Tests of chameleon gravity

Theories of modified gravity, where light scalars with non-trivial self-interactions and non-minimal couplings to matter—chameleon and symmetron theories—dynamically suppress deviations from general relativity in the solar system. On other scales, the environmental nature of the screening means that such scalars may be relevant. The highly-nonlinear nature of screening mechanisms means that they evade classical fifth-force searches, and there has been an intense effort towards designing new and novel tests to probe them, both in the laboratory and using astrophysical objects, and by reinterpreting existing datasets. The results of these searches are often presented using different parametrizations, which can make it difficult to compare constraints coming from different probes. The purpose of this review is to summarize the present state-of-the-art searches for screened scalars coupled to matter, and to translate the current bounds into a single parametrization to survey the state of the models. Presently, commonly studied chameleon models are well-constrained but less commonly studied models have large regions of parameter space that are still viable. Symmetron models are constrained well by astrophysical and laboratory tests, but there is a desert separating the two scales where the model is unconstrained. The coupling of chameleons to photons is tightly constrained but the symmetron coupling has yet to be explored. We also summarize the current bounds on f(R) models that exhibit the chameleon mechanism (Hu and Sawicki models). The simplest of these are well constrained by astrophysical probes, but there are currently few reported bounds for theories with higher powers of R. The review ends by discussing the future prospects for constraining screened modified gravity models further using upcoming and planned experiments

Antibodies that conformationally activate ADAMTS13 allosterically enhance metalloprotease domain function

Plasma ADAMTS13 circulates in a folded conformation that is stabilized by an interaction between the central Spacer domain and the C-terminal CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. Binding of ADAMTS13 to the VWF D4(-CK) domains or to certain activating murine monoclonal antibodies (mAbs) induces a structural change that extends ADAMTS13 into an open conformation that enhances its function. The objective was to characterize the mechanism by which conformational activation enhances ADAMTS13-mediated proteolysis of VWF. The activating effects of a novel anti-Spacer (3E4) and the anti-CUB1 (17G2) mAbs on the kinetics of proteolysis of VWF A2 domain fragments by ADAMTS13 were analyzed. mAb-induced conformational changes in ADAMTS13 were investigated by enzyme-linked immunosorbent assay. Both mAbs enhanced ADAMTS13 catalytic efficiency (kcat/Km) by ∼twofold (3E4: 2.0-fold; 17G2: 1.8-fold). Contrary to previous hypotheses, ADAMTS13 activation was not mediated through exposure of the Spacer or cysteine-rich domain exosites. Kinetic analyses revealed that mAb-induced conformational extension of ADAMTS13 enhances the proteolytic function of the metalloprotease domain (kcat), rather than augmenting substrate binding (Km). A conformational effect on the metalloprotease domain was further corroborated by the finding that incubation of ADAMTS13 with either mAb exposed a cryptic epitope in the metalloprotease domain that is normally concealed when ADAMTS13 is in a closed conformation. We show for the first time that the primary mechanism of mAb-induced conformational activation of ADAMTS13 is not a consequence of functional exosite exposure. Rather, our data are consistent with an allosteric activation mechanism on the metalloprotease domain that augments active site function

Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients

In autoantibody-mediated autoimmune diseases, autoantibody profiling allows to stratify patients and link autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed at developing a new type of autoantibody profiling assay for immune-mediated thrombotic thrombocytopenic purpura based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer idiotopes from 151 acute immune-mediated thrombotic thrombocytopenic purpura plasma samples. We next deciphered these anti-spacer idiotope profiles in immune-mediated thrombotic thrombocytopenic purpura patients and investigated if these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding. Thirty-five, 24 and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles revealed an until now unknown insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 idiotopes in immune-mediated thrombotic thrombocytopenic purpura patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow to identify idiotope profiles of clinical, prognostic value

Ecological Observations on Pteridophyta in the Kangra Himalaya

Volume: 44Start Page: 49End Page: 6

Observations on the Ecology of the South African Umbilicaria

Volume: 16Start Page: 39End Page: 4

The Identity of Notholaena Bipinnata Sim

Volume: 20Start Page: 125End Page: 12