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Background There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE) (figure 1). Leveraging methods initially developed for prediction of tumor-specific antigen targets, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2 (figure 2). Methods SARS-CoV-2 HLA-I and HLA-II ligands were predicted using multiple MHC binding prediction software. T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles, and co-localization of CD4+/CD8+ T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. Using murine compatible T/B cell epitopes, vaccine studies were performed with downstream ELISA/ELISpot to monitor immunogenicity. Results We observed distribution of HLA-I (n = 2486) and -II (n = 3138) ligands evenly across the SARS-CoV-2 proteome, with significant overlap between predicted human and murine ligands (figure 3). Applying a multivariable immunogenicity model trained from IEDB viral tetramer data (AUC 0.7 and 0.9 for HLA-I and -II, respectively), alongside filters for entropy and protein expression resulted in 292 CD8+ and 616 CD4+ epitopes (figure 4). From an initial pool of 58 B cell epitope candidates, three epitope regions were identified (figure 5). Combining B cell and T cell analyses, alongside manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials (figure 6). Preliminary murine studies demonstrate evidence of T and B cell activation (figure 7). Conclusions A peptide vaccine targeting B cells, CD4+ T cells, and CD8+ T cells in parallel may prove an important part of a multifaceted response to the COVID-19 pandemic. Adapting methods for predicting tumor-specific antigens, we presented a set of peptide candidates with high overlap for T and B cell epitopes and broad haplotype population coverage, with validation of immunogenicity in murine vaccine studies. Acknowledgements The authors appreciate funding support from University of North Carolina University Cancer Research Fund (AR and BGV), the Susan G. Komen Foundation (BGV), the V Foundation for Cancer Research (BGV), and the National Institutes of Health (CCS, 1F30CA225136). We would like to thank members of the #DownWithTheCrown Slack channel for helpful discussion and feedback.

Microalgae Chlorella vulgaris contains micronutrients such as mineral zinc and selenium having role to produce antibody and improve body immunity. However, the impact of Chlorella vulgaris supplementation to goat milks’s chemical compositions has not being well documented. This research’s objective is to identify Chlorella vulgaris suppmentation as zinc and selenium source to improve goat milk’s quality as health drink in COVID-19 pandemy. Fifteen Etawah cross breed or Peranakan Etawa (PE) goats groupped into 5 treatments dan 3 repetitions. The goats were fed with grass, tofu waste and tempe waste. Chlorella supplement is fed to treated goat feed every day with level 0g (P0 = control), 2, 5g (P1), 5g (P2), 7, 5g (P3), and 10g (P4). The research’s result shows that zinc content in goat milk increase 2, 12 ppm or 24, 67%, while selenium increase 0, 08 mcg or 5, 5% after getting supplementation of Chlorella 10g/goat/day (P4). The provision of Chlorella also increase as solids total, protein and milk fat. Milk production increased by 28, 36% with Chlorella vulgaris supplements (P4). Based on the results of this study it can be stated that Chlorella vulgaris supplementation in goat PE feed can be used as a source of natural zinc and selenium minerals to improve the quality of goat milk as a health drink to increase body immunity, especially during the Covid-19 pandemic.

Comperiella calauanica is a host-specific endoparasitoid and effective biological control agent of the diaspidid Aspidiotus rigidus, whose outbreak from 2010 to 2015 severely threatened the coconut industry in the Philippines. Using the maximum entropy (Maxent) algorithm, we developed a species distribution model (SDM) for C. calauanica based on 19 bioclimatic variables, using occurrence data obtained mostly from field surveys conducted in A. rigidus-infested areas in Luzon Island from 2014 to 2016. The calculated the area under the ROC curve (AUC) values for the model were very high (0.966, standard deviation = 0.005), indicating the model&rsquo, s high predictive power. Precipitation seasonality was found to have the highest relative contribution to model development. Response curves produced by Maxent suggested the positive influence of mean temperature of the driest quarter, and negative influence of precipitation of the driest and coldest quarters on habitat suitability. Given that C. calauanica has been found to always occur with A. rigidus in Luzon Island due to high host-specificity, the SDM for the parasitoid may also be considered and used as a predictive model for its host. This was confirmed through field surveys conducted between late 2016 and early 2018, which found and confirmed the occurrence of A. rigidus in three areas predicted by the SDM to have moderate to high habitat suitability or probability of occurrence of C. calauanica: Zamboanga City in Mindanao, Isabela City in Basilan Island, and Tablas Island in Romblon. This validation in the field demonstrated the utility of the bioclimate-based SDM for C. calauanica in predicting habitat suitability or probability of occurrence of A. rigidus in the Philippines.

For frequently used engineered nanomaterials (ENMs) CeO2-, SiO2-, and Ag, past, current, and future use and environmental release are investigated. Considering an extended period (1950 to 2050), we assess ENMs released through commercial activity as well as found in natural and technical settings. Temporal dynamics, including shifts in release due to ENM product application, stock (delayed use), and subsequent end-of-life product treatment were taken into account. We distinguish predicted concentrations originating in ENM use phase and those originating from end-of-life release. Furthermore, we compare Ag- and CeO2-ENM predictions with existing measurements. The correlations and limitations of the model, and the analytic validity of our approach are discussed in the context of massive use of assumptive model data and high uncertainty on the colloidal material captured by the measurements. Predictions for freshwater CeO2-ENMs range from 1 pg/l (2017) to a few hundred ng/l (2050). Relative to CeO2, the SiO2-ENMs estimates are approximately 1,000 times higher, and those for Ag-ENMs 10 times lower. For most environmental compartments, ENM pose relatively low risk; however, organisms residing near ENM ‘point sources’ (e.g., production plant outfalls and waste treatment plants), which are not considered in the present work, may be at increased risk.

Phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] is a key second messenger that regulates actin and membrane dynamics, as well as other cellular processes. Many of the effects of PtdIns(4,5)P2are mediated by binding to effector proteins that contain a pleckstrin homology (PH) domain. Here, we identify two novel effectors of PtdIns(4,5)P2in the budding yeast Saccharomyces cerevisiae: the PH domain containing protein Slm1 and its homolog Slm2. Slm1 and Slm2 serve redundant roles essential for cell growth and actin cytoskeleton polarization. Slm1 and Slm2 bind PtdIns(4,5)P2through their PH domains. In addition, Slm1 and Slm2 physically interact with Avo2 and Bit61, two components of the TORC2 signaling complex, which mediates Tor2 signaling to the actin cytoskeleton. Together, these interactions coordinately regulate Slm1 targeting to the plasma membrane. Our results thus identify two novel effectors of PtdIns(4,5)P2regulating cell growth and actin organization and suggest that Slm1 and Slm2 integrate inputs from the PtdIns(4,5)P2and TORC2 to modulate polarized actin assembly and growth.

This study aims to determine the total content of phenolic compounds and antioxidant activity of mangosteen skin powder from fresh fruit with variations of storage duration which processed mechanically. Methods of research done by determining the total content of phenolic compounds using the method of DPPH free radical scavengers. The fresh mangosteen skin was dried with a drying oven, with a capacity of 0.12 kg/h and a drying rate of 2.79 kg. Furthermore, dry mangosteen skin was milled by grinding machine with 2870 rpm rotation and obtained rendemen mangosteen skin powder as much as 38.04% with water content 8.33%. Total content of phenolic mangosteen powder with variation of storage duration 0 days, 10 days, and 20 days ranged 81.17 mgGAE / g - 195.51 mgGAE /g. The range of IC 50 for the three treatment is 6.80 ppm - 26.47 ppm. The highest total phenolic content and antioxidant activity werw found at zero days of storage.

Telomeres are areas of heterochromatin composed of TTAGGG repeats located at the ends of linear chromosomes. They play a critical role in keeping genome stable and preventing premature aging diseases and the development of cancer. Characterizing mechanisms of telomere maintenance and understanding how their deregulation contributes to human diseases are therefore important for developing novel therapies. A key mechanism driving telomere maintenance and replicative immortality in cancer cells is telomere elongation by telomerase, and many emerging potential telomere-based therapies have focused on targeting telomerase components. By contrast, recent studies on telomere maintenance mechanism suggest that disrupting telomere stability by interfering with alternative mechanisms of telomere synthesis or protection may also yield new strategies for the treatment of cancer. This review will focus on emerging regulators of telomere synthesis or maintenance, such as G4 telomeric DNA, the CST complex, the t-loop, and shelterins, and discuss their potential as targets for anti-cancer chemotherapeutic intervention in the future.

Concerns about the environmental risks of engineered nanomaterials (ENM) are growing however currently very little is known about their concentrations in the environment. Here we calculate the concentrations of five ENM (nano TiO2 nano ZnO nano Ag CNT and fullerenes) in environmental and technical compartments using probabilistic material flow modelling. We apply the newest data on ENM production volumes their allocation to and subsequent release from different product categories and their flows into and within those compartments. Further we compare newly predicted ENM concentrations to estimates from 2009 and to corresponding measured concentrations of their conventional materials e.g. TiO2 Zn and Ag. We show that the production volume and the compounds' inertness are crucial factors determining final concentrations. ENM production estimates are generally higher than a few years ago. In most cases the environmental concentrations of corresponding conventional materials are between one and seven orders of magnitude higher than those for ENM. © 2013 Elsevier Ltd. All rights reserved.

The purpose of this research is to know the total of phenolics and antioxidant activity of Strawberry that grows in the area Alahan Panjang Solok Regency and Padang Panjang city . This research was carried out at the Chemical Laboratory of Agricultural Polytechinc State of Payakumbuh with a long six months time needed. To determine the levels of phenols total used Folin-Ciocalteu methode, and as a standard also to be used galat acid, while on antioxidant activity testing used DPPH free radical absorption methode. T he results of research that methanol extract of Strawberries originally from Alahan Panjang have phenol total 180 mg/100 g of fresh sample and higher than Strawberries originally from Padang Panjang with phenol total 139.2 mg/100 g of fresh sample.

There are so many ways to do in reducing cholesterol concentration in blood. Yogurt and strawberry juice have ability to repair blood lipid profile at hypercholesterolemia. Research and lactobacillus development potention as the cholesterol killing probiotic that to be mixed with strawberry juice is necessary to do to support community health. The purpose of this reasearch was measuring the mixture of yogurt and strawberry juice effectiveness to repair blood lipid profile. The design of this research that to be used was experimental by pretest and posted randomized control design progam. The sample of this research was thirty white mice (Rattus Norvegicus). Cholesterol Total, HDL and LDL to be analyzed by WI-M-KK2 BLK-SB methode (Clinical Chemstry Auto Analyzer) using tool Selectra E Auto Analyzer. The data was analyzed by Anova test, continued by LSD test using computer program . The result after giving mixture of yogurt and strawberry juice with the dosage 2ml and 3ml per day could obviously reduce LDL Level (p 0,05). The differentiation in dosis giving showed unmeaning reduction result (p>0,05). Conclusion, the mixture of yogurt and strawberry juice could repair blood lipid profile, where it’s proved to reduce drastically choleterol Total Level, LDL in 30 days.