blood by calling him back to Washington and continued to neglect the killing, pretending to be ‘smart enough to stay the hell out of that’ (107). Bass reveals that the reason why Nixon and Kissinger ignored the bloodshed with a deafening silence, thus appeasing General Yahya Khan, was because the latter was working as their secret liaison to China. Disgusted by the hypocritical misuse of General Yahya’s vulnerability merely to accomplish their goal of fostering their relationship with China, Bass writes, ‘it is absolutely right that the normalization of the American relationship with China stands as an epochal event, but those who justifiably want to celebrate it should not overlook what it meant for the Bengalis and Indians’ (xv). Bass gives due credit to Indira Gandhi, the then Indian prime minister, for her efforts in providing shelter to the 10 million Bengali refugees, in training Bengali freedom fighters, and in midwifing the birth of Bangladesh by launching a military offensive against the Pakistani army. He also exposes how Nixon, who put a lot of effort into burnishing his image as a great statesman after a disgraceful exit from the White House, dealt with India during the conflict on the basis of his personal contempt for Indira Gandhi, whom he had called ‘the old bitch’ (252), rather than on political strategy. Focusing his research extensively on American sources and sparingly on Bangladeshi and Pakistani, the author is more interested in tarnishing the images of Nixon and Kissinger as villains and glorifying that of Archer Blood as a tragic hero of American foreign policy than with telling the horrific narrative of the birth of Bangladesh. Despite this, the book is an essential read for scholars and general readers interested in the 1971 conflict and the American diplomatic engagement in South Asia during the Cold War. The recent conviction of some of the former Pakistani army collaborators, after a four-decade long wait for justice, has heralded renewed interest in the 1971 conflict as a topic of academic and literary intervention by Bangladeshi as well as foreign scholars and writers. The Blood telegram stands out as one of the most riveting and accomplished of contemporary books on the topic.
Long-term exposure to dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP), an organophosp... more Long-term exposure to dichlorvos (O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP), an organophosphate pesticide) is reported to exert neurotoxicity, i.e., generation of reactive oxygen species (ROS), oxidative damage, and neuronal cell death along with life- and health-span reduction in nontarget organisms including humans. However, studies on genetic modulation towards neuroprotection against prolonged DDVP exposure are elusive. Hsp27 (a small heat shock protein) is involved in various cellular processes and thus has attained emphasis as a therapeutic target. We aimed to examine the protective effect of hsp27 overexpression against prolonged DDVP exposure using an in vivo model Drosophila melanogaster. Flies were exposed to 15.0 ng/ml DDVP for a prolonged period to examine neuronal cell death, locomotor performance, and lifespan. After prolonged exposure, cell death, ROS level, glutathione depletion, nicotinamide adenine dinucleotide phosphate level (NADPH), glucose-6-phosphate dehydrogenase (G6PD), and thioredoxin reductase (TrxR) activities were examined in fly brain tissues at different days of age (days 10, 20, and 30). Flies with ubiquitous overexpression of hsp27 showed better resistance (improved lifespan and locomotor performance) in comparison to that targeted to motor neurons and nervous system. These flies also exhibited lesser intracellular ROS level and glutathione depletion by restoring G6PD activity, NADPH level, and TrxR activity in their brains thereby resisted neuronal cell death. Conversely, hsp27 knockdown flies exhibited reversal of the above endpoints. The study evidenced the neuroprotective efficacy of hsp27 overexpression against prolonged DDVP exposure and favored Hsp27 as a therapeutic target towards achieving better organismal (including human) health against long-term chemical exposure.
Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hep... more Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). Immunohistochemistry of archived HCC tumors showed abundant FBP1 expression in HCC tumors with CHC background. Oncomine data analysis of normal versus HCC tumors with CHC background indicated a 4-fold increase in FBP1 expression with a concomitant 2.5-fold decrease in the expression of p53. We found that FBP1 promotes HCV replication by inhibiting p53, and regulating BCCIP and TCTP, which, respectively, are positive and negative regulators of p53. The severe inhibition of HCV replication in FBP1-knockdown Huh7.5 cells was restored to a normal level by downregulation of either p53 or BCCIP. Although p53 in Huh7.5 cells is transcriptionally inactive as a result of Y220C mutation, we found that activation and DNA binding ability of Y220C p53 were strongly suppressed by FBP1, but significantly activated upon knockdown of FBP1. Transient expression of FBP1 in FBP1...
Apoptosis : an international journal on programmed cell death, Jan 10, 2015
Apoptosis causes elimination of more than 99 % of germ cells from cohort of ovary through follicu... more Apoptosis causes elimination of more than 99 % of germ cells from cohort of ovary through follicular atresia. Less than 1 % of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic…
Computational and structural biotechnology journal, 2015
Sumoylation is a reversible post-translational modification that involves the covalent attachment... more Sumoylation is a reversible post-translational modification that involves the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to their substrate proteins. Prior to their conjugation, SUMO proteins need to be proteolytically processed from its precursor form to mature or active form. SUMO specific proteases (SENPs) are cysteine proteases that cleave the pro or inactive form of SUMO at C-terminus using its hydrolase activity to expose two glycine residues. SENPs also catalyze the de-conjugation of SUMO proteins using their isopeptidase activity, which is crucial for recycling of SUMO from substrate proteins. SENPs are important for maintaining the balance between sumoylated and unsumoylated proteins required for normal cellular physiology. Several studies reported the overexpression of SENPs in disease conditions and highlighted their role in the development of various diseases, especially cancer. In this review, we will address the current biological understandin...
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Papers by Ashutosh Pandey