Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm

Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies.     

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.     

Development of a new coated electrode with low nickel content for welding ductile iron and its response to austempering

Coated Electrodes with small amounts of nickel were developed for welding ductile iron (DI) and conversion of the same into austempered ductile iron (ADI) after austempering. Among six electrodes, Trials 3 and 4 were selected for establishing crack-free weld deposits via preheating and post-weld heat treatment. Austenitization was performed at 900℃ for 2 h and austempering at 300 or 350℃ for three different holding times to observe the results of austempering with respect to the microstructure, hardness, and austempering kinetics of the samples. The microstructures of the weld deposits showed needle-like bainitic ferrite with small amounts of retained austenite when treated at 300℃ and feathery bainitic ferrite with large amounts of retainedaustenite when treated at 350℃. The electrode labeled with Trial 3 revealed greater austenite contents than that labeled with Trial 4 when treated with a 2 h holding time regardless of the austempering temperature applied. The transformation rate of the bainitic ferrite of Trial 3 was relatively higher than that of Trial 4 and showed a lower rate constant, leading to a higher diffusion rate of carbon in austenite.     

Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins

All cells in nature are covered by a dense and complex array of carbohydrates. Given their prominence on cell surfaces, it is not surprising that these glycans mediate and/or modulate many cellular interactions. Proteins that bind sialic acid, a sugar that is found on the surface of the cell and on secreted proteins in vertebrates, are involved in a broad range of biological processes, including intercellular adhesion, signalling and microbial attachment. Studying the roles of such proteins in vertebrates has improved our understanding of normal physiology, disease and human evolution.     

Stimulation of gastric secretion by prostaglandin F2 α in rats

Summary In rats with chronic gastric fistulas, prostaglandin F₂ stimulated the gastric acid secretion in graded doses of 50. 100, 200 and 400 g/kg b. wt, while higher doses above 1 mg/kg b. wt tended to inhibit significantly. The gastric antisecretory effect of prostaglandin E₁ could not be altered or modified by subsequent treatment of prostaglandin F₂ , while the latter alone without any prior treatment of the former, stimulated output of gastric juice, HCl and pepsin without significantly affecting the concentration of these components.Acknowledgement. The gift of the prostaglandin E₁ and prostaglandin F₂ is acknowledged to Dr J.E. Pike, Upjohn, USA. This paper was read at the IXth Annual Conference of the Indian Pharmacological Society held at Benares (1976) and abstracted in the Indian J. Pharmac.9, 73 (1977).     

Filling Simulation of Three-dimension Braided Composite in Resin Transfer Molding

This paper measured permeability of three-dimension braided preform by radial technology. The results show that principal permeability tensor coincided with their braiding axial direction. The software of one dimensional flow filling mold was designed using Visual C ＋ ＋ language. Filling time is predicted and validated. The result showed that the filling time of the mold centerline agrees with the prediction value. The filling time of the mould edge is shorter than that of the prediction. An actual plate of 3 - D braided preform / modified polyarylacetylene composite is produced according to prediction value and validation analysis.