Interactions of thrombospondins with α4β1 integrin and CD47 differentially modulate T cell behavior

Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin α4β1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of α4β1 integrin, and TSP1 inhibited interaction of activated α4β1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The α4β1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the α4β1 integrin–dependent activities of TSP1. The β1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSP1 but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs

E2F-1 Directly Regulates Thrombospondin 1 Expression

Thrombospondin 1 (TSP1) has been shown to play a critical role in inhibiting angiogenesis, resulting in inhibition of tumor growth and metastases. To figure out TSP1's regulators will lead to reveal its biological function mechanistically. In this study, we show that E2F-1 could activate the transcription of TSP1 by both promoter assays and Northern blot. Analysis of various TSP1 promoter mutant constructs showed that a sequence located −144/−137 up-stream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. In consistence with up-regulation of TSP-1 activity by over-expression of E2F-1, the knockdown of endogenous E2F-1 inhibited TSP-1 promoter activity significantly, implying that E2F-1 mediated regulation of TSP-1 is relevant in vivo. In addition, E2F-1 could also directly bind to the TSP1 promoter region covering −144/−137 region as revealed by ChIP assays. Furthermore, the E2F-1-induced activation of TSP1 gene transcription is suppressed by pRB1 in a dose-dependent manner. Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression

Investigation of the Vortex Ring Transition using Scanning Tomo-PIV

The transition of a vortex ring at ReΓ = 5030 is studied by time-resolved scanning tomographic PIV technique. The transition process is first analyzed through flow quantities such as circulation and vorticity components. Using the volumetric measurement technique, vortical organization of the vortex ring at early and late transition stages are visualized respectively. Focus is paid to the instability phenomenon associated with transition. The present 4D flow data allows analysis of the temporal evolution of the wavenumber spectra. The dominant wavenumbers in transition are identified and the growth of their amplitude is revealed. The vortex ring transition is finally studied through the particle trajectories. A phase difference between the axial velocity and radial velocity is found in the beginning of transition, however, it is subject to change following the progression of transition. Statistical analysis on the velocity components helps to identify the aft portion of the inner ring as the one that is first to lose the original phase relation in velocity, which is caused by the secondary vortical activity during transition

QTL analysis and genomic selection using RADseq derived markers in Sitka spruce: the potential utility of within family data

Sitka spruce (Picea sitchensis (Bong.) Carr) is the most common commercial plantation species in Britain and a breeding programme based on traditional lines has been in operation since the early 1960s. Rotation lengths of 40-years have led breeders to adopt a process of indirect selection at younger ages based on traits well correlated with final selection, but still the generation interval is unlikely to reduce much below twenty years. Recent successful developments with genomic selection in animal breeding have led tree breeders to consider the application of this technology. In this study a RAD sequence assay was developed as a means of investigating the potential of molecular breeding in a non-model species. DNA was extracted from nearly 500 clonally replicated trees growing in a single full-sibling family at one site in Britain. The technique proved successful in identifying 132 QTLs for 5-year bud-burst and 2 QTLs for 6-year height. In addition, the accuracy of predicting phenotypes by genomic selection was strikingly high at 0.62 and 0.59 respectively. Sensitivity analysis with 200 offspring found only a slight fall in correlation values (0.54 and 0.38) although when the training population reduced to 50 offspring predictive values fell further (0.33 and 0.25). This proved an encouraging first investigation into the potential use of genomic selection in the breeding of Sitka spruce. The authors investigate how problems associated with effective population size and linkage disequilibrium can be avoided and suggest a practical way of incorporating genomic selection into a dynamic breeding programme

Evidence for the ‘Good Genes’ Model: Association of MHC Class II DRB Alleles with Ectoparasitism and Reproductive State in the Neotropical Lesser Bulldog Bat, Noctilio albiventris

The adaptive immune system has a major impact on parasite resistance and life history strategies. Immunological defence is costly both in terms of immediate activation and long-term maintenance. The ‘good genes’ model predicts that males with genotypes that promote a good disease resistance have the ability to allocate more resources to reproductive effort which favours the transmission of good alleles into future generations. Our study shows a correlation between immune gene constitution (Major Histocompatibility Complex, MHC class II DRB), ectoparasite loads (ticks and bat flies) and the reproductive state in a neotropical bat, Noctilio albiventris. Infestation rates with ectoparasites were linked to specific Noal-DRB alleles, differed among roosts, increased with body size and co-varied with reproductive state particularly in males. Non-reproductive adult males were more infested with ectoparasites than reproductively active males, and they had more often an allele (Noal-DRB*02) associated with a higher tick infestation than reproductively active males or subadults. We conclude that the individual immune gene constitution affects ectoparasite susceptibility, and contributes to fitness relevant trade-offs in male N. albiventris as suggested by the ‘good genes’ model

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease