Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1

Although thoracic aortic aneurysms and dissections (TAAD) can be inherited as a single-gene disorder, the genetic predisposition in the majority of affected people is poorly understood. In a multistage genome-wide association study (GWAS), we compared 765 individuals who had sporadic TAAD (STAAD) with 874 controls and identified common SNPs at a 15q21.1 locus that were associated with STAAD, with odds ratios of 1.6-1.8 that achieved genome-wide significance. We followed up 107 SNPs associated with STAAD with P < 1 × 10(-5) in the region, in two separate STAAD cohorts. The associated SNPs fall into a large region of linkage disequilibrium encompassing FBN1, which encodes fibrillin-1. FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD. This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD.     

Himalayan tectonics explained by extrusion of a low-viscosity crustal channel coupled to focused surface denudation.

Recent interpretations of Himalayan-Tibetan tectonics have proposed that channel flow in the middle to lower crust can explain outward growth of the Tibetan plateau, and that ductile extrusion of high-grade metamorphic rocks between coeval normal- and thrust-sense shear zones can explain exhumation of the Greater Himalayan sequence. Here we use coupled thermal-mechanical numerical models to show that these two processes-channel flow and ductile extrusion-may be dynamically linked through the effects of surface denudation focused at the edge of a plateau that is underlain by low-viscosity material. Our models provide an internally self-consistent explanation for many observed features of the Himalayan-Tibetan system.     

Evolution and transmission of stable CTL escape mutations in HIV infection.

Increasing evidence indicates that potent anti-HIV-1 activity is mediated by cytotoxic T lymphocytes (CTLs); however, the effects of this immune pressure on viral transmission and evolution have not been determined. Here we investigate mother-child transmission in the setting of human leukocyte antigen (HLA)-B27 expression, selected for analysis because it is associated with prolonged immune containment in adult infection. In adults, mutations in a dominant and highly conserved B27-restricted Gag CTL epitope lead to loss of recognition and disease progression. In mothers expressing HLA-B27 who transmit HIV-1 perinatally, we document transmission of viruses encoding CTL escape variants in this dominant Gag epitope that no longer bind to B27. Their infected infants target an otherwise subdominant B27-restricted epitope and fail to contain HIV replication. These CTL escape variants remain stable without reversion in the absence of the evolutionary pressure that originally selected the mutation. These data suggest that CTL escape mutations in epitopes associated with suppression of viraemia will accumulate as the epidemic progresses, and therefore have important implications for vaccine design.     

KINETICS OF DELIGNIFICATION AND CARBOHYDRATE DEGRADATION DURING OXYGEN BLEACHING

Carbohydrate degradation during oxygen bleaching is associated with cleavage reactions. It is apparent that the loss of the cellulose DP (degree ofpolymisation)is strongly affected by the extent of the delignification. A strong linear correlation can be established between the DP of cellulose chains and the residual lignin in the pulp. The Nuclear Growth concept and Percolation Theory for heterogenous system can be combined to formulate kinetic models for both the delignification and the degradation of carbohydrate. The models prediction is statistically robust and can be applied to different pulps at different bleaching conditions.     

Effect of potassium on isolated bovine facial and human saphenous veins

Summary A moderate elevation of external (K ₀ ⁺ ) (5–10 mM) induces relaxation in bovine facial and human saphenous veins. A further increase of (K ₀ ⁺ ) leads to biphasic reactions (relaxation followed by contraction). Concentrations of (K ₀ ⁺ ) higher than about 15 mM cause contractions only. The potassium-induced relaxation may be explained by the stimulation of an electrogenic sodium pump.     

Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand

Bone remodelling and bone loss are controlled by a balance between the tumour necrosis factor family molecule osteoprotegerin ligand (OPGL) and its decoy receptor osteoprotegerin (OPG). In addition, OPGL regulates lymph node organogenesis, lymphocyte development and interactions between T cells and dendritic cells in the immune system. The OPGL receptor, RANK, is expressed on chondrocytes, osteoclast precursors and mature osteoclasts. OPGL expression in T cells is induced by antigen receptor engagement, which suggests that activated T cells may influence bone metabolism through OPGL and RANK. Here we report that activated T cells can directly trigger osteoclastogenesis through OPGL. Systemic activation of T cells in vivo leads to an OPGL-mediated increase in osteoclastogenesis and bone loss. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe joint inflammation, bone and cartilage destruction and crippling, blocking of OPGL through osteoprotegerin treatment at the onset of disease prevents bone and cartilage destruction but not inflammation. These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology.     

小鼠腔前卵泡卵母细胞的体外培养、体外成熟和体外受精研究

小鼠腔前卵泡在体外生长过程中，于培养液中添加血清，以及ＦＳＨ和胰岛素均对小鼠腔前卵泡的体外生长、体外成熟、体外受精起促进作用，其中以胰岛素的效果最为显著，腔前卵泡的体外成熟率和体外受精率可达６９．４％和８０．６％，但是体外受精后的体外发育率低于添加ＦＳＨ的试验组，表明ＦＳＨ有益于卵母细胞生长过程中细胞质的成熟。单层培养的卵巢颗粒细胞对腔前卵泡的体外生长也具有促进作用。将体外受精后发育至２—细胞的胚胎移植入受体鼠，胚胎可以正常着床发育。同时，卵母细胞的核仁和线粒体在培养过程中也发生相应的变化。     

Aerodynamic force generation of an insect-inspired flapper actuated by a compressed unimorph actuator

We examined experimentally the flapping performance in terms of aerodynamic force generation of an insect-inspired flapper actuated by both of original LIPCA and compressed LIPCA. Flapping tests for two artificial wing shapes of horse botfly and hawk moth were conducted at the wing rotation angle of 60° and a flapping frequency range from 6 Hz to 12 Hz to find the optimum flapping frequency and to investigate the effect of compressed LIPCA and wing shape on the force generation. Flapping tests in the vacuum were also undertaken to measure the induced inertia force. The aerodynamic force was calculated by subtracting the inertia force from the total force measured in the air. It was found that the average inertia force was relatively small when compared with the average total force. The use of the compressed LIPCA could significantly improve the flapping angle of the flapper from 110° to 130° （18.2% increase） resulting in 24.5% increase in the average aerodynamic force. It was also found that flapper with hawk moth wings could produce larger force than the flapper with horse botfly wings.