A new paraclinical CSF marker for hypoxia‐like tissue damage in multiple sclerosis lesions

Recent studies on the immunopathology of multiple sclerosis revealed a heterogeneity in the patterns of demyelination, suggesting interindividual differences in the mechanism responsible for myelin destruction. One of these patterns of demyelination, characterized by oligodendrocyte dystrophy and apoptosis, closely mimics myelin destruction in acute white matter ischaemia. In the course of a systematic screening for virus antigen expression in multiple sclerosis brains, we identified a monoclonal antibody against canine distemper virus, which detects a cross‐reactive endogenous brain epitope, highly expressed in this specific subtype of actively demyelinating multiple sclerosis lesions with little or no immunoreactivity in other active multiple sclerosis cases. The respective epitope, which is a phosphorylation‐dependent sequence of one or more proteins of 50, 70 and 115kDa, is also expressed in a subset of active lesions of different virus‐induced inflammatory brain diseases, but is present most prominently and consistently in acute lesions of white matter ischaemia. Its presence is significantly associated with nuclear expression of hypoxia‐inducible factor‐1α within the lesions of both inflammatory and ischaemic brain diseases. The respective epitope is liberated into the CSF and, thus, may become a useful diagnostic tool to identify clinically a defined multiple sclerosis subtyp

Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases

Background: Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological mechanisms compared to multiple sclerosis. Objective: The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis. Methods: Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays. First, we analysed a panel of 32 cytokines/chemokines in a discovery group (nine aquaporin-4-antibody seropositive, nine myelin oligodendrocyte glycoprotein-antibody seropositive, eight encephalitis, 10 multiple sclerosis). Significantly dysregulated cytokines/chemokines were validated in a second cohort (11 aquaporin-4-antibody seropositive, 18 myelin oligodendrocyte glycoprotein-antibody seropositive, 18 encephalitis, 33 multiple sclerosis). Results: We found 11 significantly altered cytokines/chemokines in cerebrospinal fluid and serum samples in the discovery group (a proliferation-inducing ligand, fractalkine=CX3CL1, growth-regulated oncogene-\u3b1, interleukin-1 receptor antagonist, interleukin-6, interleukin-8=CXCL8, interleukin-10, interleukin-21, interferon-&3-induced protein-10=CXCL10, monokine induced by interferon-&3=CXCL9, macrophage inflammatory protein-1 f=CCL4). Most of these cytokines/chemokines were up-regulated in autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein positive patients compared to multiple sclerosis. We confirmed these results for cerebrospinal fluid interleukin-6 and serum interleukin-8, growth-regulated oncogene-\u3b1, a proliferation-inducing ligand and macrophage inflammatory protein-1\u3b2 in the validation set. Receiver-operating characteristic analysis revealed increased levels of cerebrospinal fluid interleukin-6, serum interleukin-8 and growth-regulated oncogene-\u3b1 in most patients with autoantibody-associated neurological diseases. Conclusion: This study suggests that distinctive cerebrospinal fluid and serum cytokine/chemokine profiles are associated with autoantibody-mediated demyelination, but not with multiple sclerosis

Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen’s occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area

Manual / Issue 7 / Alchemy

Manual, a journal about art and its making. Alchemy. The seventh issue. Manual 7 (Alchemy) prompts the unexpected and emergent to manifest. To engage as an alchemist/artist is to be the perpetual student of the present moment, to synthesize culture, so-called science, and the implications of existential borders into a discipline that is repeatable, a practice. Art and alchemy are not singular, unified pursuits. Their practitioners are trans-disciplinary, disjointed, and solitary in their practice, and their labor and the ordering of their lives become porous, overlaid in the pursuit of other-than or beyond-dominant modes of understanding. Alchemy and art are not about finding resolution, but building the capacity for curiosity, formulating questions that invest fields of knowledge with possibility, prompting the unexpected and emergent to manifest. —Bryan McGovern Wilson, from the introduction to Issue 7: Alchemy Softcover, 76 pages. Published 2016 by the RISD Museum. Manual 7 (Alchemy) contributors include Markus Berger, Rachel Berwick, Stephen S. Bush, CA Conrad, Florence Friedman, Doreen Garner, Michael Grugl, Kate Irvin, Mimi Leveque, Dominic Molon, Douglas R. Nickel, Emily J. Peters, Elizabeth A. Williams, Bryan McGovern Wilson, and Diming Stella Zhong.https://digitalcommons.risd.edu/risdmuseum_journals/1033/thumbnail.jp

First 3D Reconstructions of Coronal Loops with the STEREO A+B Spacecraft: IV. Magnetic Modeling with Twisted Force-Free Fields

The three-dimensional (3D) coordinates of stereoscopically triangulated loops provide strong constraints for magnetic field models of active regions in the solar corona. Here we use STEREO/A and B data from some 500 stereoscopically triangulated loops observed in four active regions (2007 Apr 30, May 9, May 19, Dec 11), together with SOHO/MDI line-of-sight magnetograms. We measure the average misalignment angle between the stereoscopic loops and theoretical magnetic field models, finding a mismatch of $\mu=19^\circ-46^\circ$ for a potential field model, which is reduced to $\mu=14^\circ-19^\circ$ for a non-potential field model parameterized by twist parameters. The residual error is commensurable with stereoscopic measurement errors ($\mu_{SE} \approx 8^\circ-12^\circ$). We developed a potential field code that deconvolves a line-of-sight magnetogram into three magnetic field components $(B_x, B_y, B_z)$, as well as a non-potential field forward-fitting code that determines the full length of twisted loops ($L \approx 50-300$ Mm), the number of twist turns (median $N_{twist}=0.06$), the nonlinear force-free $\alpha$-parameter (median $\alpha \approx 4 \times 10^{-11}$ cm$^{-1}$), and the current density (median $j_z \approx 1500$ Mx cm$^{-2}$ s$^{-1}$). All twisted loops are found to be far below the critical value for kink instability, and Joule dissipation of their currents is found be be far below the coronal heating requirement. The algorithm developed here, based on an analytical solution of nonlinear force-free fields that is accurate to second order (in the force-free parameter $\alpha$), represents the first code that enables fast forward-fitting to photospheric magnetograms and stereoscopically triangulated loops in the solar corona.Comment: The Astrophysical Journal (in press), 37 pages, 14 Figure

Maleimide-functionalised platinum(IV) complexes as synthetic platform for targeted drug delivery

Maleimide-functionalised Pt(IV) complexes with highly selective binding properties to thiol groups were synthesised as precursors for binding of thiol-containing tumour targeting molecules like human serum albumi