Fourth order gravity: equations, history, and applications to cosmology

The field equations following from a Lagrangian L(R) will be deduced and solved for special cases. If L is a non-linear function of the curvature scalar, then these equations are of fourth order in the metric. In the introduction we present the history of these equations beginning with the paper of H. Weyl from 1918, who first discussed them as alternative to Einstein's theory. In the third part, we give details about the cosmic no hair theorem, i.e., the details how within fourth order gravity with L= R + R^2 the inflationary phase of cosmic evolution turns out to be a transient attractor. Finally, the Bicknell theorem, i.e. the conformal relation from fourth order gravity to scalar-tensor theory, will be shortly presented.Comment: 51 pages, LaTeX, no figure, lecture for 42nd Karpacz Winter School 6.-11.2.06, references 99-109 and related comments are adde

International Journal of Molecular Sciences / Loss of SR-BI Down-Regulates MITF and Suppresses Extracellular Vesicle Release in Human Melanoma

Melanoma is a skin tumor with a high tendency for metastasis and thus is one of the deadliest cancers worldwide. Here, we investigated the expression of the scavenger receptor class B type 1 (SR-BI), a high-density lipoprotein (HDL) receptor, and tested for its role in melanoma pigmentation as well as extracellular vesicle release. We first analyzed the expression of SR-BI in patient samples and found a strong correlation with MITF expression as well as with the melanin synthesis pathway. Hence, we asked whether SR-BI could also play a role for the secretory pathway in metastatic melanoma cells. Interestingly, gain- and loss-of-function of SR-BI revealed regulation of the proto-oncogene MET. In line, SR-BI knockdown reduced expression of the small GTPase RABB22A, the ESCRT-II protein VPS25, and SNAP25, a member of the SNARE complex. Accordingly, reduced overall extracellular vesicle generation was detected upon loss of SR-BI. In summary, SR-BI expression in human melanoma enhances the formation and transport of extracellular vesicles, thereby contributing to the metastatic phenotype. Therapeutic targeting of SR-BI would not only interfere with cholesterol uptake, but also with the secretory pathway, therefore suppressing a key hallmark of the metastatic program.(VLID)491292