BACKGROUND To avoid pathological platelet aggregation by von Willebrand factor (VWF), VWF multimers are regulated in size and reactivity for adhesion by ADAMTS13-mediated proteolysis in a shear flow dependent manner. OBJECTIVE AND METHODS We examined whether tensile stress in VWF under shear flow activates the VWF A2 domain for cleavage by ADAMTS13 using molecular dynamics simulations. We gen...

Seven recently cultured bacterial isolates, although similar in their 16S rRNA gene sequences to Roseburia intestinalis L1-82(T) (DSM 14610(T)), were not sufficiently related for inclusion within existing species, forming three separate clusters in a 16S rRNA gene phylogenetic tree. The isolates, which were obtained from human stools, were Gram-variable or Gram-negative, strictly anaerobic, sli...

Antibodies directed to the A2 domain of factor VIII (fVIII) are usually an important component of the polyclonal response in patients who have clinically significant inhibitory antibodies to fVIII. A major determinant of the A2 epitope has been located by homolog scanning mutagenesis using recombinant hybrid human/porcine fVIII molecules to a sequence bounded by Arg484-Ile508 (Healey, J. F. , L...

Phenylamide-resistant isolates of Phytophthora infestans have gradually become an important part of populations in many countries. However, fungicide mixtures containing a phenylamide component are still an effective strategy for the control of late blight in potato and tomato. The proportion of phenylamide-resistant isolates fluctuates from year to year and within the season. Almost concurrent...

Abstract. We consider functions f(A,B) of noncommuting self-adjoint operators A and B that can be defined in terms of double operator integrals. We prove that if f belongs to the Besov class B ∞,1 (R), then we have the following Lipschitz type estimate in the trace norm: ‖f(A1, B1)− f(A2, B2)‖S1 ≤ const(‖A1 −A2‖S1 + ‖B1 −B2‖S1). However, the condition f ∈ B ∞,1 (R) does not imply the Lipschitz ...

Annexins are a family of homologous proteins that associate with anionic phospholipid (aPL) in the presence of Ca(2+). Evidence that the function of one annexin type may be regulated by another was recently reported in studies investigating cytomegalovirus-aPL interactions, where the fusogenic function of annexin 2 (A2) was attenuated by annexin 5 (A5). This observation suggested that A2 may bi...

The high incidence of hepatitis C virus (HCV) persistence raises the question of how HCV interferes with host immune responses. Studying a single-source HCV outbreak, we identified an HCV mutation that impaired correct carboxyterminal cleavage of an immunodominant HLA-A2-restricted CD8 cell epitope that is frequently recognized by recovered patients. The mutation, a conservative HCV nonstructur...

von Willebrand factor (vWF) is a large multimeric, multidomain glycoprotein found in platelets, endothelial cells and plasma. The A1, A2, and A3 domains in vWF mediate binding to glycoprotein Ib, ristocetin, botrocetin, collagen, sulphatides, and heparin and provide a protease cleavage site. Mutations causing types 2B, 2M, and 2A von Willebrand's disease (vWD) are located in the A1 and A2 domai...