Search results for "IIN"
showing 10 items of 1385 documents
International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia
2019
Objective: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. Design: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility…
Socio-Reproductive Conflicts and the Father’s Curse Dilemma
2018
Evolutionary conflicts between males and females can manifest over sexually antagonistic interactions at loci or over sexually antagonistic interests within a locus. The latter form of conflict, intralocus sexual conflict, arises from sexually antagonistic selection and constrains the fitness of individuals through a phenotypic compromise. These conflicts, and socio-reproductive interactions in general, are commonly mediated by hormones, and thus predictive insights can be gained from studying their mediating effects. Here, we integrate several lines of evidence to describe a novel, hormonally mediated reproductive dilemma that we call the father’s curse, which results from an intralocus co…
Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells
2018
Aims/hypothesis: The Coxsackie and adenovirus receptor (CAR) is a transmembrane cell-adhesion protein that serves as an entry receptor for enteroviruses and may be essential for their ability to infect cells. Since enteroviral infection of beta cells has been implicated as a factor that could contribute to the development of type 1 diabetes, it is often assumed that CAR is displayed on the surface of human beta cells. However, CAR exists as multiple isoforms and it is not known whether all isoforms subserve similar physiological functions. In the present study, we have determined the profile of CAR isoforms present in human beta cells and monitored the subcellular localisation of the princi…
On the (un)coupling of the chromophore, tongue interactions, and overall conformation in a bacterial phytochrome
2018
Phytochromes are photoreceptors in plants, fungi, and various microorganisms and cycle between metastable red light-absorbing (Pr) and far-red light-absorbing (Pfr) states. Their light responses are thought to follow a conserved structural mechanism that is triggered by isomerization of the chromophore. Downstream structural changes involve refolding of the so-called tongue extension of the phytochrome-specific GAF-related (PHY) domain of the photoreceptor. The tongue is connected to the chromophore by conserved DIP and PRXSF motifs and a conserved tyrosine, but the role of these residues in signal transduction is not clear. Here, we examine the tongue interactions and their interplay with …
Coordination of the biliverdin D-ring in bacteriophytochromes.
2018
Phytochrome proteins translate light into biochemical signals in plants, fungi and microorganisms. Light cues are absorbed by a bilin chromophore, leading to an isomerization and a rotation of the D-ring. This relays the signal to the protein matrix. A set of amino acids, which is conserved across the phytochrome superfamily, holds the chromophore in the binding pocket. However, the functional role of many of these amino acids is not yet understood. Here, we investigate the hydrogen bonding network which surrounds the D-ring of the chromophore in the resting (Pr) state. We use UV/vis spectroscopy, infrared absorption spectroscopy and X-ray crystallography to compare the photosensory domains…
Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART
2018
Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to s…
PTTG1-interacting protein (PTTG1IP/PBF) predicts breast cancer survival.
2017
Background: PTTG1-interacting protein (PTTG1IP) is an oncogenic protein, which participates in metaphase-anaphase transition of the cell cycle through activation of securin (PTTG1). PTTG1IP promotes the shift of securin from the cell cytoplasm to the nucleus, allowing the interaction between separase and securin. PTTG1IP overexpression has been previously observed in malignant disease, e.g. in breast carcinoma. However, the prognostic value of PTTG1IP in breast carcinoma patients has not previously been revealed. Methods: A total of 497 breast carcinoma patients with up to 22-year follow-up were analysed for PTTG1IP and securin immunoexpression. The results were evaluated for correlations w…
Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions
2020
Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 a…
Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver
2019
Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein homeostasis. First, we elucidated the acute (1–2 days) and 2-week effects of blocking ACVR2 ligands by soluble activin receptor 2B (sACVR2B-Fc) on unfolded protein response (UPR), heat shock proteins (HSPs) and redox balance in a healthy mouse skeletal muscle. Second, we examined UPR, autophagy and redox balance with or without sACVR2B-Fc administration in muscle and liver of C26 tumor-bearing mice. The indicators of UPR and HSPs were not altered 1–2 days after a single sAC…
Host Cell Calpains Can Cleave Structural Proteins from the Enterovirus Polyprotein
2019
Enteroviruses are small RNA viruses that cause diseases with various symptoms ranging from mild to severe. Enterovirus proteins are translated as a single polyprotein, which is cleaved by viral proteases to release capsid and nonstructural proteins. Here, we show that also cellular calpains have a potential role in the processing of the enteroviral polyprotein. Using purified calpains 1 and 2 in an in vitro assay, we show that addition of calpains leads to an increase in the release of VP1 and VP3 capsid proteins from P1 of enterovirus B species, detected by western blotting. This was prevented with a calpain inhibitor and was dependent on optimal calcium concentration, especially for calpa…