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LINC01503-MP is a mitochondrial microprotein that promotes cell proliferation and oxidative metabolism
Get PDFLong non-coding RNAs (lncRNAs) are well-established as key regulators of gene expression. However, emerging evidence reveals that some lncRNAs can also encode functional microproteins. In this study, we report the identification of an evolutionarily young microprotein encoded by LINC01503, expressed across several human tissues. This microprotein, designated as LINC01503-MP, localises to the mitochondria and exerts a proliferative effect on HCT116 colorectal cancer (CRC) cells. Functional studies reveal that LINC01503-MP regulates mitochondrial oxygen consumption rate, linking its activity to enhanced metabolic functions and cell proliferation. Interactome analyses identified multiple mitochondrial metabolism-related proteins as potential interaction partners. Our findings show that LINC01503-MP plays a role in the proliferative phenotype associated with LINC01503 upregulation in CRC, suggesting the functional significance of evolutionarily young, lncRNA-derived microproteins in cancer progression
Diagnostik und Therapie der ANCA-assoziierten Vaskulitiden: S3-Leitlinie der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie e. V. (DGRh) und Deutschen Gesellschaft für Innere Medizin e. V. (DGIM), Deutschen Gesellschaft für Nephrologie e. V. (DGfN), Deutschen Gesellschaft für HNO-Heilkunde und Kopf-Hals-Chirurgie e. V. (DGHNO-KHC), Deutschen Ophthalmologischen Gesellschaft e. V. (DOG), Deutschen Gesellschaft für Neurologie e. V. (DGN), Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP), Deutschen Gesellschaft für Pathologie e. V. (DGP), Deutschen Röntgengesellschaft, Gesellschaft für Medizinische Radiologie e. V. (DRG), Bundesverband Deutscher Pathologen, Bundesverband Niere e. V., Deutschen Rheuma-Liga Bundesverband e. V. [Diagnosis and treatment of ANCA-associated vasculitis: S3 guideline of the German Society for Rheumatology and Clinical Immunology e. V. (DGRh) and German Society for Internal Medicine e. V. (DGIM), German Society for Nephrology e. V. (DGfN), German Society for ENT Medicine and Head and Neck Surgery e. V. (DGHNO-KHC), German Ophthalmological Society e. V. (DOG), German Society for Neurology e. V. (DGN), German Society for Pneumology and Respiratory Medicine e. V. (DGP), German Society for Pathology e. V. (DGP), German Radiological Society, Society for Medical Radiology e. V. (DRG), Federal Association of German Pathologists, Federal Kidney Association e. V., German Rheumatism League Federal Association e. V.]
No full textSpatial proteomics in translational and clinical research
Get PDFSpatial proteomics offers unprecedented insights into the localization, quantity, and interactions of proteins within cells and tissues, thereby enabling researchers and clinicians to map protein networks with high precision. This powerful approach is currently revolutionizing our understanding of cellular organization and function (Method of the Year 2024: spatial proteomics, 2024), and providing deeper insights into how protein distribution and dynamics contribute to physiological and pathological processes. Here, we discuss recent advances in targeted and untargeted (exploratory) spatial proteomics, shed light on emerging multiscale approaches for tissue profiling, and highlight their translational potential
Scoping Review zu Gesundheitszustand, -verhalten und subjektiven Belastungsempfinden von Pflegekräften in Deutschland: ein Protokoll [Scoping review on health status, behavior, and perceived stress of nursing staff in Germany: a protocol]
Get PDFBACKGROUND: In view of demographic change and the increasing need for care, nursing staff play a key role in the healthcare system. As part of this important role, nurses themselves can face challenging stressful situations that may affect their own health. In order to maintain the well-being and ability to work of nursing staff and, thus, ensure high-quality care, a sound understanding of the current state of health, health behavior, and the influences of daily stressful situations on health is essential. OBJECTIVES: This a priori protocol describes the methodological approach of a planned scoping review to comprehensively examine and pool evidence on the health status, health behavior, and influences of daily stress factors of nurses. METHODS: In this review, all studies of nurses residing in Germany published since 2015 are considered. Both empirical studies and gray literature are included. The planned scoping review will be conducted according to the methodology for scoping reviews developed by the Joanna Briggs Institute (Review registration: Open Science Framework https://osf.io/hx9zm). CONCLUSION: This protocol provides a structured methodological approach to comprehensively examine the health status, health behaviors, and influences of daily stressors of nurses. By applying an established methodology, the planned review will ensure a systematic and transparent pooling of existing evidence and, thus, provide an adequate basis for future interventions and research
Acute promyelocytic leukemia: long-term outcomes from the HARMONY project
No full textPURPOSE: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with the widespread use of targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Our study aimed to validate these data in a large patient cohort, and to redefine prognostic factors. PATIENTS AND METHODS: Leveraging the HARMONY Platform, we analyzed 1438 newly-diagnosed APL patients, diagnosed between 1999 to 2022. Patient data derived from the 2 international multicenter GIMEMA-APL0406 and NCRI-AML17 trials, and 4 European registries (HOVON, AMLSG, Swedish AML Registry and SAL). RESULTS: The study cohort included 721 males and 717 females, with a median age of 50.5 years (range 16-94 years). Of 1309 patients starting therapy, 562 received ATRA-ATO, and 747 AIDA-like chemotherapy. Early death (ED) occurred in 85 of 1438 patients (5.9%) at a median of 9 days after APL diagnosis and was independently associated with increasing age and high Sanz risk score (OR:1.06, 95% C.I: 1.04-1.08, and OR:4.65, 95% C.I.:2.55-8.51, respectively).The median follow-up was 5.5 years (IQR=3.2-7.5). ATRA-ATO regimen was associated with the best outcome, reaching 91% 7-year overall survival (vs 81% for AIDA-like, HR:2.14, 95%C.I.:1.51-3.05), 89% event-free survival (vs 71% for AIDA-like, HR:2.72 95%CI: 2.01-3.69) and 3% relapse (vs 13% for AIDA-like, HR:4.19, 95%CI:2.38-7.39, p<0.001 for all outcomes). The survival advantage of ATRA/ATO was independent of patients' age, Sanz-risk score, and treatment scenario. CONCLUSIONS: Our study confirms the superiority of ATRA-ATO over ATRA-chemotherapy in APL patients. ED represents an unmet medical need, in particular in older patients and in high-risk APL
New cardiovascular biomarkers in patients with advanced cancer – a prospective study comparing MR-proADM, MR-proANP, copeptin, high-sensitivity troponin T and NT-proBNP
Get PDFAIMS: Traditional cardiovascular (CV) biomarkers (high-sensitivity troponinT [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) are important to monitor cancer patients' cardiac function and to assess prognosis. Newer CV biomarkers (mid-regional pro-adrenomedullin [MR-proADM], C-terminal pro-arginine vasopressin [copeptin], and mid-regional pro-atrial natriuretic peptide [MR-proANP]) might outperform traditional biomarkers. METHODS AND RESULTS: Overall, 442 hospitalized cancer patients without significant CV disease or current infection were enrolled (61 ± 15 years, 52% male, advanced cancer stage: 85%) and concentrations of CV biomarkers were analysed. Differences in echocardiographic, clinical, laboratory parameters were assessed. Patients were followed for up to 69 months for all-cause mortality. In univariable analyses, MR-proADM, hsTnT, copeptin, MR-proANP, and NT-proBNP predicted all-cause mortality. In multivariable analyses (adjusted for sex, age, Eastern Cooperative Oncology Group performance status, estimated glomerular filtration rate [eGFR], C-reactive protein, anti-cancer therapy, reason for hospitalization, cancer stage and type), only MR-proADM remained an independent predictor of mortality (MR-proADM per 1 ln: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.47–3.50], p 0.94 nmol/L were older, more often had cancer stage IV, showed reduced performance status, eGFR, haemoglobin, diastolic left ventricular function, and elevated systolic pulmonary artery pressure. CONCLUSION: MR-proADM is an independent predictor of mortality in advanced stage, hospitalized cancer patients without significant CV disease or current infection. The optimal MR-proADM cut-point for mortality prediction was 0.94 nmol/L with hazards for mortality being approximately 2.5 times higher. There was a continuous increase in mortality risk with stepwise increase of MR-proADM concentrations. Elevated concentrations of MR-proADM were also associated with reduced performance status and mildly reduced left ventricular diastolic function as well as higher age and more often cancer stage IV
Rethinking animal attrition in preclinical research: expressing causal mechanisms of selection bias using directed acyclic graphs
Get PDFAnimal attrition in preclinical experiments can introduce bias in the estimation of causal treatment effects, as the treatment-outcome association in surviving animals may not represent the causal effect of interest. This can compromise the internal validity of the study despite randomization at the outset. Directed Acyclic Graphs (DAGs) are useful tools to transparently visualize assumptions about the causal structure underlying observed data. By illustrating relationships between relevant variables, DAGs enable the detection of even less intuitive biases, and can thereby inform strategies for their mitigation. In this study, we present an illustrative causal model for preclinical stroke research, in which animal attrition induces a specific type of selection bias (i.e., collider stratification bias) due to the interplay of animal welfare, initial disease severity and negative side effects of treatment. Even when the treatment had no causal effect, our simulations revealed substantial bias across different scenarios. We show how researchers can detect and potentially mitigate this bias in the analysis phase, even when only data from surviving animals are available, if knowledge of the underlying causal process that gave rise to the data is available. Collider stratification bias should be a concern in preclinical animal studies with severe side effects and high post-randomization attrition
Gauging antigen recognition by human primary T-cells featuring orthotopically exchanged TCRs of choice
No full textUnderstanding human T-cell antigen recognition in health and disease is becoming increasingly instrumental for monitoring T-cell responses to pathogen challenge and for the rational design of T-cell-based therapies targeting cancer, autoimmunity and organ transplant rejection. Here we showcase a quantitative imaging platform which is based on the use of planar glass-supported lipid bilayers (SLBs). The latter are functionalized with antigen (peptide-loaded HLA) as adhesion and costimulatory molecules (ICAM-1, B7-1) to serve as surrogate antigen presenting cell for antigen recognition by T-cells, which are equipped with T-cell antigen receptors (TCRs) sequenced from antigen-specific patient T-cells. We outline in detail, how the experimental use of SLBs supports recoding and analysis of synaptic antigen engagement and calcium signaling at the single cell level in response to user-defined antigen densities for quantitative comparison
Ca2+ release-reuptake kinetics
No full textRaw data files of Fura-2 ratiometric dye in intact unloaded cardiomyocytes. (2025-03-05
Combined RNAi and localization for functionally dissecting long non-coding RNAs data
No full textWhereas methods to comprehensively study cellular roles of protein-coding genes are available, techniques to systematically investigate long noncoding RNAs (lncRNAs), which have been implicated in diverse biological pathways, are limited. Here we report combined knockdown and localization analysis of noncoding RNAs (c-KLAN) that merges functional characterization and localization approaches to study lncRNAs. Using this technique we identified transcripts that regulate mouse embryonic stem cell identity