Brachypodium distachyon as a model for defining the allergen potential of non-prolamin proteins

Epitope databases and the protein sequences of published plant genomes are suitable to identify some of the proteins causing food allergies and sensitivities. Brachypodium distachyon, a diploid wild grass with a sequenced genome and low prolamin content, is the closest relative of the allergen cereals, such as wheat or barley. Using the Brachypodium genome sequence, a workflow has been developed to identify potentially harmful proteins which may cause either celiac disease or wheat allergy-related symptoms. Seed tissue-specific expression of the potential allergens has been determined, and intact epitopes following an in silico digestion with several endopeptidases have been identified. Molecular function of allergen proteins has been evaluated using Gene Ontology terms. Biologically overrepresented proteins and potentially allergen protein families have been identified. © 2012 The Author(s)

Stigmatic attitudes towards mentally ill patients in Hungary between 2001 and 2015: results of a time-trend analysis

Background: Stigmatic attitudes towards people with the diagnosis of mental illness are widespread in the general public [1] and are the major obstacle for successful treatment, rehabilitation and reintegration of patients into the society [2]. Given the magnitude of this issue, and in the effort to develop effective anti stigma intervention programs, trend analysis studies were conducted, examining the changes in attitudes over the years [3]. The construct of social distance, which involves the desire to avoid contact with a particular group of people was commonly used to assess stigma. These studies have consistently reported that despite the improvement in mental health literacy of the public, social distance preferences concerning mentally ill patients have not changed over the last 20 years, and in some cases have even increased [3]. However, the number of studies using trend analysis is scarce and mainly limited to wealthier countries because such studies are both costly and time intensive. Consequently, most studies to date have been carried out in North Western Europe whereas data from Central and Eastern European countries, especially from former communist countries, is lacking [4,5]. Objective: In the face of underfinanced mental health system and the lack of any national anti-stigma programs or research, the aim of this study is to shed light into mental illness stigma in Hungary. More specifically, this study aimed to explore for the first time, potential changes concerning attitudes of the Hungarian population towards mentally ill patients. Method: National representative surveys (N=7605) of adults aged 18-53 years were carried out in Hungary in 2001, 2003, 2007 and 2015. An interview was conducted, asking for socio-demographic information and participants' desire for social distance from mentally ill patients, measured by Bogardus social distance scale. In order to put into context the stigmatic attitudes towards mentally ill patients, participants were also asked to report on their social distance preferences towards other minorities in the Hungarian society. Trend analysis was performed to examine the trends of social distance. Results: Time-trend analysis indicated a significant (positive) trend in public preferences for social distance towards more accepting attitudes during the years of 2001-2015. However, closer examination reveals that the effect size is very small (0.05) and the 2015 rejection level is still high (57%) compared to over 60% in both 2001 and 2003. Moreover, during a period of 15 years, mentally ill patients are among the three most rejected groups in the society (with only alcoholics and drug users being more rejected). Conclusions: As was found in other countries around the world, in Hungary as well, stigmatic attitudes towards mentally ill patients are highly prevalent, and have not changed over the last decade. While stressing a worrisome reality in Hungary, where no efforts to tackle mental illness stigma were done, this study also verifies the enormity of the stigma phenomenon. It is evident, maybe more than anything, that much effort is needed in Hungary, but also worldwide, in order to understand and defeat mental illness stigma

SUPPA2:fast, accurate, and uncertainty-aware differential splicing analysis across multiple conditions

Supplementary methods. (PDF 315 kb

The incredible complexity of RNA splicing

Alternative splice isoforms are common and important and have been shown to impact many human diseases. A new study by Nellore et al. offers a comprehensive study of splice junctions in humans by re-analyzing over 21,500 public human RNA sequencing datasets

CHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters RNA alternative splicing

Disruptive mutations in the chromodomain helicase DNA-binding protein 8 gene (CHD8) have been recurrently associated with autism spectrum disorders (ASDs). Here we investigated how chromatin reacts to CHD8 suppression by analyzing a panel of histone modifications in induced pluripotent stem cell-derived neural progenitors. CHD8 suppression led to significant reduction (47.82%) in histone H3K36me3 peaks at gene bodies, particularly impacting on transcriptional elongation chromatin states. H3K36me3 reduction specifically affects highly expressed, CHD8-bound genes and correlates with altered alternative splicing patterns of 462 genes implicated in ‘regulation of RNA splicing’ and ‘mRNA catabolic process’. Mass spectrometry analysis uncovered a novel interaction between CHD8 and the splicing regulator heterogeneous nuclear ribonucleoprotein L (hnRNPL), providing the first mechanistic insights to explain the CHD8 suppression-derived splicing phenotype, partly implicating SETD2, a H3K36me3 methyltransferase. In summary, our results point toward broad molecular consequences of CHD8 suppression, entailing altered histone deposition/maintenance and RNA processing regulation as important regulatory processes in ASD

Effects of ash removal by agitated aqueous washing and sedimentation on the physico-chemical characteristics and fast pyrolysis of trommel fines

A pre-treated trommel fines feedstock (DPT) with 35.1 wt% ash content and particle size range of 0.5–2 mm was processed through two (100% distilled water and 1% surfactant in distilled water) aqueous agitated washing and sedimentation procedures for ash reduction prior to fast pyrolysis in a bubbling fluidized bed reactor. The washing process led to more than 36% reduction in the ash/inorganic contents of the DPT feedstock and yielded about 78 wt% of organic-rich feedstocks denoted as WPT1 and WPT2. Characterisation and fast pyrolysis of all three feedstocks was carried out to evaluate the effect of the washing process on their physico-chemical characteristics and yields of fast pyrolysis products. Results showed that the ash reduction led to increase in the volatile matter contents of the washed feedstocks by 20%, while reducing nitrogen contents. In addition, fast pyrolysis of the feedstocks showed improved yield of liquid and gas products, with a dramatic reduction of reaction water, indicating that the ash removal reduced the catalytic effect of the ash on water formation during the fast pyrolysis process. The major organic compounds in the liquid products included phenols and furans from biogenic fraction of the feedstock as well as aromatic hydrocarbons such as those obtained from pyrolysis of plastics. More importantly, the overall energy yields from the fast pyrolysis process increased by over 35% after washing the feedstock, with washing with only distilled water alone giving the highest energy yield of 93%. Hence, coupling the water-washing ash reduction process with fast pyrolysis appeared to be a suitable technology for valorising feedstocks with high ash contents such as trommel fines for energy and chemicals

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144