Screening for a Potent Antibacterial Peptide to Treat Mupirocin-Resistant MRSA Skin Infections

Mupirocin is the first-line topical antibacterial drug for treating skin infections caused primarily by meticillin-resistant Staphylococcus aureus (MRSA). Its widespread use since its introduction more than 30 years ago has resulted in the global emergence of mupirocin-resistant strains of MRSA. Antimicrobial peptides (AMPs) are a promising class of antibacterial compounds that can potentially be developed to replace mupirocin due to their rapid membrane-targeting bactericidal mode of action and predicted low propensity for resistance development. Herein, we conducted and compared the antibacterial activities of 61 AMPs between 3 and 11 residues in length reported in the literature over the past decade against mupirocin-resistant MRSA. The most potent AMP, 11-residue peptide 50, was selected and tested against a panel of clinical isolates followed by a time-kill and a human dermal keratinocyte cytotoxicity assay. Lastly, peptide 50 was formulated into a topical spray which showed strong in vitro bactericidal effects against mupirocin-resistant MRSA. Our results strongly suggest that peptide 50 has the potential to be further developed into a new class of topical antibacterial agent for treating drug-resistant MRSA skin infections.     

Mapping ephemeral wetlands: manual digitisation and logistic regression modelling in Nelson Mandela Bay Municipality,South Africa

Until recently, little research has been conducted on the distribution and structure of ephemeral systems in semi-arid areas. This information is critical for appropriate wetland management and conservation. The Nelson Mandela Bay Municipality is a semi-arid area along the south-eastern coastline of the Eastern Cape Province of South Africa. The Municipality encapsulates a wide range of geological and geomorphological features as well as vegetation types within an area of some 1950 km², providing an ideal area for such research. The distribution and abundance of wetlands were defined, and a logistic regression (LR) model was used to establish whether this modelling technique is viable in semi-arid areas with highly variable rainfall patterns. Wetlands were delineated manually using geographical information systems, high-resolution aerial photographs and environmental data. More than 1700 wetland polygons were identified, with 80% of the systems being categorised as depressions, seeps and wetland flats. Unchannelled (8%) and channelled (7%) valley bottom wetlands and floodplain wetlands (5%) were also identified. The wetland database was then used to create a wetland occurrence probability model. There were 19 environmental variables used to develop the LR model, with eight variables used in the final model output. The predictive capacity of the model was good, with an area under curve value of 0.68 and an overall accuracy of 66%. This indicates that probabilistic wetland models are useful in highly variable environments with high numbers of small (<1 ha) wetlands. Such predictive models provide a tool to assist in improving the accuracy of land cover datasets in semi-arid areas, and can be used to inform management decisions on flood risk areas and key conservation zones. In addition, abiotic variables that are significant in the model output provide an indication of the factors influencing wetland functioning in the region.     

Eclalbasaponin II Ameliorates the Cognitive Impairment Induced by Cholinergic Blockade in Mice

Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 μM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3β signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction.     

CDK5-Mediated Phosphorylation-Dependent Ubiquitination and Degradation of E3 Ubiquitin Ligases GP78 Accelerates Neuronal Death in Parkinson’s Disease

The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson’s disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD. Thus, we addressed the relationship between CDK5 and GP78 in MPTP-based PD models. We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78. Importantly, overexpression of GP78 or interference of GP78 Ser516 phosphorylation protected neurons against MPP⁺-induced cell death. Thus, our research reveals that the CDK5-GP78 pathway is involved in the pathogenesis of PD and could be a novel candidate drug target for the treatment of PD.     

TAT-mediated delivery of human glutamate dehydrogenase into PC12 cells

Human glutamate dehydrogenase (GDH) gene was fused with a gene fragment encoding the nine amino acid (RKKRRQRRR) protein transduction domain of human immunodeficiency virus TAT protein in bacterial expression vector to produce genetic in-frame TAT-GDH fusion protein. The TAT-GDH protein can enter PC12 cells efficiently when added exogenously in culture media as determined by Western blot analysis and enzyme activities. Once inside the cells, the transduced denatured TAT-GDH protein showed a full activity of GDH indicating that the TAT-GDH fusion protein was correctly refolded after delivery into cells and the activities of GDH in the TAT-GDH fusion protein was not affected by the addition of the TAT sequence. TAT-GDH fusion protein and TAT itself showed no cytotoxicity in PC12 cells. Although the exact mechanism of transduction across a membrane remains unclear, the transduction activity of TAT-GDH into PC12 cells may suggest new possibilities for direct delivery of GDH into the patients with the GDH-deficient disorders.     

乳杆菌DM9811发酵液的挥发性脂肪酸组分分析

目的：通过分析乳杆菌DM9811发酵液的挥发性脂肪酸,探讨乳杆菌对机体作用的分子机制。方法：采用高压气相色谱方法。结果：乳杆菌DM9811发酵液中存在乙酸、9-十六碳烯酸,十六烷酸,9,12-十八碳二烯酸,9-十八碳烯酸,其中乙酸浓度为1.6mg/ml。结论：乳杆菌DM9811发酵液中除含有乙酸外,还含有十六～十八碳饱和与不饱和脂肪酸。     

姜黄素对沙土鼠脑缺血／再灌注损伤的海马CAl区细胞凋亡和即早基因c-fos、c-jun、NF-κB表达变化的关系

目的：探讨姜黄素对沙土鼠海马CAl区缺血／再灌注损伤的影响及与即早基因c-fos、c-jun、NF-κB在海马CAl区表达的关系及意义。方法：采用沙土鼠双侧颈总动脉阻断缺血佴灌注损伤模型。动物随机分为假手术组（SH）、脑缺血佴灌注组（VR）、姜黄素组（CU）、溶剂对照组（SC）;每组据再灌注时间点的不同又分多个亚组,每组6只动物。在预定时间点行开阔法行为学检查、TUNEL法海马CAl区凋亡细胞检测,免疫组织化学ABC法测定c-fos、c-jun、NF-κB蛋白在海马CAl区的动态变化。结果：姜黄素可显著减少沙土鼠探索活动及海马CAl区凋亡锥体细胞数量（P〈0.01）、诱导Fos蛋白及抑制Jun和NF-κB蛋白的表达（P〈0.01）。结论：姜黄素具有脑保护作用,调控即早基因c-fos、c-jun和NF-κB的袁达可能是作用机制之一。     

Microbial decolorization of spentwash: a review

Spentwash is one of the most complex and cumbersome wastewater with very high BOD, COD and other organic and inorganic toxic constituents. It is dark brown colored and difficult to treat by normal biological process such as activated sludge or anaerobic lagooning. The color is due to the presence of melanoidins, caramels and other polymers. These compounds have anti oxidant properties which render them toxic to microorganisms. Spentwash disposal into the environment is hazardous and has a considerable pollution potential. It affects the aesthetic merit. Its decolorization by physical or chemical methods have been investigated and were found unsuitable. In the recent past, increasing attention has been directed towards utilizing microbial activity for decolorization of spentwash. This review reveals various groups of microorganisms which have potential in spentwash decolorization. The role of enzymes in decolorization and the microbial degradation of individual compounds imparting color to spentwash are also discussed.     

小鼠心肌肥厚发展过程中心电图动态变化

目的：探讨小鼠心肌肥厚发展过程中心电图的动态变化。方法：复制小鼠压力超负荷性心肌肥厚模型,连续动态监测小鼠从心肌肥厚早期至心力衰竭发展过程中的不同阶段体表心电图改变。结果：①对照组和模型组术后2周内小鼠未见自发性心律失常,而模型组术后5周、9周和13周小鼠出现自发性心律失常,主要表现为频发的室性早搏以及阵发性室性心动过速,心律失常发生率分别为15％、28％和63％。②与同期对照相比,术后2周、5周、9周和13周组动物伽间期以及帆间期明显延长,分别延长20．4％、32．7％、49．7％、61．0％和27．1％、32．1％、43．9％、59．1％（P〈0．01）。③心肌肥厚小鼠心电图的另一个特征为J波变化。所有对照组动物心电图均为正向J波,而模型组动物从2周开始J波正向值下降,5周逐渐变平,到13周时完全翻转。④与同期对照相比,模型组的PR间期没有改变,但术后2周RR问期轻微缩短。结论：心肌肥厚小鼠自发性心律失常发生率逐渐增加,QT间期进行性延长,J波幅值逐渐降低,表明随着疾病的进展心室复极化异常逐渐加重。