Systemic antibody response to Chlamydia Trachomatis infection in patients either infected or reinfected with different Chlamydia serovars

© 2017 Indian Journal of Medical Microbiology | Published by Wolters Kluwer - Medknow. Introduction: Chlamydia trachomatis is the etiological agent for the most prevalent bacterial sexually transmitted infection in both developed and developing countries. The aim of present study was to characterize the antibody response between two groups of individuals, having either a single C. trachomatis infection and or repeated infections. Material and Methods: Current study consisted of two groups, one with an initial Chlamydia infection and a second with repeated infections. A titre based estimation of specific serum (IgG and IgA) levels using ELISA were performed, which further validated by western blot. In vitro neutralizing ability of each patient's serum against both homologous and heterologous strains was also determined. Results: Individuals infected with one of the C. trachomatis serovars D, E or K exhibited a strong systemic antibody response as characterized by ELISA and western blot. These individuals may have developed at least some level of protection as they only represented single infection. By comparison, individuals infected with serovar D, E or F that exhibited low systemic antibody response often presented repeated C. trachomatis infections, suggesting an association with poor immune response. An in vitro neutralizing level of 60-90% was observed in the human sera against homologous serovar D and two heterologous C. trachomatis serovars E and K, compared to <40% against heterologous serovars F. Conclusion: Individuals infected with serovars D and K showed a potential association between circulating antibody response and re-infection risk. While the patients infected with serovars E showed a disconnection between systemic antibody response and re-infection risk

Inhibition of constitutive and cxc-chemokine-induced NF-κB activity potentiates ansamycin-based HSP90-inhibitor cytotoxicity in castrate-resistant prostate cancer cells

Background: We determined how CXC-chemokine signalling and necrosis factor-B (NF-B) activity affected heat-shock protein 90 (Hsp90) inhibitor (geldanamycin (GA) and 17-allylamino-demethoxygeldanamycin (17-AAG)) cytotoxicity in castrate-resistant prostate cancer (CRPC).Methods:Geldanamycin and 17-AAG toxicity, together with the CXCR2 antagonist AZ10397767 or NF-B inhibitor BAY11-7082, was assessed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay in two CRPC lines, DU145 and PC3. Flow cytometry quantified apoptotic or necrosis profiles. Necrosis factor-B activity was determined by luciferase readouts or indirectly by quantitative PCR and ELISA-based determination of CXCL8 expression.Results:Geldanamycin and 17-AAG reduced PC3 and DU145 cell viability, although PC3 cells were less sensitive. Addition of AZ10397767 increased GA (e.g., PC3 IC 20: from 1.670.4 to 0.180.2 nM) and 17-AAG (PC3 IC 20: 43.77.8 to 0.641.8 nM) potency in PC3 but not DU145 cells. Similarly, BAY11-7082 increased the potency of 17-AAG in PC3 but not in DU145 cells, correlating with the elevated constitutive NF-B activity in PC3 cells. AZ10397767 increased 17-AAG-induced apoptosis and necrosis and decreased NF-B activity/CXCL8 expression in 17-AAG-treated PC3 cells.Conclusion:Ansamycin cytotoxicity is enhanced by inhibiting NF-B activity and/or CXC-chemokine signalling in CRPC cells. Detecting and/or inhibiting NF-B activity may aid the selection and treatment response of CRPC patients to Hsp90 inhibitors.</p

Nocturnal blood pressure fall as predictor of diabetic nephropathy in hypertensive patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Hypertensive patients with reduced blood pressure fall (BPF) at night are at higher risk of cardiovascular events (CVE).</p> <p>Methods</p> <p>We evaluated in hypertensive diabetic patients, if a reduced nocturnal BPF can precedes the development of diabetic nephropathy (DN). We followed 70 patients with normal urinary albumin excretion (UAE) for two years. We performed 24-hours ambulatory BP monitoring in baseline and at the end of the study.</p> <p>Results</p> <p>Fourteen (20%) patients (GI) developed DN (N = 11) and/or CVE (n = 4). Compared to the remaining 56 patients (GII) in baseline, GI had similar diurnal systolic (SBP) and diastolic BP (DBP), but higher nocturnal SBP (138 ± 15 vs 129 ± 16 mmHg; p < 0.05) and DBP (83 ± 12 vs 75 ± 11 mmHg; p < 0,05). Basal nocturnal SBP correlated with occurrence of DN and CVE (R = 0.26; P < 0.05) and with UAE at the end of the study (r = 0.3; p < 0.05). Basal BPF (%) correlated with final UAE (r = -0.31; p < 0.05). In patients who developed DN, reductions occurred in nocturnal systolic BPF (12 ± 5 vs 3 ± 6%, p < 0,01) and diastolic BPF (15 ± 8 vs 4 ± 10%, p < 0,01) while no changes were observed in diurnal SBP (153 ± 17 vs 156 ± 16 mmHg, NS) and DBP (91 ± 9 vs 90 ± 7 mmHg, NS). Patients with final UAE < 20 μg/min, had no changes in nocturnal and diurnal BP.</p> <p>Conclusions</p> <p>Our results suggests that elevations in nocturnal BP precedes DN and increases the risk to develop CVE in hypertensive patients with T2DM.</p

Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer

We sought to characterise whether dexamethasone (DEX) may enhance tumour response to docetaxel in in vitro and in vivo models of metastatic prostate cancer (CaP). In vitro experiments conducted on PC3 and human bone marrow endothelial cells (hBMECs) determined that administration of DEX (10 nM) reduced constitutive nuclear factor-κB (NF-κB) activity, decreasing interleukin (IL)-8, CXCL1 and VEGF gene expression in PC3 cells. Dexamethasone also attenuated docetaxel-induced NF-κB and activator protein-1 transcription and reduced docetaxel-promoted expression/secretion of IL-8 and CXCL1 in PC3 and hBMECs. Although DEX failed to enhance docetaxel cytotoxicity on PC3 cells, DEX potentiated the antiangiogenic activity of docetaxel in vitro, further reducing vessel area and vessel length in developing endothelial tubes (P<0.05). Docetaxel had a potent antiangiogenic activity in the dorsal skin flap-implanted PC3 tumours in vivo. Small blood vessel formation was further suppressed in tumours co-treated with docetaxel and DEX, substantiated by an increased average vessel diameter and segment length and a decreased number of branch points in the residual tumour vasculature (P<0.001). Our data show that DEX potentiates the antiangiogenic activity of docetaxel, suggesting a putative mechanism for the palliative and survival benefits of these agents in metastatic CaP

Constitutive and Treatment-Induced CXCL8-Signalling Selectively Modulates the Efficacy of Anti-Metabolite Therapeutics in Metastatic Prostate Cancer

<div><h3>Background</h3><p>The current study was undertaken to characterize the effect of anti-metabolites on inducing CXCL8 signaling and determining whether the constitutive and/or drug-induced CXCL8 signaling in metastatic prostate cancer (CaP) cells modulates their sensitivity to this class of agent.</p> <h3>Methods</h3><p>The response of metastatic CaP cells to 5-Fluorouracil (5-FU), Pemetrexed or Tomudex was determined using cell count assays, flow cytometry and PARP cleavage analysis. Quantitative-PCR, ELISA and immunoblots were employed to determine effects of drugs or CXCL8 administration on target gene/protein expression.</p> <h3>Results</h3><p>Administration of 5-FU but not pemetrexed potentiated CXCL8 secretion and increased CXCR1 and CXCR2 gene expression in metastatic PC3 cells. Consistent with this, the inhibition of CXCL8 signaling using a CXCR2 antagonist, AZ10397767, increased the cytotoxicity of 5-FU by 4-fold (P<0.001), and increased 5-FU-induced apoptosis in PC3 cells (P<0.01). In contrast, while administration of AZ10397767 had no effect on the sensitivity of pemetrexed, the CXCR2 antagonist exerted the greatest effect in increasing the sensitivity of PC3 cells to Tomudex, a directed thymidylate synthase (TS) inhibitor. Subsequent experiments confirmed that administration of recombinant human CXCL8 increased TS expression, a response mediated in part by the CXCR2 receptor. Moreover, siRNA-mediated knockdown of the CXCL8-target gene Bcl-2 increased the sensitivity of PC3 cells to 5-FU.</p> <h3>Conclusions</h3><p>CXCL8 signaling provides a selective resistance of metastatic prostate cancer cells to specific anti-metabolites by promoting a target-associated resistance, in addition to underpinning an evasion of treatment-induced apoptosis.</p> </div

Proliferation of Ty3/gypsy-like retrotransposons in hybrid sunflower taxa inferred from phylogenetic data

<p>Abstract</p> <p>Background</p> <p>Long terminal repeat (LTR) retrotransposons are a class of mobile genetic element capable of autonomous transposition via an RNA intermediate. Their large size and proliferative ability make them important contributors to genome size evolution, especially in plants, where they can reach exceptionally high copy numbers and contribute substantially to variation in genome size even among closely related taxa. Using a phylogenetic approach, we characterize dynamics of proliferation events of <it>Ty3/gypsy</it>-like LTR retrotransposons that led to massive genomic expansion in three <it>Helianthus </it>(sunflower) species of ancient hybrid origin. The three hybrid species are independently derived from the same two parental species, offering a unique opportunity to explore patterns of retrotransposon proliferation in light of reticulate evolutionary events in this species group.</p> <p>Results</p> <p>We demonstrate that <it>Ty3/gypsy</it>-like retrotransposons exist as multiple well supported sublineages in both the parental and hybrid derivative species and that the same element sublineage served as the source lineage of proliferation in each hybrid species' genome. This inference is based on patterns of species-specific element numerical abundance within different phylogenetic sublineages as well as through signals of proliferation events present in the distributions of element divergence values. Employing methods to date paralogous sequences within a genome, proliferation events in the hybrid species' genomes are estimated to have occurred approximately 0.5 to 1 million years ago.</p> <p>Conclusion</p> <p>Proliferation of the same retrotransposon major sublineage in each hybrid species indicates that similar dynamics of element derepression and amplification likely occurred in each hybrid taxon during their formation. Temporal estimates of these proliferation events suggest an earlier origin for these hybrid species than previously supposed.</p

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques