Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues

Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide range of human diseases including atherosclerosis and Alzheimer's disease. Efforts to understand the relationships between C. pneumoniae detected in these diseases have been hindered by the availability of sequence data for non-respiratory strains. In this study, we sequenced the whole genomes for C. pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared these to previously published C. pneumoniae genomes. Phylogenetic analyses of these new C. pneumoniae strains indicate two sub-groups within human C. pneumoniae, and suggest that both recombination and mutation events have driven the evolution of human C. pneumoniae. Further fine-detailed analyses of these new C. pneumoniae sequences show several genetically variable loci. This suggests that similar strains of C. pneumoniae are found in the brain, lungs and cardiovascular system and that only minor genetic differences may contribute to the adaptation of particular strains in human disease.

Solute induced liquid crystalline behaviour of a quaternary ammonium salt and its application to structure determination

A new liquid crystalline phase, induced by the addition of small amounts of a non-mesogenic solute (such as dimethyl sulphoxide or methyl iodide) to a quaternary ammonium salt, N-methyl-N,N,N-trioctadecylammonium iodide (MTAI), has been detected by NMR and optical microscopic studies. In some cases, there is a coexistence of nematic and smectic phases. Information on the ordering of the phases in the magnetic field of the spectrometer has been derived from NMR spectra of a dissolved molecule, C-13-enriched methyl iodide. The low order parameter of the pure thermotropic nematic phase of the salt provides first-order spectra of the dissolved oriented molecules. Analyses of spectra of cis,cis-mucononitrile exemplifies the utility of the MTAI nematic phase in the determination of structural parameters of the solute.

Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey

In our earlier study, we have observed that hypokalemia in langur monkeys, following gossypol acetic acid (GAA) treatment (5 mg dose level) when used as an antispermatogenic agent, and potassium salt supplementation partially maintained body potassium level of the animals. The aims of the present investigation was to confirm further occurrence of hypokalemia in the monkey (comparatively at two higher dose levels) and the role of potassium salt in preventing occurrence of gossypol-induced hypokalemia. Highly purified gossypol acetic acid alone at two dose levels (7.5 and 10 mg/animal/day; oral) and in combination with potassium chloride (0.50 and 0.75 mg/animal/day; oral) was given for 180 days. Treatment with gossypol alone as well as with the supplementation of potassium salt resulted in severe oligospermia and azoospermia. Animals receiving gossypol alone showed significant potassium deficiency with signs of fatigue at both dose levels. Enhanced potassium loss through urine was found in potassium-deficient animals, whereas animals receiving gossypol acetic acid plus potassium salt showed normal serum potassium with a less significant increase in urine potassium level during treatment phases. Other parameters of the body remained within normal range except gradual and significant elevation in serum transaminases activity. The animals gradually returned to normalcy following 150 and 180 days of termination of the treatment.

Tip-induced C--H activation and oligomerization of thienoanthracenes

The tip of a scanning tunneling microscope (STM) can be used to dehydrogenate freely-diffusing tetrathienoanthracene (TTA) molecules on Cu(111), trapping the molecules into metal-coordinated oligomeric structures. The process proceeds at bias voltages above ∼3 V and produces organometallic structures identical to those resulting from the thermally-activated cross-coupling of a halogenated analogue. The process appears to be substrate dependent: no oligomerization was observed on Ag(111) or HOPG. This approach demonstrates the possibility of controlled synthesis and nanoscale patterning of 2D oligomer structures on selected surfaces.

N-acetyl cysteine enhances imatinib-induced apoptosis of Bcr-Abl(+) cells by endothelial nitric oxide synthase-mediated production of nitric oxide

Imatinib, a small-molecule inhibitor of the Bcr-Abl kinase, is a successful drug for treating chronic myeloid leukemia (CML). Bcr-Abl kinase stimulates the production of H2O2, which in turn activates Abl kinase. We therefore evaluated whether N-acetyl cysteine (NAC), a ROS scavenger improves imatinib efficacy. Effects of imatinib and NAC either alone or in combination were assessed on Bcr-Abl(+) cells to measure apoptosis. Role of nitric oxide (NO) in NAC-induced enhanced cytotoxicity was assessed using pharmacological inhibitors and siRNAs of nitric oxide synthase isoforms. We report that imatinib-induced apoptosis of imatinib-resistant and imatinib-sensitive Bcr-Abl(+) CML cell lines and primary cells from CML patients is significantly enhanced by co-treatment with NAC compared to imatinib treatment alone. In contrast, another ROS scavenger glutathione reversed imatinib-mediated killing. NAC-mediated enhanced killing correlated with cleavage of caspases, PARP and up-regulation and down regulation of pro- and anti-apoptotic family of proteins, respectively. Co-treatment with NAC leads to enhanced production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS). Involvement of eNOS dependent NO in NAC-mediated enhancement of imatinib-induced cell death was confirmed by nitric oxide synthase (NOS) specific pharmacological inhibitors and siRNAs. Indeed, NO donor sodium nitroprusside (SNP) also enhanced imatinib-mediated apoptosis of Bcr-Abl(+) cells. NAC enhances imatinib-induced apoptosis of Bcr-Abl(+) cells by endothelial nitric oxide synthase-mediated production of nitric oxide.

Field imperfection induced axial secular frequency shifts in nonlinear ion traps

This article develops a simple analytical expression that relates ion axial secular frequency to field aberration in ion trap mass spectrometers. Hexapole and octopole aberrations have been considered in the present computations. The equation of motion of the ions in a pseudopotential well with these superpositions has the form of a Duffing-like equation and a perturbation method has been used to obtain the expression for ion secular frequency as a function of field imperfections. The expression indicates that the frequency shift is sensitive to the sign of the octopole superposition and insensitive to the sign of the hexapole superposition. Further, for weak multipole superposition of the same magnitude, octopole superposition causes a larger frequency shift in comparison to hexapole superposition.

Cyclone-induced mixing does not cool SST in the post-monsoon north Bay of Bengal

High-resolution data from the TRMM satellite shows that sea surface temperature (SST) cools by 3 degrees C under the tracks of pre-monsoon tropical cyclones in the north Indian Ocean. However, even the strongest post-monsoon cyclones do not cool the open north Bay of Bengal. In this region, a shallow layer of freshwater from river runoff and monsoon rain caps a deep warm layer. Therefore, storm-induced mixing is not deep, and it entrains warm subsurface water. It is possible that the hydrography of the post-monsoon north Bay favours intense cyclones.

Analysis of a Genomic DNA Expression Library of Mycobacterium tuberculosis Using Tuberculosis Patient Sera: Evidence for Modulation of Host Immune Response

DNA obtained from a human sputum isolate of Mycobacterium tuberculosis, NTI-64719, which showed extensive dissemination in the guinea pig model resulting in a high score for virulence was used to construct an expression library in the lambda ZAP vector. The size of DNA inserts in the library ranged from 1 to 3 kb, and recombinants represented 60% of the total plaques obtained. When probed with pooled serum from chronically infected tuberculosis patients, the library yielded 176 recombinants with a range of signal intensities. Among these, 93 recombinants were classified into 12 groups on the basis of DNA hybridization experiments, The polypeptides synthesized by the recombinants were predominantly LacZ fusion proteins, Serum obtained from patients who were clinically diagnosed to be in the early phase of M. tuberculosis infection was used to probe the 176 recombinants obtained. interestingly, some recombinants that gave very strong signals in the original screen did not react with early-phase serum; conversely, others whose signals were extremely weak in the original screen gave very intense signals with serum from recently infected patients, This indicates the differential nature of either the expression of these antigens or the immune response elicited by them as a function of disease progression.

Dynamic analysis of small signal voltage instability decoupled from angle instability

This paper presents a methodology for dynamic analysis of short term small signal voltage instability in a multi-machine power system. The formulation of the problem is done by decoupling the angle instability from the voltage instability. The method is based on the incremental reactive current flow network (IRCFN), where the incremental reactive current injection at each bus is related to the incremental voltage magnitude at all the buses. Small signal stability using the eigenvalue analysis is illustrated utilizing a single-machine load bus (SMLB) and three-machine system examples. The role of a static var compensator (SVC) at the load bus is also examined.

Chemotherapy-induced nausea and vomiting: A narrative review to inform dietetics practice

Chemotherapy-induced nausea and vomiting (CINV) are common nutrition-impact symptoms experienced by cancer patients. They exert a detrimental effect on dietary intake, risk of malnutrition and quality of life. While CINV are primarily managed with medication, dietitians play an important role in the management of CINV-related complications such as reduced dietary intake. This review discusses the burden of nausea and vomiting which cancer patients can experience, including its effect on quality of life, nutrition status, and treatment outcomes. Implications for dietetic practice include the need to explore the nature of reported symptoms, identify predisposing risk factors, and to consider the use of a variety of interventions that are individualised to the patient’s symptoms. There are little clinical data regarding effective dietetic interventions for nausea and vomiting. In summary, this review discusses dietetic-related issues surrounding CINV including the pathophysiology, risk factors, prevalence, and both pharmacological and dietetic treatment options.

Stress analysis of carotid atheroma in transient ischemic attack patients: Evidence for extreme stress-induced plaque rupture

Plaque rupture has been considered to be the result of its structural failure. The aim of this study is to suggest a possible link between higher stresses and rupture sites observed from in vivo magnetic resonance imaging (MRI) of transient ischemic attack (TIA) patients, by using stress analysis methods. Three patients, who had recently suffered a TIA, underwent in vivo multi-spectral MR imaging. Based on plaque geometries reconstructed from the post-rupture status, six pre-rupture plaque models were generated for each patient dataset with different reconstructions of rupture sites to bridge the gap of fibrous cap from original MRI images. Stress analysis by fluid structure interaction simulation was performed on the models, followed by analysis of local stress concentration distribution and plaque rupture sites. Furthermore, the sensitivity of stress analysis to the pre-rupture plaque geometry reconstruction was examined. Local stress concentrations were found to be located at the plaque rupture sites for the three subjects studied. In the total of 18 models created, the locations of the stress concentration regions were similar in 17 models in which rupture sites were always associated with high stresses. The local stress concentration region moved from circumferential center to the shoulder region (slightly away from the rupture site) for a case with a thick fibrous cap. Plaque wall stress level in the rupture locations was found to be much higher than the value in non-rupture locations. The good correlation between local stress concentrations and plaque rupture sites, and generally higher plaque wall stress level in rupture locations in the subjects studied could provide indirect evidence for the extreme stress-induced plaque rupture hypothesis. Local stress concentration in the plaque region could be one of the factors contributing to plaque rupture.

Similarities in the Genomic Sequence and Coat Protein-Structure of Plant Viruses

The genomic sequences of several RNA plant viruses including cucumber mosaic virus, brome mosaic virus, alfalfa mosaic virus and tobacco mosaic virus have become available recently. The former two viruses are icosahedral while the latter two are bullet and rod shaped, respectively in particle morphology. The non-structural 3a proteins of cucumber mosaic virus and brome mosaic virus have an amino acid sequence homology of 35% and hence are evolutionarily related. In contrast, the coat proteins exhibit little homology, although the circular dichroism spectrum of these viruses are similar. The non-coding regions of the genome also exhibit variable but extensive homology. Comparison of the brome mosaic virus and alfalfa mosaic virus sequences reveals that they are probably related although with a much larger evolutionary distance. The polypeptide folds of the coat protein of three biologically distinct isometric plant viruses, tomato bushy stunt virus, southern bean mosaic virus and satellite tobacco necrosis virus have been shown to display a striking resemblance. All of them consist of a topologically similar 8-standard β-barrel. The implications of these studies to the understanding of the evolution of plant viruses will be discussed.

Comparative analysis of the uropathogenic Escherichia coli surface proteome by tandem mass-spectrometry of artificially induced outer membrane vesicles

Uropathogenic Escherichia coli (UPEC) are the major cause of urinary tract infections. For successful colonisation of the urinary tract, UPEC employ multiple surface-exposed or secreted virulence factors, including adhesins and iron uptake systems. Whilst individual UPEC strains and their virulence factors have been the focus of extensive research, there have been no outer membrane (OM) proteomic studies based on large clinical UPEC collections, primarily due to limitations of traditional methods. In this study, a high-throughput method based on tandem mass-spectrometry of EDTA heat-induced outer membrane vesicles (OMVs) was developed for the characterisation of the UPEC surface-associated proteome. The method was applied to compare the OM proteome of fifty-four UPEC isolates, resulting in the identification of 8789 proteins, consisting of 619 unique proteins, which were subsequently interrogated for their subcellular origin, prevalence and homology to characterised virulence factors. Multiple distinct virulence-associated proteins were identified, including two novel putative iron uptake proteins, an uncharacterised type of chaperone-usher fimbriae and various highly prevalent hypothetical proteins. Our results give fundamental insight into the physiology of UPEC and provide a framework for understanding the composition of the UPEC OM proteome.

Instability of laminated composite thin-walled open-section beams

Instability of thin-walled open-section laminated composite beams is studied using the finite element method. A two-noded, 8 df per node thin-walled open-section laminated composite beam finite element has been used. The displacements of the element reference axis are expressed in terms of one-dimensional first order Hermite interpolation polynomials, and line member assumptions are invoked in formulation of the elastic stiffness matrix and geometric stiffness matrix. The nonlinear expressions for the strains occurring in thin-walled open-section beams, when subjected to axial, flexural and torsional loads, are incorporated in a general instability analysis. Several problems for which continuum solutions (exact/approximate) are possible have been solved in order to evaluate the performance of finite element. Next its applicability is demonstrated by predicting the buckling loads for the following problems of laminated composites: (i) two layer (45°/−45°) composite Z section cantilever beam and (ii) three layer (0°/45°/0°) composite Z section cantilever beam.

Rank regression for analysis of clustered data: A natural induced smoothing approach

We consider rank regression for clustered data analysis and investigate the induced smoothing method for obtaining the asymptotic covariance matrices of the parameter estimators. We prove that the induced estimating functions are asymptotically unbiased and the resulting estimators are strongly consistent and asymptotically normal. The induced smoothing approach provides an effective way for obtaining asymptotic covariance matrices for between- and within-cluster estimators and for a combined estimator to take account of within-cluster correlations. We also carry out extensive simulation studies to assess the performance of different estimators. The proposed methodology is substantially Much faster in computation and more stable in numerical results than the existing methods. We apply the proposed methodology to a dataset from a randomized clinical trial.