Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer's Disease

Introduction. Apolipoprotein E (APOE) is an important risk factor for Alzheimer's disease (AD) and is present in 30–50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs) are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene. Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns) SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server. Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >−1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs) score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD) values were higher for three mutant-type structures compared to the native modeled structure. Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic

Development of novel functional foods using Himalayan honey having enhanced nutraceutical and nutritional potential

This study was carried out to conduct the geographical discrimination of various types of honey, and their utilization in development of novel functional foods where in honey could be substituted in place of white sugar. Honey based apple spread and marmalade products were developed and evaluated for quality analysis. The results showed higher water activity (aw) and moisture content in Plectranthus rugosus (PR) honey based apple spread and marmalade while, TSS was highest (p < 0.05) in Multifloral (MF) honey based apple spread and marmalade. Hydroxymethylfurfural was found to be in the ranged of 6.77–7.05 (mg/kg) for honey based apple spread products and 3.09–3.46 (mg/kg) for honey based apple marmalade products. The lightness (L*) value was significantly highest in MF honey based apple spread and marmalades (p < 0.05). Redness (a*) and yellowness (b*) values were significantly highest in PR honey based apple spreads and marmalades and lowest in Robinia pseudo acacia (RSA) honey based apple spread and marmalades. In general, all MF honey based apple spreads and marmalades has the highest score for overall acceptability in comparison to RSA and PR honey based apple spreads. The values of gel strength (Fe), rupture force (FR), energy of penetration (E) and adhesiveness (A) in the given spread products were in the range of 1.50–1.54 N, 1.70–1.73 N, 17.00–17.05 Ns and −1.11–−1.08 Ns, respectively. The values of gel strength (Fe), rupture force (FR), energy of penetration (E) and adhesiveness (A) in the investigated marmalade products were in the range of 1.65–1.69 N, 2.08–2.13 N, 16.05–16.10 Ns and −1.14–−1.10 Ns, respectively

K*(892)(0) and phi(1020) production in Pb-Pb collisions at root s(NN)=2.76 TeV

The yields of the K*(892)(0) and phi(1020) resonances are measured in Pb-Pb collisions at root s(NN) = 2.76 TeV through their hadronic decays using the ALICE detector. The measurements are performed in multiple centrality intervals at mid-rapidity (vertical bar y vertical bar < 0.5) in the transverse-momentum ranges 0.3 < p(T) < 5 GeV/c for the K*(892)(0) and 0.5 < p(T) < 5 GeV/c for the phi(1020). The yields of K*(892)(0) are suppressed in central Pb-Pb collisions with respect to pp and peripheral Pb-Pb collisions (perhaps due to rescattering of its decay products in the hadronic medium), while the longer-lived phi(1020) meson is not suppressed. These particles are also used as probes to study the mechanisms of particle production. The shape of the pT distribution of the phi(1020) meson, but not its yield, is reproduced fairly well by hydrodynamic models for central Pb-Pb collisions. In central Pb-Pb collisions at low and intermediate p(T), the p/phi(1020) ratio is flat in p(T), while the p/pi and phi(1020)/pi ratios show a pronounced increase and have similar shapes to each other. These results indicate that the shapes of the p(T) distributions of these particles in central Pb-Pb collisions are determined predominantly by the particle masses and radial flow. Finally, phi(1020) production in Pb-Pb collisions is enhanced, with respect to the yield in pp collisions and the yield of charged pions, by an amount similar to the Lambda and Xi

Ubiquitin-specific peptidase 37: an important cog in the oncogenic machinery of cancerous cells.

Protein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics.This study was supported by AIIMS Intramural grant (Grant number: A514) and AIIMS IITD Grant (AI-34) from All India Institute of Medical Sciences (AIIMS) New Delhi, Delhi India to Mayank singh. Sidra Medicine Precision Program provides research funding to Mohammad Haris (5081012002). Muzafar A. Macha is supported by Ramalingaswami Fellowship (Grant number: D.O. NO.BT/HRD/35/02/2006) from the Department of Biotechnology, Govt. of India, New Delhi

Multiplicity dependence of the average transverse momentum in pp, p–Pb, and Pb–Pb collisions at the LHC

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Mental wellbeing of healthcare workers working in quarantine centers during the COVID-19 pandemic in Qatar

Background: Healthcare workers managing Coronavirus 19 (COVID-19) patients are at increased risk of poor mental wellbeing. The available literature on the psychological impact in the Arabian Gulf region is limited, and a more in-depth analysis of factors affecting frontline healthcare workers' mental wellbeing is warranted. The aim of this study was to evaluate and explore healthcare workers' wellbeing working in quarantine centers in Qatar. Methods: This study was a cross-sectional, web-based survey conducted on healthcare workers managing patients in designated quarantine centers. Healthcare workers associated with 51 COVID-19 quarantine centers were eligible to participate in this survey from April 19 to May 3, 2020. The primary outcome of interest was mental wellbeing as measured by the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). Results: A total of 127 of 169 contacted staff members completed the survey, with a participation rate of 75%. Approximately 17.4% of participants had well-being scores of less than 45, indicating suboptimal wellbeing and a high risk of psychological distress and depression. The multivariable logistic regression analysis showed that nurses are associated with increased risk (more than the fivefold higher risk of having WEMWBS score < 45) of adverse mental wellbeing (adjusted OR 5.65; 95% CI 0.57, 56.4; p = 0.140). Conclusion: The psychological impact of working in quarantine centers on healthcare workers was less than what has been reported globally. Nurses are the most vulnerable group. It is essential that health services monitor the psychological impact on its workforce and puts appropriate mitigation strategies in place.qscienc

Inclusive J/ψ production in pp collisions at √s = 2.76 TeV

The ALICE Collaboration has measured inclusive J/ψ production in pp collisions at a center-of-mass energy √s = 2.76 TeV at the LHC. The results presented in this Letter refer to the rapidity ranges |y| < 0.9 and 2.5 < y < 4 and have been obtained by measuring the electron and muon pair decay channels, respectively. The integrated luminosities for the two channels are Le int = 1.1 nb−1 and L μ int = 19.9 nb−1, and the corresponding signal statistics are Ne+e− J/ψ = 59 ± 14 and Nμ+μ− J/ψ = 1364 ± 53. We present dσJ/ψ /dy for the two rapidity regions under study and, for the forward-y range, d2σJ/ψ /dy dpt in the transverse momentum domain 0 < pt < 8 GeV/c. The results are compared with previously published results at √s = 7 TeV and with theoretical calculations

Bioinformatics Analysis Reveals FOXM1/BUB1B Signaling Pathway as a Key Target of Neosetophomone B in Human Leukemic Cells: A Gene Network-Based Microarray Analysis

Abnormal expression of Forkhead box protein M1 (FOXM1) and serine/threonine kinase Budding uninhibited by benzimidazoles 1 (BUB1B) contributes to the development and progression of several cancers, including chronic myelogenous leukemia (CML). However, the molecular mechanism of the FOXM1/BUB1B regulatory network and the role of Neosetophomone-B (NSP-B) in leukemia remains unclear. NSP-B, a meroterpenoid fungal secondary metabolite, possesses anticancer potential in human leukemic cells lines; however, the underlying mechanism has not been elucidated. The present study aimed to explore the role of NSP-B on FOXM1/BUB1B signaling and the underlying molecular mechanism of apoptosis induction in leukemic cells. We performed gene expression profiling of NSP-B-treated and untreated leukemic cells to search for differentially expressed genes (DEGs). Interestingly BUB1B was found to be significantly downregulated (logFC -2.60, adjusted p = 0.001) in the treated cell line with the highest connectivity score among cancer genes. Analysis of TCGA data revealed overexpression of BUB1B compared to normal in most cancers and overexpression was associated with poor prognosis. BUB1B also showed a highly significant positive correlation with FOXM1 in all the TCGA cancer types. We used human leukemic cell lines (K562 and U937) as an in vitro study model to validate our findings. We found that NSP-B treatment of leukemic cells suppressed the expression of FOXM1 and BUB1B in a dose-dependent manner. In addition, NSP-B also resulted in the downregulation of FOXM1-regulated genes such as Aurora kinase A, Aurora kinase B, CDK4, and CDK6. Suppression of FOXM1 either by siRNA or NSP-B reduced BUB1B expression and enhanced cell survival inhibition and induction of apoptosis. Interestingly combination treatment of thiostrepton and NSP-B suppressed of cell viability and inducted apoptosis in leukemic cells via enhancing the activation of caspase-3 and caspase-8 compared with single-agent treatment. These results demonstrate the important role of the FOXM1/BUB1B pathway in leukemia and thus a potential therapeutic target.Medical Research Center Grant no; MRC-01-21-301 (SU), Hamad Medical Corporation, Doha Qatar. The publication of this article was funded by the Qatar National Library

Математична модель поверхні тіла у неявній формі на основі інтерфлетації функцій

В роботi запропоновано, з використанням iнтерфлетацiї функцiй, новий, загальний метод побудови рiвнянь поверхонь тiл складної форми в наявнiй формi ∂G : OG(x, y, z) = 0, де ∂G — поверхня 3D-тiла G. Функцiя OG(x, y, z) що належить C^r(R^3), r ≥ 1, є найкращим середньоквадратичним наближенням до функцiї f(x, y, z) що належить C(R^3), побудованої за допомогою R-функцiй, яка входить в рiвняння f(x, y, z) = 0, (x, y, z) що належить ∂G.A new general method, which uses the interflatation of functions, of construction of the equations of surfaces of bodies with complex shape in the implicit form OG(x, y, z) = 0, (x, y, z) belongs ∂G, where ∂G is the surface of the 3D body G, is offered. The function OG(x, y, z) belongs C^r(R^3), r ≥ 1 is the best mean-square approximation of the function f(x, y, z) belongs C(R^3) which is built with the use of R-functions and satisfies the equation f(x, y, z) = 0, (x, y, z) belongs ∂G