potential biomarkers of haemophilic arthropathy correlations with compatible additive magnetic resonance imaging scores

Introduction: Although biomarkers are useful diagnostic tools to assess joint damage in osteoarthritis and rheumatoid arthritis, few data exist for biomarkers of haemophilic arthropathy. Aim: To evaluate the association between biomarkers and compatible additive magnetic resonance imaging (MRI) scores in patients with severe haemophilia A. Methods: Patients aged 12–35 years with no history of factor VIII (FVIII) inhibitors were enrolled in a controlled, cross-sectional, multinational investigation. Patients received primary or secondary prophylaxis or on-demand treatment with FVIII and underwent MRI on four joints (two ankles, two knees). Soluble biomarkers of cartilage and bone degradation, inflammation, and angiogenesis were assessed (serum levels of C-terminal telopeptides of type I collagen [CTX-I], cartilage oligomeric matrix protein [COMP], chondroitin-sulphate aggrecan turnover 846 epitope [CS846], tissue inhibitor of metalloproteinase 1 [TIMP-1]; plasma levels of vascular endothelial growth factor [VEGF], matrix metalloproteinases 3 and 9 [MMP3, MMP9]). Relationships between biomarkers and MRI scores were evaluated using Spearman rank correlation. Results: Biomarkers were assessed in 117 of 118 per-protocol patients. Mean and median CTX-I, COMP, TIMP-1, MMP3, MMP9, and VEGF values were within normal ranges (reference range not available for CS846 in healthy volunteers). No correlations between biomarkers and MRI scores were found, with the exception of CS846, which showed significant correlation in a subgroup of 22 on-demand patients (r = 0.436; P = 0.04). Conclusions: Compatible additive MRI scores showed no clear correlations with any of the potential biomarkers for haemophilic arthropathy in the overall population. CS846 levels were significantly correlated with MRI scores in patients treated on demand. (Less

Fine Mapping Major Histocompatibility Complex Associations in Psoriasis and Its Clinical Subtypes

Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C*06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 x 10(-364)). Stepwise analysis revealed multiple HLA-C*06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C*12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQ alpha 1 amino acid position 53; p \u3c 5.0 x 10(-8)), but no apparent risk conferred by MICA. We further evaluated risk of two major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (P-omnibus = 2.2 x 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC

Improved bone defect healing by a superagonistic GDF5 variant derived from a patient with multiple synostoses syndrome

Multiple synostoses syndrome 2 (SYNS2) is a rare genetic disease characterized by multiple fusions of the joints of the extremities, like phalangeal joints, carpal and tarsal joints or the knee and elbows. SYNS2 is caused by point mutations in the Growth and Differentiation Factor 5 (GDF5), which plays an essential role during skeletal development and regeneration. We selected one of the SYNS2-causing GDF5 mutations, p.N445T, which is known to destabilize the interaction with the Bone Morphogenetic Protein (BMP) antagonist NOGGIN (NOG), in order to generate the superagonistic GDF5 variant GDF5(N445T). In this study, we tested its capacity to support regeneration in a rat critical-sized defect model in vivo. MicroCT and histological analyses indicate that GDF5(N445T)-treated defects show faster and more efficient healing compared to GDF5 wild type (GDF5(wt))-treated defects. Microarray-based gene expression and quantitative PCR analyses from callus tissue point to a specific acceleration of the early phases of bone healing, comprising the inflammation and chondrogenesis phase. These results support the concept that disease-deduced growth factor variants are promising lead structures for novel therapeutics with improved clinical activities

One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration

Structured hydrogels showing form stability and elastic properties individually tailorable on different length scales are accessible in a one-step process. They support cell adhesion and differentiation and display growing pore size during degradation. In vivo experiments demonstrate their efficacy in biomaterial-induced bone regeneration, not requiring addition of cells or growth factors

Beam-helicity asymmetries for single-hadron production in semi-inclusive deep-inelastic scattering from unpolarized hydrogen and deuterium targets

A measurement of beam-helicity asymmetries for single-hadron production in deep-inelastic scattering is presented. Data from the scattering of 27.6 GeV electrons and positrons off gaseous hydrogen and deuterium targets were collected by the HERMES experiment. The asymmetries are presented separately as a function of the Bjorken scaling variable, the hadron transverse momentum, and the fractional energy for charged pions and kaons as well as for protons and anti-protons. These asymmetries are also presented as a function of the three aforementioned kinematic variables simultaneously

Understanding the proton's spin structure

We discuss the tremendous progress that has been towards an understanding of how the spin of the proton is distributed on its quark and gluon constituents. This is a problem that began in earnest twenty years ago with the discovery of the proton ``spin crisis'' by the European Muon Collaboration. The discoveries prompted by that original work have given us unprecedented insight into the amount of spin carried by polarized gluons and the orbital angular momentum of the quarks.Comment: Review article for J. Phys. G, 1 figure, 22 page

Transverse-target-spin asymmetry in exclusive ω\omega-meson electroproduction

Hard exclusive electroproduction of $\omega$ mesons is studied with the HERMES spectrometer at the DESY laboratory by scattering 27.6 GeV positron and electron beams off a transversely polarized hydrogen target. The amplitudes of five azimuthal modulations of the single-spin asymmetry of the cross section with respect to the transverse proton polarization are measured. They are determined in the entire kinematic region as well as for two bins in photon virtuality and momentum transfer to the nucleon. Also, a separation of asymmetry amplitudes into longitudinal and transverse components is done. These results are compared to a phenomenological model that includes the pion pole contribution. Within this model, the data favor a positive $\pi\omega$ transition form factor.Comment: DESY Report 15-14

Bose-Einstein correlations in hadron-pairs from lepto-production on nuclei ranging from hydrogen to xenon

Bose-Einstein correlations of like-sign charged hadrons produced in deep-inelastic electron and positron scattering are studied in the HERMES experiment using nuclear targets of $^1$H, $^2$H, $^3$He, $^4$He, N, Ne, Kr, and Xe. A Gaussian approach is used to parametrize a two-particle correlation function determined from events with at least two charged hadrons of the same sign charge. This correlation function is compared to two different empirical distributions that do not include the Bose-Einstein correlations. One distribution is derived from unlike-sign hadron pairs, and the second is derived from mixing like-sign pairs from different events. The extraction procedure used simulations incorporating the experimental setup in order to correct the results for spectrometer acceptance effects, and was tested using the distribution of unlike-sign hadron pairs. Clear signals of Bose-Einstein correlations for all target nuclei without a significant variation with the nuclear target mass are found. Also, no evidence for a dependence on the invariant mass W of the photon-nucleon system is found when the results are compared to those of previous experiments