Erythropoietin-induced hypertension and vascular injury in mice overexpressing human endothelin-1: exercise attenuated hypertension, oxidative stress, inflammation and immune response

OBJECTIVE: Erythropoietin used to correct anaemia in chronic kidney disease (CKD) has been shown to increase blood pressure (BP) in CKD patients and experimental animals. Endothelin (ET)-1 expression is increased in CKD animals and patients, and enhanced by erythropoietin. Erythropoietin-induced BP rise was blunted by ETA receptor blockers. This study was designed to determine whether preexisting endothelin (ET)-1 overexpression is required for erythropoietin to cause adverse vascular effects and whether this could be prevented by exercise training. METHODS: Eight to 10-week old male wild-type mice and mice with endothelial-specific ET-1 overexpression (eET-1) were treated or not with EPO (100 IU/kg, SC, 3 times/week). eET-1 was subjected or not to swimming exercise training (1 h/day, 6 days/week) for 8 weeks. SBP, mesenteric artery endothelial function and remodelling, NADPH oxidase activity, reactive oxygen species (ROS) generation, vascular cell adhesion protein (VCAM)-1, monocyte/macrophage infiltration, T regulatory cells (Tregs) and tissue ET-1 and plasma endothelin were determined. RESULTS: Erythropoietin increased SBP by 24 mmHg (P < 0.05) and decreased by 25% vasodilatory responses to acetylcholine (P < 0.01) in eET-1 mice. Erythropoietin enhanced ET-1 induced increase in resistance artery media/lumen ratio (31%, P < 0.05), aortic NADPH oxidase activity (50%, P < 0.05), ROS generation (93%, P < 0.001), VCAM-1 (80%, P < 0.01) and monocyte/macrophage infiltration (159%, P < 0.001), and raised plasma and aortic ET-1 levels (>/=130%, P < 0.05). EPO had no effect in wild-type mice. Exercise training prevented all of the above (P < 0.05). CONCLUSION: Erythropoietin-induced adverse vascular effects are dependent on preexisting elevated ET-1 expression. Exercise training prevented erythropoietin-induced adverse vascular effects in part by inhibiting ET-1 overexpression-induced oxidative stress, inflammation and immune activation

Low energy measurement of the 7Be(p,gamma)8B cross section

We have measured the cross section of the 7Be(p,gamma)8B reaction for E_cm = 185.8 keV, 134.7 keV and 111.7 keV using a radioactive 7Be target (132 mCi). Single and coincidence spectra of beta^+ and alpha particles from 8B and 8Be^* decay, respectively, were measured using a large acceptance spectrometer. The zero energy S factor inferred from these data is 18.5 +/- 2.4 eV b and a weighted mean value of 18.8 +/- 1.7 eV b (theoretical uncertainty included) is deduced when combining this value with our previous results at higher energies.Comment: Accepted for publication in Phys. Rev. Let

Qualitative and quantitative evaluation of microalgal biomass using portable attenuated total reflectance-Fourier transform infrared spectroscopy and machine learning analytics

BACKGROUND: Using microalgae for wastewater treatment offers an environmentally friendly method to produce microalgal biomass that can be used for many applications. However, the biochemical characteristics of microalgal biomass vary from species to species, from strain to strain, and between different growth stages within the same species/strain. This study utilized portable attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy to determine the composition of freeze-dried microalgal biomass corresponding to eight different locally isolated microalgae and a reference strain that were grown in wastewater and then harvested at the log and stationary phases, respectively. RESULTS: The results showed that the portable ATR-FTIR spectroscopy offered a rapid, non-destructive, and accurate technique for monitoring changes in the biochemical composition of algal biomass at stationary and log phases, as well as quantifying their main constituents. For qualitative analysis of species, two machine learning analytics (MLAs; correlation in wavenumber space and principal component analysis) were able to differentiate between microalgae isolates in both their stationary and log phases. For quantification, univariate or multivariate regression offered accuracy in quantifying key microalgal constituents related to proteins, lipids, and carbohydrates. In this sense, multivariate methods showed more accuracy for quantifying carbohydrates, yet proteins and lipids were more accurately quantified with univariate regression. Based on quantification, the highest relative content of carbohydrates in the log phase was for Jordan-23 (Jo-23; Desmodesmus sp.), whereas the highest content in the stationary phase was that for Jordan-29 (Jo-29; Desmodesmus sp). Regarding the relative lipid content in the log phase, Jo-23 had the highest lipid content, while the highest content in the stationary phase was for Jo-29. CONCLUSION: ATR-FTIR spectroscopy offered a rapid and sustainable method for monitoring the microalgal biomass produced during wastewater treatment processes

CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells

Hepatitis C virus (HCV) infects cells by the direct uptake of cell-free virus following virus engagement with specific cell receptors such as CD81. Recent data have shown that HCV is also capable of direct cell-to-cell transmission, although the role of CD81 in this process is disputed. Here, we generated cell culture infectious strain JFH1 HCV (HCVcc) genomes carrying an alanine substitution of E2 residues W529 or D535 that are critical for binding to CD81 and infectivity. Co-cultivation of these cells with naïve cells expressing enhanced green fluorescent protein (EGFP) resulted in a small number of cells co-expressing both EGFP and HCV NS5A, showing that the HCVcc mutants are capable of cell-to-cell spread. In contrast, no cell-to-cell transmission from JFH1ΔE1E2-transfected cells occurred, indicating that the HCV glycoproteins are essential for this process. The frequency of cell-to-cell transmission of JFH1W529A was unaffected by the presence of neutralizing antibodies that inhibit E2–CD81 interactions. By using cell lines that expressed little or no CD81 and that were refractive to infection with cell-free virus, we showed that the occurrence of viral cell-to-cell transmission is not influenced by the levels of CD81 on either donor or recipient cells. Thus, our results show that CD81 plays no role in the cell-to-cell spread of HCVcc and that this mode of transmission is shielded from neutralizing antibodies. These data suggest that therapeutic interventions targeting the entry of cell-free HCV may not be sufficient in controlling an ongoing chronic infection, but need to be complemented by additional strategies aimed at disrupting direct cell-to-cell viral transmission

A compilation of charged-particle induced thermonuclear reaction rates

Low-energy cross section data for 86 charged-particle induced reactions involving light (1 less than or equal to Z less than or equal to 14), mostly stable, nuclei are compiled. The corresponding Maxwellian-averaged thermonuclear reaction rates of relevance in astrophysical plasmas at temperatures in the range from 10(6) K to 10(10) K are calculated. These evaluations assume either that the target nuclei are in their ground state, or that the target states are thermally populated following a Maxwell-Boltzmann distribution, except in some cases involving isomeric states. Adopted values complemented with lower and upper limits of the rates are presented in tabular form. Analytical approximations to the adopted rates, as well as to the inverse/direct rate ratios, are provided. (C) 1999 Elsevier Science B.V. All rights reserved

The Reading Palaeofire Database: an expanded global resource to document changes in fire regimes from sedimentary charcoal records

Sedimentary charcoal records are widely used to reconstruct regional changes in fire regimes through time in the geological past. Existing global compilations are not geographically comprehensive and do not provide consistent metadata for all sites. Furthermore, the age models provided for these records are not harmonised and many are based on older calibrations of the radiocarbon ages. These issues limit the use of existing compilations for research into past fire regimes. Here, we present an expanded database of charcoal records, accompanied by new age models based on recalibration of radiocarbon ages using IntCal20 and Bayesian age-modelling software. We document the structure and contents of the database, the construction of the age models, and the quality control measures applied. We also record the expansion of geographical coverage relative to previous charcoal compilations and the expansion of metadata that can be used to inform analyses. This first version of the Reading Palaeofire Database contains 1676 records (entities) from 1480 sites worldwide. The database (RPDv1b – Harrison et al., 2021) is available at https://doi.org/10.17864/1947.000345

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Magnetic hyperthermia controlled drug release in the GI tract : solving the problem of detection

Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine