Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease's associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.Several species of crustose coralline algae (CCA) and their associated microbial biofilms play important roles in determining the settlement location of scleractinian corals on tropical reefs. In recent decades, peyssonnelid algal crusts (PAC) have become spatial dominants across large areas of shallow Caribbean reefs, where they appear to deter the recruitment of scleractinians. Our genetic investigations of PAC in St. John, US Virgin Islands, amplifying the large-subunit ribosomal RNA and psbA protein D1 marker genes, revealed them to be identical to Ramicrusta textilis previously reported overgrowing corals in Jamaica. Specimens of PAC sampled from the Honduras were likewise identical, confirming that this crustose alga inhabits the easternmost and westernmost regions of the Caribbean. We also analysed 16S rDNA tag amplicon libraries of the biofilms associated with PAC and sympatric CCA, which is favoured for coral settlement. Our results show that the microbial communities on PAC (vs. CCA) are characterized by significantly lower numbers of the epibiotic bacterial genus Pseudoalteromonas, which facilitates the recruitment and settlement of marine invertebrates. https://www.selleckchem.com/products/tng908.html From these data, we infer that PAC are therefore unlikely to be attractive as settlement sites for coral larvae. Given the significant ecological change anticipated on these reefs due to increasing cover of PAC, there is an urgent need to further investigate competitive interactions between PAC and scleractinian corals, and elucidate the role of PAC and their associated microbiomes in accentuating phase shifts from coral to algae on tropical reefs.The identification of femoral landmarks is a common procedure in multiple academic fields. Femoral bone coordinate systems are used particularly in orthopedics and biomechanics, and are defined by landmarks, axes and planes. A fully automatic detection overcomes the drawbacks of a labor-intensive manual identification. In this paper, a new automatic atlas- and a priori knowledge-based approach that processes femoral surface models, called the A&A method, was evaluated. The A&A method is divided in two stages. Firstly, a single atlas-based registration maps landmarks and areas from a template surface to the subject. In the second stage, landmarks, axes and planes that are used to construct several femoral bone coordinate systems are refined using a priori knowledge. Three common femoral coordinate systems are defined by the landmarks detected. The A&A method proved to be very robust against a variation of the spatial alignment of the surface models. The results of the A&A method and a manual identification were compared. No significant rotational differences existed for the bone coordinate system recommended by the International Society of Biomechanics. Minor significant differences of maximally 0.5° were observed for the two other coordinate systems. This might be clinically irrelevant, depending on the context of use and should, therefore, be evaluated by the potential user regarding the specific application. The entire source code of the A&A method and the data used in the study is open source and can be accessed via https//github.com/RWTHmediTEC/FemoralCoordinateSystem .Experiments involving food restriction are common practice in metabolic research. Under fasted conditions, **** supplement their diet with cage bedding. We aimed at identifying metabolic and microbiota-related parameters affected by the bedding type. We exposed **** housed with wooden, cellulose, or corncob cage beddings to ad libitum feeding, caloric restriction (CR), or over-night (ON) fasting. Additionally, two subgroups of the ON fast group were kept without any bedding or on a metal grid preventing coprophagy. **** under CR supplemented their diet substantially with bedding; however, the amount varied depending on the kind of bedding. Bedding-related changes in body weight loss, fat loss, cecum size, stomach weight, fecal output, blood ghrelin levels as well as a response to glucose oral tolerance test were recorded. As fiber is fermented by the gut bacteria, the type of bedding affects gut bacteria and fecal metabolites composition of CR ****. CR wood and cellulose groups showed distinct cecal metabolite and microbiome profiles when compared to the CR corncob group. While all ad libitum fed animal groups share similar profiles. We show that restriction-related additional intake of bedding-derived fiber modulates multiple physiological parameters. Therefore, the previous rodent studies on CR, report the combined effect of CR and increased fiber consumption.Cross-sectional observations have shown that the timing of eating may be important for health-related outcomes. Here we examined the stability of eating timing, using both clock hour and relative circadian time, across one semester (n = 14) at daily and monthly time-scales. At three time points ~ 1 month apart, circadian phase was determined during an overnight in-laboratory visit and eating was photographically recorded for one week to assess timing and composition. Day-to-day stability was measured using the Composite Phase Deviation (deviation from a perfectly regular pattern) and intraclass correlation coefficients (ICC) were used to determine individual stability across months (weekly average compared across months). Day-to-day clock timing of caloric events had poor stability within individuals (~ 3-h variation; ICC = 0.12-0.34). The timing of eating was stable across months (~ 1-h variation, ICCs ranging from 0.54-0.63), but less stable across months when measured relative to circadian timing (ICC = 0.
Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease's associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.Several species of crustose coralline algae (CCA) and their associated microbial biofilms play important roles in determining the settlement location of scleractinian corals on tropical reefs. In recent decades, peyssonnelid algal crusts (PAC) have become spatial dominants across large areas of shallow Caribbean reefs, where they appear to deter the recruitment of scleractinians. Our genetic investigations of PAC in St. John, US Virgin Islands, amplifying the large-subunit ribosomal RNA and psbA protein D1 marker genes, revealed them to be identical to Ramicrusta textilis previously reported overgrowing corals in Jamaica. Specimens of PAC sampled from the Honduras were likewise identical, confirming that this crustose alga inhabits the easternmost and westernmost regions of the Caribbean. We also analysed 16S rDNA tag amplicon libraries of the biofilms associated with PAC and sympatric CCA, which is favoured for coral settlement. Our results show that the microbial communities on PAC (vs. CCA) are characterized by significantly lower numbers of the epibiotic bacterial genus Pseudoalteromonas, which facilitates the recruitment and settlement of marine invertebrates. https://www.selleckchem.com/products/tng908.html From these data, we infer that PAC are therefore unlikely to be attractive as settlement sites for coral larvae. Given the significant ecological change anticipated on these reefs due to increasing cover of PAC, there is an urgent need to further investigate competitive interactions between PAC and scleractinian corals, and elucidate the role of PAC and their associated microbiomes in accentuating phase shifts from coral to algae on tropical reefs.The identification of femoral landmarks is a common procedure in multiple academic fields. Femoral bone coordinate systems are used particularly in orthopedics and biomechanics, and are defined by landmarks, axes and planes. A fully automatic detection overcomes the drawbacks of a labor-intensive manual identification. In this paper, a new automatic atlas- and a priori knowledge-based approach that processes femoral surface models, called the A&A method, was evaluated. The A&A method is divided in two stages. Firstly, a single atlas-based registration maps landmarks and areas from a template surface to the subject. In the second stage, landmarks, axes and planes that are used to construct several femoral bone coordinate systems are refined using a priori knowledge. Three common femoral coordinate systems are defined by the landmarks detected. The A&A method proved to be very robust against a variation of the spatial alignment of the surface models. The results of the A&A method and a manual identification were compared. No significant rotational differences existed for the bone coordinate system recommended by the International Society of Biomechanics. Minor significant differences of maximally 0.5° were observed for the two other coordinate systems. This might be clinically irrelevant, depending on the context of use and should, therefore, be evaluated by the potential user regarding the specific application. The entire source code of the A&A method and the data used in the study is open source and can be accessed via https//github.com/RWTHmediTEC/FemoralCoordinateSystem .Experiments involving food restriction are common practice in metabolic research. Under fasted conditions, mice supplement their diet with cage bedding. We aimed at identifying metabolic and microbiota-related parameters affected by the bedding type. We exposed mice housed with wooden, cellulose, or corncob cage beddings to ad libitum feeding, caloric restriction (CR), or over-night (ON) fasting. Additionally, two subgroups of the ON fast group were kept without any bedding or on a metal grid preventing coprophagy. Mice under CR supplemented their diet substantially with bedding; however, the amount varied depending on the kind of bedding. Bedding-related changes in body weight loss, fat loss, cecum size, stomach weight, fecal output, blood ghrelin levels as well as a response to glucose oral tolerance test were recorded. As fiber is fermented by the gut bacteria, the type of bedding affects gut bacteria and fecal metabolites composition of CR mice. CR wood and cellulose groups showed distinct cecal metabolite and microbiome profiles when compared to the CR corncob group. While all ad libitum fed animal groups share similar profiles. We show that restriction-related additional intake of bedding-derived fiber modulates multiple physiological parameters. Therefore, the previous rodent studies on CR, report the combined effect of CR and increased fiber consumption.Cross-sectional observations have shown that the timing of eating may be important for health-related outcomes. Here we examined the stability of eating timing, using both clock hour and relative circadian time, across one semester (n = 14) at daily and monthly time-scales. At three time points ~ 1 month apart, circadian phase was determined during an overnight in-laboratory visit and eating was photographically recorded for one week to assess timing and composition. Day-to-day stability was measured using the Composite Phase Deviation (deviation from a perfectly regular pattern) and intraclass correlation coefficients (ICC) were used to determine individual stability across months (weekly average compared across months). Day-to-day clock timing of caloric events had poor stability within individuals (~ 3-h variation; ICC = 0.12-0.34). The timing of eating was stable across months (~ 1-h variation, ICCs ranging from 0.54-0.63), but less stable across months when measured relative to circadian timing (ICC = 0.
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