Frustrated extended Bose-Hubbard model and deconfined quantum critical points with optical lattices at the anti-magic wavelength

The study of geometrically frustrated many-body quantum systems is of central importance to uncover novel quantum mechanical effects. We design a scheme where ultracold bosons trapped in a one-dimensional state-dependent optical lattice are modeled by a frustrated Bose-Hubbard Hamiltonian. A derivation of the Hamiltonian parameters based on Cesium atoms, further show large tunability of contact and nearest-neighbour interactions. For pure contact repulsion, we discover the presence of two phases peculiar to frustrated quantum magnets: the bond-order-wave insulator with broken inversion symmetry and a chiral superfluid. When the nearest-neighbour repulsion becomes sizeable, a further density-wave insulator with broken translational symmetry can appear. We show that the phase transition between the two spontaneously-symmetry-broken phases is continuous, thus representing a one-dimensional deconfined quantum critical point not captured by the Landau-Ginzburg-Wilson symmetry-breaking paradigm. Our results provide a solid ground to unveil the novel quantum physics induced by the interplay of non-local interactions, geometrical frustration, and quantum fluctuations.Comment: 7+3 pages, 3+3 figure

Frustrated Extended Bose-Hubbard Model and Deconfined Quantum Critical Points with Optical Lattices at the Antimagic Wavelength

The study of geometrically frustrated many-body quantum systems is of central importance to uncover novel quantum mechanical effects. We design a scheme where ultracold bosons trapped in a one-dimensional state-dependent optical lattice are modeled by a frustrated Bose-Hubbard Hamiltonian. A derivation of the Hamiltonian parameters based on Cesium atoms, further show large tunability of contact and nearest-neighbor interactions. For pure contact repulsion, we discover the presence of two phases peculiar to frustrated quantum magnets: the bond-order-wave insulator with broken inversion symmetry and a chiral superfluid. When the nearest-neighbor repulsion becomes sizable, a further density-wave insulator with broken translational symmetry can appear. We show that the phase transition between the two spontaneously symmetry-broken phases is continuous, thus representing a one-dimensional deconfined quantum critical point not captured by the Landau-Ginzburg-Wilson symmetry-breaking paradigm. Our results provide a solid ground to unveil the novel quantum physics induced by the interplay of nonlocal interactions, geometrical frustration, and quantum fluctuations

Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.This work was supported by Obra Social "La Caixa Foundation" (LCF/PR/GN16/50290001, and LCF/PR/GN19/50320002). Funders had no role in study design, data collection, data analysis, interpretation, or writing of the report

Prefrontal cortex-driven dopamine signals in the striatum show unique spatial and pharmacological properties

Dopamine (DA) signals in the striatum are critical for a variety of vital processes, including motivation, motor learning, and reinforcement learning. Striatal DA signals can be evoked by direct activation of inputs from midbrain DA neurons (DANs) as well as cortical and thalamic inputs to the striatum. In this study, we show that in vivo optogenetic stimulation of prelimbic (PrL) and infralimbic (IL) cortical afferents to the striatum triggers an increase in extracellular DA concentration, which coincides with elevation of striatal acetylcholine (ACh) levels. This increase is blocked by a nicotinic ACh receptor (nAChR) antagonist. Using single or dual optogenetic stimulation in brain slices from male and female mice, we compared the properties of these PrL/IL-evoked DA signals with those evoked by stimulation from midbrain DAN axonal projections. PrL/IL-evoked DA signals are undistinguishable from DAN evoked DA signals in their amplitudes and electrochemical properties. However, PrL/IL-evoked DA signals are spatially restricted and preferentially recorded in the dorsomedial striatum. PrL/IL-evoked DA signals also differ in their pharmacological properties, requiring activation of glutamate and nicotinic ACh receptors. Thus, both in vivo and in vitro results indicate that cortical evoked DA signals rely on recruitment of cholinergic interneurons, which renders DA signals less able to summate during trains of stimulation and more sensitive to both cholinergic drugs and temperature. In conclusion, cortical and midbrain inputs to the striatum evoke DA signals with unique spatial and pharmacological properties that likely shape their functional roles and behavioral relevance.Fil: Adrover, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. National Institutes of Health; Estados UnidosFil: Shin, Jung Hoon. National Institutes of Health; Estados UnidosFil: Quiroz, Cesar. National Institutes of Health; Estados UnidosFil: Ferré, Sergi. National Institutes of Health; Estados UnidosFil: Lemos, Julia C.. National Institutes of Health; Estados UnidosFil: Alvarez, Veronica A.. National Institutes of Health; Estados Unido

Negative Autopsy in Infant and Juvenile Population: Role of Cardiac Arrhythmias

Negative autopsy is a post-mortem examination in which a comprehensive analysis does not provide a cause of death. These include situation of death, anatomical and histological analysis, toxicology and microbiological study. A low part of autopsies remain without a conclusive cause of death, but all these cases are usually seen in young population, apparently healthy who died suddenly and unexpectedly. In these situations a cardiac arrhythmia is suspected as cause of death and genetic testing is recommended despite not regularly performed. Sudden death is a natural and unexpected decease that occurs in apparently healthy people, or whose disease was not severe enough to expect a fatal outcome. It can be due to several pathologies, usually of cardiac cause and called sudden cardiac death. In infants and young people, both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia are main causes in negative autopsies. These genetic diseases lead to ventricular fibrillation, syncope and sudden cardiac death in a normal heart. Unfortunately, sudden cardiac death could be the first manifestation of the diseases, being early identification and prevention a crucial point in current medical practice. This chapter focuses on sudden death and negative autopsy in young population, mainly due to cardiac arrhythmias

A narrative review of inherited arrhythmogenic syndromes in young population: role of genetic diagnosis in exercise recommendations

Sudden cardiac death is a rare but socially devastating event, especially if occurs in young people. Usually, this unexpected lethal event occurs during or just after exercise. One of the leading causes of sudden cardiac death is inherited arrhythmogenic syndromes, a group of genetic entities characterised by incomplete penetrance and variable expressivity. Exercise can be the trigger for malignant arrhythmias and even syncope in population with a genetic predisposition, being sudden cardiac death as the first symptom. Due to genetic origin, family members must be clinically assessed and genetically analysed after diagnosis or suspected diagnosis of a cardiac channelopathy. Early identification and adoption of personalised preventive measures is crucial to reduce risk of arrhythmias and avoid new lethal episodes. Despite exercise being recommended by the global population due to its beneficial effects on health, particular recommendations for these patients should be adopted considering the sport practised, level of demand, age, gender, arrhythmogenic syndrome diagnosed but also genetic diagnosis. Our review focuses on the role of genetic background in sudden cardiac death during exercise in child and young population

Update on Genes Associated with Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy is a rare genetic entity characterized by progressive fibro-fatty replacement of myocardium leading to malignant arrhythmias, syncope, and sudden cardiac death. Mostly it affects the right ventricle, but cases have also been described with biventricular and even isolated left ventricular involvement. The disease affects mainly young males and arrhythmias are usually induced by exercise. Arrhythmogenic cardiomyopathy has a genetic origin and is basically caused by deleterious alterations in genes encoding desmosomal proteins, especially plakophilin-2. To date, more than 400 rare genetic alterations have been identified in 18 genes, mainly with autosomal dominant inheritance, but some recessive forms have also been reported (Naxos disease and Carvajal syndrome). A comprehensive genetic analysis identifies a rare variant as potential cause of the disease in around 60% of patients, suggesting the existence of unknown genes as well as other genome alterations not yet discovered. Genetic interpretation classifies some of these rare variants as ambiguous, playing an uncertain role in arrhythmogenic cardiomyopathy. This makes a proper translation of genetic data into clinical practice difficult. Moreover, incomplete penetrance and variable phenotypic expression makes it difficult to arrive at the correct diagnosis. In the present chapter, we focus on recent advances in the knowledge regarding the genetic basis of arrhythmogenic cardiomyopathy

Short QT Syndrome: Update on Genetic Basis

Short QT syndrome (SQTS) is an extremely rare inherited arrhythmogenic entity. Nowadays, less than 200 families affected worldwide have been reported. This syndrome is characterized by the presence of a short QT interval leading to malignant ventricular tachyarrhythmias, syncope and sudden cardiac death. It is one of the most lethal heart diseases in children and young adults. Both incomplete penetrance and variable expressivity are hallmarks of this entity, making it difficult to diagnose and manage. Currently, rare variants in nine genes have been associated with SQTS (CACNA1C, CACNA2D1, CACNB2, KCNH2, KCNJ2, KCNQ1, SLC22A5, SLC4A3 and SCN5A). However, only pathogenic variants in four genes (KCNH2, KCNQ1, KCNJ2 and SLC4A3) have been found to definitively cause SQTS. The remaining genes lack a clear association with the disease, making clinical interpretation of the variants challenging. The diagnostic yield of genetic tests is currently less than 30%, leaving most families clinically diagnosed with SQTS without a conclusive genetic diagnosis. We reviewed and updated the main genetic features of SQTS, as well as recent evidence on increasingly targeted treatment