STATISTICAL STUDY OF STRONG AND EXTREME GEOMAGNETIC DISTURBANCES AND SOLAR CYCLE CHARACTERISTICS

We study the relation between strong and extreme geomagnetic storms and solar cycle characteristics. The analysis uses an extensive geomagnetic index AA data set spanning over 150 yr. complemented by the Kakioka magnetometer recordings. We apply Pearson correlation statistics and estimate the significance of the correlation with a bootstrapping technique. We show that the correlation between the storm occurrence and the strength of the solar cycle decreases from a clear positive correlation with increasing storm magnitude toward a negligible relationship. Hence, the quieter Sun can also launch superstorms that may lead to significant societal and economic impact. Our results show that while weaker storms occur most frequently in the declining phase, the stronger storms have the tendency to occur near solar maximum. Our analysis suggests that the most extreme solar eruptions do not have a direct connection between the solar large-scale dynamo-generated magnetic field, but are rather associated with smaller-scale dynamo and resulting turbulent magnetic fields. The phase distributions of sunspots and storms becoming increasingly in phase with increasing storm strength, on the other hand, may indicate that the extreme storms are related to the toroidal component of the solar large-scale field.Peer reviewe

Multiperiodicity, modulations, and flip-flops in variable star light curves III. Carrier fit analysis of LQ Hydrae photometry for 1982-2014

Conclusions. The evolution of the spot distribution of the object is found to be very chaotic, with no clear signs of an azimuthal dynamo wave that would persist over longer timescales, although the short-lived coherent structures occasionally observed do not rotate with the same speed as the mean spot distribution. The most likely explanation of the bimodal period distribution is attributed to the high-and low-latitude spot formation regions confirmed from Doppler imaging and Zeeman Doppler imaging.</p

Joint inflammation related citrullination of functional arginines in extracellular proteins

We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction. Citrullination of integrin ligands was selected for further studies since fibronectin R234 in isoDGR was among the most frequently citrullinated arginines in synovial fluid. Assays with synovial fibroblasts and integrin alpha V beta 3 indicated decreased affinity to the enzymatically citrullinated integrin binding sites. To conclude, our data indicate that in inflamed joints extensive citrullination affects the functional arginine residues in extracellular proteins

Stellar Dynamos in the Transition Regime

| openaire: EC/H2020/730897/EU//HPC-EUROPA3 | openaire: EC/H2020/818665/EU//UniSDynGlobal and semi-global convective dynamo simulations of solar-like stars are known to show a transition from an antisolar (fast poles, slow equator) to solar-like (fast equator, slow poles) differential rotation (DR) for increasing rotation rate. The dynamo solutions in the latter regime can exhibit regular cyclic modes, whereas in the former one, only stationary or temporally irregular solutions have been obtained so far. In this paper we present a semi-global dynamo simulation in the transition region, exhibiting two coexisting dynamo modes, a cyclic and a stationary one, both being dynamically significant. We seek to understand how such a dynamo is driven by analyzing the large-scale flow properties (DR and meridional circulation) together with the turbulent transport coefficients obtained with the test-field method. Neither an ??dynamo wave nor an advection-dominated dynamo are able to explain the cycle period and the propagation direction of the mean magnetic field. Furthermore, we find that the ? effectis comparable or even larger than the ? effect in generating the toroidal magnetic field, and therefore, the dynamo seems to be of ?(2)? or ?(2) type. We further find that the effective large-scale flows are significantly altered by turbulent pumping.Peer reviewe

Leukocyte integrins alpha(L)beta(2), alpha(M)beta(2) and alpha(X)beta(2) as collagen receptors - Receptor activation and recognition of GFOGER motif

Integrins alpha(L)beta(2), alpha(M)beta(2) and alpha(X)beta(2) are expressed on leukocytes. Their primary ligands are counter transmembrane receptors or plasma proteins, such as intercellular cell adhesion molecule-1 (ICAM-1) or components of complement system (iC3b, iC4b), respectively. Function blocking antibodies for these integrins may also reduce cell adhesion to collagens. To make the first systematical comparison of human alpha(L)beta(2), alpha(M)beta(2) and alpha(X)beta(2) as collagen receptors, we produced the corresponding integrin alpha I domains both in wild-type and activated form and measured their binding to collagens I-VI. In the &quot;closed&quot; (wild-type) conformation, the alpha I-L and alpha I-M domains bound with low avidity to their primary ligands, and the interaction with collagens was also very weak. Gain-of-function mutations alpha(L) I306G, alpha(L) K287C/K294C and alpha(M) I316G are considered to mimic &quot;open&quot;, activated alpha I domains. The binding of these activated alpha I domains to the primary ligands was clearly stronger and they also recognized collagens with moderate avidity (K-d &lt; 400 nM). After activation, the alpha I-L domain favored collagen I (K-d approximate to 0 nM) when compared to collagen IV. The integrin alpha I-X domain acted in a very different manner since already in native, wild-type form it bound to collagen IV and iC3b (K-d approximate to 200-400 nM). Antibodies against alpha(X)beta(2) and alpha(M)beta(2) blocked promyelocytic leukemia cell adhesion to the collagenous GFOGER motif, a binding site for the beta(1) integrin containing collagen receptors. In brief, leukocyte beta(2) integrins may act as collagen receptors in a heterodimer specific manner. (C) 2013 Elsevier Ltd. All rights reserved.</p

Structure of Collagen Receptor Integrin alpha I-1 Domain Carrying the Activating Mutation E317A

We have analyzed the structure and function of the integrin alpha I-1 domain harboring a gain-of-function mutation E317A. To promote protein crystallization, a double variant with an additional C139S mutation was used. In cell adhesion assays, the E317A mutation promoted binding to collagen. Similarly, the double mutation C139S/E317A increased adhesion compared with C139S alone. Furthermore, soluble alpha I-1 C139S/E317A was a higher avidity collagen binder than alpha I-1 C139S, indicating that the double variant represents an activated form. The crystal structure of the activated variant of alpha I-1 was solved at 1.9 angstrom resolution. The E317A mutation results in the unwinding of the alpha C helix, but the metal ion has moved toward loop 1, instead of loop 2 in the open alpha I-2. Furthermore, unlike in the closed alpha I domains, the metal ion is pentacoordinated and, thus, prepared for ligand binding. Helix 7, which has moved downward in the open alpha I-2 structure, has not changed its position in the activated alpha I-1 variant. During the integrin activation, Glu(335) on helix 7 binds to the metal ion at the metal ion-dependent adhesion site (MIDAS) of the beta(1) subunit. Interestingly, in our cell adhesion assays E317A could activate collagen binding even after mutating Glu(335). This indicates that the stabilization of helix 7 into its downward position is not required if the alpha(1) MIDAS is already open. To conclude, the activated alpha I-1 domain represents a novel conformation of the alpha I domain, mimicking the structural state where the Arg(287)-Glu(317) ion pair has just broken during the integrin activation

Effects of conformational activation of integrin alpha 1I and alpha 2I domains on selective recognition of laminin and collagen subtypes. – Integrin alpha I domain activation

Collagen receptor integrins alpha 1 beta 1 and alpha 2 beta 1 can selectively recognize different collagen subtypes. Here we show that their alpha I domains can discriminate between laminin isoforms as well: alpha 1I and alpha 2I recognized laminin-111, -211 and -511, whereas their binding to laminin-411 was negligible. Residue Arg-218 in alpha1 was found to be instrumental in high-avidity binding. The gain-of-function mutation E318W makes the alpha 2I domain to adopt the "open" high-affinity conformation, while the wild-type alpha 2I domain favors the "closed" low-affinity conformation. The E318W mutation markedly increased alpha 2I domain binding to the laminins (-111, -211 and -511), leading us to propose that the activation state of the alpha 2 beta 1 integrin defines its role as a laminin receptor. However, neither wild-type nor alpha 2IE318W domain could bind to laminin-411. alpha 2IE318W also bound tighter to all collagens than alpha 2I wild-type, but it showed reduced ability to discriminate between collagens I, IV and IX. The corresponding mutation, E317A, in the alpha 1I domain transformed the domain into a high-avidity binder of collagens I and IV. Thus, our results indicate that conformational activation of integrin alpha 1I and alpha 2I domains leads to high-avidity binding to otherwise disfavored collagen subtypes

Integrin alpha 11 beta 1 is a receptor for collagen XIII

Collagen XIII is a conserved transmembrane collagen mainly expressed in mesenchymal tissues. Previously, we have shown that collagen XIII modulates tissue development and homeostasis. Integrins are a family of receptors that mediate signals from the environment into the cells and vice versa. Integrin alpha 11 beta 1 is a collagen receptor known to recognize the GFOGER (O=hydroxyproline) sequence in collagens. Interestingly, collagen XIII and integrin alpha 11 beta 1 both have a role in the regulation of bone homeostasis. To study whether alpha 11 beta 1 is a receptor for collagen XIII, we utilized C2C12 cells transfected to express alpha 11 beta 1 as their only collagen receptor. The interaction between collagen XIII and integrin alpha 11 beta 1 was also confirmed by surface plasmon resonance and pull-down assays. We discovered that integrin alpha 11 beta 1 mediates cell adhesion to two collagenous motifs, namely GPKGER and GF(S)QGEK, that were shown to act as the recognition sites for the integrin alpha 11-I domain. Furthermore, we studied the in vivo significance of the alpha 11 beta 1-collagen XIII interaction by crossbreeding alpha 11 null mice (Itga11(-/-)) with mice overexpressing Col13a1 (Col13a1(oe)). When we evaluated the bone morphology by microcomputed tomography, Col13a1(oe) mice had a drastic bone overgrowth followed by severe osteoporosis, whereas the double mutant mouse line showed a much milder bone phenotype. To conclude, our data identifies integrin alpha 11 beta 1 as a new collagen XIII receptor and demonstrates that this ligand-receptor pair has a role in the maintenance of bone homeostasis