Optimal network topologies: Expanders, Cages, Ramanujan graphs, Entangled networks and all that

We report on some recent developments in the search for optimal network topologies. First we review some basic concepts on spectral graph theory, including adjacency and Laplacian matrices, and paying special attention to the topological implications of having large spectral gaps. We also introduce related concepts as ``expanders'', Ramanujan, and Cage graphs. Afterwards, we discuss two different dynamical feautures of networks: synchronizability and flow of random walkers and so that they are optimized if the corresponding Laplacian matrix have a large spectral gap. From this, we show, by developing a numerical optimization algorithm that maximum synchronizability and fast random walk spreading are obtained for a particular type of extremely homogeneous regular networks, with long loops and poor modular structure, that we call entangled networks. These turn out to be related to Ramanujan and Cage graphs. We argue also that these graphs are very good finite-size approximations to Bethe lattices, and provide almost or almost optimal solutions to many other problems as, for instance, searchability in the presence of congestion or performance of neural networks. Finally, we study how these results are modified when studying dynamical processes controlled by a normalized (weighted and directed) dynamics; much more heterogeneous graphs are optimal in this case. Finally, a critical discussion of the limitations and possible extensions of this work is presented.Comment: 17 pages. 11 figures. Small corrections and a new reference. Accepted for pub. in JSTA

Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination

Basic helix-loop-helix transcription factors Olig1 and Olig2 critically regulate oligodendrocyte development. Initially identified as a downstream effector of Olig1, an oligodendrocyte-specific zinc finger transcription repressor, Zfp488, cooperates with Olig2 function. Although Zfp488 is required for oligodendrocyte precursor formation and differentiation during embryonic development, its role in oligodendrogenesis of adult neural progenitor cells is not known. In this study, we tested whether Zfp488 could promote an oligodendrogenic fate in adult subventricular zone (SVZ) neural stem/progenitor cells (NSPCs). Using a cuprizone-induced demyelination model in mice, we examined the effect of retrovirus-mediated Zfp488 overexpression in SVZ NSPCs. Our results showed that Zfp488 efficiently promoted the differentiation of the SVZ NSPCs into mature oligodendrocytes in vivo. After cuprizone-induced demyelination injury, Zfp488-transduced mice also showed significant restoration of motor function to levels comparable to control mice. Together, these findings identify a previously unreported role for Zfp488 in adult oligodendrogenesis and functional remyelination after injury

The HEV Ventilator

HEV is a low-cost, versatile, high-quality ventilator, which has been designed in response to the COVID-19 pandemic. The ventilator is intended to be used both in and out of hospital intensive care units, and for both invasive and non-invasive ventilation. The hardware can be complemented with an external turbine for use in regions where compressed air supplies are not reliably available. The standard modes provided include PC-A/C(Pressure Assist Control),PC-A/C-PRVC(Pressure Regulated Volume Control), PC-PSV (Pressure Support Ventilation) and CPAP (Continuous Positive airway pressure). HEV is designed to support remote training and post market surveillance via a web interface and data logging to complement the standard touch screen operation, making it suitable for a wide range of geographical deployment. The HEV design places emphasis on the quality of the pressure curves and the reactivity of the trigger, delivering a global performance which will be applicable to ventilator needs beyond theCOVID-19 pandemic. This article describes the conceptual design and presents the prototype units together with their performance evaluation.Comment: 34 pages, 18 figures, Extended version of the article submitted to PNA

The auditory cortex of the bat Phyllostomus discolor: Localization and organization of basic response properties

<p>Abstract</p> <p>Background</p> <p>The mammalian auditory cortex can be subdivided into various fields characterized by neurophysiological and neuroarchitectural properties and by connections with different nuclei of the thalamus. Besides the primary auditory cortex, echolocating bats have cortical fields for the processing of temporal and spectral features of the echolocation pulses. This paper reports on location, neuroarchitecture and basic functional organization of the auditory cortex of the microchiropteran bat <it>Phyllostomus discolor </it>(family: Phyllostomidae).</p> <p>Results</p> <p>The auditory cortical area of <it>P. discolor </it>is located at parieto-temporal portions of the neocortex. It covers a rostro-caudal range of about 4800 μm and a medio-lateral distance of about 7000 μm on the flattened cortical surface.</p> <p>The auditory cortices of ten adult <it>P. discolor </it>were electrophysiologically mapped in detail. Responses of 849 units (single neurons and neuronal clusters up to three neurons) to pure tone stimulation were recorded extracellularly. Cortical units were characterized and classified depending on their response properties such as best frequency, auditory threshold, first spike latency, response duration, width and shape of the frequency response area and binaural interactions.</p> <p>Based on neurophysiological and neuroanatomical criteria, the auditory cortex of <it>P. discolor </it>could be subdivided into anterior and posterior ventral fields and anterior and posterior dorsal fields. The representation of response properties within the different auditory cortical fields was analyzed in detail. The two ventral fields were distinguished by their tonotopic organization with opposing frequency gradients. The dorsal cortical fields were not tonotopically organized but contained neurons that were responsive to high frequencies only.</p> <p>Conclusion</p> <p>The auditory cortex of <it>P. discolor </it>resembles the auditory cortex of other phyllostomid bats in size and basic functional organization. The tonotopically organized posterior ventral field might represent the primary auditory cortex and the tonotopically organized anterior ventral field seems to be similar to the anterior auditory field of other mammals. As most energy of the echolocation pulse of <it>P. discolor </it>is contained in the high-frequency range, the non-tonotopically organized high-frequency dorsal region seems to be particularly important for echolocation.</p

Contribution of spatially explicit models to climate change adaptation and mitigation plans for a priority forest habitat

Climate change will impact forest ecosystems, their biodiversity and the livelihoods they sustain. Several adaptation and mitigation strategies to counteract climate change impacts have been proposed for these ecosystems. However, effective implementation of such strategies requires a clear understanding of how climate change will influence the future distribution of forest ecosystems. This study uses maximum entropy modelling (MaxEnt) to predict environmentally suitable areas for cork oak (Quercus suber) woodlands, a socio-economically important forest ecosystem protected by the European Union Habitats Directive. Specifically, we use two climate change scenarios to predict changes in environmental suitability across the entire geographical range of the cork oak and in areas where stands were recently established. Up to 40 % of current environmentally suitable areas for cork oak may be lost by 2070, mainly in northern Africa and southern Iberian Peninsula. Almost 90 % of new cork oak stands are predicted to lose suitability by the end of the century, but future plantations can take advantage of increasing suitability in northern Iberian Peninsula and France. The predicted impacts cross-country borders, showing that a multinational strategy, will be required for cork oak woodland adaptation to climate change. Such a strategy must be regionally adjusted, featuring the protection of refugia sites in southern areas and stimulating sustainable forest management in areas that will keep long-term suitability. Afforestation efforts should also be promoted but must consider environmental suitability and land competition issues

Muscle Dystroglycan Organizes the Postsynapse and Regulates Presynaptic Neurotransmitter Release at the Drosophila Neuromuscular Junction

International audienceBACKGROUND: The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site. CONCLUSION/SIGNIFICANCE: Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg

A putative functional role for oligodendrocytes in mood regulation

Altered glial structure and function is implicated in several major mental illnesses and increasing evidence specifically links changes in oligodendrocytes with disrupted mood regulation. Low density and reduced expression of oligodendrocyte-specific gene transcripts in postmortem human subjects points toward decreased oligodendrocyte function in most of the major mental illnesses. Similar features are observed in rodent models of stress-induced depressive-like phenotypes, such as the unpredictable chronic mild stress and chronic corticosterone exposure, suggesting an effect downstream from stress. However, whether oligodendrocyte changes are a causal component of psychiatric phenotypes is not known. Traditional views that identify oligodendrocytes solely as nonfunctional support cells are being challenged, and recent studies suggest a more dynamic role for oligodendrocytes in neuronal functioning than previously considered, with the region adjacent to the node of Ranvier (i.e., paranode) considered a critical region of glial–neuronal interaction. Here, we briefly review the current knowledge regarding oligodendrocyte disruptions in psychiatric disorders and related animal models, with a focus on major depression. We then highlight several rodent studies, which suggest that alterations in oligodendrocyte structure and function can produce behavioral changes that are informative of mood regulatory mechanisms. Together, these studies suggest a model, whereby impaired oligodendrocyte and possibly paranode structure and function can impact neural circuitry, leading to downstream effects related to emotionality in rodents, and potentially to mood regulation in human psychiatric disorders

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)