Angiotensin II is Required to Induce Exaggerated Salt Sensitivity in Dahl Rats Exposed to Maternal Separation

We previously reported that maternal separation, rat model of early life stress, enhances pressor responses to acute and chronic stressors. The aims of this study were to determine whether Dahl salt-sensitive (DS) rats subjected to maternal separation (MatSep-DS) as compared to normally reared DS (Ctl-DS) rats show exaggerated blood pressure responses to acute behavioral stressors, such as restraint stress or air jet stress (AJS), or, hypertensive stimuli including chronic high-salt diet (4% NaCl) and angiotensin II (AngII) infusion (200 ng/Kg/min) during 1 week. MatSep was performed in male DS rats for 3 h/day from postnatal days 2-14. At 8 weeks of age, rats were implanted with telemetry transmitters and allowed to recover. Mean arterial pressure (MAP) was not different between MatSep-DS and Ctl-DS rats at baseline (120 ± 2 mmHg vs. 118 ± 1 mmHg, n = 4-8). Blood pressure responses during AJS and restraint stress were not different between MatSep-DS and Ctl-DS at 3 min. However, blood pressure recovery from AJS was significantly impaired in MatSep-DS rats compared to Ctl-DS rats (P \u3c 0.05). 3-h stress-induced similar responses in MatSep and Ctl-DS rats. Chronic blood pressure responses to AngII infusion in rats fed a high-salt diet displayed enhanced MAP in MatSep-DS when compared with Ctl-DS rats (167 ± 5 mmHg vs. 152 ± 2 mmHg, pinteraction \u3c0.05). However, MAP increased similarly in both groups in response to AngII infusion or high-salt diet separately. Renal parameters such as proteinuria, urine flow rate, and urine electrolytes were not different between groups in response to each treatment. In summary, salt sensitivity induces exaggerated blood pressor responses only in presence of AngII due to early life stress

Renal response to seven days of lower body positive pressure in the squirrel monkey

As a ground-based model for weightlessness, the response of the chair-trained squirrel monkey to lower body positive pressure (LBPP) was evaluated in a length of study similar to a typical Space Shuttle mission (7 days). Results were compared to time control experiments that included chair-sitting without exposure to LBPP. Chronic exposure to LBPP results in an acute diuretic and natriuretic response independent of changes in plasma aldosterone concentrations and produces a chronic reduction in fluid volume lasting the duration in the stimulus

Seismic Performance of Confined Sill Plate Connections

In the aftermath of the 1994 Northridge earthquake, extensive field investigations revealed damage in wood frame construction in the form of splitting of the 2 X 4 or 2 X 6 wood sill plates along the line of anchor bolts that typically connect shear walls to the masonry or concrete foundation. Due to the severity of such brittle failures, the city of Los Angeles has recently restricted the use of 2X dimension lumber in sill plates and requires the use of 3X dimension lumber. This paper presents an experimental investigation of the performance of 2X dimension lumber sill plate connections at the yield and ultimate limit states during incremental quasi-static reversed cyclic loading and suggests possible cost-effective retrofit strategies for their improved seismic performance without having to increase the sill plate thickness. Proposed retrofit strategies are based on providing confinement to the sill plate using metal reinforcing straps and reinforcing clamps to increase the deformation capability and energy dissipation capacity of the connection, while maintaining substantial levels of connection strengths

Dietary potassium supplementation improves vascular structure and ameliorates the damage caused by cerebral ischemia in normotensive rats

<p>Abstract</p> <p>Background</p> <p>Dietary potassium supplementation in hypertensive rats is cardioprotective. This protection includes a blood pressure independent reduction in the amount of damage caused by cerebral ischemia. Therefore, we hypothesized that dietary potassium supplementation would improve the outcome of ischemic stroke by improving cerebral vessel structure in normotensive rats.</p> <p>Methods</p> <p>Wistar Kyoto (WKY) rats were fed a high (HK) or low potassium (LK) diet for six weeks from six weeks of age. At the end of treatment, cerebral ischemia was induced by middle cerebral artery (MCA) occlusion and the resultant infarct was quantified and expressed as a percentage of the hemisphere infarcted (%HI). MCA structure was assessed in an additional group of rats using a pressurized arteriograph.</p> <p>Results</p> <p>The cerebral infarct was significantly smaller in rats fed the HK diet, compared to rats fed the LK diet (21 ± 5.4 vs 33.5 ± 4.8 %HI HK vs LK p < 0.05). Vessel structure was improved in WKY rats fed the HK diet as indicated by an increase in the MCA lumen (298 ± 6.3 vs 276 ± 3.9 μm HK vs LK p < 0.05) and outer diameters (322 ± 7.6 vs 305 ± 4.8 μm HK vs LK p < 0.05). Wall thickness and area were unchanged, suggesting an outward euthrophic remodelling process. The HK diet had no effect on body weight or telemetry blood pressure.</p> <p>Conclusion</p> <p>These studies are the first to show a beneficial effect of dietary potassium in rats with normal blood pressure.</p

Arabidopsis \u3ci\u3eGLABROUS1\u3c/i\u3e Gene Requires Downstream Sequences for Function

The Arabidopsis GLABROUSl (GL1) gene is a myb gene homolog required for the initiation of trichome development. In situ hybridiration revealed that the highest levels of GL1 transcripts were present in developing trichomes. In contrast, previous work had shown that putative promoter sequences from the 5‘ noncoding region of the GL1 gene directed the expression of a β-glucuronidase (GUS) reporter gene only in stipules. Deletion analysis of the 3’ noncoding region of GL1 has identified an enhancer that is essential for GL1 function. Sequences fmm the region containing the enhancer, in conjunction with GL1 upstream sequences, direct the expression of a GUS reporter gene in leaf primordia and developing trichomes in addition to stipules, indicating that the downstream enhancer is required for the normal expression pattern of GL1

Clover species cover on summer dry hill country in Central Otago

The prevalence of annual clover species and white clover (Trifolium repens) during the critical late winter to early summer period (mid Aug – Dec) are compared in relation to aspect, altitude, temperature and rainfall on Mt Grand at Hawea Flat. Measurements were at four north facing sites (450, 620, 750, 910 m a.s.l.) and one shady site at 630 m a.s.l. The rainfall was similar for all altitudes and aspects but annual clovers dominated on sunny faces and the perennial white clover dominated on the shady face with suckling (T. dubium) the only adventive annual clover present. Annual cluster clover (T. glomeratum) dominated on the lower sunny faces at 450 and 620 m and sub clover (T. subterraneum) dominated at 750 m. Suckling and striated clover (T. striatum) were present on all sunny aspect sites and were unaffected by altitude while haresfoot (T. arvense) presence increased with altitude. Air thermal time accumulation for the mid Aug-Dec period was 1440 °Cd at the 450 m site and declined at 100 °Cd per 100 m of elevation (r² = 0.99). Thermal time at 910 m was <1000 °Cd and may limit seed production of some annual clover species at or above this altitude. The dominance of adventive annual clovers on the sunny aspects indicates areas that are probably suitable for introduction of improved annual species such as balansa clover (T. michelianum) or modern cultivars of sub. Productivity of perennial white clover which has persisted on the shady faces may be increased by more intensive grazing management

Withdrawal Strength of Ring-shank Nails Embedded in Southern Pine Lumber

Ring-shank nails are used extensively in post-frame construction due to their superior performance, yet surprisingly little testing has been done on nail sizes above 12d. Experience in the post-frame industry suggests that published allowable design values for ring-shank nails may be overly conservative and need revision. The goal of the research reported herein was to characterize the withdrawal strength of ring-shank nails embedded in Southern Pine lumber. Three sizes ofgalvanized and ungalvanized (bright) ring-shank nails from two manufacturers were studied. Ring-shank nails had approximately twice the withdrawal resistance of smooth-shank nails of the same diameter. Galvanizing slightly reduced withdrawal strength (approximately 8%) due to partial filling of the threads. Nail head pull-through was studied as a possible failure mode. Even allowing for galvanizing and head pull-through, strong evidence is presentedfor increasing withdrawal design valuesfor ring-shank nails

Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P &lt; .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P &lt; .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).ConclusionNot only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed

Characterization of the OCO-2 instrument line shape functions using on-orbit solar measurements

Accurately characterizing the instrument line shape (ILS) of the Orbiting Carbon Observatory-2 (OCO-2) is challenging and highly important due to its high spectral resolution and requirement for retrieval accuracy (0. 25 %) compared to previous spaceborne grating spectrometers. On-orbit ILS functions for all three bands of the OCO-2 instrument have been derived using its frequent solar measurements and high-resolution solar reference spectra. The solar reference spectrum generated from the 2016 version of the Total Carbon Column Observing Network (TCCON) solar line list shows significant improvements in the fitting residual compared to the solar reference spectrum currently used in the version 7 Level 2 algorithm in the O₂ A band. The analytical functions used to represent the ILS of previous grating spectrometers are found to be inadequate for the OCO-2 ILS. Particularly, the hybrid Gaussian and super-Gaussian functions may introduce spurious variations, up to 5 % of the ILS width, depending on the spectral sampling position, when there is a spectral undersampling. Fitting a homogeneous stretch of the preflight ILS together with the relative widening of the wings of the ILS is insensitive to the sampling grid position and accurately captures the variation of ILS in the O₂ A band between decontamination events. These temporal changes of ILS may explain the spurious signals observed in the solar-induced fluorescence retrieval in barren areas

Endothelin.

The endothelins comprise three structurally similar 21-amino acid peptides. Endothelin-1 and -2 activate two G-protein coupled receptors, ETA and ETB, with equal affinity, whereas endothelin-3 has a lower affinity for the ETA subtype. Genes encoding the peptides are present only among vertebrates. The ligand-receptor signaling pathway is a vertebrate innovation and may reflect the evolution of endothelin-1 as the most potent vasoconstrictor in the human cardiovascular system with remarkably long lasting action. Highly selective peptide ETA and ETB antagonists and ETB agonists together with radiolabeled analogs have accurately delineated endothelin pharmacology in humans and animal models, although surprisingly no ETA agonist has been discovered. ET antagonists (bosentan, ambrisentan) have revolutionized the treatment of pulmonary arterial hypertension, with the next generation of antagonists exhibiting improved efficacy (macitentan). Clinical trials continue to explore new applications, particularly in renal failure and for reducing proteinuria in diabetic nephropathy. Translational studies suggest a potential benefit of ETB agonists in chemotherapy and neuroprotection. However, demonstrating clinical efficacy of combined inhibitors of the endothelin converting enzyme and neutral endopeptidase has proved elusive. Over 28 genetic modifications have been made to the ET system in mice through global or cell-specific knockouts, knock ins, or alterations in gene expression of endothelin ligands or their target receptors. These studies have identified key roles for the endothelin isoforms and new therapeutic targets in development, fluid-electrolyte homeostasis, and cardiovascular and neuronal function. For the future, novel pharmacological strategies are emerging via small molecule epigenetic modulators, biologicals such as ETB monoclonal antibodies and the potential of signaling pathway biased agonists and antagonists.We (APD, JJM) thank the British Heart Foundation (PS/02/001, PG/05/127/19872, FS/12/64/130001), Wellcome Trust Programme in Metabolic and Cardiovascular Disease 096822/Z/11/Z NIHR Cambridge Biomedical Research Centre and the Pulmonary Hypertension Association UK; Wellcome Biomedical Resources Grant 099156/Z/12/Z for support for IUPHAR/BPS Guide to PHARMACOLOGY (CS). We acknowledge National Heart, Lung, and Blood Institute Grants P01 HL95499 (D.E.K., K.A.H., D.M.P., J.S.P.), P01 HL69999 (D.M.P., J.S.P.), U01HL117684 (D.M.P.).This is the final version of the article. It first appeared from the American Society for Pharmacology and Experimental Therapeutics via https://doi.org/10.1124/pr.115.01183