Neonatal thymus provides all the information required for tolerance induction against all the non-thymic organ-specific minor histocompatibility antigens

Using our original "in vivo MLR" technique, we demonstrated that B10.D2 cells grafted into irradiated (DBA/2 x B10.D2)F1 mice (H-2d/H-2d) were stimulated to divide by the whole non-H-2 minor histocompatibility antigens (MiHA) of the DBA/2 background in each organ where these MiHA are expressed. When B10.D2 cells were grafted into N7 mice (generation descending from six successive backcrosses with B10.D2 after an initial cross DBA/2 x B10.D2) which had kept 1/64 of the DBA/2 genetic background, a lack of correlation between the levels of stimulation in the different organs of the same mouse was demonstrated. We established that the number of expressed MiHA lies between 7 and more than 100, depending on the organ, and that the organ specificity is a feature of the expression of these MiHA. Furthermore, using a different technique, we demonstrated that B10.D2 T cells can acquire a specific tolerance state towards the whole DBA/2 antigen background throughout maturation and differentiation in a fully syngeneic environment with the exception of a neonate-(DBA/2 x B10.D2)F1 grafted thymus. We concluded, therefore, that all information corresponding to the adult- and organ-specific MiHA is available in the neonatal thymus. Three working hypotheses are proposed to reconcile the two lines of results.     

拐芹根化学成分研究Ⅱ

从伞型科当归属植物拐芹(Angelica polymorpha Maxim)的根及根茎中又分得4个结晶性化合物。经物理常数测定、光谱分析,分别鉴定为欧前胡素Ⅰ,异氧化前胡内酯Ⅱ,Pabulenol Ⅲ,Phellopterin Ⅳ。     

Identification and quantitation of electron-transport components in human polymorphonuclear neutrophils

Using dithionite difference spectra we have detected cytochrome b in highly purified human neutrophils at a concentration of 0.08 nmol/mg protein. The presence of quinone was identified in lipid extracts at a concentration of approx. 0.06 nmol/mg protein. It was identified as ubiquinone-10 by mass spectrographic analysis. Simultaneous measurements of cytochrome oxidase indicated that these compounds could not be attributed to mitochondrial contamination. These results are compatible with the hypothesis that initiation of the respiratory burst in human neutrophils involves a multicomponent electron-transport system.     

Physicochemical study of trisequence copolymers, poly(gamma-benzyl-L-glutamate)-poly(ethylene oxide)-poly(gamma-benzyl-L-glutamate). Role of polydispersity in the determination of conformation of the molecules in dilute solution

We have prepared a series of three-block copolymers containing the same central block of poly(ethylene oxide) (POE) and two side blocks poly(γ-L -glutamate) (PBLG) of variable lengths. These molecules could present an unusual conformational model when dissolved in solvents where PBLG exhibits a helical structure: a helical structure: a gaussian chain connected at each end to a rigid rod. We checked this hypothesis by light scattering, viscosimetry, and dielectric adsorption measurements. In order to take into account the possibility that the orientations of the two rods may not be completely independent, we have introduced in the calculations the angle θ, formed by the two rigid segments. We have mainly considered three types of conformation which can be described by assimilating the lods of PBLG of two vectors having their origin at the juncture with the POE chain: depending whether cos θ (the average value of cos θ) is equals to ?1,0, or +1 ( where the two vectors are antiparalles, oriented independently, or parallel, respectively). We have tried to establish a theoretical expression for the molecular size obtained by each method of investigation, as a function of cos θ . We corrected this value to account for the effect of the polydispersity on the molecular size and then compared the theoretical values thus calculated with the experimental results. The measurements of the radius of gyration, R, by light scattering does not permit the unambiguous determination of cos θ . As soon as the system is not perfectly monodisperse, the variation of R as a funciton of cos θ is not very large. The viscosity results are also difficult to interpret because the effect of the polydispersity on the viscosity cannot be established fo each conformational model. However, a clear answer can be obtained by the dielectric absorption technique for two reasons: the variation of the dielectric absorption as a function of cos θ is very important and the influence of the polydispersity on the measurements is weaker than for the two former methods. The results show that cos θ is equal to ?1, demonstrating that the two vectors are antiparallel. From the dielectric dispersion, one sees that the total length of the molecule is roughly equals to the sum of the lengths of the two rigid blocks. To explain this result we propose a new conformational model. Since it is known that in some solvents and mixtures of solvents the molecules of PBLG tend to associate, we assume that the two rigid rods are antiparallel and partly associated. The associated part of the molecule is assumed to be surrounded by the mixture of POE and solvent, which acts as a poor solvent (ef. Fig. 2.).     

A family of double helices of alternating poly(gamma-benzyl-D-L-glutamate), a stereochemical model for gramicidin A.

Poly(γ-benzyl-d-l-glutamate) with strict alternation of l and d residues is found to exist, in addition to the α_DL and π_DL^4.4 helical structures already described (Heitz et al., 1975a), in four more helical structures. Models based on double helices made of antiparallel strands are proposed for all four structures, based on infrared, X-ray and electron diffraction data. These double helices are, like the single-stranded π_DL helices, specific to polypeptides with a strict stereosequence of alternating l and d residues. The diameter of the helical core of three of these helices appears to depend on the dimensions of the solvent molecules. Conformational angles (located in the β regions) and atomic co-ordinates determined by conformational energy analysis are given for the four structures. Experimental conditions used to obtain these helices, and to induce transconformations between the various helical structures of PBd-lG are described. The present investigations on PBd-lG help to make more precise the structure and geometry of models proposed (Veatch et al., 1974) for the antibiotic gramicidin A.     

270-MHz nuclear-magnetic-resonance study on linear gramicidin A in dimethylsulfoxide. A new interpretation.

On the basis of the finding of two sets of coupling constants (8.8 Hz and 6.7 Hz) in the 270-MHz proton magnetic resonance spectra of linear Gramicidin in dimethylsulfoxide and the comparison of its infrared spectrum with those of known conformations of alternating poly(gamma-benzyl-D-glutamate--gamma-benzyl-L-glutamate), it is proposed that the antibiotic has an LD-ribbon structure.     

Redescription and palaeobiology of Palaeoscorpius devonicus Lehmann, 1944 from the Lower Devonian Hunsrück Slate of Germany

Abstract: Palaeoscorpius devonicus Lehmann, 1944 is known from only a single specimen, found in the Eschenbach Pit near Bundenbach in the Lower Devonian Hunsrück Slate of Germany. It is a key fossil, having been interpreted both as the most basal member of the Scorpiones and as one of the order’s most likely candidates for an aquatic mode of life. Prepared both ventrally and dorsally, some aspects of its morphology remain problematic. Here, with the aid of new techniques, including computed tomography, we present a re‐investigation of this scorpion’s anatomy and a new reconstruction, with a particular focus on the species’ original habitat. On the basis of the environmental interpretation of the Hunsrück Slate and the completeness of the specimen, previous authors concluded that P. devonicus was marine, but none offered convincing morphological evidence. Recent studies of the deposit’s environment suggest that the Hunsrück Sea was part of an intrashelf basin, relatively close to the coastline, and fossils of land plants show that terrestrial wash‐in occasionally occurred. Our revised interpretation of the fossil’s morphology demonstrates that the scorpion was most probably terrestrial. Internal mesosomal organs are interpreted as book lungs, but other terrestrial adaptations are lacking. The absence of both coxapophyses and gnathobases makes determining the scorpion’s feeding mechanism difficult. Interpreting the scorpion’s character states within a phylogenetic framework, especially the possible presence of book lungs, implies either that the plesiomorphic position of P. devonicus is no longer supported or that the development of book lungs had already taken place early in the scorpion lineage.     

Offering an American Graduate Medical HIV Course to Health Care Workers in Resource-Limited Settings via the Internet

Background

Western accredited medical universities can offer graduate-level academic courses to health care workers (HCWs) in resource-limited settings through the internet. It is not known whether HCWs are interested in these online courses, whether they can perform as well as matriculated students, or whether such courses are educationally or practically relevant.

Methods and Findings

In 2011, the University of Washington (UW) Schools of Medicine and Nursing offered the graduate course, “Clinical Management of HIV”, to HCWs that included a demographic survey, knowledge assessment, and course evaluation. UW faculty delivered HIV clinical topics through ten 2-hour weekly sessions from the perspectives of practicing HIV medicine in developed and developing settings. HCWs viewed lectures through Adobe Acrobat Connect Pro (Adobe Systems, San Jose, CA), and completed online homework on HIV Web Study (http://depts.washington.edu/hivaids/) and online quizzes. HCWs, who met the same passing requirements as UW students by attending 80% lectures, completing ≥90% homework, and achieving a cumulative ≥70% grade on quizzes, were awarded a certificate. 369 HCWs at 33 sites in 21 countries joined the course in 2011, a >15-fold increase since the course was first offered in 2007. The majority of HCWs came from Africa (72%), and most were physicians (41%), nurses (22%), or midlevel practitioners (20%). 298 HCWs (81%) passed all requirements and earned a certificate. In a paired analysis of pre- and post-course HIV knowledge assessments, 56% of HCWs improved their post-course score (p<0.0001) with 27% improving by at least 30%. In the course evaluation, most HCWs rated the course as excellent (53%) or very good (39%).

Conclusions

This online HIV course demonstrated that opening a Western graduate medical and nursing curriculum to HCWs in resource-limited settings is feasible, popular, and valuable, and may address logistic and economic barriers to the provision of high quality education in these settings.