Comparisons on the nutritive values of local and introduced forages and feed mixture for ruminant feed in central dry zone of Myanmar

This study aimed to compare nutritive values of local (Sorghum) and introduced (Mombasa) forages and their feed mixtures for ruminant feed in central dry zone of Myanmar. Sorghum based feed mixtures (FeedMix-1, 2 and 3) were the commonly used feed mixtures for cattle in dry zone of Myanmar and other feed mixtures (FeedMix-4, 5 and 6) were based on Mombasa. The lower CP and higher fibre contents (P<0.05) were observed in sorghum and its feed mixtures. The highest gas volumes (P<0.05) were observed in the FeedMix-4 and 6, and then the lowest gas volume (P<0.05) was observed in FeedMix-3. The gas production from quickly soluble fraction (a) of sorghum was significantly higher (P<0.05) than that of Mombasa, inversely the gas production from insoluble fraction (b) of sorghum was significantly lower (P<0.05) than that of Mombasa. Moreover, potential gas production (a+b), ME, OMD and SCFA of sorghum were also significantly lower (P<0.05) than those of Mombasa. The value of “a” was lowest (P<0.05) in FeedMix-1, whereas the highest value was found in FeedMix-6. The lowest values (P<0.05) of “b”, “a+b”, ME, OMD and SCFA were observed in FeedMix-3 and the highest values (P<0.05) of those parameters were found in FeedMix-4. Thus, the higher nutritive values observed in the introduced forage, Mombasa and its feed mixtures were indicating that Mombasa should be used instead of sorghum for the feed of cattle in dry zone of Myanmar.&nbsp

Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2

BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function

Measuring Five Dimensions of Religiosity Across Adolescence

This paper theorizes and tests a latent variable model of adolescent religiosity in which five dimensions of religiosity are interrelated: religious beliefs, religious exclusivity, external religiosity, private practice, and religious salience. Research often theorizes overlapping and independent influences of single items or dimensions of religiosity on outcomes such as adolescent sexual behavior, but rarely operationalizes the dimensions in a measurement model accounting for their associations with each other and across time. We use longitudinal structural equation modeling (SEM) with latent variables to analyze data from two waves of the National Study of Youth and Religion. We test our hypothesized measurement model as compared to four alternate measurement models and find that our proposed model maintains superior fit. We then discuss the associations between the five dimensions of religiosity we measure and how these change over time. Our findings suggest how future research might better operationalize multiple dimensions of religiosity in studies of the influence of religion in adolescence

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults.

Elevated fibroblast growth factor-23 (FGF23) is an established marker of cardiovascular disease. The underlying reason(s) for the rise accompanying cardiovascular health decline are unclear. Prior studies have shown that FGF23 concentrations are associated with markers of inflammation and insulin resistance but they have been limited by a focus on persons with chronic kidney disease (CKD) and lack of race and sex diversity. The objective of this study was to examine the associations of FGF23 and markers of inflammation, insulin resistance, and anthropometrics in a large cohort of community-dwelling adults.Associations of FGF23 with markers of inflammation [interleukin-6 (IL-6), IL-10, high sensitivity-CRP (hsCRP)], insulin utilization [resistin, adiponectin, homeostatic model assessment of insulin resistance (HOMA-IR)] and anthropometrics [BMI and waist circumference (WC)] were examined cross-sectionally in a 1,040 participants randomly selected from the Reason for Geographic and Racial Differences in Stroke (REGARDS) Study, a national study of black and white adults ≥45 years. Effect modification by race and CKD status was tested, and stratified models were analyzed accordingly.Median FGF23 concentration was 69.6 RU/ml (IQR: 53.2, 102.7). Higher quartiles of FGF23 were associated with higher mean concentrations of IL-6, IL-10, hsCRP and resistin (Ptrend<0.001 for all). There were no significant differences in HOMA-IR, adiponectin concentrations, BMI, or WC across FGF23 quartiles in the crude analyses. CKD significantly modified the relationships between FGF23 and inflammatory markers, HOMA-IR, BMI and WC (P ≤ 0.01 for all). In linear regression models adjusted for sociodemographic and clinical variables, FGF23 was positively associated with IL-6, hsCRP, IL-10, HOMA-IR, BMI and WC in individuals without CKD, but not among individuals with CKD. Additionally, FGF23 was positively associated with resistin irrespective of CKD status.Elevated FGF23 concentrations may be considered a biomarker for decline in metabolic function among individuals with normal kidney function

Markers of inflammation, insulin utilization and anthropometrics overall and by quartile of FGF23.

<p>The first column represents the overall sample, and the subsequent columns represent FGF23 quartiles 1–4, respectively, in each panel. Values are presented as geometric means, 95% confidence intervals (interleukin-6, high sensitivity C-Reactive protein, interleukin-10, resistin, adiponectin, HOMA-IR)) or mean ± standard deviation (body mass index, waist circumference).</p

Participant characteristics overall and by quartile of fibroblast growth factor-23 level.

<p>Data are given as mean (standard error), median [interquartile range] or frequencies.</p><p>Abbreviations: UACR, urinary albumin to creatinine ratio; eGFR, estimated glomerular filtration rate.</p><p>* (≤7 and 14 drinks/d for women and men, respectively)</p><p>**(>7 and 14 drinks/d for women and men, respectively)</p><p>***In answer to “How many times per week do you engage in intense physical activity, enough to work up a sweat?”</p><p>Participant characteristics overall and by quartile of fibroblast growth factor-23 level.</p

Multivariable-adjusted associations between natural log-transformed fibroblast growth factor-23 and natural log-transformed markers of inflammation in the overall sample and by chronic kidney disease (CKD) status.

<p>Model 1 is adjusted for age, sex, race, region of residence. Model 2 is adjusted for variables in Model 1 plus indices of socioeconomic status, history of diabetes, coronary heart disease, stroke, lifestyle habits (tobacco usage, alcohol consumption, physical activity), serum calcium, serum phosphorus, eGFR and UACR. In models stratified by CKD status, Model 2 was not adjusted for eGFR and UACR. IL-6 = interleukin-6, hsCRP = high-sensitivity c-reactive protein, IL-10 = interleukin-10.</p><p>Multivariable-adjusted associations between natural log-transformed fibroblast growth factor-23 and natural log-transformed markers of inflammation in the overall sample and by chronic kidney disease (CKD) status.</p

Multivariable-adjusted associations between natural log-transformed fibroblast growth factor-23 and anthropometrics (BMI and WC, waist circumference) in the overall sample and by chronic kidney disease (CKD) status.

<p>Model 1 is adjusted for age, sex, race, and region of residence. Model 2 is adjusted for indices of socioeconomic status, history of coronary heart disease and/or stroke, lifestyle habits (tobacco usage, alcohol consumption, physical activity), serum calcium, phosphorus, eGFR and UACR. In models stratified by CKD status, Model 2 was not adjusted for eGFR and UACR.</p><p>Multivariable-adjusted associations between natural log-transformed fibroblast growth factor-23 and anthropometrics (BMI and WC, waist circumference) in the overall sample and by chronic kidney disease (CKD) status.</p