Genome Sequence and Comparative Genomics Analysis of a Vibrio cholerae O1 Strain Isolated from a Cholera Patient in Malaysia

The genome sequence analysis of a clinical Vibrio cholerae VC35 strain from an outbreak case in Malaysia indicates multiple genes involved in host adaptation and a novel Na⁺-driven multidrug efflux pump-coding gene in the genome of Vibrio cholerae with the highest similarity to VMA_001754 of Vibrio mimicus VMA223.     

Experimental study on aggregation of model dipeptide molecules. V. Stereoselective association of leucine dipeptides

Infrared spectroscopy and ¹H nmr have been used to elucidate the association modes of leucine dipeptides in carbon tetrachloride solution. Two stereoselective types of aggregates have been evidenced. Homochiral molecules are associated in oligomeric aggregates and accommodate a β-parallel-like structure which was characterized by x-ray diffraction. Heterochiral molecules are paired in centrosymmetrical dimers; the latter aggregation mode restricted to the dimer stage predominates in racemic solutions. A theoretical model proposed to account for this aggregation process is consistent with the experimental nmr data. Both homo- and heterochiral association constants are estimated from vapor pressure and nmr experiments.     

Effector cell activity in antibody mediated cell dependent immune lysis. II. Evidence for different populations of effector cells for different targets.

Using the adhering property of certain types of cells to glass or plastic in human peripheral blood lymphocyte preparations, two populations of effector cells can be identified in the ABCIL system, each with a selective killing directed toward a different antibody coated target. The adherent cells which are radioresistant functionally, with the morphology of macrophages, exhibit strong cytotoxicity against the antibody-coated erythroid target while lacking any killing effect toward the antibodycoated target lymphocytes. The nonadherent cells which are radiosensitive and with the morphology of small lymphocytes, selectively kill the antibody-coated lymphocyte target without possessing any cytotoxicity against the antibody-coated target erythrocytes.     

Effects of the bark beetle nematode, Contortylenchus reversus, on gallery construction,fecundity, and egg viability of the Douglas Fir beetle, Dendroctonus pseudotsugae (Coleoptera: Scolytidae)

Healthy and Contortylenchus reversus infected Douglas Fir beetles were colonized in logs in the laboratory. At 7, 14, and 23 days after introduction of the beetles into the logs, the bark was removed from some of the logs and the length and shape of the primary gallery, the number of eggs laid, and the egg viability were determined for each pair of parent beetles. Parasitism caused a 25, 28, and 27% reduction in the length of the primary egg gallery built by the infected female at 7, 14, and 23 days, respectively, after the start of colonization. In addition, the number of eggs laid by the infected females by 7, 14, and 23 days after the start of colonization were 50, 33, and 45%, respectively, lower than that of healthy female beetles. Despite the differences in gallery length between control and infected females, linear regression analysis showed that the rates of gallery construction were not significantly different. However, infected female beetles showed significantly lower rates of egg-laying than did healthy female beetles. Nematode parasitism did not affect gallery shape and egg viability of female Douglas Fir beetles. Mating of healthy female beetles with infected males affected neither the gallery length nor the fecundity of the uninfected females.     

Risk Factors of Treatment-Limiting Anemia after Substitution of Zidovudine for Stavudine in HIV-Infected Adult Patients on Antiretroviral Treatment

Background

Anemia is the main concern among patients using a zidovudine (AZT)-based antiretroviral treatment (ART). Some studies suggested weight-adjusted AZT dosing as a way to reduce toxicity. We analyzed the risk factors associated with AZT-induced anemia in a cohort using AZT as substitution for stavudine (D4T).

Methods

We retrospectively studied HIV-infected patients in a referral hospital in Phnom Penh, Cambodia between 2003 and 2011. Factors associated with AZT-related anemia requiring AZT-discontinuation within the first year after AZT initiation were analyzed using Cox regression.

Results

Overall, 1180 patients, 60.5% female, were included. At AZT initiation, the median hemoglobin was 12.7 g/dL (IQR 11.7–13.9), the median weight: 51 kg (IQR 45–58) and the median time on ART prior to AZT substitution: 1.4 years (IQR 1.0–2.0). Within one year follow-up, 139 patients (11.8%) developed anemia requiring AZT discontinuation. Overall, there was no independent association of body weight with AZT discontinuation. AZT discontinuation was associated with lower hemoglobin level when starting AZT; older age and taking D4T-based ART less than one year prior to AZT. In exploratory analysis, a linear increase in risk of grade 2–4 anemia with lower body weight was seen if starting AZT substitution within less than one year of D4T-based ART.

Conclusion

Our findings argue against the need of weight-based dosing of AZT to reduce anemia among patients using AZT as substitution for D4T. Whether this also applies to ART-naïve individuals remains to be assessed. Future studies with AZT dose reduction should assess efficacy and overall tolerance of AZT.     

Comparison of human and mouse E-selectin binding to Sialyl-Lewis<Superscript>x</Superscript>

Background

During inflammation, leukocytes are captured by the selectin family of adhesion receptors lining blood vessels to facilitate exit from the bloodstream. E-selectin is upregulated on stimulated endothelial cells and binds to several ligands on the surface of leukocytes. Selectin:ligand interactions are mediated in part by the interaction between the lectin domain and Sialyl-Lewis x (sLe^x), a tetrasaccharide common to selectin ligands. There is a high degree of homology between selectins of various species: about 72 and 60 % in the lectin and EGF domains, respectively. In this study, molecular dynamics, docking, and steered molecular dynamics simulations were used to compare the binding and dissociation mechanisms of sLe^x with mouse and human E-selectin. First, a mouse E-selectin homology model was generated using the human E-selectin crystal structure as a template.

Results

Mouse E-selectin was found to have a greater interdomain angle, which has been previously shown to correlate with stronger binding among selectins. sLe^x was docked onto human and mouse E-selectin, and the mouse complex was found to have a higher free energy of binding and a lower dissociation constant, suggesting stronger binding. The mouse complex had higher flexibility in a few key residues. Finally, steered molecular dynamics was used to dissociate the complexes at force loading rates of 2000–5000 pm/ps². The mouse complex took longer to dissociate at every force loading rate and the difference was statistically significant at 3000 pm/ps². When sLe^x-coated microspheres were perfused through microtubes coated with human or mouse E-selectin, the particles rolled more slowly on mouse E-selectin.

Conclusions

Both molecular dynamics simulations and microsphere adhesion experiments show that mouse E-selectin protein binds more strongly to sialyl Lewis x ligand than human E-selectin. This difference was explained by a greater interdomain angle for mouse E-selectin, and greater flexibility in key residues. Future work could introduce similar amino acid substitutions into the human E-selectin sequence to further modulate adhesion behavior.

     

Characterization of structural and optical properties of Mn2+-doped Zn2GeO4 nanorods as an efficient green phosphor for solid-state lighting

A series of Mn²⁺-doped zinc germinate ZGO:xMn²⁺ (x = 0–0.05) nanorods was synthesized successfully using a hydrothermal method. XRD revealed that crystal phases of the ZGO:xMn²⁺ were rhombohedral and in the R-3 space group. The Williamson–Hall equation was also used to explain the strain, nanocrystalline size, and stacking fault. Green LEDs were successfully fabricated by coating ZGO:Mn²⁺ nanorods onto UV-LED chips. For high color purity, CIE of the fabricated green LEDs were (0.2404, 0.5428), which made this material a promising candidate for fabrication of UV-based green LEDs.     

Comparative effects of tetrandrine and berbamine on production of the inflammatory cytokines interleukin-1 and tumor necrosis factor.

Tetrandrine and berbamine are bisbenzylisoquinoline compounds which differ from each other in a minor way in terms of chemical structure, yet tetrandrine is 6-18 times more potent than berbamine in terms of inhibitory effects on production of interleukin-1 and tumor necrosis factor (TNF alpha) by monocytes and macrophages, and TNF beta production by lymphocytes. Moreover, tetrandrine significantly suppressed phosphoinositide turnover while berbamine did not. These findings may provide important insights into structure-activity relationships and the design of novel analogues and congeners useful in the therapy of chronic inflammatory and auto-immune diseases.