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Abstract Omniphobic membranes, due to their exceptional properties, have drawn significant attention for overcoming the bottleneck in membrane distillation (MD) technology. This study demonstrates an innovative method for fabricating an omniphobic membrane that is simple and facile compared to other methods such as wet/dry etching and photolithography. The surface morphology of springtails was imitated using electrospraying technique to coat a polyvinylidene fluoride substrate with concave-shaped polystyrene beads that were successfully developed by controlling the electrical traction (voltage) and air resistance (humidity). Then, the lipid coating of springtail surfaces was mimicked by dip-coating the membrane in a low-toxicity short-chain perfluoropolyether lubricant. The concave structure’s tiny air pockets increased membrane hydrophobicity significantly, indicated by the fact that the first round of water bouncing took only 16.3 ms. Finally, in MD treatment of seawater containing 1.0 mM sodium dodecyl sulfate, the optimized omniphobic membrane maintained a stable 99.9% salt rejection rate.

Abstract In the present study, green synthetic pathway was adapted to synthesize CuO–ZnO bimetallic nanoparticles (BNPs) using Eryngium foetidum leaf extract and their anti-cancer activity against MCF7 breast cancer cell lines, anti-microbial activity and in vitro anti-oxidant activity were evaluated. Various bio-active compounds present in leaf extract were responsible for the reduction of CuO–ZnO NPs from respective Cu2+ and Zn2+ metal precursors. In the present study, the involvement of bio-active compounds present in E. foetidum extract before and after green synthesis of BNPs were evaluated for the first time. Rod-shaped and spherical structural morphology of synthesized BNPs were revealed by using FESEM, TEM, and XRD analysis with particle size ranged from 7 to 23 nm with an average size of 16.49 nm. The distribution of Cu and Zn were confirmed by elemental mapping. The green synthesized CuO–ZnO NPs showed significant cytotoxic effect with the inhibition rate 89.20 ± 0.03% at concentration of 500 μg/mL. Again, good antioxidant activity with IC50; 0.253 mg/mL and antimicrobial activity of BNPs were also evaluated with the increasing order of MIC; E. coli (7.81 μg/mL)

Abstract Triple Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype suffering from limited targeted treatment options. Following recent reports correlating Fibroblast growth factor-inducible 14 (Fn14) receptor overexpression in Estrogen Receptor (ER)-negative breast cancers with metastatic events, we show that Fn14 is specifically overexpressed in TNBC patients and associated with poor survival. We demonstrate that constitutive Fn14 signalling rewires the transcriptomic and epigenomic landscape of TNBC, leading to enhanced tumour growth and metastasis. We further illustrate that such mechanisms activate TNBC-specific super enhancers (SE) to drive the transcriptional activation of cancer dependency genes via chromatin looping. In particular, we uncover the SE-driven upregulation of Nicotinamide phosphoribosyltransferase (NAMPT), which promotes NAD+ and ATP metabolic reprogramming critical for filopodia formation and metastasis. Collectively, our study details the complex mechanistic link between TWEAK/Fn14 signalling and TNBC metastasis, which reveals several vulnerabilities which could be pursued for the targeted treatment of TNBC patients.

Abstract Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype “O”. Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P 2 months 2 months

Abstract In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.

Hepatic factors secreted by the liver promote homeostasis and are pivotal for maintaining the liver-gut axis. Bile acid metabolism is one such example wherein, bile acid synthesis occurs in the liver and its biotransformation happens in the intestine. Dysfunctional interactions between the liver and the intestine stimulate varied pathological outcomes through its bidirectional portal communication. Indeed, aberrant bile acid metabolism has been reported in inflammatory bowel disease (IBD). However, the molecular mechanisms underlying these crosstalks that perpetuate intestinal permeability and inflammation remain obscure. Here, we identify a novel hepatic gene program regulated by Rela and Stat3 that accentuates the inflammation in an acute experimental colitis model. Hepatocyte-specific ablation of Rela and Stat3 reduces the levels of primary bile acids in both the liver and the gut and shows a restricted colitogenic phenotype. On supplementation of chenodeoxycholic acid (CDCA), knock-out mice exhibit enhanced colitis-induced alterations. This study provides persuasive evidence for the development of multi-organ strategies for treating IBD and identifies a hepatocyte-specific Rela-Stat3 network as a promising therapeutic target.

Filamentous cyanobacteria are one of the oldest and today still most abundant lifeforms on earth, with manifold implications in ecology and economics. Their flexible filaments, often several hundred cells long, exhibit gliding motility in contact with solid surfaces. The underlying force generating mechanism is not yet understood. Here, we demonstrate that propulsion forces and friction coefficients are strongly coupled in the gliding motility of filamentous cyanobacteria. We directly measure their bending moduli using micropipette force sensors, and quantify propulsion and friction forces by analyzing their self-buckling behavior, complemented with analytical theory and simulations. The results indicate that slime extrusion unlikely generates the gliding forces, but support adhesion-based hypotheses, similar to the better-studied single-celled myxobacteria. The critical self-buckling lengths align well with the peaks of natural length distributions, indicating the importance of self-buckling for the organization of their collective in natural and artificial settings.

Calcium (Ca2+), a critical secondary messenger, is also known as the molecule of life and death. The cell responds to a minute change in Ca2+ concentration and tightly maintains Ca2+ homeostasis. Therefore, determining the cell Ca2+ level is critical to understand Ca2+ distribution in the cell and various cell processes. Many techniques have been developed to measure Ca2+ in the cell. We review here different methods used to detect and measure Ca2+ in filamentous fungi. Ca2+-sensitive fluorescent chlortetracycline hydrochloride (CTC), Ca2+-selective microelectrode, Ca2+ isotopes, aequorins, and RGECOs are commonly used to measure the Ca2+ level in filamentous fungi. The use of CTC was one of the earliest methods, developed in 1988, to measure the Ca2+ gradient in the filamentous fungus Neurospora crassa. Subsequently, Ca2+-specific microelectrodes were developed later in the 1990s to identify Ca2+ ion flux variations, and to measure Ca2+ concentration. Another method for quantifying Ca2+ is by using radio-labeled Ca2+ as a tracer. The usage of 45Ca to measure Ca2+ in Saccharomyces cerevisiae was reported previously and the same methodology was also used to detect Ca2+ in N. crassa recently. Subsequently, genetically engineered Ca2+ indicators (GECIs) like aequorins and RGECOs have been developed as Ca2+ indicators to detect and visualize Ca2+ inside the cell. In this review, we summarize various methodologies used to detect and measure Ca2+ in filamentous fungi with their advantages and limitations. • Chlortetracycline (CTC) fluorescence assay is used for visualizing Ca2+ level, whereas microelectrodes technique is used to determine Ca2+ flux in the cell. • Radioactive 45Ca is useful for quantification of Ca2+ in the cellular compartments. • Genetically modified calcium indicators (GECIs) are used to study Ca2+ dynamics in the cell.

Abstract The traditional rice genotypes of Assam are considered to have biological value due to the presence of several bioactive compounds like flavonoids, polyphenols, and anthocyanins, which have antioxidant, anti-cancer, anti-diabetic, and anti-aging properties. The pigmented genotypes are considered to have high iron (Fe) content. However, the effect of Fe and Zinc (Zn) accumulation on anthocyanin content is yet to be studied in pigmented rice of Assam. We studied the Fe, Zn, and anthocyanin content in grains of 204 traditional rice of Assam, which are traditionally preferred for their nutraceutical properties. We performed phenotypic and biochemical compositional analyses of 204 genotypes to identify those having high Fe, Zn, and anthocyanin. We also carried out the differential expression of a few selected Fe and Zn transporter genes along with the expression of anthocyanin biosynthesis genes. Interestingly, all pigmented rice genotypes contained a higher amount of phenolic compound than the non-pigmented form of rice. We found the highest (32.73 g) seed yield per plant for genotype Jengoni followed by Kajoli chokuwa and Khau Pakhi 1. We also listed 30 genotypes having high levels of Fe and Zn content. The genotype Jengoni accumulated the highest (186.9 μg g−1) Fe, while the highest Zn (119.9 μg g−1) content was measured in genotype Bora (Nagaon), The levels of Ferritin 2 gene expression were found to be significantly higher in Bora (Nagaon) (> 2-fold). For Zn accumulation, the genotype DRR Dhan-45, which was released as a high Zn content variety, showed significant up-regulation of the ZIP4 gene at booting (> 7-fold), post-anthesis (7.8-fold) and grain filling (> 5-fold) stages followed by Bora (Nagaon) (> 3-fold) at post-anthesis. Anthocyanidin synthase gene, Flavanone 3-dioxygenase 1-like (FDO1), and Chalcone-flavanone isomerase-like genes were up-regulated in highly pigmented genotype Bora (Nagaon) followed by Jengoni. Based on our data there was no significant correlation between iron and zinc content on the accumulation of anthocyanin. This challenges the present perception of the higher nutritive value in terms of the micronutrient content of the colored rice of Assam. This is the first report on the detailed characterization of traditional rice genotypes inclusive of phenotypic, biochemical, nutritional, and molecular attributes, which would be useful for designing the breeding program to improve Fe, Zn, or anthocyanin content in rice.

Abstract Contrary to popular belief, agriculture is becoming more data-driven with artificial intelligence and Internet-of-Things (IoT) playing crucial roles. In this paper, the integrated processing executed by various sensors combined as an IoT pack and driving an intelligent agriculture management system designed for rainfall prediction and fruit health monitoring have been included. The proposed system based on an AI aided model makes use of a Convolutional Neural Network (CNN) with long short-term memory (LSTM) layer for rainfall prediction and a CNN with SoftMax layer along with a few deep learning pre-trained models for fruit health monitoring. Another model that works as a combined rainfall predictor and fruit health recognizer is designed using a CNN + LSTM and a multi-head self-attention mechanism which proves to be effective. The entire system is cloud resident and available for use through an application.

Abstract Moringa oleifera Lam and Moringa stenopetala (Baker f.) Cufod are being widely promoted as multipurpose trees across the tropics for their nutritional, medicinal and soil health benefits. Different parts of these species are edible, have therapeutic values and their seeds are used for water purification. Although the two species are similar in many ways, they have contrasting distributions. However, their current promotion is not guided by adequate knowledge of the suitability of the target areas. Information is also scanty on the suitability of habitats for these species under the current and future climate change scenarios. Therefore, the objective of this study was to predict the habitat suitability of M. oleifera and M. stenopetala under current and future climate change scenarios using an ensemble of models assuming four shared socio-economic pathways, namely, SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 for 2050 and 2070. The results suggest that areas that are highly suitable for M. oleifera will increase by 0.1% and 3.2% under SSP1-2.6 to SSP5-8.5 by 2050, respectively. By 2070, the area suitable for M. oleifera would likely decrease by 5.4 and 10.6% under SSP1-2.6 and SSP5-8.5 scenarios, respectively. The habitat that is highly suitable for M. stenopetala was predicted to increase by 85–98% under SSP3-7.0 and SSP5-8.5 scenarios by 2050 and by 2070, while suitable areas could increase by up to 143.6% under SSP5-8.5. The most influential bioclimatic variables for both species were mean diurnal temperature range, mean temperature of driest quarter, precipitation of wettest month, and isothermality. Additionally, soil pH, elevation and water holding capacity were influential variables in the distribution of M. oleifera, while soil pH, soil salinity and slope were influential in M. stenopetala distribution. This study has provided baseline information on the current distribution and possible future habitat suitability, which will be helpful to guide formulation of good policies and practices for promoting Moringa species outside their current range.

Jute plant retting is a preferential rotting process in which jute plants are submerged in water and subsequently jute fibers are extracted out by decomposing the cellular tissues and pectin surrounding the fiber bundles through the joint action of water and aquatic/soil microorganisms. Due to the shortage of water during retting period of jute, all crops cannot be stacked at a time and therefore farmers are often compelled to harvest over-matured plants and use the same water body repeatedly for retting. This generates inferior quality of fiber. Traditional retting is also labor intensive and not environment friendly and takes longer time to ret. A feasibility study has been undertaken for dry retting of jute plants on land under water limiting condition using a defined microbial consortium. Field trials of dry retting of jute plants carried out at farmer’s level have shown promising results wherein jute plant retting can be achieved in shorter time without submerging jute plants in water body. Quality of jute fibers obtained from such dry retting process is comparable to the conventionally retted jute process.

Abstract Anthrax is caused by, Bacillus anthracis, a soil-borne bacterium that infects grazing animals. Kenya reported a sharp increase in livestock anthrax cases from 2005, with only 12% of the sub-counties (decentralised administrative units used by Kenyan county governments to facilitate service provision) accounting for almost a third of the livestock cases. Recent studies of the spatial extent of B. anthracis suitability across Kenya have used approaches that cannot capture the underlying spatial and temporal dependencies in the surveillance data. To address these limitations, we apply the first Bayesian approach using R-INLA to analyse a long-term dataset of livestock anthrax case data, collected from 2006 to 2020 in Kenya. We develop a spatial and a spatiotemporal model to investigate the distribution and socio-economic drivers of anthrax occurrence and incidence at the national and sub-county level. The spatial model was robust to geographically based cross validation and had a sensitivity of 75% (95% CI 65–75) against withheld data. Alarmingly, the spatial model predicted high intensity of anthrax across the Northern counties (Turkana, Samburu, and Marsabit) comprising pastoralists who are often economically and politically marginalized, and highly predisposed to a greater risk of anthrax. The spatiotemporal model showed a positive link between livestock anthrax risk and the total human population and the number of exotic dairy cattle, and a negative association with the human population density, livestock producing households, and agricultural land area. Public health programs aimed at reducing human-animal contact, improving access to healthcare, and increasing anthrax awareness, should prioritize these endemic regions.

Abstract To reduce the veterinary, public health, environmental, and economic burden associated with anthrax outbreaks, it is vital to identify the spatial distribution of areas suitable for Bacillus anthracis, the causative agent of the disease. Bayesian approaches have previously been applied to estimate uncertainty around detected areas of B. anthracis suitability. However, conventional simulation-based techniques are often computationally demanding. To solve this computational problem, we use Integrated Nested Laplace Approximation (INLA) which can adjust for spatially structured random effects, to predict the suitability of B. anthracis across Uganda. We apply a Generalized Additive Model (GAM) within the INLA Bayesian framework to quantify the relationships between B. anthracis occurrence and the environment. We consolidate a national database of wildlife, livestock, and human anthrax case records across Uganda built across multiple sectors bridging human and animal partners using a One Health approach. The INLA framework successfully identified known areas of species suitability in Uganda, as well as suggested unknown hotspots across Northern, Eastern, and Central Uganda, which have not been previously identified by other niche models. The major risk factors for B. anthracis suitability were proximity to water bodies (0–0.3 km), increasing soil calcium (between 10 and 25 cmolc/kg), and elevation of 140–190 m. The sensitivity of the final model against the withheld evaluation dataset was 90% (181 out of 202 = 89.6%; rounded up to 90%). The prediction maps generated using this model can guide future anthrax prevention and surveillance plans by the relevant stakeholders in Uganda.

The Rayleigh limit and low signal-to-noise ratio (SNR) scenarios pose significant limitations to optical imaging systems used in remote sensing, infrared thermal imaging, and space domain awareness. In this study, we introduce a stochastic sub-Rayleigh imaging (SSRI) algorithm to localize point objects and estimate their positions, brightnesses, and number in low SNR conditions, even below the Rayleigh limit. Our algorithm adopts a maximum likelihood approach and exploits the Poisson distribution of incoming photons to overcome the Rayleigh limit in low SNR conditions. In our experimental validation, which closely mirrors practical scenarios, we focus on conditions with closely spaced sources within the sub-Rayleigh limit (0.49–1.00 R) and weak signals (SNR less than 1.2). We use the Jaccard index and Jaccard efficiency as a figure of merit to quantify imaging performance in the sub-Rayleigh region. Our approach consistently outperforms established algorithms such as Richardson–Lucy and CLEAN by 4X in the low SNR, sub-Rayleigh regime. Our SSRI algorithm allows existing telescope-based optical/infrared imaging systems to overcome the extreme limit of sub-Rayleigh, low SNR source distributions, potentially impacting a wide range of fields, including passive thermal imaging, remote sensing, and space domain awareness.

The increasing production of cement as a basic material for making concrete is due to the increasing demand for concrete throughout the world. Innovative materials are needed as a substitute for cement to reduce the greenhouse effect, fly ash is pozzolanic which in fact has the potential to replace Portland cement as the main ingredient of concrete, and duck eggshell flour has good prospects to be used as an additional precursor material for geopolymer concrete. This study aims to determine further variations of the proportion of duck egg shells, the mechanical properties of the concrete produced using duck egg shell ash with fly ash. This study used an experimental method with the percentage of duck egg shell ash at 0%, 5%, 10%, and 15% of the total use of cement. Using Na₂SiO₃ and NaOH as activator with a concentration of 14M. At the age of 7 and 28 days with room temperature treatment. This study resulted in duck egg shell ash being able to increase the compressive strength of concrete at the age of 28 days with the percentage of substitution up to 5% with a value of 59.26 MPa, in the porosity test the minimum value was at the age of 28 days at a percentage of 5% 0.403%, and the value of the modulus of elasticity. experienced an increase in value at a percentage of 5% with the result 36071.43 MPa. Duck egg shell ash with a proportion of 5% is the optimum substitution where the compressive strength, porosity and modulus of elasticity tests on geopolymer concrete have linear values.

Abstract Planar hypercoordinate structures are gaining immense attention due to the shift from common paradigm. Herein, our high level ab initio calculations predict that planar pentacoordinate aluminium and gallium centres in Cu5Al2+ and Cu5Ga2+ clusters are global minima in their singlet ground states. These clusters are thermodynamically and kinetically very stable. Detailed electronic structure analyses reveal the presence of σ-aromaticity which is the driving force for the stability of the planar form.

Abstract Salicylic acid phenylethyl ester (SAPE) was synthesized by Zn(OTf)2-catalyzed selective esterification of salicylic acid and phenylethyl alcohol and studied for its role as an immunomodulatory and anticancer agent. Low toxicity and favorable physical, Lipinski-type, and solubility properties were elucidated by ADME-tox studies. Molecular docking of SAPE against COX-2 revealed favorable MolDockscore, rerank score, interaction energy, internal pose energy, and hydrogen bonding as compared to ibuprofen and indomethacin. An average RMSD of ~ 0.13 nm for the docked complex with stable dynamic equilibrium condition was noted during the 20 ns MD simulation. A low band gap predicting a strong binding affinity at the enzyme’s active site was further predicted by DFT analysis. The ester caused a reduction in the percentage of erythrocyte hemolysis and was shown to be non-cytotoxic against human lymphocytes, CaCo-2, and HepG-2 cells by the MTT assay. Moreover, it’s in vitro efficacy in inhibiting COX-2 enzyme under both LPS stimulated intestinal cells and direct sequestration assays was found to be higher than salicylic acid and indomethacin. The anticancer activity of SAPE was tested on the breast cancer cell line MCF-7, and potential efficacy was exhibited in terms of decreased cell viability. Flow cytometry analysis exhibited the arrest of the cell cycle at G1/G0 and S phases, during which induction of autophagic vesicle formation and decrease in mitochondrial membrane potential was observed owing to increased ROS production. Furthermore, at these phases, the onset of apoptosis along with DNA damage was also observed. Pre-treatment with SAPE in colitis-induced Wistar rats displayed low disease activity index and reduction in the extent of intestinal tissue disruption and lipid peroxidation. A marked increase of anti-oxidative enzymes viz., catalase, GGT, and GST, and a decrease of pro-inflammatory cytokines IL-6 and TNF-α in the intestinal tissue extracts of the treated groups was noted. The results of this study have sufficient credence to support that the synthesised ester (SAPE) be considered as an anti-oxidative and anti-inflammatory compound with therapeutic potential for the effective management of cancer.

Measurement(s) built-up areas Technology Type(s) visual interpretation of satellite imagery Factor Type(s) geographic location Sample Characteristic - Environment land • area of developed space Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.17068160

The mechanisms of energy generation and carbon-source utilization in the syphilis spirochete Treponema pallidum have remained enigmatic despite complete genomic sequence information. Whereas the bacterium harbors enzymes for glycolysis, the apparatus for more efficient use of glucose catabolites, namely the citric-acid cycle, is apparently not present. Yet, the organism's energy needs likely exceed the modest output from glycolysis alone. Recently, building on our structure-function studies of T. pallidum lipoproteins, we proposed a "flavin-centric" metabolic lifestyle for the organism that partially resolves this conundrum. As a part of the hypothesis, we have proposed that T. pallidum contains an acetogenic energy-conservation pathway that catabolizes D-lactate, yielding acetate, reducing equivalents for the generation and maintenance of chemiosmotic potential, and ATP. We already have confirmed the D-lactate dehydrogenase activity in T. pallidum necessary for this pathway to operate. In the current study, we focused on another enzyme ostensibly involved in treponemal acetogenesis, phosphotransacetylase (Pta). This enzyme is putatively identified as TP0094 and, in this study, we determined a high-resolution (1.95 Å) X-ray crystal structure of the protein, finding that its fold comports with other known Pta enzymes. Further studies on its solution behavior and enzyme activity confirmed that it has the properties of a Pta. These results are consistent with the proposed acetogenesis pathway in T. pallidum, and we propose that the protein be referred to henceforth as TpPta.

Abstract We report strong second-harmonic generation (SHG) from 2H polytype of multilayer Tin diselenide (SnSe2) for fundamental excitation close to the indirect band-edge in the absence of excitonic resonances. Comparison of SHG and Raman spectra from exfoliated SnSe2 flakes of different polytypes shows strong (negligible) SHG and Raman Eg mode at 109 cm−1 (119 cm−1), consistent with 2H (1T) polytypes. The difference between the A1g–Eg Raman peak positions is found to exhibit significant thickness dependent for the 1T form, which is found to be absent for the 2H form. The observed thickness dependence of SHG with rapid oscillations in signal strength for small changes in flake thickness are in good agreement with a nonlinear wave propagation model considering nonlinear polarization with alternating sign from each monolayer. The nonlinear optical susceptibility extracted from SHG signal comparison with standard quartz samples for 1040 nm excitation is found to be more than 4-times higher than that at 1550 nm. This enhanced nonlinear response at 1040 nm is attributed to the enhanced nonlinear optical response for fundamental excitation close to the indirect band-edge. We also study SHG from heterostructures of monolayer MoS2/multilayer SnSe2 which allows us to unambiguously compare the nonlinear optical response of SnSe2 with MoS2. We find the SHG signal and any interference effect in the overlap region to be dominated by the SnSe2 layer for the excitation wavelengths considered. The comparison of SHG from SnSe2 and MoS2 underscores that the choice of the 2D material for a particular nonlinear optical application is contextual on the wavelength range of interest and its optical properties at those wavelengths. The present works further highlights the usefulness of near band-edge enhancement of nonlinear processes in emerging 2D materials towards realizing useful nanophotonic devices.

Abstract Density functional theory method combined with docking and molecular dynamics simulations are used to understand the interaction of carmustine with human glutathione reductase enzyme. The active site of the enzyme is evaluated by docking simulation is used for molecular dynamics simulation to deliver the carmustine molecule by (5,5) single walled carbon nanotube (SWCNT). Our model of carmustine in the active site of GR gives a negative binding energy that is further refined by QM/MM study in gas phase and solvent phase to confirm the stability of the drug molecule inside the active site. Once released from SWCNT, carmustine forms multiple polar and non-polar hydrogen bonding interactions with Tyr180, Phe209, Lys318, Ala319, Leu320, Leu321, Ile350, Thr352 and Val354 in the range of 2–4 Å. The SWCNT vehicle itself is held fix at its place due to multiple pi-pi stacking, pi-amide, pi-sigma interactions with the neighboring residues. These interactions in the range of 3–5 Å are crucial in holding the nanotube outside the drug binding region, hence, making an effective delivery. This study can be extended to envisage the potential applications of computational studies in the modification of known drugs to find newer targets and designing new and improved controlled drug delivery systems.

Pollination is crucial for oil palm yield, and its efficiency is influenced by multiple factors, including the effectiveness of Elaeidobius kamerunicus weevils as pollinators in Southeast Asia. Weevils transfer pollen between male and female flowers, leading to successful fertilization and fruit development, which contributes to higher oil palm yields and increased production of valuable oil. Understanding and conserving the weevil population is important for sustainable oil palm cultivation practices. The interaction between pollinators, including weevils, and environmental factors is complex, involving aspects such as pollinator behavior, abundance, diversity, and effectiveness, which are influenced by weather, landscape composition, and pesticide use. Understanding these interactions is critical for promoting sustainable pollination practices, including effective pest management and maintaining optimal pollinator populations. This review discusses various abiotic and biotic factors that affect pollination and pollinators in oil palm plantations, with a particular focus on weevils as primary pollinators. Factors such as rainfall, humidity, oil palm species, temperature, endogamy, parasitic nematodes, insecticides, predators, and proximity to natural forests can impact the weevil population. Further research is recommended to fill knowledge gaps and promote sustainable pollination practices in the oil palm industry.

Abstract Hydrocarbons or crude oil contamination of soil is still a burning problem around the globe. The herbs competent that are to survive in hydrocarbons contaminated habitats have some adaptive advantages to cope up with the adverse situations prevailing in that environment. In the present study, the adaptive response of Cyperus brevifolius in the heavily polluted soil with crude oil has been investigated in terms of survivability, changes in productivity, antioxidants, phytochemicals and functional group pro files of the plant species. Besides, changes in enzymes, beneficial bacterial population and physico-chemical conditions of contaminated soil were also studied during 60 days of experimental trials. The results showed significant enhancement in activities of soil dehydrogenase, urease, alkaline phosphatase, catalase, and amylase whereas reduction in cellulase, polyphenol oxidase and peroxidase activities. There was a significant increase in nitrogen fixing, phosphate and potassium solubilizing bacterial population, improvement in physico-chemical conditions and a decrease in total oil and grease (TOG) levels. Besides there was significant variations in the productivity parameters and antioxidant profiles of Cyperus brevifolius in hydrocarbons stress condition suggesting enzymatic defense of the herb. The fourier-transform infrared (FT-IR) analysis indicated uptake and metabolism of some hydrocarbon components by the experimental plant from the hydrocarbons polluted soil.

PurposeTo determine the prevalence and risk factors for pterygium in geographically diverse regions of India.MethodsA population-based, cross-sectional multicentric study was conducted in adults aged ≥40 years in plains, hilly and coastal regions of India. All participants underwent a detailed questionnaire-based assessment for sun exposure, usage of sun protective measures, exposure to indoor smoke, and smoking. Detailed ocular and systemic examinations were performed. Pterygium was diagnosed and graded clinically by slit-lamp examination. Association of pterygium with sociodemographic, ophthalmological, and systemic parameters was assessed. Physical environmental parameters for the study period were estimated.ResultsOf the 12,021 eligible subjects, 9735 (81% response rate) participated in the study. The prevalence of pterygium in any eye was 13.2% (95% CI: 12.5%-13.9%), and bilateral pterygium was 6.7% (95% CI: 6.2-7.2). The prevalence increased with age (ConclusionPterygium prevalence is high in the rural Indian population. The association of pterygium with several potentially modifiable risk factors reflects its multifactorial etiology and provides targets for preventive measures.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Handwritten signature represents a person’s identity. Although overall patterns among the signatures of same person remain same, there can appear natural variations because two or more signatures of same person written within a moment and keeping a sufficient time gap, cannot be exactly same. These natural variations result in intrapersonal variations. In the present study, signature samples were collected from each participant under different situations of body position, paper texture, paper position etc. to successfully capture the intrapersonal variations. Two features, namely area and height-width ratio (HWR) were extracted for each signature using appropriate image processing techniques. These features were then modelled to the Single Exponential Smoothing Time Series Technique as well as our developed methodology to predict the variations. Using this technique the Positive Predictive Values (PPV) and False Rejection Rate (FRR) for both these features were found to be 88% , 12% and 95.78%, 4.22% respectively.

Background and Objective. The primary responsibility of an orthodontist is to preserve the dental enamel structure during debonding ceramic brackets. The enamel injury caused at the time of bracket removal causes inconvenience to the patient and disturbs the treating orthodontist. This paper aims for an effective evidence-based debonding protocol to keep the enamel surface intact. Methods. The current study includes 80 extracted premolars of human from the patient visiting for orthodontic treatment of Coorg Institute of Dental Sciences, Karnataka, India. The brackets were debonded using four different methods. The enamel surface damage after the procedure was assessed with the Enamel Surface Index (ESI); similarly, the Adhesive Remnant Index (ARI) score was used to determine the adhesive residual deposit. Scanning electron microscopy (SEM) was used to visualize better microporosities and micromechanical retention of adhesive remnants on the enamel surface. The normality of the data was tested using the Kolmogorov–Smirnov test. Depending upon the normality test result, the one-way ANOVA test or Kruskal–Wallis test was used to test the mean ESI and mean ARI differences among different debonding methods along with the appropriate post hoc tests. The necessary ethical clearance was obtained from the Ethics Committee of the institute. Results. The ultrasonic scaler (US) technique led to more significant enamel surface damage, with 13 (65%) samples in the ESI scores III and IV against the satisfactory surface in 2 (10%) samples with the ligature cutter (LC) technique (ESI-I) reflecting LC as a better technique. The ESI scores (III and IV) for debonding plier (DP) and thermal method (TM) reflected a higher value in 12 (60%) and 10 (50%) samples and caused more damage to the enamel surface as compared to the LC technique. The ARI score was highest (ARI-1 = 40%) with the LC technique, followed by the US (ARI-1 = 20%), TM (ARI-1 = 15%), and DP (ARI-1 = 5%) methods. We have observed a significant association (p value

All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays.

All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays.

PURPOSE:To determine the prevalence of cataract and its association with sun exposure and other environmental risk factors in three different geographically diverse populations of India. DESIGN:Population based cross sectional study during 2010-2016. PARTICIPANTS:People aged ≥ 40 years residing in randomly sampled villages were enumerated (12021) and 9735 (81%) underwent ophthalmic evaluation from plains, hilly and coastal regions (3595, 3231, 2909 respectively). METHODS:A detailed questionnaire-based interview about outdoor activity in present, past and remote past, usage of sun protective measures, exposure to smoke, and detailed ophthalmic examination including assessment of uncorrected and best corrected visual acuity, measurement of intraocular pressure, slit lamp examination, lens opacities categorization using LOCS III and posterior segment evaluation was done. Lifetime effective sun exposure was calculated using Melbourne formula and expressed as quintiles. These were supplemented with physical environmental measurements. MAIN OUTCOME MEASURES:Lifetime sun exposure hours, smoking, indoor kitchen smoke exposure and their association with cataract and subtypes. Prevalence of cataract calculated based on lens opacities or evidence of cataract surgery. RESULTS:Cataract was identified in 3231 (33.3%) participants. Prevalence of cataract in males (32.3%) and females (34.1%) was similar. Nuclear cataract was the commonest sub-type identified in 94.7% of affected eyes. Sun exposure had a significant association with cataract with odds ratio (OR) increasing from 1.6 (95% Confidence Intervals [CI]: 1.4, 1.9) in 3rd quintile, to 2.6 (CI: 2.2, 3.1) in 4th quintile and 9.4 (CI: 7.9, 11.2) in 5th quintile (p

BackgroundAs per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population.MethodsBlood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies.ResultsOur findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade.ConclusionTherefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression.

Natural disasters like hurricanes, floods or earthquakes can damage power grid devices and create cascading blackouts and islands. The nature of failure propagation and extent of damage, among other factors, is dependent on the structural features of the grid, that are distinct from that of random networks. This paper analyzes the structural vulnerability of real power grids to impending disasters and presents intuitive graphical metrics to quantify the extent of topological damage. We develop two improved graph eigen-value based bounds on the grid vulnerability. Further we study adversarial attacks aimed at weakening the grid's structural robustness and present three combinatorial algorithms to determine the optimal topological attack. Simulations on power grid networks and comparison with existing work show the improvements of the proposed measures and attack schemes.

India has experienced significant Land-Use and Land-Cover Change (LULCC) over the past few decades. In this context, careful observation and mapping of LULCC using satellite data of high to medium spatial resolution is crucial for understanding the long-term usage patterns of natural resources and facilitating sustainable management to plan, monitor and evaluate development. The present study utilizes the satellite images to generate national level LULC maps at decadal intervals for 1985, 1995 and 2005 using onscreen visual interpretation techniques with minimum mapping unit of 2.5 hectares. These maps follow the classification scheme of the International Geosphere Biosphere Programme (IGBP) to ensure compatibility with other global/regional LULC datasets for comparison and integration. Our LULC maps with more than 90% overall accuracy highlight the changes prominent at regional level, i.e., loss of forest cover in central and northeast India, increase of cropland area in Western India, growth of peri-urban area, and relative increase in plantations. We also found spatial correlation between the cropping area and precipitation, which in turn confirms the monsoon dependent agriculture system in the country. On comparison with the existing global LULC products (GlobCover and MODIS), it can be concluded that our dataset has captured the maximum cumulative patch diversity frequency indicating the detailed representation that can be attributed to the on-screen visual interpretation technique. Comparisons with global LULC products (GlobCover and MODIS) show that our dataset captures maximum landscape diversity, which is partly attributable to the on-screen visual interpretation techniques. We advocate the utility of this database for national and regional studies on land dynamics and climate change research. The database would be updated to 2015 as a continuing effort of this study.

Calcineurin is a calcium/calmodulin dependent protein phosphatase in eukaryotes that consists of a catalytic subunit A and a regulatory subunit B. Previous studies in the filamentous fungus Neurospora crassa had suggested that the catalytic subunit of calcineurin might be an essential protein. We generated N. crassa strains expressing the A (cna-1) and B (cnb-1) subunit genes under the regulation of Ptcu-1, a copper-responsive promoter. In these strains, addition of bathocuproinedisulfonic acid (BCS), a copper chelator, results in induction of cna-1 and cnb-1, while excess Cu2+ represses gene expression. Through analysis of these strains under repressing and inducing conditions, we found that the calcineurin is required for normal growth, asexual development and female fertility in N. crassa. Moreover, we isolated and analyzed cnb-1 mutant alleles generated by repeat-induced point mutation (RIP), with the results further supporting roles for calcineurin in growth and fertility in N. crassa. We demonstrated a direct interaction between the CNA-1 and CNB-1 proteins using an assay system developed to study protein-protein interactions in N. crassa.

Treponema pallidum, the bacterium that causes syphilis, is an obligate human parasite. As such, it must acquire energy, in the form of carbon sources, from the host. There is ample evidence that the principal source of energy for this spirochete is D-glucose acquired from its environment, likely via an ABC transporter. Further, there is genetic evidence of a D-glucose chemotaxis system in T. pallidum. Both of these processes may be dependent on a single lipidated chemoreceptor: Tp0684, also called TpMglB-2 for its sequence homology to MglB of Escherichia coli. To broaden our understanding of this potentially vital protein, we determined a 2.05-Å X-ray crystal structure of a soluble form of the recombinant protein. Like its namesake, TpMglB-2 adopts a bilobed fold that is similar to that of the ligand-binding proteins (LBPs) of other ABC transporters. However, the protein has an unusual, circularly permuted topology. This feature prompted a series of biophysical studies that examined whether the protein's topological distinctiveness affected its putative chemoreceptor functions. Differential scanning fluorimetry and isothermal titration calorimetry were used to confirm that the protein bound D-glucose in a cleft between its two lobes. Additionally, analytical ultracentrifugation was employed to reveal that D-glucose binding is accompanied by a significant conformational change. TpMglB-2 thus appears to be fully functional in vitro, and given the probable central importance of the protein to T. pallidum's physiology, our results have implications for the viability and pathogenicity of this obligate human pathogen.

The aim of the present study was to determine the prevalence of Dirofilaria immitis in stray, pet, and working dogs (n=413, 266, and 103, resp.) from Guwahati (Assam) and Aizawl (Mizoram), areas located in two Northeastern States of India. Diagnostic methods applied were microscopy (wet film and Knott’s concentration technique), immunological test (Ag ELISA by SNAP 4Dx ELISA kit), and molecular tools (polymerase chain reaction and sequencing), which evidenced 11.38, 18.03, and 13.93% of positive animals, respectively. No significant differences were observed by area (18.23% versus 17.68%) nor by sex (18.1% versus 17.9%), whereas stray dogs proved more infected than other groups (P

Dyslipidemia and overweight are common issues in children. Identifying genetic markers of risk could lead to targeted interventions. A polymorphism of SNP rs7566605 near insulin-induced gene 2 (INSIG2) has been identified as a strong candidate gene for obesity, through its feedback control of lipid synthesis.To identify polymorphisms in INSIG2 which are associated with overweight (BMI ≥ 85% for age) and dyslipidemia in children.The C allele of rs7566605 would be significantly associated with BMI and LDL.We genotyped 15 SNPs in/near INSIG2 in 1,058 healthy children (53% non-Hispanic white (NHW), 37% overweight) participating in a school based study. Genotype was compared with BMI and lipid markers, adjusting for age, gender, and puberty.We found a significant association between the SNP rs12464355 and LDL in NHW children, p < 0.001. The G allele is protective (lower LDL). A different SNP was associated with overweight in NHW: rs17047757. SNP rs7566605 was not associated with overweight or lipid levels.We identified novel genetic associations between INSIG2 and both overweight and LDL in NHW children. Polymorphisms in INSIG2 may be important in the development of obesity through its effects on lipid regulation.

Biodiesel was produced from high free fatty acid (FFA) Jatropha curcas oil (JCO) by two-stage process in which esterification was performed by Brønsted acidic ionic liquid 1-(1-butylsulfonic)-3-methylimidazolium chloride ([BSMIM]Cl) followed by KOH catalyzed transesterification. Maximum FFA conversion of 93.9% was achieved and it reduced from 8.15 wt% to 0.49 wt% under the optimum reaction conditions of methanol oil molar ratio 12 : 1 and 10 wt% of ionic liquid catalyst at 70°C in 6 h. The ionic liquid catalyst was reusable up to four times of consecutive runs under the optimum reaction conditions. At the second stage, the esterified JCO was transesterified by using 1.3 wt% KOH and methanol oil molar ratio of 6 : 1 in 20 min at 64°C. The yield of the final biodiesel was found to be 98.6% as analyzed by NMR spectroscopy. Chemical composition of the final biodiesel was also determined by GC-MS analysis.

Insulin resistance is a characteristic feature of Type 2 diabetes. Insulin resistance has also been implicated in the pathogenesis of cardiovascular disease. Currently used thiazolidinedione (TZD) insulin sensitizers although effective, have adverse side effects of weight gain, fluid retention and heart failure. Using fat cell-based phenotypic drug discovery approach we identified P1736, a novel antidiabetic molecule that has completed Phase II clinical trials. The present study evaluated the in vitro and in vivo pharmacological properties of P1736. P1736 is a non-TZD and it did not activate human PPAR(Peroxisome Proliferator Activated Receptor Gamma )receptors. P1736 caused dose dependent increase in glucose uptake (EC50-400 nM) in the insulin resistant 3T3 adipocytes. The compound (10 µM) induced translocation of GLUT-4 (Glucose Transporter type 4) transporters in these adipocytes while metformin (1.0mM) was inactive. In diabetic db/db mice, P1736 (150 mg/kg) was more efficacious than metformin in lowering plasma glucose (35% vs 25%) and triglyceride levels (38% vs 31%). P1736 tested at 5mg/kg, twice daily doses, reduced glucose by 41% and triglycerides by 32%, in db/db mice. These effects were not associated with adverse effects on body weight or liver function. Rosiglitazone (5mg/kg, twice daily) caused 60% and 40 % decreases in glucose and triglyceride levels, respectively. However, rosiglitazone induced 13% weight gain (p

Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value

Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia.In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent.We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.

Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with "body fatness" measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of "body fatness". However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for "body fatness", two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).The current study confirmed the association of common variants of FTO gene with "body fatness" measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with "body fatness".