Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey

Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system

A Real-Time Space Debris Detection System for BIRALES

The ever increasing satellite population in near-Earth orbit has made the monitoring and tracking of cooperative and non-cooperative objects ever more important. Non-cooperative objects, or space debris, pose a threat to existing and future satellites as they cannot avoid potential collisions. Furthermore, the orbit of the smaller debris is often not actively monitored. As the population grows, the risk of a collision increases. Thus, various institutions around the world have been upgrading their space detection capabilities in order to better monitor the objects orbiting Earth down to a few centimetres in diameter. One of the latest such systems is the BIstatic RAdar for LEo Survey (BIRALES) space debris detection system based in Italy. The BIRALES system is a bistatic radar composed of a radio transmitter in Sardinia and the Medicina Northern Cross radio telescope near Bologna as the receiver. The backend of this system includes a digital beamformer able to synthetize 32 beams covering the instrument's Field of View (FoV). As a high-velocity object transits, its Doppler shift signature (or track) can be measured. Whilst a number of streak detection algorithms have been proposed for optical telescopes, the number of detection algorithms for high-speed objects for bistatic radars is limited. This work describes the detection algorithm used in the BIRALES space debris detection pipeline. The detection algorithm takes the beamformed, channelized data as input. Firstly, the data undergoes a number of pre-processing stages before the potential space debris candidates are identified. Secondly, the candidates are validated against a number of criteria in order to improve the detection quality. The algorithm was designed to process the incoming data across 32 beams in real-time. Initial validation results on known objects are positive and the system has been shown to reliably determine orbiting objects with minimal false positives

Copper-Triggered Aggregation of Ubiquitin

Neurodegenerative disorders share common features comprising aggregation of misfolded proteins, failure of the ubiquitin-proteasome system, and increased levels of metal ions in the brain. Protein aggregates within affected cells often contain ubiquitin, however no report has focused on the aggregation propensity of this protein. Recently it was shown that copper, differently from zinc, nickel, aluminum, or cadmium, compromises ubiquitin stability and binds to the N-terminus with 0.1 micromolar affinity. This paper addresses the role of copper upon ubiquitin aggregation. In water, incubation with Cu(II) leads to formation of spherical particles that can progress from dimers to larger conglomerates. These spherical oligomers are SDS-resistant and are destroyed upon Cu(II) chelation or reduction to Cu(I). In water/trifluoroethanol (80∶20, v/v), a mimic of the local decrease in dielectric constant experienced in proximity to a membrane surface, ubiquitin incubation with Cu(II) causes time-dependent changes in circular dichroism and Fourier-transform infrared spectra, indicative of increasing β-sheet content. Analysis by atomic force and transmission electron microscopy reveals, in the given order, formation of spherical particles consistent with the size of early oligomers detected by gel electrophoresis, clustering of these particles in straight and curved chains, formation of ring structures, growth of trigonal branches from the rings, coalescence of the trigonal branched structures in a network. Notably, none of these ubiquitin aggregates was positive to tests for amyloid and Cu(II) chelation or reduction produced aggregate disassembly. The early formed Cu(II)-stabilized spherical oligomers, when reconstituted in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes and in POPC planar bilayers, form annular and pore-like structures, respectively, which are common to several neurodegenerative disorders including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis, and prion diseases, and have been proposed to be the primary toxic species. Susceptibility to aggregation of ubiquitin, as it emerges from the present study, may represent a potential risk factor for disease onset or progression while cells attempt to tag and process toxic substrates

- Philippe Bourgois e Jeff Schonberg, Reietti e Fuorilegge.Antropologia della violenza nella metropoli americana

Una lettura critica sul test

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