Calcineurin/NFAT Signaling in Activated Astrocytes Drives Network Hyperexcitability in A\u3cem\u3eβ\u3c/em\u3e-Bearing Mice

Hyperexcitable neuronal networks are mechanistically linked to the pathologic and clinical features of Alzheimer\u27s disease (AD). Astrocytes are a primary defense against hyperexcitability, but their functional phenotype during AD is poorly understood. Here, we found that activated astrocytes in the 5xFAD mouse model were strongly associated with proteolysis of the protein phosphatase calcineurin (CN) and the elevated expression of the CN-dependent transcription factor nuclear factor of activated T cells 4 (NFAT4). Intrahippocampal injections of adeno-associated virus vectors containing the astrocyte-specific promoter Gfa2 and the NFAT inhibitory peptide VIVIT reduced signs of glutamate-mediated hyperexcitability in 5xFAD mice, measured in vivo with microelectrode arrays and ex vivo brain slices, using whole-cell voltage clamp. VIVIT treatment in 5xFAD mice led to increased expression of the astrocytic glutamate transporter GLT-1 and to attenuated changes in dendrite morphology, synaptic strength, and NMDAR-dependent responses. The results reveal astrocytic CN/NFAT4 as a key pathologic mechanism for driving glutamate dysregulation and neuronal hyperactivity during AD

Deconstruction of Crystalline Networks into Underlying Nets: Relevance for Terminology Guidelines and Crystallographic Databases

This communication briefly reviews why network topology is an important tool (for understanding, comparing, communicating, designing, and solving crystal structures from powder diffraction data) and then discusses the terms of an IUPAC project dealing with various aspects of network topology. One is the ambiguity in node assignment, and this question is addressed in more detail. First, we define the most important approaches: the "all node" deconstruction considering all branch points of the linkers, the "single node" deconstruction considering only components mixed, and the ToposPro "standard representation" also considering linkers as one node but, if present, takes each metal atom as a separate node. These methods are applied to a number of metal organic framework structures (MOFs, although this is just one example of materials this method is applicable on), and it is concluded that the "all node" method potentially yields more information on the structure in question but cannot be recommended as the only way of reporting the network topology. In addition, several terms needing definitions are discussed

Straining and relaxation properties of wet paper during heating

The influence of increasing temperature on the strength and relaxation of wet press-dry paper was studied using a tensile tester equipped with a special heating chamber. The heating chamber made fast heating possible without detectable moisture loss. The results showed that temperature had a significant influence on the straining, relaxation and re-straining behavior of wet paper. The majority of observed changes due to increased temperature seem to originate from the softening of wet fibers. The observed short time scale phenomena in wet paper have practical significance for fiber webs dried under tension in paper machines. Straining–relaxation–de-straining cycles were used to analyze the effect of heating on the work of straining and apparent plastic and elastic work. Heating affected the amount of mechanical energy absorbed by the sample and the amount of elastic energy recoverable in a straining–relaxation–de-straining cycle. Increased temperature reduced the work of straining and both elastically and plastically absorbed energy. The hysteresis work of the examined wet papers was estimated to correspond to a 1–22 mK temperature change. This suggests that temperature changes in wet paper induced by straining play no role in practice. After mechanical conditioning, tensile stiffness in the re-straining of wet paper depended only marginally on temperature, whereas in initial straining the effect of temperature was clearly stronger. The linear thermal expansion coefficient of wet paper in the machine direction was estimated and the influence of moisture content on the linear thermal expansion coefficient of paper was found to be relatively small