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AR, a member of the nuclear receptor (NR) superfamily, functions mainly as a ligand-dependent transcription factor. Upon binding of the androgenic hormone testosterone or its more active analog dihydrotestosterone (DHT) in the cytoplasm, AR translocates into the nucleus to bind DNA and regulate gene expression. AR has a wide range of regulatory roles in prostate growth and function, including but not limited to cellular proliferation, differentiation, apoptosis, metabolism and secretory activity . While many of its direct activation targets have been characterized, the key downstream effectors, especially those playing a role in carcinogenesis or modulated during targeted therapy, remain to be determined; even less is known about the genes directly repressed by AR , though they may also be important contributors to AR function in disease and treatment settings.
Novel AR antagonists utilized in this study. (A) Chemical structures (compound number listed below structure). (B) Nuclear Translocation of AR was impeded by these compounds. LNAR cells were treated with 0.1nM R1881 alone or in combination with the antagonist compounds at various doses to determine IC50 values. Nuclear translocation values were calculated as indicated under Methods. (C) Treatment of VCaP cells with small molecule AR antagonist induced similar genome-wide transcriptional effects as AR inhibition by siRNA. Left: fold change from the two types of treatments; Right: SAM d-score of differential expression from the two types of treatments.
For agonism, values obtained from the AR antagonist compounds were compared to those of untreated cells, which were assigned an arbitrary number of 1.0 to indicate no agonism. For antagonism, cells were treated with 0.1nM R1881 alone (corresponding to max receptor activation = 100%) or in combination with the antagonist compounds at various doses to determine IC50 values. Nuclear translocation and cell proliferation values were calculated as indicated under materials and methods.
Signature enrichment analysis of drug-modulated direct activation (top panel) and repression targets (bottom panel) of AR. Shown are enriched gene signatures, with size of each node proportional to number of genes in the signature and width of each line proportional to statistical significance of the overlap between the signatures at the two ends. The signatures were colored by related biological concepts. Direct_AR-activation/Compound30-down_regulated targets refer to genes whose associated AR binding are impacted as well as mRNA level are significantly down-regulated upon Compound 30 treatment. Direct_AR-repression/Compound30-up_regulated targets refer to genes whose associated AR binding are impacted as well as mRNA level are significantly up-regulated upon Compound 30 treatment.
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A key to the chelonine species (Braconidae) (both recorded and recently collected) from Egypt is given. It includes 16 species, of which five species are new to the Egyptian fauna and two (Phanerotoma (Phanerotoma) elbaiensissp. n. and Phanerotoma (Bracotritoma) pontisp. n.) are new for science. A faunistic list and the description for the two new species are added.
Mesosoma: Mesoscutum finely granulated; propodeum finely punctate. Fore wing with vein r as long as vein 3-SR; maximum width of pterostigma 1.7 times vein 3-SR; veins 2-SR and 1-SR straight; middle tibia without distinct blister; outer hind tibial spur 1.1 times the inner one and 0.3 times basitarsus, basitarsus about 0.9 times as long as following tarsomeres combined.
This species is closely related to Phanerotoma (Bracotritoma) bouceki van Achterberg, but ponti hasthe parastigma dark brown, vein 1-M slightly paler than in bouceki, middle tibia is darker and the blister of the middle tibia is much less apparent than in bouceki.
Mesosoma: Finely and densely punctate; mesoscutum coarsely striated laterally (near base of fore wing); metanotum smooth and shiny; propodeum with very fine longitudinal rugae that are curved towards its center and become transverse and much coarser postero-medially. Vein r of fore wing 0.5 times 3-SR; maximum width of pterostigma 0.6 times 3-SR; 2-SR and 1-SR are nearly straight; middle tibia with distinct blister; outer hind tibial spur 1.2 times as long as inner one, slightly longer than 0.3 times basitarsus; hind basitarsus about 0.6 times the following tarsomeres combined.
This species is related to Phanerotoma (Bracotritoma) bilinea Lyle, but elbaiensis hasthe middle tibia with a distinct blister; the parastigma brownish basally; the vein 1-M darker and the apical spine of the hypopygium relatively small. It is similar to Phanerotoma (Bracotritoma) maculata (Wollaston), especially because of the long protruding ovipositor, but differs by its general colour, especially by the yellowish parastigma and basal third of pterostigma (dark brown in maculata). In addition, the characters of the subgenus Phanerotoma, to which the new species belongs, are different. 2b1af7f3a8