Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub.

Infection and tissue damage induces assembly of supramolecular organizing centres (SMOCs)), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate inflammatory signaling. SMOC assembly is thought to drive digital all-or-none responses, yet TLR activation by diverse microbes induces anything from mild to severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in living macrophages, we find that MyDDosomes assemble within minutes of TLR4 stimulation. TLR4/MD2 activation leads only to formation of TLR4/MD2 heterotetramers, but not oligomers, suggesting a stoichiometric mismatch between activated receptors and MyDDosomes. The strength of TLR4 signalling depends not only on the number and size of MyDDosomes formed but also how quickly these structures assemble. Activated TLR4, therefore, acts transiently nucleating assembly of MyDDosomes, a process that is uncoupled from receptor activation. These data explain how the oncogenic mutation of MyD88 (L265P) assembles MyDDosomes in the absence of receptor activation to cause constitutive activation of pro-survival NF-κB signalling

Oxidation Resistance 1 Modulates Glycolytic Pathways in the Cerebellum via an Interaction with Glucose-6-Phosphate Isomerase

Glucose metabolism is essential for the brain: it not only provides the required energy for cellular function and communication but also participates in balancing the levels of oxidative stress in neurons. Defects in glucose metabolism have been described in neurodegenerative disease; however, it remains unclear how this fundamental process contributes to neuronal cell death in these disorders. Here, we investigated the molecular mechanisms driving the selective neurodegeneration in an ataxic mouse model lacking oxidation resistance 1 (Oxr1) and discovered an unexpected function for this protein as a regulator of the glycolytic enzyme, glucose-6-phosphate isomerase (GPI/Gpi1). Initially, we present a dysregulation of metabolites of glucose metabolism at the pre-symptomatic stage in the Oxr1 knockout cerebellum. We then demonstrate that Oxr1 and Gpi1 physically and functionally interact and that the level of Gpi1 oligomerisation is disrupted when Oxr1 is deleted in vivo. Furthermore, we show that Oxr1 modulates the additional and less well-understood roles of Gpi1 as a cytokine and neuroprotective factor. Overall, our data identify a new molecular function for Oxr1, establishing this protein as important player in neuronal survival, regulating both oxidative stress and glucose metabolism in the brain

An IoT-Aware Approach for Elderly-Friendly Cities

The ever-growing life expectancy of people requires the adoption of proper solutions for addressing the particular needs of elderly people in a sustainable way, both from service provision and economic point of view. Mild cognitive impairments and frailty are typical examples of elderly conditions which, if not timely addressed, can turn out into more complex diseases that are harder and costlier to treat. Information and communication technologies, and in particular Internet of Things technologies, can foster the creation of monitoring and intervention systems, both on an ambient-assisted living and smart city scope, for early detecting behavioral changes in elderly people. This allows to timely detect any potential risky situation and properly intervene, with benefits in terms of treatment's costs. In this context, as part of the H2020-funded City4Age project, this paper presents the data capturing and data management layers of the whole City4Age platform. In particular, this paper deals with an unobtrusive data gathering system implementation to collect data about daily activities of elderly people, and with the implementation of the related linked open data (LOD)-based data management system. The collected data are then used by other layers of the platform to perform risk detection algorithms and generate the proper customized interventions. Through the validation of some use-cases, it is demonstrated how this scalable approach, also characterized by unobtrusive and low-cost sensing technologies, can produce data with a high level of abstraction useful to define a risk profile of each elderly person

ldomic/lintools: LINTools v0.3

This release of LINTools contains some major updates to the functionality and user friendliness of the software, such as configuration file more choice in colorschemes for the plots numeric output files from the analysis proces

Cryopreservation of germ cells for the production of marine species

Germ cell cryopreservation is a safe method to store and preserve genetic material. Cryobanks in aquatic species were developed with different aims, benefiting fish farming, from management of reproduction to genetic selection of sperm from males with high reproductive value. Research has been conducted on the development of protocols for new/problematic species, for commercial species to improve gamete quality during storage or for conservation purposes.This work was supported by COST AQUAGAMETE (FA1205), CRIOBIV and REPLING projects (PROMAR).info:eu-repo/semantics/publishedVersio

LINTools - dynamic representation of protein-ligand interactions

<p>This is the first full release of LINTools (Ligand Interaction Network Tools). This script will analyse and display protein-ligand interactions from single frames or trajectories. Therefore, it is possible to view dynamic 3D data from molecular dynamics simulations in 2D static representation of ligand molecule and the surrounding residues. At the moment, LINTools will analyse occurrence of residues within cutoff and RMSF (root-mean-square fluctuation) of ligand atoms in the trajectory, as well as display hydrogen bonds.</p> <p>The LINTools Team</p