Identification of critical residues of the serotype modifying O-acetyltransferase of Shigella flexneri

BACKGROUND Thirteen serotypes of Shigella flexneri (S. flexneri) have been recognised, all of which are capable of causing bacillary dysentery or shigellosis. With the emergence of the newer S. flexneri serotypes, the development of an effective vaccine has only become more challenging. One of the factors responsible for the generation of serotype diversity is an LPS O-antigen modifying, integral membrane protein known as O-acetyltransferase or Oac. Oac functions by adding an acetyl group to a specific O-antigen sugar, thus changing the antigenic signature of the parent S. flexneri strain. Oac is a membrane protein, consisting of hydrophobic and hydrophilic components. Oac bears homology to several known and predicted acetyltransferases with most homology existing in the N-terminal transmembrane (TM) regions. RESULTS In this study, the conserved motifs in the TM regions and in hydrophilic loops of S. flexneri Oac were targeted for mutagenesis with the aim of identifying the amino acid residues essential for the function of Oac. We previously identified three critical arginines-R73, R75 and R76 in the cytoplasmic loop 3 of Oac. Re-establishing that these arginines are critical, in this study we suggest a catalytic role for R73 and a structural role for R75 and R76 in O-acetylation. Serine-glycine motifs (SG 52-53, GS 138-139 and SYG 274-276), phenylalanine-proline motifs (FP 78-79 and FPV 282-84) and a tryptophan-threonine motif (WT141-142) found in TM segments and residues RK 110-111, GR 269-270 and D333 found in hydrophilic loops were also found to be critical to Oac function. CONCLUSIONS By studying the effect of the mutations on Oac's function and assembly, an insight into the possible roles played by the chosen amino acids in Oac was gained. The transmembrane serine-glycine motifs and hydrophilic residues (RK 110-111, GR 269-270 and D333) were shown to have an affect on Oac assembly which suggests a structural role for these motifs. The phenylalanine-proline and the tryptophan-threonine motifs affect Oac function which could suggest a catalytic role for these amino acids.This work was supported by a grant from the National Health and Medical Research Council of Australia

Oscillating non-singular relativistic spherical model

A particular choice of the time function in the recently presented spherical solution by Dadhich [1] leads to a singularity free cosmological model which oscillates between two regular states. The energy-stress tensor involves anisotropic pressure and a heat flux term but is consistent with the usual energy conditions (strong, weak and dominant). By choosing the parameters suitably one can make the model consistent with observational data. An interesting feature of the model is that it involves blue shifts as in the quasi steady state model [2] but without violating general relativity.Comment: 6 pages, REVTEX versio

Sickle cell disease status among school adolescents and their tribal community in South Gujarat

Objectives: to create awareness, to screen samples of school adolescents and then to reach their community through them by doing surveillance for sickle cell disease. Design: Field based cross-sectional study. Settings: St Xavier`s high school and Vanraj high school of Umarpada taluka of Surat district. Subjects: School adolescents, their parents and friends. Method: After taking permission from school authority, blood samples of 948 school adolescents were taken for DTT test and then for electrophoresis. Blood samples of motivated parents and friends of those adolescents found positive for DTT was taken in subsequent visit and results were communicated to them. Results: Blood samples of 948 school adolescents, out of 1081 were tested for DTT test. It was positive in 242 samples, giving a prevalence of 25.5% for sickle cell disease. On subjecting the positive blood samples to electrophoresis, the proportion of sickle cell trait and sickle cell disease was found to be 92% and 8% respectively. Then electrophoresis was done in 64 parents and friends, 24 (37.5%) of them were found positive of which, 14 (58%) were having sickle cell trait and 10 (42%) having sickle cell disease. Conclusion: approaching community can be possible through school adolescents for conduction of surveillance of sickle cell anemi