Apolipoprotein E Polymorphism Interacts with Cigarette Smoking in Progression of Multiple Sclerosis

BACKGROUND AND PURPOSE: The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients. METHODS: Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated. RESULTS: There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS (P = 0.033) and MSSS (P = 0.023) in comparison with non-smokers. CONCLUSION: Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.info:eu-repo/semantics/publishedVersio

Hydrodynamic conditions affect the proteomic profile of marine biofilms formed by filamentous cyanobacterium

Proteomic studies on cyanobacterial biofilms can be an effective approach to unravel metabolic pathways involved in biofilm formation and, consequently, obtain more efficient biofouling control strategies. Biofilm development by the filamentous cyanobacterium Toxifilum sp. LEGE 06021 was evaluated on different surfaces, glass and perspex, and at two significant shear rates for marine environments (4 s(-1) and 40 s(-1)). Higher biofilm development was observed at 4 s(-1). Overall, about 1877 proteins were identified, and differences in proteome were more noticeable between hydrodynamic conditions than those found between surfaces. Twenty Differentially Expressed Proteins (DEPs) were found between 4 s(-1) vs. 40 s(-1). On glass, some of these DEPs include phage tail proteins, a carotenoid protein, cyanophynase glutathione-dependent formaldehyde dehydrogenase, and the MoaD/ThiS family protein, while on perspex, DEPs include transketolase, dihydroxy-acid dehydratase, iron ABC transporter substrate-binding protein and protein NusG. This study contributes to developing a standardized protocol for proteomic analysis of filamentous cyanobacterial biofilms. This kind of proteomic analysis can also be useful for different research fields, given the broad spectrum of promising secondary metabolites and added-value compounds produced by cyanobacteria, as well as for the development of new antibiofilm strategies

Evaluation of chemical strategies for improving the stability and oral toxicity of insecticidal peptides

© 2018 by the authors. Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack of stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies to increase the stability and oral potency of the potent insecticidal spider-venom peptide !-HXTX-Hv1a (Hv1a). Selective chemical replacement of disulfide bridges with diselenide bonds and N- to C-terminal cyclization were anticipated to improve Hv1a resistance to proteolytic digestion, and thereby its activity when delivered orally. We found that native Hv1a is orally active in blowflies, but 91-fold less potent than when administered by injection. Introduction of a single diselenide bond had no effect on the susceptibility to scrambling or the oral activity of Hv1a. N- to C-terminal cyclization of the peptide backbone did not significantly improve the potency of Hv1a when injected into blowflies and it led to a significant decrease in oral activity. We show that this is likely due to a dramatically reduced rate of translocation of cyclic Hv1a across the insect midgut, highlighting the importance of testing bioavailability in addition to toxin stability

Relationship Between Non-Hodgkin's Lymphoma and Blood Levels of Epstein-Barr Virus in Children in North-Western Tanzania: A Case Control Study.

Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Measurement of J/ψ production in association with a W ± boson with pp data at 8 TeV

A measurement of the production of a prompt J/ψ meson in association with a W± boson with W± → μν and J/ψ → μ+μ− is presented for J/ψ transverse momenta in the range 8.5–150 GeV and rapidity |yJ/ψ| < 2.1 using ATLAS data recorded in 2012 at the LHC. The data were taken at a proton-proton centre-of-mass energy of s = 8 TeV and correspond to an integrated luminosity of 20.3 fb−1. The ratio of the prompt J/ψ plus W± cross-section to the inclusive W± cross-section is presented as a differential measurement as a function of J/ψ transverse momenta and compared with theoretical predictions using different double-parton-scattering cross-sections. [Figure not available: see fulltext.]

Combination of searches for Higgs boson pairs in pp collisions at s=13TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb−1 of proton–proton collision data at a centre-of-mass energy s=13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the bb¯bb¯, bb¯W+W−, bb¯τ+τ−, W+W−W+W−, bb¯γγ and W+W−γγ final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (κλ) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to −5.0<κλ<12.0 (−5.8<κλ<12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza–Klein Randall–Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model

BMN vacua, superstars and non-abelian T-duality

Acting with non-Abelian T-duality on the $S^3$ inside the $AdS_5$ subspace of $AdS_5\times S^5$ with $N$ units of flux, we generate a new half-BPS solution with $SU(2|4)$ symmetry that belongs to the Lin-Lunin-Maldacena class of geometries. The analysis of the asymptotics, quantised charges and probe branes in this geometry suggests an interpretation as the gravity dual to the Berenstein-Maldacena-Nastase Plane Wave Matrix Model, in a particular vacuum associated to a partition of $N$, in which the multiplicity of each $SU(2)$ irreducible representation is equal to its dimension. This vacuum is interpreted in M-theory in terms of giant gravitons backreacting in the maximally supersymmetric pp-wave geometry. Consistently with this, we show that the non-Abelian T-dual solution exactly agrees with the Penrose limit of the superstar solution in $AdS_7\times S^4$. This suggests an interesting global completion of the non-Abelian T-dual solution in terms of an M5-brane geometry.Comment: 28 pages, discussion in section 5.1 improved, results unchanged, reference added. Matches published versio