Bayesian Integration in a Spiking Neural System for Sensorimotor Control

The brain continuously estimates the state of body and environment, with specific regions that are thought to act as Bayesian estimator, optimally integrating noisy and delayed sensory feedback with sensory predictions generated by the cerebellum. In control theory, Bayesian estimators are usually implemented using high-level representations. In this work, we designed a new spike-based computational model of a Bayesian estimator. The state estimator receives spiking activity from two neural populations encoding the sensory feedback and the cerebellar prediction, and it continuously computes the spike variability within each population as a reliability index of the signal these populations encode. The state estimator output encodes the current state estimate. We simulated a reaching task at different stages of cerebellar learning. The activity of the sensory feedback neurons encoded a noisy version of the trajectory after actual movement, with an almost constant intrapopulation spiking variability. Conversely, the activity of the cerebellar output neurons depended on the phase of the learning process. Before learning, they fired at their baseline not encoding any relevant information, and the variability was set to be higher than that of the sensory feedback (more reliable, albeit delayed). When learning was complete, their activity encoded the trajectory before the actual execution, providing an accurate sensory prediction; in this case, the variability was set to be lower than that of the sensory feedback. The state estimator model optimally integrated the neural activities of the afferent populations, so that the output state estimate was primarily driven by sensory feedback in prelearning and by the cerebellar prediction in postlearning. It was able to deal even with more complex scenarios, for example, by shifting the dominant source during the movement execution if information availability suddenly changed. The proposed tool will be a critical block within integrated spiking, brain-inspired control systems for simulations of sensorimotor tasks

Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.

Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of \u3b1 catalytic and \u3b2 regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2\u3b1 immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-\u3baB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL

Brain-Inspired Spiking Neural Network Controller for a Neurorobotic Whisker System

It is common for animals to use self-generated movements to actively sense the surrounding environment. For instance, rodents rhythmically move their whiskers to explore the space close to their body. The mouse whisker system has become a standard model for studying active sensing and sensorimotor integration through feedback loops. In this work, we developed a bioinspired spiking neural network model of the sensorimotor peripheral whisker system, modeling trigeminal ganglion, trigeminal nuclei, facial nuclei, and central pattern generator neuronal populations. This network was embedded in a virtual mouse robot, exploiting the Human Brain Project's Neurorobotics Platform, a simulation platform offering a virtual environment to develop and test robots driven by brain-inspired controllers. Eventually, the peripheral whisker system was adequately connected to an adaptive cerebellar network controller. The whole system was able to drive active whisking with learning capability, matching neural correlates of behavior experimentally recorded in mice

The Importance of Cerebellar Connectivity on Simulated Brain Dynamics

The brain shows a complex multiscale organization that prevents a direct understanding of how structure, function and dynamics are correlated. To date, advances in neural modeling offer a unique opportunity for simulating global brain dynamics by embedding empirical data on different scales in a mathematical framework. The Virtual Brain (TVB) is an advanced data-driven model allowing to simulate brain dynamics starting from individual subjects’ structural and functional connectivity obtained, for example, from magnetic resonance imaging (MRI). The use of TVB has been limited so far to cerebral connectivity but here, for the first time, we have introduced cerebellar nodes and interconnecting tracts to demonstrate the impact of cerebro-cerebellar loops on brain dynamics. Indeed, the matching between the empirical and simulated functional connectome was significantly improved when including the cerebro-cerebellar loops. This positive result should be considered as a first step, since issues remain open about the best strategy to reconstruct effective structural connectivity and the nature of the neural mass or mean-field models generating local activity in the nodes. For example, signal processing is known to differ remarkably between cortical and cerebellar microcircuits. Tackling these challenges is expected to further improve the predictive power of functional brain activity simulations, using TVB or other similar tools, in explaining not just global brain dynamics but also the role of cerebellum in determining brain states in physiological conditions and in the numerous pathologies affecting the cerebro-cerebellar loop

Calpionellid and calcareous nannofossil evolution and calcification across Tithonian-Berriasian interval (Tethys Ocean).

The Tithonian-Berriasian interval is characterized by the appearance of calpionellid and by a major calcareous nannofossil speciation episode: several genera and species first appear and evolve, showing an increase in diversity, abundance and calcification degree. Monte Pernice and Torre de Busi sections (Southern Alps, Italy) have been analyzed for calcareous nannofossil and calpionellid biostratigraphy, relative and absolute abundances and to reconstruct biogenic calcite palaeofluxes. Calcareous nannofossils have been investigated on simple smear slides and ultra-thin sections (7-8 \ub5m thick) calpionellids on the same thin sections (20-30 \u3bcm thick). All nannofossil specimens have been counted on 1 mm2 of ultra-thin section; all calpionellid specimens on 1 cm2 of thin sections to reconstruct paleofluxes. In the Tithonian- Berriasian interval all known calcareous nannofossil Zones and corresponding Subzones (Bralower et al., 1989) have been recognized. Chitinoidella, Crassicollaria and Calpionella Zones have been identified (Remane, 1986; Pop, 1994b; Reh\ue1kov\ue1 & Michal\uedk, 1997; Andreini et al., 2007). Quantitative calpionellid and nannofossil analyses point out major changes during the Tithonian \u2013 Berriasian interval: nannolith taxa (F.multicolumnatus, C.mexicana, P.beckmannii) increase in abundance, size and calcification degree in discrete steps across the Lower Tithonian, coeval with the occurrence of first calcified calpionellids (Tintinopsella). Nannoconids and calcified calpionellids (Crassicollaria, Calpionella, Remaniella) increase across the Tithonian/Berriasian boundary reaching lithogenetic abundances: the rise in high-calcified nannoconids roughly corresponds with the Acme of C. alpina spherical forms. The diversification and biomineralization of highly-calcified microplankton produced a major increase in pelagic carbonate sedimentation due to the onset of paleoenvrionmental conditions favorable to calcification

Calcareous Nannofossil and Calpionellid calcification events across Tithonian \u2013 Berriasian time interval and low latitudes paleoceanographic implications.

The Tithonian-Berriasian time interval is characterized by a major calcareous nannofossil speciation episode and by the appearance of calpionellid group: several genera and species first appear and evolve, showing an increase in diversity, abundance and particularly in calcification degree. This time interval is also characterized by a significant low latitudes increase of carbonate-rich sediments (Rosso ad Aptici fm. toward Maiolica fm.). Calcareous nannofossil and calpionellid biostratigraphy and absolute abundances have been performed on low latitudes selected sections in order to reconstruct biogenic calcite palaeofluxes. Calpionellid has been investigated on thin sections (25\u3bcm thick), while calcareous nannofossil on the same thinnered thin sections (up to 7\ub5m thick) used for calpionellid. All specimens have been counted on 1 cm2 of thin section or 1 mm2 of ultra-thin section respectively for calpionellid and calcareous nannofossil. Paleofluxes have been obtained integrating absolute abundance with single speciment mass weigh (10-12gr of calcareous carbonate) per area unit (cm2) per time unit (yr). Calcareous biogenic paleofluxes point out a link between the lithologic changes and calcified plankton evolution across the Tithonian \u2013 Berriasian interval. During Lower Tithonian (Rosso ad Aptici Fm.) a first calcification event is characterized by nannolith (F.multicolumnatus, C.mexicana, P.beckmannii) increase in abundance, size and calcification degree, followed by the occurrence of first calcified calpionellid (Tintinopsella). Across Upper Tithonian to Lower Berriasian (Rosso ad Aptici fm. \u2013 Maiolica transition and Maiolica fm.) a second bigger calcification event is characterized by a dramatic increase of nannoconid abundance and calcification degree reaching lithogenetic amounts, concomitant with a moderate abundance increase of calcified calpionellid (genera Crassicollaria, Calpionella, Remaniella). Linkages between calcareous nannofossil and calpionellid evolutions with geologic, palaeoceanographic or palaeoclimatic events are inferred. The diversification and biomineralization of high-calcified plankton produced a major increase in pelagic carbonate sedimentation due to the onset of paleoenvrionmental conditions favorable to calcification. The diversification and proliferation of nannolith and nannoconid, interpreted as inhabitants of the lower photic zone, might indicate the establishment of a thermocline/nutricline in the deep photic zone, suggesting the develope of oligotrophic and stable oceanic conditions. It is also suggested that Tithonian-Berriasian calcified plankton evolution could be controlled by a decrease in pCO2, due to decreased spreading rate and/or increased weathering rate (87Sr/86Sr) and cool climatic conditions, concomitant with a decrease in oceanic Mg/Ca ratio values. Both factors thermodynamically promoted low Mg-CaCO3 and CaCO3 biomineralization supporting calpionellid and calcareous nannofossil abundance and calcification rate increases

Integrated bio- and magnetostratigraphy of the Tithonian \u2013 Berriasian interval in the Tethys Ocean: implications for the definition of the Jurassic/Cretaceous boundary.

The Jurassic/Cretaceous boundary time interval is characterized by a major calcareous nannofossil speciation episode: several successful genera and species first appear and rapidly evolve, particularly nannolith genera show a progressive increase in diversity, abundance and degree of calcification through time (Roth, 1989; Bralower et al., 1989; Erba & Quadrio, 1989; Bornemann et al., 2003; Bown et al., 2004; Tremolada et al., 2006; Casellato & Erba, 2007). In the Tethys ocean this event is associated with a major change in pelagic sedimentation from predominantly siliceous to mostly calcareous (transition from Rosso ad Aptici /Rosso Ammonitico Superiore to Maiolica). Magneto- and calcareous nannofossil biostratigraphy, and nannofloral relative and absolute abundances have been investigated on selected Tethyan land sections (Monte Pernice, Torre de Busi, Foza, Colma di Vignole, Frisoni - Southern Alps, Italy) in order to integrate calcareous nannofossil events with the polarity chron sequence and, where available, with calpionellid biostratigraphy. Biostratigraphic investigations have been performed directly on un-heated magneto-core end pieces: calcareous nannofossil biostratigraphy, relative and absolute abundances have been performed on simple smear slides and ultra-thin sections (7-8 \ub5m thick), calpionellid biostratigraphy has been investigated on thin sections. All known calcareous nannofossil Zones and Subzones (Bralower et al., 1989) have been recognized. Differences in some taxa ranges have been also pointed out, due to the high-resolution sampling (one sample every 5 - 40 cm). Chitinoidella, Crassicollaria and Calpionella Zones have been identified across the Jurassic/Cretaceous boundary (Remane, 1986; Pop, 1994b; Reh\ue1kov\ue1 & Michal\uedk, 1997). Nine polarity chrons (from CM24 to CM17) have been identified. Quantitative nannofossil studies indicate that nannolith taxa (firstly F.multicolumnatus, then C.mexicana, finally P.beckmannii) increase significantly in abundance, size and degree of calcification gaining lithogenetic proportion. The abundance acmes are reached in discrete steps between calcareous nannofossil Zones NJ-20B and NJK-A, in the interval marked by the first occurrence of calcified calpionellids. Nannoconids also appear and rapidly evolve across the Tithonian/Berriasian boundary, reaching lithogenetic abundances from calcareous nannofossil Subzone NJK-C to NK-1. High nannoconid abundances are concomitant with the well known Acme of Calpionella alpina spherical forms, both contributing to most Maiolica micrite. Calibration with magnetostratigraphy indicates that these trends could be very useful as additional bio-horizons in the Tithonian and for locating the Jurassic/Cretaceous boundary, especially when ammonites are absent, as in the Tethyan Maiolica. In particular, the speciation of highly-calcified nannofossil forms, and the remarkable abundance and size increase, could provide new reliable stratigraphic events for the Jurassic/Cretaceous boundary interval in low latitudinal pelagic and hemipelagic sequences. We emphasize that integrated stratigraphy based on calcareous nannofossil and capionellid events and magnetostratigraphy, is a powerful tool for characterizing the Jurassic/Cretaceous boundary interval at enhanced resolution

Urinary N-acetyl-β-glucosaminidase and eGFR may identify patients to be treated with immuno-suppression at diagnosis in idiopathic membranous nephropathy

Background The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). Selecting patients with high risk of progression for immunosuppressive therapy is mandatory. Methods 86 IMN subjects were followed for median of 69\u2009months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or eGFR reduction 6550% of baseline. Results Among all, 24 subjects had progression. Area under the ROC curve of N-acetyl-\u3b2-glucosaminidase/creatinine ratio (NAG/C) were significantly higher than proteinuria/24\u2009h (0.770 and 0.637 respectively, p\u2009=\u20090.018). In Cox proportional hazards regression analysis, NAG/C and eGFR were independent predictors of progression. Compared to lowest tertile of NAG/C (<9.4 UI/gC) or highest tertile of eGFR ( 6588\u2009ml/min/1.73\u2009m2), the multivariable-adjusted hazard ratio of highest tertile of NAG/C ( 6519.2) was 18.97 (95%CI, 1.70-211.86) and lowest tertile of eGFR (<59) was 11.58 (95%CI, 2.02-66.29). Subjects with high NAG/C or low eGFR (high-risk, n\u2009=\u200943) had greater progression rate compared to moderate to low NAG/C and high eGFR (low-risk, n\u2009=\u200943) with or without NS at baseline (Log-rank test p\u2009=\u20090.001 and 0.006, respectively). In NS subjects (n\u2009=\u200965), high-risk group progression rate was significantly higher (91% vs. 29%, p\u2009=\u20090.003) and remission rate significantly lower (0% vs. 42%, p\u2009<\u20090.001) in non-immunosuppressed compared to steroids and cyclophosphamide treated patients; no significant differences were observed in low-risk group. Conclusion IMN subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis

Are Amphipod invaders a threat to the regional biodiversity? Conservation prospects for the Loire River

The impact of invasions on local biodiversity is well established, but their impact on regional biodiversity has so far been only sketchily documented. To address this question, we studied the impact at various observation scales (ranging from the microhabitat to the whole catchment) of successive arrivals of non-native amphipods on the amphipod assemblage of the Loire River basin in France. Amphipod assemblages were studied at 225 sites covering the whole Loire catchment. Non-native species were dominant at all sites in the main channel of the Loire River, but native species were still present at most of the sites. We found that the invaders have failed to colonize most of tributaries of the Loire River. At the regional scale, we found that since the invaders first arrived 25 years ago, the global amphipod diversity has increased by 33% (from 8 to 12 species) due to the arrival of non-native species. We discuss the possibility that the lack of any loss of biodiversity may be directly linked to the presence of refuges at the microhabitat scale in the Loire channel and in the tributaries, which invasive species have been unable to colonize. The restoration of river quality could increase the number of refuges for native species, thus reducing the impact of invader