The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, yet the molecular basis of AF remains incompletely understood. To determine the cell type-specific transcriptional changes underlying AF, we perform single-nucleus RNA-seq (snRNA-seq) on left atrial (LA) samples from patients with AF and controls. From more than 175,000 nuclei we find that only cardiomyocytes (CMs) and macrophages (MΦs) have a significant number of differentially expressed genes in patients with AF.

Semi-Automated Assessment of Long-Term Olfactory Habituation in Using the Olfactory Arena.

Long-lasting memories are a core aspect of an animal's life. Such memories are characterized by unique molecular mechanisms and often unique circuitry, neither of which are completely understood in vivo. The deep knowledge of the identity and connectivity of neurons of the fruit fly , as well as the sophisticated genetic tools that allow in vivo perturbations and physiology monitoring, make it a remarkably useful organism in which to investigate the molecular mechanisms of long-term memories.

Rare coding variant analysis for human diseases across biobanks and ancestries.

Large-scale sequencing has enabled unparalleled opportunities to investigate the role of rare coding variation in human phenotypic variability. Here, we present a pan-ancestry analysis of sequencing data from three large biobanks, including the All of Us research program. Using mixed-effects models, we performed gene-based rare variant testing for 601 diseases across 748,879 individuals, including 155,236 with ancestry dissimilar to European.

Integrating Clinical, Genetic, and Electrocardiogram-Based Artificial Intelligence to Estimate Risk of Incident Atrial Fibrillation.

Background: AF risk estimation is feasible using clinical factors, inherited predisposition, and artificial intelligence (AI)-enabled electrocardiogram (ECG) analysis.

Objective: To test whether integrating these distinct risk signals improves AF risk estimation.

Methods: In the UK Biobank prospective cohort study, we estimated AF risk using three models derived from external populations: the well-validated Cohorts for Aging in Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) clinical score, a 1,113,667-variant AF polygenic risk score (PRS), and a published AI-enabled ECG-based AF risk model (ECG-AI).

A roadmap for the implementation of a renewable energy community.

Environmental problems due to climate change, that have been affecting our planet for years, are the main issues which prompted European Union to establish the ambitious target of achieving carbon neutrality by 2050. This occurrence encouraged all Member States to undergo significant changes of their energy sectors, favouring the extensive use of renewable energy sources. In this scenario, the European Union introduced Renewable Energy Communities, innovative energy systems based on a new model of renewable energy production, consumption and sharing, guaranteeing environmental, economic, energy and social benefits.

Cardiovascular Significance and Genetics of Epicardial and Pericardial Adiposity.

Importance: Epicardial and pericardial adipose tissue (EPAT) has been associated with cardiovascular diseases such as atrial fibrillation or flutter (AF) and coronary artery disease (CAD), but studies have been limited in sample size or drawn from selected populations. It has been suggested that the association between EPAT and cardiovascular disease could be mediated by local or paracrine effects.

Objective: To evaluate the association of EPAT with prevalent and incident cardiovascular disease and to elucidate the genetic basis of EPAT in a large population cohort.

Chemical characterization of baby food consumed in Italy.

In this study, a total of 30 elements (essential and non-essential or toxic) were determined in 25 foods consumed in Italy by children aged 0-6 months and produced in Europe. Inductively Coupled Plasma-Atomic Emission Spectrometry and Inductively Coupled Plasma-Mass Spectrometry were used as measurement techniques for the elements of interest. The estimated intakes for one-year-old infants were compared with risk estimators and nutritional requirements.

Theta synchronization as a neural marker of flexible (re-)use of socio-cognitive mechanisms for a new category of (artificial) interaction partners.

Previous work shows that in some instances artificial agents, such as robots, can elicit higher-order socio-cognitive mechanisms, similar to those elicited by humans. This suggests that these socio-cognitive mechanisms, such as mentalizing processes, originally developed for interaction with other humans, might be flexibly (re-)used, or "hijacked", for approaching this new category of interaction partners (Wykowska, 2020). In this study, we set out to identify neural markers of such flexible reuse of socio-cognitive mechanisms.

High-levels of toxic elements and radioactivity in an abandoned sulphur mine: Insights on the origin and associated environmental concerns.

Natural fibrous epsomite crystals containing high amounts of toxic and radioactive elements have recently been discovered in the abandoned sulphur mine of Perticara (Italy). In the present study, all the different matrices that characterize the Perticara mine (air, water, host-rock, minerals, and bitumen) were sampled and investigated employing a multi-analytical approach to define the distribution and origin of these hazardous elements. Water samples showed high Al, Fe, Pb, Mg, and Mn content but not radioactive elements.

Effect of Fetal Pituitary-Testes Suppression on Brain Sexual Differentiation and Reproductive Function in Male Sheep.

We previously demonstrated that treating fetal lambs on gestational day 62 with the long-acting gonadotrophin-releasing hormone (GnRH) antagonist degarelix (DG) suppresses pituitary-testicular function during midgestation. The objective of this study was to investigate whether impaired gonadotrophic drive during this fetal period has enduring effects on sexual differentiation and reproductive function in adult male sheep. We assessed the effects of prenatal administration of DG, with or without testosterone (T) replacement, on various sexually dimorphic behavioral traits in adult rams, including sexual partner preferences, as well as neuroendocrine responsiveness and testicular function.

The Cardiovascular Impact and Genetics of Pericardial Adiposity.

Background: While previous studies have reported associations of pericardial adipose tissue (PAT) with cardiovascular diseases such as atrial fibrillation and coronary artery disease, they have been limited in sample size or drawn from selected populations. Additionally, the genetic determinants of PAT remain largely unknown. We aimed to evaluate the association of PAT with prevalent and incident cardiovascular disease and to elucidate the genetic basis of PAT in a large population cohort.

Nrf2-Mediated Pathway Activated by L. (Rosaceae) Fruit Extract: Bioinformatics Analyses and Experimental Validation.

In our previous studies, fruit (PSF) ethanol extract was showed to exert antioxidant, antimicrobial, anti-inflammatory and wound healing activities. In the present study, an integrated bioinformatics analysis combined with experimental validation was carried out to investigate the biological mechanism(s) that are responsible for the reported PSF beneficial effects as an antioxidant during a pro-inflammatory TLR4 insult. Bioinformatics analysis using miRNet 2.

The impact of facial expression and communicative gaze of a humanoid robot on individual Sense of Agency.

Sense of Agency (SoA) is the feeling of control over one's actions and their outcomes. A well-established implicit measure of SoA is the temporal interval estimation paradigm, in which participants estimate the time interval between a voluntary action and its sensory consequence. In the present study, we aimed to investigate whether the valence of action outcome modulated implicit SoA.

Association of genetic risk and outcomes in patients with atrial fibrillation: interactions with early rhythm control in the EAST-AFNET4 trial.

Aims: The randomized Early Treatment of Atrial Fibrillation for Stroke Prevention Trial found that early rhythm control reduces cardiovascular events in patients with recently diagnosed atrial fibrillation (AF) compared with usual care. How genetic predisposition to AF and stroke interacts with early rhythm-control therapy is not known.

Methods And Results: Array genotyping and imputation for common genetic variants were performed.

Genetics of myocardial interstitial fibrosis in the human heart and association with disease.

Myocardial interstitial fibrosis is associated with cardiovascular disease and adverse prognosis. Here, to investigate the biological pathways that underlie fibrosis in the human heart, we developed a machine learning model to measure native myocardial T1 time, a marker of myocardial fibrosis, in 41,505 UK Biobank participants who underwent cardiac magnetic resonance imaging. Greater T1 time was associated with diabetes mellitus, renal disease, aortic stenosis, cardiomyopathy, heart failure, atrial fibrillation, conduction disease and rheumatoid arthritis.

Sleep benefits different stages of memory in .

Understanding the physiological mechanisms that modulate memory acquisition and consolidation remains among the most ambitious questions in neuroscience. Massive efforts have been dedicated to deciphering how experience affects behavior, and how different physiological and sensory phenomena modulate memory. Our ability to encode, consolidate and retrieve memories depends on internal drives, and sleep stands out among the physiological processes that affect memory: one of the most relatable benefits of sleep is the aiding of memory that occurs in order to both prepare the brain to learn new information, and after a learning task, to consolidate those new memories.

The precuneus as a central node in declarative memory retrieval.

Both, the hippocampal formation and the neocortex are contributing to declarative memory, but their functional specialization remains unclear. We investigated the differential contribution of both memory systems during free recall of word lists. In total, 21 women and 17 men studied the same list but with the help of different encoding associations.

Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.

Importance: The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective: To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, Setting, And Participants: This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci.

Androgen receptors immunoreactivity in the rat brain of males with same-sex preference.

Androgen receptors (AR) are crucial in the control of male sexual behavior and sex preference. AR are particularly concentrated in areas related with the neuroendocrine control of sex preference including the medial amygdala (MeA), the ventromedial nucleus of the hypothalamus (VMH), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA), the nucleus accumbens (Acb), the suprachiasmatic (SCh) and supraoptic (SO) nuclei, but also seem to be important for the control of reproductive processes in the hippocampus (CA1-CA4 and dentate gyrus, DG). In the present study we analyzed the density of AR in these brain areas of adult male rats with sexual preference (established in a three-compartment box).