Ludwig-Maximilians-Universität München
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Novel Tet3 enzymes for next-generation epigenetic sequencing
No full textEpigenetic regulation of gene expression is essential for cellular development and differentiation processes in higher eukaryotes. Modifications of cytosine, in particular 5-methylcytosine (5mdC), in DNA play a central role through impacting chromatin structure, repressing transposons, and regulating transcription. DNA methylation is actively installed by DNA methyltransferases and reversed through Tet-dioxygenase-mediated oxidation of 5mdC to 5-hydroxylmethylcytosine (5hmdC), 5-formylcytosine (5fdC), and 5-carboxycytosine (5cadC). It is crucial to understand the role of these epigenetic DNA modifications in cellular differentiation and developmental processes, as well as in disease state mapping and tracing of 5mdC and its oxidized forms. In bisulfite sequencing, which has been the benchmark for mapping 5mdC for the last few decades, degradation of the majority of genetic material occurs through harsh chemical treatment. Alternative sequencing methods often utilize Tet-enzyme-mediated oxidation of 5mdC to locate 5mdC and 5hmdC in genomic DNA. Herein, we report the development of novel Tet3-variants for oxidation-based bisulfite-free 5mdC- sequencing
Perioperative complications and mid-term outcomes in total hip and knee joint arthroplasty among solid organ transplant recipients: lowest reoperation-free survival and patient survivorship in lung transplant recipients
No full text[18F]SiTATE-PET/CT for detection of pheochromocytomas and paragangliomas: comparison of biochemical secretion, genotype and imaging metrics
No full textInsights into pathophysiology, biomarkers, and therapeutics in tauopathies: Proceedings of the Tau2024 Global Conference
Full text linkRecent years have seen major advances in tau-associated brain disorders through interdisciplinary research spanning molecular biology, neuroimaging, clinical trials, and therapeutic development. The Tau2024 Global Conference, hosted by the Alzheimer's Association, CurePSP, and Rainwater Charitable Foundation, showcased these efforts by bringing together researchers and experts worldwide to discuss the latest advancements in tau research. The conference aimed to attract talent and funding to study tauopathies, particularly among early-career researchers, and to foster interdisciplinary alignment and collaboration around challenges in tau research. In this manuscript, we summarize proceedings of the Tau2024 Global Conference, covering a wide range of topics, including lived experiences of individuals with genetic forms of tauopathies, global perspectives on tauopathies, and molecular mechanisms, brain microenvironments, biomarker developments, clinical trials, and therapeutic approaches to tauopathies. Through international, collaborative efforts, innovative research, and a commitment to inclusivity, researchers worldwide have demonstrated transformative breakthroughs toward diagnosing, treating, and, ultimately, preventing tau-related diseases
Comparing loss of individual fragile X proteins suggests strong links to cellular senescence and aging
Full text linkMembers of the fragile X protein (FXP) family (FMR1, FXR1 and FXR2) are differentially expressed in most types of cancer and major neurodegenerative diseases. While increased expression of FXR1 in cancer has been linked to senescence evasion and consequently tumor initiation and progression, decreased expression of FXPs in neurodegeneration may contribute to pathogenic protein aggregation and death of vulnerable neurons. However, due the causal role in fragile x syndrome, most data are available about loss of FMR1 in neurons while functions of FXR1 and especially FXR2 remain largely unexplored. To address this knowledge gap, and to directly compare functions of the FXPs, we used proteomics of CRISPR/Cas9 edited HAP1 cells carrying knockouts of the individual FXPs for identification of cellular mechanisms associated with these proteins. Further exploration of proteomic findings suggests roles of the FXPs in ribosome biogenesis, autophagy and mitochondrial health linked to organismal aging, and cellular senescence. Validation of FXP induced defects relevant for neurodegenerative diseases in neuroblastoma cell line SH-SY5Y upon FXP knockdown revealed high cell type specificity of individual FXP functions. Overall, we provide a comprehensive overview and comparison of cellular mechanisms related to the individual FXPs, as well as starting points for further studying this protein family in respective cell types of FXP associated diseases, and in aging in general
Small-Scale Farming, Pesticide Exposure, and Respiratory Health: A Cross-Sectional Study in Bolivia
Full text linkThis study analyzed the relationship between pesticide exposure with respiratory symptoms
and lung function among small-scale farm workers in rural communities of
Sucre, Bolivia. A cross-sectional study was conducted including 277 farmers and
214 non-farmers ≥ 16 years. Pesticide exposure and respiratory symptoms were assessed
by questionnaire, and lung function was assessed by spirometry. Logistic regression
models were used to estimate odds ratios and 95% confidence intervals for associations
between pesticide exposure and respiratory symptoms, while multiple linear regression
was employed to estimate associations with lung function. The adjusted regression models
indicated a positive association between pesticide exposure and chronic cough or phlegm
(aOR 1.22; 95% CI 1.0 to 1.5), chest tightness (1.14; 1.0 to 1.3), and nasal allergies (1.21; 1.0
to 1.4). Also, pesticide exposure showed a slight positive association with FVC (β = 0.04;
95% CI = 0.01 to 0.07). Agricultural work (vs. non-agricultural work) showed a dual effect;
on the one hand, it showed a negative association with lung function (FEV1/FVC (%):
−1.57; 95% CI = −3.25 to −0.11); on the other hand, it seemed to be a protective factor
for nasal allergies (aOR 0.31; 95% CI 0.1–0.8). Our study suggests an association between
pesticide exposure and respiratory symptoms and farm work with lung function parameters.
The results underscore the need to enhance programs that regulate and train farmers
on the use of pesticides, thereby reducing health effects on workers and agricultural and
neighboring communities
Replication of the 2023 radiologically isolated syndrome criteria in a multi-centre cohort
Full text linkRadiologically isolated syndrome (RIS) represents a pivotal stage for identifying individuals at high risk of transitioning into multiple sclerosis (MS). Early therapy initiation reduces the risk of conversion. The 2023-RIS criteria were proposed to identify presymptomatic individuals earlier. We aimed to replicate the diagnostic value of the 2023-RIS criteria in an independent cohort. In this retrospective cohort study, individuals diagnosed with RIS and longitudinally followed in three centres were stratified by the 2009- and 2023-RIS criteria. We conducted comparative analyses, including survival, hazard ratio and performance evaluations. Among n = 136 individuals, 27.2% converted to MS between 2009 and 2024 (observation time 55.4 months). We confirmed improved identification of individuals at risk using the 2023-RIS criteria (HR 4.30, P < 0.05; HR 4.71, P < 0.05) compared to 2009-RIS criteria (HR 1.32, P = 0.4; HR 1.43; P = 0.3) in 5- and 10-year intervals, respectively. 2023-RIS criteria demonstrated high sensitivity (94%) and negative predictive value (94%) but low specificity (29%). Adding CSF immunoglobulin G and M indices as an additional parameter following RIS diagnosis enhanced risk prediction specificity. We confirm the high sensitivity and predictive value of the 2023-RIS criteria for identifying individuals at risk of conversion to MS and suggest adding immunoglobulin indices to further improve specificity