Understanding aerobic/anaerobic metabolism in Caldibacillus debilis through a comparison with model organisms

Caldibacillus debilis GB1 is a facultative anaerobe isolated from a thermophilic aero-tolerant cellulolytic enrichment culture. There is a lack of representative proteomes of facultative anaerobic thermophilic Bacillaceae, exploring aerobic/anaerobic expression. The C. debilis GB1 genome was sequenced and annotated, and the proteome characterized under aerobic and anaerobic conditions while grown on cellobiose. The draft sequence of C. debilis GB1 contains a 3,340,752 bp chromosome and a 5,386 bp plasmid distributed over 49 contigs. Two-dimensional liquid chromatography mass spectrometry/mass spectrometry was used with Isobaric Tags for Relative and Absolute Quantification (iTRAQ) to compare protein expression profiles, focusing on energy production and conversion pathways. Under aerobic conditions, proteins in glycolysis and pyruvate fermentation pathways were down-regulated. Simultaneously, proteins within the tricarboxylic acid cycle, pyruvate dehydrogenase, the electron transport chain, and oxygen scavenging pathways showed increased amounts. Under anaerobic conditions, protein levels in fermentation pathways were consistent with the generated end-products: formate, acetate, ethanol, lactate, and CO₂. Under aerobic conditions CO₂ and acetate production was consistent with incomplete respiration. Through a direct comparison with gene expression profiles from Escherichia coli, we show that global regulation of core metabolism pathways is similar in thermophilic and mesophilic facultative anaerobes of the Phylum Proteobacteria and Firmicutes.     

Investigation of the effect of Interleukin-1 receptor antagonist (IL-1ra) on markers of inflammation in non-ST elevation acute coronary syndromes (The MRC-ILA-HEART Study)

Background

Point of care testing (PoCT) may be a useful adjunct in the management of chronic conditions in general practice (GP). The provision of pathology test results at the time of the consultation could lead to enhanced clinical management, better health outcomes, greater convenience and satisfaction for patients and general practitioners (GPs), and savings in costs and time. It could also result in inappropriate testing, increased consultations and poor health outcomes resulting from inaccurate results. Currently there are very few randomised controlled trials (RCTs) in GP that have investigated these aspects of PoCT.

Design/Methods

The Point of Care Testing in General Practice Trial (PoCT Trial) was an Australian Government funded multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost effectiveness and satisfaction of PoCT in a GP setting. The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes, hyperlipidaemia and patients on anticoagulant therapy. The primary outcome measure was the proportion of patients within target range, a measure of therapeutic control. In addition, the PoCT Trial investigated the safety of PoCT, impact of PoCT on patient compliance to medication, stakeholder satisfaction, cost effectiveness of PoCT versus laboratory testing, and influence of geographic location.

Discussion

The paper provides an overview of the Trial Design, the rationale for the research methodology chosen and how the Trial was implemented in a GP environment. The evaluation protocol and data collection processes took into account the large number of patients, the broad range of practice types distributed over a large geographic area, and the inclusion of pathology test results from multiple pathology laboratories. The evaluation protocol developed reflects the complexity of the Trial setting, the Trial Design and the approach taken within the funding provided. The PoCT Trial is regarded as a pragmatic RCT, evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that, in these circumstances, internal and external validity was maintained.

Trial Registration

12612605000272695     

The effects of infliximab therapy on the serum proteome of rheumatoid arthritis patients

Introduction  

Although the clinical effects of infliximab therapy in rheumatoid arthritis have been documented extensively, the biological effects of this intervention continue to be defined. We sought to examine the impact of infliximab therapy on the serum proteome of rheumatoid arthritis patients by means of a mass spectrometry-based approach.     

菲律宾Boracay岛和Mambukal岛三种共栖狐蝠对人类活动的行为和激素反应

栖息地丧失和捕猎导致许多大型狐蝠濒危。尽管在东半球热带地区已经禁止捕猎和采伐,狐蝠的数量仍然在下降。既能维护当地居民利益又能保护狐蝠的折衷对策是生态旅游。然而,人类活动对狐蝠的影响还是未知的。菲律宾Boracay和Mambukal都是旅游区,前者游人少而稳定,后者游人密集且变异较大。我们用非损伤取样法研究了这两个旅游区三种狐蝠的生理紧张情况。在Mambukal,当狐蝠外出采食时,采集狐蝠的粪样,实验室分析粪样肾上腺皮质激素代谢物(GCM)浓度。我们观察记录了紧张反应等一些行为,同时记录了环境因素和人类活动情况。结果表明狐蝠已经习惯了游人的活动,表现在:(1)我们发现两个旅游区游人数量和活动强度差异显著,但是两地狐蝠的行为没有明显的差异;并且在有干扰和无干扰的日期之间,狐蝠的行为也无显著差异;两个旅游区的狐蝠行为表达一致;(2)各种行为与测定的粪样GCM浓度都不相关;(3)尽管在不同研究地点人类活动变异很大,我们发现人类活动并未影响粪样GCM浓度;不过,栖息在狐蝠群中心位置个体的粪样GCM浓度低于在群外围个体的GCM浓度;(4)一些环境因素(如干扰以及与栖息群的距离)影响狐蝠一些行为(如不安、身体护理和哈欠)的表达。如果干扰没有造成狐蝠紧张反应,那么生态旅游将不失为一种保护濒危狐蝠栖息地的理想方案。不过,我们还应认识到,人类干扰对狐蝠行为的影响可能比本研究观察到的更加复杂。因此,对于保护濒危狐蝠,时刻保持干扰最小是最好的选择。     

Laboratory evaluation of certain natural compounds against the melon ladybird beetle,Epilachna chrysomelina F. attacking cucurbit plants

Neem Azal-T/S, Neudosan and Spruzit flüssig at different concentrations were evaluated against the second and fourth instar larvae of E. chrysomelina under laboratory conditions. In case of acute effects, the highest mortality was recorded when larvae were offered squash leaves treated with the highest concentration (2%) of Neem Azal-T/S, and the lowest mortality was, however recorded after treating them with the lowest concentration (0.25%). On the other hand, the second instar larvae were more susceptible to any compound at any concentration than the fourth instar one. One per cent Neudosan formulation showed the highest toxicity to both the 2nd and 4th instar larvae. As the concentration of this compound decreased the mortality percentage of treated larvae decreased to reach the minimum at the lowest concentration (0.25%). The same trend could be applied for Spruzit flüssig compound. When Neem Azal-T/S was compared with Neudosan, the later at any concentration was more toxic than the former. Generally, Neudosan and Spruzit flüssig seemed to be active against E. chrysomelina during the first three days after treatment, then, deterioration occurred among this compound. In case of latent effects, the duration of the treated fourth instar larvae of E. chrysomelina with any tested compound, was prolonged. An increase in the concentration caused prolongation of this period to reach the longest at the highest concentration. This prolongation, was more pronounced after Neem Azal-T/S treatment followed by Neudosan and Spruzit flüssig. The same trend could be applied for the duration of the pupal stage as being affected by the different concentrations of the tested compounds which were applied to the fourth instar larvae. However, adults of E. Chrysomelina treated as fourth instar larvae with high concentrations of Neem Azal-T/S showed some adult malformations. The sex ratios of adults produced from fourth instar larvae treated with different concentrations of the tested natural compounds were about 1?:?1, except for two cases; 1% Neudosan where the number of females were double the number of males and 0.5% Spruzit flüssig where the number of males were double the number of females. An increase in the concentration of any tested compound caused an obvious decrease in the percentage of emerged adults. The least emergence percentage was recorded in the case of Spruzit flüssig, followed by Neudosan and Neem Azal-T/S. Treating the fourth instar larvae with the different concentrations of the tested natural compounds significantly shortened the longevity of produced adults and decreased the fecundity.     

Can the presence of curved forms of the diatom Aulacoseira ambigua in the Nile (Egypt) and Vaal (South Africa) Rivers be ascribed to similar water quality conditions?

Spiral colonies of the diatom Aulacoseira ambigua were assigned the rank of forma (Aulacoseira ambigua f. japonica). This spiral-shaped, colonial, centric diatom has limited geographical distribution and is currently reported to occur in only a few countries in the world. In Africa this species was described for the first time from the Vaal River, South Africa, but recent research on the Nile River also revealed its presence in Egypt. Physical and chemical data on water quality in these two river systems were compared to determine whether the presence of this uncommon ‘phenoecodeme’ could be ascribed to similar environmental conditions. Results indicate that the rivers are dissimilar with regard to many variables, but both rivers provide turbid, warm and eutrophic waters with medium to high mineral content and it was concluded that these factors favour and sustain the growth of this curved form.     

Characterization of IQGAP1-containing complexes in NK-like cells: evidence for Rac 2 and RACK1 association during homotypic adhesion

IQGAP1 is a scaffolding protein that binds to a diverse array of signaling and structural molecules that are often associated with cell polarization and adhesion. Through interaction with its target proteins, IQGAP1 participates in multiple cellular functions, including Ca2+-calmodulin signaling, definition of cytoskeletal architecture, regulation of Cdc42 and Rac1 dependent cytoskeletal changes, and control of E-cadherin mediated intercellular adhesion. These analysis have been largely restricted to cells of epithelial and fibroblast origin. The present studies were initiated to examine the role of IQGAP1 in cellular interactions involving the lymphoid cells. A mass spectrometric based analysis of IQGAP1 containing complexes isolated from the human NK-like cell line, YTS, identified several known and new potential IQGAP1 interaction partners including receptor of activated C kinase 1 (RACK1) and the small GTPase, Rac2. Immunofluorescence analysis of YTS cells indicated that a minor component of IQGAP1 was localized at the cell membrane with the remainder diffusely distributed through out the cytoplasm. However, at sites of cellular contact, there was a marked accumulation of IQGAP1. Staining for RACK1 and Rac2 revealed that both of these proteins accumulated these contact sites. Antibody-based studies suggested that a subset of RACK1 was associated in an IQGAP1-containing complex, which prevented recognition of RACK1 by monoclonal antibody. These results suggest that RACK1, Rac2, and IQGAP1 are components of complexes involved in NK cell homotypic adhesion.