Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population

Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10(-8), including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves' disease (P = 3.5 × 10(-4) and 2.9 × 10(-4), respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.     

Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia

For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing cells with the number of dying cells. Although compensatory cell division can be triggered by dying cells, it is unknown how cell death might relieve overcrowding due to proliferation. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier. Extrusion occurs by cells destined to die signalling to surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out. However, it is not clear what drives cell death during normal homeostasis. Here we show in human, canine and zebrafish cells that overcrowding due to proliferation and migration induces extrusion of live cells to control epithelial cell numbers. Extrusion of live cells occurs at sites where the highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro. Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires sphingosine 1-phosphate signalling and Rho-kinase-dependent myosin contraction, but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum cause overcrowding that leads to their extrusion and consequent death owing to the loss of survival factors. These results suggest that live cell extrusion could be a tumour-suppressive mechanism that prevents the accumulation of excess epithelial cells.     

25例帕金森病的临床与病理学特征

目的:研究帕金森病(PD)的临床和病理学特征及与路易体痴呆(DLB)病理学的关系。方法:对25例PD的临床和病理学特征进行研究。结果:在25例中5例为伴痴呆的帕金森病(PDD),初发症状为震颤11例,步行障碍6例,运动迟缓4例及吞咽困难1例。16例(69.9%)出现了视幻觉,24例(96%)对左旋多巴有反应,15例(65%)死于肺炎,3例死于肠梗阻。按DLB的病理学分类,25例中新皮质型5例,边缘型6例,脑干优势型14例。结论:本组PD的病理学特点主要是DLB的脑干优势型改变。PDD的病理类型是DLB的新皮质型和边缘型。病理上诊断为PD的患者,在临床上有很高的左旋多巴的反应率,晚期患者多数死于肺炎并发症。     

Fluorometric study of interaction between ACTH fragments and bovine adrenocortical membranes.

Corticotropin 1-24 and [Gly1]corticotropin1-18 amide increased the fluorescence of 1-anilinonaphthalene-8-sulfonate which bound to the bovine adrenocortical membranes. The two ACTH fragments interacted with the protein of the membranes and membranes and increased the net positive charge of the membranes.     

Avian flu: isolation of drug-resistant H5N1 virus

The persistence of H5N1 avian influenza viruses in many Asian countries and their ability to cause fatal infections in humans have raised serious concerns about a global flu pandemic. Here we report the isolation of an H5N1 virus from a Vietnamese girl that is resistant to the drug oseltamivir, which is an inhibitor of the viral enzyme neuraminidase and is currently used for protection against and treatment of influenza. Further investigation is necessary to determine the prevalence of oseltamivir-resistant H5N1 viruses among patients treated with this drug.     

Effect of sodium chloride on the respiratory function of Staphylococcus aureus.

Sodium chloride at concentrations below 0.5 M, enhanced the respiratory activity (O2-consumption) of Staphylococcus aureus under endogenous and sugar-supported conditions, but did not overcome the inhibitory action of sodium azide. Several sugars, including the glucose analogue alpha-methylglucoside, and their metabolites enhanced bacterial O2-consumption, but acetylmethylcarbinol was ineffective.     

ATP drives lamina propria T(H)17 cell differentiation

Interleukin (IL)-17-producing CD4(+) T lymphocytes (T(H)17 cells) constitute a subset of T-helper cells involved in host defence and several immune disorders. An intriguing feature of T(H)17 cells is their selective and constitutive presence in the intestinal lamina propria. Here we show that adenosine 5'-triphosphate (ATP) that can be derived from commensal bacteria activates a unique subset of lamina propria cells, CD70(high)CD11c(low) cells, leading to the differentiation of T(H)17 cells. Germ-free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to specific-pathogen-free mice. Systemic or rectal administration of ATP into these germ-free mice results in a marked increase in the number of lamina propria T(H)17 cells. A CD70(high)CD11c(low) subset of the lamina propria cells expresses T(H)17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor-beta-activating integrin-alphaV and -beta8, in response to ATP stimulation, and preferentially induces T(H)17 differentiation of co-cultured naive CD4(+) T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T-cell-mediated colitis model with enhanced T(H)17 differentiation. These observations highlight the importance of commensal bacteria and ATP for T(H)17 differentiation in health and disease, and offer an explanation of why T(H)17 cells specifically present in the intestinal lamina propria.