Search results for "patho"

Global emergence of the widespread Pseudomonas aeruginosa ST235 clone

2018

Abstract Objectives Despite the non-clonal epidemic population structure of Pseudomonas aeruginosa , several multi-locus sequence types are distributed worldwide and are frequently associated with epidemics where multidrug resistance confounds treatment. ST235 is the most prevalent of these widespread clones. In this study we aimed to understand the origin of ST235 and the molecular basis for its success. Methods The genomes of 79 P. aeruginosa ST235 isolates collected worldwide over a 27-year period were examined. A phylogenetic network was built, using a Bayesian approach to find the Most Recent Common Ancestor, and we identified antibiotic resistance determinants and ST235-specific genes…

2017

Aqueous humour (AH) is an important biologic fluid that maintains normal intraocular pressure and contains proteins that regulate the homeostasis of ocular tissues. Any alterations in the protein compositions are correlated to the pathogenesis of various ocular disorders. In recent years, gender-based medicine has emerged as an important research focus considering the prevalence of certain diseases, which are higher in a particular sex. Nevertheless, the inter-gender variations in the AH proteome are unknown. Therefore, this study endeavoured to characterize the AH proteome to assess the differences between genders. Thirty AH samples of patients who underwent cataract surgery were categoriz…

2016

Psoriasis is an autoimmune skin disease that is associated with aberrant activity of immune cells and keratinocytes. In mice, topical application of TLR7/8 agonist IMQ leads to a skin disorder resembling human psoriasis. Recently, it was shown that the IL-23/ IL-17 axis plays a deciding role in the pathogenesis of human psoriasis, as well as in the mouse model of IMQ-induced psoriasis-like skin disease. A consequence of IL-17A production in the skin includes increased expression and production of IL-6, resulting in the recruitment of neutrophils and other myelomonocytic cells to the site of inflammation. To further investigate and characterize the exact role of IL-6 signaling in myelomonocy…

Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

2016

Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGI…

The Mouse Cytomegalovirus Gene m42 Targets Surface Expression of the Protein Tyrosine Phosphatase CD45 in Infected Macrophages

2016

The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264.7 macrophage cell line led to comparable regulation of CD45 expression. In immunocompetent mice infected with an m42 del…

Morphological Evidence of Telocytes in Skeletal Muscle Interstitium of Exercised and Sedentary Rodents

2021

Skeletal muscle atrophy, resulting from states of hypokinesis or immobilization, leads to morphological, metabolic, and functional changes within the muscle tissue, a large variety of which are supported by the stromal cells populating the interstitium. Telocytes represent a recently discovered population of stromal cells, which has been increasingly identified in several human organs and appears to participate in sustaining cross-talk, promoting regenerative mechanisms and supporting differentiation of local stem cell niche. The aim of this morphologic study was to investigate the presence of Telocytes in the tibialis anterior muscle of healthy rats undergoing an endurance training protoco…

Different rates of spontaneous mutation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing

2017

[EN] Mutation rates vary by orders of magnitude across biological systems, being higher for simpler genomes. The simplest known genomes correspond to viroids, subviral plant replicons constituted by circular non-coding RNAs of few hundred bases. Previous work has revealed an extremely high mutation rate for chrysanthemum chlorotic mottle viroid, a chloroplastreplicating viroid. However, whether this is a general feature of viroids remains unclear. Here, we have used high-fidelity ultra-deep sequencing to determine the mutation rate in a common host (eggplant) of two viroids, each representative of one family: the chloroplastic eggplant latent viroid (ELVd, Avsunviroidae) and the nuclear pot…

Human norovirus hyper-mutation revealed by ultra-deep sequencing

2016

Human noroviruses (NoVs) are a major cause of gastroenteritis worldwide. It is thought that, similar to other RNA viruses, high mutation rates allow NoVs to evolve fast and to undergo rapid immune escape at the population level. However, the rate and spectrum of spontaneous mutations of human NoVs have not been quantified previously. Here, we analyzed the intra-patient diversity of the NoV capsid by carrying out RT-PCR and ultra-deep sequencing with 100,000-fold coverage of 16 stool samples from symptomatic patients. This revealed the presence of low-frequency sequences carrying large numbers of U-to-C or A-to-G base transitions, suggesting a role for hyper-mutation in NoV diversity. To mor…

One NF1 Mutation may Conceal Another

2019

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the NF1 and SPRED1 genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent NF1 variants. All NF1 variants were classified as pathogenic, according to t…

2016

Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Gα subunits of heterotrimeric G proteins. The mutations were det…