Nuclear pore complexes serve as essential gatekeepers of the nuclear envelope, playing crucial roles in regulating transport across the nuclear envelope and maintaining compartmentalization between the nucleus and cytoplasm. While they are fundamental to all nucleated cells, the nucleoporins that make up these complexes are associated with various inherited diseases, often affecting specific cells, tissues, or organs. In this overview, we describe the clinical features, summarize genotype-phenotype correlations at the level of individual genes and specific alleles, and relate this information to insights from cellular biology regarding nucleoporins to illuminate potential disease mechanisms. Our aim is to include significant clinical perspectives that are frequently overlooked in standard cell biology reviews, while ensuring accessibility for readers without a medical background. At the same time, we hope to provide valuable insights for geneticists and clinicians interested in the discussed pathologies, but may have limited background in molecular cell biology. Mutations in nucleoporin-encoding genes, the proteins that form nuclear pore complexes, are associated with various hereditary diseases. We summarize our emerging knowledge to connect clinical manifestations with insights from cell biology.
Post-COVID syndrome (PCS) refers to persistent or new-onset symptoms 3 months after SARS-CoV-2 infection lasting for at least 2 months. The characterization of PCS varies across studies, with a substantial heterogeneity regarding different study samples, survey instruments, and follow-up periods. This is particularly the case in hospitalized patients vs. outpatients, as well as regarding different variants of concern (VOCs) and their impact on the frequency and severity of specific symptoms. The study population of Beyond COVID was recruited in six German cities by inviting (1) individuals registered as SARS-CoV-2 PCR positive at the local Public Health Authorities and (2) previously hospitalized patients with infection date after 1st March 2021. Participants were allocated to the predominant VOC of their first infection. Questionnaires to assess pre-existing conditions, symptoms during infection, and persisting symptomswere performed. Follow-up at sixth-month intervals is planned for 3 years. The study is ongoing. This publication describes the parameters at the baseline visit (BV). We included 1257 participants (13
Sepsis is increasingly recognized as a highly dynamic immunological disorder in which hyperinflammation and anti-inflammatory processes occur simultaneously. The clinical phenotype depends on which arm predominates at a given time, resulting in an early phase that is typically dominated by hyperinflammation and a subsequent phase characterized by hypoinflammation, also referred to as immunoparalysis (IP). Epstein-Barr virus (EBV) reactivation has been associated with an immunosuppressive status. However, its interaction with IP and resulting immune phenotypes remains poorly defined so far. In this current study, we investigated the temporal dynamics of EBV reactivation and IP status, and assessed their impact on immune signatures and mortality in sepsis. In this retrospective cohort of 124 intensive care unit (ICU) patients with sepsis, we performed analysis of EBV load by qPCR and analyzed the inflammatory stage by quantifying HLA-DR molecules on monocytes (mHLA-DR) using flow cytometry. Patients with < 5,000 mHLA-DR/monocyte were classified positive for immunoparalysis (IP+). Cytokine profiles and vital sign were analyzed in parallel. Patients were assigned to four sepsis groups based on EBV/IP status (EBV- IP-, EBV + IP-, EBV- IP+, EBV + IP+). Time-dependent Cox models (start-stop structure) were used to estimate hazard ratios (HR) for mortality, adjusted for age, sex and Sequential Organ Failure Assessment (SOFA) score. Cytokines and clinical markers were compared using Kruskal-Wallis and rank-based analyses. EBV positivity was associated with higher hazard of death (HR 3.30, 95
Local anesthetics are widely used in medical care. However, their sodium channel blocking properties not only explain their analgesic potency but also their possible cardiotoxic effects. Due to the different pharmacodynamics and pharmacokinetics of different local anesthetics as well as the divergent cellular electrophysiological effects, we aimed to investigate and compare the electrophysiological effects of different local anesthetics in an established Langendorff model of the isolated rabbit heart. 50 hearts of New Zealand White rabbits were retrogradely perfused employing a Langendorff-setup. Eight catheters were placed endo- and epicardially, thereby recording monophasic action potentials. Hearts were paced at seven different cycle lengths (300–900 ms), thus obtaining cycle-length dependent action potential duration at 90
In meningiomas, the value of the Simpson classification system to estimate the risk of tumor relapse is increasingly discussed. While raising the question about the indication of routine postoperative magnetic resonance imaging (MRI), the value of the residual tumor volume and of the absolute and relative volume reduction to predict tumor relapse is largely unexplored. Extent of resection (EOR) according to the Simpson classification system, postoperative tumor volume, absolute and relative volume reduction on MRI after surgery were analyzed in 475 patients operated for intracranial WHO grade 1–3 meningiomas. Predictors for recurrence were compared in uni- and multivariate analyses. Despite designated gross total resection in 374 cases, postoperative MRI revealed residual tumor in 7 κ = 0.766, p < 0.001). In univariate analysis, the EOR (p < 0.001), the postoperative tumor volume (HR: 1.002 per ccm, 95
