Regulation of estrogen receptor beta activity and implications in health and disease

Together with the estrogen receptor (ER) alpha, estrogen receptor beta (ERβ) mediates many of the physiological effects of estrogens. As ERβ is crucially involved in a variety of important physiological processes, its activity should be tightly regulated. ERβ regulation is achieved by hormone binding as well as by posttranslational modifications of the receptor. Furthermore, ERβ expression levels are under circadian control and can be regulated by DNA methylation of the ERβ promoter region. There are also a number of factors that can interfere with ERβ activity, such as phytoestrogens, endocrine disruptive chemicals, and growth factors. In this article, we outline different mechanisms of ERβ regulation and how they are implicated in various diseases. We also discuss how these insights might help to specifically target ERβ in drug design.     

RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.

Neurotransmitters are released by synaptic vesicle fusion at the active zone. The active zone of a synapse mediates Ca2+-triggered neurotransmitter release, and integrates presynaptic signals in regulating this release. Much is known about the structure of active zones and synaptic vesicles, but the functional relation between their components is poorly understood. Here we show that RIM1alpha, an active zone protein that was identified as a putative effector for the synaptic vesicle protein Rab3A, interacts with several active zone molecules, including Munc13-1 (ref. 6) and alpha-liprins, to form a protein scaffold in the presynaptic nerve terminal. Abolishing the expression of RIM1alpha in mice shows that RIM1alpha is essential for maintaining normal probability of neurotransmitter release, and for regulating release during short-term synaptic plasticity. These data indicate that RIM1alpha has a central function in integrating active zone proteins and synaptic vesicles into a molecular scaffold that controls neurotransmitter release.     

A Combinatorial Approach to Assess the Separability of Clusters

Separability of clusters is an issue that arises in many different areas, and is often used in a rather vague and subjective manner. We introduce a combinatorial notion of interiority to derive a global view on separability of a set of entities. We develop this approach further to evaluate the overall separability of a partition in the context of cluster analysis. Our approach captures combinatorial and geometrical aspects of data and provides, in addition to numerical evaluations, graphical representations particularly useful when data are not easily visualized. We illustrate the methodology on some real and simulated datasets.     

Strategies for the Study of Complex Socio-Economic Systems: an Approach Using Agent-Based Simulation

The present paper proposes a research strategy that integrates top-down and bottom-up approaches, aimed at the study of complex socio-economic systems. Through a theoretical analysis, it is demonstrated throughout the text a strategy that allows the articulation between agent-based simulation approaches and methods of deductive and phenomenological basis capable of providing social sciences with unprecedented accuracy due to ethical and methodological limitations imposed by the study object until then. This is because this type of hybrid approach allows the construction of a deep systemic articulation between the micro and the macro, as advocated by the General Theory of Systems, at the same time as it is supported by systematic experiments that give new light to the study of the socio-economic complexity.     

Über die submikroskopische Organisation der Glanzstreifen (Eberthlinien) der Vorhof- und Kammermuskulatur des Herzens

Summary By means of polarization microscope, the submicroscopic structure of intercalated discs in auricle and ventricle muscles of rat heart were investigated using an imbibition method and precipitation anisotropic staining. The investigation proved that the protein and lipid parts in intercalated discs of auricle muscles are, on the contrary, arranged like intercalated discs of ventricle muscles.The ultrastructural variance revealed can be explained by mechanical effects exerted by the myofibrils on the plasma membranes which separate the adjacent heart muscle cells.