The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones

The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 microg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of alpha-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.     

Rerouting carbon flux to enhance photosynthetic productivity

The bioindustrial production of fuels, chemicals, and therapeutics typically relies upon carbohydrate inputs derived from agricultural plants, resulting in the entanglement of food and chemical commodity markets. We demonstrate the efficient production of sucrose from a cyanobacterial species, Synechococcus elongatus, heterologously expressing a symporter of protons and sucrose (cscB). cscB-expressing cyanobacteria export sucrose irreversibly to concentrations of >10 mM without culture toxicity. Moreover, sucrose-exporting cyanobacteria exhibit increased biomass production rates relative to wild-type strains, accompanied by enhanced photosystem II activity, carbon fixation, and chlorophyll content. The genetic modification of sucrose biosynthesis pathways to minimize competing glucose- or sucrose-consuming reactions can further improve sucrose production, allowing the export of sucrose at rates of up to 36.1 mg liter(-1) h illumination(-1). This rate of production exceeds that of previous reports of targeted, photobiological production from microbes. Engineered S. elongatus produces sucrose in sufficient quantities (up to ～80% of total biomass) such that it may be a viable alternative to sugar synthesis from terrestrial plants, including sugarcane.     

The role of circulating serotonin in the development of chronic obstructive pulmonary disease

Background

Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age.

Methods

The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA).

Results

The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = −0.149, p = 0.108).

Conclusion

Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.     

Determinants of Compliance Behaviours among Patients Undergoing Hemodialysis in Malaysia

Background

Patients with end stage renal disease often fail to follow prescribed dietary and fluid regimen, leading to undesirable outcomes. This study aimed to examine and identify factors influencing dietary, fluid, medication and dialysis compliance behaviours in patients undergoing hemodialysis.

Methods

This was a cross-sectional study which employed purposive sampling design. A total of 188 respondents were recruited from 14 dialysis centres in Malaysia between 2008–2011. Self-reported compliance behaviours and biochemical measurements were used as evaluation tools.

Results

Compliance rates of dietary, fluid, medication and dialysis were 27.7%, 24.5%, 66.5% and 91.0%, respectively. Younger, male, working patients and those with longer duration on hemodialysis were found more likely to be non-compliant. Lacks of adequate knowledge, inadequate self-efficacy skills, forgetfulness and financial constraints were the major perceived barriers towards better compliance to fluid, dietary, medication and dialysis, respectively.

Conclusions

Healthcare professionals should recognise the factors hindering compliance from the patients'' perspective while assisting them with appropriate skills in making necessary changes possible.     

Leptospira spp. strain identification by MALDI TOF MS is an equivalent tool to 16S rRNA gene sequencing and multi locus sequence typing (MLST)

ABSTRACT: BACKGROUND: In this study mass spectrometry was used for evaluating extracted leptospiral protein samples and results were compared with molecular typing methods. For this, an extraction protocol for Leptospira spp. was independently established in two separate laboratories. Reference spectra were created with 28 leptospiral strains, including pathogenic, non-pathogenic and intermediate strains. This set of spectra was then evaluated on the basis of measurements with well-defined, cultured leptospiral strains and with 16 field isolates of veterinary or human origin. To verify discriminating peaks for the applied pathogenic strains, statistical analysis of the protein spectra was performed using the software tool ClinProTools. In addition, a dendrogram of the reference spectra was compared with phylogenetic trees of the 16S rRNA gene sequences and multi locus sequence typing (MLST) analysis. RESULTS: Defined and reproducible protein spectra using MALDI-TOF MS were obtained for all leptospiral strains. Evaluation of the newly-built reference spectra database allowed reproducible identification at the species level for the defined leptospiral strains and the field isolates. Statistical analysis of three pathogenic genomospecies revealed peak differences at the species level and for certain serovars analyzed in this study. Specific peak patterns were reproducibly detected for the serovars Tarassovi, Saxkoebing, Pomona, Copenhageni, Australis, Icterohaemorrhagiae and Grippotyphosa. Analysis of the dendrograms of the MLST data, the 16S rRNA sequencing, and the MALDI-TOF MS reference spectra showed comparable clustering. CONCLUSIONS: MALDI-TOF MS analysis is a fast and reliable method for species identification, although Leptospira organisms need to be produced in a time-consuming culture process. All leptospiral strains were identified, at least at the species level, using our described extraction protocol. Statistical analysis of the three genomospecies L. borgpetersenii, L. interrogans and L. kirschneri revealed distinctive, reproducible differentiating peaks for seven leptospiral strains which represent seven serovars. Results obtained by MALDI-TOF MS were confirmed by MLST and 16S rRNA gene sequencing.     

Enhanced growth and nodulation of pigeon pea by co-inoculation of Bacillus strains with Rhizobium spp

Endophytic bacteria which are known to reside in plant tissues have often been shown to promote plant growth. Present study deals with the isolation of putative endophytes from the surface sterilized root nodules of pigeon pea (Cajanus cajan) designated as non-rhizobial (NR) isolates. Three of these non-rhizobial isolates called NR2, NR4 and NR6 showed plant growth promotion with respect to increase in plant fresh weight, chlorophyll content, nodule number and nodule fresh weight when co-inoculated with the rhizobial bioinoculant strain IC3123. The three isolates were neither able to nodulate C. cajan nor did they show significant plant growth promotion when inoculated alone without Rhizobium spp. IC3123. All the three isolates were gram positive rods with NR2 and NR4 showing endospore formation and formed one single cluster in Amplified Ribosomal DNA Restriction Analysis (ARDRA). Partial sequences of 16S rRNA genes of NR4 and NR6 showed 97% similarity to Bacillus megaterium. The Bacillus strains NR4 and NR6 were able to produce siderophores which the rhizobial bioinoculant IC3123 was able to cross-utilize. Under iron starved conditions IC3123 showed enhanced growth in the presence of the Bacillus isolates indicating that siderophore mediated interactions may be underlying mechanism of beneficial effect of the NR isolates on nodulation by IC3123.     

Analysis and Design of an Agent Searching Algorithm for e-Marketplaces

Recently, agent techniques in electronic marketplaces (e-marketplaces) bring B-to-B trading into a new era. However, not much analysis on the behavior of agents has been reported. In this paper, based on the ant algorithm in network routing, we introduce a jumping (searching) model for agents in an e-marketplace network. However, we should be aware that if there are too many agents in the e-marketplace network, they will use up all communication bandwidth and computing resource. It is inevitable to investigate the behavior of agents, such as agent population. Based on the existing results in the ant algorithm in network routing, we present the behavior of agents in an e-marketplace network. Hence, we can control the agent population by setting the appropriate agent generation rate.     

A role for N-WASP in invasin-promoted internalisation.

Phagocytosis of Yersinia pseudotuberculosis occurs through interaction of the bacterial protein invasin with beta1-integrins. Here we report that N-WASP plays a role in internalisation of an invasin-expressing, avirulent strain of Y. pseudotuberculosis. Ectopic expression of N-WASP mutants, which affect recruitment of the Arp2/3 complex to the phagosome, reduces uptake of Yersinia. In addition, expression of the Cdc42/Rac-binding (CRIB) region of N-WASP has an inhibitory effect on uptake. Using GFP-tagged Rho GTPase mutants, we provide evidence that Rac1, but not Cdc42, is important for internalisation. Furthermore, activated Rac1 rescues Toxin B, CRIB and Src family kinase inhibitor PP2-mediated impairment of uptake. Our observations indicate that invasin-mediated phagocytosis occurs via a Src and WASP family-dependent mechanism(s), involving the Arp2/3 complex and Rac, but does not require Cdc42.     

麻栗坡兜兰及其近缘植物的分类研究

对麻栗坡兜兰Paphiopedilum malipoense及其近亲种作了对比研究。它们被作为一个种之下的4个变种：麻栗坡兜兰（原变种）Paph.malipoense var.malipoense,浅斑兜兰（变种）var.jackii,钩唇兜兰（变种）var.hiepii;窄瓣兜兰（变种）var.angustatum（变种,新等级）。其鉴别特征已列入表中,还附有一幅图版。