Impaired Intracellular Transport and Cell Surface Expression of Nonpolymorphic HLA-E

The assembly of the classical, polymorphic major histocompatibility complex class I molecules in the endoplasmic reticulum requires the presence of peptide ligands and ~2-microglobulin (~2m). Formation of this trimolecular complex is a prerequisite for e~cient transport to the cell surface, where presented peptides are scanned by T lymphocytes. The function of the other class I molecules is in dispute. The human, nonclassical class I gene, HLA-E, was found to be ubiquitously transcribed, whereas cell surface expression was dif~cult to detect upon transfection. Pulse chase experiments revealed that the HLA-E heavy chain in transfectants, obtained with the murine myeloma cell line P3X63-Ag8.653 (X63), displays a significant reduction in oligosaccharide maturation and intracellular transport compared with HLA-B27 in corresponding transfectants. The accordingly low HLA-E cell surface expression could be significantly enhanced by either reducing the culture temperature or by supplementing the medium with human ~2m, suggesting inefficient binding of endogenous peptides to HLA-E. To analyze whether HLA-E binds peptides and to identify the corresponding ligands, fractions of acid-extracted material from HLA-E/X63 transfectants were separated by reverse phase HPLC and were tested for their ability to enhance HLA-E cell surface expression. Two fractions specifically increased the HLA class I expression on the HLA-E transfectant clone

Simulations of isolated dwarf galaxies formed in dark matter halos with different mass assembly histories

We present high-resolution N-body/hydrodynamics simulations of dwarf galaxies formed in isolated CDM halos with the same virial mass, Mv~2.5x10^10 Msun at z=0, in order to (1) study the mass assembly histories (MAHs) of the halo, stars, and gas components, and (2) explore the effects of the halo MAHs on the stellar/baryonic assembly of the simulated dwarfs and on their z~0 properties. Overall, the simulated dwarfs are roughly consistent with observations. Our main results are: a) The stellar-to-halo mass ratio is ~0.01 and remains roughly constant since z~1 (the stellar MAHs follow closely the halo MAHs), with a smaller value at higher z's for those halos that assemble their mass later. b) The evolution of the galaxy gas fraction, fg, is episodic and higher, most of the time, than the stellar fraction. When fg decreases (increases), the gas fraction in the halo typically increases (decreases), showing that the SN driven outflows play an important role in regulating the gas fractions -and hence the SFR- of the dwarfs. However, in most cases, an important fraction of the gas escapes the virial radius, Rv; at z=4 the total baryon fraction inside Rv is 1.5-2 times smaller than the universal one, while at z=0 is 2-6 times smaller, with the earlier assembled halos ejecting more gas. c) The SF histories are episodic with changes in the SFRs of factors 2-10 on average. d) Although the dwarfs formed in late assembled halos show more extended SF histories, their z~0 SFRs are still below the ones measured for local isolated dwarfs. e) The effects of baryons on Mv are such that at almost any time Mv is 10-20% smaller than the corresponding Mv obtained in pure N-body simulations. Our results suggest that rather than increasing the strength of the SN-driven outflows, processes that reduce the SF efficiency even more will help to solve the potential issues faced by the CDM-based simulations of dwarfs.Comment: 14 pages, 12 figures. ApJ, published. Minor changes after final Referee's repor

A geometric framework for modelling similarity search

The aim of this paper is to propose a geometric framework for modelling similarity search in large and multidimensional data spaces of general nature, which seems to be flexible enough to address such issues as analysis of complexity, indexability, and the `curse of dimensionality.' Such a framework is provided by the concept of the so-called similarity workload, which is a probability metric space $\Omega$ (query domain) with a distinguished finite subspace $X$ (dataset), together with an assembly of concepts, techniques, and results from metric geometry. They include such notions as metric transform, \e-entropy, and the phenomenon of concentration of measure on high-dimensional structures. In particular, we discuss the relevance of the latter to understanding the curse of dimensionality. As some of those concepts and techniques are being currently reinvented by the database community, it seems desirable to try and bridge the gap between database research and the relevant work already done in geometry and analysis.Comment: 11 pages, LaTeX 2.

Complexity of the Ruminococcus flavefaciens FD-1 cellulosome reflects an expansion of family-related protein-protein interactions

This work was supported in part by the European Union, Area NMP.2013.1.1–2: Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number: 604530, and by the EU Seventh Framework Programme (FP7 2007–2013) under the WallTraC project (Grant Agreement no 263916), and BioStruct-X (grant agreement no 283570). This paper reflects the author’s views only. The European Community is not liable for any use that may be made of the information contained herein. CMGAF is also supported by Fundação para a Ciência e a Tecnologia (Lisbon, Portugal) through grants PTDC/BIA-PRO/103980/2008 and EXPL/BIA-MIC/1176/2012. EAB is also funded by a grant (No. 1349/13) from the Israel Science Foundation (ISF), Jerusalem, Israel and by a grant (No. 2013284) from the U.S.-Israel Binational Science Foundation (BSF). E.A.B. is the incumbent of The Maynard I. and Elaine Wishner Chair of Bio-organic Chemistry.Peer reviewedPublisher PD