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

Right Ventricular Dysfunction in the R6/2 Transgenic Mouse Model of Huntington's Disease is Unmasked by Dobutamine

Background: Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 mouse model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence.Objective: To investigate RV function in the R6/2 mouse model of Huntington's disease (HD).Methods: Cardiac cine- magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice. Results: There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent.Conclusions: This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD

Physical decline and cognitive impairment in frail hypertensive elders during COVID-19

Background: Hypertension is common in older adults and its incidence increases with age. We investigated the correlation between physical and cognitive impairment in older adults with frailty and hypertension. Methods: We recruited frail hypertensive older adults during the COVID-19 pandemic, between March 2021 and December 2021. Global cognitive function was assessed through the Montreal Cognitive Assessment (MoCA), physical frailty assessment was performed following the Fried criteria, and all patients underwent physical evaluation through 5-meter gait speed test. Results: We enrolled 203 frail hypertensive older adults and we found a significant correlation between MoCA score and gait speed test (r: 0.495; p<0.001) in our population. To evaluate the impact of comorbidities and other factors on our results, we applied a linear regression analysis with MoCA score as a dependent variable, observing a significant association with age, diabetes, chronic obstructive pulmonary disease (COPD), and gait speed test. Conclusions: Our study revealed for the first time a significant correlation between physical and cognitive impairment in frail hypertensive elderly subjects

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

Elabela/Toddler is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of its Expression in Pulmonary Arterial Hypertension

BACKGROUND: -Elabela/Toddler (ELA) is a critical cardiac developmental peptide that acts through the G protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is down-regulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model. METHODS: -In silico docking analysis, competition binding experiments and down-stream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using RT-qPCR, dual-labelling immunofluorescent staining and immunoassays. Acute cardiac effects of ELA-32 and [Pyr(1)]apelin-13 were assessed by magnet resonance imaging and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline (MCT) and Sugen/hypoxia exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the MCT rat model. RESULTS: -ELA competed for binding of apelin in human heart with overlap for the two peptides indicated by in silico modeling. ELA activated G protein- and Β-arrestin-dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, cardiac output and elicited vasodilatation in rat in vivo ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in MCT exposed rats. CONCLUSIONS: -These results show ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile comparable to apelin, is down-regulated in human disease and rodent PAH models and exogenous peptide can reduce the severity of cardiopulmonary remodeling and function in PAH in rats. This study provides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH in man.Supported by the Wellcome Trust 107715/Z/15/Z and Programme in Metabolic and Cardiovascular Disease 096822/Z/11/Z, Medical Research Council MC_PC_14116, British Heart Foundation PS/02/001, PG/05/127/19872, FS/14/59/31282 and in part by the National Institute for Health Research Cambridge Biomedical Research Centre and the Pulmonary Hypertension Association UK

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