Increased serum lysyl oxidase-like 2 levels correlate with the degree of left atrial fibrosis in patients with atrial fibrillation

Atrial fibrillation (AF) progression is generally accompanied by increased atrial fibrosis and atrial structural remodeling. Lysyl oxidase-like 2 (LOXL2) is known to play an important role in many fibrotic conditions, including cardiac fibrosis. The present study aimed to explore the relationship between serum LOXL2 levels and AF. Fifty-four AF patients and 32 control subjects were enrolled in the study. High-density three-dimensional electroanatomic mapping was performed, and mean bipolar voltage was assessed in AF patients. LOXL2 levels were measured by enzyme-linked immunosorbent assay. All patients underwent echocardiography to assess left atrium size and left ventricle function. Serum LOXL2 levels were significantly elevated in AF patients compared with the control group (526.81 ± 316.82 vs 240.94 ± 92.51 pg/ml, P<0.01). In addition, serum LOXL2 level was significantly correlated with the size of the left atrium (LAD) (r2 = 0.38, P<0.01). Furthermore, the serum LOXL2 levels were significantly higher in AF patients with LAD ≥ 40 mm compared with those with LAD < 40 mm (664.34 ± 346.50 vs 354.90 ± 156.23 pg/ml, P<0.01). And the Spearman’s correlation analysis further revealed that the mean bipolar left atrial voltage was inversely correlated with the LOXL2 (r2 = −0.49, P<0.01) in AF patients. Multivariate regression analysis further demonstrated that serum LOXL2 [odds ratio (OR) 1.013, 95% confidence interval (CI) 1.002–1.024, P<0.05] and LAD (OR 1.704, 95% CI 1.131–2.568, P<0.01) were independent predictors of AF. In conclusion, serum LOXL2 levels were significantly elevated and were correlated with the degree of left atrial fibrosis in AF patients

A rare case of schizophrenia coexistence with antiphospholipid syndrome, β-thalassemia, and monoclonal gammopathy of undetermined significance

A patient with schizophrenia who was treated with chlorpromazine developed lupus anticoagulant (LA) and antiphospholipid syndrome (APS). On protein electrophoresis, a monoclonal immunoglobulin A peak was seen in this patient, defining a condition of monoclonal gammopathy of undetermined significance. Additionally, β-thalassemia was diagnosed with the CD41-42 genotype. This condition is extremely rare, particularly in patients with schizophrenia and APS. We present a case of a patient with schizophrenia and secondary APS who had a positive LA, a significantly prolonged activated partial thromboplastin time, endogenous coagulation factor deficiency and inhibitor, no bleeding, and an unexpected finding of β-thalassemia and monoclonal IgA. Following that, a literature review on the disorders was presented

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation

The exocyst/aPKC complex controls the spatiotemporal activation of the kinases JNK and ERK at the leading edge of migrating cells and thereby controls the dynamic behaviour of the adhesion protein paxillin during cell migration

Direct and indirect effects of climate on richness drive the latitudinal diversity gradient in forest trees

Data accessibility statement: Full census data are available upon reasonable request from the ForestGEO data portal, http://ctfs.si.edu/datarequest/ We thank Margie Mayfield, three anonymous reviewers and Jacob Weiner for constructive comments on the manuscript. This study was financially supported by the National Key R&D Program of China (2017YFC0506100), the National Natural Science Foundation of China (31622014 and 31570426), and the Fundamental Research Funds for the Central Universities (17lgzd24) to CC. XW was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB3103). DS was supported by the Czech Science Foundation (grant no. 16-26369S). Yves Rosseel provided us valuable suggestions on using the lavaan package conducting SEM analyses. Funding and citation information for each forest plot is available in the Supplementary Information Text 1.Peer reviewedPostprin

Bioinformatic Analysis and Post-Translational Modification Crosstalk Prediction of Lysine Acetylation

Recent proteomics studies suggest high abundance and a much wider role for lysine acetylation (K-Ac) in cellular functions. Nevertheless, cross influence between K-Ac and other post-translational modifications (PTMs) has not been carefully examined. Here, we used a variety of bioinformatics tools to analyze several available K-Ac datasets. Using gene ontology databases, we demonstrate that K-Ac sites are found in all cellular compartments. KEGG analysis indicates that the K-Ac sites are found on proteins responsible for a diverse and wide array of vital cellular functions. Domain structure prediction shows that K-Ac sites are found throughout a wide variety of protein domains, including those in heat shock proteins and those involved in cell cycle functions and DNA repair. Secondary structure prediction proves that K-Ac sites are preferentially found in ordered structures such as alpha helices and beta sheets. Finally, by mutating K-Ac sites in silico and predicting the effect on nearby phosphorylation sites, we demonstrate that the majority of lysine acetylation sites have the potential to impact protein phosphorylation, methylation, and ubiquitination status. Our work validates earlier smaller-scale studies on the acetylome and demonstrates the importance of PTM crosstalk for regulation of cellular function