A Turner syndrome neurocognitive phenotype maps to Xp22.3

BACKGROUND: Turner syndrome (TS) is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47) of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. METHODS: Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS) score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. RESULTS: We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject\u27s age, were unrelated to the TSCS score. CONCLUSION: Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb) of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1). Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are attractive candidates for this neurocognitive phenotype

Shortcuts to adiabaticity in a time-dependent box

A method is proposed to drive an ultrafast non-adiabatic dynamics of an ultracold gas trapped in a box potential. The resulting state is free from spurious excitations associated with the breakdown of adiabaticity, and preserves the quantum correlations of the initial state up to a scaling factor. The process relies on the existence of an adiabatic invariant and the inversion of the dynamical self-similar scaling law dictated by it. Its physical implementation generally requires the use of an auxiliary expulsive potential analogous to those used in soliton control. The method is extended to a broad family of many-body systems. As illustrative examples we consider the ultrafast expansion of a Tonks-Girardeau gas and of Bose-Einstein condensates in different dimensions, where the method exhibits an excellent robustness against different regimes of interactions and the features of an experimentally realizable box potential.Comment: 6 pp, 4 figures, typo in Eq. (6) fixe

Sliding Mode Control of Two-Level Quantum Systems

This paper proposes a robust control method based on sliding mode design for two-level quantum systems with bounded uncertainties. An eigenstate of the two-level quantum system is identified as a sliding mode. The objective is to design a control law to steer the system's state into the sliding mode domain and then maintain it in that domain when bounded uncertainties exist in the system Hamiltonian. We propose a controller design method using the Lyapunov methodology and periodic projective measurements. In particular, we give conditions for designing such a control law, which can guarantee the desired robustness in the presence of the uncertainties. The sliding mode control method has potential applications to quantum information processing with uncertainties.Comment: 29 pages, 4 figures, accepted by Automatic

Engineered swift equilibration of a Brownian particle

A fundamental and intrinsic property of any device or natural system is its relaxation time relax, which is the time it takes to return to equilibrium after the sudden change of a control parameter [1]. Reducing $tau$ relax , is frequently necessary, and is often obtained by a complex feedback process. To overcome the limitations of such an approach, alternative methods based on driving have been recently demonstrated [2, 3], for isolated quantum and classical systems [4--9]. Their extension to open systems in contact with a thermostat is a stumbling block for applications. Here, we design a protocol,named Engineered Swift Equilibration (ESE), that shortcuts time-consuming relaxations, and we apply it to a Brownian particle trapped in an optical potential whose properties can be controlled in time. We implement the process experimentally, showing that it allows the system to reach equilibrium times faster than the natural equilibration rate. We also estimate the increase of the dissipated energy needed to get such a time reduction. The method paves the way for applications in micro and nano devices, where the reduction of operation time represents as substantial a challenge as miniaturization [10]. The concepts of equilibrium and of transformations from an equilibrium state to another, are cornerstones of thermodynamics. A textbook illustration is provided by the expansion of a gas, starting at equilibrium and expanding to reach a new equilibrium in a larger vessel. This operation can be performed either very slowly by a piston, without dissipating energy into the environment, or alternatively quickly, letting the piston freely move to reach the new volume

Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis

Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival

Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis

Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival.Peer reviewe

Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis.

Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival

Integrating Blue Energy in Maritime Spatial Planning of Mediterranean Regions

Blue Energy (BE) is expected to play a strategic role in the energy transition of Europe, particularly toward the 2050 horizon. It refers to a set of Marine Energy Sources (MES), including offshore wind, waves, tides, marine currents, sea thermal energy, salinity gradients, and marine biomass, which are exploited by different BE technologies. Nevertheless, the implementation of integrated solutions to exploit MES in marine areas does not just concern technological issues; it requires inclusive planning practices considering different aspects regarding climate and environmental impacts, landscape compatibility, interference with other marine activities (such as shipping, fishing, and tourism), and social acceptance. A replicable BE planning framework has been developed based on interdisciplinary knowledge in three Mediterranean sites in Greece, Croatia, and Cyprus, under the scope of the Interreg Med BLUE DEAL project. It has been implemented by some interdisciplinary experts through a collaborative and iterative process of data elaboration, mapping, evaluation, and visualization. Results concern the localization of suitable sites to install BE plants and the estimation of potential energy production and avoided emissions in selected scenarios. Together with visual simulations, this study shows the potential effects of the implementation of BE in specific marine areas, with a special focus on the most promising offshore floating wind farms and wave energy converters (WECs), as basic information for participative design and stakeholder engagement initiatives, including public authorities, businesses, and citizens

Brain Region–Specific Decrease in the Activity and Expression of Protein Kinase A in the Frontal Cortex of Regressive Autism

Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA), a cyclic AMP–dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α), a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α) between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling