Kinin-mediated inflammation in neurodegenerative disorders

The mediatory role of kinins in both acute and chronic inflammation within nervous tissues has been widely described. Bradykinin, the major representative of these bioactive peptides, is one of a few mediators of inflammation that directly stimulates afferent nerves due to the broad expression of specific kinin receptors in cell types in these tissues. Moreover, kinins may be delivered to a site of injury not only after their production at the endothelium surface but also following their local production through the enzymatic degradation of kininogens at the surface of nerve cells. A strong correlation between inflammatory processes and neurodegeneration has been established. The activation of nerve cells, particularly microglia, in response to injury, trauma or infection initiates a number of reactions in the neuronal neighborhood that can lead to cell death after the prolonged action of inflammatory substances. In recent years, there has been a growing interest in the effects of kinins on neuronal destruction. In these studies, the overexpression of proteins involved in kinin generation or of kinin receptors has been observed in several neurologic disorders including neurodegenerative diseases such Alzheimer's disease and multiple sclerosis as well as disorders associated with a deficiency in cell communication such as epilepsy. This review is focused on recent findings that provide reliable evidence of the mediatory role of kinins in the inflammatory responses associated with different neurological disorders. A deeper understanding of the role of kinins in neurodegenerative diseases is likely to promote the future development of new therapeutic strategies for the control of these disorders. An example of this could be the prospective use of kinin receptor antagonists.     

家蚕溶茧酶基因的真核表达及其产物的生物活性检测

为了研究家蚕 Bombyx mori 溶茧酶基因 （cocoonae）真核表达及其产物的生物活性,将溶茧酶基因（GenBank 登录号 EF428980）克隆至杆状病毒转移载体 pFastBac^TM 1 中获得 pFast-cocoonase,将其转化 DH10Bac 感受态细胞后,PCR 方法检测证实所分离的重组病毒 DNA 中含有目的片段溶茧酶基因。用脂质体法 转染家蚕 BmN 细胞,获得重组病毒。SDS-PAGE 分析显示,感染重组杆状病毒 Bac-cocoonase 的细胞表达产物在约为 27.6 kD 处出现特异性条带,这与预测的蛋白大小相符。用该表达产物与茧丝反应后,电镜下观察茧丝的形态,结果表明表达产物对茧丝的丝胶层有一定的水解作用。     

蛋白质组学进展

在蛋白质水平上定量、动态、整体性研究生物体的蛋白质组学 ,将在后基因组时代大大增进我们对基因功能的理解。简要介绍了蛋白质组学的概念、研究手段 ,及最新进展     

Cyclase-associated protein is essential for the functioning of the endo-lysosomal system and provides a link to the actin cytoskeleton

Data from mutant analysis in yeast and Dictyostelium indicate a role for the cyclase-associated protein (CAP) in endocytosis and vesicle transport. We have used genetic and biochemical approaches to identify novel interacting partners of Dictyostelium CAP to help explain its molecular interactions in these processes. Cyclase-associated protein associates and interacts with subunits of the highly conserved vacuolar H(+)-ATPase (V-ATPase) and co-localizes to some extent with the V-ATPase. Furthermore, CAP is essential for maintaining the structural organization, integrity and functioning of the endo-lysosomal system, as distribution and morphology of V-ATPase- and Nramp1-decorated membranes were disturbed in a CAP mutant (CAP bsr) accompanied by an increased endosomal pH. Moreover, concanamycin A (CMA), a specific inhibitor of the V-ATPase, had a more severe effect on CAP bsr than on wild-type cells, and the mutant did not show adaptation to the drug. Also, the distribution of green fluorescent protein-CAP was affected upon CMA treatment in the wildtype and recovered after adaptation. Distribution of the V-ATPase in CAP bsr was drastically altered upon hypo-osmotic shock, and growth was slower and reached lower saturation densities in the mutant under hyper-osmotic conditions. Taken together, our data unravel a link of CAP with the actin cytoskeleton and endocytosis and suggest that CAP is an essential component of the endo-lysosomal system in Dictyostelium.     

Neuropeptides in the gastrointestinal canal of Necturus maculosus

Summary The presence and distribution of regulatory peptides in nerves and endocrine cells of the stomach, intestine and rectum of a urodele amphibian, the mudpuppy, Necturus maculosus, was studied immunohistochemically in sections or whole-mount preparations of the gut wall. The effect of the occurring peptides on gut motility was studied in isolated strip preparations of circular and longitudinal smooth muscle from different parts of the gut.Bombesin-, neurotensin-, substance P- and VIP-like immunoreactivity was present in abundant nerve fibres in the myenteric plexus of both stomach, intestine and rectum. Single fibres or bundles were present in the circular muscle layer and in a well-developed deep muscular plexus in the intestine and rectum. Immunoreactive nerve cells were found in the myenteric plexus of the stomach, intestine (neurotensin only) and rectum. Gastrin/CCK-like immunoreactivity was observed only in a few fibres in stomach and rectum.Endocrine cells containing bombesin-, met-enkephalin-, gastrin/CCK-, neurotensin-, somatostatin- or substance P- like immunoreactivity were present in the mucosa.The effect of bombesin was an inhibition of the rhythmic activity in circular muscle preparations and in longitudinal muscle from the rectum, while longitudinal muscle from the stomach usually responded with a weak increase in tonus. Neurotensin, like bombesin, was inhibitory on the spontaneous rhythmic activity of circular muscle throughout the gut, while the effect on longitudinal muscle was an increase in tonus. Met-enkephalin and substance P increased the tonus of all types of preparations, and often, in addition, initiated a rhythmic activity superimposed on this maintained tonus. VIP had a general inhibitory effect on the preparations, decreasing tonus and/or abolishing rhythmic activity.It is concluded that bombesin-, neurotensin-, substance P- and VIP-like peptides are present in nerves throughout the urodele gut and may have physiological functions in regulating the motility of the gut. The gastrin/CCK-like peptide present in nerves of the stomach and rectum may affect the function of these parts of the gut. The regulatory peptides present in endocrine cells may, perhaps with the exception of the somatostatin-like peptide, affect the motility humorally.     

Physiologic and innate immunity responses to bacterial lipopolysaccharide administration in beef heifers supplemented with OmniGen-AF

Nutritional alternatives to strengthen animal immunocompetence are critical for welfare and productivity in livestock systems, such as beef cattle operations. This experiment evaluated physiological and innate immunity effects of supplementing an immunomodulatory feed ingredient (Omnigen-AF; Phibro Animal Health, Teaneck, NJ, USA) to beef heifers administered bacterial lipopolysaccharide (LPS). In total, 8 non-pregnant, non-lactating nulliparous Angus×Hereford heifers (676±4 days of age) were ranked by BW (473±8 kg), and assigned to crossover design containing two periods of 34 days each. Heifers were housed in individual pens and had ad libitum access to meadow foxtail (Alopecurus pratensis L.) hay, water and a granulated commercial vitamin+mineral mix. Within each period, heifers received (as-fed basis) 227 g/day of dried distillers grains including (OMN) or not (CON) 56 g of Omnigen-AF for 34 days. On day 28 of each period (0800 h), heifers received an intravenous bolus dose (0.5 μg/kg of BW, diluted in 5 ml of 0.9% sterile saline) of bacterial LPS (Escherichia coli 0111:B4). Hay DM intake was recorded daily from day 0 to 34. Blood was collected at −1, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 24, 48, 72, 96, 120 and 144 h relative to LPS administration. Heifer intravaginal temperature was recorded every 10 min from −0.5 to 10 h relative to LPS administration. No treatment effect was detected (P=0.35) for hay DM intake during the experiment. No treatment effects were detected (P⩾0.64) for intravaginal temperature and plasma concentrations of tumor necrosis-α, cortisol and haptoglobin, which increased (time effect, P<0.01) for OMN and CON heifers and peaked at 4.5, 2, 4 and 48 h, respectively, after LPS administration. No treatment effects were detected (P⩾0.35) for whole blood mRNA expression of chemokine ligand 5, tumor necrosis-α, cyclooxygenase 2 and interleukin 8, which also increased (time effect, P<0.01) for OMN and CON heifers and peaked at 0.5, 1.5, 2 and 2.5 h, respectively, after LPS administration. Whole blood mRNA expression of interleukin 8 receptor and L-selectin were also similar (P⩾0.61) between OMN and CON heifers, and decreased (time effect, P<0.01) for both treatments reaching nadir levels at 1 and 2.5 h, respectively, after LPS administration. Collectively, OMN supplementation did not modulate the physiological and innate immunity responses of beef heifers to bacterial LPS administration.     

Drosophila melanogaster as a model system to study long-chain fatty acid amide metabolism

Long-chain fatty acid amides are cell-signaling lipids identified in mammals and, recently, in invertebrates, as well. Many details regarding fatty acid amide metabolism remain unclear. Herein, we demonstrate that Drosophila melanogaster is an excellent model system for the study long-chain fatty acid amide metabolism as we have quantified the endogenous levels of N-acylglycines, N-acyldopamines, N-acylethanolamines, and primary fatty acid amides by LC/QTOF-MS. Growth of D. melanogaster on media supplemented with [1-¹³C]-palmitate lead to a family of ¹³C-palmitate-labeled fatty acid amides in the fly heads. The [1-¹³C]-palmitate feeding studies provide insight into the biosynthesis of the fatty acid amides.     

南海北部生态系统食物网结构、能量流动及系统特征

根据20072008年在南海北部(107°00'120°00'E、17°00'23°30'N)进行的海洋生态综合调查数据,应用Ecopath with Ecosim软件构建了南海北部生态系统的生态通道模型,并通过模型分析了南海北部海洋生态系统的食物网结构、能量流动和系统的总体特征,并简要总结过度捕捞生态系统的基本特征。结果表明,南海北部海洋生态系统以捕食食物链为主要能流通道,初级生产者是系统能量的主要来源。各功能群的营养级范围为13.99,哺乳动物占据了最高的营养层,平均渔获物营养级为2.93。利用生态网络分析,系统的能量流动主要有6级,来自初级生产者的能流效率为12.6%,来自碎屑的转换效率为10.4%,平均能量转换效率为11.5%。系统连接指数(Connectance Index,CI)和系统杂食指数(System Omnivory Index,SOI)分别为0.290和0.239;Finn’s循环指数(Finn’scy cling index,FCI)和系统平均路径长度(Finn’s mean path length,MPL)分别为4.380和2.476;总初级生产力/总呼吸为2.596,综合研究表明当前南海北部海洋生态系统处于不成熟阶段。