Astrocyte morphology determines properties of the astroglial networks

Astrocytes are very abundant glial cells in the brain. They perform many functions: provision of nutrient to the neurons, maintenance of extracellular ion balance, shaping of network operations and synaptic signaling and plasticity. Astrocytes can form large heterogeneous networks throughout the brain. In the hippocampal CA1 region, astrocytes are connected by GJs that are mainly composed of GJα1 (Cx43) and GJβ6 (Cx30). Together, these proteins form hexameric structures called connexons which can connect two adjacent cells by creating GJs. The astroglial GJ coupling is important for various processes such as i) distribution of metabolites, ii) regulation of synaptic transmission and iii) plasticity and biochemical support to the endothelial cells which form the BBB. These networks were proposed to counteract hyperactivity by facilitating glutamate removal, thereby attenuating synaptic transmission. Moreover, coupled astrocyte networks are limited by the presence of the CA1 pyramidal cell layer which works as an anatomical barrier. This layer also impacts on the diffusion of astrocytes within the network they form. Previous experiments performed in the laboratory of Prof. Dr. Henneberger showed that induction of LTP or epileptiform activity rapidly changes the morphology of astrocyte and the diffusion within and between astrocytes in acute hippocampal slices. These changes may modify the tortuosity of intracellular space affecting diffusion of molecules within one cell and to neighboring ones. Therefore, the aim of this thesis was to investigate the fundamental relationship between astrocytic structure and the strength of astroglial coupling using combinations of 2-photon excitation fluorescence microscopy and electrophysiology. This study found that the primary morphological determinant of coupling strength is the complexity of the astroglial branching pattern (segmentation) rather than the total intracellular volume available for diffusion (VF). Using the FRAP technique, this project could also reveal that changes of intracellular diffusivity do not explain the link between astroglial morphological complexity and coupling. Moreover, this study also showed, by analyzing the location and density of Cx30 and Cx43, that the astrocyte structure does not define the pattern of GJ formation between astrocytes. Finally, astrocyte morphology was specifically manipulated by injecting two recombinant viruses in mice dorsal hippocampi. These viruses were able to affect the actin polymerization by altering the activity of RhoA GTPase and LIMK. The over-expression of the mutant variants of RhoA but not the LIMK inhibitor S3 peptide, resulted in a significant reduction of the astrocytic VF while both constructs were able to reduce the coupling strength in the glial coupled network. By a controlled manipulation of the astrocyte cytoskeleton rearrangement via viral injections this study was able to show how glial morphology shapes connections within the astrocyte network. This provides the basis for further studies of network diffusivity in both physiological and pathophysiological conditions

Microglia and infiltrating macrophages in ictogenesis and epileptogenesis

Phagocytes maintain homeostasis in a healthy brain. Upon injury, they are essential for repairing damaged tissue, recruiting other immune cells, and releasing cytokines as the first line of defense. However, there seems to be a delicate balance between the beneficial and detrimental effects of their activation in a seizing brain. Blocking the infiltration of peripheral phagocytes (macrophages) or their depletion can partially alleviate epileptic seizures and prevent the death of neurons in experimental models of epilepsy. However, the depletion of resident phagocytes in the brain (microglia) can aggravate disease outcomes. This review describes the role of resident microglia and peripheral infiltrating monocytes in animal models of acutely triggered seizures and epilepsy. Understanding the roles of phagocytes in ictogenesis and the time course of their activation and involvement in epileptogenesis and disease progression can offer us new biomarkers to identify patients at risk of developing epilepsy after a brain insult, as well as provide novel therapeutic targets for treating epilepsy

Finding Minimal and Non-Minimal Surfaces through the Natural Force Density Method

This paper discusses the Natural Force Density Method, an extension of the well known Force Density Method for the shape finding of continuous membrane structures, which preserves the linearity of the original method, overcoming the need for regular meshes. The method is capable of providing viable membrane configurations, comprising the membrane shape and its associates stress field in a single iteration. Besides, if the NFDM is applied iteratively, it is capable of converging to a configuration under a uniform and isotropic plane stress field. This means that a minimal surface for a membrane can be achieved through a succession of viable configurations, in such a way that the process can be stopped at any iteration, and the result assumed as good. The NFDM can also be employed to the shape finding of non-minimal surfaces. In such cases, however, there is no guarantee that a prescribed, non-isotropic stress field can be achieved through iterations. The paper presents several examples of application of the NFDM to the shape finding of minimal and nonminimal membrane surfaces

Narcissism, Attraction, and Self-Esteem: Comparing Agentic and Communal Subtypes

The current study investigated self-esteem as a moderator of the relationships between both agentic and communal narcissism and romantic attraction. The attraction to the prospective targets, and self-esteem’s influence on the relationships, differed in direction, strength, and significance

Formulaçao de um elemento finito de cabo incorporando o efeito do atrito (Elemento de cabos escorregando)

O trabalho apresenta a formulacáo geometricamente exata e a implementaçao computacional de um elemento finito de cabo que permite o escorregamento em presenca de atrito. O novo elemento fornece procedimentos naturais para simular o processo de montagem e a resposta aos carregamentos de estruturas de cabos em geral, além de ter campos promissores de aplicaçáo no modelamento de estruturas de concreto protendido e no estudo de oscilaçoes auto-excitáveis. Resultados de exemplos elementares sáo discutidos.Peer Reviewe

Formulaçao de um elemento finito de cabo incorporando o efeito do atrito (Elemento de cabos escorregando)

O trabalho apresenta a formulacáo geometricamente exata e a implementaçao computacional de um elemento finito de cabo que permite o escorregamento em presenca de atrito. O novo elemento fornece procedimentos naturais para simular o processo de montagem e a resposta aos carregamentos de estruturas de cabos em geral, além de ter campos promissores de aplicaçáo no modelamento de estruturas de concreto protendido e no estudo de oscilaçoes auto-excitáveis. Resultados de exemplos elementares sáo discutidos.Peer Reviewe

Direct area minimization through dynamic relaxation

Minimal surfaces, characterized by the property of a minimal area within a fixed boundary, offer an interesting design option for membrane structures, since they are uniquely defined and provide economy of material and more regular fabric patterns. Analytical solution for the non-linear equation governing area minimization may be rather difficult for complex boundaries, leaving numerical solution as the only general way to tackle with the problem. In this paper we show that the dynamic relaxation method offers an interesting alternative to solve the area minimization problem, first interpreted as a nonlinear equilibrium problem, then replaced by a pseudo-dynamic analysis, where fictitious masses and damping matrices are arbitrarily chosen to control the stability of the time integration process