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221.
222.
The complete mitochondrial DNA sequence of the shark Mustelus manazo: evaluating rooting contradictions to living bony vertebrates 总被引:5,自引:0,他引:5
A remarkable example of a misleading mitochondrial protein tree is
presented, involving ray-finned fishes, coelacanths, lungfishes, and
tetrapods, with sea lampreys as an outgroup. In previous molecular
phylogenetic studies on the origin of tetrapods, ray-finned fishes have
been assumed as an outgroup to the tetrapod/lungfish/coelacanth clade, an
assumption supported by morphological evidence. Standard methods of
molecular phylogenetics applied to the protein-encoding genes of
mitochondria, however, give a bizarre tree in which lamprey groups with
lungfish and, therefore, ray-finned fishes are not the outgroup to a
tetrapod/lungfish/coelacanth clade. All of the dozens of published
phylogenetic methods, including every possible modification to maximum
likelihood known to us (such as inclusion of site heterogeneity and
exclusion of potentially misleading hydrophobic amino acids), fail to place
the ray-finned fishes in a biologically acceptable position. A likely cause
of this failure may be the use of an inappropriate outgroup. Accordingly,
we have determined the complete mitochondrial DNA sequence from the shark,
Mustelus manazo, which we have used as an alternative and more proximal
outgroup than the lamprey. Using sharks as the outgroup, lungfish appear to
be the closest living relative of tetrapods, although the possibility of a
lungfish/coelacanth clade being the sister group of tetrapods cannot be
excluded.
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Joseph M. Salvino Yellamelli V.V. Srikanth Rongliang Lou Halley M. Oyer Nan Chen Felix J. Kim 《Bioorganic & medicinal chemistry letters》2017,27(10):2216-2220
Prostate cancer is the most frequently diagnosed malignancy and the leading cause of cancer related death in men. First line therapy for disseminated disease relies on androgen deprivation, leveraging the addiction of these tumors on androgens for both growth and survival. Treatment typically involves antagonizing the androgen receptor (AR) or blocking the synthesis of androgens. Recurrence is common and within 2–3 years patients develop castration resistant tumors that become unresponsive to AR-axis targeted therapies. In order to provide a more effective treatment, we are utilizing an approach that targets a key scaffolding protein, Sigma1 (also known as sigma-1 receptor), a unique 26-kilodalton integral membrane protein that is critical in stabilizing the AR. Herein we report on a new series of Sigma1 compounds for lead optimization derived from a hybrid pharmacophore approach. 相似文献
226.
Decomposable graphical Gaussian model determination 总被引:8,自引:0,他引:8
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