Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation

BACKGROUND: X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes. RESULTS: Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing. CONCLUSIONS: This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis

Ambipolar Nernst effect in NbSe2_2

The first study of Nernst effect in NbSe$_2$ reveals a large quasi-particle contribution with a magnitude comparable and a sign opposite to the vortex signal. Comparing the effect of the Charge Density Wave(CDW) transition on Hall and Nernst coefficients, we argue that this large Nernst signal originates from the thermally-induced counterflow of electrons and holes and indicates a drastic change in the electron scattering rate in the CDW state. The results provide new input for the debate on the origin of the anomalous Nernst signal in high-T$_c$ cuprates.Comment: 5 pages including 4 figure

Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma

SARS-CoV-2 viral contagion has given rise to a worldwide pandemic. Although most children experience minor symptoms from SARS-CoV-2 infection, some have severe complications including Multisystem Inflammatory Syndrome in Children. Neuroblastoma patients may be at higher risk of severe infection as treatment requires immunocompromising chemotherapy and SARS-CoV-2 has demonstrated tropism for nervous cells. To date, there is no sufficient epidemiological data on neuroblastoma patients with SARS-CoV-2. Therefore, we evaluated datasets of non-SARS-CoV-2 infected neuroblastoma patients to assess for key genes involved with SARS-CoV-2 infection as possible neuroblastoma prognostic and infection biomarkers. We hypothesized that ACE2, CD147, PPIA and PPIB, which are associated with viral-cell entry, are potential biomarkers for poor prognosis neuroblastoma and SARS-CoV-2 infection. We have analysed three publicly available neuroblastoma gene expression datasets to understand the specific molecular susceptibilities that high-risk neuroblastoma patients have to the virus. Gene Expression Omnibus (GEO) GSE49711 and GEO GSE62564 are the microarray and RNA-Seq data, respectively, from 498 neuroblastoma samples published as part of the Sequencing Quality Control initiative. TARGET, contains microarray data from 249 samples and is part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. ACE2, CD147, PPIA and PPIB were identified through their involvement in both SARS-CoV-2 infection and cancer pathogenesis. In-depth statistical analysis using Kaplan-Meier, differential gene expression, and Cox multivariate regression analysis, demonstrated that overexpression of ACE2, CD147, PPIA and PPIB is significantly associated with poor-prognosis neuroblastoma samples. These results were seen in the presence of amplified MYCN, unfavourable tumour histology and in patients older than 18 months of age. Previously, we have shown that high levels of the nerve growth factor receptor NTRK1 together with low levels of the phosphatase PTPN6 and TP53 are associated with increased relapse-free survival of neuroblastoma patients. Interestingly, low levels of expression of ACE2, CD147, PPIA and PPIB are associated with this NTRK1-PTPN6-TP53 module, suggesting that low expression levels of these genes are associated with good prognosis. These findings have implications for clinical care and therapeutic treatment. The upregulation of ACE2, CD147, PPIA and PPIB in poor-prognosis neuroblastoma samples suggests that these patients may be at higher risk of severe SARS-CoV-2 infection. Importantly, our findings reveal ACE2, CD147, PPIA and PPIB as potential biomarkers and therapeutic targets for neuroblastoma

Smoothing effect and delocalization of interacting Bose-Einstein condensates in random potentials

We theoretically investigate the physics of interacting Bose-Einstein condensates at equilibrium in a weak (possibly random) potential. We develop a perturbation approach to derive the condensate wavefunction for an amplitude of the potential smaller than the chemical potential of the condensate and for an arbitrary spatial variation scale of the potential. Applying this theory to disordered potentials, we find in particular that, if the healing length is smaller than the correlation length of the disorder, the condensate assumes a delocalized Thomas-Fermi profile. In the opposite situation where the correlation length is smaller than the healing length, we show that the random potential can be significantly smoothed and, in the meanfield regime, the condensate wavefunction can remain delocalized, even for very small correlation lengths of the disorder.Comment: The word "screening" has been changed to "smoothing" to avoid confusions with other effects discussed in the literature. This does not affect the content of paper, nor the results, nor the physical discussio

Self-regulatory goal motivational processes in sustained New Year resolution pursuit and mental wellbeing

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Anonymous data was collected and saved on an SPSS datafile. This SPSS dataset is deposited at Edith Cowan University’s data repository: https://ro.ecu.edu.au/datasets/57/Recent research suggests people typically “give up” pursuing their New Year resolutions within the first month. The present study investigated goal features proposed to be implicated in promoting both mental wellbeing and sustained New Year resolution pursuit. Australian and UK participants (n = 182) took part in an online longitudinal study, including four timepoints over a two-month period. At baseline, participants listed the New Year resolution to which they were most committed, and completed self-report measures to assess mental wellbeing, goal flexibility and tenacity. At the follow-up surveys, participants completed the wellbeing measure and their New Year resolution commitment, effort and stickability. As predicted, flexibility predicted wellbeing across time, however, tenacity did not. Counter to prediction, neither flexibility nor tenacity reported at baseline predicted “sticking” with one’s New Year resolution. The predicted interaction between flexibility and tenacity was not significant. New Year resolutions focused predominantly on “diet” and “exercise” were predominantly the same resolutions previously pursued and tended to be relatively abstract. Although goal flexibility predicted greater wellbeing, the findings overall tend to support the view that people are not particularly good at sticking with their New Year resolutions. Implications of the findings are discussed

Large Possible retardation effects of quark confinement on the meson spectrum II

We present the results of a study of heavy-light-quark bound states in the context of the reduced Bethe-Salpeter equation with relativistic vector and scalar interactions. We find that satisfactory fits may also be obtained when the retarded effect of the quark-antiquark interaction is concerned.Comment: 11 pages, RevTex, to appear in PR

Gene Ontology: Pitfalls, Biases, and Remedies.

The Gene Ontology (GO) is a formidable resource, but there are several considerations about it that are essential to understand the data and interpret it correctly. The GO is sufficiently simple that it can be used without deep understanding of its structure or how it is developed, which is both a strength and a weakness. In this chapter, we discuss some common misinterpretations of the ontology and the annotations. A better understanding of the pitfalls and the biases in the GO should help users make the most of this very rich resource. We also review some of the misconceptions and misleading assumptions commonly made about GO, including the effect of data incompleteness, the importance of annotation qualifiers, and the transitivity or lack thereof associated with different ontology relations. We also discuss several biases that can confound aggregate analyses such as gene enrichment analyses. For each of these pitfalls and biases, we suggest remedies and best practices

Possible retardation effects of quark confinement on the meson spectrum

The reduced Bethe-Salpeter equation with scalar confinement and vector gluon exchange is applied to quark-antiquark bound states. The so called intrinsic flaw of Salpeter equation with static scalar confinement is investigated. The notorious problem of narrow level spacings is found to be remedied by taking into consideration the retardation effect of scalar confinement. Good fit for the mass spectrum of both heavy and light quarkomium states is then obtained.Comment: 14 pages in LaTex for

Numerical study of one-dimensional and interacting Bose-Einstein condensates in a random potential

We present a detailed numerical study of the effect of a disordered potential on a confined one-dimensional Bose-Einstein condensate, in the framework of a mean-field description. For repulsive interactions, we consider the Thomas-Fermi and Gaussian limits and for attractive interactions the behavior of soliton solutions. We find that the disorder average spatial extension of the stationary density profile decreases with an increasing strength of the disordered potential both for repulsive and attractive interactions among bosons. In the Thomas Fermi limit, the suppression of transport is accompanied by a strong localization of the bosons around the state k=0 in momentum space. The time dependent density profiles differ considerably in the cases we have considered. For attractive Bose-Einstein condensates, a bright soliton exists with an overall unchanged shape, but a disorder dependent width. For weak disorder, the soliton moves on and for a stronger disorder, it bounces back and forth between high potential barriers.Comment: 13 pages, 13 figures, few typos correcte

Ab Initio Calculation of Relativistic Corrections to the Static Interquark potential I: SU(2) Gauge Theory

We test the capability of state-of-the-art lattice techniques for a precise determination of relativistic corrections to the static interquark potential, by use of SU(2) gauge theory. Emphasis is put on the short range structure of the spin dependent potentials, with lattice resolution a ranging from a approx 0.04 fm (at beta=2.74) down to a approx 0.02 fm (at beta=2.96) on volumes of 32^4 and 48^4 lattice sites. We find a new short range Coulomb-like contribution to the spin-orbit potential V_1'.Comment: 37 pages REVTeX with 20 encapsuled ps figure