Statistical properties of eigenstate amplitudes in complex quantum systems

We study the eigenstates of quantum systems with large Hilbert spaces, via their distribution of wavefunction amplitudes in a real-space basis. For single-particle 'quantum billiards', these real-space amplitudes are known to have Gaussian distribution for chaotic systems. In this work, we formulate and address the corresponding question for many-body lattice quantum systems. For integrable many-body systems, we examine the deviation from Gaussianity and provide evidence that the distribution generically tends toward power-law behavior in the limit of large sizes. We relate the deviation from Gaussianity to the entanglement content of many-body eigenstates. For integrable billiards, we find several cases where the distribution has power-law tails.Comment: revised version, with appendices; 15 pages, 10 figure

Assessing the impact of exposome on the course of chronic obstructive pulmonary disease and cystc fibrosis:The REMEDIA European Project Approach

International audienceBecause of the direct interaction of lungs with the environment, respiratory diseases are among the leading causes of environment-related deaths in the world. Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are two highly debilitating diseases that are of particular interest in the context of environmental studies; they both are characterized by a similar progressive loss of lung function with small bronchi alterations, and a high phenotypic variability of unknown origin, which prevents a good therapeutic efficacy. In the last years, there has been an evolution in the apprehension of the study of diseases going from a restricted "one exposure, one disease" approach to a broader concept with other associating factors, the exposome. The overall objective of the REMEDIA project is to extend the understanding of the contribution of the exposome to COPD and CF diseases. To achieve our aim, we will (1) exploit data from existing cohorts and population registries to create a unified global database gathering phenotype and exposome information; (2) develop a flexible individual sensor device combining environmental and biomarker toolkits; (3) use a versatile atmospheric simulation chamber to simulate the health effects of complex exposomes; (4) use machine learning supervised analyses and causal inference models to identify relevant risk factors; and (5) develop econometric and cost-effectiveness models to assess the costs, performance, and cost-effectiveness of a selection of prevention strategies. The results will be used to develop guidelines to better predict disease risks and constitute the elements of the REMEDIA toolbox. The multidisciplinary approach carried out by the REMEDIA European project should represent a major breakthrough in reducing the morbidity and mortality associated with COPD and CF diseases

Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases

Background: In approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce. Aims: To quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls. Methods: Patients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls. Results: (i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation. Conclusion: Our data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation

The rotational γ-continuum in the mass region A≈110

Abstract Unresolved γ transitions of 114 Te and of 112 Sn sorted into one-dimensional and two-dimensional spectra have been studied. The reaction 64 Ni + 54 Cr at bombarding energies 230, 240, 250, 260, 270 MeV was used and the γ -rays were detected with the EUROBALL array. In the case of the nucleus 114 Te the values of the multiplicity as a function of bombarding energy and of the moment of inertia were obtained. The effective moment of inertia was found to be almost constant in the interval I=20 – 40 ℏ , in contrast to the decreasing behaviour of the dynamic moment of inertia for the terminating yrast band. The ridge valley structures in E γ 1 ×E γ 2 spectra of 114 Te and of 112 Sn were analysed with the fluctuation analysis technique. The analysis of the two nuclei are compared to simulations based on microscopic cranking calculations with residual interactions included. A rather good agreement is found between data and predictions

STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity

Healthy adipose tissue (AT) contains ST2(+) Tregs, ILC2s, and alternatively activated macrophages that are lost in mice or humans on high caloric diet. Understanding how this form of type 2 immunity is regulated could improve treatment of obesity. The STE20 kinase Thousand And One amino acid Kinase-3 (TAOK3) has been linked to obesity in mice and humans, but its precise function is unknown. We found that ST2(+) Tregs are upregulated in visceral epididymal white AT (eWAT) of Taok3(-/-) mice, dependent on IL-33 and the kinase activity of TAOK3. Upon high fat diet feeding, metabolic dysfunction was attenuated in Taok3(-/-) mice. ST2(+) Tregs disappeared from eWAT in obese wild-type mice, but this was not the case in Taok3(-/-) mice. Mechanistically, AT Taok3(-/-) Tregs were intrinsically more responsive to IL-33, through higher expression of ST2, and expressed more PPAR & gamma; and type 2 cytokines. Thus, TAOK3 inhibits adipose tissue Tregs and regulates immunometabolism under excessive caloric intake. Maes et al. reveal an unexpected role of TAOK3 in regulating ST2(+) regulatory T cells in mouse adipose tissue. Absence of TAOK3 sustains Tregs in obesity and improves metabolic dysfunction

Effect of E1 decay in the population of superdeformed structures

Abstract Spectra of the yrast and excited superdeformed bands, forming the E2 quasi-continuum, are measured with the EUROBALL array for the nucleus 143 Eu, in coincidence with high-energy γ-rays (Eγ>3 MeV). It is found that the intensity population of the superdeformed states is enhanced by a factor of ≈1.6 when a coincidence with a γ-ray with energy >6 MeV is required, in reasonable agreement with the increase of the line shape of the Giant Dipole Resonance built on a superdeformed configuration. This result shows that when an high energy E1 γ-ray is involved in the decay it is more likely connected with a SD rather than a ND nucleus. In addition, the analysis of the rotational quasi-continuum suggests the presence of a superdeformed component. The data are also compared and found consistent with simulation calculations of the relative intensities of the SD states, including the E1 decay of superdeformed nature

MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus

Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs) in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense). The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms “mental retardation”. To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus

Epstein Barr Virus-Encoded EBNA1 Interference with MHC Class I Antigen Presentation Reveals a Close Correlation between mRNA Translation Initiation and Antigen Presentation

Viruses are known to employ different strategies to manipulate the major histocompatibility (MHC) class I antigen presentation pathway to avoid recognition of the infected host cell by the immune system. However, viral control of antigen presentation via the processes that supply and select antigenic peptide precursors is yet relatively unknown. The Epstein-Barr virus (EBV)-encoded EBNA1 is expressed in all EBV-infected cells, but the immune system fails to detect and destroy EBV-carrying host cells. This immune evasion has been attributed to the capacity of a Gly-Ala repeat (GAr) within EBNA1 to inhibit MHC class I restricted antigen presentation. Here we demonstrate that suppression of mRNA translation initiation by the GAr in cis is sufficient and necessary to prevent presentation of antigenic peptides from mRNAs to which it is fused. Furthermore, we demonstrate a direct correlation between the rate of translation initiation and MHC class I antigen presentation from a certain mRNA. These results support the idea that mRNAs, and not the encoded full length proteins, are used for MHC class I restricted immune surveillance. This offers an additional view on the role of virus-mediated control of mRNA translation initiation and of the mechanisms that control MHC class I restricted antigen presentation in general

Caspase-11 Controls Interleukin-1 beta Release through Degradation of TRPC1

Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1 beta (IL-1 beta) secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide (LPS) and Gram-negative bacteria. However, we still know very little about the downstream mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. Here, we identify the cationic channel subunit transient receptor potential channel 1 (TRPC1) as a substrate of caspase-11. TRPC1 deficiency increases the secretion of IL-1 beta without modulating caspase-1 cleavage or cell death in cultured macrophages. Consistently, trpc1(-/-) mice show higher IL-1 beta secretion in the sepsis model of intraperitoneal LPS injection. Altogether, our data suggest that caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1