Epigenetic alterations in skin homing CD4+CLA+ T cells of atopic dermatitis patients

T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations (CD4+, CD4+CD45RA+ naïve, CD4+CLA+, and CD8+) from adult AD patients and healthy controls (HC). Skin homing CD4+CLA+ T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in CD4+CLA+ T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in CD4+CLA+ T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing CD4+CLA+ T cells and uncover putative molecules participating in AD pathways. © 2020, The Author(s).Peer reviewe

Oxygen-related band gap state in single crystal rubrene

A molecular exciton signature is established and investigated under different ambient conditions in rubrene single crystals. An oxygen-related band gap state is found to form in the ambient atmosphere. This state acts as an acceptor center and assists in the fast dissociation of excitons, resulting in a higher dark and photoconductivity of oxidized rubrene. The band gap state produces a well-defined photoluminescence band at an energy 0.25 eV below the energy of the 0-0 molecular exciton transition. Two-photon excitation spectroscopy shows that the states are concentrated near the surface of naturally oxidized rubrene

Genetic mapping of APP and amyloid-β biology modulation by trisomy 21

Individuals who have Down syndrome (DS) frequently develop early onset Alzheimer's disease (AD), a neurodegenerative condition caused by the build-up of aggregated amyloid-β and tau proteins in the brain. Amyloid-β is produced by amyloid precursor protein (APP), a gene located on chromosome 21. People who have Down syndrome have three copies of chromosome 21 and thus also an additional copy of APP; this genetic change drives the early development of Alzheimer's disease in these individuals. Here we use a combination of next-generation mouse models of Down syndrome (Tc1, Dp3Tyb, Dp(10)2Yey and Dp(17)3Yey) and a knockin mouse model of amyloid-β accumulation (AppNL-F ) to determine how chromosome 21 genes, other than APP, modulate APP/amyloid-β in the brain when in three copies. Using both male and female mice, we demonstrate that three copies of other chromosome 21 genes are sufficient to partially ameliorate amyloid-β accumulation in the brain. We go on to identify a subregion of chromosome 21 that contains the gene/genes causing this decrease in amyloid-β accumulation and investigate the role of two lead candidate genes Dyrk1a and Bace2 Thus an additional copy of chromosome 21 genes, other than APP, can modulate APP/amyloid-β in the brain under physiological conditions. This work provides critical mechanistic insight into the development of disease and an explanation for the typically later age of onset of dementia in people who have AD-DS, compared to those who have familial AD caused by triplication of APP Significance Statement:Trisomy of chromosome 21 is a commonly occurring genetic risk factor for early-onset Alzheimer's disease, which has been previously attributed to people with Down syndrome having three copies of the APP gene, which is encoded on chromosome 21. However, we have shown that an extra copy of other chromosome 21 genes modifies AD-like phenotypes independently of APP copy number (Wiseman et al. 2018, Brain; Tosh et al. 2021 Scientific Reports). Here, we use a mapping approach to narrow-down the genetic cause of the modulation of pathology; demonstrating that gene(s) on chromosome 21 decrease amyloid-β accumulation in the brain, independently of alterations to full-length APP or C-terminal fragment abundance and that just 38 genes are sufficient to cause this

Bioclipse: an open source workbench for chemo- and bioinformatics

BACKGROUND: There is a need for software applications that provide users with a complete and extensible toolkit for chemo- and bioinformatics accessible from a single workbench. Commercial packages are expensive and closed source, hence they do not allow end users to modify algorithms and add custom functionality. Existing open source projects are more focused on providing a framework for integrating existing, separately installed bioinformatics packages, rather than providing user-friendly interfaces. No open source chemoinformatics workbench has previously been published, and no sucessful attempts have been made to integrate chemo- and bioinformatics into a single framework. RESULTS: Bioclipse is an advanced workbench for resources in chemo- and bioinformatics, such as molecules, proteins, sequences, spectra, and scripts. It provides 2D-editing, 3D-visualization, file format conversion, calculation of chemical properties, and much more; all fully integrated into a user-friendly desktop application. Editing supports standard functions such as cut and paste, drag and drop, and undo/redo. Bioclipse is written in Java and based on the Eclipse Rich Client Platform with a state-of-the-art plugin architecture. This gives Bioclipse an advantage over other systems as it can easily be extended with functionality in any desired direction. CONCLUSION: Bioclipse is a powerful workbench for bio- and chemoinformatics as well as an advanced integration platform. The rich functionality, intuitive user interface, and powerful plugin architecture make Bioclipse the most advanced and user-friendly open source workbench for chemo- and bioinformatics. Bioclipse is released under Eclipse Public License (EPL), an open source license which sets no constraints on external plugin licensing; it is totally open for both open source plugins as well as commercial ones. Bioclipse is freely available at

Impedance analysis of secondary phases in a Co-implanted ZnO single crystal

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XMPP for cloud computing in bioinformatics supporting discovery and invocation of asynchronous web services

Background: Life sciences make heavily use of the web for both data provision and analysis. However, the increasing amount of available data and the diversity of analysis tools call for machine accessible interfaces in order to be effective. HTTP-based Web service technologies, like the Simple Object Access Protocol (SOAP) and REpresentational State Transfer (REST) services, are today the most common technologies for this in bioinformatics. However, these methods have severe drawbacks, including lack of discoverability, and the inability for services to send status notifications. Several complementary workarounds have been proposed, but the results are ad-hoc solutions of varying quality that can be difficult to use. Results: We present a novel approach based on the open standard Extensible Messaging and Presence Protocol (XMPP), consisting of an extension (IO Data) to comprise discovery, asynchronous invocation, and definition of data types in the service. That XMPP cloud services are capable of asynchronous communication implies that clients do not have to poll repetitively for status, but the service sends the results back to the client upon completion. Implementations for Bioclipse and Taverna are presented, as are various XMPP cloud services in bio- and cheminformatics. Conclusion: XMPP with its extensions is a powerful protocol for cloud services that demonstrate several advantages over traditional HTTP-based Web services: 1) services are discoverable without the need of an external registry, 2) asynchronous invocation eliminates the need for ad-hoc solutions like polling, and 3) input and output types defined in the service allows for generation of clients on the fly without the need of an external semantics description. The many advantages over existing technologies make XMPP a highly interesting candidate for next generation online services in bioinformatics

An eScience-Bayes strategy for analyzing omics data

<p>Abstract</p> <p>Background</p> <p>The omics fields promise to revolutionize our understanding of biology and biomedicine. However, their potential is compromised by the challenge to analyze the huge datasets produced. Analysis of omics data is plagued by the curse of dimensionality, resulting in imprecise estimates of model parameters and performance. Moreover, the integration of omics data with other data sources is difficult to shoehorn into classical statistical models. This has resulted in <it>ad hoc </it>approaches to address specific problems.</p> <p>Results</p> <p>We present a general approach to omics data analysis that alleviates these problems. By combining eScience and Bayesian methods, we retrieve scientific information and data from multiple sources and coherently incorporate them into large models. These models improve the accuracy of predictions and offer new insights into the underlying mechanisms. This "eScience-Bayes" approach is demonstrated in two proof-of-principle applications, one for breast cancer prognosis prediction from transcriptomic data and one for protein-protein interaction studies based on proteomic data.</p> <p>Conclusions</p> <p>Bayesian statistics provide the flexibility to tailor statistical models to the complex data structures in omics biology as well as permitting coherent integration of multiple data sources. However, Bayesian methods are in general computationally demanding and require specification of possibly thousands of prior distributions. eScience can help us overcome these difficulties. The eScience-Bayes thus approach permits us to fully leverage on the advantages of Bayesian methods, resulting in models with improved predictive performance that gives more information about the underlying biological system.</p

Degeneracy of non-abelian quantum Hall states on the torus: domain walls and conformal field theory

We analyze the non-abelian Read-Rezayi quantum Hall states on the torus, where it is natural to employ a mapping of the many-body problem onto a one-dimensional lattice model. On the thin torus--the Tao-Thouless (TT) limit--the interacting many-body problem is exactly solvable. The Read-Rezayi states at filling $\nu=\frac k {kM+2}$ are known to be exact ground states of a local repulsive $k+1$-body interaction, and in the TT limit this is manifested in that all states in the ground state manifold have exactly $k$ particles on any $kM+2$ consecutive sites. For $M\neq 0$ the two-body correlations of these states also imply that there is no more than one particle on $M$ adjacent sites. The fractionally charged quasiparticles and quasiholes appear as domain walls between the ground states, and we show that the number of distinct domain wall patterns gives rise to the nontrivial degeneracies, required by the non-abelian statistics of these states. In the second part of the paper we consider the quasihole degeneracies from a conformal field theory (CFT) perspective, and show that the counting of the domain wall patterns maps one to one on the CFT counting via the fusion rules. Moreover we extend the CFT analysis to topologies of higher genus.Comment: 15 page

Immigrant and non-immigrant women's experiences of maternity care: A systematic and comparative review of studies in five countries

Background: Understanding immigrant women’s experiences of maternity care is critical if receiving country care systems are to respond appropriately to increasing global migration. This systematic review aimed to compare what we know about immigrant and non-immigrant women’s experiences of maternity care. Methods: Medline, CINAHL, Health Star, Embase and PsychInfo were searched for the period 1989–2012. First, we retrieved population-based studies of women’s experiences of maternity care (n = 12). For countries with identified population studies, studies focused specifically on immigrant women’s experiences of care were also retrieved (n = 22). For all included studies, we extracted available data on experiences of care and undertook a descriptive comparison. Results: What immigrant and non-immigrant women want from maternity care proved similar: safe, high quality, attentive and individualised care, with adequate information and support. Immigrant women were less positive about their care than non-immigrant women. Communication problems and lack of familiarity with care systems impacted negatively on immigrant women’s experiences, as did perceptions of discrimination and care which was not kind or respectful. Conclusion: Few differences were found in what immigrant and non-immigrant women want from maternity care. The challenge for health systems is to address the barriers immigrant women face by improving communication,increasing women’s understanding of care provision and reducing discrimination