Identifying optimal substrate classes of membrane transporters.

Membrane transporters are responsible for moving a wide variety of molecules across biological membranes, making them integral to key biological pathways in all organisms. Identifying all membrane transporters within a (meta-)proteome, along with their specific substrates, provides important information for various research fields, including biotechnology, pharmacology, and metabolomics. Protein datasets are frequently annotated with thousands of molecular functions that form complex networks, often with partial or full redundancy and hierarchical relationships.

Subsequent Thyroid Carcinomas in Children and Adolescents Registered in the German MET Consortium (1997-2023).

Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence.

Discovery of 7,9-Dibromo-dihydrodibenzofuran as a Potent Casein Kinase 2 (CK2) Inhibitor: Synthesis, Biological Evaluation, and Structural Studies on /-Isomers.

The human protein kinase CK2 is a promising target for cancer treatment. Only two CK2 inhibitors have reached clinical trials until today. Among others, a dibenzofuran scaffold has emerged as highly prospective for the development of new CK2 inhibitors.

Challenging granulomatous differential diagnosis of CNS lesions in a 75-year-old patient with indolent lymphoma.

We report here on a patient with concomitant indolent lymphoma who showed a rapid progressive deterioration of his general condition and emerging neurological symptoms. The combination of severe B symptoms with hypermetabolic involvement of the adrenal glands and multiple central nervous system (CNS) lesions initially suggested a malignant disease. However, when the patient presented to us with biopsy results from one of the CNS lesions, the biopsy revealed granulomatous inflammation but no evidence of malignancy.

Required minimal protein domain of flower for synaptobrevin2 endocytosis in cytotoxic T cells.

Flower, a highly conserved protein, crucial for endocytosis and cellular fitness, has been implicated in cytotoxic T lymphocyte (CTL) killing efficiency through its role in cytotoxic granule (CG) endocytosis at the immune synapse (IS). This study explores the molecular cues that govern Flower-mediated CG endocytosis by analyzing uptake of Synaptobrevin2, a protein specific to CG in mouse CTL. Using immunogold electron microscopy and total internal fluorescence microscopy, we found that Flower translocates in a stimulus-dependent manner from small vesicles to the IS, thereby ensuring specificity in CG membrane protein recycling.

Standardized Assessment of Health-Related Quality of Life in Patients with Congenital Aniridia.

Introduction: Congenital aniridia is a rare panocular disorder that is associated with varying degrees of impairment of visual acuity. The COST Action (CA18116) developed a survey (aniridia-net.eu) to assess patient-reported experiences with congenital aniridia and its impacts on vision and daily life.

GOLD COPD Exacerbation History Categories and Disease Outcomes.

Importance: Previous exacerbations of chronic obstructive pulmonary disease (ECOPD) are associated with future events. For more than a decade, patients at high risk have been defined as individuals with a history of 2 or more moderate ECOPD, 1 or more severe ECOPD, or both within 12 months, and treatments have been allocated accordingly, but these cutoffs lack validation.

Objectives: To validate ECOPD history categories by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and explore alternative cutoffs to estimate moderate and severe ECOPD and all-cause mortality in COPD.

Evaluation of immunohistochemical TRPC3 and TRPC6 expression patterns in human endometriosis.

Background: Although to date the pathogenesis of endometriosis remains largely unexplained, it is known that processes of migration, proliferation and revascularization and thus calcium as a messenger substance play an important role. Consecutively, the present study examines the immunohistochemical expression of the calcium transient receptor potential channels 3 and 6 (TRPC3 and TRPC6) in ectopically located (outside the uterine cavity) endometrial tissue.

Methods: Laparoscopically collected and histomorphologically verified endometriosis tissues from several different intraabdominal locations were examined (n = 20) and immunohistochemical stainings were performed with anti-TRPC3 and anti-TRPC6 antibodies (Alomone Labs, Jerusalem).

The Effect of Lens Properties on Visual Acuity, Aniridia Associated Keratopathy and Secondary Glaucoma in Congenital Aniridia Subjects.

Purpose: The potential risks and benefits of cataract surgery, in context of congenital aniridia (CA), are not widely understood, yet. Our purpose was to investigate the effect of lens properties on visual acuity (VA), aniridia-associated keratopathy (AAK) stage and presence of glaucoma at the Homburg Aniridia Center.

Methods: CA subjects, examined at the Department of Ophthalmology of Saarland University between June 2003 and January 2022, were included.

Clinical utility of the Fibrosis-4 index for predicting mortality in patients with heart failure with or without metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

Background: The liver-heart axis potentially influences the risk of mortality in patients with heart failure. We aimed to identify the clinical utility of the fibrosis-4 (FIB-4) index in patients with heart failure for predicting mortality in the context of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Patients with heart failure and a subsample of healthy participants were enrolled in the MyoVasc study (NCT04064450) and followed for nine years.

Endovascular thrombectomy: an effective and safe therapy for perioperative ischemic stroke.

Background: Perioperative ischemic stroke is a rare but devastating complication. Mechanical thrombectomy is a promising therapeutic method, but very little data is available on its efficacy and safety. This study aims to answer this question by comparing the clinical outcomes of perioperative and community-onset stroke patients after endovascular therapy.

Multifunctional Sensor Array for User Interaction Based on Dielectric Elastomers with Sputtered Metal Electrodes.

The integration of textile-based sensing and actuation elements has become increasingly important across various fields, driven by the growing demand for smart textiles in healthcare, sports, and wearable electronics. This paper presents the development of a small, smart dielectric elastomer (DE)-based sensing array designed for user control input in applications such as human-machine interaction, virtual object manipulation, and robotics. DE-based sensors are ideal for textile integration due to their flexibility, lightweight nature, and ability to seamlessly conform to surfaces without compromising comfort.

Selenium Disulfide from Sustainable Resources: An Example of "Redneck" Chemistry with a Pinch of Salt.

Selenium disulfide (often referred to as SeS) encompasses a family of mixed selenium-sulfide eight-membered rings, traditionally used as an anti-dandruff agent in shampoos. SeS can be produced by reacting hydrogen sulfide (HS) with selenite (SeO) under acidic conditions. This chemistry is also possible with natural spring waters that are rich in HS, thus providing an avenue for the more sustainable, green production of high-quality SeS particles from an abundant natural source.

Cytomegalovirus-Specific T-Cell-Receptor-like Antibodies Target In Vivo-Infected Human Leukocytes Inducing Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity.

Cytomegalovirus (CMV) reactivation after stem cell or solid organ transplantation remains a major cause of morbidity and mortality in this setting. T-cell receptor (TCR)-like antibodies bind to intracellular peptides presented in major histocompatibility complex (MHC) molecules on the cell surface and may have the potential to replace T-cell function in immunocompromised patients. Three previously selected CMV-specific, human leukocyte antigen (HLA)-restricted (HLA-A*0101, HLA-A*0201 and HLA-B*0702) Fab-antibodies (A6, C1 and C7) were produced as IgG antibodies with Fc optimization.

Only Infant -Rearranged Leukemia Is Susceptible to an Inhibition of Polo-like Kinase 1 (PLK-1) by Volasertib.

-rearranged (r) leukemia is characterized by a poor prognosis. Depending on the cell of origin, it differs in the aggressiveness and therapy response. For instance, in adults, volasertib blocking Polo-like kinase 1 (PLK-1) exhibited limited success.

Genetic Downregulation of GABA Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord.

GABAergic signaling and GABA receptors play crucial roles in regulating the physiology of oligodendrocyte-lineage cells, including their proliferation, differentiation, and myelination. Therefore, they are promising targets for studying how spinal oligodendrocyte precursor cells (OPCs) respond to injuries and neurodegenerative diseases like multiple sclerosis. Taking advantage of the temporally controlled and cell-specific genetic downregulation of GABA receptors from OPCs, our investigation addresses their specific influence on OPC behavior in the gray and white matter of the mouse spinal cord.

Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition - a randomized controlled trial.

Fatigue is the most prevalent symptom within the post-COVID condition (PCC). Furthermore, many patients suffer from decreased physical performance capacity and post-exertional malaise. Although exercise has been proposed as an effective therapeutic strategy for PCC, there is limited evidence on individualised and symptom-titrated exercise interventions in patients with fatigue and PEM.

Probiotics as an adjunctive therapy in periodontitis treatment-reality or illusion-a clinical perspective.

Periodontitis, a prevalent oral health issue, involves various microorganisms and clinical effects. This review examines probiotics as adjunctive therapy for periodontitis by analyzing forty clinical studies. Findings showed mixed results due to differences in study design, probiotic types, and clinical parameters; however, probiotics improved outcomes in severe cases.

Development, validation, and prognostic evaluation of LiverPRO for the prediction of significant liver fibrosis in primary care: a prospective cohort study.

Background: Clinically significant liver fibrosis is associated with future adverse events in patients with steatotic liver disease. We designed a software tool for detection of clinically significant liver fibrosis in primary care.

Methods: In this prospective cohort study, we developed and validated LiverPRO using six independent cohorts from Denmark, Germany, and England that included patients from primary and secondary care with steatotic liver disease related to alcohol or metabolic dysfunction.

Temperature adaptation of yeast phospholipid molecular species at the acyl chain positional level.

Yeast is a poikilothermic organism and adapts its lipid composition to the environmental temperature to maintain membrane physical properties. Studies addressing temperature-dependent adaptation of the lipidome have described changes in the phospholipid composition at the level of sum composition (e.g.

Examination of the Corneal Endothelium in Patients With Congenital Aniridia With a PAX6 Mutation Using In Vivo Confocal Laser Scanning Microscopy.

Purpose: In PAX6 syndrome, it is still not clear, whether prenatally, parallel to the iris tissue developmental anomaly, there is neural ectodermal, neural crest, or mesodermal cell deposition at the corneal endothelium, affecting endothelial structure and function. In addition, because of the postnatal corneal inflammation and commonly appearing secondary glaucoma, progressive endothelial changes are expected. Our purpose was to study the corneal endothelium in subjects with PAX6 aniridia, using in vivo confocal laser scanning microscopy.

Systematic Investigations of the Solid Solution Zr(V1-xAlx)2 Adopting the Laves Phase Structures.

Laves phases are an interesting field of research when it comes to structural chemistry and physical properties. Investigations of the ternary system Zr-V-Al showed, in contrast to the system Hf-V-Al, that no superstructures can be observed within the solid solution Zr(V1-xAlx)2. High values of x form aluminum rich phases that adopt the hexagonal MgZn2 type structure while low values of x lead to vanadium rich phases that adopt the cubic MgCu2 type.