Epithelial Na \u3csup\u3e+\u3c/sup\u3e sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei

The epithelial Na + channels (ENaCs) are present in kidney and contribute to Na + and water homeostasis. All three ENaC subunits (α, β, and γ) were demonstrated in the cardiovascular regulatory centers of the rat brain, including the magnocellular neurons (MNCs) in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). However, the functional significance of ENaCs in vasopressin (VP) and oxytocin (OT) synthesizing MNCs is completely unknown. In this study, we show with immunocytochemical double-labeling that the α-ENaC is colocalized with either VP or OT in MNCs in the SON and PVN. In addition, parvocellular neurons in the dorsal, ventrolateral, and posterior subregions of the PVN (not immunoreactive to VP or OT) are also immunoreactive for α-ENaC. In contrast, immunoreactivity to β- and γ-ENaC is colocalized with VP alone within the MNCs. Furthermore, immunoreactivity for a known target for ENaC expression, the mineralcorticoid receptor (MR), is colocalized with both VP and OT in MNCs. Using single-cell RT-PCR, we detected mRNA for all three ENaC subunits and MR in cDNA libraries derived from single MNCs. In whole cell voltage clamp recordings, application of the ENaC blocker benzamil reversibly reduced a steady-state inward current and decreased cell membrane conductance approximately twofold. Finally, benzamil caused membrane hyperpolarization in a majority of VP and about one-half of OT neurons in both spontaneously firing and quiet cells. These results strongly suggest the presence of functional ENaCs that may affect the firing patterns of MNCs, which ultimately control the secretion of VP and OT. © 2012 the American Physiological Society

Increased chromatin accessibility facilitates intron retention in specific cell differentiation states

Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type or condition-specific IR regulation by trans-regulatory and epigenetic mechanisms demand an unbiased and systematic analysis of IR in a controlled experimental setting. We integrated matched mRNA sequencing (RNA-seq), whole-genome bisulfite sequencing (WGBS), nucleosome occupancy methylome sequencing (NOMe-Seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data from primary human myeloid and lymphoid cells. Using these multi-omics data and machine learning we trained two complementary models to determine the role of epigenetic factors in the regulation of IR in cells of the innate immune system. We show that increased chromatin accessibility, as revealed by nucleosome-free regions, contributes substantially to the retention of introns in a cell-specific manner. We also confirm that intrinsic characteristics of introns are key for them to evade splicing. This study suggests an important role of chromatin architecture in IR regulation. With an increasing appreciation that pathogenic alterations are linked to RNA processing, our findings may provide useful insights for the development of novel therapeutic approaches that target aberrant splicing

Ab initio many-body calculations on infinite carbon and boron-nitrogen chains

In this paper we report first-principles calculations on the ground-state electronic structure of two infinite one-dimensional systems: (a) a chain of carbon atoms and (b) a chain of alternating boron and nitrogen atoms. Meanfield results were obtained using the restricted Hartree-Fock approach, while the many-body effects were taken into account by second-order M{\o}ller-Plesset perturbation theory and the coupled-cluster approach. The calculations were performed using 6-31$G^{**}$ basis sets, including the d-type polarization functions. Both at the Hartree-Fock (HF) and the correlated levels we find that the infinite carbon chain exhibits bond alternation with alternating single and triple bonds, while the boron-nitrogen chain exhibits equidistant bonds. In addition, we also performed density-functional-theory-based local density approximation (LDA) calculations on the infinite carbon chain using the same basis set. Our LDA results, in contradiction to our HF and correlated results, predict a very small bond alternation. Based upon our LDA results for the carbon chain, which are in agreement with an earlier LDA calculation calculation [ E.J. Bylaska, J.H. Weare, and R. Kawai, Phys. Rev. B 58, R7488 (1998).], we conclude that the LDA significantly underestimates Peierls distortion. This emphasizes that the inclusion of many-particle effects is very important for the correct description of Peierls distortion in one-dimensional systems.Comment: 3 figures (included). To appear in Phys. Rev.

Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder

Aim: Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. Materials & methods: We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. Results: Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). Conclusion: PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts

Hearing loss and cognitive decline in the general population: a prospective cohort study

Background: Previous studies identifying hearing loss as a promising modifiable risk factor for cognitive decline mostly adjusted for baseline age solely. As such a faster cognitive decline at a higher age, which is expected considering the non-linear relationship between cognition and age, may have been overlooked. Therefore it remains uncertain whether effects of hearing loss on cognitive decline extend beyond age-related declines of cognitive function. Methods: 3,590 non-demented participants were eligible for analysis at baseline, and a maximum of 837 participants were eligible for the longitudinal analysis. Hearing loss was defined at baseline. Cognitive function was measured at baseline and at follow-up (4.4 years [SD: 0.2]). Multivariable linear regression analysis was used for the cross-sectional analysis. Linear mixed models were used to assess the longitudinal association between hearing loss and cognitive decline over time while adjusting for confounders and the interaction of age and follow-up time. Results: Hearing loss was associated with lower cognitive function at baseline. Moreover, hearing loss was associated with accelerated cognitive decline over time on a memory test. After additionally adjusting for the interaction between age and follow-up time, we found that hearing loss did not accelerate cognitive decline anymore. Conclusions: Hearing loss was associated with lowe

Long-Term Results After the Glycoprotein IIb/IIIa Inhibitor Abciximab in Unstable Angina

BACKGROUND: This study was designed to investigate long-term effects of the glycoprotein IIb/IIIa inhibitor abciximab in patients with acute coronary syndrome without ST elevation who were not scheduled for coronary intervention. METHODS AND RESULTS: A total of 7800 patients were included with an acute coronary syndrome without ST elevation, documented by either elevated cardiac troponin or transient or persistent ST-segment depression. They were randomized to abciximab bolus and 24-hour infusion, abciximab bolus and 48-hour infusion, or matching placebo. The overall 1-year mortality rate was 8.3% (649 patients). One-year mortality was 7.8% in the placebo group and 8.2% in the 24-hour and 9.0% in the 48-hour abciximab infusion group. Compared with placebo, the hazard ratio for the 24-hour infusion of abciximab was 1.1 (95% CI 0.86 to 1.29), and for the 48-hour infusion, it was 1.2 (95% CI 0.95 to 1.41). The lack of benefit of abciximab was observed in every subgroup studied. Patients with negative troponin or elevated C-reactive protein had a higher mortality rate after treatment with abciximab for 48 hours than with placebo: 8.5% versus 5.8% in those with negative troponin (P=0.02), 16.3% versus 12.1% in those with elevated C-reactive protein (P=0.04). CONCLUSIONS: Compared with placebo, abciximab did not provide any survival benefit at 1 year in patients admitted with an acute coronary syndrome with ST depression and/or elevated troponin who were not scheduled to undergo early coronary revascularization. In subgroups of patients, in particular those with low cardiac troponin or elevated C-reactive protein, abciximab was associated with excess mortality

Liquid-phase approach to glass-microfiber-reinforced sulfide solid electrolytes for all-solid-state batteries

Deformable, fast-ion conducting sulfides enable the construction of bulk-type solid-state batteries that can compete with current Li-ion batteries in terms of energy density and scalability. One approach to optimizing the energy density of these cells is to minimize the size of the electrolyte layer by integrating the solid electrolyte in thin membranes. However, additive-free thin membranes, as well as many membranes based on preprepared scaffolds, are difficult to prepare or integrate in solid cells on a large scale. Here, we propose a scalable solution-based approach to produce bulk-type glass-microfiber-reinforced composites that restore the deformability of sulfide electrolytes and can easily be shaped into thin membranes by cold pressing. This approach supports both the ease of preparation and enhancement of the energy density of sulfide-based solid-state batteries

Microstructural evolution and transmutation in tungsten under ion and neutron irradiation

This study aims to compare the effects of neutron and self-ion irradiation on the mechanical properties and microstructural evolution in W. Neutron irradiation at the HFR reactor to 1.67 dpa at 800 °C resulted in the formation of large Re and Os rich clusters and voids. The post-irradiation composition was measured using APT and verfified against FISPACT modelling. The measured Re and Os concentration was used to create alloys with equivalent concentrations of Re and Os. These alloys were exposed to self-ion irradiation to a peak dose of 1.7 dpa at 800 °C. APT showed that self-ion irradiation leads to the formation of small Os clusters, wheras under neutron irradiation large Re/Os clusters form. Voids are formed by both ion and neutron irradiation, but the voids formed by neutron irradiation are larger. By comparing the behaviour of W-1.4Re and W-1.4Re-0.1Os, suppression of Re cluster formation was observed. Irradiation hardening was measured using nanoindentation and was found to be 2.7 GPa, after neutron irradiation and 1.6 GPa and 0.6 GPa for the self-ion irradiated W-1.4Re and W-1.4Re-0.1Os. The higher hardening is attributed to the barrier strength of large voids and Re/Os clusters that are observed after neutron irradiation

Properties of heavy quarkonia and B_c mesons in the relativistic quark model

The mass spectra and electromagnetic decay rates of charmonium, bottomonium and B_c mesons are comprehensively investigated in the relativistic quark model. The presence of only heavy quarks allows the expansion in powers of their velocities. All relativistic corrections of order v^2/c^2, including retardation effects and one-loop radiative corrections, are systematically taken into account in the computations of the mass spectra. The obtained wave functions are used for the calculation of radiative magnetic dipole (M1) and electric dipole (E1) transitions. It is found that relativistic effects play a substantial role. Their account and the proper choice of the Lorentz structure of the quark-antiquark interaction in a meson is crucial for bringing theoretical predictions in accord with experimental data. A detailed comparison of the calculated decay rates and branching fractions with available experimental data for radiative decays of charmonium and bottomonium is presented. The possibilities to observe the currently missing spin-singlet S and P states as well as D states in bottomonium are discussed. The results for B_c masses and decays are compared with other quark model predictions.Comment: 31 pages, 2 figures, minor correction

Higher moments of nucleon spin structure functions in heavy baryon chiral perturbation theory and in a resonance model

The third moment $d_2$ of the twist-3 part of the nucleon spin structure function $g_2$ is generalized to arbitrary momentum transfer $Q^2$ and is evaluated in heavy baryon chiral perturbation theory (HBChPT) up to order ${\mathcal{O}}(p^4)$ and in a unitary isobar model (MAID). We show how to link $d_2$ as well as higher moments of the nucleon spin structure functions $g_1$ and $g_2$ to nucleon spin polarizabilities. We compare our results with the most recent experimental data, and find a good description of these available data within the unitary isobar model. We proceed to extract the twist-4 matrix element $f_2$ which appears in the $1/Q^2$ suppressed term in the twist expansion of the spin structure function $g_1$ for proton and neutron.Comment: 30 pages, 7 figure