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New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation.
2018
New thiazole nortopsentin analogues were conveniently synthesized and evaluated for their activity as inhibitors of biofilm formation of relevant Gram-positive and Gram-negative pathogens. All compounds were able to interfere with the first step of biofilm formation in a dose-dependent manner, showing a selectivity against the staphylococcal strains. The most active derivatives elicited IC50 values against Staphylococcus aureus ATCC 25923, ranging from 0.40&ndash
Lack of evidence of mimivirus replication in human PBMCs
2018
The Acanthamoeba polyphaga mimivirus (APMV) was first isolated during a pneumonia outbreak in Bradford, England, and since its discovery many research groups devoted efforts to understand whether this virus could be associated to human diseases, in particular clinical signs and symptoms of pneumonia. In 2013, we observed cytopathic effect in amoebas (rounding and lysis) inoculated with APMV inoculated PBMCs (peripheral blood mononuclear cell) extracts, and at that point we interpreted those results as mimivirus replication in human PBMCs. Based on these results we decided to further investigate APMV replication in human PBMCs, by transmission electron microscopy (TEM) and qPCR. No viral fac…
Protoparvovirus Knocking at the Nuclear Door
2017
Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural chan…
Real-life practice: rapid improvement in itch symptomatology in patients with atopic dermatitis treated with dupilumab
2019
Sir,Atopic dermatitis is a chronic relapsing inflammatory skin disorder that affects up to 20% of children and 2–5% of the adult population (1). The disease is characterized by erythematous, xeroti...
Guidelines Have a Key Role in Driving HCV Elimination by Advocating for Simple HCV Care Pathways.
2021
The availability of pangenotypic direct-acting antivirals for treatment of hepatitis C (HCV) has provided an opportunity to simplify patient pathways. Recent clinical practice guidelines have recognised the need for simplification to ensure that elimination of HCV as a public health concern remains a priority. Despite the move towards simplified treatment algorithms, there remains some complexity in the recommendations for the management of genotype 3 patients with compensated cirrhosis. In an era where additional clinical trial data are not anticipated, clinical guidance should consider experience gained in real-world settings. Although more experience is required for some pangenotypic the…
Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-…
2019
Introduction There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. Methods We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized…
Merit-based exclusion in Finnish music schools
2019
In this article I analyse merit-based exclusion in Finnish music schools for children and young people. I base my study on my earlier research on meritocracy and written data collected online from current and former music school students in the autumn and winter of 2015–2016. I am able to show there are implicit and explicit merit-based hierarchies in the music school. Hierarchies and exclusion are shown to be connected to the institution’s meritocratic features. As the hierarchies are merit-based, it is hard to question them. The hierarchies justify excluding students from certain practices such as performances. These practices are in fact learning opportunities, as has been established by…
Nuclear Pore Complex Acetylation Regulates mRNA Export and Cell Cycle Commitment in Budding Yeast
2021
AbstractNuclear pore complexes (NPCs) mediate communication between the nucleus and the cytoplasm and regulate gene expression by interacting with transcription and mRNA export factors. Lysine acetyl-transferases (KATs) promote transcription through acetylation of chromatin-associated proteins. We find that Esa1, the KAT subunit of the yeast NuA4 complex, also acetylates the nuclear pore basket component Nup60 to promote mRNA export. Acetylation of Nup60 recruits to the nuclear basket the mRNA export factor Sac3, the scaffolding subunit of the Transcription and Export 2 (TREX-2) complex. Esa1-dependent nuclear export of mRNAs promotes entry into S phase, and is inhibited by the Hos3 deacety…
Imaging Noncanonical Autophagy and LC3-Associated Phagocytosis in Cultured Cells
2019
International audience; Monitoring of ATG8 proteins by western blotting and immunofluorescence microscopy are the most common methods to monitor the autophagy pathway. However, it has recently been shown that ATG8 proteins can be lipidated to non-autophagosome, single-membrane compartments through a noncanonical autophagy pathway. This is commonly found to occur during macro-endocytic processes such as phagocytosis, where it has been termed LC3-associated phagocytosis, and upon lysosomotropic drug treatment. Therefore, care is required when interpreting data based on ATG8 in order to conclude whether a signal relates to the canonical or noncanonical pathway. Here we provide methods to monit…
Discovering unbounded unions of regular pattern languages from positive examples
1996
The problem of learning unions of certain pattern languages from positive examples is considered. We restrict to the regular patterns, i.e., patterns where each variable symbol can appear only once, and to the substring patterns, which is a subclass of regular patterns of the type xαy, where x and y are variables and α is a string of constant symbols. We present an algorithm that, given a set of strings, finds a good collection of patterns covering this set. The notion of a ‘good covering’ is defined as the most probable collection of patterns likely to be present in the examples, assuming a simple probabilistic model, or equivalently using the Minimum Description Length (MDL) principle. Ou…