The role of adhesin in the polymeric structure of Vi-antigen

Samples of Vi-antigen subjected to hydrolysis of different duration have been studied. As revealed in this study, 12-hour hydrolysis causes the depolymerization of the preparation. The fragments thus obtained have been found to possess Vi-specificity. The polymeric form of Vi-antigen contains adhesin differing in specificity from Vi-determinant. This component is absent in the low-molecular fraction of Vi-antigen. Adhesin is the binding element of the molecule of Vi-antigen and ensures its polymeric structure.     

Vi antigen and microbial adhesion factors. The detection of adhesins in commercial Vi antigen preparations

Enterobacterial Vi-antigen inhibit the Escherichia coli-induced agglutination of red blood cells of guinea pigs and other animals, which indicates that Vi-antigen contains the admixture of adhesion associated with type I pili. The amount of adhesion contained in Vi-antigen can be determined from the degree to which its hemagglutination-inhibiting effect is manifested.     

Career Preferences of First-year Students at Canadian Medical Schools, 1966-67 to 1968-69

The principal findings of this study of the career preferences of first-year Canadian medical students were:Over 70% of the first-year students expressed a preference for specialty practice, with only 20% oriented towards practice as a family practitioner.There were considerable differences between the medical schools in the proportion of medical students preferring general practice, ranging from less than 10% at McGill to nearly 33% at Queen''s.Nearly one-third of the students stated that they preferred primarily salaried practice. These students were largely those who preferred specialty practice or a career in an area such as public health or research.Nearly 70% of the students looked for a career with part-time teaching, while 8% preferred a full-time teaching career.Only 1% preferred a full-time research career although 90% expected to have at least some research involvement.Students from smaller communities were more likely to express a preference for general practice than those from large urban areas.Men and women had similar practice preferences in terms of general practice and clinical specialty, but significantly more women than men preferred a career in salaried practice. Significantly fewer women expressed a preference for major involvement in either teaching or research.     

Contribution of Glucosinolate Transport to Arabidopsis Defense Responses

Accumulation of glucosinolates, a class of defense-related secondary metabolites found almost exclusively in the Capparales, is induced in response to a variety of biological stresses. It is often assumed that elevated glucosinolate levels result from de novo biosynthesis, but glucosinolate transport from other parts of the plant to the site of herbivory or pathogen infection can also contribute to the defense response. Several studies with Arabidopsis and other crucifers have demonstrated that glucosinolates from vegetative tissue are transported to developing seeds. Here we discuss evidence that long-chain aliphatic glucosinolates are transported to the site of herbivory in response to Myzus persicae (green peach aphid) feeding on Arabidopsis.Key Words: glucosinolate, transport, graft, Arabidopsis, Myzus persicae, aphid     

Design and synthesis of dihydrobenzofuran amides as orally bioavailable, centrally active γ-secretase modulators

We report the discovery and optimization of a novel series of dihydrobenzofuran amides as γ-secretase modulators (GSMs). Strategies for aligning in vitro potency with drug-like physicochemical properties and good microsomal stability while avoiding P-gp mediated efflux are discussed. Lead compounds such as 35 and 43 have moderate to good in vitro potency and excellent selectivity against Notch. Good oral bioavailability was achieved as well as robust brain Aβ42 lowering activity at 100 mg/kg po dose.     

Consequences of N-acylation on structure and membrane binding properties of dermaseptin derivative K4-S4-(1-13)

Acyl conjugation to antimicrobial peptides is known to enhance antimicrobial properties. Here, we investigated the consequences of aminolauryl (NC(12)) conjugation to the dermaseptin derivative K(4)-S4-(1-13) (P) on binding properties to bilayer models mimicking bacterial plasma membrane, which is often cited as the ultimate site of action. Isothermal titration calorimetry revealed that acylation was responsible for enhancing the binding affinity of NC(12)-P compared with P (K = 13 x 10(5) and 1.5 x 10(5) m(-1), respectively). Surface plasmon resonance measurements confirmed the isothermal titration calorimetry results (K(app) = 12.6 x 10(5) and 1.53 x 10(5) m(-1), respectively) and further indicated that enhanced adhesion affinity (K(adhesion) = 3 x 10(5) and 1 x 10(5) m(-1), respectively) was coupled to enhanced tendency to insert within the bilayer (K(insertion) = 4.5 and 1.5, respectively). To gain insight into the molecular basis for these observations, we investigated the three-dimensional structures in the presence of dodecylphosphocholine using NMR. The ensemble of NMR-calculated structures (backbone root mean square deviation <0.6 A) showed that the acyl moiety was responsible for a significant molecular reorganization, possibly affecting the electrostatic potential distribution in NC(12)-P relative to that of P. The combined data present compelling evidence in support of the hypothesis that N-acylation affects antimicrobial properties by modifying the secondary structure of the peptide in a manner that facilitates contact with the membrane and consequently increases its disruption.