307 research outputs found
Effective degrees of freedom during the radiation era
We update the curves of the effective degrees of freedom for the energy
density and for the entropy density during the era of
radiation domination in the Universe. We find that a plain count of effective
degrees of freedom sets an upper limit to the temperature of the quark-hadron
transition at MeV for the energy density and MeV for the
entropy density.Comment: 3 pages, 2 figure
Gambogic Acid, a Natural Product Inhibitor of Hsp90
A high-throughput screening of natural product libraries identified (−)-gambogic acid (1), a component of the exudate of Garcinia harburyi, as a potential Hsp90 inhibitor, in addition to the known Hsp90 inhibitor celastrol (2). Subsequent testing established that 1 inhibited cell proliferation, brought about the degradation of Hsp90 client proteins in cultured cells, and induced the expression of Hsp70 and Hsp90, which are hallmarks of Hsp90 inhibition. Gambogic acid also disrupted the interaction of Hsp90, Hsp70, and Cdc37 with the heme-regulated eIF2α kinase (HRI, an Hsp90-dependent client) and blocked the maturation of HRI in vitro. Surface plasmon resonance spectroscopy indicated that 1 bound to the N-terminal domain of Hsp90 with a low micromolar Kd, in a manner that was not competitive with the Hsp90 inhibitor geldanamycin (3). Molecular docking experiments supported the posit that 1 binds Hsp90 at a site distinct from Hsp90s ATP binding pocket. The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors
Dilaton stabilization by massive fermion matter
The study started in a former work about the Dilaton mean field stabilization
thanks to the effective potential generated by the existence of massive
fermions, is here extended. Three loop corrections are evaluated in addition to
the previously calculated two loop terms. The results indicate that the Dilaton
vacuum field tend to be fixed at a high value close to the Planck scale, in
accordance with the need for predicting Einstein gravity from string theory.
The mass of the Dilaton is evaluated to be also a high value close to the
Planck mass, which implies the absence of Dilaton scalar signals in modern
cosmological observations. These properties arise when the fermion mass is
chosen to be either at a lower bound corresponding to the top quark mass, or
alternatively, at a very much higher value assumed to be in the grand
unification energy range. One of the three 3-loop terms is exactly evaluated in
terms of Master integrals. The other two graphs are however evaluated in their
leading logarithm correction in the perturbative expansion. The calculation of
the non leading logarithmic contribution and the inclusion of higher loops
terms could made more precise the numerical estimates of the vacuum field value
and masses, but seemingly are expected not to change the qualitative behavior
obtained. The validity of the here employed Yukawa model approximation is
argued for small value of the fermion masses with respect to the Planck one. A
correction to the two loop calculation done in the previous work is here
underlined.Comment: 18 pages, 5 figures, the study was extended and corrections on the
former calculations and redaction were done. The paper had been accepted for
publication in "Astrophysics and Space Science
Elucidation of the Hsp90 C-terminal Inhibitor Binding Site
The Hsp90 chaperone machine is required for the folding, activation and/or stabilization of more than 50 proteins directly related to malignant progression. Hsp90 contains small molecule binding sites at both its N- and C-terminal domains, however, limited structural and biochemical data regarding the C-terminal binding site is available. In this report, the small molecule binding site in
the Hsp90 C-terminal domain was revealed by protease fingerprinting and photoaffinity labeling utilizing LC-MS/MS. The identified site was characterized by generation of a homology model for hHsp90α using the SAXS open structure of HtpG and docking the bioactive conformation of NB into the generated model. The resulting model for the bioactive conformation of NB bound to Hsp90α is presented herein
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