Effects of PNA Sequence and Target Site Selection on Function of a 4.5S Non-Coding RNA.

Peptide nucleic acid (PNA) based antisense strategy is a promising therapeutic approach to specifically inhibit target gene expression. However, unlike protein coding genes, identification of an ideal PNA binding site for non-coding RNA is not straightforward. Here, we compare the inhibitory activities of PNA molecules that bind a non-coding 4.5S RNA called SRP RNA, a key component of the bacterial signal recognition particle (SRP). A 9-mer PNA (PNA9) complementary to the tetraloop region of the RNA was more potent in inhibiting its interaction with the SRP protein, compared to an 8-mer PNA (PNA8) targeting a stem-loop. PNA9, which contained a homo-pyrimidine sequence could form a triplex with the complementary stretch of RNA in vitro as confirmed using a fluorescent derivative of PNA9 (F-PNA13). The RNA-PNA complex formation resulted in inhibition of SRP function with PNA9 and F-PNA13, but not PNA8 highlighting the importance of target site selection. Surprisingly, F-PNA13 which was more potent in inhibiting SRP function in vitro, showed weaker antibacterial activity compared to PNA9 likely due to poor cell penetration of the longer PNA. Our results underscore the importance of suitable target site selection and optimum PNA length to develop better antisense molecules against non-coding RNA.

Ni-Catalyzed Diastereoconvergent Intramolecular Alkene-Aldehyde Reductive Coupling: A Route to syn-Chromanols.

We demonstrate for the first time a nickel-catalyzed diastereoconvergent reductive coupling of a heteroatom-attached allyl moiety with aldehydes, viz., O-allyl, O-cinnamyl salicylaldehydes, and others, to afford syn-chromanols exclusively. The reaction proceeds through a [2 + 2 + 1] oxidative cycloaddition involving the active catalyst. This method is applicable to both terminal and internal olefin substrates. The formal syntheses of CP-199.330, CP-199.331, and CP-85.958 have been demonstrated. Control experiments, mass spectrometric analysis, and DFT studies supported the plausible mechanism and the origin of exclusive syn-selectivity.

Assessment of human health hazard associated with heavy metal accumulation in popular freshwater, coastal and marine fishes from south-west region, Bangladesh.

An analysis was conducted on both freshwater, coastal and marine fish species to evaluate the concentrations of heavy metals, with the aim of assessing their levels and examining the potential health risks for humans linked to the consumption of contaminated fish. This study estimate concentrations of Cr, Fe, Cu, As, Cd and Pb in 60 individuals belonging to 20 species (10 species for freshwater and another 10 for coastal and marine fishes) by using Atomic Absorption Spectrophotometer. Metal concentrations of Cr, Fe, and Pb in freshwater fishes and Cr, Fe, As, and Pb in marine fishes were exceeded the maximum allowable concentration (MAC). The Estimated Daily Intake (EDI), Average Pollution Load Index (APLI), Target Hazard Quotient (THQ), Hazard Index (HI) and Target Cancer Risk (TCR) of heavy metals were determined for the assessment of human health risk. Ranking order of the values of EDI for freshwater fishes, coastal and marine fishes were Cd > Fe > Pb > Cr > Cu > As and Cd > Fe > Pb > Cr > As > Cu. Highest APLI value of 8.14 (Puntius ticto) that is seriously polluted and 3.003 observed in Otolichthoides pama in freshwater and marine fishes, respectively. THQPb and THQAs for all the fish species were exceed the safe limit (THQ>1) suggesting potential health risk to consumers. The hazard index for both the fish samples were exceeded the USEPA (United States Environmental Protection Agency) permitted risk level (HI > 1). The target carcinogenic risk value for Cr and As were crossed the USEPA standard limit (TCR> 1E-04), which denotes that continuous consumption of studied fishes may cause health risk to the consumers. On the other hand, sensitivity analysis of freshwater, coastal and marine fishes indicates that all the metal concentrations were responsible factor for health risk.

Angiotensin-Converting Enzyme (ACE) gene polymorphism and arterial blood pressure among the Tawang Monpa of Eastern Himalayan Mountains: Is there a signature of natural selection?

OBJECTIVES: The present paper aims to characterize the Angiotensin-converting enzyme (ACE) genotype, with particular emphasis on its association with arterial oxygen saturation, arterial blood pressure, hemoglobin [Hb] concentration, and ventilatory measures among the Tawang Monpa, a high-altitude native population of the Eastern Himalaya, India. METHODS: A cross-sectional sample of 168Monpa participants from Tawang town, Arunachal Pradesh, India, was selected who live at an altitude of ∼3,200 meters (m) above sea level. For each participant, height, weight, and skinfold thickness were measured, based on which body mass index (BMI, kg/m2) and percentage of body fat (%BF) were calculated. Physiological measures, such as the transcutaneous arterial oxygen saturation (SaO2), hemoglobin [Hb] concentration, forced vital capacity (FVC), forced expiratory volume in 1-second (FEV1), and systemic arterial blood pressure were measured. First, the peripheral venous blood samples (four ml) were drawn, and then white blood cells were separated for the ACE genotyping of each participant. RESULTS: Unlike high-altitude natives from Peru and Ladakh, who exhibit high frequencies of II homozygotes, the Tawang Monpa shows a significantly high frequency of ID heterozygotes (p<0.0001). In addition, no significant association was identified between ACE gene polymorphism and arterial blood pressure, oxygen saturation at rest, vital capacity, or [Hb] concentration. DISCUSSION: The results suggest that the association of the ACE gene with resting SaO2 is inconsistent across native populations living under hypobaric hypoxia. Further, ACE I/D gene polymorphism may not be under natural selection in specific native populations, including Tawang Monpa, for their adaptation to high-altitude hypoxia.

Human adaptation to cold and warm climatic conditions: A comparison between two geographically diverse Indigenous populations.

OBJECTIVES: The present study aims to compare body adiposity and blood pressure (BP) in two climatically and ethnically diverse populations, examining whether thermoregulatory adaptive mechanism may protect Indigenous populations from exhibiting adverse consequences of increased adiposity. METHODS: A cross sectional sample of 404 subjects, of which 200 were Monpa and 204 were Santhal, from two ethnically and geographically distinct populations of India were studied. Body mass index (BMI; kg/m2 ), fat mass (FM; kg), fat free mass (kg), and percent body fat (%BF) were calculated for evaluation of body adiposity. Multivariate multiple regression analysis was adopted to examine the influence of age and sex of populations under study, on body adiposity and BP variables. RESULTS: BMI, %BF, and FM were found to be significantly higher (p ˂ .001) among the Monpa males and females compared with their Santhal counterparts. In contrast, the prevalence of hypertension among Monpa and Santhal is comparable (3.5%Monpa vs. 3.9%Santhal for systolic BP; 8.5%Monpa vs. 8.3%Santhal for diastolic BP). Adiposity, as quantitated by the fat mass index and %BF was significantly (p ˂ .001) correlated to age and sex of study population, explaining ~75.3% and ~75.4% of total variations of these variables, respectively. CONCLUSIONS: Overall the present study suggests that modern human populations follow thermoregulatory mechanism for adaptation to different climatic conditions. Consequently, greater adiposity was evident among the Monpa who adapt to the cold climate, in comparison to their Santhal counterparts who dwell in warm climate.

Prevalence of hypertension among the indigenous population in North-East India: Is this a consequence of "nutritional transition"?

OBJECTIVES: This article aims to understand the influence of residential status on the prevalence of cardiovascular disease (CVD) risk factors among adult Angami Naga of Nagaland. METHODS: A total number of 194 (100 rural and 94 urban) adult Angami Naga participated in the study. Blood pressure, both systolic and diastolic, was measured for each participant. Nutritional status was evaluated through body mass index. Metabolic health was measured through waist circumference, waist-hip ratio and percent body fat (%BF). Multiple regression analysis was done to examine the influence of residential status and other bio-social factors on the prevalence of obesity and hypertension. RESULTS: Results indicate high prevalence of systolic hypertension among urban residents, in both males (29.6%Urban vs. 20.4%Rural ; p > .05) and females (17.4%Urban vs. 11.6%Rural ; p > .05), with gender inequality favoring females. Similar trend was observed in diastolic hypertension as well. On the other hand, obesity was found to be greater in rural males (8.3%Urban vs.10.2%Rural ; p = .002), and urban females (11.6%Urban vs. 3.5%Rural ; p > .05). However in %BF, only negligible percentages of urban females (2.3%Urban vs. 0.0%Rural ; p > .05) were found to be moderately overweight or obese and no males were found to be overweight. Further, regression analyzes indicate that age, sex, and residential status are the most important (p < .001) causal factors behind the prevalence of obesity and hypertension among the Angami Naga. CONCLUSIONS: It was observed that elderly urban males were the most susceptible section of this community in developing CVD risk factors related vulnerabilities. However, we propose understanding this prevalence from an evolutionary approach of physiological mechanism toward nutritional transition in Angami Naga, like many other indigenous populations of northeast India.

Biophysical characterisation of the Bcl-x pre-mRNA and binding specificity of the ellipticine derivative GQC-05: Implication for alternative splicing regulation.

The BCL2L1 gene expresses two isoforms of Bcl-x protein via the use of either of two alternative 5' splice sites (5'ss) in exon 2. These proteins have antagonistic actions, Bcl-XL being anti-apoptotic and Bcl-XS pro-apoptotic. In a number of cancers the Bcl-XL isoform is over-expressed, resulting in cancer cell survival and growth, so switching splicing to the Xs isoform could have therapeutic benefits. We have previously proposed that a putative G-quadruplex (G4) exists downstream of the XS 5'ss and shown that the ellipticine derivative GQC-05, a previously identified DNA G4-specific ligand, induces an increase in the XS/XL ratio both in vitro and in cells. Here, we demonstrate that this G4 forms in vitro and that the structure is stabilised in the presence of GQC-05. We also show that GQC-05 binds RNA non-specifically in buffer conditions, but selectively to the Bcl-x G4 in the presence of nuclear extract, highlighting the limitations of biophysical measurements taken outside of a functional environment. We also demonstrate that GQC-05 is able to shift the equilibrium between competing G4 and duplex structures towards the G4 conformation, leading to an increase in accessibility of the XS 5'ss, supporting our previous model on the mechanism of action of GQC-05.

A comparative analysis of dietary intake and body composition among two ethnically distinct tribal populations from India.

OBJECTIVES: The present paper is an attempt to understand ethnic variations in the association of dietary intake with body composition in two geographically and genetically diverse adult populations, i.e., Santhal, an indigenous group from the plain regions of eastern India and Monpa, an indigenous population from the high-altitude regions of north-eastern India. METHODS: A total number of 200 adult Monpa and 204 adult Santhal were recruited for the present investigation, which was conducted in phases. Multiple and multivariate regression frameworks were used in the paper to evaluate the influence of dietary intake on body composition. RESULTS: In somatotype, the Santhal were found to be predominantly mesomorphic, whereas the Monpa were predominantly endomorphic, irrespective of their gender. Similarly, significantly (p < 0.001) greater percentages of overweight and obese individuals were found among the Monpa, but not among the Santhal. CONCLUSIONS: Despite the fact that both these tribes are engaged in primitive technology-based agriculture that requires a lot of physical labour, such difference in their body composition could be due to fundamental differences in the physical environment and great dietary/nutritional intake. In fact, it was found that Monpa follow a daily diet that is highly rich in dairy fat and animal protein, as compared to their counterpart Santhal. Santhal's daily diet generally consists of rice and boil vegetables, with protein consumption as low as once or twice a month. However, despite these differences the paper revealed no significant influence of dietary intake on the body composition of these populations. Hence, an adaptive approach is proposed to understand the substantial proportion of body composition variations in these two ethnically diverse populations.

Is craniofacial morphology and body composition related by common genes: Comparative analysis of two ethnically diverse populations.

OBJECTIVES: The overarching hypothesis of the present paper is that ethnically and/or genetically diverse human populations may exhibit similarity in correlations between various aspects of human phenotypes due to the morphological integration process during the ontogenetic stages. To test this we investigated whether an association between craniofacial (CF) features and body composition (BC) variations is present in humans and the extent to which such possible associations are comparable in different populations. Furthermore, the paper examines the contribution of common genetic (additive) and shared familial environmental factors in assessing the correlation between CF and BC characteristics in humans. MATERIALS AND METHODS: Two pedigree-based samples were collected from two distinct populations, including India (Santhal) and Europe (Chuvash). Canonical correlation analysis was used to compare the association between CF and BC characteristics in the two studied samples. The contribution of genetic and familial environmental factors on the correlation between CF and BC features was analyzed through variance decomposition analysis by implementing the Mendelian Analysis package (MAN). RESULTS: Our study suggests that CF morphology is significantly (p < 0.001) associated with BC variation in both samples. CF characteristics and BC phenotypes revealed a consistent trend in both samples where condensed and broad CF morphology was significantly associated with increased fat accumulation, with slight variations between the Santhal and Chuvash samples. Despite the variations observed between the samples, the heritability estimates were impressively equivalent for traits like total facial height (55.6%Santhal vs.56.1%Chuvash ) and nasal index (42.8%Santhal vs. 43.3%Chuvash ). DISCUSSION: The genetic contribution of CF morphology appeared to be extensive and the contribution of common genetic and shared family environmental correlations between CF and BC measures were suggestively substantial. Accordingly, these correlations were consistently observed across ethnically diverse populations, despite drastic morphological differences between the samples under comparison.

Screening of Ischemic Heart Disease based on PPG Signals using Machine Learning Techniques.

The increasing rate of cardiac ailments has led to the rise in the scrutinization of ones cardiac health. The prevalent techniques for detecting heart diseases are costly and require expert supervision as well as modern equipment. Thus there is a need for an alternative low cost and easily available technique. Finger-tip photoplethysmography (PPG) signals can be used for identifying Ischemic Heart Disease (IHD). This technique of screening the disease will be very helpful to the inhabitants of remote, underdeveloped and unprivileged areas. Time-domain analysis of the signal was done for extracting different features. Segregation of diseased and healthy subjects was performed using Decision Trees, Discriminant Analysis, Logistic Regression, Support Vector Machine, KNN, and Boosted trees. Ten different performance metrics was studied using the confusion matrix. After analysis, the accuracy, sensitivity, specificity, and precision of 0.94, 0.95, 0.95 and 0.97 respectively was obtained using Boosted tress classifier. ROC and AUC were calculated to establish the robustness of the classification methods for determining IHD patients.

Small-Molecule Inhibitor Prevents Insulin Fibrillogenesis and Preserves Activity.

Amyloidosis is a well-known but poorly understood phenomenon caused by the aggregation of proteins, often leading to pathological conditions. For example, the aggregation of insulin poses significant challenges during the preparation of pharmaceutical insulin formulations commonly used to treat diabetic patients. Therefore, it is essential to develop inhibitors of insulin aggregation for potential biomedical applications and for important mechanistic insights into amyloidogenic pathways. Here, we have identified a small molecule M1, which causes a dose-dependent reduction in insulin fibril formation. Biophysical analyses and docking results suggest that M1 likely binds to partially unfolded insulin intermediates. Further, M1-treated insulin had lower cytotoxicity and remained functionally active in regulating cell proliferation in cultured Drosophila wing epithelium. Thus, M1 is of great interest as a novel agent for inhibiting insulin aggregation during biopharmaceutical manufacturing.

Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude.

Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO2max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene (EGLN1) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O2 sensor that controls levels of the Hypoxia Inducible Factor-α (HIF-α), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO2max (L⋅min-1 and mL⋅min-1⋅kg-1) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO2max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO2max genotype categories differing by ∼11% (e.g., for rs1769793 SNP genotype TT = 34.2 mL⋅min-1⋅kg-1 vs. CC = 30.5 mL⋅min-1⋅kg-1). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O2 delivery or use during exercise at altitude in Peruvian Quechua.

Exhaled nitric oxide in ethnically diverse high-altitude native populations: A comparative study.

OBJECTIVES: Andean and Tibetan high-altitude natives exhibit a high concentration of nitric oxide (NO) in the lungs, suggesting that NO plays an adaptive role in offsetting hypobaric hypoxia. We examined the exhaled NO concentration as well as partial pressure of several additional high-altitude native populations in order to examine the possibility that this putative adaptive trait, that is, high exhaled NO, is universal. METHODS: We recruited two geographically diverse highland native populations, Tawang Monpa (TM), a Tibetan derived population in North-Eastern India (n = 95, sampled at an altitude of ~3,200 m), and Peruvian Quechua from the highland Andes (n = 412). The latter included three distinct subgroups defined as those residing at altitude (Q-HAR, n = 110, sampled at 4,338 m), those born and residing at sea-level (Q-BSL, n = 152), and those born at altitude but migrant to sea-level (Q-M, n = 150). In addition, we recruited a referent sample of lowland natives of European ancestry from Syracuse, New York. Fraction of exhaled NO concentrations were measured using a NIOX NIMO following the protocol of the manufacturer. RESULTS: Partial pressure of exhaled nitric oxide (PENO) was significantly lower (p < .05) in both high-altitude resident groups (TM = 6.2 ± 0.5 nmHg and Q-HAR = 5.8 ± 0.5 nmHg), as compared to the groups measured at sea level (USA = 14.6 ± 0.7 nmHg, Q-BSL = 18.9 ± 1.6 nmHg, and Q-M = 19.2 ± 1.7 nmHg). PENO was not significantly different between TM and Q-HAR (p < .05). CONCLUSION: In contrast to previous work, we found lower PENO in populations at altitude (compared to sea-level) and no difference in PENO between Tibetan and Andean highland native populations. These results do not support the hypothesis that high nitric oxide in human lungs is a universal adaptive mechanism of highland native populations to offset hypobaric hypoxia.

Estimation of echocardiogram parameters with the aid of impedance cardiography and artificial neural networks.

The advent of cardiovascular diseases as a disease of mass catastrophy, in recent years is alarming. It is expected to spread as an epidemic by 2030. Present methods of determining the health of one's heart include doppler based echocardiogram, MDCT (Multi Detector Computed Tomography), among various other invasive and non-invasive hemodynamic monitoring techniques. These methods require expert supervision and costly clinical set-ups, and cannot be employed by a common individual to perform a self diagnosis of one's cardiac health, unassisted. In this work, the authors propose a novel methodology using impedance cardiography (ICG), for the determination of a person's cardio-vascular health. The recorded ICG signal helps in extraction of features which are used for estimating parameters for cardiac health monitoring. The proposed methodology with the aid of artificial neural network is able to determine Stroke Volume (SV), Left Ventricular End Systolic Volume (LVESV), Left Ventricular End Diastolic Volume (LVEDV), Left Ventricular Ejection Fraction (LVEF), Iso Volumetric Contraction Time (IVCT), Iso Volumetric Relaxation Time (IVRT), Left Ventricular Ejection Time (LVET), Total Systolic Time (TST), Total Diastolic Time (TDT), and Myocardial Performance Index (MPI), with error margins of ±8.9%, ±3.8%, ±1.4%, ±7.8%, ±16.0%, ±9.0%, ±9.7%, ±6.9%, ±6.2%, and ±0.9%, respectively. The proposed methodology could be used in screening of precursors to cardiac ailments, and to keep a check on the cardio-vascular health.

Stroke Volume, Ejection Fraction and Cardiac Health Monitoring using Impedance Cardiography.

In recent years occurrence of cardiac ailments have seen an exponential rise. In view of this it is highly important to monitor one's cardiac health. Currently employed methods for cardiac health monitoring are costly, require expert supervision and are available only at central hospitals. In order to overcome these obstacles, we have proposed a novel, non-invasive, cardiac health monitoring mechanism based on Impedance Cardiography (ICG). In this work we have proposed a methodolgy for determination of stroke volume (SV), left ventricular ejection fraction (LVEF), left ventricular end systolic volume (LVESV), and iso-volumetric relaxation time (IVRT), based on ICG. The proposed models report $\mathrm{r}^{2}$ values of 0.86, 0.97, 0.99, and 0.96 for SV, LVESV, LVEF, and IVRT, respectively. The proposed methodology also provides us an insight into the use of ICG for cardiac health monitoring, and diagnosis of critical cardiac ailments.

A Deep Convolutional Neural Network Based Classification Of Multi-Class Motor Imagery With Improved Generalization.

Motor imagery (MI) based brain-computer interface (BCI) plays a crucial role in various scenarios ranging from post-traumatic rehabilitation to control prosthetics. Computer-aided interpretation of MI has augmented prior mentioned scenarios since decades but failed to address interpersonal variability. Such variability further escalates in case of multi-class MI, which is currently a common practice. The failures due to interpersonal variability can be attributed to handcrafted features as they failed to extract more generalized features. The proposed approach employs convolution neural network (CNN) based model with both filtering (through axis shuffling) and feature extraction to avail end-to-end training. Axis shuffling is performed adopted in initial blocks of the model for 1D preprocessing and reduce the parameters required. Such practice has avoided the overfitting which resulted in an improved generalized model. Publicly available BCI Competition-IV 2a dataset is considered to evaluate the proposed model. The proposed model has demonstrated the capability to identify subject-specific frequency band with an average and highest accuracy of 70.5% and S3.6% respectively. Proposed CNN model can classify in real time without relying on accelerated computing device like GPU.

Synthesis, characterization and unravelling the molecular interaction of new bioactive 4-hydroxycoumarin derivative with biopolymer: Insights from spectroscopic and theoretical aspect.

In the progress of small molecule as drug candidates, 4-hydroxycoumarin based compounds bearing a crucial place as potent antibiotic agents with appreciable safety in drug invention. Being synthetically and easily obtainable, 4-hydroxycoumarin related compounds with planar structure have been promoted predominantly as DNA targeting agent. Nevertheless, here we elucidate the synthesis, characterization and theoretical study of bio-active small molecule 4-hydroxy-3,4'-bichromenyl-2,2'-dione (4HBD). Then we have illuminated the binding interactions of 4HBD with calf thymus DNA (ctDNA), which is particularly designed for biological application. Extensive investigations of the binding of 4HBD with ctDNA are provided by utilizing multi-spectroscopic and molecular docking approaches, including UV-vis absorbance, steady-state, time-resolved fluorescence spectroscopy and circular dichroism study. The calculated binding and quenching constant value from quantitative data analysis of absorption and emission spectroscopy shows that 4HBD binds to the ctDNA groove. Further confirmation of the same is found by comparative displacement and iodide quenching studies. Negative enthalpy, negative free energy and positive entropy change imply a hydrophobic force monitors the association of 4HBD with the biomacromolecule. Interestingly the small molecule (4HBD) shows potential anti-bacterial activity against the model pathogenic gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria. The noncytotoxic nature of the 4HBD is demonstrated in vitro with the help of MTT assay by normal kidney epithelial (NKE), breast cancer cells (MCF-7) and human prostate cancer cell (PC3) lines. Hemolytic assay exhibits insignificant hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. In this regard the present invention of 4-hydroxycoumarin based antimicrobial and noncytotoxic 4HBD molecule holds future promise in the development of new antibiotics.

Peptide nucleic acid mediated inhibition of the bacterial signal recognition particle.

We have identified the bacterial signal recognition particle (SRP) as a novel antibacterial target. As a proof of principle, we used an antisense peptide nucleic acid to target a key SRP RNA. The PNA molecules showed efficient inhibition of SRP function and bacterial cell growth, thereby validating our hypothesis.

Seasonal Transition in PM10 Exposure and Associated All-Cause Mortality Risks in India.

Lack of a consistent PM10 (particulate matter smaller than 10 µm) database at high spatial resolution hinders in assessing the environmental impact of PM10 in India. Here we propose an alternate approach to estimate the PM10 database. Aerosol extinction coefficients at the surface are calculated from midvisible aerosol optical depth from MERRA-2 reanalysis data using characteristics vertical profiles from CALIOP and then are converted to PM10 mass using aerosol property information and microphysical data. The retrieved PM10 are bias-corrected and evaluated ( R2 = 0.85) against coincident ground-based data maintained under the Central Pollution Control Board network. PM10 exposure exceeds Indian annual air quality standard in 72.3% districts. Transition in PM10 exposure from the monsoon (Jun-Sep) to postmonsoon season (Oct-Nov) translates to 1-2% higher all-cause mortality risk over the polluted Indo-Gangetic Basin (IGB). Mortality risk increases in the central to eastern IGB and central India and reduces in Delhi national capital region in the winter (Dec-Feb) relative to the postmonsoon season. Mortality risk decreases by 0.5-1.8% in most parts of India in the premonsoon season (Mar-May). Our results quantify the vulnerability in terms of seasonal transition in all-cause mortality risks due to PM10 exposure at district level for the first time in India.