Using targeted proteomics-based detection of collagen propeptides to quantify fibrillar collagen biogenesis in vitro.

The collagen superfamily, as the major structural component of the extracellular matrix, encompasses 28 distinct subtypes, with type-I and -III forming fibrils crucial for the matrix scaffold. During collagen biogenesis, trimers of type-I and -III procollagen are secreted into the extracellular matrix. The N- and C-terminal propeptides of these trimers are proteolytically cleaved from procollagen during secretion, initiating collagen fibril formation.

Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction.

Desbuquois dysplasia type 2 (DBQD2) and spondylo-ocular syndrome (SOS) are autosomal recessive disorders affecting the extracellular matrix (ECM) and categorized as glycosaminoglycan (GAG) linkeropathies. Linkeropathies result from mutations within glycosyltransferases involved in the synthesis of the tetrasaccharide linker, a linker between the core protein of proteoglycan (PG) and GAG. DBQD2 and SOS are caused by the isolated mutations of the xylosyltransferase (XT) isoforms.

A novel SPE-UPLC-MS/MS-based assay for the selective, simultaneous quantification of xylosyltransferase-I and -II activity.

Xylosyltransferase-I and -II (XT-I, -II) possess a central role during the glycosylation of proteoglycans (PGs). They catalyze the formation of an O-glycosidic bond between the xylosyl residue of uridinediphosphate-xylose and the core protein of a PG. Thereafter, three following glycosyltransferases lead to the generation of a tetrasaccharide linker, which connects the PG core protein to the respective glycosaminoglycan.

Dyspareunia, signs of epithelial disruption, sexual abstinence, and HIV status in female sex workers in Nairobi: a cross-sectional study.

Background: Epithelial trauma is a risk factor of HIV infection in men who have sex with men (MSM) and female sex workers (FSWs). Painful intercourse may be indicative of epithelial tissue disruption. Previous studies on a cohort of Kenyan FSWs established an association between prolonged sexual abstinence and late HIV seroconversion.

Understanding of arthrofibrosis: New explorative insights into extracellular matrix remodeling of synovial fibroblasts.

Arthrofibrosis following total knee arthroplasty is a fibroproliferative joint disorder marked by dysregulated biosynthesis of extracellular matrix proteins, such as collagens and proteoglycans. The underlying cellular events remain incompletely understood. Myofibroblasts are highly contractile matrix-producing cells characterized by increased alpha-smooth muscle actin expression and xylosyltransferase-I (XT-I) secretion.

Human Xylosyltransferase I-An Important Linker between Acute Senescence and Fibrogenesis.

The human xylosyltransferase isoform XT-I catalyzes the initial step in proteoglycan biosynthesis and represents a biomarker of myofibroblast differentiation. Furthermore, XT-I overexpression is associated with fibrosis, whereby a fibrotic process initially develops from a dysregulated wound healing. In a physiologically wound healing process, extracellular matrix-producing myofibroblasts enter acute senescence to protect against fibrosis.

Analysis of a German blood donor cohort reveals a high number of undetected SARS-CoV-2 infections and sex-specific differences in humoral immune response.

Seroprevalence studies can contribute to a better assessment of the actual incidence of infection. Since long-term data for Germany are lacking, we determined the seroprevalence of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in residual plasma samples of 3,759 German regular blood donors between July 2020 and June 2021. Over almost the entire study period, the incidences determined based on our data were higher than those officially reported by the Robert Koch Institute, the public health institute in Germany.

Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response.

Background: We report the results of a prospective study on the immunogenicity of a 3rd dose of BNT162b2 in thoracic organ recipients with no or minimal response following a two-dose BNT162b2 vaccination scheme.

Methods: A total of 243 transplant recipients received a homologue 3rd dose. Anti-SARS-CoV2-immunoglobulins (IgGs) were monitored immediately before (T1), 4 weeks (T2) as well as 2 and 4 months after the 3rd dose.

Humoral and cellular immune response levels at a 1-year follow-up after mild COVID-19.

The primary objective of this study was to establish a 1-year follow-up of patients after mild COVID-19 with no or only short-term detection of antibodies shortly after disease. At 1 year after disease, cellular memory against SARS-CoV-2, as measured by IFN-γ release by T cells, was detected in 76% (38/50) of participants. The data suggest that even if antibody levels decline after the primary infection has resolved, a cellular immune response may be detectable for longer.

Cellular and Humoral Immune Response to a Third Dose of BNT162b2 COVID-19 Vaccine - A Prospective Observational Study.

Background: Since the introduction of various vaccines against SARS-CoV-2 at the end of 2020, infection rates have continued to climb worldwide. This led to the establishment of a third dose vaccination in several countries, known as a booster. To date, there has been little real-world data about the immunological effect of this strategy.

The Impact of Inflammatory Stimuli on Xylosyltransferase-I Regulation in Primary Human Dermal Fibroblasts.

Inflammation plays a vital role in regulating fibrotic processes. Beside their classical role in extracellular matrix synthesis and remodeling, fibroblasts act as immune sentinel cells participating in regulating immune responses. The human xylosyltransferase-I (XT-I) catalyzes the initial step in proteoglycan biosynthesis and was shown to be upregulated in normal human dermal fibroblasts (NHDF) under fibrotic conditions.

Short-Term Drop in Antibody Titer after the Third Dose of SARS-CoV-2 BNT162b2 Vaccine in Adults.

Little is known about the longevity of antibodies after a third dose of the mRNA-based SARS-CoV-2 vaccine BNT162b2 (BioNTech/Pfizer, Mainz, Germany). Therefore, serum antibody levels were evaluated after a third dose of BNT162b2 in healthy adult healthcare workers in Germany. These antibody levels dropped significantly within a short period of 11 weeks from 4155.

First Characterization of Human Dermal Fibroblasts Showing a Decreased Xylosyltransferase-I Expression Induced by the CRISPR/Cas9 System.

Background: Xylosyltransferases-I and II (XT-I and XT-II) catalyze the initial and rate limiting step of the proteoglycan (PG) biosynthesis and therefore have an import impact on the homeostasis of the extracellular matrix (ECM). The reason for the occurrence of two XT-isoforms in all higher organisms remains unknown and targeted genome-editing strategies could shed light on this issue.

Methods: XT-I deficient neonatal normal human dermal fibroblasts were generated by using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated proteins (Cas) 9 system.

Persistence of Immune Response in Health Care Workers After Two Doses BNT162b2 in a Longitudinal Observational Study.

Background: The mRNA-based vaccine BNT162b2 of BioNTech/Pfizer has shown high efficacy against SARS-CoV-2 infection and a severe course of the COVID-19 disease. However, little is known about the long-term durability of the induced immune response resulting from the vaccination.

Methods: In a longitudinal observational study in employees at a German hospital we compared the humoral and cellular immune response in 184 participants after two doses of the BioNTech/Pfizer vaccine (BNT162b2) with a mid-term follow-up after 9 months.

SARS-CoV-2-antibody response in health care workers after vaccination or natural infection in a longitudinal observational study.

Background: Following a year of development, several vaccines have been approved to contain the global COVID-19 pandemic. Real world comparative data on immune response following vaccination or natural infection are rare.

Methods: We conducted a longitudinal observational study in employees at a secondary care hospital affected by the COVID-19 pandemic.

Half-Year Longitudinal Seroprevalence of SARS-CoV-2-Antibodies and Rule Compliance in German Hospital Employees.

COVID-19, which is caused by SARS-CoV-2, is an occupational health risk, especially for healthcare employees due to their higher exposure and consequently higher risk of symptomatic and asymptomatic infections. This study was designed to determine the longitudinal seroprevalence of specific immunoglobulin-G (IgG) antibodies in employees in a hospital setting. All employees in a secondary care hospital, including healthcare and non-healthcare workers, were invited to participate in this single-center study.

A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories.

The determination of anti-SARS-CoV-2 neutralizing antibodies (NAbs) is of interest in many respects. High NAb titers, for example, are the most important criterion regarding the effectiveness of convalescent plasma therapy. However, common cell culture-based NAb assays are time-consuming and feasible only in special laboratories.

Evidence of Long-Lasting Humoral and Cellular Immunity against SARS-CoV-2 Even in Elderly COVID-19 Convalescents Showing a Mild to Moderate Disease Progression.

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years).

Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients.

Aims: Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients.

Cytokine-mediated induction of human xylosyltransferase-I in systemic sclerosis skin fibroblasts.

Systemic sclerosis (SSc) is an inflammatory fibrotic disease characterized by an excessive extracellular matrix deposition in the skin and internal organs. One fibrotic key event remains the fibroblast-to-myofibroblast differentiation that is controlled by a combination of mechanical and soluble factors, such as transforming growth factor-β1 (TGF-β1) and interleukin-1β (IL-1β). One important myofibroblast biomarker is human xylosyltransferase-I (XT-I), the initial enzyme in proteoglycan biosynthesis.

Retrospective analysis of 426 donors of a convalescent collective after mild COVID-19.

Background: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the world. The aim of our study was to characterize mild courses and to determine the antibody status for these patients.

Methods: We initiated an appeal for convalescent plasma donations.

Development of a xylosyltransferase-I-selective UPLC MS/MS activity assay using a specific acceptor peptide.

Xylosyltransferases-I and -II (XT-I and -II) play an important role regarding the homeostasis of the extracellular matrix. Both enzymes catalyze the initial step of the proteoglycan (PG) biosynthesis by the transfer of xylose from their natural substrate uridine diphosphate (UDP) -xylose to a PG-core protein. The subsequent addition of further sugars, catalyzed by different glycosyltransferases, leads to the formation of a tetrasaccharide linker, which connects the PG-core protein and glycosaminoglycans.

Identification of Putative Non-Substrate-Based XT-I Inhibitors by Natural Product Library Screening.

Fibroproliferative diseases are characterized by excessive accumulation of extracellular matrix (ECM) components leading to organ dysfunction. This process is characterized by an increase in myofibroblast content and enzyme activity of xylosyltransferase-I (XT-I), the initial enzyme in proteoglycan (PG) biosynthesis. Therefore, the inhibition of XT-I could be a promising treatment for fibrosis.

Prospective Sero-epidemiological Evaluation of SARS-CoV-2 among Health Care Workers in a German Secondary Care Hospital.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the pulmonary disease coronavirus disease 2019 (COVID-19, which has challenged health care facilities worldwide. The sustainability of health care systems is largely reliant on the health status of their health care workers (HCW). This study aimed to detect the SARS-CoV-2 virus and specific antibodies among HCWs in a German hospital as a model system for the potential spread of the pandemic.

After-Action Reviews and Long-Term Performance: An Experimental Examination in the Context of an Emergency Simulation.

Objective: The present study examined the effectiveness of after-action reviews (AARs; also known as debriefing) in mitigating skill decay.

Background: Research on the long-term effectiveness of AARs is meager. To address this gap in the literature, we conducted an experimental study that also overcomes some research design issues that characterize the limited extant research.