Function of the lectin domain of Mac-1/complement receptor type 3 (CD11b/CD18) in regulating neutrophil adhesion

A lectin function within CD11b mediates both cytotoxic priming of Mac-1/complement receptor type 3 (CR3) by beta-glucan and the formation of transmembrane signaling complexes with GPI-anchored glycoproteins such as CD16b (FcgammaRIIIb). A requirement for GPI-anchored urokinase plasminogen activator receptor (uPAR; CD87) in neutrophil adhesion and diapedesis has been demonstrated with uPAR-knockout mice. In this study, neutrophil activation conditions generating high-affinity (H-AFN) or low-affinity (L-AFN) beta(2) integrin adhesion were explored. A role for the Mac-1/CR3 lectin domain and uPAR in mediating H-AFN or L-AFN adhesion was suggested by the inhibition of Mac-1/CR3-dependent adhesion to ICAM-1 or fibrinogen by beta-glucan or anti-uPAR. The formation of uPAR complexes with Mac-1/CR3 activated for L-AFN adhesion was demonstrated by fluorescence resonance energy transfer. Conversely, Jurkat cell LFA-1 H-AFN-adhesion to ICAM-1 was not associated with uPAR/LFA-1 complexes, any requirement for GPI-anchored glycoproteins, or inhibition by beta-glucan. A single CD11b lectin site for beta-glucan and uPAR was suggested because the binding of either beta-glucan or uPAR to Mac-1/CR3 selectively masked two CD11b epitopes adjacent to the transmembrane domain. Moreover, treatment with phosphatidylinositol-specific phospholipase C that removed GPI-anchored proteins increased CD11b-specific binding of (125)I-labeled beta-glucan by 3-fold and this was reversed with soluble recombinant uPAR. Conversely, neutrophil activation for generation of Mac-1/CR3/uPAR complexes inhibited CD11b-dependent binding of (125)I-labeled beta-glucan by 75%. These data indicate that the same lectin domain within CD11b regulates both the cytotoxic and adhesion functions of Mac-1/CR3.     

Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder

Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum.     

Insulin Resistance Induces Posttranslational Hepatic Sortilin 1 Degradation in Mice

Insulin promotes hepatic apolipoprotein B100 (apoB100) degradation, whereas insulin resistance is a major cause of hepatic apoB100/triglyceride overproduction in type 2 diabetes. The cellular trafficking receptor sortilin 1 (Sort1) was recently identified to transport apoB100 to the lysosome for degradation in the liver and thus regulate plasma cholesterol and triglyceride levels. Genetic variation of SORT1 was strongly associated with cardiovascular disease risk in humans. The major goal of this study is to investigate the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Treatment of PI3K or AKT inhibitors decreased Sort1 protein, whereas expression of constitutively active AKT induced Sort1 protein in AML12 cells. Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. Administration of a PI3K inhibitor to mice decreased hepatic Sort1 protein and increased plasma cholesterol and triglyceride levels. Adenovirus-mediated overexpression of Sort1 in the liver prevented PI3K inhibitor-induced Sort1 down-regulation and decreased plasma triglyceride but had no effect on plasma cholesterol in mice. This study identified Sort1 as a novel target of insulin signaling and suggests that Sort1 may play a role in altered hepatic apoB100 metabolism in insulin-resistant conditions.     

水东湾海域浮游植物潮汐分布特征及其与环境因子的关系

2014年秋、冬两季,每个季节在大潮期和小潮期对水东湾海域浮游植物群落结构和环境因子进行了调查,共鉴定出4门57属134种。其中硅藻门42属106种,占浮游植物种类数的79.1%;甲藻门13属26种,占浮游植物种类数的19.4%;蓝藻门1属1种,占浮游植物种类数的0.8%;针胞藻纲1属1种,占浮游植物种类数的0.8%。优势种15种,主要为尖布纹藻Gyrosigma aluminatum、圆海链藻Thalassiosira rotula、中肋骨条藻Skeletonema costatum、丹麦细柱藻Leptocylindrus danicus和舟形鞍链藻Campylosira cymbelliformis等。4个航次共有种类数在18—40种,Jaccard种类相似性指数范围在0.200—0.404,多样性指数和均匀度平均值分别为2.60和0.60。秋季大、小潮期多样性指数差异较显著(P0.05),冬季细胞丰度、多样性指数和均匀度大、小潮期均无明显差异。浮游植物细胞丰度变化范围为0.95×10~4个/L—28.0×10~4个/L,平均为6.86×10~4个/L,平均丰度冬季小潮期(9.46×10~4个/L)秋季小潮期(7.56×10~4个/L)冬季大潮期(5.97×10~4个/L)秋季大潮期(4.44×10~4个/L)。主成分分析(PCA)表明:盐度和营养盐可能是影响水东湾海域生态环境的主导因子。对水东湾海域浮游植物群落结构与主要环境因子进行Spearman相关性分析,细胞丰度与盐度在秋季大、小潮期为负相关,在冬季大、小潮期呈显著正相关;与无机氮和磷酸盐在冬季大、小潮期呈极显著负相关,在秋季大、小潮期均无相关性。冬季小潮期水温与多样性指数、均匀度和细胞丰度均呈正相关;从测定结果来看浮游植物细胞丰度、多样性指数和均匀度与叶绿素a含量均无统计学意义上的相关性。     

流沙湾海草床海域浮游植物的时空分布及其影响因素

2008年2月至11月对广东省流沙湾海草床海域的浮游植物进行了周年的季节调查,结果共检出浮游植物151种:冬季57种、春季66种、夏季73种、秋季66种,其中硅藻门44属123种,占浮游植物种类数的81.4%;甲藻门11属26种,占浮游植物种类数的17.2%;绿藻门和蓝藻门各1属1种,各占浮游植物种类数的0.7%。优势种共有26种,主要为夜光藻Noctiluca scintillans、威氏角毛藻Chaetoceros weissflogii、圆海链藻Thalassiosira rotula、菱形海线藻Thalassionema nitzschioides等,都是链状群体或个体较细长或较大的种类,没有个体较短小的优势种群;各季节间共有种类数在22-43种,Jaccard种类相似性指数范围在0.211-0.448,多样性指数和均匀度平均值分别为2.12和0.35,群落结构较脆弱;细胞丰度在0.24×10⁴-5.72×10⁴ 个/L,秋季最高,夏季次之,冬季最低,属季节单峰型变化,与一般亚热带春、秋季出现丰度高峰不一致。相关性分析发现,浮游植物丰度与活性硅酸盐呈极显著的正相关,与盐度呈显著的负相关,与其他因子不存在明显的相关性;叶绿素a浓度与水温呈极显著的负相关,与浮游动物丰度呈显著的负相关。从浮游植物吸收N、P的配比分析,N为四季的营养限制因子,但从N、P的绝对值看,N和P都是全年的营养限制因子,因此其水质营养类型属于亚热带贫营养型。     

Fish Oil and Fenofibrate Prevented Phosphorylation-dependent Hepatic Sortilin 1 Degradation in Western Diet-fed Mice

Obesity and diabetes are associated with hepatic triglyceride overproduction and hypertriglyceridemia. Recent studies have found that the cellular trafficking receptor sortilin 1 (Sort1) inhibits hepatic apolipoprotein B secretion and reduces plasma lipid levels in mice, and its hepatic expression was negatively associated with plasma lipids in humans. This study investigated the regulation of hepatic Sort1 under diabetic conditions and by lipid-lowering fish oil and fenofibrate. Results showed that hepatic Sort1 protein, but not mRNA, was markedly lower in Western diet-fed mice. Knockdown of hepatic Sort1 increased plasma triglyceride in mice. Feeding mice a fish oil-enriched diet completely restored hepatic Sort1 levels in Western diet-fed mice. Fenofibrate also restored hepatic Sort1 protein levels in Western diet-fed wild type mice, but not in peroxisome proliferator-activated receptor α (PPARα) knock-out mice. PPARα ligands did not induce Sort1 in hepatocytes in vitro. Instead, fish oil and fenofibrate reduced circulating and hepatic fatty acids in mice, and n-3 polyunsaturated fatty acids prevented palmitate inhibition of Sort1 protein in HepG2 cells. LC/MS/MS analysis revealed that Sort1 phosphorylation at serine 793 was increased in obese mice and in palmitate-treated HepG2 cells. Mutations that abolished phosphorylation at Ser-793 increased Sort1 stability and prevented palmitate inhibition of Sort1 ubiquitination and degradation in HepG2 cells. In summary, therapeutic strategies that prevent posttranslational hepatic Sort1 down-regulation in obesity and diabetes may be beneficial in improving dyslipidemia.     

Effects of different influent C/N ratios on the performance of various earthworm eco-filter systems: nutrient removal and greenhouse gas emission

In this study, we sought to identify influent carbon-to-nitrogen (C/N) ratios that yield relatively high nutrient removal efficiency with relatively low greenhouse gas (GHG) emissions. The earthworm eco-filter (EE) system, which is composed of earthworms and plants (EP group), was found to be optimal for maximizing nutrient removal while reducing GHG emissions. In this EE system, the optimal influent C/N ratio for nutrient removal and GHG emission under C2N treatment conditions. Nutrient removal efficiency under this condition was 85.19 ± 6.40 % chemical oxygen demand, 71.99 ± 11.28 % total nitrogen, and 77.91 ± 8.51 % total phosphorus, while the CO₂ emission rate was 678.89 ± 201.87 mg m^?2 h^?1. Moreover, the highest nutrient removal and GHG emission rates were both achieved in late summer (August). Thus, carbon variation, season, system variation, as well as synergistic interaction between system variations and seasons, significantly affect nutrient removal efficiencies and GHG emissions.     

“海油雪”的形成机制及其生态效应

2010年深水地平线事故发生后,在被石油污染的墨西哥湾观察到大量的"海油雪"形成,海油雪的相关研究成为人们关注的焦点。海油雪是指石油、浮游植物、细菌黏液等组成的团聚物,能够将石油从海面沉降至海底,对石油的风化过程产生深远影响。因此,研究海油雪的形成机制和生态效应,对于深入认识海油雪在石油-海洋系统中的作用具有重要意义。本文从物理凝聚、微生物和石油分散剂三个方面对海油雪的形成机制展开探讨,分析了海油雪对石油风化、底栖生物毒性和其他污染物迁移转化的影响,并结合现有研究进行了展望。