Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen.

The complete cDNA for a human mitochondrial protein designated P1, which was previously identified as a microtubule-related protein, has been cloned and sequenced. The deduced amino acid sequence of P1 shows strong homology (40 to 50% identical residues and an additional 20% conservative replacements) to the 65-kilodalton major antigen of mycobacteria, to the GroEL protein of Escherichia coli, and to the ribulose 1,5-bisphosphate carboxylase-oxygenase (rubisco) subunit binding protein of plant chloroplasts. Similar to the case with the latter two proteins, which have been shown to act as chaperonins in the posttranslational assembly of oligomeric protein structures, it is suggested that P1 may play a similar role in mammalian cells. The observed high degree of homology between human P1 and mycobacterial antigen also suggests the possible involvement of this protein in certain autoimmune diseases.     

Food Vacuole Associated Enolase in Plasmodium Undergoes Multiple Post-Translational Modifications: Evidence for Atypical Ubiquitination

Plasmodium enolase localizes to several sub-cellular compartments viz. cytosol, nucleus, cell membrane, food vacuole (FV) and cytoskeleton, without having any organelle targeting signal sequences. This enzyme has been shown to undergo multiple post-translational modifications (PTMs) giving rise to several variants that show organelle specific localization. It is likely that these PTMs may be responsible for its diverse distribution and moonlighting functions. While most variants have a MW of ~50 kDa and are likely to arise due to changes in pI, food vacuole (FV) associated enolase showed three forms with MW~50, 65 and 75 kDa. Evidence from immuno-precipitation and western analysis indicates that the 65 and 75 kDa forms of FV associated enolase are ubiquitinated. Using mass spectrometry (MS), definitive evidence is obtained for the nature of PTMs in FV associated variants of enolase. Results showed several modifications, viz. ubiquitination at K147, phosphorylation at Y148 and acetylation at K142 and K384. MS data also revealed the conjugation of three ubiquitin (Ub) molecules to enolase through K147. Trimeric ubiquitin has a linear peptide linkage between the NH₂-terminal methionine of the first ubiquitin (Ub1) and the C-terminal G76 of the second (Ub2). Ub2 and third ubiquitin (Ub3) were linked through an atypical isopeptide linkage between K6 of Ub2 and G76 of Ub3, respectively. Further, the tri-ubiquitinated form was found to be largely associated with hemozoin while the 50 and 65 kDa forms were present in the NP-40 soluble fraction of FV. Mass spectrometry results also showed phosphorylation of S42 in the cytosolic enolase from P. falciparum and T337 in the cytoskeleton associated enolase from P . yoelii . The composition of food vacuolar proteome and likely interactors of enolase are also being reported.     

Rps5-Rps16 communication is essential for efficient translation initiation in yeast S. cerevisiae

Conserved ribosomal proteins frequently harbor additional segments in eukaryotes not found in bacteria, which could facilitate eukaryotic-specific reactions in the initiation phase of protein synthesis. Here we provide evidence showing that truncation of the N-terminal domain (NTD) of yeast Rps5 (absent in bacterial ortholog S7) impairs translation initiation, cell growth and induction of GCN4 mRNA translation in a manner suggesting incomplete assembly of 48S preinitiation complexes (PICs) at upstream AUG codons in GCN4 mRNA. Rps5 mutations evoke accumulation of factors on native 40S subunits normally released on conversion of 48S PICs to 80S initiation complexes (ICs) and this abnormality and related phenotypes are mitigated by the SUI5 variant of eIF5. Remarkably, similar effects are observed by substitution of Lys45 in the Rps5-NTD, involved in contact with Rps16, and by eliminating the last two residues of the C-terminal tail (CTT) of Rps16, believed to contact initiator tRNA base-paired to AUG in the P site. We propose that Rps5-NTD-Rps16-NTD interaction modulates Rps16-CTT association with Met-tRNA_i^Met to promote a functional 48S PIC.     

A Study of Unusual Pacemaker Infection by Mycobacterium Tuberculosis in Indian Patients

Background

The expanding clinical indications of cardiac rhythm management have led to an increased use of pacemaker implantation which is associated with increased incidence of pacemaker infections. Staphylococcus aureus and epidermidis account for the vast majority of pacemaker infections. Pacemaker infection due to Mycobacterium tuberculosis (M. tuberculosis) is very rare, only few cases having been reported till date.

Methods

We describe here a study of three patients of pacemaker pocket infection with M. tuberculosis.

Conclusion

The possibility of mycobacterial pacemaker infection should always be kept in mind in patients with delayed pacemaker infection.     

No association of DNA ligase-I polymorphism with the risk of lung cancer in north-Indian population

DNA ligases play an essential role in repair, replication, and recombination of DNA, and catalyzes the formation of a phosphodiester bond at a nick junction on single- and double-strand breaks. We have conducted a hospital-based case-control study to examine the role of polymorphism of DNA repair gene ligase I (LIGI) in the context of lung cancer risk for north Indian population. One hundred, fifty-one primary lung cancer cases and an equal number of matching hospital controls were collected. The LIGI polymorphism was determined by using the PCR-RFLP method. The association between polymorphisms in the LIGI gene with the risk of lung cancer was estimated by computing odds ratios (ORs) and a 95% confidence interval (CI) using a Multivariate Logistic Regression Analysis. The risk for lung cancer was not associated for individuals featuring LIGI (AC) (OR -0.8, 95% CI = 0.44-1.40) and (AA) (OR -0.8, 95% CI = 0.41-1.80) genotypes. The DNA repair gene (LIGI) may not be playing an important role in modulating the risk of lung cancer in the north Indian population.     

E93R Substitution of Escherichia coli FtsZ Induces Bundling of Protofilaments,Reduces GTPase Activity,and Impairs Bacterial Cytokinesis

Recently, we found that divalent calcium has no detectable effect on the assembly of Mycobacterium tuberculosis FtsZ (MtbFtsZ), whereas it strongly promoted the assembly of Escherichia coli FtsZ (EcFtsZ). While looking for potential calcium binding residues in EcFtsZ, we found a mutation (E93R) that strongly promoted the assembly of EcFtsZ. The mutation increased the stability and bundling of the FtsZ protofilaments and produced a dominating effect on the assembly of the wild type FtsZ (WT-FtsZ). Although E93R-FtsZ was found to bind to GTP similarly to the WT-FtsZ, it displayed lower GTPase activity than the WT-FtsZ. E93R-FtsZ complemented for its wild type counterpart as observed by a complementation test using JKD7–1/pKD3 cells. However, the bacterial cells became elongated upon overexpression of the mutant allele. We modeled the structure of E93R-FtsZ using the structures of MtbFtsZ/Methanococcus jannaschi FtsZ (MjFtsZ) dimers as templates. The MtbFtsZ-based structure suggests that the Arg⁹³-Glu¹³⁸ salt bridge provides the additional stability, whereas the effect of mutation appears to be indirect (allosteric) if the EcFtsZ dimer is similar to that of MjFtsZ. The data presented in this study suggest that an increase in the stability of the FtsZ protofilaments is detrimental for the bacterial cytokinesis.     

Model for compression of fullerenes and carbon nanotubes

The new materials of carbon, solid C₆₀ and carbon nanotubes (CNT) [1 Chesnokov, S.A., Nalimova, V.A., Rinzler, A.G., Smalley, R.E. and Fischer, E. 1999. Mechanical energy storage in carbon nanotube springs. PRL, 82: 343[Crossref], [Web of Science ®] , [Google Scholar],4 V.K. Jindal, Shuchi Gupta, K. Dharamvir, Bulk and lattice properties for rigid carbon nanotubes materials. http://arxiv.org/abs/cond-mat/0008382  [Google Scholar]] are important for various technological applications. One of the reasons for their technological applications could be based upon the fact that they have a lot of empty space in their molecules as well as in their unit cells when bulk quantities of these are taken in the form of either C₆₀ solid or nanoropes. Their compressibility studies have revealed extremely interesting results showing tremendous reversible compression which has aroused curiosity and interest. CNT have been found to be compressible reversibly up to about 65% of their original volume when subjected to pressures of about 20 kbar. This enormous volume compression in such materials under moderate pressures is conceived to be of great significance for understanding and interpreting the mechanism based on molecular level understanding related to shock compression in these materials.

We undertake a model study accounting for unit cell deformations by applying pressures up to 3 Gpa and develop a pressure compression relation. We use the anharmonicity of the intermolecular potential energy to calculate Gruneisen parameters and the temperature increase due to an adiabatic pressure application. This work uses some components calculated from a rigid molecule model, whereas others are taken from experimental pressure compression data.     

Oviposition and feeding behavior of the maize borer,Chilo partellus,in response to eight essential oil allelochemicals

Eight essential oil compounds were evaluated against the maize borer, Chilo partellus (Swinhoe) (Lepidoptera: Pyralidae), to determine their influence on oviposition and feeding behavior. Thymol was the most active compound against C. partellus when evaluated as an oviposition deterrent (ODI₅₀ = 1.36 mg ml^?1), an ovicide (LC₅₀ = 2.06 mg ml^?1), or a feeding deterrent (FI₅₀ = 141.8 μg cm^?2) in laboratory experiments. The results corroborated with greenhouse experiments, in which egg laying on maize plants was inhibited significantly when the treatment was 15 times the concentration used in the laboratory experiments. However, there was neither any correlation between oviposition deterrence and feeding inhibition, nor between oviposition deterrence and ovicidal action. Apparently, toxicity per se or ovicidal action does not play any role in choice of oviposition in C. partellus. This was more obvious when the efficacy of compounds was compared in greenhouse experiments where ODI values and number of eggs laid on the treated leaves did not differ significantly in choice and no‐choice situations. Apparently, toxicity plays an important role in predicting host plant choice, but behavioral response in terms of oviposition preference is independent of toxic action, particularly for non‐host toxins. Thus, the same compounds affecting oviposition behavior on the one hand and having ovicidal or feeding deterrent properties on the other could be useful in field situations in any area‐wide integrated pest management model.