Isolation and Detection of Pathological Tau Species in a Tauopathy Mouse Model.

Tau protein in Alzheimer's disease (AD) and tauopathies becomes insoluble due to hyperphosphorylation, conformational alterations, and aggregation. To analyze insoluble tau and pathological tau species, this study employs a methodology that utilizes wild-type and transgenic tau mice (P310S Tau) tissue extraction using 1% Sarkosyl or N-Lauroylsarcosine sodium salt and the radio immunoprecipitation assay (RIPA) buffer. However, the commonly used methods to study the insoluble tau fraction using detergents like Sarkosyl and RIPA require a large amount of homogenate, which can pose challenges when dealing with small tissue samples. Additionally, the study employs immunohistochemistry to visualize and quantify the pathological tau species in the brain tissue of transgenic mice, aiming to identify and analyze pathological tau species such as hyperphosphorylated tau to further our understanding of tauopathies such as Alzheimer's disease.

Heavy metal geochemistry and toxicity assessment of water environment from Ib valley coalfield, India: Implications to contaminant source apportionment and human health risks.

The present study aims to investigate the hydrogeochemical evolution of heavy metals and assesses impacts of mining activities on the groundwater resources and potential human health risks in the coal mining areas of Ib valley coalfield. In this perspective, a total of one hundred and two mine water and groundwater samples were collected from different locations. The water samples were analysed for some selected heavy metals i.e. Mn, Cu, Pb, Zn, Ni, Co, As, Se, Al, Sr, Ba, Cd, Cr, V and Fe using ICP-MS. In addition, pH and SO42- concentration were also measured following APHA procedure. The water pH in the Ib valley coalfields ranged from 3.26 to 8.18 for mine water and 5.23 to 8.52 for groundwater, indicating acidic to alkaline nature of water. Mn in mine water and Zn in groundwater environment were observed as the most dominant metals. The water hazard index (WHI) reflects that around 80% of mine water are non-toxic (WHI<5), 5% slightly toxic (510) and 15% extremely toxic (WHI>15). Relatively high pH and low concentration of dissolved metals and SO42- in groundwater as compared to mine water indicate lesser impact of mining activities. The calculated drinking water quality index (DWQI) suggests that Mn, Al, Ni and Fe in mine water and Mn, Fe, Ni and Pb in groundwater were the major objectionable metals which caused the water quality deterioration for drinking uses. Further, the non-carcinogenic health risk assessment for adult male, female and child populations identifies Co, Mn, Ni as the key elements making the water hazardous for human health. Comparatively higher ratio of ingestion rate and body weight in child population might be causing higher health risks in child population as compared to adult male and adult female population.

Snow Cover Response to Climatological Factors at the Beas River Basin of W. Himalayas from MODIS and ERA5 Datasets.

Glaciers and snow are critical components of the hydrological cycle in the Himalayan region, and they play a vital role in river runoff. Therefore, it is crucial to monitor the glaciers and snow cover on a spatiotemporal basis to better understand the changes in their dynamics and their impact on river runoff. A significant amount of data is necessary to comprehend the dynamics of snow. Yet, the absence of weather stations in inaccessible locations and high elevation present multiple challenges for researchers through field surveys. However, the advancements made in remote sensing have become an effective tool for studying snow. In this article, the snow cover area (SCA) was analysed over the Beas River basin, Western Himalayas for the period 2003 to 2018. Moreover, its sensitivity towards temperature and precipitation was also analysed. To perform the analysis, two datasets, i.e., MODIS-based MOYDGL06 products for SCA estimation and the European Centre for Medium-Range Weather Forecasts (ECMWF) Atmospheric Reanalysis of the Global Climate (ERA5) for climate data were utilized. Results showed an average SCA of ~56% of its total area, with the highest annual SCA recorded in 2014 at ~61.84%. Conversely, the lowest annual SCA occurred in 2016, reaching ~49.2%. Notably, fluctuations in SCA are highly influenced by temperature, as evidenced by the strong connection between annual and seasonal SCA and temperature. The present study findings can have significant applications in fields such as water resource management, climate studies, and disaster management.

Gastrointestinal Manifestations of SARS-CoV-2: Transmission, Pathogenesis, Immunomodulation, Microflora Dysbiosis, and Clinical Implications.

The clinical manifestation of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the respiratory system of humans is widely recognized. There is increasing evidence suggesting that SARS-CoV-2 possesses the capability to invade the gastrointestinal (GI) system, leading to the manifestation of symptoms such as vomiting, diarrhea, abdominal pain, and GI lesions. These symptoms subsequently contribute to the development of gastroenteritis and inflammatory bowel disease (IBD). Nevertheless, the pathophysiological mechanisms linking these GI symptoms to SARS-CoV-2 infection remain unelucidated. During infection, SARS-CoV-2 binds to angiotensin-converting enzyme 2 and other host proteases in the GI tract during the infection, possibly causing GI symptoms by damaging the intestinal barrier and stimulating inflammatory factor production, respectively. The symptoms of COVID-19-induced GI infection and IBD include intestinal inflammation, mucosal hyperpermeability, bacterial overgrowth, dysbiosis, and changes in blood and fecal metabolomics. Deciphering the pathogenesis of COVID-19 and understanding its exacerbation may provide insights into disease prognosis and pave the way for the discovery of potential novel targets for disease prevention or treatment. Besides the usual transmission routes, SARS-CoV-2 can also be transmitted via the feces of an infected person. Hence, it is crucial to implement preventive and control measures in order to mitigate the fecal-to-oral transmission of SARS-CoV-2. Within this context, the identification and diagnosis of GI tract symptoms during these infections assume significance as they facilitate early detection of the disease and the development of targeted therapeutics. The present review discusses the receptors, pathogenesis, and transmission of SARS-CoV-2, with a particular focus on the induction of gut immune responses, the influence of gut microbes, and potential therapeutic targets against COVID-19-induced GI infection and IBD.

Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting.

Molecules involved in drug resistance can be targeted for better therapeutic efficacies. Research on midkine (MDK) has escalated in the last few decades, which affirms a positive correlation between disease progression and MDK expression in most cancers and indicates its association with multi-drug resistance in cancer. MDK, a secretory cytokine found in blood, can be exploited as a potent biomarker for the non-invasive detection of drug resistance expressed in various cancers and, thereby, can be targeted. We summarize the current information on the involvement of MDK in drug resistance, and transcriptional regulators of its expression and highlight its potential as a cancer therapeutic target.

Consequences of pre and post confinement on the atmospheric air pollutants during spread of COVID-19 in India.

COVID-19, a severe respiratory syndrome, was diagnosed in Wuhan, China, and in the last week of January 2020, it was reported in India. The drastic speed of spreading of COVID-19 imposed a total lockdown in India for the first time in four stages. This leads to restrictions on transport, industries, coal-based power plants, etc. During these stages of lockdown, a detailed analysis was done to study the effect of confinement on various air pollutants, PM10, PM2.5, SO2, CO, NH3, and NOx (NO, NO2) over the thirteen different stations situated at different states in India. The data were compared with pre-confinement duration at different locations in India. During confinement, the air pollutants showed less value when compared with the pre-confinement stage alarming everyone and also the Indian government to bring up rules and regulations for better air quality index so that such pandemics should be reduced.

Assessment of metal pollution and human health risks in road dust from mineral rich zone of East Singhbhum, India.

A detailed study of heavy metals in the road dust of a mineral rich zone of Jharkhand state, India is reported herein. Metal concentrations in the road dust exceeded the corresponding values in the average shale as well as world average of soil. Metal pollution due to the road dust and the possible health impact arising there from was appraised through a number of indices such as Geo-accumulation Index (Igeo), Pollution Load Index, Enrichment Factor (EF), Contamination Factor and US EPA Hazard Index and Cancer Risk. Cu contamination was highest as per EF and Igeo, followed by Pb and Zn. Aggravated heavy metal loading in the road dust was conspicuous in the proximity of copper mines and processing units. Both geogenic and anthropogenic sources were responsible for heavy metals in road dust according to principal component analysis. Hazard Quotient, Hazard Index and Cancer Risk were calculated to ascertain non-carcinogenic and carcinogenic health risks in adults and children. Local inhabitants, particularly children, were under appreciable cancer and non-cancer risk. Oral ingestion was the major pathway for risk to the local commuters followed by dermal pathway. Present study underscored the importance of regular heavy metal monitoring of road dust in this zone and administer proactive road dust management practices to reduce metal pollution.

Interaction of Tau with Kinesin-1: Effect of Kinesin-1 Heavy Chain Elimination on Autophagy-Mediated Mutant Tau Degradation.

Natively unfolded tau has a low propensity to form aggregates, but in tauopathies, such as Alzheimer's disease (AD), tau aggregates into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). Multiple intracellular transport pathways utilize kinesin-1, a plus-end-directed microtubule-based motor. Kinesin-1 is crucial in various neurodegenerative diseases as it transports multiple cargoes along the microtubules (MT). Kinesin-1 proteins cannot progress along MTs due to an accumulation of tau on their surfaces. Although kinesin-1-mediated neuronal transport dysfunction is well-documented in other neurodegenerative diseases, its role in AD has received less attention. Very recently, we have shown that knocking down and knocking out of kinesin-1 heavy chain (KIF5B KO) expression significantly reduced the level and stability of tau in cells and tau transgenic mice, respectively. Here, we report that tau interacts with the motor domain of KIF5B in vivo and in vitro, possibly through its microtubule-binding repeat domain. This interaction leads to the inhibition of the ATPase activity of the motor domain. In addition, the KIF5B KO results in autophagy initiation, which subsequently assists in tau degradation. The mechanisms behind KIF5B KO-mediated tau degradation seem to involve its interaction with tau, promoting the trafficking of tau through retrograde transport into autophagosomes for subsequent lysosomal degradation of tau. Our results suggest how KIF5B removal facilitates the movement of autophagosomes toward lysosomes for efficient tau degradation. This mechanism can be enabled through the downregulation of kinesin-1 or the disruption of the association between kinesin-1 and tau, particularly in cases when neurons perceive disturbances in intercellular axonal transport.

Reduction of kinesin I heavy chain decreases tau hyperphosphorylation, aggregation, and memory impairment in Alzheimer's disease and tauopathy models.

Many neurodegenerative diseases, such as Alzheimer's disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome 17, are characterized by tau pathology. Numerous motor proteins, many of which are involved in synaptic transmission, mediate transport in neurons. Dysfunction in motor protein-mediated neuronal transport mechanisms occurs in several neurodegenerative disorders but remains understudied in AD. Kinesins are the most important molecular motor proteins required for microtubule-dependent transport in neurons, and kinesin-1 is crucial for neuronal transport among all kinesins. Although kinesin-1 is required for normal neuronal functions, the dysfunction of these motor domains leading to neurodegenerative diseases is not fully understood. Here, we reported that the kinesin-I heavy chain (KIF5B), a key molecular motor protein, is involved in tau homeostasis in AD cells and animal models. We found that the levels of KIF5B in P301S tau mice are high. We also found that the knockdown and knockout (KO) of KIFf5B significantly decreased the tau stability, and overexpression of KIF5B in KIF5B-KO cells significantly increased the expression of phosphorylated and total tau levels. This suggested that KIF5B might prevent tau accumulation. By conducting experiments on P301S tau mice, we showed that partially reducing KIF5B levels can reduce hyperphosphorylation of the human tau protein, formation of insoluble aggregates, and memory impairment. Collectively, our results suggested that decreasing KIF5B levels is sufficient to prevent and/or slow down abnormal tau behavior of AD and other tauopathies.

Critical pathways of oral squamous cell carcinoma: molecular biomarker and therapeutic intervention.

The rapid growth of oral cancer is a significant concern, especially in developing countries due to the advanced lifestyle and 5-year survival despite advanced multimodality of cancer care. The poor modality might be due to the detection of disease in the advanced stage. Early detection and development of novel therapies can improve oral cancer patient survival. The PI3K/AKT/mTOR and RAS-RAF-MEK-ERK are very extensively exploited pathways in oral cancer. These pathways are very critical in the progression of tumorigenesis in oral cancer. This review focuses on the association of Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways in terms of protein expression level, genetic mutation, and therapeutic intervention in oral cancer.

Evaluation of metal contamination, flux and the associated human health risk from atmospheric dustfall in metal mining areas of Southern Jharkhand, India.

Metals can be apprehended in the atmospheric environment of copper and iron mining areas of Jharkhand, which falls in one of the most mineralized areas of India with extensive mining and industrial activities. The study was taken up to appraise the metal contamination in the atmospheric dust to evaluate the metal fluxes and associated health risk considering the seasonal variations. Sixty samples were analyzed for As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn using the inductively coupled plasma mass spectrometer (ICP-MS) and the contamination levels were assessed by various indices. The metal content of dustfall samples exceeded the average shale values for most of the metals. Higher metal concentrations were found in the locations in close vicinity of mining and industrial areas. The principal component analysis suggested both geogenic and anthropogenic sources for metals in the atmospheric dustfall. Human health risk as determined by hazard quotient (HQ) and hazard index (HI) suggested considerable risk to the child populace through the ingestion pathway for both the mining areas, higher being in iron mining areas. The metal flux and the health risk were higher in summers as compared to winters for both the mining areas. Consequently, the results advocate the necessity of periodic monitoring of the freefall dust of the mining areas and development of proper management strategies to reduce the metal pollution.

Prevalence of Supernumerary Teeth and Its Associated Complications among School-going Children between the Ages of 6 and 15 Years of Jamshedpur, Jharkhand, India.

Background: Supernumerary teeth (ST) are those that exceed the normal dental formula. This phenomenon is also known as hyperdontia, and can occur in solitary or multiple forms, might be unilateral or bilateral, and affect one or both jaws. Aim: To study the prevalence, gender variations in terms of frequency, characteristic, distribution, and associated complications with the presence of ST in 3,000 school-going children of age 6-15 years in Jamshedpur, Jharkhand, India. Materials and methods: The study consisted of an examination of randomly selected 3,000 children, female (group I) and male (group II), between the age-group of 6 and 15 years, from both private and government-aided schools. Clinical examinations were carried out by a single investigator under natural daylight in a systematic manner using a mouth mirror and straight probe only. The demographic profiles and number of teeth, including the presence of any ST (site, region, eruption status, morphology, and whether it was present unilaterally or bilaterally), were ascertained. Malocclusion or any complications associated with ST were also noted. Results: ST prevalence was found to be 1.87%, with male to female ratio of 2.29:1. Out of 56 children with ST, eight children had double ST while 48 had single, 53 ST were present in maxilla, and only three in mandible. Based on the region, 51 ST were present in the midline, four in the central incisor region, and one in the molar region. According to morphology, 38 ST were conical, 11 ST were tuberculate, and seven ST were supplementary. Twenty-two ST had associated complications, while 34 ST were asymptomatic. Conclusion: ST prevalence is relatively less, but if left neglected, it can pose serious associated dental problems in the child. How to cite this article: Singh AK, Soni S, Jaiswal D, et al. Prevalence of Supernumerary Teeth and Its Associated Complications among School-going Children between the Ages of 6 and 15 Years of Jamshedpur, Jharkhand, India. Int J Clin Pediatr Dent 2022;15(5):504-508.

Evaluation of Oral Hygiene Status among 12-14-Year-Old School Children.

BACKGROUND: Oral diseases such as dental caries, gingivitis, and periodontitis are common among population. The present study was conducted to assess dental caries status and oral hygiene practice among school children. MATERIALS AND METHODS: This school-based study was conducted on 520 children of age group of 12-14 years of both genders. Location, education, and employment status of parents, use of toothbrush, frequency of brushing, dental floss, total number of meals in a day, number of snacks between meals and sugar consumption, and decayed, missing, filled teeth were recorded. RESULTS: There were 266 males and 254 females. Age group 12 years had 80 males and 90 females, 13 years had 70 males and 60 females, and 14 years had 116 males and 104 females. Ninety-six males and 110 females were from urban and 170 males and 144 females were from rural. The mean plaque score in 12-year male children was 0.61 ± 0.32, in 13-year children was 0.68 ± 0.45, and in 14 years was 0.74 ± 0.48. In males, the mean plaque score was 0.70 ± 0.38 and in females was 0.66 ± 0.42. In children from urban area, the mean plaque score was 0.62 ± 0.34 and from rural area was 0.74 ± 0.40. Four hundred and eighteen children were using toothpaste and they had plaque score of 0.76 and 102 children were using floss and they had plaque score of 0.89. Three hundred and twenty children were brushing once, 90 twice, and 110 irregular and there mean plaque score was 0.70, 0.61, and 0.76, respectively. The difference was significant (P < 0.05). CONCLUSION: Authors found that oral health status of children consuming high sugar, more snacks per day, and brushing occasionally was poor.

Multivariate linear regression models for predicting metal content and sources in leafy vegetables and human health risk assessment in metal mining areas of Southern Jharkhand, India.

The present study was intended to investigate the metal concentrations in the leafy vegetables, irrigation water, soil, and atmospheric dust deposition in the iron and copper mining areas of Southern Jharkhand, India. The study aimed to develop a multivariate linear regression (MVLR) model to predict the concentration of metals in leafy vegetables from the metals in associated environmental factors and assessment of the risk to the local population through the consumption of leafy vegetables and other allied pathways. The developed species-specific MVLR models were well fitted to predict the concentration of metals in the leafy vegetables. The coefficient of determination values (R2) was greater than 0.8 for all the species-specific models. Risk assessment was carried out considering multiple pathways of ingestion, inhalation, and dermal contact of vegetables, soil, water, and free-fall dust. Consumption of leafy vegetables was the major route of metal exposure to the local population in both the metal mining areas. The average hazard index (HI) value considering all the metals and pathways was calculated to be 5.13 and 12.1, respectively for iron and copper mining areas suggesting considerable risk to the local residents. Fe, As, and Cu were the major contributors to non-carcinogenic risk in the Iron mining areas while in the case of copper mining areas, the main contributors were Co, As, and Cu.

A study on the interdependence of heavy metals while contributing to groundwater pollution index.

The contribution of heavy metal to the groundwater pollution index (m-HPI) is dependent on other heavy metals present in it. This contribution may be synergistic or anti-synergistic (antagonistic) depending upon the constituent matrix. Both heavy metal type and its concentration are important. m-HPI, a variant of heavy metal pollution index in water, may be calibrated against USEPA hazard index (HI) using a generic multivariate non-linear regression (MVNLR) model. Excellent correlation may be obtained between HI and m-HPI through optimization of normalized weightage factors of constituent metals that contribute to m-HPI. MVNLR model was employed on groundwater samples of ten sites having different heavy metal matrix. The synergistic/antagonistic contribution of heavy metals to m-HPI was well discernible at each site. This study clearly showed that the individual contribution of a particular heavy metal to pollution index might be altered (enhanced or reduced) in the presence of other heavy metals. A calibrated MVNLR model was successfully used for predicting the hazard index (HI) of water samples.

Evaluation of atmospheric dust deposition rates and their mineral characterization in copper and iron mining areas, Singhbhum, India.

Atmospheric dust can play a very important role in the polluted atmosphere. This has a direct impact on human health, global warming, climate change, visibility, precipitation, cloud formation, and so on. To evaluate the atmospheric dustfall rate and their mineralogical aspects, three separate sites were selected, namely mining, suburban, and control for dust sampling. Dustfall samples were collected at monthly intervals from copper and iron mining areas, in Singhbhum, India. The average atmospheric dustfall rate varied from 7.51 to 28.58 g/m2/month, and 7.40 to 26.37 g/m2/month during the summer and winter seasons, respectively, in the copper mining areas. At the same time, an average atmospheric dustfall rate varied from 7.23 to 76.99 g/m2/month during summer season and 6.48 to73.92 g/m2/month during the winter season in the iron mining area. The major minerals identified by X-ray diffraction (XRD) analysis of dustfall samples from copper mining area were quartz, kaolinite, pyrite, albite, and magnesio hornblende. However, in the case of iron mining area, the major minerals found were quartz, cristobalite, hematite, magnetite, biotite, albite, ilmenete, pyrite, rutile, and dolomite. Overall, the intensity of dust pollution is greater in the vicinity of mining and industrial sites of the copper and iron mining areas. Implications: The study has been conducted in the copper and iron mining areas of East and West Singhbhum districts of Jharkhand state, respectively. The aim of the present study was twofold, namely, (i) to evaluate the dustfall rates (ii) and to characterize the mineralogy of atmospheric dust. East and West Singhbhum are the significantly industrialized areas of India known for the mining of copper and iron ores, steel production, power generation, and other related activities. In order to improve local people's living conditions, there is an urgent need for baseline data of dust pollution and its general characteristics based on scientific disclosures to allow policy recommendations and their implementation. Therefore, the study falls within the scope of the journal. The atmospheric dustfall rates were found to be higher during the summer season due to increased dispersion caused by the high wind speed during the summer season. During the winter season, lower rates were observed due to monsoonal rainfall washout and higher relative humidity, which reduces dust resuspension. However, the present study considered the extent of dustfall rates and their mineral characteristics. An immediate need arises to regularly monitor the dust pollution and to implement suitable dust control system like wet dust suppression and airborne dusts capture for dust abatement.

TAF15 contributes to the radiation-inducible stress response in cancer.

Resistance to radiation therapy is a significant problem in the treatment of non-small cell lung cancer (NSCLC). There is an unmet need to discover new molecular targets for drug development in combination with standard of care cancer therapy. We found that TAF15 was radiation-inducible using phage-displayed peptide libraries. In this study, we report that overexpression of TAF15 is correlated with worsened survival in NSCLC patients. Radiation treatment led to surface induction of TAF15 in vitro and in vivo. We genetically silenced TAF15 which led to a significant reduction in proliferation of NSCLC cells. Cells depleted of TAF15 exhibited cell cycle arrest and enhanced apoptosis through activation and accumulation of p53. In combination with radiation, TAF15 knockdown led to a significant reduction in the surviving fraction of NSCLC cell lines. To determine the importance of TAF15 surface expression, we targeted TAF15 with an antibody. In combination with radiation, the anti-TAF15 antibody led to a reduction in the surviving fraction of cancer cells. These studies show that TAF15 is a radiation-inducible molecular target that is accessible to anti-cancer antibodies and enhances cell viability in response to radiation.

Human health risk assessment due to metals in cow's milk from Singhbhum copper and iron mining areas, India.

The concentration of Al, As, Ba, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se and Zn were determined in the milk collected from the locally rearing cows from the vicinity of copper mining areas of East Singhbhum and iron mining areas of West Singhbhum using inductively coupled plasma-mass spectrometry for a risk assessment and source apportionment study. Principal component analysis suggested both natural and anthropogenic activities as causative sources of metals in the milk. The hazard indices ranged from 0.26 to 0.89 with a mean of 0.56 in the iron mining areas and 0.29-1.89 with a mean of 1.17 in the copper mining areas due to ingestion of milk, which indicated that the risk is negligible in the iron mining areas while there is an appreciable risk to the health of consumers of milk in the copper mining areas.

Monte Carlo simulation-based probabilistic health risk assessment of metals in groundwater via ingestion pathway in the mining areas of Singhbhum copper belt, India.

Probabilistic health risk assessment was conducted for metal exposure through groundwater in mining areas of Singhbhum Copper Belt, India. The concentrations of metals showed notable spatial variation exceeding drinking water standards at some of the locations. Hazard Quotient revealed that chronic risks to the local population were largely contributed by Mn, Co and As. The 95th percentiles of Hazard Index (HI) calculated using Monte Carlo simulations showed that the HI for male, female and child populations was 2.87, 2.54 and 4.57 for pre-monsoon, 2.16, 1.88 and 3.49 for monsoon and 2.28, 2.02 and 3.75 for post-monsoon seasons, respectively. The Hazard Indices indicated that amongst the populations, risk was greater for child population and considering the seasons the risk was higher during the pre-monsoon season. The sensitivity analysis suggested that concentration of metals in groundwater and exposure duration were 2 most influential input variables that contributed to the total risk.