Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo

Developing a Benchmark Suite for Semantic Web Data from Existing Workflows

This paper presents work in progress towards developing a new benchmark for federated query processing systems. Unlike other popular benchmarks, our queryset is not driven by technical evaluation, but is derived from workflows established by the pharmacology community. The value of this queryset is that it is realistic but at the same time it comprises complex queries that test all features of modern query processing systems

Differences in sex distribution between genetic and sporadic FTD

AbstractBackgroundThe reported sex distribution differs between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that have resulted in variable findings. Our aim was to determine the sex distribution in a large international retrospective cohort of sporadic and genetic FTD.MethodWe included patients with probable and definite behavioural variant frontotemporal dementia (bvFTD), non‐fluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA) and right temporal variant frontotemporal dementia (rtvFTD) from the Amsterdam Dementia Cohort, the Montreal Neurological Institute Cohort, the University of Ulm and Technical University of Munich Cohort (part of the German Consortium of Frontotemporal Lobal Degeneration), the Policlinico Milan Cohort and the Sydney FRONTIER Cohort. We compared sex distribution between genetic and sporadic FTD using χ2 tests.ResultA total of 910 subjects were included (56.3% male), of whom 654 had bvFTD, 99 nfvPPA, 117 svPPA and 40 rtvFTD. Of these, 215 had genetic FTD and the sex distribution was equal (51.2% male), which did not differ significantly from sporadic FTD (57.8% male, χ2 p=0.081). In the sporadic bvFTD subgroup, we found a male predominance (61.6% males compared to 52.9% males in the bvFTD genetic group, χ 2 p=0.04). No sex distribution differences between sporadic and genetic cases were found in the other clinical FTD subgroups (all p>0.05).ConclusionDifferences in sex distribution between genetic and sporadic behavioural variant of FTD may provide important clues for its differential pathogenesis and warrants further research

Acción : diario de Teruel y su provincia: Año III Número 633 - (11/12/34)

New types of phenotyping tools generate large amounts of data on many aspects of plant physiology and morphology with high spatial and temporal resolution. These new phenotyping data are potentially useful to improve understanding and prediction of complex traits, like yield, that are characterized by strong environmental context dependencies, i.e., genotype by environment interactions. For an evaluation of the utility of new phenotyping information, we will look at how this information can be incorporated in different classes of genotype-to-phenotype (G2P) models. G2P models predict phenotypic traits as functions of genotypic and environmental inputs. In the last decade, access to high-density single nucleotide polymorphism markers (SNPs) and sequence information has boosted the development of a class of G2P models called genomic prediction models that predict phenotypes from genome wide marker profiles. The challenge now is to build G2P models that incorporate simultaneously extensive genomic information alongside with new phenotypic information. Beyond the modification of existing G2P models, new G2P paradigms are required. We present candidate G2P models for the integration of genomic and new phenotyping information and illustrate their use in examples. Special attention will be given to the modelling of genotype by environment interactions. The G2P models provide a framework for model based phenotyping and the evaluation of the utility of phenotyping information in the context of breeding programs.</p

Врожденный гипотиреоз и роль неонатального скрининга в раннем диагнозе в Республике Молдова.

Congenital hypothyroidism and the role of neonatal screening in early diagnosis of CH in the Republic of Moldova.Hipotiroidismul congenital (CH) reprezintă una dintre cele mai frecvente cauze de retard mental care poate fi prevenit, cu o incidență la nivel mondial de 1:3000-4000 de nou-născuți. Manifestările clinice sunt adesea subtile sau nu sunt prezente la naștere. Lu&acirc;nd &icirc;n considerație că diagnosticul de HC poate fi omis &icirc;n perioada postnatală, iar printre consecințele acestuia este retardul mental ireversibil, se recomandă prezența unui screening neonatal al HC pentru inițierea unui tratament c&acirc;t mai precoce. &Icirc;n Republica Moldova, screening-ul HC a fost restabilit pe o perioada de 4 luni, printr-un proiect pilot cu IBL International (Germania). Materialul cercetării au servit fi șe de screening neonatala 7956 nou-născuți aleși aleatoriu. Evaluarea fi șelor a fost realizată prin metoda ELISA cu utilizarea reactivelor din setul &rdquo;TSH neonatal screening ELISA&rdquo;, furnizată de IBL International (Germania). Valori ale TSH &gt;20 mIU/L au fost considerate pragul de cut-off pentru hipotiroidism congenital. &Icirc;n urma analizei primare, 7941 nou-născuți aveau valorile normale ale TSH (&lt;10 mIU/L), 10 copii aveau valori cuprinse &icirc;ntre 10 și 20 mIU/L; 5 copii &ndash; valori &gt;20 mIU/L. Drept urmare, 1:530 nou-născuți au fost suspecți pentru HC, iar 1:3978 nou-născuți s-au confi rmat cu Hipotiroidism Congenital &icirc;n cohorta analizată. Se recomandă reinițierea screeningului neonatal pentru Hipotiroidism Congenital. &nbsp;Врожденный гипотиреоз и роль неонатального скрининга в раннем диагнозе в Республике Молдова

Antisense Therapy Attenuates Phospholamban p.(Arg14del) Cardiomyopathy in Mice and Reverses Protein Aggregation

Inherited cardiomyopathy caused by the p.(Arg14del) pathogenic variant of the phospholamban (PLN) gene is characterized by intracardiomyocyte PLN aggregation and can lead to severe dilated cardiomyopathy. We recently reported that pre-emptive depletion of PLN attenuated heart failure (HF) in several cardiomyopathy models. Here, we investigated if administration of a Pln-targeting antisense oligonucleotide (ASO) could halt or reverse disease progression in mice with advanced PLN-R14del cardiomyopathy. To this aim, homozygous PLN-R14del (PLN-R14 (Δ/Δ)) mice received PLN-ASO injections starting at 5 or 6 weeks of age, in the presence of moderate or severe HF, respectively. Mice were monitored for another 4 months with echocardiographic analyses at several timepoints, after which cardiac tissues were examined for pathological remodeling. We found that vehicle-treated PLN-R14 (Δ/Δ) mice continued to develop severe HF, and reached a humane endpoint at 8.1 ± 0.5 weeks of age. Both early and late PLN-ASO administration halted further cardiac remodeling and dysfunction shortly after treatment start, resulting in a life span extension to at least 22 weeks of age. Earlier treatment initiation halted disease development sooner, resulting in better heart function and less remodeling at the study endpoint. PLN-ASO treatment almost completely eliminated PLN aggregates, and normalized levels of autophagic proteins. In conclusion, these findings indicate that PLN-ASO therapy may have beneficial outcomes in PLN-R14del cardiomyopathy when administered after disease onset. Although existing tissue damage was not reversed, further cardiomyopathy progression was stopped, and PLN aggregates were resolved

Cardiac dysfunction in cancer patients : beyond direct cardiomyocyte damage of anticancer drugs. Novel cardio-oncology insights from the joint 2019 meeting of the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: [email protected] reviewedPostprin

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Background: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). Methods and results: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test.In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (. P-value for heterogeneity=0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. Conclusions: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD