Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl reabsorption

Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl reabsorption.BackgroundIntrarenal nitric oxide (NO) production and signaling effects are influenced by NaCl loading. To gain further insight into NO mechanisms we determined whether rat distal tubular fluid (DTF) [NO] and collected NO may acutely change when NaCl loop delivery is altered.MethodsAn NO microelectrode was used to measure real-time DTF [NO] and DT-collected NO. With proximal flow blocked (open system), 150mmol/L NaCl, with and without 10−4 mol/L furosemide was perfused with measurement of loop [Cl] reabsorption. Using a closed system, DTF [NO] was also determined using several different loop perfusates.ResultsIn the open system, perfusion with 40 nL/min of 150mmol/L NaCl to which 10−4 mol/L furosemide was added, DT [NO] and DT-collected NO was approximately twice that measured with perfusion of 150mmol/L NaCl alone, while loop Cl reabsorption decreased by half. In the closed system, perfusion at 10 nL/min of 150mmol/L NaCl + furosemide 10−4 mol/L also induced a significant rise in DTF [NO] and collected NO. Perfusion of 10−3 mol/L S-methyl-L-thiocitrulline (SMTC) with 150mmol/L NaCl, induces a significant drop in DT [NO], but without a significant increase in collected NO. Furthermore, with addition of 10−3 mol/L SMTC to the 150mmol/L NaCl + 10−4 furosemide perfusate, the rise in DT [NO] was prevented. Analysis of covariance showed that flow changes within, or between all groups, had no significant additional effect.ConclusionIn both open and closed loop perfusion systems, 10−4 mol/L furosemide inhibition of NaCl transport stimulates net loop NO emission independent of flow; 10−3 mol/L SMTC + 150mmol/L NaCl reduces DT [NO], but not DT-collected NO. Short-term net NO emission from the entire loop, as collected in distal tubule fluid, increases with inhibition of loop NaCl transport

Comparison of Target-Capture and Restriction-Site Associated DNA Sequencing for Phylogenomics: A Test in Cardinalid Tanagers (Aves, Genus: Piranga)

This is a pre-copyedited, author-produced version of an article accepted for publication in Systematic Biology following peer review. The version of record, Joseph D. Manthey, Luke C. Campillo, Kevin J. Burns, Robert G. Moyle; Comparison of Target-Capture and Restriction-Site Associated DNA Sequencing for Phylogenomics: A Test in Cardinalid Tanagers (Aves, Genus: Piranga), Systematic Biology, Volume 65, Issue 4, 1 July 2016, Pages 640–650, is available online at: ttps://doi.org/10.1093/sysbio/syw005.Restriction-site associated DNA sequencing (RAD-seq) and target capture of specific genomic regions, such as ultraconserved elements (UCEs), are emerging as two of the most popular methods for phylogenomics using reduced-representation genomic data sets. These two methods were designed to target different evolutionary timescales: RAD-seq was designed for population-genomic level questions and UCEs for deeper phylogenetics. The utility of both data sets to infer phylogenies across a variety of taxonomic levels has not been adequately compared within the same taxonomic system. Additionally, the effects of uninformative gene trees on species tree analyses (for target capture data) have not been explored. Here, we utilize RAD-seq and UCE data to infer a phylogeny of the bird genus Piranga. The group has a range of divergence dates (0.5–6 myr), contains 11 recognized species, and lacks a resolved phylogeny. We compared two species tree methods for the RAD-seq data and six species tree methods for the UCE data. Additionally, in the UCE data, we analyzed a complete matrix as well as data sets with only highly informative loci. A complete matrix of 189 UCE loci with 10 or more parsimony informative (PI) sites, and an approximately 80% complete matrix of 1128 PI single-nucleotide polymorphisms (SNPs) (from RAD-seq) yield the same fully resolved phylogeny of Piranga. We inferred non-monophyletic relationships of Pirangalutea individuals, with all other a priori species identified as monophyletic. Finally, we found that species tree analyses that included predominantly uninformative gene trees provided strong support for different topologies, with consistent phylogenetic results when limiting species tree analyses to highly informative loci or only using less informative loci with concatenation or methods meant for SNPs alone

Male New Zealand robins (Petroica longipes) cater to their mate's desire when sharing food in the wild.

In many species that have bi-parental care, food-sharing males provide vital nutritional resources to their mates during reproduction. However, it is currently unknown whether females can signal specific desires to their mates, or if males can cater to female desire in the wild. Here we investigate whether and how wild male North Island robins (Petroica longipes) respond to changes in their mates' desires and nutritional need when sharing food. We demonstrate that wild female robins' desire for particular foods changes over short time periods; when given the choice between two types of insect larvae, females prefer the type they have not recently eaten. In our experiments, wild male robins preferentially shared the larvae type that their mate was most likely to desire and also increased the quantity of food shared if she had begun incubating. Males catered to their mates' desire when female behaviour was the only cue available to guide their choices. This is the first evidence that females may behaviourally communicate their specific food desires to their mates, enabling males to cater to fine-scale changes in their mates' nutritional requirements in the wild. Such a simple behaviour-reading mechanism has the potential to be widespread among other food-sharing species

Memory Performance Influences Male Reproductive Success in a Wild Bird.

Not applicableMarsden Fund (Royal Society of New Zealand

Simulation of fluidized beds and other fluid-particle systems using statistical mechanics

The expansion behavior and structural phenomena of fluid-particle systems was simulated using a method analogous to the Monte Carlo method for molecular systems. Individual particles are moved, and the resulting moves are accepted or declined based on the change in the system's potential energy and the average kinetic energy of the system. Several fluid–particle systems have been successfully predicted with the model including colloidal particle concentration profiles and random packing of uniform spheres. Additionally, predictions of steady-state fluidized-bed expansion characteristics for uniformly sized stainless-steel spheres and narrowly distributed nickel and glass spheres show excellent agreement with the theoretical model used in the simulation and satisfactory agreement with experimental data. Dynamic expansion predictions of both bed height and overall bed structure as a function of time also agree with the experimental data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37439/1/690420307_ftp.pd

Treatment Intensification in Patients With Kawasaki Disease and Coronary Aneurysm at Diagnosis.

BackgroundCoronary artery aneurysms (CAA) are a serious complication of Kawasaki disease. Treatment with intravenous immunoglobulin (IVIg) within 10 days of fever onset reduces the risk of CAA from 25% to <5%. Corticosteroids and infliximab are often used in high-risk patients or those with CAA at diagnosis, but there are no data on their longer-term impact on CAA.MethodsRetrospective multicenter study including children who had CAA with a z score ≥2.5 and <10 at time of diagnosis and who received primary therapy with IVIg alone or in combination with either corticosteroids or infliximab within 10 days of onset of fever.ResultsOf 121 children, with a median age of 2.8 (range 0.1-15.5) years, 30 (25%) received primary therapy with corticosteroids and IVIg, 58 (48%) received primary therapy with infliximab and IVIg, and 33 (27%) received primary therapy with IVIg only. Median coronary z scores at the time of diagnosis did not differ among treatment groups (P = .39). Primary treatment intensification with either corticosteroids or infliximab were independent protective factors against progression of coronary size on follow-up (coefficient: -1.31 [95% confidence interval: -2.33 to -0.29]; coefficient: -1.07 [95% confidence interval: -1.95 to -0.19], respectively).ConclusionsAmong a high-risk group of patients with Kawasaki disease with CAA on baseline echocardiography, those treated with corticosteroids or infliximab in addition to IVIg had less progression in CAA size compared with those treated with IVIg alone. Prospective randomized trials are needed to determine the best adjunctive treatment of patients who present with CAA

Health-related quality of life and well-being in people over 75 years of age with end-stage kidney disease managed with dialysis or comprehensive conservative care: A cross-sectional study in the UK and Australia

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To measure health-related quality of life (HRQoL) and well-being in older people with end-stage kidney disease (ESKD) and to determine the association between treatment type and sociodemographic characteristics on these outcome measures. In addition, to assess the convergent validity between the HRQoL and well-being measure and their feasibility and acceptability in this population. Design Prospective cross-sectional study. Setting Three renal units in the UK and Australia. Participants 129 patients with ESKD managed with dialysis or with an estimated glomerular filtration ≤10 mL/min/1.73 m 2 and managed with comprehensive conservative, non-dialytic care. Outcome measures HRQoL and well-being were assessed using Short-Form six dimensions (SF-6D, 0-1 scale); Kidney Disease Quality of Life (KDQOL-36) (0-100 scale) and Investigating Choice Experiments Capability Measure-Older people (ICECAP-O, 0-1 scale). Linear regression assessed associations between treatment, HRQoL and well-being. Pearson's correlation coefficient assessed convergent validity between instruments. Results Median age of 81 years (IQR 78-85), 65% males; 83 (64%) were managed with dialysis and 46 (36%) with conservative care. When adjusted for treatment type and sociodemographic variables, those managed on dialysis reported lower mean SF-6D utility (-0.05, 95% CI-0.12 to 0.01); lower KDQOL Physical Component Summary score (-3.17, 95% CI-7.61 to 1.27); lower Mental Component Summary score (-2.41, 95% CI-7.66 to 2.84); lower quality of life due to burden (-28.59, 95% CI-41.77 to-15.42); symptoms (-5.93, 95% CI-14.61 to 2.73) and effects of kidney disease (-16.49, 95% CI-25.98 to-6.99) and lower overall ICECAP-O well-being (-0.07, 95% CI-0.16 to 0.02) than those managed conservatively. Correlation between ICECAP-O well-being and SF-6D utility scores was strong overall, 0.65 (

Restoration of pharyngeal dilator muscle force in dystrophin-deficient (mdx) mice following co-treatment with neutralizing interleukin-6 receptor antibodies and urocortin-2

New Findings: What is the central question of this study? We previously reported impaired upper airway dilator muscle function in the mdx mouse model of Duchenne muscular dystrophy (DMD). Our aim was to assess the effect of blocking interleukin-6 receptor signalling and stimulating corticotrophin-releasing factor receptor 2 signalling on mdx sternohyoid muscle structure and function. What is the main finding and its importance? The interventional treatment had a positive inotropic effect on sternohyoid muscle force, restoring mechanical work and power to wild-type values, reduced myofibre central nucleation and preserved the myosin heavy chain type IIb fibre complement of mdx sternohyoid muscle. These data might have implications for development of pharmacotherapies for DMD with relevance to respiratory muscle performance. The mdx mouse model of Duchenne muscular dystrophy shows evidence of impaired pharyngeal dilator muscle function. We hypothesized that inflammatory and stress-related factors are implicated in airway dilator muscle dysfunction. Six-week-old mdx (n = 26) and wild-type (WT; n = 26) mice received either saline (0.9% w/v) or a co-administration of neutralizing interleukin-6 receptor antibodies (0.2 mg kg−1) and corticotrophin-releasing factor receptor 2 agonist (urocortin 2; 30 μg kg−1) over 2 weeks. Sternohyoid muscle isometric and isotonic contractile function was examined ex vivo. Muscle fibre centronucleation and muscle cellular infiltration, collagen content, fibre-type distribution and fibre cross-sectional area were determined by histology and immunofluorescence. Muscle chemokine content was examined by use of a multiplex assay. Sternohyoid peak specific force at 100 Hz was significantly reduced in mdx compared with WT. Drug treatment completely restored force in mdx sternohyoid to WT levels. The percentage of centrally nucleated muscle fibres was significantly increased in mdx, and this was partly ameliorated after drug treatment. The areal density of infiltrates and collagen content were significantly increased in mdx sternohyoid; both indices were unaffected by drug treatment. The abundance of myosin heavy chain type IIb fibres was significantly decreased in mdx sternohyoid; drug treatment preserved myosin heavy chain type IIb complement in mdx muscle. The chemokines macrophage inflammatory protein 2, interferon-γ-induced protein 10 and macrophage inflammatory protein 3α were significantly increased in mdx sternohyoid compared with WT. Drug treatment significantly increased chemokine expression in mdx but not WT sternohyoid. Recovery of contractile function was impressive in our study, with implications for Duchenne muscular dystrophy. The precise molecular mechanisms by which the drug treatment exerts an inotropic effect on mdx sternohyoid muscle remain to be elucidated

The KRESCENT Program (2005-2015) : an evaluation of the state of Kidney Research Training in Canada

Background: The Kidney Research Scientist Core Education and National Training (KRESCENT) Program was launched in 2005 to enhance kidney research capacity in Canada and foster knowledge translation across the 4 themes of health research. Objective: To evaluate the impact of KRESCENT on its major objectives and on the careers of trainees after its first 10 years. Methods: An online survey of trainees (n = 53) who had completed or were enrolled in KRESCENT was conducted in 2015. Information was also obtained from curriculum vitae (CVs). A bibliometric analysis assessed scientific productivity, collaboration, and impact in comparison with unsuccessful applicants to KRESCENT over the same period. The analysis included a comparison of Canadian with international kidney research metrics from 2000 to 2014. Results: Thirty-nine KRESCENT trainees completed the survey (74%), and 44 trainees (83%) submitted CVs. KRESCENT trainees had a high success rate at obtaining grant funding from the Canadian Institutes of Health Research (CIHR; 79%), and 76% of Post-Doctoral Fellows received academic appointments at the Assistant Professor level within 8 months of completing training. The majority of trainees reported that KRESCENT had contributed significantly to their success in securing CIHR funding (90%), and to the creation of knowledge (93%) and development of new methodologies (50%). Bibliometric analysis revealed a small but steady decline in total international kidney research output from 2000 to 2014, as a percentage of all health research, although overall impact of kidney research in Canada increased from 2000-2005 to 2009- 2014 compared with other countries. KRESCENT trainees demonstrated increased productivity, multiauthored papers, impact, and international collaborations after their training, compared with nonfunded applicants. Conclusions: The KRESCENT Program has fostered kidney research career development and contributed to increased capacity, productivity, and collaboration. To further enhance knowledge creation and translation in kidney research in Canada, programs such as KRESCENT should be sustained via long-term funding partnerships.Mise en contexte: Le programme KRESCENT (Kidney Research Scientist Core Education and National Training) a été lancé en 2005 pour augmenter la capacité de la recherche sur les maladies du rein à travers le Canada, et pour encourager la transmission des connaissances au sein des quatre axes de recherche en santé. Objectifs de l’étude: Cette étude avait pour but d’évaluer les répercussions du programme KRESCENT sur ses principaux objectifs ainsi que des retombées sur la carrière des stagiaires participants, dix ans après sa création. Méthodologie: Un sondage en ligne a été mené en 2015 auprès des stagiaires (n = 53) ayant été admis ou ayant complété le programme KRESCENT. Des renseignements ont également été obtenus par la consultation de curriculum vitae (CV). Une analyse bibliométrique a évalué la productivité scientifique et la collaboration des participants ainsi que les répercussions de leur participation à KRESCENT sur leur carrière. Les données de cette analyse ont été comparées à celles des candidats n’ayant pas été retenus au cours de la même période. L’analyse comprenait également une comparaison des données canadiennes avec celles obtenues en recherche sur les maladies du rein ailleurs dans le monde

A novel method for comparison of arterial remodeling in hypertension: Quantification of arterial trees and recognition of remodeling patterns on histological sections

Remodeling of spatially heterogeneous arterial trees is routinely quantified on tissue sections by averaging linear dimensions, with lack of comparison between different organs and models. The impact of experimental models or hypertension treatment modalities on organ-specific vascular remodeling remains undefined. A wide variety of arterial remodeling types has been demonstrated for hypertensive models, which include differences across organs. The purpose of this study was to reassess methods for measurement of arterial remodeling and to establish a morphometric algorithm for standard and comparable quantification of vascular remodeling in hypertension in different vascular beds. We performed a novel and comprehensive morphometric analysis of terminal arteries in the brain, heart, lung, liver, kidney, spleen, stomach, intestine, skin, skeletal muscle, and adrenal glands of control and Goldblatt hypertensive rats on routinely processed tissue sections. Mean dimensions were highly variable but grouping them into sequential 5 μm intervals permitted creation of reliable linear regression equations and complex profiles. Averaged arterial dimensions demonstrated seven remodeling patterns that were distinct from conventional inward-outward and hypertrophic-eutrophic definitions. Numerical modeling predicted at least nineteen variants of arterial spatial conformations. Recognition of remodeling variants was not possible using averaged dimensions, their ratios, or the remodeling and growth indices. To distinguish remodeling patterns, a three dimensional modeling was established and tested. The proposed algorithm permits quantitative analysis of arterial remodeling in different organs and may be applicable for comparative studies between animal hypertensive models and human hypertension. Arterial wall tapering is the most important factor to consider in arterial morphometry, while perfusion fixation with vessel relaxation is not necessary. Terminal arteries in organs undergo the same remodeling pattern in Goldblatt rats, except for organs with hemodynamics affected by the arterial clip. The existing remodeling nomenclature should be replaced by a numerical classification applicable to any type of arterial remodeling