Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe ...Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe acute respiratory syndrome(SARS),cognitive dysfunction like brain fog,and cardiovascular defects.Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer's disease remain understudied.Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye,we found that misexpression of nonstructural protein 3(Nsp3),a papain-like protease,ablates the eye and generates dark necrotic spots.Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters,terminal deoxynucleotidyl transferase(TdT)dUTP Nick-end labeling(TUNEL)assay,and dihydroethidium staining.Furthermore,Nsp3 misexpression activates both apoptosis and autophagy mechanism(s)to regulate tissue homeostasis.Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma,Neuro-2a cells,significantly reduced the metabolic activity of these cells and triggers cell death.Misexpression of SARS-CoV2 Nsp3 in an Alzheimer's disease transgenic fly eye model(glass multiple repeats[GMR]>amyloidβ42)further enhances the neurodegenerative rough eye phenotype due to increased cell death.These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.展开更多
Alzheimer＇s disease（AD）, a fatal progressive neurodegenerative disorder, has no cure to date. One of the causes of AD is the accumulation of amyloid-beta 42（Aβ42） plaques, which result in the onset of neurodegen...Alzheimer＇s disease（AD）, a fatal progressive neurodegenerative disorder, has no cure to date. One of the causes of AD is the accumulation of amyloid-beta 42（Aβ42） plaques, which result in the onset of neurodegeneration. It is not known how these plaques trigger the onset of neurodegeneration. There are several animal models developed to（i） study etiology of disease,（ii） look for genetic modifiers, and（iii） identify chemical inhibitors that can block neurodegeneration and help to find cure for this disease. An insect model of Drosophila melanogaster has also provided new insights into the disease. Here we will discuss the utility of the Drosophila eye model to study Alzheimer＇s disease.展开更多
During development,regulation of organ size requires a balance between cell proliferation,growth and cell death.Dysregulation of these fundamental processes can cause a variety of diseases.Excessive cell proliferation...During development,regulation of organ size requires a balance between cell proliferation,growth and cell death.Dysregulation of these fundamental processes can cause a variety of diseases.Excessive cell proliferation results in cancer whereas excessive cell death results in neurodegenerative disorders.Many signaling pathways known-to-date have a role in growth regulation.Among them,evolutionarily conserved Hippo signaling pathway is unique as it controls both cell proliferation and cell death by a variety of mechanisms during organ sculpture and development.Neurodegeneration,a complex process of progressive death of neuronal population,results in fatal disorders with no available cure to date.During normal development,cell death is required for sculpting of an organ.However,aberrant cell death in neuronal cell population can result in neurodegenerative disorders.Hippo pathway has gathered major attention for its role in growth regulation and cancer,however,other functions like its role in neurodegeneration are also emerging rapidly.This review highlights the role of Hippo signaling in cell death and neurodegenerative diseases and provide the information on the chemical inhibitors employed to block Hippo pathway.Understanding Hippo mediated cell death mechanisms will aid in development of reliable and effective therapeutic strategies in future.展开更多
Air pollution is an issue of great concern in any urban region due to its serious health implications.The capital of India,New Delhi continues to be in the list of most polluted cities since 2014.The air quality of an...Air pollution is an issue of great concern in any urban region due to its serious health implications.The capital of India,New Delhi continues to be in the list of most polluted cities since 2014.The air quality of any region depends on the ability of dispersion of air pollutants.The height or depth of the atmospheric boundary layer(ABL)is one measure of dispersion of air pollutants.Ventilation coefficient is another crucial parameter in determining the air quality of any region.Both of these parameters are obtained over Delhi from the operational global numerical weather prediction(NWP)model of National Centre for Medium Range Weather forecasting(NCMRWF)known as NCMRWF Unified Model(NCUM).The height of ABL over Delhi,is also obtained from radiosonde observations using the parcel method.A good agreement is found between the observed and predicted values of ABL height.The maximum height of ABL is obtained during summer season and minimum is obtained in winter season.High values of air pollutants are found when the values of ABL height and ventilation coefficient are low.展开更多
An attempt has been made in the present study to forecast fog with a diagnostic method using the outputs of global NWP model.The diagnostic method is based on the combination of thresholds of meteorological variables ...An attempt has been made in the present study to forecast fog with a diagnostic method using the outputs of global NWP model.The diagnostic method is based on the combination of thresholds of meteorological variables involved in fog formation.The thresholds are computed using the observations during fog.These thresholds are applied to the output of a global NWP model for forecasting fog.The occurrence of fog is a common phenomenon during winter season over the northern plains of India.The diagnostic method is used to predict fog occurrences over three stations in north India.The proposed method is able to predict both occurrences and non-occurrences of fog at all the three stations.It is found that 94%of the fog events forecasted by the model using the diagnostic method have been actually observed at the selected stations.The performance of method in predicting fog is found best over Delhi with the highest accuracy(0.61)and probability of detection(0.60).The study signifies that diagnostic approach based on the output of a global model is a useful tool for predicting fog over a single location.展开更多
基金supported by 1RO1EY032959-01 from NIHSchuellein Chair Endowment FundSTEM Catalyst Grant from the University of Dayton(all to AS)。
文摘Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe acute respiratory syndrome(SARS),cognitive dysfunction like brain fog,and cardiovascular defects.Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer's disease remain understudied.Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye,we found that misexpression of nonstructural protein 3(Nsp3),a papain-like protease,ablates the eye and generates dark necrotic spots.Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters,terminal deoxynucleotidyl transferase(TdT)dUTP Nick-end labeling(TUNEL)assay,and dihydroethidium staining.Furthermore,Nsp3 misexpression activates both apoptosis and autophagy mechanism(s)to regulate tissue homeostasis.Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma,Neuro-2a cells,significantly reduced the metabolic activity of these cells and triggers cell death.Misexpression of SARS-CoV2 Nsp3 in an Alzheimer's disease transgenic fly eye model(glass multiple repeats[GMR]>amyloidβ42)further enhances the neurodegenerative rough eye phenotype due to increased cell death.These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.
文摘Alzheimer＇s disease（AD）, a fatal progressive neurodegenerative disorder, has no cure to date. One of the causes of AD is the accumulation of amyloid-beta 42（Aβ42） plaques, which result in the onset of neurodegeneration. It is not known how these plaques trigger the onset of neurodegeneration. There are several animal models developed to（i） study etiology of disease,（ii） look for genetic modifiers, and（iii） identify chemical inhibitors that can block neurodegeneration and help to find cure for this disease. An insect model of Drosophila melanogaster has also provided new insights into the disease. Here we will discuss the utility of the Drosophila eye model to study Alzheimer＇s disease.
基金The authors are supported by the University of Dayton Graduate program of BiologyThis work was supported by NIH1R15GM124654-01 from the National Institutes of Health,Schuellein Chair Endowment Fund,and start-up support from the University of Dayton(to Amit S).
文摘During development,regulation of organ size requires a balance between cell proliferation,growth and cell death.Dysregulation of these fundamental processes can cause a variety of diseases.Excessive cell proliferation results in cancer whereas excessive cell death results in neurodegenerative disorders.Many signaling pathways known-to-date have a role in growth regulation.Among them,evolutionarily conserved Hippo signaling pathway is unique as it controls both cell proliferation and cell death by a variety of mechanisms during organ sculpture and development.Neurodegeneration,a complex process of progressive death of neuronal population,results in fatal disorders with no available cure to date.During normal development,cell death is required for sculpting of an organ.However,aberrant cell death in neuronal cell population can result in neurodegenerative disorders.Hippo pathway has gathered major attention for its role in growth regulation and cancer,however,other functions like its role in neurodegeneration are also emerging rapidly.This review highlights the role of Hippo signaling in cell death and neurodegenerative diseases and provide the information on the chemical inhibitors employed to block Hippo pathway.Understanding Hippo mediated cell death mechanisms will aid in development of reliable and effective therapeutic strategies in future.
文摘Air pollution is an issue of great concern in any urban region due to its serious health implications.The capital of India,New Delhi continues to be in the list of most polluted cities since 2014.The air quality of any region depends on the ability of dispersion of air pollutants.The height or depth of the atmospheric boundary layer(ABL)is one measure of dispersion of air pollutants.Ventilation coefficient is another crucial parameter in determining the air quality of any region.Both of these parameters are obtained over Delhi from the operational global numerical weather prediction(NWP)model of National Centre for Medium Range Weather forecasting(NCMRWF)known as NCMRWF Unified Model(NCUM).The height of ABL over Delhi,is also obtained from radiosonde observations using the parcel method.A good agreement is found between the observed and predicted values of ABL height.The maximum height of ABL is obtained during summer season and minimum is obtained in winter season.High values of air pollutants are found when the values of ABL height and ventilation coefficient are low.
文摘An attempt has been made in the present study to forecast fog with a diagnostic method using the outputs of global NWP model.The diagnostic method is based on the combination of thresholds of meteorological variables involved in fog formation.The thresholds are computed using the observations during fog.These thresholds are applied to the output of a global NWP model for forecasting fog.The occurrence of fog is a common phenomenon during winter season over the northern plains of India.The diagnostic method is used to predict fog occurrences over three stations in north India.The proposed method is able to predict both occurrences and non-occurrences of fog at all the three stations.It is found that 94%of the fog events forecasted by the model using the diagnostic method have been actually observed at the selected stations.The performance of method in predicting fog is found best over Delhi with the highest accuracy(0.61)and probability of detection(0.60).The study signifies that diagnostic approach based on the output of a global model is a useful tool for predicting fog over a single location.
