Multidecadal Signal of Solar Variability in the Upper Troposphere During the 20th Century

Studies based on data from the past 25-45 years show that irradiance changes related to the 11-yr solar cycle affect the circulation of the upper troposphere in the subtropics and midlatitudes. The signal has been interpreted as a northward displacement of the subtropical jet and the Ferrel cell with increasing solar irradiance. In model studies on the 11-yr solar signal this could be related to a weakening and at the same time broadening of the Hadley circulation initiated by stratospheric ozone anomalies. Other studies, focusing on the direct thermal effect at the Earth's surface on multidecadal scales, suggest a strengthening of the Hadley circulation induced by an increased equator-to-pole temperature gradient. In this paper we analyse the solar signal in the upper troposphere since 1922, using statistical reconstructions based on historical upper-air data. This allows us to address the multidecadal variability of solar irradiance, which was supposedly large in the first part of the 20th century. Using a simple regression model we find a consistent signal on the 11-yr time scale which fits well with studies based on later data. We also find a significant multidecadal signal that is similar to the 11-yr signal, but somewhat stronger. We interpret this signal as a poleward shift of the subtropical jet and the Ferrel cell. Comparing the magnitude of the two signals could provide important information on the feedback mechanisms involved in the solar climate relationship with respect to the Hadley and Ferrel circulations. However, in view of the uncertainty in the solar irradiance reconstructions, such interpretations are not currently possibl

Pathogenicity of proteinase 3-anti-neutrophil cytoplasmic antibody in granulomatosis with polyangiitis: Implications as biomarker and future therapies

Granulomatosis with polyangiitis (GPA) is a rare but serious necrotizing auto-immune vasculitis. GPA is mostly associated with the presence of Anti-Neutrophil Cytoplasmic Antibody (ANCA) targeting proteinase 3 (PR3-ANCA), a serine protease contained in neutrophil granules but also exposed at the membrane. PR3-ANCAs have a proven fundamental role in GPA: they bind neutrophils allowing their auto-immune activation responsible for vasculitis lesions. PR3-ANCAs bind neutrophil surface on the one hand by their Fab binding PR3 and on the other by their Fc binding Fc gamma receptors. Despite current therapies, GPA is still a serious disease with an important mortality and a high risk of relapse. Furthermore, although PR3-ANCAs are a consistent biomarker for GPA diagnosis, relapse management currently based on their level is inconsistent. Indeed, PR3-ANCA level is not correlated with disease activity in 25% of patients suggesting that not all PR3-ANCAs are pathogenic. Therefore, the development of new biomarkers to evaluate disease activity and predict relapse and new therapies is necessary. Understanding factors influencing PR3-ANCA pathogenicity, i.e. their potential to induce auto-immune activation of neutrophils, offers interesting perspectives in order to improve GPA management. Most relevant factors influencing PR3-ANCA pathogenicity are involved in their interaction with neutrophils: level of PR3 autoantigen at neutrophil surface, epitope of PR3 recognized by PR3-ANCA, isotype and glycosylation of PR3-ANCA. We detailed in this review the advances in understanding these factors influencing PR3-ANCA pathogenicity in order to use them as biomarkers and develop new therapies in GPA as part of a personalized approach

First steps towards a stable neon compound: observation and bonding analysis of [B 12 (CN) 11 Ne] −

Noble gas (Ng) containing molecular anions are much scarcer than Ng containing cations. No neon containing anion has been reported so far. Here, the experimental observation of the molecular anion [B12(CN)11Ne]− and a theoretical analysis of the boron–neon bond is reported

Features of MOG required for recognition by patients with MOG antibody-associated disorders

Antibodies to myelin oligodendrocyte glycoprotein (MOG-Abs) define a distinct disease entity. Here we aimed to understand essential structural features of MOG required for recognition by autoantibodies from patients. We produced the N-terminal part of MOG in a conformationally correct form; this domain was insufficient to identify patients with MOG-Abs by ELISA even after site-directed binding. This was neither due to a lack of lipid embedding nor to a missing putative epitope at the C-terminus, which we confirmed to be an intracellular domain. When MOG was displayed on transfected cells, patients with MOG-Abs recognized full-length MOG much better than its N-terminal part with the first hydrophobic domain (P < 0.0001). Even antibodies affinity-purified with the extracellular part of MOG recognized full-length MOG better than the extracellular part of MOG after transfection. The second hydrophobic domain of MOG enhanced the recognition of the extracellular part of MOG by antibodies from patients as seen with truncated variants of MOG. We confirmed the pivotal role of the second hydrophobic domain by fusing the intracellular part of MOG from the evolutionary distant opossum to the human extracellular part; the chimeric construct restored the antibody binding completely. Further, we found that in contrast to 8-18C5, MOG-Abs from patients bound preferentially as F(ab')(2) rather than Fab. It was previously found that bivalent binding of human IgG1, the prominent isotype of MOG-Abs, requires that its target antigen is displayed at a distance of 13-16 nm. We found that, upon transfection, molecules of MOG did not interact so closely to induce a Forster resonance energy transfer signal, indicating that they are more than 6 nm apart. We propose that the intracellular part of MOG holds the monomers apart at a suitable distance for bivalent binding; this could explain why a cell-based assay is needed to identify MOG-Abs. Our finding that MOG-Abs from most patients require bivalent binding has implications for understanding the pathogenesis of MOG-Ab associated disorders. Since bivalently bound antibodies have been reported to only poorly bind C1q, we speculate that the pathogenicity of MOG-Abs is mostly mediated by other mechanisms than complement activation. Therefore, therapeutic inhibition of complement activation should be less efficient in MOG-Ab associated disorders than in patients with antibodies to aquaporin-4

Kinstate intervention in ethnic conflicts : Albania and Turkey compared

Albania and Turkey did not act in overtly irredentist ways towards their ethnic brethren in neighboring states after the end of communism. Why, nonetheless, did Albania facilitate the increase of ethnic conflict in Kosovo and Macedonia, while Turkey did not, with respect to the Turks of Bulgaria? I argue that kin-states undergoing transition are more prone to intervene in external conflicts than states that are not, regardless of the salience of minority demands in the host-state. The transition weakens the institutions of the kin-state. Experiencing limited institutional constraints, self-seeking state officials create alliances with secessionist and autonomist movements across borders alongside their own ideological, clan-based and particularistic interests. Such alliances are often utilized to advance radical domestic agendas. Unlike in Albania's transition environment, in Turkey there were no emerging elites that could potentially form alliances and use external movements to legitimize their own domestic existence or claims

Исследование кинетики процесса полимеризации 5-норборнен-2,3дикарбоксимид-n-метил ацетата

Previous family studies revealed a large number of calpain 3 (CAPN3) mutations that cause recessive forms of limb girdle muscular dystrophy (LGMD2A) with selective atrophy of the proximal limb muscles. Correlations between the nature and site of a particular mutation and its corresponding phenotype, however, can only be established from homozygous mutations, which are particularly rare in the alternatively spliced NS, IS1 and IS2 regions of CAPN3. Here we identified a sibling pair with LGMD2A-type muscular dystrophy caused by a homozygous Ser606Leu (S606L) substitution in the IS2 linker domain. Normal protein levels, unaltered myofibrillar targeting and conserved calcium-induced autocatalytic activity of the mutated protein could be demonstrated in muscle biopsies from one patient. Despite this inconspicuous modification of the IS2 linker between domains III and IV, both patients developed signs and symptoms of the disease within their second decade of life. The unexpected severity of the clinical manifestation points to the high relevance of the calpain 3-specific IS2 segment between domains III and IV. We conclude that the structural motif around the Ser606 residue represents an important functional site that may regulate the transient activation and limited proteolysis of calpain 3