Traditionally, masculinization of the rodent brain is believed to depend on estrogen receptors (ERs) and not androgen receptors (ARs). According to the aromatization hypothesis, circulating testosterone from the testes is converted locally PI3K inhibitor in the brain by aromatase to estrogens, which then activate ERs to masculinize the brain. However, an emerging body of evidence indicates that the aromatization hypothesis cannot fully account for sex differences in brain morphology and behavior, and that androgens acting on ARs also play a role. The testicular feminization mutation (Tfm) in rodents, which produces a nonfunctional AR protein, provides an excellent model to probe the role of ARs in the development of brain
and behavior. Tfm rodent models indicate that ARs are normally involved in the masculinization of many sexually dimorphic brain regions and a variety of behaviors, including sexual behaviors, stress response
and cognitive processing. We review the role of ARs in the development of the brain and behavior, with an emphasis on what has been learned from Tfm rodents as well as from related mutations in humans causing complete androgen insensitivity. (c) 2008 Elsevier Inc. All rights reserved.”
“Eukaryotic cells exposed to DNA damaging agents activate important defensive pathways by inducing multiple proteins involved in DNA repair, cell cycle checkpoint control and potentially apoptosis. After the acceptance of Alvocidib the hypothesis that oxidatively generated clustered DNA lesions (OCDL: closely spaced DNA lesions) can be induced even by low doses of ionizing radiation or even endogenously, and significant advances have been made in the understanding of the biochemistry underlying the
PF-6463922 research buy repair of closely spaced DNA lesions, many questions still remain unanswered. The major questions that have to be answered in the near future are: 1) how human cells process these types of DNA damage if they repair them at all, 2) under what conditions a double strand break (DSB) may be created during the processing of two closely spaced DNA lesions and 3) what type of repair protein interactions govern the processing of complex DNA damage? The data existing so far on human cells and tissues are very limited and in some cases contradicting. All of them though agree however on the major importance of gaining mechanistic insights on the pathways used by the cell to confront and process complex DNA damage located in a small DNA volume and the need of more in depth analytical studies. We selectively review recently-obtained data on the processing of non-DSB DNA damage clusters in human cells and tissues and discuss the current status of knowledge in the field.”
“Aminoglycoside antibiotics participate in a large variety of binding processes involving both RNA and proteins. The description, in recent years, of several clinically relevant aminoglycoside/receptor complexes has greatly stimulated the structural-based design of new bioactive derivatives.