Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis

Objectives. ACPA is a highly specific marker for RA. It was recently reported that ACPA can be used to classify RA into two disease subsets, ACPA-positive and ACPA-negative RA. ACPA-positive RA was found to be associated with the HLA-DR shared epitope (SE), but ACPA negative was not. However, the suspicion remained that this result was caused by the ACPA-negative RA subset containing patients with non-RA diseases. We examined whether this is the case even when possible non-RA ACPA-negative RA patients were excluded by selecting only patients with bone erosion

Genetics of rheumatoid arthritis: what have we learned?

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting 0.5–1% of the population worldwide. The disease has a heterogeneous character, including clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although the pathogenesis of RA is poorly understood, progress has been made in identifying genetic factors that contribute to the disease. The most important genetic risk factor for RA is found in the human leukocyte antigen (HLA) locus. In particular, the HLA molecules carrying the amino acid sequence QKRAA, QRRAA, or RRRAA at positions 70–74 of the DRβ1 chain are associated with the disease. The HLA molecules carrying these “shared epitope” sequences only predispose for ACPA-positive disease. More than two decades after the discovery of HLA-DRB1 as a genetic risk factor, the second genetic risk factor for RA was identified in 2003. The introduction of new techniques, such as methods to perform genome-wide association has led to the identification of more than 20 additional genetic risk factors within the last 4 years, with most of these factors being located near genes implicated in immunological pathways. These findings underscore the role of the immune system in RA pathogenesis and may provide valuable insight into the specific pathways that cause RA

Trafficking mechanisms of synaptogenic cell adhesion molecules

Nearly every aspect of neuronal function, from wiring to information processing, critically depends on the highly polarized architecture of neurons. Establishing and maintaining the distinct molecular composition of axonal and dendritic compartments requires precise control over the trafficking of the proteins that make up these cellular domains. Synaptic cell adhesion molecules (CAMs), membrane proteins with a critical role in the formation, differentiation and plasticity of synapses, require targeting to the correct pre- or postsynaptic compartment for proper functioning of neural circuits. However, the mechanisms that control the polarized trafficking, synaptic targeting, and synaptic abundance of CAMs are poorly understood. Here, we summarize current knowledge about the sequential trafficking events along the secretory pathway that control the polarized surface distribution of synaptic CAMs, and discuss how their synaptic targeting and abundance is additionally influenced by post-secretory determinants. The identification of trafficking-impairing mutations in CAMs associated with various neurodevelopmental disorders underscores the importance of correct protein trafficking for normal brain function.status: publishe

Ruthenium indenylidene complexes bearing bis(N-Alkyl/N’-Mesityl)-sided heterocyclic carbene ligands

We report on the synthesis and characterization of new ruthenium indenylidene complexes bearing two unsymmetrical N-heterocyclic carbene (NHC) ligands denoted as RuCl2(3-phenyl-1-indenylidene)bis(1-mesityl-3-R-4,5-dihydroimidazole-2-ylidene) in which R is methyl 7a and cyclohexyl 7b. Complexes 7a and 7b were analyzed using single-crystal X-ray diffraction analysis, elemental analysis, IR, NMR spectroscopy, and HRMS. The catalytic activities of complexes 7a and 7b were evaluated in olefin metathesis reactions: ring-opening metathesis polymerization (ROMP) of cis,cis-1,5-cyclooctadiene (COD) and ringclosing metathesis (RCM) of diethyl diallyl malonate (DEDAM) as well as in the isomerization of allylic alcohols. Complexes 7a and 7b failed to initiate the reactions at room temperature in all tested reactions, which might be due to the high thermal stability and low degree of lability of the Ru-CNHC bonds. At 80 °C, the complex 7a showed the best performance due to an increased initiation and a decreased steric obstruction towards the incoming substrates

Concurrent adsorption and micro-electrolysis of Cr(VI) by nanoscale zerovalent iron/biochar/Ca-alginate composite

202308 bcchAccepted ManuscriptRGCOthersKey Technology R&D Program of Hubei Province; National Natural Science Foundation of China; Tongji University; Fundamental Research Funds for the Central UniversitiesPublishe

Coordination of a Ru(II)-Complex to a Tetrafunctional P-ligand: a Model for Ru-P Carbosilane dendrimers

Organophosphine-functionalised carbosilane (CS) dendrimers (5, 6) can be synthesised in high yield. Furthermore, new kinds of metallodendrimers (7, 8) are obtained by coordination of a Ru(II) complex, containing the tridentate triamine ligand: 2, 6-bis[(dimethylamino)methyl]pyridine, to these P-functionalised CS-dendrimers