LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation.

During autophagy, actin filament networks move and remodel cellular membranes to form autophagosomes that enclose and metabolize cytoplasmic contents. Two actin regulators, WHAMM and JMY, participate in autophagosome formation, but the signals linking autophagy to actin assembly are poorly understood. We show that, in nonstarved cells, cytoplasmic JMY colocalizes with STRAP, a regulator of JMY's nuclear functions, on nonmotile vesicles with no associated actin networks. Upon starvation, JMY shifts to motile, LC3-containing membranes that move on actin comet tails. LC3 enhances JMY's de novo actin nucleation activity via a cryptic actin-binding sequence near JMY's N terminus, and STRAP inhibits JMY's ability to nucleate actin and activate the Arp2/3 complex. Cytoplasmic STRAP negatively regulates autophagy. Finally, we use purified proteins to reconstitute LC3- and JMY-dependent actin network formation on membranes and inhibition of network formation by STRAP. We conclude that LC3 and STRAP regulate JMY's actin assembly activities in trans during autophagy

Phenotypic landscape of systemic lupus erythematosus: An analysis of the Kyoto Lupus Cohort

Objectives: The present study aimed to clarify comprehensive relationships among the clinical variables of systemic lupus erythematosus (SLE). Methods: We retrospectively surveyed 32 clinical variables in 581 patients and conducted comprehensive association studies among SLE clinical phenotypes. A univariate analysis of all possible combinations was performed, and the results of phenotypic correlations were reduced into two dimensions. We also created a regression formula using L1 regularisation (LASSO) to calculate the probability of exhibiting each phenotype. Results: The univariate analysis identified 26 correlations, including multiple phenotypes with low complement. Some unpredicted correlations were identified, including fever and the anti-Sm antibody (odds ratio; OR = 2.3, p = 1.6 × 10⁻⁵) or thrombocytopenia and psychosis (OR = 3.7, p = 3.2 × 10⁻⁵). The multivariate analysis accurately estimated the probability of exhibiting each phenotype (area under the curve > 0.7) in 10 out of 20 phenotypes. Conclusions: The present results show the phenotypic architecture of SLE and represent a model for estimating the probability of exhibiting each phenotype. They also offer insights into the pathology of SLE and estimating the probability of the onset of new phenotypes in clinical practice

Quantification of (-)-epigallocatechin-3-gallate Inhibition of Migration and Invasion of Oral Squamous Cell Carcinoma Cell Lines Using Real-time Cell Analysis

Catechins found in green tea, in particular (−)-epigallocatechin-3-gallate (EGCG), have antitumor activity. The primary antitumor actions of catechins are anti-oxidative, anti-angiogenic, and anti-metastatic effects. Cell migration and invasion contribute to the metastatic potential of tumors. Real-time cell analysis (RTCA) measures cell migration and invasion in vitro. In the present study, using RTCA, we investigated whether the cell migration and invasion of oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth were inhibited by EGCG. Studies were performed using the human SCC-4 and SAS cell lines, which are poorly differentiated OSCCs of the tongue, and the HO-1-u-1 cell line, an OSCC of the floor of the mouth. SCC-4 cells exhibited high cell migration and invasion compared with the SAS and HO-1-u-1 cells. EGCG was most effective in inhibiting the migration and invasion of SCC-4 cells, and inhibited OSCC cell invasion more strongly than it inhibited cell migration. EGCG inhibited the expression of matrix metalloproteinase (MMP)-2, MMP-9, and integrin α1 and β1 mRNA in the OSCC cell lines, particularly SCC-4 cells. The findings of the present study suggest that EGCG inhibits OSCC cell migration and invasion by inhibiting MMP-2, MMP-9, and integrin α1and β1 expression. Thus, EGCG may be a suitable agent or lead compound for the inhibition of OSCC metastasis

Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis - Analysis Using More than 17,000 Assessments in the KURAMA Database.

Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis

An analysis of Pseudomonas genomic diversity in take-all infected wheat fields reveals the lasting impact of wheat cultivars on the soil microbiota

Manipulation of the soil microbiota associated with crop plants has huge promise for the control of crop pathogens. However, to fully realize this potential we need a better understanding of the relationship between the soil environment and the genes and phenotypes that enable microbes to colonize plants and contribute to biocontrol. A recent 2 years of investigation into the effect of wheat variety on second year crop yield in the context of take-all fungal infection presented the opportunity to examine soil microbiomes under closely defined field conditions. Amplicon sequencing of second year soil samples showed that Pseudomonas spp. were particularly affected by the wheat cultivar grown in year one. Consequently, 318 rhizosphere-associated Pseudomonas fluorescens strains were isolated and characterized across a variety of genetic and phenotypic traits. Again, the wheat variety grown in the first year of the study was shown to exert considerable selective pressure on both the extent and nature of Pseudomonas genomic diversity. Furthermore, multiple significant correlations were identified within the phenotypic/genetic structure of the Pseudomonas population, and between individual genotypes and the external wheat field environment. The approach outlined here has considerable future potential for our understanding of plant-microbe interactions, and for the broader analysis of complex microbial communities

Hydrophobia of gymnosperms: myth or reality? A global analysis

According to the classical textbooks, the gymnosperms are the only seed plants without aquatic species. Recently, however, a set of virtually complete compilations on gymnosperms has been published, enabling a new evaluation of the putative hydrophobia of gymnosperms. This synthesis aims at portraying the relation of all extant gymnosperm species to aquatic and wetland habitats. We present a database of all 986 extant gymnosperm species with their ecological characteristics including 291 cycads, 80 gnetophytes, one ginkgophyte and 614 conifers. We define four categories reflecting the level of hydrophobia and hydrophily of all species and their possible adaptation to wetlands and/or aquatic habitats. Eighty-two percent (805) of the extant species of gymnosperms are clearly hydrophobic, but 18% (180) are classified as hydrophilic. The podocarp Retrophyllum minus is the only obligate inhabitant of aquatic habitats. This contribution classifies gymnosperms into four categories in reference to their physiological and morphological adaptation to a moisture gradient. It relativizes the putative hydrophobia of gymnosperms and provides new perspectives for research on gymnosperms

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling

GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr50−/− mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60