Unique pathogen peptidomes facilitate pathogen-specific selection and specialization of MHC alleles

A key component of pathogen-specific adaptive immunity in vertebrates is the presentation of pathogen-derived antigenic peptides by major histocompatibility complex (MHC) molecules. The excessive polymorphism observed at MHC genes is widely presumed to result from the need to recognize diverse pathogens, a process called pathogen-driven balancing selection. This process assumes that pathogens differ in their peptidomes—the pool of short peptides derived from the pathogen’s proteome—so that different pathogens select for different MHC variants with distinct peptide-binding properties. Here, we tested this assumption in a comprehensive data set of 51.9 Mio peptides, derived from the peptidomes of 36 representative human pathogens. Strikingly, we found that 39.7\% of the 630 pairwise comparisons among pathogens yielded not a single shared peptide and only 1.8\% of pathogen pairs shared more than 1\% of their peptides. Indeed, 98.8\% of all peptides were unique to a single pathogen species. Using computational binding prediction to characterize the binding specificities of 321 common human MHC class-I variants, we investigated quantitative differences among MHC variants with regard to binding peptides from distinct pathogens. Our analysis showed signatures of specialization toward specific pathogens especially by MHC variants with narrow peptide-binding repertoires. This supports the hypothesis that such fastidious MHC variants might be maintained in the population because they provide an advantage against particular pathogens. Overall, our results establish a key selection factor for the excessive allelic diversity at MHC genes observed in natural populations and illuminate the evolution of variable peptide-binding repertoires among MHC variants

The Path Integral for 1+1-dimensional QCD

We derive a path integral expression for the transition amplitude in 1+1-dimensional QCD starting from canonically quantized QCD. Gauge fixing after quantization leads to a formulation in terms of gauge invariant but curvilinear variables. Remainders of the curved space are Jacobians, an effective potential, and sign factors just as for the problem of a particle in a box. Based on this result we derive a Faddeev-Popov like expression for the transition amplitude avoiding standard infinities that are caused by integrations over gauge equivalent configurations.Comment: 16 pages, LaTeX, 3 PostScript figures, uses epsf.st

The optimal P3M algorithm for computing electrostatic energies in periodic systems

We optimize Hockney and Eastwood's Particle-Particle Particle-Mesh (P3M) algorithm to achieve maximal accuracy in the electrostatic energies (instead of forces) in 3D periodic charged systems. To this end we construct an optimal influence function that minimizes the RMS errors in the energies. As a by-product we derive a new real-space cut-off correction term, give a transparent derivation of the systematic errors in terms of Madelung energies, and provide an accurate analytical estimate for the RMS error of the energies. This error estimate is a useful indicator of the accuracy of the computed energies, and allows an easy and precise determination of the optimal values of the various parameters in the algorithm (Ewald splitting parameter, mesh size and charge assignment order).Comment: 31 pages, 3 figure

Discriminating changes in intracellular NADH/NAD+ levels due to anoxicity and H2 supply in R. eutropha cells using the Frex fluorescence sensor

The hydrogen-oxidizing “Knallgas” bacterium Ralstonia eutropha can thrive in aerobic and anaerobic environments and readily switches between heterotrophic and autotrophic metabolism, making it an attractive host for biotechnological applications including the sustainable H2-driven production of hydrocarbons. The soluble hydrogenase (SH), one out of four different [NiFe]-hydrogenases in R. eutropha, mediates H2 oxidation even in the presence of O2, thus providing an ideal model system for biological hydrogen production and utilization. The SH reversibly couples H2 oxidation with the reduction of NAD+ to NADH, thereby enabling the sustainable regeneration of this biotechnologically important nicotinamide cofactor. Thus, understanding the interaction of the SH with the cellular NADH/NAD+ pool is of high interest. Here, we applied the fluorescent biosensor Frex to measure changes in cytoplasmic [NADH] in R. eutropha cells under different gas supply conditions. The results show that Frex is well-suited to distinguish SH-mediated changes in the cytoplasmic redox status from effects of general anaerobiosis of the respiratory chain. Upon H2 supply, the Frex reporter reveals a robust fluorescence response and allows for monitoring rapid changes in cellular [NADH]. Compared to the Peredox fluorescence reporter, Frex displays a diminished NADH affinity, which prevents the saturation of the sensor under typical bacterial [NADH] levels. Thus, Frex is a valuable reporter for on-line monitoring of the [NADH]/[NAD+] redox state in living cells of R. eutropha and other proteobacteria. Based on these results, strategies for a rational optimization of fluorescent NADH sensors are discussed

A Double-Mode RR Lyrae Star with a Strong Fundamental Mode Component

NSVS 5222076, a thirteenth magnitude star in the Northern Sky Variability Survey, was identified by Oaster as a possible new double-mode RR Lyrae star. We confirm the double-mode nature of NSVS 5222076, supplementing the survey data with new V band photometry. NSVS 5222076 has a fundamental mode period of 0.4940 day and a first overtone period of 0.3668 day. Its fundamental mode light curve has an amplitude twice as large as that of the first overtone mode, a ratio very rarely seen. Data from the literature are used to discuss the location in the Petersen diagram of double-mode RR Lyrae stars having strong fundamental mode pulsation. Such stars tend to occur toward the short period end of the Petersen diagram, and NSVS 5222976 is no exception to this rule.Comment: 14 pages, 4 figures, To be published in the March, 2006, issue of PAS

Deformed Gaussian Orthogonal Ensemble Analysis of the Interacting Boson Model

A Deformed Gaussian Orthogonal Ensemble (DGOE) which interpolates between the Gaussian Orthogonal Ensemble and a Poissonian Ensemble is constructed. This new ensemble is then applied to the analysis of the chaotic properties of the low lying collective states of nuclei described by the Interacting Boson Model (IBM). This model undergoes a transition order-chaos-order from the $SU(3)$ limit to the $O(6)$ limit. Our analysis shows that the quantum fluctuations of the IBM Hamiltonian, both of the spectrum and the eigenvectors, follow the expected behaviour predicted by the DGOE when one goes from one limit to the other.Comment: 10 pages, 4 figures (avaiable upon request), IFUSP/P-1086 Replaced version: in the previous version the name of one of the authors was omitte

Brief review on semileptonic B decays

We concisely review semileptonic B decays, focussing on recent progress on both theoretical and experimental sides.Comment: 18 pages, 2 figures; version to be published in Mod. Phys. Lett.

Interference scheme to measure light-induced nonlinearities in Bose-Einstein condensates

Light-induced nonlinear terms in the Gross-Pitaevskii equation arise from the stimulated coherent exchange of photons between two atoms. For atoms in an optical dipole trap this effect depends on the spatial profile of the trapping laser beam. Two different laser beams can induce the same trapping potential but very different nonlinearities. We propose a scheme to measure light-induced nonlinearities which is based on this observation.Comment: 2 figure

Local Spectral Density for a Periodically Driven System of Coupled Quantum States with Strong Imperfection in Unperturbed Energies

A random matrix theory approach is applied in order to analyze the localization properties of local spectral density for a generic system of coupled quantum states with strong static imperfection in the unperturbed energy levels. The system is excited by an external periodic field, the temporal profile of which is close to monochromatic one. The shape of local spectral density is shown to be well described by the contour obtained from a relevant model of periodically driven two-states system with irreversible losses to an external thermal bath. The shape width and the inverse participation ratio are determined as functions both of the Rabi frequency and of parameters specifying the localization effect for our system in the absence of external field.Comment: 6 pages, 5 figures, submitted to Optics and Spectroscop