Laquinimod Modulates Human Astrocyte Function and Dampens Astrocyte-Induced Neurotoxicity during Inflammation

Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte–neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally, in vitro experiments with rat spinal neurons showed that laquinimod did not exert neuroprotection directly on the neuron but dampened astrocyte-induced neurodegeneration. Our findings indicate that fibroblast-derived human astrocytes represent a suitable model to study astrocyte–neuron crosstalk and demonstrate indirect, partial neuroprotective efficacy for laquinimod.     

Processing of W/Si and Si/W bilayers and multilayers with single and multiple excimer-laser pulses

Interdiffusion phenomena, thermal damage and ablation of W/Si and Si/W bilayers and multilayers under XeCl-excimer laser (=308 nm) irradiation at fluences of 0.15, 0.3 and 0.6 J/cm² were studied. Samples were prepared by UHV e-beam evaporation onto oxidized Si. The thickness of W and Si layers and the total thickness of the structures were 1–20 nm and 40–100 nm, respectively. 1 to 300 laser pulses were directed to the same irradiation site. At 0.6 J/cm² the samples were damaged even by a single laser pulse. At 0.3 J/cm² WSi₂ silicide formation, surface roughening and ablation were observed. The threshold for significant changes depends on the number of pulses: it was between 3–10 pulses and 10–30 pulses for bilayers with W and Si surfaces, respectively, and more than 100 pulses for multilayers with the same total thickness of tungsten. At 0.15 J/cm² the periodicity of the multilayers was preserved. Temperature profiles in layered structures were obtained by numerical simulations. The observed differences of the resistance of various bilayers and multilayers against UV irradiation are discussed.     

Averaging, Conley index continuation and recurrent dynamics in almost-periodic parabolic equations

We study a non-autonomous parabolic equation with almost-periodic, rapidly oscillating principal part and nonlinear interactions. We associate to the equation a skew-product semiflow and, for a special class of nonlinearities, we define the Conley index of isolated compact invariant sets. As the frequency of the oscillations tends to infinity, we prove that every isolated compact invariant set of the averaged autonomous equation can be continued to an isolated compact invariant set of the skew-product semiflow associated to the non-autonomous equation. Finally, we illustrate some examples in which the Conley index can be explicitly computed and can be exploited to detect the existence of recurrent dynamics in the equation.     

Allometry and growth: A unified view

Allometry is crucial in biology; scaling relations are implied in laws of growth of living systems. The self similarity of Gompertzian growths of biological organisms plays a key role, in this regard, in biological similitude. The origin of allometric relationships and values of the scaling exponents is a source of debate, as well as the origin of the range of biological scales. But, besides biology, scaling and growth characterize many different complex systems. Encompassing these aspects in a unified view is an interesting target. In this paper we propose a coarse but significant model that is applied to astrophysical structures and biological organisms. The inclusion of such different systems suggests applications to fields where allometry is emerging, such as economics, urban planning and the social sciences.     

Homology computation for a class of contact structures on T^3

We consider a family of tight contact forms on the three-dimensional torus and we compute the relative Contact Homology by using the variational theory of critical points at infinity. We will also show local stability.     

Chemical promenades: Exploring potential-energy surfaces with immersive virtual reality

The virtual-reality framework AVATAR (Advanced Virtual Approach to Topological Analysis of Reactivity) for the immersive exploration of potential-energy landscapes is presented. AVATAR is based on modern consumer-grade virtual-reality technology and builds on two key concepts: (a) the reduction of the dimensionality of the potential-energy surface to two process-tailored, physically meaningful generalized coordinates, and (b) the analogy between the evolution of a chemical process and a pathway through valleys (potential wells) and mountain passes (saddle points) of the associated potential energy landscape. Examples including the discovery of competitive reaction paths in simple A + BC collisional systems and the interconversion between conformers in ring-puckering motions of flexible rings highlight the innovation potential that augmented and virtual reality convey for teaching, training, and supporting research in chemistry.