1,721,649 research outputs found
Chromatin Architecture Shapes the Immune System : Chromatinopathies Perspective
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Aspergillus fumigatus morphology and dynamic host interactions
Aspergillus fumigatus is an environmental filamentous fungus that can cause life-threatening disease in immunocompromised individuals. The interactions between A. fumigatus and the host environment are dynamic and complex. The host immune system needs to recognize the distinct morphological forms of A. fumigatus to control fungal growth and prevent tissue invasion, whereas the fungus requires nutrients and needs to adapt to the hostile environment by escaping immune recognition and counteracting host responses. Understanding these highly dynamic interactions is necessary to fully understand the pathogenesis of aspergillosis and to facilitate the design of new therapeutics to overcome the morbidity and mortality caused by A. fumigatus. In this Review, we describe how A. fumigatus adapts to environmental change, the mechanisms of host defence, and our current knowledge of the interplay between the host immune response and the fungus
How Trained Immunity Shapes Atherosclerosis : From Mechanism to Disease
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Role of Molecular Biology in Diagnosis and Characterization of Vulvo-Vaginitis in Clinical Practice
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180464.pdf (Publisher’s version ) (Open Access
Impact of Human Genetic Variation on C-Reactive Protein Concentrations and Acute Appendicitis
BACKGROUND: Acute appendicitis is one of the most common abdominal emergencies worldwide. Both environmental and genetic factors contribute to the disease. C-reactive protein (CRP) is an important biomarker in the diagnosis of acute appendicitis. CRP concentrations are significantly affected by genetic variation. However, whether such genetic variation is causally related to appendicitis risk remains unclear. In this study, the causal relationship between single-nucleotide polymorphisms (SNPs) associated with circulating CRP concentrations and the risk and severity of acute appendicitis was investigated. METHODS: CRP concentrations in serum of appendicitis patients (n = 325) were measured. Appendicitis was categorized as complicated/uncomplicated and gangrenous/non-gangrenous. Imputed SNP data (n = 287) were generated. A genome-wide association study (GWAS) on CRP concentrations and appendicitis severity was performed. Intersection and colocalization of the GWAS results were performed with appendicitis and CRP-associated loci from the Pan-UKBB cohort. A functional-genomics approach to prioritize genes was employed. RESULTS: Thirteen percent of significant CRP quantitative trait loci (QTLs) that were previously identified in a large cohort of healthy individuals were replicated in our small patient cohort. Significant enrichment of CRP-QTLs in association with appendicitis was observed. Among these shared loci, the two top loci at chromosomes 1q41 and 8p23.1 were characterized. The top SNP at chromosome 1q41 is located within the promoter of H2.0 Like Homeobox (HLX) gene, which is involved in blood cell differentiation, and liver and gut organogeneses. The expression of HLX is increased in the appendix of appendicitis patients compared to controls. The locus at 8p23.1 contains multiple genes, including cathepsin B (CTSB), which is overexpressed in appendix tissue from appendicitis patients. The risk allele of the top SNP in this locus also increases CTSB expression in the sigmoid colon of healthy individuals. CTSB is involved in collagen degradation, MHC class II antigen presentation, and neutrophil degranulation. CONCLUSIONS: The results of this study prioritize HLX and CTSB as potential causal genes for appendicitis and suggest a shared genetic mechanism between appendicitis and CRP concentrations
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Lesion size is associated with genetic polymorphisms in TLR1, TLR6, and TIRAP genes in patients with major abscesses and diabetic foot infections
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218691.pdf (Publisher’s version ) (Open Access)Genetic variation in Toll-like receptors (TLRs) has previously been associated with susceptibility to complicated skin and skin structure infections (cSSSIs). The aim of this study was to investigate associations between the severity of cSSSIs, i.e., major abscesses and diabetic foot infections (DFIs), and a set of genetic polymorphisms in the Toll-like receptor pathway. A total of 121 patients with major abscesses and 132 with DFIs participating in a randomized clinical trial were genotyped for 13 nonsynonymous single-nucleotide polymorphisms (SNPs) in genes coding for TLRs and the signaling adaptor molecule TIRAP. Infection severity was defined by lesion size at clinical presentation for both types of infections. The PEDIS infection score was also used to define severity of DFIs. Linear regression models were used to study factors independently associated with severity. In patients with large abscesses, hetero- or homozygosity for the allelic variant TLR6 (P249S) was associated with significantly smaller lesions while homozygosity for the allelic variant TLR1 (R80T) was associated with significantly larger lesions. PRRs genes were not significantly associated with PEDIS. However, patients with DFI hetero- or homozygous for the allelic variant TLR1 (S248N) had significantly larger lesions. Polymorphisms in TLR1 and TLR6 influence the severity of cSSSIs as assessed by the lesion size of major abscesses and DFIs. ClinicalTrial.gov Identifier: NCT00402727
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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