Stem cells, particularly human iPSCs, constitute a powerful tool for tissue engineering, notably through spheroid and organoid models. While the sensitivity of stem cells to the viscoelastic properties of their direct microenvironment is well-described, stem cell differentiation still relies on biochemical factors. Our aim is to investigate the role of the viscoelastic properties of hiPSC spheroids' direct environment on their fate.
View Article and Find Full Text PDFCongenital myasthenic syndromes (CMS) are predominantly characterized by muscle weakness and fatigability and can be caused by a variety of mutations in genes required for neuromuscular junction formation and maintenance. Among them, AGRN encodes agrin, an essential synaptic protein secreted by motoneurons. We have identified severe CMS patients with uncharacterized p.
View Article and Find Full Text PDFAt a time when complex diseases affect globally 280 million people and claim 14 million lives every year, there is an urgent need to rapidly increase our knowledge into their underlying etiologies. Though critical in identifying the people at risk, the causal environmental factors (microbiome and/or pollutants) and the affected pathophysiological mechanisms are not well understood. Herein, we consider the variations of autophagy-related () genes at the heart of mechanisms of increased susceptibility to environmental stress.
View Article and Find Full Text PDFIn less than eleven months, the world was brought to a halt by the COVID-19 outbreak. With hospitals becoming overwhelmed, one of the highest priorities concerned critical care triage to ration the scarce resources of intensive care units. Which patient should be treated first? Based on what clinical and biological criteria? A global joint effort rapidly led to sequencing the genomes of tens of thousands of COVID-19 patients to determine the patients' genetic signature that causes them to be at risk of suddenly developing severe disease.
View Article and Find Full Text PDFMycoplasmas (a generic name for Mollicutes) are a predominant bacterial contaminant of cell culture and cell derived products including viruses. This prokaryote class is characterized by very small size and lack of a cell wall. Consequently, mycoplasmas escape ultrafiltration and visualization under routine microscopic examination, hence the ease with which cells in culture can be contaminated, with routinely more than 10% of cell lines being contaminated.
View Article and Find Full Text PDFThe ATP-binding cassette (ABC) transporters of class G display a different domain organisation than P-glycoprotein/ABCB1 and bacterial homologues with a nucleotide-binding domain preceding the transmembrane domain. The linker region connecting these domains is unique and its function and structure cannot be predicted. Sequence analysis revealed that the human ABCG2 linker contains a LSGGE sequence, homologous to the canonical C-motif/ABC signature present in all ABC nucleotide-binding domains.
View Article and Find Full Text PDFObjective: The purpose of this meta-analysis is to evaluate the effectiveness of different systemic antibiotics in combination with scaling and root planing (SRP) compared to SRP alone in patients with untreated aggressive periodontitis.
Background: In patients with aggressive periodontitis, SRP is often combined with the use of systemic antibiotics. However, the effectiveness of these antibiotics over time and differences in effectiveness between different antibiotics are hardly known.
Objective: The purpose of this meta-analysis is to evaluate the effectiveness of different systemic antibiotics in combination with scaling and root planing (SRP) when compared to SRP alone in patients with untreated chronic periodontitis.
Background: Although chronic periodontitis is mostly treated without adjunctive systemic antibiotics, some recent meta-analyses have shown clinical benefit for some systemic antibiotics when used as an adjunct to SRP. However, there is a wide variety of systemic antibiotic regimens used today.
We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.
View Article and Find Full Text PDFNipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection.
View Article and Find Full Text PDFA predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis.
View Article and Find Full Text PDFWe have previously reported that the measles virus (MV) could productively infect human dendritic cells (DC), derived in vitro from CD34+ cord blood progenitors in the presence of GM-CSF and TNF-alpha. In this study, we provide evidence that freshly isolated Langerhans cells (LC), which are immature dendritic cells located in skin and mucosal epithelia, are susceptible to MV infection in vitro as assessed by viral antigen expression by both LC syncytia and LC remaining as single cells. Moreover, MV-infected LC completely block naive allogeneic CD4+ T cell proliferation in response to uninfected LC.
View Article and Find Full Text PDFMeasles causes a profound immune suppression which is responsible for the high morbidity and mortality induced by secondary infections. Dendritic cells (DC) are professional antigen-presenting cells required for initiation of primary immune responses. To determine whether infection of DC by measles virus (MV) may play a role in virus-induced suppression of cell-mediated immunity, we examined the ability of CD1a+ DC derived from cord blood CD34+ progenitors and Langerhans cells isolated from human epidermis to support MV replication.
View Article and Find Full Text PDFPrevious studies have documented a role for membrane-bound CD23 (the low affinity Fc epsilon RII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte-associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B-EBV cell lines to casein-specific HLA-DP-restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance.
View Article and Find Full Text PDFIntestinal epithelial cells from the mouse small intestine were immortalized by SV40 large T gene transfer through a murine ecotropic virus. The resulting cell lines expressed the SV40 large T mRNA and exhibited morphological and phenotypic characteristics of normal enterocytes, including intercellular junctions, and expression of cytokeratin, villin, poly-Ig receptor (i.e.
View Article and Find Full Text PDFIn previous studies, we demonstrated that intestinal epithelial cells of the mouse small intestine could present exogenous antigen to specific CD4+ T cell hybridomas. We now report on the ability of normal enterocytes to present the self superantigen Mls1a. Enterocytes from Mls1a but not from Mls1b strains stimulated interleukin-2 production through a V beta 6+ T cell hybridoma specific for Mls1a determinants.
View Article and Find Full Text PDFImmunohistochemical analysis of normal human intestine revealed that two anti-CD23 monoclonal antibodies (mAb), EBVCS 1 and EBVCS 2, reacted with human intestinal epithelial cells. Both mAb exhibited an exclusive reactivity with epithelial cells of the small and large bowels. Staining with both EBVCS 1 and EBVCS 2 was localized on the apical and basal sides of enterocytes.
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