Subject(s)
Sepsis , Humans , Middle Aged , Female , Sepsis/diagnosis , Sepsis/etiology , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Bacteremia/diagnosis , Bacteremia/microbiology , Bacteremia/drug therapy , Multiple Organ Failure/etiology , Multiple Organ Failure/diagnosis , Fatal Outcome , Procalcitonin/bloodABSTRACT
Sedoreoviridae is a large family of icosahedral viruses that are usually regarded as non-enveloped with segmented (10-12 linear segments) dsRNA genomes of 18-26 kbp. Sedoreovirids have a broad host range, infecting mammals, birds, crustaceans, arthropods, algae and plants. Some of them have important pathogenic potential for humans (e.g. rotavirus A), livestock (e.g. bluetongue virus) and plants (e.g. rice dwarf virus). This is a summary of the ICTV Report on the family Sedoreoviridae, which is available at ictv.global/report/sedoreoviridae.
Subject(s)
Mammals , RNA, Double-Stranded , Animals , Birds , Genome, Viral , Humans , Plants , Virion , Virus ReplicationABSTRACT
[Figure: see text].
Subject(s)
Carotid Artery Injuries/metabolism , DNA-Binding Proteins/deficiency , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Neointima , Animals , Carotid Artery Injuries/genetics , Carotid Artery Injuries/pathology , Carotid Artery, Common/metabolism , Carotid Artery, Common/pathology , Case-Control Studies , Cell Movement , Cell Proliferation , Coronary Artery Disease/genetics , Coronary Artery Disease/metabolism , Coronary Stenosis/genetics , Coronary Stenosis/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Knockout Techniques , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , Phenotype , RAW 264.7 Cells , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Signal TransductionABSTRACT
Human interleukin-11 (hIL-11) is a pleiotropic cytokine administered to patients with low platelet counts. From a structural point of view hIL-11 belongs to the long-helix cytokine superfamily, which is characterized by a conserved core motif consisting of four α-helices. We have investigated the region of hIL-11 that does not belong to the α-helical bundle motif, and that for the purpose of brevity we have termed "non-core region." The primary sequence of the interleukin was altered at various locations within the non-core region by introducing glycosylation sites. Functional consequences of these modifications were examined in cell-based as well as biophysical assays. Overall, the data indicated that the non-core region modulates the function of hIL-11 in two ways. First, the majority of muteins displayed enhanced cell-stimulatory properties (superagonist behavior) in a glycosylation-dependent manner, suggesting that the non-core region is biologically designed to limit the full potential of hIL-11. Second, specific modification of a predicted mini α-helix led to cytokine inactivation, demonstrating that this putative structural element belongs to site III engaging a second copy of cell-receptor gp130. These findings have unveiled new and unexpected elements modulating the biological activity of hIL-11, which may be exploited to develop more versatile medications based on this important cytokine.
