Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta - regulation by selective estrogen receptor modulators and importance in breast cancer

Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents

Supernova remnants: the X-ray perspective

Supernova remnants are beautiful astronomical objects that are also of high scientific interest, because they provide insights into supernova explosion mechanisms, and because they are the likely sources of Galactic cosmic rays. X-ray observations are an important means to study these objects.And in particular the advances made in X-ray imaging spectroscopy over the last two decades has greatly increased our knowledge about supernova remnants. It has made it possible to map the products of fresh nucleosynthesis, and resulted in the identification of regions near shock fronts that emit X-ray synchrotron radiation. In this text all the relevant aspects of X-ray emission from supernova remnants are reviewed and put into the context of supernova explosion properties and the physics and evolution of supernova remnants. The first half of this review has a more tutorial style and discusses the basics of supernova remnant physics and thermal and non-thermal X-ray emission. The second half offers a review of the recent advances.The topics addressed there are core collapse and thermonuclear supernova remnants, SN 1987A, mature supernova remnants, mixed-morphology remnants, including a discussion of the recent finding of overionization in some of them, and finally X-ray synchrotron radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2 column-layout. 78 pages, 42 figures. This replaced version has some minor language edits and several references have been correcte

The Development and Validation of the Empathy Components Questionnaire (ECQ)

Key research suggests that empathy is a multidimensional construct comprising of both cognitive and affective components. More recent theories and research suggest even further factors within these components of empathy, including the ability to empathize with others versus the drive towards empathizing with others. While numerous self-report measures have been developed to examine empathy, none of them currently index all of these wider components together. The aim of the present research was to develop and validate the Empathy Components Questionnaire (ECQ) to measure cognitive and affective components, as well as ability and drive components within each. Study one utilized items measuring cognitive and affective empathy taken from various established questionnaires to create an initial version of the ECQ. Principal component analysis (PCA) was used to examine the underlying components of empathy within the ECQ in a sample of 101 typical adults. Results revealed a five-component model consisting of cognitive ability, cognitive drive, affective ability, affective drive, and a fifth factor assessing affective reactivity. This five-component structure was then validated and confirmed using confirmatory factor analysis (CFA) in an independent sample of 211 typical adults. Results also showed that females scored higher than males overall on the ECQ, and on specific components, which is consistent with previous findings of a female advantage on self-reported empathy. Findings also showed certain components predicted scores on an independent measure of social behavior, which provided good convergent validity of the ECQ. Together, these findings validate the newly developed ECQ as a multidimensional measure of empathy more in-line with current theories of empathy. The ECQ provides a useful new tool for quick and easy measurement of empathy and its components for research with both healthy and clinical populations