The face of TSR revealed: an extracellular signaling domain is exposed

In this issue, Tan et al. (2002) report the first high resolution (1.9 Å) structural data for thrombospondin (TSP)-1, a large multifunctional protein that regulates cell adhesion, angiogenesis, cell proliferation and survival, TGFβ activation, and protease function (for review see Chen et al., 2000). Because TSP-1 has multiple binding partners and many functions, precise structural information is crucial to understanding its biology. The structure now reported, derived from crystals of the second and third type I repeats of TSP-1 is of particular interest because of the specific functions attributed to these repeats and because domains homologous to the repeats appear in many other proteins in nature. The novel layered fold motif described brings great insight into how the complicated functions of TSP-1 and related molecules are affected

Modification of HDL by reactive aldehydes alters select cardioprotective functions of HDL in macrophages

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154382/1/febs15034_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154382/2/febs15034.pd

R-parity violation in split supersymmetry

In the recently proposed `split supersymmetry' scenario, the squark and slepton masses are allowed to be at a high scale while the gauginos and Higgsinos are within a TeV. We show that in a theory with broken R-parity, the parameter space of such a scenario allows a situation where the lightest neutralino is still stable on the cosmological scale and can be a dark matter candidate. We also separate the cases where (a) it may be invisible but not a dark matter candidate, or (b) it may decay showing a displaced vertex. It is also emphasized how the constraint on the simultaneous violation of baryon and lepton numbers gets relaxed in this scenario.Comment: LaTex 11 pages, 3 figures, uses axodraw. Final version to appear in Phys.Lett.B. Added references and comments. Title changed in journa

Platelet CD36 Signaling Through ERK5 Promotes Caspase-Dependent Procoagulant Activity and Fibrin Deposition In Vivo

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure

Non-linear sigma models with anti-de Sitter target spaces

We present evidence that there is a non-trivial fixed point for the AdS_{D+1} non-linear sigma model in two dimensions, without any matter fields or additional couplings beyond the standard quadratic action subject to a quadratic constraint. A zero of the beta function, both in the bosonic and supersymmetric cases, appears to arise from competition between one-loop and higher loop effects. A string vacuum based on such a fixed point would have string scale curvature. The evidence presented is based on fixed-order calculations carried to four loops (corresponding to O(\alpha'^3) in the spacetime effective action) and on large D calculations carried to O(D^{-2}) (but to all orders in \alpha'). We discuss ways in which the evidence might be misleading, and we discuss some features of the putative fixed point, including the central charge and an operator of negative dimension. We speculate that an approximately AdS_5 version of this construction may provide a holographic dual for pure Yang-Mills theory, and that quotients of an AdS_3 version might stand in for Calabi-Yau manifolds in compactifications to four dimensions.Comment: 44 pages, 4 figures. v2: references adde

Clinical outcomes in youth beyond the first year of type 1 diabetes: Results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138914/1/pedi12459.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138914/2/pedi12459_am.pd

A cross‐sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136377/1/pedi12377_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136377/2/pedi12377.pd