University of Kansas

About: University of Kansas is a education organization based out in Lawrence, Kansas, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 38183 authors who have published 81381 publications receiving 2986312 citations. The organization is also known as: KU & Univ of Kansas.

Mutations in the colony stimulating factor 1 receptor ( CSF1R ) gene cause hereditary diffuse leukoencephalopathy with spheroids

Abstract: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS In one kindred, we confirmed the de novo occurrence of the mutation Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis

Large Deviations for Stochastic Processes

Abstract: Introduction: Introduction An overview The general theory of large deviations: Large deviations and exponential tightness Large deviations for stochastic processes Large deviations for Markov processes and semigroup convergence: Large deviations for Markov processes and nonlinear semigroup convergence Large deviations and nonlinear semigroup convergence using viscosity solutions Extensions of viscosity solution methods The Nisio semigroup and a control representation of the rate function Examples of large deviations and the comparison principle: The comparison principle Nearly deterministic processes in $R^d$ Random evolutions Occupation measures Stochastic equations in infinite dimensions Appendix: Operators and convergence in function spaces Variational constants, rate of growth and spectral theory for the semigroup of positive linear operators Spectral properties for discrete and continuous Laplacians Results from mass transport theory Bibliography Index.

Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts : purification and activation of the precursor and enzymic properties

Abstract: Human rheumatoid synovial cells in culture secrete at least three related metalloproteinases that digest extracellular matrix macromolecules. One of them, termed matrix metalloproteinase 2 (MMP-2), has been purified as an inactive zymogen (proMMP-2). The final product is homogeneous on SDS/PAGE with Mr = 72,000 under reducing conditions. The NH2-terminal sequence of proMMP-2 is Ala-Pro-Ser-Pro-Ile-Ile-Lys-Phe-Pro-Gly-Asp-Val-Ala-Pro-Lys-Thr, which is identical to that of the so-called '72-kDa type IV collagenase/gelatinase'. The zymogen can be rapidly activated by 4-aminophenylmercuric acetate to an active form of MMP-2 with Mr = 67,000, and the new NH2-terminal generated is Tyr-Asn-Phe-Phe-Pro-Arg-Lys-Pro-Lys-Trp-Asp-Lys-Asn-Gln-Ile. However, following 4-aminophenylmercuric acetate activation, MMP-2 is gradually inactivated by autolysis. Nine endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, neutrophil elastase, cathepsin G, matrix metalloproteinase 3, and thermolysin) were tested for their abilities to activate proMMP-2, but none had this ability. This contrasts with the proteolytic activation of proMMP-1 (procollagenase) and proMMP-3 (prostromelysin). The optimal activity of MMP-2 against azocoll is around pH 8.5, but about 50% of activity is retained at pH 6.5. Enzymic activity is inhibited by EDTA, 1,10-phenanthroline or tissue inhibitor of metalloproteinases, but not by inhibitors of serine, cysteine or aspartic proteinases. MMP-2 digests gelatin, fibronectin, laminin, and collagen type V, and to a lesser extent type IV collagen, cartilage proteoglycan and elastin. Comparative studies on digestion of collagen types IV and V by MMP-2 and MMP-3 (stromelysin) indicate that MMP-3 degrades type IV collagen more readily than MMP-2, while MMP-2 digests type V collagen effectively. Biosynthetic studies of MMPs using cultured human rheumatoid synovial fibroblasts indicated that the production of both proMMP-1 and proMMP-3 is negligible but it is greatly enhanced by the treatment with rabbit-macrophage-conditioned medium, whereas the synthesis of proMMP-2 is constitutively expressed by these cells and is not significantly affected by the treatment. This suggests that the physiological and/or pathological role of MMP-2 and its site of action may be different from those of MMP-1 and MMP-3.

Macromolecular modeling and design in Rosetta: recent methods and frameworks

Abstract: The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.