Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Exploring a variance decomposition approach integrated with the Monte Carlo method to evaluate groundwater fluoride exposure on the residents of a typical fluorosis endemic semi-arid tract of India.

This study appraised the groundwater fluoride (F-) endemicity and the exposure levels under the Central Tendency Exposure (CTE) condition and the Reasonable Maximum Exposure (RME) condition on the residents of the semi-arid parts of the Birbhum district of Peninsular India using a Variance Decomposition (Sobol Sensitivity Indices) approach combined with Monte Carlo Simulations. The study finds the national scale drinking water standard limit for F- (1.5 mg L-1) is inappropriate for the present survey area where F- concentration in groundwater varied between 0.26 and 11.82 mg L-1 and ~54.5% of the samples (N = 400) exceeded this limit. Therefore, estimated the optimum F- concentration of 0.733 mg L-1 for the region using the method recommended by the World Health Organization (WHO) to calculate the optimum F- limit at a regional scale. The average value of F- concentrations for this region (1.71 mg L-1) is considerably higher than the estimated optimum concentration or even the maximum permissible limits recommended for the subtropical regions (0.5-0.7 mg L-1). The exposure analysis revealed the infants and children as potentially vulnerable populations compared to adolescents and adults of the study area for CTE and RME scenarios. The multi-exposure pathways indicated oral intake as the main exposure pathway whereas exposure through dermal contact was insignificant for the residents of all age groups of this region. Based on the first, second and total order Sobol Sensitivity Indices, F- concentration (C) in groundwater, the groundwater ingestion rate and their combined interaction are the greatest significant parameters for the oral exposure model whereas C and its interaction effects with the proportion of the skin surface area in contact with groundwater as the utmost sensitive variables for the dermal health risks assessment model. The present study insists the inhabitants to intake defluoridated groundwater.

Cooperativity of membrane-protein and protein-protein interactions control membrane remodeling by epsin 1 and affects clathrin-mediated endocytosis.

Membrane remodeling is a critical process for many membrane trafficking events, including clathrin-mediated endocytosis. Several molecular mechanisms for protein-induced membrane curvature have been described in some detail. Contrary, the effect that the physico-chemical properties of the membrane have on these processes is far less well understood. Here, we show that the membrane binding and curvature-inducing ENTH domain of epsin1 is regulated by phosphatidylserine (PS). ENTH binds to membranes in a PI(4,5)P2-dependent manner but only induces curvature in the presence of PS. On PS-containing membranes, the ENTH domain forms rigid homo-oligomers and assembles into clusters. Membrane binding and membrane remodeling can be separated by structure-to-function mutants. Such oligomerization mutants bind to membranes but do not show membrane remodeling activity. In vivo, they are not able to rescue defects in epidermal growth factor receptor (EGFR) endocytosis in epsin knock-down cells. Together, these data show that the membrane lipid composition is important for the regulation of protein-dependent membrane deformation during clathrin-mediated endocytosis.

Evaluation of groundwater quality for irrigation water supply using multi-criteria decision-making techniques and GIS in an agroeconomic tract of Lower Ganga basin, India.

Groundwater irrigation has evolved the monocropping cultivation pattern to multi-cropping, especially in many arid/semi-arid tracts globally. Irrigation practices with the groundwater of poor quality can limit the selection of the crop, reduce crop yields and degrade the soil quality. The present study has been undertaken to identify the hydrogeochemical phenomena of groundwater systems in the south-western Birbhum district, India and to analyze groundwater suitability for irrigation during the pre-and post-monsoon cycles by adopting the Irrigation Water Quality Index (IWQI) using Multivariate Factor Analysis along with some traditional methods viz. sodium adsorption ratio, sodium percentage, magnesium hazards, residual sodium bicarbonate (RSBC) and carbonate (RSC), Wilcox's and USSL diagrams, permeability index and Kelly's index. The hydrogeochemical analysis revealed that chemical weathering and evaporation are predominant in the aquifer systems. Groundwater quality reflected soil salinity, sodicity and magnesium hazards risks and water toxicity to the sensitive plants at 0-46.4% of the post-monsoon samples and 0-38.4% of the pre-monsoon samples based on the individual traditional methods whereas about 97.73-98.88% of the total area was classified as moderate to severely unsuitable for irrigation during both seasons when integrated multiple parameters using the IWQI method. Prolonged use of such groundwater for irrigation is susceptible to causing moderate to severe infiltration problems at a greater extent of the study area. The study recommends adaptation of salinity, sodicity and RSC/RSBC reduction procedures (e.g., the use of acid and gypsum amendments in the irrigation lands and through water blending) and advanced irrigation practices (viz. drips, sprinklers and micro irrigations) to prevent soil degradation and increase crops productivity. Adopting Managed Aquifer Recharge procedures as well as rainwater harvesting in the areas bearing unsuitable water quality can dilute the ionic concentrations of the groundwater facies which in turn will improve the groundwater quality for irrigation.

Groundwater fluoride contamination, probable release, and containment mechanisms: a review on Indian context.

Fluoride contamination in the groundwater has got great attention in last few decades due to their toxicity, persistent capacity and accumulation in human bodies. There are several sources of fluoride in the environment and different pathways to enter in the drinking water resources, which is responsible for potential effect on human health. Presence of high concentration of fluoride ion in groundwater is a major issue and it makes the water unsuitable for drinking purpose. Availability of fluoride in groundwater indicates various geochemical processes and subsurface contamination of a particular area. Fluoride-bearing aquifers, geological factors, rate of weathering, ion-exchange reaction, residence time and leaching of subsurface contaminants are major responsible factors for availability of fluoride in groundwater. In India, several studies have reported that the groundwater of several states are contaminated with high fluoride. The undesirable level of fluoride in groundwater is one of the most natural groundwater quality problem, which affects large portion of arid and semiarid regions of India. Rajasthan, Andhra Pradesh, Telangana, Tamil Nadu, Gujarat, and West Bengal are the relatively high-fluoride-contaminated states in India. Chronic ingestion of high doses of fluoride-rich water leads to fluorosis on human and animal. Over 66 million Indian populations are at risk due to excess fluoride-contaminated water. Therefore, groundwater contamination subject to undesirable level of fluoride needs urgent attention to understand the role of geochemistry, hydrogeology and climatic factors along with anthropogenic inputs in fluoride pollution.

Examination of Sec22 Homodimer Formation and Role in SNARE-dependent Membrane Fusion.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein complexes play essential roles in catalyzing intracellular membrane fusion events although the assembly pathway and molecular arrangement of SNARE complexes in membrane fusion reactions are not well understood. Here we monitored interactions of the R-SNARE protein Sec22 through a cysteine scanning approach and detected efficient formation of cross-linked Sec22 homodimers in cellular membranes when cysteine residues were positioned in the SNARE motif or C terminus of the transmembrane domain. When specific Sec22 cysteine derivatives are present on both donor COPII vesicles and acceptor Golgi membranes, the formation of disulfide cross-links provide clear readouts on trans- and cis-SNARE arrangements during this fusion event. The Sec22 transmembrane domain was required for efficient homodimer formation and for membrane fusion suggesting a functional role for Sec22 homodimers. We propose that Sec22 homodimers promote assembly of higher-order SNARE complexes to catalyze membrane fusion. Sec22 is also reported to function in macroautophagy and in formation of endoplasmic reticulum-plasma membrane contact sites therefore homodimer assembly may regulate Sec22 activity across a range of cellular processes.

New immune horizons in therapeutics and diagnostic approaches to Preeclampsia.

Hypertensive disorders of pregnancy (HDP) are one of the commonest maladies, affecting 5%-10% of pregnancies worldwide. The American College of Obstetricians and Gynecologists (ACOG) identifies four categories of HDP, namely gestational hypertension (GH), Preeclampsia (PE), chronic hypertension (CH), and CH with superimposed PE. PE is a multisystem, heterogeneous disorder that encompasses 2%-8% of all pregnancy-related complications, contributing to about 9% to 26% of maternal deaths in low-income countries and 16% in high-income countries. These translate to 50 000 maternal deaths and over 500 000 fetal deaths worldwide, therefore demanding high priority in understanding clinical presentation, screening, diagnostic criteria, and effective management. PE is accompanied by uteroplacental insufficiency leading to vascular and metabolic changes, vasoconstriction, and end-organ ischemia. PE is diagnosed after 20 weeks of pregnancy in women who were previously normotensive or hypertensive. Besides shallow trophoblast invasion and inadequate remodeling of uterine arteries, dysregulation of the nonimmune system has been the focal point in PE. This results from aberrant immune system activation and imbalanced differentiation of T cells. Further, a failure of tolerance toward the semi-allogenic fetus results due to altered distribution of Tregs such as CD4+FoxP3+ or CD4+CD25+CD127(low) FoxP3+ cells, thereby creating a cytotoxic environment by suboptimal production of immunosuppressive cytokines like IL-10, IL-4, and IL-13. Also, intracellular production of complement protein C5a may result in decreased FoxP3+ regulatory T cells. With immune system dysfunction as a major driver in PE pathogenesis, it is logical that therapeutic targeting of components of the immune system with pharmacologic agents like anti-inflammatory and immune-modulating molecules are either being used or under clinical trial. Cholesterol synthesis inhibitors like Pravastatin may improve placental perfusion in PE, while Eculizumab (monoclonal antibody inhibiting C5) and small molecular inhibitor of C5a, Zilucoplan are under investigation. Monoclonal antibody against IL-17(Secukinumab) has been proposed to alter the Th imbalance in PE. Autologous Treg therapy and immune checkpoint inhibitors like anti-CTLA-4 are emerging as new candidates in immune horizons for PE management in the future.

Monosodium Glutamate Perturbs Human Trophoblast Invasion and Differentiation through a Reactive Oxygen Species-Mediated Pathway: An In-Vitro Assessment.

The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food additive, which is widely used in Asian cuisine and is an ingredient that brings out the "umami" meat flavor. MSG consumption in rats is associated with ROS generation. Owing to its consumption as part of the fast-food culture and concerns about its possible effects on pregnancy, we aimed to study the impact of MSG on placental trophoblast cells. MSG exposure influenced trophoblast invasion and differentiation, two of the most critical functions during placentation through enhanced production of ROS. Similar findings were also observed on MSG-treated placental explants, as confirmed by elevated Nrf2 levels. Ultrastructural studies revealed signs of subcellular injury by MSG exposure. Mechanistically, MSG-induced oxidative stress with endoplasmic reticulum stress pathways involving Xbp1s and IRE1α was observed. The effect of MSG through an increased ROS production indicates that its long-term exposure might have adverse health effect by compromising key trophoblast functions.

Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance.

Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings.

Hydrogeochemical characterizations and quality evaluation of groundwater in the major river basins of a geologically and anthropogenically driven semi-arid tract of India.

Access to clean drinking water has been acknowledged as a human right and assessing the hydrogeochemistry and groundwater quality status plays an important role in proving cleaner and safer water for human consumption. This study evaluated the sources and driving factors of the groundwater facies in the five major river basins (viz. Ajay, Mayurakshi, Kopai, Brahmani and Dwarka) of an agroeconomic semi-arid Indian tract through hydrogeochemical and principal component analyses based on 2200 groundwater samples (Ns = 2200) obtained during the pre- and post-monsoon cycles from 1100 wells (Nw = 1100). The results revealed that minerals weathering, ion/reverse ion exchange, mixing and evaporation processes along with anthropogenic inputs are responsible for the deteriorated groundwater quality of the river basins. The study has considered the cokriging approach that uses geostatistical and multivariate statistical techniques to interpolate a dataset. To determine the spatio-seasonal variabilities of the groundwater facies more accurately, the estimation accuracies of different interpolation techniques viz. inverse distance weighting, kriging/cokriging and splines techniques were compared and kriging/cokriging was found to represent the variability more accurately. Shannon's entropy theory was employed to assess the groundwater quality of the river basins as it eliminates the subjective bias and inherent uncertainties of the groundwater systems. Groundwater in ~37.45-38.42% of the total area was moderate to extremely poor for human consumption where 10.40-12.14%, 9.09-12.40%, 21.18-22.35%, 15.20-19.93% and 6.48-8.80% samples from the Ajay (Nw = 175), Brahmani (Nw = 175), Dwarka (Nw = 180), Kopai (Nw = 350) and Mayurakshi (Nw = 220) river basins exhibited unfit to drink water quality. The sensitivity of the water quality model was analyzed to identify the influences of the individual parameters which revealed that the outcome does not depend solely on one parameter. The study recommends adaptation of the treatment techniques to ensure clean drinking water for the residents. Managed aquifer recharge techniques might also improve the groundwater quality in certain areas.

Characterization of groundwater nitrate exposure using Monte Carlo and Sobol sensitivity approaches in the diverse aquifer systems of an agricultural semiarid region of Lower Ganga Basin, India.

Prevalence of nitrate in different aquifer systems is a growing environmental and public health concern. Efforts were made for the first-time to achieve a higher accuracy in health risks characterization associated with the nitrate in groundwater of the diverse aquifer systems on the residents of a semi-arid rural tract of Lower Ganga Basin using Monte Carlo Simulations and Sobol Sensitivity analyses. The nitrate levels in groundwater varied between 0 and 508.3 mg/L with a mean of 19.79 ± 32.78 mg/L and 0-435.0 mg/L with a mean of 24.44 ± 35.15 mg/L during the pre-monsoon and post-monsoon periods, respectively. About 847.12-1000.25 km2 area of the survey area (total area 4545 km2) exhibited nitrate concentrations (C) > the pre-intervention limits (45-50 mg/L). Minor populations, especially the infants from the granite gneiss, Rajmahal traps, laterite, recent alluvial and old alluvial aquifer zones under the Central Tendency Exposure (CTE) condition and all the aquifer zones (including the Gondwana supergroup aquifer zone) under Reasonable Maximum Exposure (RME) scenarios, were characterized as being at high risks of methemoglobinemia, primarily due to ingestion of untreated nitrate contaminated groundwater. Residents of the alluvial aquifer zones of the study area were found to the most vulnerable to the groundwater nitrate toxicity through oral and dermal exposures. The study validated the prediction accuracies of different interpolation methods including the Spline, Kriging, polynomial and Inverse Distance Weighted and revealed that Kriging predicted the Spatio-seasonal variations of groundwater nitrate of the district more accurately. Sobol Sensitivity analysis revealed C and the interaction effects of C and groundwater Ingestion Rate (IR), and C and Fraction of skin area contacted with groundwater (F) as the influential parameters for oral and dermal health risks exposure models. Therefore, the study recommends to residents of the study area to consume treated groundwater to mitigate nitrate related health morbidities.

MICOS and the mitochondrial inner membrane morphology - when things get out of shape.

Mitochondria play a key role in cellular signalling, metabolism and energetics. Proper architecture and remodelling of the inner mitochondrial membrane are essential for efficient respiration, apoptosis and quality control in the cell. Several protein complexes including mitochondrial contact site and cristae organizing system (MICOS), F1 FO -ATP synthase, and Optic Atrophy 1 (OPA1), facilitate formation, maintenance and stability of cristae membranes. MICOS, the F1 FO -ATP synthase, OPA1 and inner membrane phospholipids such as cardiolipin and phosphatidylethanolamine interact with each other to organize the inner membrane ultra-structure and remodel cristae in response to the cell's demands. Functional alterations in these proteins or in the biosynthesis pathway of cardiolipin and phosphatidylethanolamine result in an aberrant inner membrane architecture and impair mitochondrial function. Mitochondrial dysfunction and abnormalities hallmark several human conditions and diseases including neurodegeneration, cardiomyopathies and diabetes mellitus. Yet, they have long been regarded as secondary pathological effects. This review discusses emerging evidence of a direct relationship between protein- and lipid-dependent regulation of the inner mitochondrial membrane morphology and diseases such as fatal encephalopathy, Leigh syndrome, Parkinson's disease, and cancer.

Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway.

Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia-reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.

EMTiness in pseudo-malignant behavior of trophoblasts during embryo implantation.

Implantation in humans is a multistep process that involves apposition, adhesion, and invasion of the developing blastocyst into the receptive maternal endometrium. Though significant volume of research in this direction has identified important players orchestrating this delicate process, there are still gaps in our understanding of all the sequence of events during embryo implantation. Also, the early pregnancy-related complications that lead to fetal loss and miscarriage often occur in this critical window of implantation, which is primarily defined as the time when the maternal endometrium is supposed to be most receptive to the free blastocyst that emerges out from the zona pellucida. Studies in humans and rodents have identified several mediators like folliculin, LIF, IL11Ra, splicing factor SC35, etc. to be essential for early implantation. Trophoblasts, that form the outer epithelial layer of the blastocyst, participate in the formation of the placenta. During placentation, invasive extravillous trophoblasts (EVTs), migrate into the endometrium, and a transient epithelial to mesenchymal transition (EMT) and remodel the uterine arteries for blood and nutrient exchange.

Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions - An in-silico study.

BACKGROUND: Though a large number of pregnant females have been affected by COVID-19, there is a dearth of information on the effects of SARS-CoV-2 infection on trophoblast function. We explored in silico, the potential interactions between SARS-CoV-2 proteins and proteins involved in the key functions of placenta. METHODS: Human proteins interacting with SARS-CoV-2 proteins were identified by Gordon et al. (2020). Genes that are upregulated in trophoblast sub-types and stages were obtained by gene-expression data from NCBI-GEO and by text-mining. Genes altered in pathological states like pre-eclampsia and gestational diabetes mellitus were also identified. Genes crucial in placental functions thus identified were compared to the SARS-CoV-2 interactome for overlaps. Proteins recurring across multiple study scenarios were analyzed using text mining and network analysis for their biological functions. RESULTS: The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta. Other proteins that interact with SARS-CoV-2 like LOX, Fibulins-2 and 5, NUP98, GDF15, RBX1, CUL3, HMOX1, PLAT, MFGE8, and MRPs are vital in placental functions like trophoblast invasion and migration, syncytium formation, differentiation, and implantation. TLE3, expressed across first trimester placental tissues and cell lines, is involved in formation of placental vasculature, and is important in SARS-CoV (2003) budding and exit from the cells by COPI vesicles. CONCLUSION: SARS-CoV-2 can potentially interact with proteins having crucial roles in the placental function. Whether these potential interactions identified in silico have effects on trophoblast functions in biological settings needs to be addressed by further in vitro and clinical studies.

Characterization of heavy metal pollution in an anthropogenically and geologically influenced semi-arid region of east India and assessment of ecological and human health risks.

The present study evaluated the heavy metal contamination in groundwater and associated ecological and human health risks of a geologically and anthropogenically diverse semi-arid region of Birbhum district, India. For a reliable evaluation, concentrations of nine heavy metals in 680 groundwater samples (N = 680) which were collected during premonsoon and postmonsoon seasons of consecutive two years from 170 wells were measured. The human health risk assessment using the USEPA model which is based on single value for each parameter may inherit certain inaccuracy and uncertainties in the evaluation. Unlike earlier studies, a higher degree of accuracy in carcinogenic and noncarcinogenic health risk assessments was achieved through Monte Carlo simulations, sensitivity analysis and uncertainty analysis. The study revealed the occurrence of the target heavy metals in groundwater with mean dominance order of Fe > Zn > Sr > Mn > Cr > Pb > Ni > Cu > Cd where mean concentrations of the carcinogens, Pb and Fe exceeded their maximum permissible limits. The water quality status evaluated using the modified heavy metal pollution index, Nemerow index and Heavy metal evaluation index methods resulted in medium to high heavy metal contamination in groundwater within a large portion of the study area which indicated its unsuitability for drinking purpose. The study suspects a moderate to very high risk for the groundwater dependent ecosystems in major part of the study area. The study further revealed cancer risks, ranging from high to very high within the residents due to accumulative exposure of the carcinogenic heavy metals in groundwater through ingestion and dermal contact. Minor populations of the study area were found to be more vulnerable to the carcinogenic and noncarcinogenic diseases than teenagers and adults, mainly through oral exposure. The study recommends the residents to consume treated groundwater since the primary route of heavy metal exposure was identified to be the ingestion route.

Exploring a multi-exposure-pathway approach to assess human health risk associated with groundwater fluoride exposure in the semi-arid region of east India.

Human health risks associated with groundwater fluoride have been assessed using USEPA method in few parts of India, but those assessments were conducted based on a single value for each parameter, which may lead to certain inaccuracy and uncertainties in results. In this study, a higher degree of accuracy in health risk assessment was achieved through Monte Carlo simulations, sensitivity analysis and uncertainty analysis. As fluoride hazards to human health are chronic, a total of 4560 water samples (N = 4560) were collected during consecutive four seasons (2 pre-monsoon and 2 post-monsoon seasons; 1140 samples/season) from the entire Birbhum district, covering all the blocks and geological settings to obtain the spatiotemporal variation of fluoride level. The Empirical Bayesian Kriging geostatistical model was employed to determine fluoride endemic areas. Amongst all blocks, Nalhati-1 had exhibited the highest fluoride level (18.25 mg/L). The study revealed that most of the blocks are vulnerable to groundwater fluoride due to its occurrences in excess level. The average and 95th percentile values of total hazard index indicate that the infants and children populations of the district are more susceptible than the adults and teens. The sensitivity analysis revealed that water ingestion rate and fluoride concentration are the most influential parameters for higher risk of fluoride-related health hazards. Health risks were evaluated through ingestion and dermal exposure routes for infants, children, teens, and adult residents. The exposure was much higher through ingestion than dermal contacts. Ingestion of defluoridated water will reduce the health risks associated with groundwater fluoride exposure.

Draft genome of Ompok bimaculatus (Pabda fish).

OBJECTIVE: Pabda (Ompok bimaculatus) is a freshwater catfish, largely available in Asian countries, especially in Bangladesh, India, Pakistan and Nepal. This fish is highly valued for its fabulous taste and high nutritional value and is very popular as a rich source of proteins, omega-3 and omega-6 fatty acids, vitamins and mineral for growing children, pregnant females and elders. We performed de-novo sequencing of Ompok bimaculatus using a hybrid approach and present here a draft assembly for this species for the first time. DATA DESCRIPTION: The genome of Ompok bimaculatus (Fig. 1: Table 1, Data file 3) from Ganges river, has been sequenced by hybrid approach using Illumina short reads and PacBio long reads followed by structural annotations. The draft genome assembly was found to be 718 Mb with N50 size of 81 kb. MAKER gene annotation tool predicted 21,371 genes.

De novo assembly of the Indian blue peacock (Pavo cristatus) genome using Oxford Nanopore technology and Illumina sequencing.

BACKGROUND: The Indian peafowl (Pavo cristanus) is native to South Asia and is the national bird of India. Here we present a draft genome sequence of the male blue peacock using Illumina and Oxford Nanopore technology (ONT). RESULTS: ONT sequencing gave ∼2.3-fold sequencing coverage, whereas Illumina generated 150-base pair paired-end sequence data at 284.6-fold coverage from 5 libraries. Subsequently, we generated a 0.915-gigabase pair de novo assembly of the peacock genome with a scaffold N50 of 0.23 megabase pairs (Mb). We predict that the peacock genome contains 23,153 protein-coding genes and 75.3 Mb (7.33%) of repetitive sequences. CONCLUSIONS: We report a high-quality assembly of the peacock genome using a hybrid approach of sequences generated by both Illumina and ONT. The long-read chemistry generated by ONT was useful for addressing challenges related to de novo assembly, particularly at regions containing repetitive sequences spanning longer than the read length, and which could not be resolved with only short-read-based assembly. Contig assembly of Illumina short reads gave an N50 of 1,639 bases, whereas with ONT, the N50 increased by >9-fold to 14,749 bases. The initial contig assembly based on Illumina sequencing reads alone gave 685,241 contigs. Further scaffolding on assembled contigs using both Illumina and ONT sequencing reads resulted in a final assembly of 15,025 super-scaffolds, with an N50 of ∼0.23 Mb. Ninety-five percent of proteins predicted by homology matched with those in a public repository, verifying the completeness of our assembly. Like other phylogenetic studies of avian conserved genes, we found P. cristatus to be most closely related to Gallus gallus, followed by Meleagris gallopavo and Anas platyrhynchos. Compared with the recently published peacock genome assembly, the current, superior, hybrid assembly has greater sequencing depth, fewer non-ATGC sequences, and fewer scaffolds.

The Boring Billion, a slingshot for Complex Life on Earth.

The period 1800 to 800 Ma ("Boring Billion") is believed to mark a delay in the evolution of complex life, primarily due to low levels of oxygen in the atmosphere. Earlier studies highlight the remarkably flat C, Cr isotopes and low trace element trends during the so-called stasis, caused by prolonged nutrient, climatic, atmospheric and tectonic stability. In contrast, we suggest a first-order variability of bio-essential trace element availability in the oceans by combining systematic sampling of the Proterozoic rock record with sensitive geochemical analyses of marine pyrite by LA-ICP-MS technique. We also recall that several critical biological evolutionary events, such as the appearance of eukaryotes, origin of multicellularity & sexual reproduction, and the first major diversification of eukaryotes (crown group) occurred during this period. Therefore, it appears possible that the period of low nutrient trace elements (1800-1400 Ma) caused evolutionary pressures which became an essential trigger for promoting biological innovations in the eukaryotic domain. Later periods of stress-free conditions, with relatively high nutrient trace element concentration, facilitated diversification. We propose that the "Boring Billion" was a period of sequential stepwise evolution and diversification of complex eukaryotes, triggering evolutionary pathways that made possible the later rise of micro-metazoans and their macroscopic counterparts.