Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivo...Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.展开更多
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
Highly fluorescent binary and ternary hybrid materials based on polyaniline, polyethylene glycol (PEG) and arsenic sulphide have been prepared via oxidative chemical polymerization and characterized by FT-IR and powde...Highly fluorescent binary and ternary hybrid materials based on polyaniline, polyethylene glycol (PEG) and arsenic sulphide have been prepared via oxidative chemical polymerization and characterized by FT-IR and powder X-ray diffraction techniques. Thermogravimetric analysis showed that all the materials are thermally stable up to 250℃. The optical behaviour was investigated using UV-Vis. and fluorescence spectroscopy. Fluorescence spectra of polyaniline and its hybrids were found to be concentration dependent, and concentrations were optimized to achieve maximum intensity of emission. Aggregation caused quenching (ACQ) may be the possible reason for concentration dependent emission. Hybrids showed significantly enhanced fluorescence than polyaniline. The AC electrical conductivity was also measured and found to be better for hybrids than the polyaniline. In the PAni-PEG-As2S3 hybrid, the conductivity was found to be 9.57 × 10<sup>-1</sup> S/cm at 100 KHz. This valuable improvement in luminescent property and conducting behaviour may be useful in various optoelectronic and electronic applications.展开更多
Alzheimer’s disease(hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 pla...Alzheimer’s disease(hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library or natural products that may block or prevent onset of AD. Historically, natural products have been used in many cultures for the treatment of various diseases. The research on natural products have gained importance as the active compounds extracted from them have medicinal values with reduced side effects, and they are bioavailable. The natural products may target the proteins or members of signaling pathways that get altered in specific diseases. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target for AD, and to address questions about how these natural products can rescue AD or other neurodegenerative disorders. Some of these products are in clinical trials and results are promising because of their neuroprotective, anti-inflammatory, antioxidant, anti-amyloidogenic, anticholinesterase activities and easy availability. This review summarizes the use of animal model systems to identify natural products, which may serve as potential therapeutic targets for AD.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
The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may...The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may help prevent widespread cell death.Evidence has pointed towards selective cell death of diseased neurons playing a potentially protective role.As the disease progresses,dysregulation of signaling pathways that govern cell death contributes to neurodegeneration.Aberrant activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42-or tau-mediated neurodegeneration.Clonal mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type cells.This review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type neurons.Cell competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal cells.Somatic clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying neurodegeneration.Generating genetic mosaics with labeled clones of amyloid-beta 42-or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s disease.These approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.展开更多
Chronic neuroinflammation and protein aggregation are the fundamental events mainly responsible for the progression of neurodegenerative diseases(NDs).Potential neurotoxic changes in the intra-and extracellular enviro...Chronic neuroinflammation and protein aggregation are the fundamental events mainly responsible for the progression of neurodegenerative diseases(NDs).Potential neurotoxic changes in the intra-and extracellular environment are typical hallmarks of many NDs.Treatment of ND is challenging,as the symptoms in these patients arises when a significant numbers of neurons have already been destroyed.Heat shock proteins(HSPs)can bind to recipient cells that are susceptible to stress,such as neurons,in the extracellular environment,therefore enhancing stress resistance.Among all,HSP60,HSP70,and HSP90 are highly conserved molecular chaperones involved in protein folding and assembly,maintaining cellular homeostasis in the central nervous system.Notably,α-synuclein accumulation is a major pathophysiology in Parkinson's disease,where HSP90 modulates the assembly ofα-synuclein in vesicles to prevent its accumulation.Moreover,HSP90 regulates the activity of the glycogen synthase kinase-3βprotein,which is crucial in diabetes mellitus-associated neurocognitive disorder.Therefore,understanding the molecular mechanism by which HSPs facilitate protein aggregation and respond to inflammatory stimuli,including metabolic disease such as diabetes,is essential for understanding the significance of HSPs in NDs.This review emphasizes the role of various HSPs in the progression of NDs such as Alzheimer's,Parkinson's,multiple sclerosis,and Huntington's disease,including diabetes,which is one of the major risk factors for neurodegeneration.展开更多
Purpose:Hoffa fracture is a femoral condyle fracture in the coronal plane.The lateral condyle is more commonly involved.The diagnosis is often difficult to detect with routine radiographs.Conservative management in th...Purpose:Hoffa fracture is a femoral condyle fracture in the coronal plane.The lateral condyle is more commonly involved.The diagnosis is often difficult to detect with routine radiographs.Conservative management in this type of fracture resulted in nonunion,malunion,and other complications,such as stiff knee.Therefore,surgical management is mandatory in displaced fractures.Previous studies suggest only application of cancellous screw fixation,but these are not enough to counter vertical shear stress.Therefore,this study will evaluate the clinical outcomes of open reduction and internal fixation of Letenneur type I Hoffa fracture using cancellous screws with posterior buttressing plate.Method:This was a prospective cohort study conducted from March 2017 to July 2022 in orthopaedics department of tertiary care center after approval of institutional ethical committee.The study included 36 patients with Letenneur type I fractures treated by open reduction and internal fixation using posterior buttress plate and cancellous screws.Radiographs and clinical outcomes,range of movement(ROM),bone union,and knee society score(KSS)of patients were assessed at the end of 4 and 12 months in the follow-ups.All statistical analysis was done using Epi info version 7.2.1.0.Results:In the 36 patients with Letenneur type I fracture,the majority belong to younger age group between 25 and 54 years with 22 males and 14 females.The modes of injury were road traffic accidents in 25 patients and fall from height in 11 patients.The right knee was involved in 21 cases and left was involved in 15 cases.Lateral condyle involvement was seen in 27 cases and medial condyle in 9 cases.All 36 patients with Letenneur type I Hoffa fracture were evaluated 4 months after surgical intervention.The notable improvements were observed in terms of ROM 120.4°±5.0°and KSS 85.0±4.2.At the 12-month follow-up,considerably better outcomes were maintained regarding ROM 128.1°±5.2°and KSS 89.3±4.8 with p<0.05 which was statistically significant.At the final follow-up,all patients had routine fracture healing with a union time of(3.2±3.4)months.Conclusions:Fixation of Letenneur type I Hoffa fracture with cancellous screws and posterior buttress plate is effective,reliable and capable of providing adequate stability.Buttress plate assisted fixation is a valuable enhancement of the conventional technique of lag screw fixation of Hoffa fractures.展开更多
This study highlighted a high wave case by severe tropical cyclone Harold and conducted a simulation with a newly developed wave forecasting system for the South Pacific based on the Japan Meteorological Agency third ...This study highlighted a high wave case by severe tropical cyclone Harold and conducted a simulation with a newly developed wave forecasting system for the South Pacific based on the Japan Meteorological Agency third generation wave model(JMA MRI-III)using the National Center for Environment Prediction Global Forecast System(GFS)winds.Harold was a very intense tropical cyclone(TC)and very high waves up to 10 m affected parts of Vanuatu and Fiji.The model results were reasonable and verified against observations of orbital satellites and a wave buoy at Komave in Fiji.The statistical verifications were carefully analysed.The Root Mean Squared Error(RSME),Scatter Index(SI),Bias and R2 are all showing very impressive results.The new wave forecasting system is the first high resolution operational model at Fiji Meteorological Service(FMS),which covers the whole Fiji area.The system will provide guidance to FMS in preparing marine alerts and warning better and more confidence in providing the marine forecast accurately.展开更多
Erianthus produces substantial biomass,exhibits a good Brix value,and shows wide environmental adaptability,making it a potential biofuel plant.In contrast to closely related sorghum and sugarcane,Erianthus can grow i...Erianthus produces substantial biomass,exhibits a good Brix value,and shows wide environmental adaptability,making it a potential biofuel plant.In contrast to closely related sorghum and sugarcane,Erianthus can grow in degraded soils,thus releasing pressure on agricultural lands used for biofuel production.However,the lack of genomic resources for Erianthus hinders its genetic improvement,thus limiting its potential for biofuel production.In the present study,we generated a chromosome-scale reference genome for Erianthus fulvus Nees.The genome size estimated by flow cytometry was 937 Mb,and the assembled genome size was 902 Mb,covering 96.26%of the estimated genome size.A total of 35065 proteincoding genes were predicted,and 67.89%of the genome was found to be repetitive.A recent wholegenome duplication occurred approximately 74.10 million years ago in the E.fulvus genome.Phylogenetic analysis showed that E.fulvus is evolutionarily closer to S.spontaneum and diverged after S.bicolor.Three of the 10 chromosomes of E.fulvus formed through rearrangements of ancestral chromosomes.Phylogenetic reconstruction of the Saccharum complex revealed a polyphyletic origin of the complex and a sister relationship of E.fulvus with Saccharum sp.,excluding S.arundinaceum.On the basis of the four amino acid residues that provide substrate specificity,the E.fulvus SWEET proteins were classified as monoand disaccharide sugar transporters.Ortho-QTL genes identified for 10 biofuel-related traits may aid in the rapid screening of E.fulvus populations to enhance breeding programs for improved biofuel production.The results of this study provide valuable insights for breeding programs aimed at improving biofuel production in E.fulvus and enhancing sugarcane introgression programs.展开更多
The long period fiber grating （LPFG） is widely used as a sensor due to its high sensitivity and resolution. However, the broad bandwidth of the attenuation bands formed by the mode coupling between the fundamental c...The long period fiber grating （LPFG） is widely used as a sensor due to its high sensitivity and resolution. However, the broad bandwidth of the attenuation bands formed by the mode coupling between the fundamental core mode and the cladding modes constitutes a difficulty when the device is used as a conventional sensor. To overcome this limitation, a Michelson interferometer-type sensor configuration has been developed, using an LPFG grating pair formed by coating a mirror at the distal end of the LPFG. This sensor configuration is more convenient to use and is able to overcome the limitations of the single LPFG based sensor as the shifts in the attenuation bands being more easily detectable due to the formation of the sharp spectral fringe pattern in the LPFG based Michelson interferometer. In this work, I studied the LPFG based Michelson interferometer as the refractive index sensor and discussed the sensitivity enhancement of the LPFG based Michelson interferometer as a refractive index sensor by employing higher order cladding modes and by reducing the cladding radius. The results demonstrated the HE17 mode with a cladding radius of 62.5 μm, in the range of surrounding refractive index （SRI） of 1 - 1.45, and its resonant peak showed a wavelength shift of 26.99nm/RIU. When the cladding region was further reduced to 24μm, the resonant peak showed a wavelength shift of 569.88 nm/RIU, resulting in a sensitivity enhancement of nearly 21 times. However, as the cladding region was etched further, then the HE17 order cladding mode and higher mode would be cut off. Therefore, the implementation of high sensitivity for SRI sensing with the reduced cladding in the LPFG based Michelson interferometer is dependent on the proper combination of the cladding radius and cladding mode order.展开更多
The author studied and demonstrated the various modeling aspects of long period fiber grating （LPFG） such as the core effective index, cladding effective index, coupling coefficient, coupled mode theory, and transmi...The author studied and demonstrated the various modeling aspects of long period fiber grating （LPFG） such as the core effective index, cladding effective index, coupling coefficient, coupled mode theory, and transmission spectrum of the LPFG using three-layer fiber geometry. Actually, there are two different techniques used for theoretical modeling of the long period fiber grating. The first technique was used by Vengsarkar et al who described the phenomenon of long-period fiber gratings, and the second technique was reported by Erdogan who revealed the inaccuracies and shortcomings of the original method, thereby providing an accurate and updated alternative. The main difference between these two different approaches lies in their fiber geometry. Venserkar et al used two-layer fiber geometry which is simple but employs weakly guided approximation, whereas Erdogan used three-layer fiber geometry which is complex but also the most accurate technique for theoretical study of the LPFG. The author further discussed about the behavior of the transmission spectrum by altering different grating parameters such as the grating length, ultraviolet （UV） induced-index change, and grating period to achieve the desired flexibility. The author simulated the various results with the help of MATLAB.展开更多
This review summarizes experiences at operational centers to forecast tropical cyclone(TC)intensity change as presented to the International Workshop on Tropical Cyclones(IWTC-9)in Hawaii in 2018.Some operational fore...This review summarizes experiences at operational centers to forecast tropical cyclone(TC)intensity change as presented to the International Workshop on Tropical Cyclones(IWTC-9)in Hawaii in 2018.Some operational forecast centers have been able to leverage advances in intensity guidance to increase forecast skill,albeit incrementally,while others have struggled to make any significant improvements.Rapid intensity changes continue to present major challenges to operational centers and individual difficult cases illustrate the forecasting challenges.It is noteworthy that the realization of a recommendation from IWTC-8 in 2014,to adapt guidance initially developed for the North Atlantic and North-East Pacific to other basins,has led to improved forecast skill of some agencies.Recent worldwide difficult cases are presented so that the research community can further investigate,potentially leading to improved intensity forecasts when similar cases are observed in the future.展开更多
Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were use...Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were used to retrieve the ligands and target protein structure.The molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics simulation.Results:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter protein.Docking score analysis revealed that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead compounds.Conclusion:The in-silico study demonstrated that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.展开更多
Objective:To study the bioactivity of methanolic extract of Brassica juncea on animal model of diabetes mellitus along with its effect on diabetic and metabolic parameters.Methods:Diabetes mellitus was induced in rats...Objective:To study the bioactivity of methanolic extract of Brassica juncea on animal model of diabetes mellitus along with its effect on diabetic and metabolic parameters.Methods:Diabetes mellitus was induced in rats by injecting streptozotocin(60 mg/kg)intraperitonealy.Blood glucose was measured on day 3 by GOD-POD method to confirm the diabetes mellitus.Rats having fasting blood glucose>250 mg/d L were further selected for study and they were divided into four groups,control,control+streptozotocin,streptozotocin+metformin(75 mg/kg)and streptozotocin+extract of B.juncea(450 mg/kg).Each group consisted of six rats of either sex.Metformin and experimental extract were administered for 21 d.Triglyceride,cholesterol level were measured on day 21 by commercially available kit.Blood glucose was measured on days 7 and 21.Anti-oxidant potential was assessed by estimating extent of lipid peroxidation(LPO)by malondialdehyde(MDA),nitric oxide(NO),superoxide dismutase(SOD)and glutathione(GSH)in liver,kidney,pancreas,muscle tissues on day 21.Unpaired and paired student’s t-test was applied for statistical analysis.Results:The extract of B.juncea showed significant decrease in blood glucose level on day 21.The treatment group showed significant difference in oxidative stress by increasing SOD and GSH and decreasing LPO and NO activity on day 21.The treatment did not show statistically significant difference of cholesterol,and triglycerides level on day 21.Conclusion:The study showed anti-hyperglycemic and anti-oxidative properties of methanolic extract of B.juncea.展开更多
This review article summarizes the current understanding and recent updates to tropical cyclone outer size and structure forecasting and research primarily since 2018 as part of the World Meteorological Organization&#...This review article summarizes the current understanding and recent updates to tropical cyclone outer size and structure forecasting and research primarily since 2018 as part of the World Meteorological Organization's 10th International Workshop on Tropical Cyclones.A more complete understanding of tropical cyclone outer wind and precipitation is key to anticipating storm intensification and the scale and magnitude of landfalling hazards.We first discuss the relevance of tropical cyclone outer size and structure,improvements in our understanding of its life cycle and inter-basin variability,and the processes that impact outer size changes.We next focus on current forecasting practices and differences among warning centers,recent advances in operational forecasting,and new observations of the storm outer wind field.We also summarize recent research on projected tropical cyclone outer size and structure changes by the late 21st century.Finally,we discuss recommendations for the future of tropical cyclone outer size forecasting and research.展开更多
This paper introduces a deep learning(DL)algorithm for estimating doubly-selective fading channel and detecting signals in orthogonal frequency division multiplexing(OFDM)communication systems affected by hardware imp...This paper introduces a deep learning(DL)algorithm for estimating doubly-selective fading channel and detecting signals in orthogonal frequency division multiplexing(OFDM)communication systems affected by hardware impairments(HIs).In practice,hardware imperfections are present at the transceivers,which are modeled as direct current(DC)offset,carrier frequency offset(CFO),and in-phase and quadrature-phase(IQ)imbalance at the transmitter and the receiver in OFDM system.In HIs,the explicit system model could not be mathematically derived,which limits the performance of conventional least square(LS)or minimum mean square error(MMSE)estimators.Thus,we consider time-frequency response of a channel as a 2D image,and unknown values of the channel response are derived using known values at the pilot locations with DL-based image super-resolution,and image restoration techniques.Further,a deep neural network(DNN)is designed to fit the mapping between the received signal and transmit symbols,where the number of outputs equals to the size of the modulation order.Results show that there are no significant effects of HIs on channel estimation and signal detection in the proposed DL-assisted algorithm.The proposed DL-assisted detection improves the OFDM performance as compared to the conventional LS/MMSE under severe Hls.展开更多
基金supported by 1RO1EY032959-01 and RO1 supplement from NIH,Schuellein Chair Endowment Fund and STEM Catalyst Grant from the University of Dayton(to AS).
文摘Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.
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Highly fluorescent binary and ternary hybrid materials based on polyaniline, polyethylene glycol (PEG) and arsenic sulphide have been prepared via oxidative chemical polymerization and characterized by FT-IR and powder X-ray diffraction techniques. Thermogravimetric analysis showed that all the materials are thermally stable up to 250℃. The optical behaviour was investigated using UV-Vis. and fluorescence spectroscopy. Fluorescence spectra of polyaniline and its hybrids were found to be concentration dependent, and concentrations were optimized to achieve maximum intensity of emission. Aggregation caused quenching (ACQ) may be the possible reason for concentration dependent emission. Hybrids showed significantly enhanced fluorescence than polyaniline. The AC electrical conductivity was also measured and found to be better for hybrids than the polyaniline. In the PAni-PEG-As2S3 hybrid, the conductivity was found to be 9.57 × 10<sup>-1</sup> S/cm at 100 KHz. This valuable improvement in luminescent property and conducting behaviour may be useful in various optoelectronic and electronic applications.
基金Schuellein Chair Endowment Fund to AS supports PD and Graduate program of Biology supports NGsupported by National Institute of General Medical Sciences(NIGMS)-1 R15 GM124654-01+2 种基金Schuellein Chair Endowment Fund(to AS)STEM Catalyst Grant from University of Daytonstart-up support from UD(to AS)
文摘Alzheimer’s disease(hereafter AD) is a progressive neurodegenerative disorder that affects the central nervous system. There are multiple factors that cause AD, viz., accumulation of extracellular Amyloid-beta 42 plaques, intracellular hyper-phosphorylated Tau tangles, generation of reactive oxygen species due to mitochondrial dysfunction and genetic mutations. The plaques and tau tangles trigger aberrant signaling, which eventually cause cell death of the neurons. As a result, there is shrinkage of brain, cognitive defects, behavioral and psychological problems. To date, there is no direct cure for AD. Thus, scientists have been testing various strategies like screening for the small inhibitor molecule library or natural products that may block or prevent onset of AD. Historically, natural products have been used in many cultures for the treatment of various diseases. The research on natural products have gained importance as the active compounds extracted from them have medicinal values with reduced side effects, and they are bioavailable. The natural products may target the proteins or members of signaling pathways that get altered in specific diseases. Many natural products are being tested in various animal model systems for their role as a potential therapeutic target for AD, and to address questions about how these natural products can rescue AD or other neurodegenerative disorders. Some of these products are in clinical trials and results are promising because of their neuroprotective, anti-inflammatory, antioxidant, anti-amyloidogenic, anticholinesterase activities and easy availability. This review summarizes the use of animal model systems to identify natural products, which may serve as potential therapeutic targets for AD.
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.
基金supported by 1RO1EY032959-01,NIH1R15GM124654-01 from NIHSchuellein Chair Endowment Fund and STEM Catalyst Grant and start-up support from the University of Dayton(to AS,MKS is Co-PI on NIH RO1 and Co-I on NIH R15)。
文摘The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may help prevent widespread cell death.Evidence has pointed towards selective cell death of diseased neurons playing a potentially protective role.As the disease progresses,dysregulation of signaling pathways that govern cell death contributes to neurodegeneration.Aberrant activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42-or tau-mediated neurodegeneration.Clonal mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type cells.This review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type neurons.Cell competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal cells.Somatic clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying neurodegeneration.Generating genetic mosaics with labeled clones of amyloid-beta 42-or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s disease.These approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.
基金supported by the Department of Health Research,Ministry of Health and Family Welfare,Government of IndiaIndian Council of Medical Research,Ministry of Health and Family Welfare,Government of IndiaCCRH,Ministry of Ayush,Government of India.
文摘Chronic neuroinflammation and protein aggregation are the fundamental events mainly responsible for the progression of neurodegenerative diseases(NDs).Potential neurotoxic changes in the intra-and extracellular environment are typical hallmarks of many NDs.Treatment of ND is challenging,as the symptoms in these patients arises when a significant numbers of neurons have already been destroyed.Heat shock proteins(HSPs)can bind to recipient cells that are susceptible to stress,such as neurons,in the extracellular environment,therefore enhancing stress resistance.Among all,HSP60,HSP70,and HSP90 are highly conserved molecular chaperones involved in protein folding and assembly,maintaining cellular homeostasis in the central nervous system.Notably,α-synuclein accumulation is a major pathophysiology in Parkinson's disease,where HSP90 modulates the assembly ofα-synuclein in vesicles to prevent its accumulation.Moreover,HSP90 regulates the activity of the glycogen synthase kinase-3βprotein,which is crucial in diabetes mellitus-associated neurocognitive disorder.Therefore,understanding the molecular mechanism by which HSPs facilitate protein aggregation and respond to inflammatory stimuli,including metabolic disease such as diabetes,is essential for understanding the significance of HSPs in NDs.This review emphasizes the role of various HSPs in the progression of NDs such as Alzheimer's,Parkinson's,multiple sclerosis,and Huntington's disease,including diabetes,which is one of the major risk factors for neurodegeneration.
文摘Purpose:Hoffa fracture is a femoral condyle fracture in the coronal plane.The lateral condyle is more commonly involved.The diagnosis is often difficult to detect with routine radiographs.Conservative management in this type of fracture resulted in nonunion,malunion,and other complications,such as stiff knee.Therefore,surgical management is mandatory in displaced fractures.Previous studies suggest only application of cancellous screw fixation,but these are not enough to counter vertical shear stress.Therefore,this study will evaluate the clinical outcomes of open reduction and internal fixation of Letenneur type I Hoffa fracture using cancellous screws with posterior buttressing plate.Method:This was a prospective cohort study conducted from March 2017 to July 2022 in orthopaedics department of tertiary care center after approval of institutional ethical committee.The study included 36 patients with Letenneur type I fractures treated by open reduction and internal fixation using posterior buttress plate and cancellous screws.Radiographs and clinical outcomes,range of movement(ROM),bone union,and knee society score(KSS)of patients were assessed at the end of 4 and 12 months in the follow-ups.All statistical analysis was done using Epi info version 7.2.1.0.Results:In the 36 patients with Letenneur type I fracture,the majority belong to younger age group between 25 and 54 years with 22 males and 14 females.The modes of injury were road traffic accidents in 25 patients and fall from height in 11 patients.The right knee was involved in 21 cases and left was involved in 15 cases.Lateral condyle involvement was seen in 27 cases and medial condyle in 9 cases.All 36 patients with Letenneur type I Hoffa fracture were evaluated 4 months after surgical intervention.The notable improvements were observed in terms of ROM 120.4°±5.0°and KSS 85.0±4.2.At the 12-month follow-up,considerably better outcomes were maintained regarding ROM 128.1°±5.2°and KSS 89.3±4.8 with p<0.05 which was statistically significant.At the final follow-up,all patients had routine fracture healing with a union time of(3.2±3.4)months.Conclusions:Fixation of Letenneur type I Hoffa fracture with cancellous screws and posterior buttress plate is effective,reliable and capable of providing adequate stability.Buttress plate assisted fixation is a valuable enhancement of the conventional technique of lag screw fixation of Hoffa fractures.
文摘This study highlighted a high wave case by severe tropical cyclone Harold and conducted a simulation with a newly developed wave forecasting system for the South Pacific based on the Japan Meteorological Agency third generation wave model(JMA MRI-III)using the National Center for Environment Prediction Global Forecast System(GFS)winds.Harold was a very intense tropical cyclone(TC)and very high waves up to 10 m affected parts of Vanuatu and Fiji.The model results were reasonable and verified against observations of orbital satellites and a wave buoy at Komave in Fiji.The statistical verifications were carefully analysed.The Root Mean Squared Error(RSME),Scatter Index(SI),Bias and R2 are all showing very impressive results.The new wave forecasting system is the first high resolution operational model at Fiji Meteorological Service(FMS),which covers the whole Fiji area.The system will provide guidance to FMS in preparing marine alerts and warning better and more confidence in providing the marine forecast accurately.
基金supported by grants from the Major Science and Technology Projects in Yunnan Province(202202AE090021)a special project of Yunnan Key Laboratory of Crop Production and Smart Agriculture(202105AG070007)+3 种基金a sub-project of the National Key Research and Development Program of China(2018YFD1000503)the National Natural Science Foundation of China(31960451,31560417)a Key Project of Applied Basic Research Program of Yunnan Province(2015FA024)the ESI Discipline Promotion Program of Yunnan Agricultural University(2019YNAUESIMS01).
文摘Erianthus produces substantial biomass,exhibits a good Brix value,and shows wide environmental adaptability,making it a potential biofuel plant.In contrast to closely related sorghum and sugarcane,Erianthus can grow in degraded soils,thus releasing pressure on agricultural lands used for biofuel production.However,the lack of genomic resources for Erianthus hinders its genetic improvement,thus limiting its potential for biofuel production.In the present study,we generated a chromosome-scale reference genome for Erianthus fulvus Nees.The genome size estimated by flow cytometry was 937 Mb,and the assembled genome size was 902 Mb,covering 96.26%of the estimated genome size.A total of 35065 proteincoding genes were predicted,and 67.89%of the genome was found to be repetitive.A recent wholegenome duplication occurred approximately 74.10 million years ago in the E.fulvus genome.Phylogenetic analysis showed that E.fulvus is evolutionarily closer to S.spontaneum and diverged after S.bicolor.Three of the 10 chromosomes of E.fulvus formed through rearrangements of ancestral chromosomes.Phylogenetic reconstruction of the Saccharum complex revealed a polyphyletic origin of the complex and a sister relationship of E.fulvus with Saccharum sp.,excluding S.arundinaceum.On the basis of the four amino acid residues that provide substrate specificity,the E.fulvus SWEET proteins were classified as monoand disaccharide sugar transporters.Ortho-QTL genes identified for 10 biofuel-related traits may aid in the rapid screening of E.fulvus populations to enhance breeding programs for improved biofuel production.The results of this study provide valuable insights for breeding programs aimed at improving biofuel production in E.fulvus and enhancing sugarcane introgression programs.
文摘The long period fiber grating （LPFG） is widely used as a sensor due to its high sensitivity and resolution. However, the broad bandwidth of the attenuation bands formed by the mode coupling between the fundamental core mode and the cladding modes constitutes a difficulty when the device is used as a conventional sensor. To overcome this limitation, a Michelson interferometer-type sensor configuration has been developed, using an LPFG grating pair formed by coating a mirror at the distal end of the LPFG. This sensor configuration is more convenient to use and is able to overcome the limitations of the single LPFG based sensor as the shifts in the attenuation bands being more easily detectable due to the formation of the sharp spectral fringe pattern in the LPFG based Michelson interferometer. In this work, I studied the LPFG based Michelson interferometer as the refractive index sensor and discussed the sensitivity enhancement of the LPFG based Michelson interferometer as a refractive index sensor by employing higher order cladding modes and by reducing the cladding radius. The results demonstrated the HE17 mode with a cladding radius of 62.5 μm, in the range of surrounding refractive index （SRI） of 1 - 1.45, and its resonant peak showed a wavelength shift of 26.99nm/RIU. When the cladding region was further reduced to 24μm, the resonant peak showed a wavelength shift of 569.88 nm/RIU, resulting in a sensitivity enhancement of nearly 21 times. However, as the cladding region was etched further, then the HE17 order cladding mode and higher mode would be cut off. Therefore, the implementation of high sensitivity for SRI sensing with the reduced cladding in the LPFG based Michelson interferometer is dependent on the proper combination of the cladding radius and cladding mode order.
文摘The author studied and demonstrated the various modeling aspects of long period fiber grating （LPFG） such as the core effective index, cladding effective index, coupling coefficient, coupled mode theory, and transmission spectrum of the LPFG using three-layer fiber geometry. Actually, there are two different techniques used for theoretical modeling of the long period fiber grating. The first technique was used by Vengsarkar et al who described the phenomenon of long-period fiber gratings, and the second technique was reported by Erdogan who revealed the inaccuracies and shortcomings of the original method, thereby providing an accurate and updated alternative. The main difference between these two different approaches lies in their fiber geometry. Venserkar et al used two-layer fiber geometry which is simple but employs weakly guided approximation, whereas Erdogan used three-layer fiber geometry which is complex but also the most accurate technique for theoretical study of the LPFG. The author further discussed about the behavior of the transmission spectrum by altering different grating parameters such as the grating length, ultraviolet （UV） induced-index change, and grating period to achieve the desired flexibility. The author simulated the various results with the help of MATLAB.
文摘This review summarizes experiences at operational centers to forecast tropical cyclone(TC)intensity change as presented to the International Workshop on Tropical Cyclones(IWTC-9)in Hawaii in 2018.Some operational forecast centers have been able to leverage advances in intensity guidance to increase forecast skill,albeit incrementally,while others have struggled to make any significant improvements.Rapid intensity changes continue to present major challenges to operational centers and individual difficult cases illustrate the forecasting challenges.It is noteworthy that the realization of a recommendation from IWTC-8 in 2014,to adapt guidance initially developed for the North Atlantic and North-East Pacific to other basins,has led to improved forecast skill of some agencies.Recent worldwide difficult cases are presented so that the research community can further investigate,potentially leading to improved intensity forecasts when similar cases are observed in the future.
基金support from the Indian Council of Medical Research(ICMR),India in the form of ICMR Senior Research fellowship.SK acknowledges the University Grants Commission(UGC),India and Department of Science and Technology(DST),India for providing financial support in the form of UGC-BSR Research Start-Up-Grant[No.F.30-372/2017(BSR)]and DST-SERB Grant(EEQ/2016/000350)respectively.SK also acknowledges DST,India for providing the Departmental DST-FIST grant to the Department of Biochemistry,Central University of Punjab,India.AKS and MS acknowledges CSIR and ICMR,India funding agencies respectively for providing financial assistance in the form of a Senior Research Fellowship.KSP acknowledge DBT,India funding agencies for providing financial assistance in the form of Junior Research Fellowship.
文摘Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(B.frutescens)phytochemicals.Methods:Several previous studies and databases were used to retrieve the ligands and target protein structure.The molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics simulation.Results:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter protein.Docking score analysis revealed that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead compounds.Conclusion:The in-silico study demonstrated that B.frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.
基金Banaras Hindu University(BHU)for providing grant to carry out study.
文摘Objective:To study the bioactivity of methanolic extract of Brassica juncea on animal model of diabetes mellitus along with its effect on diabetic and metabolic parameters.Methods:Diabetes mellitus was induced in rats by injecting streptozotocin(60 mg/kg)intraperitonealy.Blood glucose was measured on day 3 by GOD-POD method to confirm the diabetes mellitus.Rats having fasting blood glucose>250 mg/d L were further selected for study and they were divided into four groups,control,control+streptozotocin,streptozotocin+metformin(75 mg/kg)and streptozotocin+extract of B.juncea(450 mg/kg).Each group consisted of six rats of either sex.Metformin and experimental extract were administered for 21 d.Triglyceride,cholesterol level were measured on day 21 by commercially available kit.Blood glucose was measured on days 7 and 21.Anti-oxidant potential was assessed by estimating extent of lipid peroxidation(LPO)by malondialdehyde(MDA),nitric oxide(NO),superoxide dismutase(SOD)and glutathione(GSH)in liver,kidney,pancreas,muscle tissues on day 21.Unpaired and paired student’s t-test was applied for statistical analysis.Results:The extract of B.juncea showed significant decrease in blood glucose level on day 21.The treatment group showed significant difference in oxidative stress by increasing SOD and GSH and decreasing LPO and NO activity on day 21.The treatment did not show statistically significant difference of cholesterol,and triglycerides level on day 21.Conclusion:The study showed anti-hyperglycemic and anti-oxidative properties of methanolic extract of B.juncea.
基金supported by funding from NOAA/Office of Oceanic and Atmospheric Research under NOAAUniversity of Oklahoma Cooperative Agreement#NA21OAR4320204U.S.Department of Commerce,and NSF AGS#2028151+5 种基金Daniel Chavas is supported by NSF AGS#1945113.Kelvin T.F.Chan was jointly supported by the National Science Foundation,United States,National Key R&D Program of China(2019YFC1510400)the National Natural Science Foundation of China(41975052)the Guangdong Basic and Applied Basic Research Foundation(2023A1515010741)the Innovation Group Project of the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai311021001)the Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies(2020B1212060025).
文摘This review article summarizes the current understanding and recent updates to tropical cyclone outer size and structure forecasting and research primarily since 2018 as part of the World Meteorological Organization's 10th International Workshop on Tropical Cyclones.A more complete understanding of tropical cyclone outer wind and precipitation is key to anticipating storm intensification and the scale and magnitude of landfalling hazards.We first discuss the relevance of tropical cyclone outer size and structure,improvements in our understanding of its life cycle and inter-basin variability,and the processes that impact outer size changes.We next focus on current forecasting practices and differences among warning centers,recent advances in operational forecasting,and new observations of the storm outer wind field.We also summarize recent research on projected tropical cyclone outer size and structure changes by the late 21st century.Finally,we discuss recommendations for the future of tropical cyclone outer size forecasting and research.
基金supported by the Ministry of Science and Technology,SERB under Grant SRG/2021/000199 and by the Indian National Academy of Engineering(INAE)Project with Sanction under Grant 2023/INTW/10.
文摘This paper introduces a deep learning(DL)algorithm for estimating doubly-selective fading channel and detecting signals in orthogonal frequency division multiplexing(OFDM)communication systems affected by hardware impairments(HIs).In practice,hardware imperfections are present at the transceivers,which are modeled as direct current(DC)offset,carrier frequency offset(CFO),and in-phase and quadrature-phase(IQ)imbalance at the transmitter and the receiver in OFDM system.In HIs,the explicit system model could not be mathematically derived,which limits the performance of conventional least square(LS)or minimum mean square error(MMSE)estimators.Thus,we consider time-frequency response of a channel as a 2D image,and unknown values of the channel response are derived using known values at the pilot locations with DL-based image super-resolution,and image restoration techniques.Further,a deep neural network(DNN)is designed to fit the mapping between the received signal and transmit symbols,where the number of outputs equals to the size of the modulation order.Results show that there are no significant effects of HIs on channel estimation and signal detection in the proposed DL-assisted algorithm.The proposed DL-assisted detection improves the OFDM performance as compared to the conventional LS/MMSE under severe Hls.
