Dysregulation of microtubule stability impairs morphofunctional connectivity in primary neuronal networks

Functionally related neurons assemble into connected networks that process and transmit electrochemical information. To do this in a coordinated manner, the number and strength of synaptic connections is tightly regulated. Synapse function relies on the microtubule (MT) cytoskeleton, the dynamics of which are in turn controlled by a plethora of MT-associated proteins, including the MT-stabilizing protein Tau. Although mutations in the Tau-encodingMAPT gene underlie a set of neurodegenerative disorders, termed tauopathies, the exact contribution of MT dynamics and the perturbation thereof to neuronal network connectivity has not yet been scrutinized. Therefore, we investigated the impact of targeted perturbations of MT stability on morphological (e.g., neurite- and synapse density) and functional (e.g., synchronous calcium bursting) correlates of connectivity in networks of primary hippocampal neurons. We found that treatment with MT-stabilizing or -destabilizing compounds impaired morphofunctional connectivity in a reversible manner. We also discovered that overexpression of MAPT induced significant connectivity defects, which were accompanied by alterations in MT dynamics and increased resistance to pharmacological MT depolymerization. Overexpression of a MAPT variant harboring the P301L point mutation in the MT-binding domain did far less, directly linking neuronal connectivity with Tau's MT binding affinity. Our results show that MT stability is a vulnerable node in tauopathies and that its precise pharmacological tuning may positively affect neuronal network connectivity. However, a critical balance in MT turnover causes it to be a difficult therapeutic target with a narrow operating window

Quantum Polariton Simulators

Spin-glass graphs are simulated with a novel scheme using exciton-polaritons. Acting as an effective Monte Carlo solver, the ground state is found efficiently. By tuning a parameter, the system either solves XY or Ising problems. Unlike previous proposals, our setup with auxiliary micropillars naturally avoids any bias from amplitute heterogenity. We demonstrate that the simulator is able to find the ground state asymptotically for arbitrary large graphs. These findings show explicitly how polariton simulators could be useful in practice. We furthermore provide strong evidence for the system's ability to harness a quantum speedup

A well applied ballast tank coating = green ballast tank coating

When a ship reaches the end of its service life it is broken down at a demolition site to recover steel and other useful items. The recycling process itself imposes risks to the human health and safety, as well as to our habitat by sending toxic components into the atmosphere and the maritime environment. Not all parts and products can be recycled and thus waste, toxic and non-toxic, is generated. Extending the service life of a ship can contribute to the protection of human life and the environment.The same is valid when looking at the service life from the ship construction point of view. If the service life of a ship is extended less ships have to be built. To estimate the energy consumption of steel production Javaherdashti (2008) suggests that the energy required to produce one ton of steel is approximately equal to the energy an average family consumes over 3 months and roughly worldwide one ton of steel turns into rust every 90 seconds (Javaherdashti, 2008). The service life of a ship is not determined by the external battering of the ship's hull by wind and waves but mainly by the internal gradual corrosion of the ballast tanks (Thapar, 2013). The latter implicates that a coating with a longer service life will have a direct impact on the life cycle of the ship, the toxic components send into the atmosphere and the energy consumption.Most ballast tanks are prepared and coated according to the IMO Performance Standard for Protective Coating (PSPC), using a light-coloured epoxy coating that, when on board maintenance is being performed by the crew, should remain in a good condition for 15 years. Ship owners are not only pushed by international legislation (IMO, 2009) but also by commercial needs in preserving a good reputation, to keep the ballast tanks of their vessels in a good condition to avoid extra inspections and costs. Aiming to extend the service life of your vessel to 25 years with ballast tanks in a good condition, a full-recoat must be considered. Recoating is bad for the environment as toxic components are sent into the atmosphere

Ideally embedded space-times

Due to the growing interest in embeddings of space-time in higher-dimensional spaces we consider a specific type of embedding. After proving an inequality between intrinsically defined curvature invariants and the squared mean curvature, we extend the notion of ideal embeddings from Riemannian geometry to the indefinite case. Ideal embeddings are such that the embedded manifold receives the least amount of tension from the surrounding space. Then it is shown that the de Sitter spaces, a Robertson-Walker space-time and some anisotropic perfect fluid metrics can be ideally embedded in a five-dimensional pseudo-Euclidean space.Comment: layout changed and typos corrected; uses revtex

Single-cell and neuronal network alterations in an in vitro model of Fragile X syndrome

The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signaling, and an altered balance between excitation and inhibition has been hypothesized to underlie the clinical consequences of absence of the protein. Using Fmrp knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. The loss of FMRP also caused a structural increase in the number of excitatory synaptic terminals. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best our experimental observations during the ex vivo formation of the network connections

Do we still need animals? Surveying the role of animal-free models in Alzheimer’s and Parkinson’s disease research

The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the “3R” principle of “Refining, Reducing and Replacing” animal experiments, and across the globe, different initiatives stimulate the use of animal-free methods. Based on an extensive literature screen to map the development and adoption of animal-free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal-derived models. Among the animal-free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal-free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non-animal-based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal-free approaches