is essential for zebrafish embryogenesis and pronephros formation.

Background And Objectives: Friedreich's Ataxia (FRDA) is a genetic disease that affects a variety of different tissues. The disease is caused by a mutation in the gene ( which is important for the synthesis of iron-sulfur clusters. The primary pathologies of FRDA are loss of motor control and cardiomyopathy.

Noninvasive Stool RNA Test Approximates Disease Activity in Patients With Crohn's Disease.

Background And Aims: Management of Crohn's disease (CD) requires frequent monitoring for disease activity and response to therapy. In this study, we examined the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic in patients with CD.

Methods: Stool samples were collected from 68 individuals for up to 3 time points prior to, and after initiation of an advanced therapy.

Analytical Validation of the Multitarget Stool RNA Test for Colorectal Cancer Screening.

The multitarget stool RNA (mt-sRNA) test (ColoSense) is a noninvasive diagnostic test that screens for colorectal cancer and advanced adenomas in average-risk individuals aged 45 years and older. The mt-sRNA test incorporates a commercially available fecal immunochemical test, concentration of eight RNA transcripts, and participant-reported smoking status. As part of the CRC-PREVENT (Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test) clinical trial, 12 analytical validation studies were conducted to assess analytical sensitivity, linearity, precision, interfering substances, cross-reactivity, carry-over, cross-contamination, and robustness.

Activation of the aryl hydrocarbon receptor improves allergen-specific immunotherapy of murine allergic airway inflammation: a novel adjuvant option?

Background: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies.

SARS-CoV-2 NSP14 MTase activity is critical for inducing canonical NF-κB activation.

Upon SARS-CoV-2 infection, patients with severe forms of COVID-19 often suffer from a dysregulated immune response and hyperinflammation. Aberrant expression of cytokines and chemokines is associated with strong activation of the immunoregulatory transcription factor NF-κB, which can be directly induced by the SARS-CoV-2 protein NSP14. Here, we use NSP14 mutants and generated cells with host factor knockouts (KOs) in the NF-κB signaling pathways to characterize the molecular mechanism of NSP14-induced NF-κB activation.

Modulation of pre-mRNA structure by hnRNP proteins regulates alternative splicing of .

Alternative splicing plays key roles for cell type-specific regulation of protein function. It is controlled by cis-regulatory RNA elements that are recognized by RNA binding proteins (RBPs). The MALT1 paracaspase is a key factor of signaling pathways that mediate innate and adaptive immune responses.

Alteration of Ligamento-Muscular Reflex Patterns After Cutaneous and Periarticular Desensitization of the Basal Thumb Joint: An Electromyographic Study.

Purpose: Stimulation of the dorsoradial ligament (DRL) of the first carpometacarpal joint (CMC-1) has shown a ligamento-muscular reflex pathway between the DRL and CMC-1 stabilizing muscles in healthy volunteers. However, it remains unclear how this ligamento-muscular reflex pattern is altered after anesthetizing sensory skin receptors and administering a further periarticular block around the CMC-1 joint, which may influence the dynamic aspects of joint stability.

Methods: Ligamento-muscular reflexes were obtained from the extensor pollicis longus, abductor pollicis longus, abductor pollicis brevis, and the first dorsal interosseous muscles in 10 healthy participants after establishing superficial anesthesia of the skin around the CMC-1.

Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells.

CARD11 acts as a gatekeeper for adaptive immune responses after T cell or B cell antigen receptor (TCR/BCR) ligation on lymphocytes. PKCθ/β-catalyzed phosphorylation of CARD11 promotes the assembly of the CARD11-BCL10-MALT1 (CBM) complex and lymphocyte activation. Here, we demonstrated that PKCθ/β-dependent CARD11 phosphorylation also suppressed CARD11 functions in T or B cells.

Graft survival of Descemet membrane endothelial keratoplasty (DMEK) in corneal endothelial decompensation after glaucoma surgery.

Purpose: This study aims to assess the results, rebubbling rate, and graft survival after Descemet membrane endothelial keratoplasty (DMEK) with regard to the number and type of previous glaucoma surgeries.

Methods: This is a clinical retrospective review of 1845 consecutive DMEK surgeries between 07/2011 and 08/2017 at the Department of Ophthalmology, University of Cologne. Sixty-six eyes were included: group 1 (eyes with previous glaucoma drainage devices (GDD); n = 27) and group 2 (eyes with previous trabeculectomy (TE); n = 39).

TRAF6 prevents fatal inflammation by homeostatic suppression of MALT1 protease.

Balanced control of T cell signaling is critical for adaptive immunity and protection from autoimmunity. By combining genetically engineered mouse models, biochemical analyses and pharmacological interventions, we describe an unexpected dual role of the tumor necrosis factor receptor–associated factor 6 (TRAF6) E3 ligase as both a positive and negative regulator of mucosa-associated lymphoid tissue 1 (MALT1) paracaspase. Although MALT1-TRAF6 recruitment is indispensable for nuclear factor κB signaling in activated T cells, TRAF6 counteracts basal MALT1 protease activity in resting T cells.

Methods to Study CARD11-BCL10-MALT1 Dependent Canonical NF-κB Activation in Jurkat T Cells.

Jurkat T cells have been of central importance for the discovery of signalling mediators driving NF-κB activation in response to T cell antigen receptor (TCR)/CD28 co-stimulation. The critical function of the key regulators identified in Jurkat T cells has subsequently been verified in primary murine and human T cells. CRISPR/Cas9-mediated genomic editing techniques in combination with viral reconstitution are powerful tools that now enable the investigation of the exact molecular mechanisms that govern T cell signalling, especially the impact of protein-protein interactions, protein modifications, or cancer-associated gain- or loss-of-function mutations.

MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells.

The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation.

Cancer-associated fibroblasts lead tumor invasion through integrin-β3-dependent fibronectin assembly.

Cancer-associated fibroblasts (CAFs) are the most abundant cells of the tumor stroma. Their capacity to contract the matrix and induce invasion of cancer cells has been well documented. However, it is not clear whether CAFs remodel the matrix by other means, such as degradation, matrix deposition, or stiffening.

XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation.

X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear.

Impact of the post-anesthetic care unit opening hours on fast-track success in cardiac surgery.

Background: Fast-track (FT) treatment in cardiac anesthesia is a state-of-the-art technique. The aim of our study was to compare FT treatment in a post-anesthetic care unit (PACU) with limited opening hours with a PACU opened for unlimited hours. Primary endpoints were extubation time (ET), length of stay (LOS) in PACU and LOS in intermediate care unit (IMC).

Design for risk control: the role of usability engineering in the management of use-related risks.

The majority of medical device incident reports can primarily be attributed to use error. Greater attention to human factors and usability during development of a medical device could improve this situation. However, recent studies have shown that companies do not find the application of a sound usability engineering process according to international standards a simple task.

Obstructive sleep apnea syndrome is associated with overactive bladder and urgency incontinence in men.

Study Objective: To investigate the incidence of overactive bladder (OAB) and urgency incontinence (UI) in men with obstructive sleep apnea syndrome (OSAS).

Design: Prospective questionnaire study

Setting: Saarland University Hospital

Patients: All male patients who underwent full-night in-laboratory polysomnography between November 2006 and April 2007.

Interventions: Overactive bladder symptom score (OABSS) and International Consultation on Incontinence Questionnaire, Short-Form (ICIQ-SF).

[EasyScope - an alternative to the conventional Macintosh laryngoscope?].

Objective: This study was conducted to compare two different techniques used for tracheal intubation (TI). We evaluated airway management conditions for a conventional Macintosh laryngoscope and the Brummert EasyScope, a new device.

Methods: A prospective trial was conducted with 20 medical students who had no prior airway management experience.

Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair.

Objective: To characterize the impact of abdominal aortic aneurysm repair (AAAR) on spontaneous as well as lipopolysaccharide (LPS)-induced gene expression of pro- and anti-inflammatory cytokines.

Design: Prospective, controlled in vivo/ex vivo study.

Setting: University hospital.

Characterization of monoclonal antibodies for prostate-specific antigen and development of highly sensitive free prostate-specific antigen assays.

Background: The recent elucidation of the importance of serological free prostate-specific antigen (PSA) in the diagnosis of prostate cancer has created a demand for immunoassays specific for free PSA.

Methods: We developed and characterized 11 monoclonal antibodies with high affinities for PSA (Ka values from 1.1 x 10(8) to 1.