Structure of the glycosyltransferase EryCIII in complex with its activating P450 homologue EryCII

In the biosynthesis of the clinically important antibiotic erythromycin D, the glycosyltransferase (GT) EryCIII, in concert with its partner EryCII, attaches a nucleotide-activated sugar to the macrolide scaffold with high specificity. To understand the role of EryCII, we have determined the crystal structure of the EryCIII·EryCII complex at 3.1 Å resolution. The structure reveals a heterotetramer with a distinctive, elongated quaternary organization. The EryCIII subunits form an extensive self-complementary dimer interface at the center of the complex, and the EryCII subunits lie on the periphery. EryCII binds in the vicinity of the putative macrolide binding site of EryCIII but does not make direct interactions with this site. Our biophysical and enzymatic data support a model in which EryCII stabilizes EryCIII and also functions as an allosteric activator of the GT.     

Discovery and optimization of a series of liver X receptor antagonists

The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents.     

Interactive effects of pH and temperature on the bacteriocin stability by response surface analysis

The combined influence of pH and temperature on bacteriocins produced by three lactic acid bacteria, Pediococcus pentosaceus MMZ26, Enterococcus faecium MMZ17 and Lactococcus lactis MMZ25, isolated from Tunisian traditional dry fermented meat was studied using a second order orthogonal factorial design and response-surface methodology (RSM). This method allows estimating the interactive effects of pH and temperature on the stability of each bacteriocin. The high heat stability of the three bacteriocins was demonstrated, with optimum values at light acidic pH around 5.0, temperature below 90 degrees C and short incubation times. This study contributes to a better understanding of relation between bacteriocins production and stability in order to enhance their, in situ, application as a food and feed biopreservative in fermented and/or heated food products.     

Epigenetic Inheritance: What News for Evolution?

Whether epigenetic variation is important in adaptive evolution has been contentious. Two recent studies in Arabidopsis thaliana significantly add to our understanding of genome-wide variation and stability of an epigenetic mark, and thus help pave the path for realistically incorporating epigenetics into evolutionary theory.     

Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state

To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). Output data was analysed through ArrayAssist software (Agilent, San Jose CA). More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05). Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87%) had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.     

What you may not see might slow you down anyway: masked images and driving

Many theories of driver behaviour suggest that unconscious or implicit emotions play a functional role in the shaping and control of behaviour. This has not been experimentally tested however. Therefore, in this study the effects of emotive masked images on driver behaviour were examined. While driving a simulator, participants were repeatedly exposed to negative or neutral emotionally laden target images that were sandwich masked by emotionally neutral images. These images were encountered across two different trials each of which consisted of 3-4 minutes of driving on a rural road. The results indicate an effect of the negative target images primarily in reducing the extent of familiarisation occurring between the first and second experimental drives. This is evident in a reduced decrease in heart rate and a reduced increase in high band heart rate variability and actual travelling speed from the first to second drives if the negative target image was presented in the second drive. In addition to these findings there was no clear effect of the target image on subjective ratings of effort or feelings of risk. There was however an effect of gender, with the majority of the effects found in the study being limited to the larger female dataset. These findings suggest that unconscious or implicit emotional stimuli may well influence driver behaviour without explicit awareness.