Inferring adaptive codon preference to understand sources of selection shaping codon usage bias.

Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify “adaptive codon preference,” a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated “preference” largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome

SU(4) Instantons on Calabi-Yau Threefolds with Z_2 x Z_2 Fundamental Group

Structure group SU(4) gauge vacua of both weakly and strongly coupled heterotic superstring theory compactified on torus-fibered Calabi-Yau threefolds Z with Z_2 x Z_2 fundamental group are presented. This is accomplished by constructing invariant, stable, holomorphic rank four vector bundles on the simply connected cover of Z. Such bundles can descend either to Hermite-Yang-Mills instantons on Z or to twisted gauge fields satisfying the Hermite-Yang-Mills equation corrected by a non-trivial flat B-field. It is shown that large families of such instantons satisfy the constraints imposed by particle physics phenomenology. The discrete parameter spaces of those families are presented, as well as a lower bound on the dimension of the continuous moduli of any such vacuum. In conjunction with Z_2 x Z_2 Wilson lines, these SU(4) gauge vacua can lead to standard-like models at low energy with an additional U(1)_{B-L} symmetry. This U(1)_{B-L} symmetry is very helpful in naturally suppressing nucleon decay.Comment: 68 pages, no figure

Cytotoxic T cells and mycobacteria

How the immune system kills Mycobacterium tuberculosis is still a puzzle. the classical picture of killing due to phagocytosis by activated macrophages may be only partly correct. Based on recent evidence, we express here the view that cytotoxic T lymphocytes also make an important contribution and suggest that DNA vaccines might be a good way to enhance this. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.Univ São Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Bromatol & Toxicol, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol & Immunol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol & Immunol, São Paulo, BrazilWeb of Scienc

Accretions of Various Types of Dark Energies onto Morris-Thorne Wormhole

In this work, we have studied accretion of the dark energies onto Morris-Thorne wormhole. For quintessence like dark energy, the mass of the wormhole decreases and phantom like dark energy, the mass of wormhole increases. We have assumed two types of dark energy like variable modified Chaplygin gas (VMCG) and generalized cosmic Chaplygin gas (GCCG). We have found the expression of wormhole mass in both cases. We have found the mass of the wormhole at late universe and this is finite. For our choices the parameters and the function $B(a)$, these models generate only quintessence dark energy (not phantom) and so wormhole mass decreases during evolution of the universe. Next we have assumed 5 kinds of parametrizations of well known dark energy models. These models generate both quintessence and phantom scenarios. So if these dark energies accrete onto the wormhole, then for quintessence stage, wormhole mass decreases upto a certain value (finite value) and then again increases to infinite value for phantom stage during whole evolution of the universe. We also shown these results graphically.Comment: 9 pages, 7 figures. arXiv admin note: text overlap with arXiv:1112.615

Integrable models: from dynamical solutions to string theory

We review the status of integrable models from the point of view of their dynamics and integrability conditions. Some integrable models are discussed in detail. We comment on the use it is made of them in string theory. We also discuss the Bethe Ansatz solution of the SO(6) symmetric Hamiltonian with SO(6) boundary. This work is especially prepared for the seventieth anniversaries of Andr\'{e} Swieca (in memoriam) and Roland K\"{o}berle.Comment: 24 pages, to appear in Brazilian Journal of Physic

Evaluation of rK39 rapid diagnostic tests for canine visceral leishmaniasis : longitudinal study and meta-analysis

Canine visceral leishmaniasis is a vector-borne disease caused by the intracellular parasite Leishmania infantum. It is an important veterinary disease, and dogs are also the main animal reservoir for human infection. The disease is widespread in the Mediterranean area, and parts of Asia and South and Central America, and is potentially fatal in both dogs and humans unless treated. Diagnosis of canine infections requires serological or molecular tests. Detection of infection in dogs is important prior to treatment, and in epidemiological studies and control programmes, and a sensitive and specific rapid diagnostic test would be very useful. Rapid diagnostic tests (RDTs) have been developed, but their diagnostic performance has been reported to be variable. We evaluated the sensitivity of a RDT based on serological detection of the rK39 antigen in a cohort of naturally infected Brazilian dogs. The sensitivity of the test to detect infection was relatively low, but increased with time since infection and the severity of infection. We then carried out a meta-analysis of published studies of rK39 RDTs, evaluating the sensitivity to detect disease and infection. The results suggest that rK39 RDTs may be useful in a veterinary clinical setting, but the sensitivity to detect infection is too low for operational control programmes

DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes

Abstract\ud \ud \ud \ud Background\ud \ud Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases.\ud \ud \ud \ud Methods\ud \ud In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ.\ud \ud \ud \ud Results\ud \ud DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete.\ud \ud \ud \ud Conclusion\ud \ud The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.The authors are grateful to Mrs. Izaíra T Brandão and Mrs. Ana Paula Masson for technical assistance. This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development) and the Rede Brasileira de Pesquisa em TB (REDETB, Brazilian Tuberculosis Research Network).The authors are grateful to Mrs. Izaíra T Brandão and Mrs. Ana Paula Masson for technical assistance. This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development) and the Rede Brasileira de Pesquisa em TB (REDE-TB, Brazilian Tuberculosis Research Network)