High frequency of SEN virus infection in thalassemic patients and healthy blood donors in Iran

<p>Abstract</p> <p>Background</p> <p>SEN virus is a blood-borne, circular ssDNA virus and possessing nine genotypes (A to I). Among nine genotypes, SENV-D and SENV-H genotypes have the strong link with patients with unknown (none-A to E) hepatitis infections. Infection with blood-borne viruses is the second important cause of death in thalassemic patients. The aim of this study was to determine the frequency of SENV-D and SENV-H genotypes viremia by performing nested-PCR in 120 and 100 sera from healthy blood donors and thalassemic patients in Guilan Province, North of Iran respectively. Also, to explicate a possible role of SEN virus in liver disease and established changes in blood factors, the serum aminotransferases (ALT and AST) and some of the blood factors were measured.</p> <p>Results</p> <p>Frequency of SENV-D, SENV (SENV-H or SENV-D) and co-infection (both SENV-D and SENV-H) viremia was significantly higher among thalassemic patients than healthy individuals. Frequency of SENV-H viremia was significantly higher than SENV-D among healthy individuals. In comparison to SENV-D negative patients, the mean of mean corpuscular hemoglobin was significantly higher in SENV-D positive and co-infection cases (<it>P </it>< 0.05). The means of AST and ALT were significantly higher in thalassemic patients than healthy blood donors, but there were not any significant differences in the means of the liver levels between SENV-positive and -negative individuals in healthy blood donors and thalassemic patients. High nucleotide homology observed among PCR amplicon's sequences in healthy blood donors and thalassemic patients.</p> <p>Conclusions</p> <p>The high rate of co-infection shows that different genotypes of SENV have no negative effects on each other. The high frequency of SENV infection among thalassemic patients suggests blood transfusion as main route of transmission. High frequency of SENV infection in healthy individuals indicates that other routes rather than blood transfusion also are important. Frequency of 90.8% of SENV infection among healthy blood donors as well as high nucleotide homology of sequenced amplicons between two groups can probably suggest that healthy blood donors infected by SENV act partly as a source of SENV transmission to the thalassemic patients. In conclusion, SENV-D isolate in Guilan Province may be having a pathogenic agent for thalassemic patients.</p

Z' signals in polarised top-antitop final states

We study the sensitivity of top-antitop samples produced at all energy stages of the Large Hadron Collider (LHC) to the nature of an underlying Z' boson, in presence of full tree level standard model (SM) background effects and relative interferences. We concentrate on differential mass spectra as well as both spatial and spin asymmetries thereby demonstrating that exploiting combinations of these observables will enable one to distinguish between sequential Z's and those pertaining to Left-Right symmetric models as well as E6 inspired ones, assuming realistic final state reconstruction efficiencies and error estimates.Comment: 21 pages, 6 colour figures, 10 table

Dynamical Patterns of Cattle Trade Movements

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions

Dynamical Patterns of Cattle Trade Movements

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions

Viability testing of material derived from Mycobacterium tuberculosis prior to removal from a Containment Level-III Laboratory as part of a Laboratory Risk Assessment Program

BACKGROUND: In the field of clinical mycobacteriology, Mycobacterium tuberculosis (MTB) can be a difficult organism to manipulate due to the restrictive environment of a containment level 3 (CL3) laboratory. Tests for rapid diagnostic work involving smears and molecular methods do not require CL3 practices after the organism has been rendered non-viable. While it has been assumed that after organism deactivation these techniques can be performed outside of a CL3, no conclusive study has consistently confirmed that the organisms are noninfectious after the theoretical 'deactivation' steps. Previous studies have shown that initial steps (such as heating /chemical fixation) may not consistently kill MTB organisms. METHODS: An inclusive viability study (n = 226) was undertaken to determine at which point handling of culture extraction materials does not necessitate a CL3 environment. Four different laboratory protocols tested for viability included: standard DNA extractions for IS6110 fingerprinting, crude DNA preparations for PCR by boiling and mechanical lysis, protein extractions, and smear preparations. For each protocol, laboratory staff planted a proportion of the resulting material to Bactec 12B medium that was observed for growth for 8 weeks. RESULTS: Of the 208 isolates initially tested, 21 samples grew within the 8-week period. Sixteen (7.7%) of these yielded positive results for MTB that included samples of: deactivated culture resuspensions exposed to 80°C for 20 minutes, smear preparations and protein extractions. Test procedures were consequently modified and tested again (n = 18), resulting in 0% viability. CONCLUSIONS: This study demonstrates that it cannot be assumed that conventional practices (i.e. smear preparation) or extraction techniques render the organism non-viable. All methodologies, new and existing, should be examined by individual laboratories to validate the safe removal of material derived from MTB to the outside of a CL3 laboratory. This process is vital to establish in house biosafety-validated practices with the aim of protecting laboratory workers conducting these procedures

Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies

γ-H2AX Kinetics as a Novel Approach to High Content Screening for Small Molecule Radiosensitizers

Persistence of γ-H2AX after ionizing radiation (IR) or drug therapy is a robust reporter of unrepaired DNA double strand breaks in treated cells.DU-145 prostate cancer cells were treated with a chemical library ±IR and assayed for persistence of γ-H2AX using an automated 96-well immunocytochemistry assay at 4 hours after treatment. Hits that resulted in persistence of γ-H2AX foci were tested for effects on cell survival. The molecular targets of hits were validated by molecular, genetic and biochemical assays and in vivo activity was tested in a validated Drosophila cancer model.We identified 2 compounds, MS0019266 and MS0017509, which markedly increased persistence of γ-H2AX, apoptosis and radiosensitization in DU-145 cells. Chemical evaluation demonstrated that both compounds exhibited structurally similar and biochemical assays confirmed that these compounds inhibit ribonucleotide reductase. DNA microarray analysis and immunoblotting demonstrates that MS0019266 significantly decreased polo-like kinase 1 gene and protein expression. MS0019266 demonstrated in vivo antitumor activity without significant whole organism toxicity.MS0019266 and MS0017509 are promising compounds that may be candidates for further development as radiosensitizing compounds as inhibitors of ribonucleotide reductase

Higher Infection of Dengue Virus Serotype 2 in Human Monocytes of Patients with G6PD Deficiency

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency is high in Asia. An ex vivo study was conducted to elucidate the association of G6PD deficiency and dengue virus (DENV) infection when many Asian countries are hyper-endemic. Human monocytes from peripheral mononuclear cells collected from 12 G6PD-deficient patients and 24 age-matched controls were infected with one of two DENV serotype 2 (DENV-2) strains–the New Guinea C strain (from a case of dengue fever) or the 16681 strain (from a case of dengue hemorrhagic fever) with a multiplicity of infection of 0.1. The infectivity of DENV-2 in human monocytes was analyzed by flow cytometry. Experimental results indicated that the monocytes of G6PD-deficient patients exhibited a greater levels of infection with DENV-2 New Guinea C strain than did those in healthy controls [mean±SD:33.6%±3.5 (27.2%∼39.2%) vs 20.3%±6.2 (8.0%∼30.4%), P<0.01]. Similar observations were made of infection with the DENV-2 16681 strain [40.9%±3.9 (35.1%∼48.9%) vs 27.4%±7.1 (12.3%∼37.1%), P<0.01]. To our knowledge, this study demonstrates for the first time higher infection of human monocytes in G6PD patients with the dengue virus, which may be important in increasing epidemiological transmission and perhaps with the potential to develop more severe cases pathogenically

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page