ROCKing cytokine secretion balance in human T cells

Balanced regulation of cytokine secretion in T cells is critical for maintenance of immune homeostasis and prevention of autoimmunity. The Rho-associated kinase (ROCK) 2 signaling pathway was previously shown to be involved in controlling of cellular movement and shape. However, recent work from our group and others has demonstrated a new and important role of ROCK2 in regulating cytokine secretion in T cells. We found that ROCK2 promotes pro-inflammatory cytokines such as IL-17 and IL-21, whereas IL-2 and IL-10 secretion are negatively regulated by ROCK2 under Th17-skewing activation. Also, in disease, but not in steady state conditions, ROCK2 contributes to regulation of IFN-γ secretion in T cells from rheumatoid arthritis patients. Thus, ROCK2 signaling is a key pathway in modulation of T-cell mediated immune responses underscoring the therapeutic potential of targeted inhibition of ROCK2 in autoimmunity.     

Economic values and dominant providers of key ecosystem services of wetlands in Beijing,China

This study estimates the economic values of and the dominant contributors to five key ecosystem services of wetlands in Beijing, by using the wetland inventory data in 2014 and economic valuation methods. Results indicate that the 51,434 ha of wetlands in Beijing annually provide 2.07 billion m³ of flood regulation, 944.01 million m³ of water provision, 42,154 tons of chemical oxygen demand (COD) purification, 3.03 PJ of heat absorption, and 9587 ha of habitat. Their economic values are estimated to be 15.89 billion RMB, 1.19 billion RMB, 169 million RMB, 421 million RMB, and 1.08 billion RMB in 2014 (RMB: Chinese currency, US$1 = RMB 6.14), respectively. The total values of five key wetland ecosystem services reach 18.76 billion RMB. In addition, the reservoir and river wetlands in Miyun, Yanqing, Fangshan, Huairou, and Mentougou Districts contribute 78% of key ecosystem services, whereas the urban wetlands in Xicheng, Dongcheng, Haidian, Chaoyang, and Tongzhou Districts more conveniently serve densely local people, hence they should be given particular attentions. In this paper, we develop the valuation methods of wetland ecosystem services, and recommend diversified strategies, regulations, and programs to protect the remaining wetlands in Beijing. This work can also provide a reference for the valuating of wetland ecosystem services for other urban-rural areas.     

p11 modulates calcium handling through 5-HT4R pathway in rat ventricular cardiomyocytes

BackgroundThe role of the serotonin receptor 4 (5-HT₄R) pathway in cardiac excitation-contraction coupling (ECC) remains unclear. In the brain, induction of the calcium (Ca²⁺)-binding protein p11 enhances 5-HT₄R translocation and signaling and could therefore be considered as a modulator of the 5-HT₄R pathway in the myocardium. p11 expression is increased by brain-derived neurotrophic factor (BDNF) or antidepressant drugs (imipramine). Thus, we investigated whether p11 regulates the 5-HT₄R pathway in the heart in physiological conditions or under pharmacological induction and the effects on calcium handling.Methods and resultsp11 expression was induced in vivo in healthy Wistar rats by imipramine (10 mg/kg/21 days) and in vitro in left ventricular cardiomyocytes exposed to BDNF (50 ng/ml/8 h). Cell shortening and real-time Ca²⁺ measurements were processed on field-stimulated intact cardiomyocytes with the selective 5-HT₄R agonist, prucalopride (1 μM). Both imipramine and BDNF-induced cardiomyocyte p11 expression unmasked a strong response to prucalopride characterized by an increase of both cell shortening and Ca²⁺ transient amplitude compared to basal prucalopride associated with a high propensity to trigger diastolic Ca²⁺ events. Healthy rats treated with BDNF (180 ng/day/14 days) exhibited a sustained elevated heart rate following a single injection of prucalopride (0.1 mg/kg) which was not observed prior to treatment.ConclusionsWe have identified a novel role for p11 in 5-HT₄R signaling in healthy rat ventricular cardiomyocytes. Increased p11 expression by BDNF and imipramine unraveled a 5-HT₄R-mediated modulation of cardiac Ca²⁺ handling and ECC associated with deleterious Ca²⁺ flux disturbances. Such mechanism could partly explain some cardiac adverse effects induced by antidepressant treatments.     

Degradation of cholecystokinin octapeptide,related fragments and analogs by human and rat plasma in vitro

The rate of degradation of cholecystokinin octapeptide, related fragments and analogs by human and rat plasma was investigated, using high pressure liquid chromatography for the separation and identification of the degradation products.CCK tetrapeptide showed a half-life of 13 min in human plasma while its cleavage in rat plasma occurred at a very high rate (half-life of less than 1 min).The kinetics of disappearance of both sulphated and unsulphated CCK-8 indicated more than a single rate of degradation; the faster degrading system showed a half-life of 18 min for unsulphated CCK-8 and of 50 min for the sulphated peptide in human plasma as compared respectively with 5 and 17 min in rat plasma. The cleavage of CCK-8 was inhibited by bestatin and puromycin, suggesting that aminopeptidases play a major role in the breakdown of this peptide.CCK-9 analogs were rapidly converted into their corresponding octapeptides (half-life of 2.7 min in human plasma). This conversion was inhibited by puromycin and bestatin, suggesting the participation of aminopeptidase(s) probably specific for basic amino acids.CCK decapeptide exhibited a greater stability than the nonapeptides (half-life of 30 and 45 min in human and rat plasma respectively) and also gave rise to CCK-8 as degradation product. This cleavage was not affected by aminopeptidase inhibitors but was decreased by aprotinin (Trasylol®), suggesting that trypsin-like and/or kallikrein-like enzyme(s) were involved in the plasma metabolism of this peptide.     

10-nonacosanol,sitosterol and nonacosanediols in Juniperus pinchotii

GC of juniper leaf non-saponifiables gave three peaks of sterol-triterpenes which were identified as 10-nonacosanol, sitosterol and a mixture of nonacosanediols.     

Environmental and genetic control of crassulacean acid metabolism in two crassulacean species and an F1 hybrid with differing biomass δ13C values

Abstract The growth, biomass δ¹³C values, and ability to accumulate titratable acidity at night were compared in eight environmental treatments for Cremnophila linguifolia, Sedum greggii, and their F₁ hybrid. In the phytotron, differences in treatment daylength, day/night temperature and water availability were all found to have effects on total plant dry weight, nocturnal accumulation of titratable acidity and biomass δ¹³C value of at least some of the genotypes. However, there were differences between the genotypes both in the magnitude and direction of response of the phenotypic properties to the treatment variables. The phytotron δ¹³C values ranged from -12.9 to -19.2‰ for C. linguifolia, from -22.2 to -33.4‰ for S. greggii, and from -19.2 to -24.9‰ for the hybrid. After with-holding water for 76 h both C. linguifolia and the hybrid had midday Ψ_leaf values of -0.23 MPa; however, S. greggii had a value of -1.05 MPa. In contrast to past observations of other species, the daily watered plants of C. linguifolia had less negative δ¹³C values than did the plants watered only weekly.     

Magnification of the therapeutic uses of pomegranate fruits and peel in rats injected with carbon tetrachloride (Ccl4)

The liver is more prone to infections that cause fibrosis, such as steatosis, non-alcoholic steatohepatitis, hepatotoxicity, cirrhosis, and hepatocellular carcinoma. Also, Viral hepatitis is a common condition worldwide it worsens into chronic inflammation of the liver. One of the healthiest fruits is the pomegranate for the body and health, as it contains a high nutritional value of minerals, vitamins, antioxidants, so we worked on this investigation to magnify the therapeutic applications of pomegranate fruits (POF) and peel (POP) in carbon tetrachloride-injected rats (Ccl4). The experiment was carried out in a caged animal. All rats were fed a basal diet for one week before the study, and they were divided into seven groups, each with six rats. As a control negative group (C–ve), the first group sample was fed only the basal diet for 28 days. The remaining rats (n = 36) were injected with carbon tetrachloride (Ccl4). Five groups were fed varying concentrations of (5 %, 10 %, 15 % POF, 5 %, and 10 % pomegranate peel (POP)), whereas one group was diagnosed with the illness and disease, and didn't even feed the experimental diet. The results revealed significant increases in T.BIL, D.BIL, and BIL in the serum of rats injected by CC14 to induce hepatopathy compared to the healthy group (normal rats). Also, the best treatment considering the serum D.BIL was recorded for the 5 % POF.