Vitamin D and Disease Severity in Multiple Sclerosis-Baseline Data From the Randomized Controlled Trial (EVIDIMS)

Objective: To investigate the associations between hypovitaminosis D and disease activity in a cohort of relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) patients. Methods: In 51 RRMS and 2 CIS patients on stable interferon-β-1b (IFN-β-1b) treatment recruited to the EVIDIMS study (Efficacy of Vitamin D Supplementation in Multiple Sclerosis (NCT01440062) baseline serum vitamin D levels were evaluated. Patients were dichotomized based on the definition of vitamin D deficiency which is reflected by a < 30 vs. ≥ 30 ng/ml level of 25-hydroxyvitamin D (25(OH)D). Possible associations between vitamin D deficiency and both clinical and MRI features of the disease were analyzed. Results: Median (25, 75% quartiles, Q) 25(OH)D level was 18 ng/ml (12, 24). Forty eight out of 53 (91%) patients had 25(OH)D levels < 30 ng/ml (p < 0.001). Patients with 25(OH)D ≥ 30 ng/ml had lower median (25, 75% Q) T2-weighted lesion counts [25 (24, 33)] compared to patients with 25(OH)D < 30 ng/ml [60 (36, 84), p = 0.03; adjusted for age, gender and disease duration: p < 0.001]. Expanded disability status scale (EDSS) score was negatively associated with serum 25(OH)D levels in a multiple linear regression, including age, sex, and disease duration (adjusted: p < 0.001). Interpretation: Most patients recruited in the EVIDIMS study were vitamin D deficient. Higher 25(OH)D levels were associated with reduced T2 weighted lesion count and lower EDSS scores

RAB family gene expression in breast cancer cells under influence of paclitaxel

The aim of this study was to investigate the role of paclitaxel on RAB family of genes in primary breast cancer cell lines. The cancer breast cells obtained from 40 women during mastectomy were used to address this issue. The group included patients with intraductal breast cancer - lesions in I or II advancement level by TNM classification and G1-G2 by Bloom classification. (tumor dimensions up to 2.0 cm without metastases to lymph nodes). Cytostatic drugs before surgery were not administered to these patients. The cultures were conducted in 25 cm^2^ plastic containers at RPMI medium with addiction of 10% fetal bovine serum (FBS) at the standard conditions. After reaching concentration levels of 10 000/ml of the cells, the cultures were treated with 60 ng/ml and 300 ng/ml doses of paclitaxel. The concentrations were calculated in relation to therapeutic doses of paclitaxel, applied in polytherapy in patients with breast cancer. The cell cultures untreated for cytostatic were used as a control group. Analysis was conducted for RAB family of genes: RAB3D, RAB5B, RAB5C, RAB7, RAB7L1, RAB9P1, RAB10. RAB11A, RAB311B, RAB13, RAB18, RAB22A, RAB23, RAB26, RAB27A, RAB27B, RAB28, RAB30, RAB31, RAB33A, RAB3D6, RAB 38, RABL2B Total RNA was extracted from the harvest control group and the treated cells, and this was followed by cDNA synthesis, which was used for hybridization assays using arrays. A lower dose of paclitaxel (60 ng/ml) treatment resulted in an increase (2-4 fold- statistically significant), whereas a higher dose (300 ng/ml) caused a decrease (2-fold - statistically insignificant) in expression of examined oncogenes, compared to that of the control group.In summary, this data indicates that 60 ng/ml paclitaxel dose induced the RAB gene expression in an up-regulated pathway. A higher concentration of cytostatic (300 ng/ml) is a toxic dose for primary breast cells in vitro

BMP2 and TGF-β Cooperate Differently during Synovial-Derived Stem-Cell Chondrogenesis in a Dexamethasone-Dependent Manner

Recent studies highlighting mesenchymal stem cell (MSC) epigenetic memory suggest that a different differentiation medium may be required depending on the tissue of origin. As synovial-derived stem cells (SDSCs) attract interest we aimed to investigate the influence of TGF-β1, BMP-2 and dexamethasone on SDSC chondrogenesis in vitro. We demonstrate that dexamethasone-free medium led to enhanced chondrogenic differentiation at both the mRNA and matrix level. The greatest COL2A1/COL10A1 ratio was detected in cells exposed to a combination medium containing 10 ng/mL BMP-2 and 1 ng/mL TGF-β1 in the absence of dexamethasone, and this was reflected in the total amount of glycosaminoglycans produced. In summary, dexamethasone-free medium containing BMP-2 and TGF-β1 may be the most suitable when using SDSCs for cartilage tissue regeneration

IL-13R alpha 2 reverses the effects of IL-13 and IL-4 on bronchial reactivity and acetylcholine-induced Ca2+ signaling

Background: The interleukins IL-4 and IL-13 play a key role in the pathophysiology of asthma. The interleukin receptor IL-13R alpha 2 is believed to act as a decoy receptor, but until now, the functional significance of IL-13R alpha 2 remains vague. Methods: Bronchial reactivity was quantified in murine lung slices by digital video microscopy and acetylcholine (ACH)-induced Ca2+ signaling was measured in human airway smooth muscle cells (ASMC) using fluorescence microscopy. Results: IL-4 or IL-13 up to 50 ng/ml induced bronchial hyperreactivity. But after incubation with 100 ng/ml this effect was lost and bronchial responsiveness was again comparable to the control level. The effects of IL-4 and IL-13 on bronchial reactivity were paralleled by the effects on ASMC proliferation. Fifty nanograms per milliliter of IL-4 and IL-13 increased the Ca2+ response of human ASMC to ACH. At 100 ng/ml, however, the effects of the cytokines on the Ca2+ response were no longer evident. The expression of IL-13R alpha 2 increased with increasing concentrations of IL-4 or IL-13, reaching its maximum at 100 ng/ml. Blocking IL-13R alpha 2, the loss of the effect of IL-4 and IL-13 at 100 ng/ml on human ASMC proliferation and the ACH-induced Ca2+ response were no longer present. Conclusions: IL-4 and IL-13 induce bronchial hyperreactivity by changing the Ca2+ homeostasis of ASMC. These effects are counteracted by IL-13R alpha 2. The biological significance of IL-13R alpha 2 might be a protective function by regulating IL-13- and IL-4-mediated signal transduction and thereby limiting pathological alterations in Th2-mediated inflammatory diseases. Copyright (c) 2007 S. Karger AG, Basel

New limits on extragalactic magnetic fields from rotation measures

We take advantage of the wealth of rotation measures data contained in the NRAO VLA Sky Survey catalogue to derive new, statistically robust, upper limits on the strength of extragalactic magnetic fields. We simulate the extragalactic magnetic field contribution to the rotation measures for a given field strength and correlation length, by assuming that the electron density follows the distribution of Lyman-$\alpha$ clouds. Based on the observation that rotation measures from distant radio sources do not exhibit any trend with redshift, while the extragalactic contribution instead grows with distance, we constrain fields with Jeans' length coherence length to be below 1.7~nG at the $2\sigma$ level, and fields coherent across the entire observable Universe below 0.65~nG. These limits do not depend on the particular origin of these cosmological fields.Comment: 5 pages, 3 figures -- v2 to match PRL versio

Multi-gluon helicity amplitudes with one off-shell leg within high energy factorization

Basing on the Slavnov-Taylor identities, we derive a new prescription to obtain gauge invariant tree-level scattering amplitudes for the process g*g->Ng within high energy factorization. Using the helicity method, we check the formalism up to several final state gluons, and we present analytical formulas for the the helicity amplitudes for N=2. We also compare the method with Lipatov's effective action approach.Comment: 25 pages, quite a few figures, an appendix added, typos correcte

Probability of Color Rearrangement at Partonic Level in Hadronic W^+W^- Decays

A strict method to calculate the color rearrangement probability at partonic level in hadronic $W^+W^-$ decays is proposed. The color effective Hamiltonian $H_c$ is constructed from invariant amplitude for the process $e^+e^- \to W^+W^- \to q_1\bar{q}_2 q_3\bar{q}_4+ng$ (n=0, 1, 2, ...) and is used to calculate the cross sections of various color singlets and the color rearrangement probability. The true meaning of the color rearrangement is clarified and its difference from color interference is discussed.Comment: 16 pages, Late

Constraints on Primordial Magnetic Fields from Planck combined with the South Pole Telescope CMB B-mode polarization measurements

A primordial magnetic field (PMF) present before recombination can leave specific signatures on the cosmic microwave background (CMB) fluctuations. Of particular importance is its contribution to the B-mode polarization power spectrum. Indeed, vortical modes sourced by the PMF can dominate the B-mode power spectrum on small scales, as they survive damping up to a small fraction of the Silk length. Therefore, measurements of the B-mode polarization at high-$\ell$ , such as the one recently performed by the South Pole Telescope (SPT), have the potential to provide stringent constraints on the PMF. We use the publicly released SPT B-mode polarization spectrum, along with the temperature and polarization data from the Planck satellite, to derive constraints on the magnitude, the spectral index and the energy scale at which the PMF was generated. We find that, while Planck data constrains the magnetic amplitude to $B_{1 \, \text{Mpc}} < 3.3$ nG at 95\% confidence level (CL), the SPT measurement improves the constraint to $B_{1 \, \text{Mpc}} < 1.5$ nG. The magnetic spectral index, $n_B$, and the time of the generation of the PMF are unconstrained. For a nearly scale-invariant PMF, predicted by simplest inflationary magnetogenesis models, the bound from Planck+SPT is $B_{1 \, \text{Mpc}} < 1.2$ nG at 95% CL. For PMF with $n_B=2$, expected for fields generated in post-inflationary phase transitions, the 95% CL bound is $B_{1 \, \text{Mpc}} < 0.002$ nG, corresponding to the magnetic fraction of the radiation density $\Omega_{B\gamma} < 10^{-3}$ or the effective field $B_{\rm eff} < 100$ nG. The patches for the Boltzmann code CAMB and the Markov Chain Monte Carlo engine CosmoMC, incorporating the PMF effects on CMB, are made publicly available.Comment: 12 pages, 9 figures, 4 table