Levels of selected minerals, nitric oxide, and vitamins in aborted Sakis sheep raised under semitropical conditions

The serum levels of calcium, phosphorus, magnesium, copper, zinc and iron and of nitric oxide, retinol, and β-carotene were determined in Sakiz ewes that had experienced an abortion and in healthy controls. Ten healthy and 25 aborted Sakiz sheep were selected from Afyon zone in western Turkey. Their ages ranged between 2 and 4 years weighing between 40 and 60 kg at the time of experiment. All of the abortions occurred in October. The concentrations of retinol, β-carotene, phosphorus, and zinc were significantly lower and those of calcium and nitric oxide were increased in aborted ewes relative to healthy controls. The serum levels of iron, copper, and magnesium were not significantly different among the two groups. In conclusion, abortion is an important problem in commercially important species of ruminants in many regions in the tropics including of western Turkey. Deficiencies of retinol, β-carotene, phosphorus and zinc, and the increase of calcium and nitric oxide concentration may play an important role in the etiology of abortion in ewes. Prophylactic measures such as vitamin and mineral supplementation may be of help to prevent or reduce the incidence of abortion in sheep

Complement C3 Deficiency Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in Mice

Background: Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension. Methodology/Principal Findings: Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice. Conclusions: Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans. © 2011 Bauer et al

Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition

Audio-Motor Integration for Robot Audition

International audienceIn the context of robotics, audio signal processing in the wild amounts to dealing with sounds recorded by a system that moves and whose actuators produce noise. This creates additional challenges in sound source localization, signal enhancement and recognition. But the speci-ficity of such platforms also brings interesting opportunities: can information about the robot actuators' states be meaningfully integrated in the audio processing pipeline to improve performance and efficiency? While robot audition grew to become an established field, methods that explicitly use motor-state information as a complementary modality to audio are scarcer. This chapter proposes a unified view of this endeavour, referred to as audio-motor integration. A literature review and two learning-based methods for audio-motor integration in robot audition are presented, with application to single-microphone sound source localization and ego-noise reduction on real data

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL- 12–dependent IFN-? immunity and IL-23–dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL- 12Rß2 or IL-23R deficiency, lacking responses to IL-12 or IL- 23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that aß T, ?d T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-? in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-? in response to IL-23. We also show that the development of IFN-?–producing CD4+ T cells, including, in particular, mycobacterium-specific TH1* cells (CD45RA-CCR6+), is dependent on both IL-12 and IL-23. Last, we show that IL12RB1, IL12RB2, and IL23R have similar frequencies of deleterious variants in the general population. The comparative rarity of symptomatic patients with IL-12Rß2 or IL-23R deficiency, relative to IL-12Rß1 deficiency, is, therefore, due to lower clinical penetrance. There are fewer symptomatic IL-23R– and IL-12Rß2–deficient than IL-12Rß1–deficient patients, not because these genetic disorders are rarer, but because the isolated absence of IL-12 or IL-23 is, in part, compensated by the other cytokine for the production of IFN-?, thereby providing some protection against mycobacteria. These experiments of nature show that human IL-12 and IL-23 are both required for optimal IFN-?–dependent immunity to mycobacteria, both individually and much more so cooperatively

Predictive modelling of soils’ hydraulic conductivity using artificial neural network and multiple linear regression

As a result of heterogeneity nature of soils and variation in its hydraulic conductivity over several orders of magnitude for various soil types from fine-grained to coarse-grained soils, predictive methods to estimate hydraulic conductivity of soils from properties considered more easily obtainable have now been given an appropriate consideration. This study evaluates the performance of artificial neural network (ANN) being one of the popular computational intelligence techniques in predicting hydraulic conductivity of wide range of soil types and compared with the traditional multiple linear regression (MLR). ANN and MLR models were developed using six input variables. Results revealed that only three input variables were statistically significant in MLR model development. Performance evaluations of the developed models using determination coefficient and mean square error show that the prediction capability of ANN is far better than MLR. In addition, comparative study with available existing models shows that the developed ANN and MLR in this study performed relatively better