Modeling brain connectivity dynamics in functional Magnetic Resonance Imaging via Particle Filtering

Interest in the studying of functional connections in the brain has grown considerably in the last decades, as many studies have pointed out that alterations in the interaction among brain areas can play a role as markers of neurological diseases. Most studies in this field treat the brain network as a system of connections stationary in time, but dynamic features of brain connectivity can provide useful information, both on physiology and pathological conditions of the brain. In this paper, we propose the application of a computational methodology, named Particle Filter (PF), to study non-stationarities in brain connectivity in functional Magnetic Resonance Imaging (fMRI). The PF algorithm estimates time-varying hidden parameters of a first-order linear time-varying Vector Autoregressive model (VAR) through a Sequential Monte Carlo strategy. On simulated time series, the PF approach effectively detected and enabled to follow time-varying hidden parameters and it captured causal relationships among signals. The method was also applied to real fMRI data, acquired in presence of periodic tactile or visual stimulations, in different sessions. On these data, the PF estimates were consistent with current knowledge on brain functioning. Most importantly, the approach enabled to detect statistically significant modulations in the cause-effect relationship between brain areas, which correlated with the underlying visual stimulation pattern presented during the acquisition

A novel cyclic biased agonist of the apelin receptor, MM07, is disease modifying in the rat monocrotaline model of pulmonary arterial hypertension.

BACKGROUND AND PURPOSE: Apelin is an endogenous vasodilatory and inotropic peptide that is down-regulated in human pulmonary arterial hypertension, although the density of the apelin receptor is not significantly attenuated. We hypothesised that a G protein-biased apelin analogue MM07, which is more stable than the endogenous apelin peptide, may be beneficial in this condition with the advantage of reduced β-arrestin-mediated receptor internalisation with chronic use. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats received either monocrotaline to induce pulmonary arterial hypertension or saline and then daily i.p. injections of either MM07 or saline for 21 days. The extent of disease was assessed by right ventricular catheterisation, cardiac MRI, and histological analysis of the pulmonary vasculature. The effect of MM07 on signalling, proliferation, and apoptosis of human pulmonary artery endothelial cells was investigated. KEY RESULTS: MM07 significantly reduced the elevation of right ventricular systolic pressure and hypertrophy induced by monocrotaline. Monocrotaline-induced changes in cardiac structure and function, including right ventricular end-systolic and end-diastolic volumes, ejection fraction, and left ventricular end-diastolic volume, were attenuated by MM07. MM07 also significantly reduced monocrotaline-induced muscularisation of small pulmonary blood vessels. MM07 stimulated endothelial NOS phosphorylation and expression, promoted proliferation, and attenuated apoptosis of human pulmonary arterial endothelial cells in vitro. CONCLUSION AND IMPLICATIONS: Our findings suggest that chronic treatment with MM07 is beneficial in this animal model of pulmonary arterial hypertension by addressing disease aetiology. These data support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease.the Medical Research Council MC_PC_14116 [to APD] Wellcome Trust [107715/Z/15/Z to APD], Programme in Metabolic and Cardiovascular Disease [096822/Z/11/Z to PY; 203814/Z/16/A to TLW], Parke Davis Fellowship [to PY], British Heart Foundation [FS/14/59/31282 to CR] and in part by the National Institute for Health Research Cambridge Biomedical Research Centre

Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and mast cell degranulation lead to adverse cardiac remodeling in diabetes.

Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic animals, but the mechanisms remain unknown. Equally elusive is the interplay between the cardiomyocyte alterations induced by hyperglycemia and the accompanying inflammation. Here we show that exposure of primary cardiomyocytes to high glucose and pro-inflammatory stimuli leads to MAO-dependent increase in reactive oxygen species that causes permeability transition pore opening and mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum (ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the role of these flavoenzymes in the ER/mitochondria cross-talk. In vivo, streptozotocin administration to mice induced oxidative changes and ER stress in the heart, events that were abolished by pargyline. Moreover, MAO inhibition prevented both mast cell degranulation and altered collagen deposition, thereby normalizing diastolic function. Taken together, these results elucidate the mechanisms underlying MAO-induced damage in diabetic cardiomyopathy and provide novel evidence for the role of MAOs in inflammation and inter-organelle communication. MAO inhibitors may be considered as a therapeutic option for diabetic complications as well as for other disorders in which mast cell degranulation is a dominant phenomenon

The Botanical Record of Archaeobotany Italian Network - BRAIN: a cooperative network, database and website

The BRAIN (Botanical Records of Archaeobotany Italian Network) database and network was developed by the cooperation of archaeobotanists working on Italian archaeological sites. Examples of recent research including pollen or other plant remains in analytical and synthetic papers are reported as an exemplar reference list. This paper retraces the main steps of the creation of BRAIN, from the scientific need for the first research cooperation to the website which has a free online access since 2015

The Botanical Record of Archaeobotany Italian Network - BRAIN: a cooperative network, database and website

The BRAIN (Botanical Records of Archaeobotany Italian Network) database and network was developed by the cooperation of archaeobotanists working on Italian archaeological sites. Examples of recent research including pollen or other plant remains in analytical and synthetic papers are reported as an exemplar reference list. This paper retraces the main steps of the creation of BRAIN, from the scientific need for the first research cooperation to the website which has a free online access since 2015

The physics case of a 3 TeV muon collider stage

In the path towards a muon collider with center of mass energy of 10 TeV ormore, a stage at 3 TeV emerges as an appealing option. Reviewing the physicspotential of such muon collider is the main purpose of this document. In orderto outline the progression of the physics performances across the stages, a fewsensitivity projections for higher energy are also presented. There are manyopportunities for probing new physics at a 3 TeV muon collider. Some of themare in common with the extensively documented physics case of the CLIC 3 TeVenergy stage, and include measuring the Higgs trilinear coupling and testingthe possible composite nature of the Higgs boson and of the top quark at the 20TeV scale. Other opportunities are unique of a 3 TeV muon collider, and stemfrom the fact that muons are collided rather than electrons. This isexemplified by studying the potential to explore the microscopic origin of thecurrent $g$-2 and $B$-physics anomalies, which are both related with muons.<br

The physics case of a 3 TeV muon collider stage

In the path towards a muon collider with center of mass energy of 10 TeV ormore, a stage at 3 TeV emerges as an appealing option. Reviewing the physicspotential of such muon collider is the main purpose of this document. In orderto outline the progression of the physics performances across the stages, a fewsensitivity projections for higher energy are also presented. There are manyopportunities for probing new physics at a 3 TeV muon collider. Some of themare in common with the extensively documented physics case of the CLIC 3 TeVenergy stage, and include measuring the Higgs trilinear coupling and testingthe possible composite nature of the Higgs boson and of the top quark at the 20TeV scale. Other opportunities are unique of a 3 TeV muon collider, and stemfrom the fact that muons are collided rather than electrons. This isexemplified by studying the potential to explore the microscopic origin of thecurrent $g$-2 and $B$-physics anomalies, which are both related with muons.<br

Observation of the Decay Λ0b→Λ+cτ−¯ν

The first observation of the semileptonic b-baryon decay Λb0→Λc+τ-ν¯τ, with a significance of 6.1σ, is reported using a data sample corresponding to 3 fb-1 of integrated luminosity, collected by the LHCb experiment at center-of-mass energies of 7 and 8 TeV at the LHC. The τ- lepton is reconstructed in the hadronic decay to three charged pions. The ratio K=B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+π-π+π-) is measured to be 2.46±0.27±0.40, where the first uncertainty is statistical and the second systematic. The branching fraction B(Λb0→Λc+τ-ν¯τ)=(1.50±0.16±0.25±0.23)% is obtained, where the third uncertainty is from the external branching fraction of the normalization channel Λb0→Λc+π-π+π-. The ratio of semileptonic branching fractions R(Λc+)B(Λb0→Λc+τ-ν¯τ)/B(Λb0→Λc+μ-ν¯μ) is derived to be 0.242±0.026±0.040±0.059, where the external branching fraction uncertainty from the channel Λb0→Λc+μ-ν¯μ contributes to the last term. This result is in agreement with the standard model prediction