Regulation of alternative polyadenylation in the yeast Saccharomyces cerevisiae by histone H3K4 and H3K36 methyltransferases.

Adjusting DNA structure via epigenetic modifications, and altering polyadenylation (pA) sites at which precursor mRNA is cleaved and polyadenylated, allows cells to quickly respond to environmental stress. Since polyadenylation occurs cotranscriptionally, and specific patterns of nucleosome positioning and chromatin modifications correlate with pA site usage, epigenetic factors potentially affect alternative polyadenylation (APA). We report that the histone H3K4 methyltransferase Set1, and the histone H3K36 methyltransferase Set2, control choice of pA site in Saccharomyces cerevisiae, a powerful model for studying evolutionarily conserved eukaryotic processes. Deletion of SET1 or SET2 causes an increase in serine-2 phosphorylation within the C-terminal domain of RNA polymerase II (RNAP II) and in the recruitment of the cleavage/polyadenylation complex, both of which could cause the observed switch in pA site usage. Chemical inhibition of TOR signaling, which causes nutritional stress, results in Set1- and Set2- dependent APA. In addition, Set1 and Set2 decrease efficiency of using single pA sites, and control nucleosome occupancy around pA sites. Overall, our study suggests that the methyltransferases Set1 and Set2 regulate APA induced by nutritional stress, affect the RNAP II C-terminal domain phosphorylation at Ser2, and control recruitment of the 3 end processing machinery to the vicinity of pA sites.post-print1.432 K

The Economic Contribution of Instream Flows to the Lower Connecticut River Watershed, New England, USA

River recreation is a rapidly expanding source of economic productivity. Angler spending has been used as the basis for estimating the regional economic estimates of local income and jobs in several water-limited systems of the western United States and Mexico. However, the contribution of outdoor recreation to the economies of regions that do not experience water scarcity continues to be underappreciated. This paper estimates the economic contribution of angling to the lower Connecticut River Watershed (CRW) economy. The authors draw upon existing angler expenditure, river flow and geographic information system (GIS) data to relate anger use of the lower CRW and expenditures to river flows. The authors then translate angler expenditures into state income and employment using a regional economic multiplier. The results show that fishing expenditures of $62.8 million per year equate to$74.2 million annually in supply chain revenues which supports 1660 jobs. The authors identified a significant positive relationship between fishing intensity and river flow rates, which suggests that decreasing current water diversions on the lower CRW by just 25% would add an additional $37 million and 638 jobs to Connecticut’s economy. The findings demonstrate that investments in managing the health the CRW through flow restoration can have large economic and ecological pay-offs

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer\u27s disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain

Pre-ART Levels of Inflammation and Coagulation Markers Are Strong Predictors of Death in a South African Cohort with Advanced HIV Disease

BACKGROUND: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART. METHODS: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels. RESULTS: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95%CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.8-7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001). CONCLUSIONS: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted. TRIAL REGISTRATION: Parent study: ClinicalTrials.gov NCT00342355

Evaluation of the Impact of the Trivedi Effect® -Energy of Consciousness on the Structure and Isotopic Abundance Ratio of Magnesium Gluconate Using LC-MS and NMR Spectroscopy

Magnesium gluconate is a classical pharmaceutical/nutraceutical compound used as a magnesium ion source for the prevention and treatment of hypomagnesemia. The present study was aimed to investigate the effect of The Trivedi Effect® - Energy of Consciousness Healing Treatment (Biofield Energy Healing Treatment) on magnesium gluconate for the change in the structural properties and isotopic abundance ratio (PM+1/PM and PM+2/PM) using LC-MS and NMR spectroscopy. Magnesium gluconate was divided into two parts – one part was control, and another part was treated with The Trivedi Effect® - Biofield Energy Healing Treatment remotely by twenty renowned Biofield Energy Healers and defined as The Trivedi Effect® Treated sample. The LC-MS analysis of both the control and treated samples indicated the presence of mass of the protonated magnesium gluconate at m/z 415 at the retention time of 1.52 min and fragmentation pattern of the both sample were almost similar. The relative peak intensities of the fragment ions were significantly changed in the treated sample compared with the control sample. The proton and carbon signals for CH, CH2 and CO groups in the proton and carbon NMR spectra were observed almost similar for the control and the treated samples. The percentage change in the isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 17O/16O or 25Mg/24Mg) was significantly decreased in the treated sample by 17.51% compared with the control sample. Consequently, the isotopic abundance ratio of PM+2/PM (18O/16O or 26Mg/24Mg) in the treated sample was significantly increased by 79.44% compared to the control sample. Briefly, 13C, 2H, 17O, and 25Mg contributions from (C12H23MgO14)+ to m/z 416; 18O and 26Mg contributions from (C12H23MgO14)+ to m/z 417 in treated sample were significantly altered compared with the control sample. Thus, The Trivedi Effect® Treated magnesium gluconate might be supportive to design the novel potent enzyme inhibitors using its kinetic isotope effects. Consequently, The Trivedi Effect® Treated magnesium gluconate would be valuable for designing better pharmaceutical and/or nutraceutical formulations through its changed physicochemical and thermal properties, which might be providing better therapeutic response against various diseases such as diabetes mellitus, allergy, aging, inflammatory diseases, immunological disorders, and other chronic infections. Source: https://www.trivedieffect.com/science/evaluation-of-the-impact-of-the-trivedi-effect-energy-of-consciousness-on-the-structure-and-isotopic-abundance-ratio-of-magnesium-gluconate-using-lc-ms-and-nmr-spectroscopy http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=655&doi=10.11648/j.ajbls.20170501.1

Evaluation of the Physicochemical, Structural, Thermal, and Behavioral Properties of the Energy of Consciousness Healing Treated Zinc Chloride

Zinc chloride is a source of zinc used in various pharmaceutical/nutraceutical formulations. The objective of the current study was to investigate the impact of The Trivedi Effect® - Energy of Consciousness Healing Treatment (Biofield Energy Treatment) on physical, structural, thermal, and behavioral properties of zinc chloride using PXRD, PSD, FT-IR, UV-vis, and DSC analysis. Zinc chloride was divided into two parts – one part was control, while another part was treated with The Trivedi Effect® remotely by twenty renowned Biofield Energy Healers and defined as The Trivedi Effect® Treated sample. A significant alteration of the crystallite size and relative intensities of the PXRD peaks was observed in The Trivedi Effect® treated sample compared with the control sample. The average crystallite size of the treated sample was significantly increased by 23.18% compared with the control sample. The particle size values at d10, d50, and d90 values were significantly decreased by 3.70%, 4.13%, and 6.13%, respectively in the treated sample compared with the control sample. Therefore, the surface area of the treated sample was increased by 4.21% compared with the control sample. The FT-IR spectroscopic analysis revealed that Zn-Cl stretching in the control sample was found at 512 cm-1, whereas it was significantly shifted upward to 520 cm-1 in the treated sample. The UV-vis analysis exhibited that wavelength of the maximum absorbance (λmax) of the control and treated samples were at 197.6 nm and 197.1 nm, respectively. The DSC analysis exhibited that the melting temperature was decreased by 0.22%, while decomposition temperature was increased by 2.56% in the treated sample compared to the control sample. The latent heat of fusion of the treated sample (320.44 J/g) was significantly decreased by 16.70% compared with the control sample (284.67 J/g). Similarly, the enthalpy of decomposition of the treated sample (952.53 J/g) was significantly increased by 122.61% compared with the control sample (427.90 J/g). Thus, the results indicated that the thermal stability of the treated zinc chloride was improved compared with the control sample. The current study anticipated that The Trivedi Effect® - Energy of Consciousness Healing Treatment might lead to produce a thermally stable new polymorphic form of zinc chloride, which would be more soluble and bioavailable compared with the untreated compound. Hence, the treated zinc chloride would be very useful to design better nutraceutical/pharmaceutical formulations that might offer better therapeutic response against inflammatory diseases, immunological disorders, aging, stress, cancer, etc. https://www.trivedieffect.com/science/evaluation-of-the-physicochemical-structural-thermal-and-behavioral-properties-of-the-energy-of-consciousness-healing-treated-zinc-chloride http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=217&doi=10.11648/j.bio.20170502.1

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer