Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC) Damages

Here, we studied the underlying mechanism of aldosterone (Aldo)-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L) inhibited human umbilical vein endothelial cells (HUVEC) survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18) production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P), an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS) inhibitor PDMP or the ceramide (C6) potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR) antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1) is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.     

黄土旱塬裸地土壤呼吸特征及其影响因子

于中国科学院长武生态试验站(始于1984年),采用动态密闭气室法(Li-8100,USA)于2008年3月至2009年3月监测了裸地土壤呼吸日变化、季节变化以及0-60cm土层的温度和含水量,研究了裸地土壤呼吸的日变化、季节变化特征及其与土壤温度和含水量之间的关系。结果表明:裸地土壤呼吸四季的日变化和季节变化均呈单峰型曲线,与气温变化趋势一致;日变化峰值出现在14:00左右或16:00左右,最低值出现在0:00左右或者6:00左右;季节变化表现为夏季最高,冬季最低,春秋季无明显差异,年平均呼吸速率为0.94μmolCO₂·m^-2·s^-1。土壤呼吸与温度具有极显著(P<0.01)的正相关关系,且可以用R_s=ae^bx形式的指数函数很好地拟合,其中与5cm深度的土壤温度相关性最好。水分对土壤呼吸的影响复杂。裸地土壤呼吸的双变量模型关系显著(P<0.01),比相应的单变量模型更好地解释了土壤呼吸变异。     

A conserved mechanism for sulfonucleotide reduction

Sulfonucleotide reductases are a diverse family of enzymes that catalyze the first committed step of reductive sulfur assimilation. In this reaction, activated sulfate in the context of adenosine-5'-phosphosulfate (APS) or 3'-phosphoadenosine 5'-phosphosulfate (PAPS) is converted to sulfite with reducing equivalents from thioredoxin. The sulfite generated in this reaction is utilized in bacteria and plants for the eventual production of essential biomolecules such as cysteine and coenzyme A. Humans do not possess a homologous metabolic pathway, and thus, these enzymes represent attractive targets for therapeutic intervention. Here we studied the mechanism of sulfonucleotide reduction by APS reductase from the human pathogen Mycobacterium tuberculosis, using a combination of mass spectrometry and biochemical approaches. The results support the hypothesis of a two-step mechanism in which the sulfonucleotide first undergoes rapid nucleophilic attack to form an enzyme-thiosulfonate (E-Cys-S-SO(3-)) intermediate. Sulfite is then released in a thioredoxin-dependent manner. Other sulfonucleotide reductases from structurally divergent subclasses appear to use the same mechanism, suggesting that this family of enzymes has evolved from a common ancestor.     

Treatment with IL-7 Prevents the Decline of Circulating CD4+ T Cells during the Acute Phase of SIV Infection in Rhesus Macaques

Although treatment with interleukin-7 (IL-7) was shown to transiently expand the naïve and memory T-cell pools in patients with chronic HIV-1 infection receiving antiretroviral therapy (ART), it is uncertain whether a full immunologic reconstitution can be achieved. Moreover, the effects of IL-7 have never been evaluated during acute HIV-1 (or SIV) infection, a critical phase of the disease in which the most dramatic depletion of CD4⁺ T cells is believed to occur. In the present study, recombinant, fully glycosylated simian IL-7 (50 µg/kg, s.c., once weekly for 7 weeks) was administered to 6 rhesus macaques throughout the acute phase of infection with a pathogenic SIV strain (mac251); 6 animals were infected at the same time and served as untreated controls. Treatment with IL-7 did not cause clinically detectable side effects and, despite the absence of concomitant ART, did not induce significant increases in the levels of SIV replication except at the earliest time point tested (day 4 post-infection). Strikingly, animals treated with IL-7 were protected from the dramatic decline of circulating naïve and memory CD4⁺ T cells that occurred in untreated animals. Treatment with IL-7 induced only transient T-cell proliferation, but it was associated with sustained increase in the expression of the anti-apoptotic protein Bcl-2 on both CD4⁺ and CD8⁺ T cells, persistent expansion of all circulating CD8⁺ T-cell subsets, and development of earlier and stronger SIV Tat-specific T-cell responses. However, the beneficial effects of IL-7 were not sustained after treatment interruption. These data demonstrate that IL-7 administration is effective in protecting the CD4⁺ T-cell pool during the acute phase of SIV infection in macaques, providing a rationale for the clinical evaluation of this cytokine in patients with acute HIV-1 infection.     

Foliar Spraying of 6-Benzylaminopurine Promotes Growth and Flavonoid Accumulation in Mulberry (Morus alba L.)

Journal of Plant Growth Regulation - Mulberry (Morus alba L.) leaf, a “source of both medicine and food”, contains antioxidant ingredients such as flavonoids, alkaloids and polyphenols....     

Predicting Prostate Biopsy Outcomes: A Preliminary Investigation on Screening with Ultrahigh B-Value Diffusion-Weighted Imaging as an Innovative Diagnostic Biomarker

Background

Routine screening of prostate specific antigen (PSA) is no longer recommended because of a high rate of over-diagnosis of prostate cancer (PCa).

Objective

To evaluate the efficacy of diffusion-weighted magnetic resonance imaging (DW-MRI) for PCa detection, and to explore the clinical utility of ultrahigh b-value DW-MRI in predicting prostate biopsy outcomes.

Methodology

73 male patients were selected for the study. They underwent 3T MRI using T2WI conventional DW-MRI with b-value 1000 s/mm², and ultrahigh b-value DW-MRI with b-values of 2000 s/mm² and 3000 s/mm². Two radiologists evaluated individual prostate gland images on a 5-point rating scale using PI-RADS, for the purpose of region-specific comparisons among modalities. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios (LR) were investigated for each MRI modality. The area under the receiver operating characteristic (ROC) curve (AUC) was also calculated.

Results

Results showed the improved diagnostic value of ultrahigh b-value DWI-MRI for detection of PCa when compared to other b values and conventional MRI protocols. Sensitivity values for 3000 s/mm² in both peripheral zone (PZ) and transition zone (TZ) were significantly higher than those observed with conventional DW-MRI—Specificity values for 3000 s/mm² in the TZ were significantly higher than other b-value images, whereas specificity values using 3000 s/mm² in the PZ were not significantly higher than 2000 s/mm² images. PPV and NPV between 3000 s/mm² and the other three modalities were significantly higher for both PZ and TZ images. The PLRs and NLRs of b-value 3000 s/mm² DW-MRI in the PZ and TZ were also recorded. ROC analysis showed greater AUCs for the b value 3000 s/mm² DWI than for the other three modalities.

Conclusions

DW-MRI with a b-value of 3000 s/mm² was found to be the most accurate and reliable MRI modality for PCa tumor detection and localization, particularly for TZ lesion discrimination. It may be stated that the b-value of 3000 s/mm² is a novel, improved diagnostic biomarker with greater predictive accuracy for PCa prior to biopsy.     

PDGF-AA Promotes Osteogenic Differentiation and Migration of Mesenchymal Stem Cell by Down-Regulating PDGFRα and Derepressing BMP-Smad1/5/8 Signaling

Platelet-derived growth factors (PDGFs) play important roles in skeletal development and bone fracture healing, yet how PDGFs execute their functions remains incompletely understood. Here we show that PDGF-AA, but not -AB or -BB, could activate the BMP-Smad1/5/8 pathway in mesenchymal stem cells (MSCs), which requires BMPRIA as well as PDGFRα. PDGF-AA promotes MSC osteogenic differentiation through the BMP-Smad1/5/8-Runx2/Osx axis and MSC migration via the BMP-Smad1/5/8-Twist1/Atf4 axis. Mechanistic studies show that PDGF-AA activates BMP-Smad1/5/8 signaling by feedback down-regulating PDGFRα, which frees BMPRI and allows for BMPRI-BMPRII complex formation to activate smad1/5/8, using BMP molecules in the microenvironment. This study unravels a physical and functional interaction between PDGFRα and BMPRI, which plays an important role in MSC differentiation and migration, and establishes a link between PDGF-AA and BMPs pathways, two essential regulators of embryonic development and tissue homeostasis.     

基于能值的陆域受威胁和濒危物种价值估算——以福建省厦门市为例

开展受威胁和濒危物种价值评估是生物多样性研究的关键问题之一。当前受威胁和濒危物种研究正处于濒危等级界定和保护优先性确定阶段,存在不同保护等级交叉管理、价值评估方法欠缺及重复性计算等多方面问题。利用IUCN濒危等级和中国特有种等级名录确定厦门市不同濒危等级物种数,在此基础上利用能值转换率和修正的中国能值/货币比率对厦门市陆域受威胁和濒危物种价值进行估算。结果显示,通过多途径整理纳入估算的厦门市陆域野生动植物物种数为1444种,其中受威胁和濒危物种数为318种;2015年厦门市物种能值价值约为3.53×10~(11)元,2010年约为3.08×10~(11)元,其中两期受威胁和濒危物种能值价值均占物种总价值的88.31%;中国特有种等级对价值贡献最大达73.25%,其次是IUCN濒危等级达23.24%。研究表明,能值评估法能够客观凸显受威胁和濒危物种价值,研究结果可为生物多样性及物种保育的管理决策提供技术支撑。     

城市环境中树木年轮的变异及其与工业发展的关系

通过对污染敏感树种油松年轮宽度和元素含量的变异与沈阳工业发展的相关分析。追溯和重建沈阳地区的生态环境变迁史,揭示城市环境质量与树木年轮变异之间的相关规律。结果表明,在城市污染条件下,树木年轮宽度和微量元素含量均发生了明显的变异,而且这些变异与沈阳工业发展显著相关．