Although the precise mechanisms for neurodegeneration in Parkinson’s disease (PD) are unknown, ev... more Although the precise mechanisms for neurodegeneration in Parkinson’s disease (PD) are unknown, evidence suggests that neuroinflammation is a critical factor in the pathogenic process. Here, we sought to determine whether the voltage-gated proton channel, Hv1 (HVCN1), which is expressed in microglia and regulates NADPH oxidase, is associated with dopaminergic neurodegeneration. We utilized data mining to evaluate the mRNA expression of HVCN1 in the brains of PD patients and controls and uncovered increased expression of the gene encoding Hv1, HVCN1, in the brains of PD patients compared to controls, specifically in male PD patients. In an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 4 × 16 mg/kg) mouse model of PD, Hvcn1 gene expression was increased 2-fold in the striatum. MPTP administration to wild-type (WT) mice resulted in a ~65% loss of tyrosine hydroxylase positive neurons (TH+) in the substantia nigra (SN), while a ~39% loss was observed in Hv1 knockout (KO) mice...
Endoplasmic reticulum (ER) stress and neuroinflammation are involved in the pathogenesis of many ... more Endoplasmic reticulum (ER) stress and neuroinflammation are involved in the pathogenesis of many neurodegenerative disorders. Previously, we reported that exposure to pyrethroid insecticide deltamethrin causes hippocampal ER stress apoptosis, a reduction in neurogenesis, and learning deficits in adult male mice. Recently, we found that deltamethrin exposure also increases the markers of neuroinflammation in BV2 cells. Here, we investigated the potential mechanistic link between ER stress and neuroinflammation following exposure to deltamethrin. We found that repeated oral exposure to deltamethrin (3 mg/kg) for 30 days caused microglial activation and increased gene expressions and protein levels of TNF-α, IL-1β, IL-6, gp91phox, 4HNE, and iNOS in the hippocampus. These changes were preceded by the induction of ER stress as the protein levels of CHOP, ATF-4, and GRP78 were significantly increased in the hippocampus. To determine whether induction of ER stress triggers the inflammatory...
Due to routine maintenance of aircraft on the concrete pavement at army airbases, a large part of... more Due to routine maintenance of aircraft on the concrete pavement at army airbases, a large part of the pavement surface is often found saturated with different hydrocarbon-based oil, fuel, and fluid. In addition, the pavement concrete is subjected to the aircraft’s exhaust temperature during operation. This study examined the resistance ability of 3 different cementitious materials: (i) epoxy, (ii) fly ash (FA) based geopolymer with various alkali to fly ash (AL/FA) ratios and (iii) Portland cement (PC) mortar under a simulated airfield circumstance. The mortar specimens were repetitively exposed to a mixture of synthetic engine oil, hydraulic fluids, jet fuel and elevated temperatures (175 °C) for 5 months simultaneously. During the exposures, geopolymer and PC mortar both suffered saponification. The degree of saponification of geopolymer samples is found to be highly reliant on the AL/FA ratios. On the contrary, the epoxy mortar was found to be resistant to saponification. It was ...
Software is ubiquitous, spanning from our everyday life to space station. With a significant incr... more Software is ubiquitous, spanning from our everyday life to space station. With a significant increase in the processing power of modern computing devices, the number of software that deals with sensitive data rises exponentially, providing incentives for performing attacks against these systems. The devices may face various adversarial attacks based on cache side channel, Spectre, Meltdown, Ransomware, buffer and integer overflow, etc. The primary objective of software security is to enhance security in such a way so that software becomes resilient against various malicious attacks during run-time. However, many software-based approaches have been implemented to protect the software from the adversarial attacks. Unfortunately, these techniques cannot provide comprehensive protection as most software vulnerabilities arise not only for the development faults but also for weak hardware architecture. Additionally, software-based approaches may create backdoors for future attacks. Therefore, it is not practical to enhance security only from a software or hardware point of view in a mutually exclusive fashion. This chapter explores various software and hardware vulnerabilities to understand the potential exploitable scenarios better and protect the software from hardware and software perspectives.
This work examines and compares the Malcolm Baldrige National Quality Award (MBNQA) model and the... more This work examines and compares the Malcolm Baldrige National Quality Award (MBNQA) model and the Business Performance Management (BPM) Framework. We use the literature in both areas to posit about the relationships among the two models and to propose a single integrated model. The intent is to provide insight that will allow maintaining organizational MBNQA initiatives while helping to create an agile organization that is capable of developing and increasing competitive advantage.
This study explores the intra-organizational factors and employee job practice area affecting tur... more This study explores the intra-organizational factors and employee job practice area affecting turnover intention. We propose that turnover intention is influenced by two intra-organizational factors, namely, finesse factor and firm factor, and employees’ association to a specific job area. Data were obtained from a diversified multinational company with many job practice areas. The findings suggest that all three factors have significant impact on turnover intention. This implies that the more positively the employees perceive the intra-organizational factors (i.e., the firm and finesse factors) in an organization, the lower their intention to leave the organization. The results also suggest that employees’ associations to various job practice areas have differing significant impact on their intention to leave an organization. For example, employees in the building engineering will have a differing degree of intention to leave the organization compared to those in architecture.
Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis,... more Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3 mg/kg every 3 days for 1 month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure signific...
Over the years, leaked fluids from aircraft have caused severe deterioration of airfield pavement... more Over the years, leaked fluids from aircraft have caused severe deterioration of airfield pavement. The combined effect of hot exhaust from the auxiliary power unit of military aircraft and spilt aviation oils have caused rapid pavement spalling. If the disintegrated concreted pieces caused by spalling are sucked into the jet engine, they may cause catastrophic damage to the aircraft engine or physical injury to maintenance crews. This study investigates the effectiveness of incorporating hybrid fibres into ordinary concrete to improve the residual mechanical and thermal properties to prevent spalling damage of pavement. Three fibre-reinforced concrete samples were made with micro steel fibre and polyvinyl alcohol fibre with a fibre content of zero, 0.3%, 0.5% and 0.7% by volume fraction. These samples were exposed to recurring high temperatures and aviation oils. Tests were conducted to measure the effects of repeated exposure on the concrete’s mechanical, thermal and chemical chara...
Neurotrophins are a family of growth factors crucial for growth and survival of neurons in the de... more Neurotrophins are a family of growth factors crucial for growth and survival of neurons in the developing and adult brain. Reduction in neurotrophin levels is associated with reduced neurogenesis and cognitive deficits in rodents. Recently, we demonstrated that long-term exposure to low levels of the pyrethroid pesticide deltamethrin causes hippocampal endoplasmic reticulum (ER) stress and learning deficits in mice. Here, we found that nerve growth factor (NGF) mRNA and protein were selectively reduced in the hippocampus of deltamethrin-treated mice. To explore potential mechanisms responsible for this observation, we employed mouse primary hippocampal neurons. Exposure of neurons to deltamethrin (1–5 μM) caused ER stress as indicated by increased levels of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 (GRP78). These changes were accompanied by increased levels of caspase-12, activated caspase-3, and decreased levels of NGF. Inhibition of ER stress with the eukary...
Parkinson's disease (PD), the second most common age-related progressive neurodegenerative di... more Parkinson's disease (PD), the second most common age-related progressive neurodegenerative disorder, is characterized by dopamine depletion and the loss of dopaminergic (DA) neurons with accompanying neuroinflammation. Zonisamide is an-anti-convulsant drug that has recently been shown to improve clinical symptoms of PD through its inhibition of monoamine oxidase B (MAO-B). However, zonisamide has additional targets, including voltage-gated sodium channels (Na), which may contribute to its reported neuroprotective role in preclinical models of PD. Here, we report that Na1.6 is highly expressed in microglia of post-mortem PD brain and of mice treated with the parkinsonism-inducing neurotoxin MPTP. Administration of zonisamide (20 mg/kg, i.p. every 4 h × 3) following a single injection of MPTP (12.5 mg/kg, s.c.) reduced microglial Na 1.6 and microglial activation in the striatum, as indicated by Iba-1 staining and mRNA expression of F4/80. MPTP increased the levels of the pro-infla...
The Journal of pharmacology and experimental therapeutics, 2015
Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the... more Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and diquat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both sepiapterin reduction and redox cycling. The most potent inhibitors of sepiapterin reduction (IC50s = 31-180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher concentrations of the sulfa drugs (IC50s = 0.37-19.4 μM) were required to inhibit redox cycling, presu...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 28, 2015
Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age childr... more Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Here, we used behavioral, molecular, and neurochemical techniques to characterize the effects of developmental exposure to the pyrethroid pesticide deltamethrin. We also used epidemiologic methods to determine whether there is an association between pyrethroid exposure and diagnosis of ADHD. Mice exposed to the pyrethroid pesticide deltamethrin during development exhibit several features reminiscent of ADHD, including elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased DAT and D1 dopamine receptor levels appear to be responsible for the behavioral deficits. Epidemiologic data reveal that...
The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combi... more The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the ...
Although the precise mechanisms for neurodegeneration in Parkinson’s disease (PD) are unknown, ev... more Although the precise mechanisms for neurodegeneration in Parkinson’s disease (PD) are unknown, evidence suggests that neuroinflammation is a critical factor in the pathogenic process. Here, we sought to determine whether the voltage-gated proton channel, Hv1 (HVCN1), which is expressed in microglia and regulates NADPH oxidase, is associated with dopaminergic neurodegeneration. We utilized data mining to evaluate the mRNA expression of HVCN1 in the brains of PD patients and controls and uncovered increased expression of the gene encoding Hv1, HVCN1, in the brains of PD patients compared to controls, specifically in male PD patients. In an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 4 × 16 mg/kg) mouse model of PD, Hvcn1 gene expression was increased 2-fold in the striatum. MPTP administration to wild-type (WT) mice resulted in a ~65% loss of tyrosine hydroxylase positive neurons (TH+) in the substantia nigra (SN), while a ~39% loss was observed in Hv1 knockout (KO) mice...
Endoplasmic reticulum (ER) stress and neuroinflammation are involved in the pathogenesis of many ... more Endoplasmic reticulum (ER) stress and neuroinflammation are involved in the pathogenesis of many neurodegenerative disorders. Previously, we reported that exposure to pyrethroid insecticide deltamethrin causes hippocampal ER stress apoptosis, a reduction in neurogenesis, and learning deficits in adult male mice. Recently, we found that deltamethrin exposure also increases the markers of neuroinflammation in BV2 cells. Here, we investigated the potential mechanistic link between ER stress and neuroinflammation following exposure to deltamethrin. We found that repeated oral exposure to deltamethrin (3 mg/kg) for 30 days caused microglial activation and increased gene expressions and protein levels of TNF-α, IL-1β, IL-6, gp91phox, 4HNE, and iNOS in the hippocampus. These changes were preceded by the induction of ER stress as the protein levels of CHOP, ATF-4, and GRP78 were significantly increased in the hippocampus. To determine whether induction of ER stress triggers the inflammatory...
Due to routine maintenance of aircraft on the concrete pavement at army airbases, a large part of... more Due to routine maintenance of aircraft on the concrete pavement at army airbases, a large part of the pavement surface is often found saturated with different hydrocarbon-based oil, fuel, and fluid. In addition, the pavement concrete is subjected to the aircraft’s exhaust temperature during operation. This study examined the resistance ability of 3 different cementitious materials: (i) epoxy, (ii) fly ash (FA) based geopolymer with various alkali to fly ash (AL/FA) ratios and (iii) Portland cement (PC) mortar under a simulated airfield circumstance. The mortar specimens were repetitively exposed to a mixture of synthetic engine oil, hydraulic fluids, jet fuel and elevated temperatures (175 °C) for 5 months simultaneously. During the exposures, geopolymer and PC mortar both suffered saponification. The degree of saponification of geopolymer samples is found to be highly reliant on the AL/FA ratios. On the contrary, the epoxy mortar was found to be resistant to saponification. It was ...
Software is ubiquitous, spanning from our everyday life to space station. With a significant incr... more Software is ubiquitous, spanning from our everyday life to space station. With a significant increase in the processing power of modern computing devices, the number of software that deals with sensitive data rises exponentially, providing incentives for performing attacks against these systems. The devices may face various adversarial attacks based on cache side channel, Spectre, Meltdown, Ransomware, buffer and integer overflow, etc. The primary objective of software security is to enhance security in such a way so that software becomes resilient against various malicious attacks during run-time. However, many software-based approaches have been implemented to protect the software from the adversarial attacks. Unfortunately, these techniques cannot provide comprehensive protection as most software vulnerabilities arise not only for the development faults but also for weak hardware architecture. Additionally, software-based approaches may create backdoors for future attacks. Therefore, it is not practical to enhance security only from a software or hardware point of view in a mutually exclusive fashion. This chapter explores various software and hardware vulnerabilities to understand the potential exploitable scenarios better and protect the software from hardware and software perspectives.
This work examines and compares the Malcolm Baldrige National Quality Award (MBNQA) model and the... more This work examines and compares the Malcolm Baldrige National Quality Award (MBNQA) model and the Business Performance Management (BPM) Framework. We use the literature in both areas to posit about the relationships among the two models and to propose a single integrated model. The intent is to provide insight that will allow maintaining organizational MBNQA initiatives while helping to create an agile organization that is capable of developing and increasing competitive advantage.
This study explores the intra-organizational factors and employee job practice area affecting tur... more This study explores the intra-organizational factors and employee job practice area affecting turnover intention. We propose that turnover intention is influenced by two intra-organizational factors, namely, finesse factor and firm factor, and employees’ association to a specific job area. Data were obtained from a diversified multinational company with many job practice areas. The findings suggest that all three factors have significant impact on turnover intention. This implies that the more positively the employees perceive the intra-organizational factors (i.e., the firm and finesse factors) in an organization, the lower their intention to leave the organization. The results also suggest that employees’ associations to various job practice areas have differing significant impact on their intention to leave an organization. For example, employees in the building engineering will have a differing degree of intention to leave the organization compared to those in architecture.
Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis,... more Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3 mg/kg every 3 days for 1 month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure signific...
Over the years, leaked fluids from aircraft have caused severe deterioration of airfield pavement... more Over the years, leaked fluids from aircraft have caused severe deterioration of airfield pavement. The combined effect of hot exhaust from the auxiliary power unit of military aircraft and spilt aviation oils have caused rapid pavement spalling. If the disintegrated concreted pieces caused by spalling are sucked into the jet engine, they may cause catastrophic damage to the aircraft engine or physical injury to maintenance crews. This study investigates the effectiveness of incorporating hybrid fibres into ordinary concrete to improve the residual mechanical and thermal properties to prevent spalling damage of pavement. Three fibre-reinforced concrete samples were made with micro steel fibre and polyvinyl alcohol fibre with a fibre content of zero, 0.3%, 0.5% and 0.7% by volume fraction. These samples were exposed to recurring high temperatures and aviation oils. Tests were conducted to measure the effects of repeated exposure on the concrete’s mechanical, thermal and chemical chara...
Neurotrophins are a family of growth factors crucial for growth and survival of neurons in the de... more Neurotrophins are a family of growth factors crucial for growth and survival of neurons in the developing and adult brain. Reduction in neurotrophin levels is associated with reduced neurogenesis and cognitive deficits in rodents. Recently, we demonstrated that long-term exposure to low levels of the pyrethroid pesticide deltamethrin causes hippocampal endoplasmic reticulum (ER) stress and learning deficits in mice. Here, we found that nerve growth factor (NGF) mRNA and protein were selectively reduced in the hippocampus of deltamethrin-treated mice. To explore potential mechanisms responsible for this observation, we employed mouse primary hippocampal neurons. Exposure of neurons to deltamethrin (1–5 μM) caused ER stress as indicated by increased levels of C/EBP-homologous protein (CHOP) and glucose-regulated protein 78 (GRP78). These changes were accompanied by increased levels of caspase-12, activated caspase-3, and decreased levels of NGF. Inhibition of ER stress with the eukary...
Parkinson's disease (PD), the second most common age-related progressive neurodegenerative di... more Parkinson's disease (PD), the second most common age-related progressive neurodegenerative disorder, is characterized by dopamine depletion and the loss of dopaminergic (DA) neurons with accompanying neuroinflammation. Zonisamide is an-anti-convulsant drug that has recently been shown to improve clinical symptoms of PD through its inhibition of monoamine oxidase B (MAO-B). However, zonisamide has additional targets, including voltage-gated sodium channels (Na), which may contribute to its reported neuroprotective role in preclinical models of PD. Here, we report that Na1.6 is highly expressed in microglia of post-mortem PD brain and of mice treated with the parkinsonism-inducing neurotoxin MPTP. Administration of zonisamide (20 mg/kg, i.p. every 4 h × 3) following a single injection of MPTP (12.5 mg/kg, s.c.) reduced microglial Na 1.6 and microglial activation in the striatum, as indicated by Iba-1 staining and mRNA expression of F4/80. MPTP increased the levels of the pro-infla...
The Journal of pharmacology and experimental therapeutics, 2015
Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the... more Sepiapterin reductase (SPR) catalyzes the reduction of sepiapterin to dihydrobiopterin (BH2), the precursor for tetrahydrobiopterin (BH4), a cofactor critical for nitric oxide biosynthesis and alkylglycerol and aromatic amino acid metabolism. SPR also mediates chemical redox cycling, catalyzing one-electron reduction of redox-active chemicals, including quinones and bipyridinium herbicides (e.g., menadione, 9,10-phenanthrenequinone, and diquat); rapid reaction of the reduced radicals with molecular oxygen generates reactive oxygen species (ROS). Using recombinant human SPR, sulfonamide- and sulfonylurea-based sulfa drugs were found to be potent noncompetitive inhibitors of both sepiapterin reduction and redox cycling. The most potent inhibitors of sepiapterin reduction (IC50s = 31-180 nM) were sulfasalazine, sulfathiazole, sulfapyridine, sulfamethoxazole, and chlorpropamide. Higher concentrations of the sulfa drugs (IC50s = 0.37-19.4 μM) were required to inhibit redox cycling, presu...
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 28, 2015
Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age childr... more Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Here, we used behavioral, molecular, and neurochemical techniques to characterize the effects of developmental exposure to the pyrethroid pesticide deltamethrin. We also used epidemiologic methods to determine whether there is an association between pyrethroid exposure and diagnosis of ADHD. Mice exposed to the pyrethroid pesticide deltamethrin during development exhibit several features reminiscent of ADHD, including elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased DAT and D1 dopamine receptor levels appear to be responsible for the behavioral deficits. Epidemiologic data reveal that...
The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combi... more The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the ...
Uploads
Papers by Muhammad Mokter Hossain