keyword
https://read.qxmd.com/read/35915179/temporally-divergent-regulatory-mechanisms-govern-neuronal-diversification-and-maturation-in-the-mouse-and-marmoset-neocortex
#21
JOURNAL ARTICLE
Wen Yuan, Sai Ma, Juliana R Brown, Kwanho Kim, Vanessa Murek, Lucia Trastulla, Alexander Meissner, Simona Lodato, Ashwin S Shetty, Joshua Z Levin, Jason D Buenrostro, Michael J Ziller, Paola Arlotta
Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. Here we present an integrated single-cell epigenomic and transcriptional analysis of individual mouse and marmoset cortical neuron classes, spanning both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration...
August 2022: Nature Neuroscience
https://read.qxmd.com/read/35864460/accommodating-heterogeneous-missing-data-patterns-for-prostate-cancer-risk-prediction
#22
JOURNAL ARTICLE
Matthias Neumair, Michael W Kattan, Stephen J Freedland, Alexander Haese, Lourdes Guerrios-Rivera, Amanda M De Hoedt, Michael A Liss, Robin J Leach, Stephen A Boorjian, Matthew R Cooperberg, Cedric Poyet, Karim Saba, Kathleen Herkommer, Valentin H Meissner, Andrew J Vickers, Donna P Ankerst
BACKGROUND: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. METHODS: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group ≥ 2 on standard TRUS prostate biopsy...
July 21, 2022: BMC Medical Research Methodology
https://read.qxmd.com/read/35864192/hijacking-of-transcriptional-condensates-by-endogenous-retroviruses
#23
JOURNAL ARTICLE
Vahid Asimi, Abhishek Sampath Kumar, Henri Niskanen, Christina Riemenschneider, Sara Hetzel, Julian Naderi, Nina Fasching, Niko Popitsch, Manyu Du, Helene Kretzmer, Zachary D Smith, Raha Weigert, Maria Walther, Sainath Mamde, David Meierhofer, Lars Wittler, René Buschow, Bernd Timmermann, Ibrahim I Cisse, Stefan L Ameres, Alexander Meissner, Denes Hnisz
Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV derepression is associated with lethality during early development has been a mystery. Here, we report that rapid and selective degradation of the heterochromatin adapter protein TRIM28 triggers dissociation of transcriptional condensates from loci encoding super-enhancer (SE)-driven pluripotency genes and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of SE-enriched transcription factors rescued condensate localization at SEs in TRIM28-degraded cells...
July 21, 2022: Nature Genetics
https://read.qxmd.com/read/35839561/single-cell-technologies-a-new-lens-into-epigenetic-regulation-in-development
#24
REVIEW
Adriano Bolondi, Helene Kretzmer, Alexander Meissner
The totipotent zygote gives rise to diverse cell types through a series of well-orchestrated regulatory mechanisms. Epigenetic modifiers play an essential, though still poorly understood, role in the transition from pluripotency towards organogenesis. However, recent advances in single-cell technologies have enabled an unprecedented, high-resolution dissection of this crucial developmental window, highlighting more cell-type-specific functions of these ubiquitous regulators. In this review, we discuss and contextualize several recent studies that explore epigenetic regulation during mouse embryogenesis, emphasizing the opportunities presented by single-cell technologies, in vivo perturbation approaches as well as advanced in vitro models to characterize dynamic developmental transitions...
October 2022: Current Opinion in Genetics & Development
https://read.qxmd.com/read/35787262/the-role-of-pornography-in-the-sex-life-of-young-adults-a-cross-sectional-cohort-study-on-female-and-male-german-medical-students
#25
JOURNAL ARTICLE
Matthias Jahnen, Leopold Zeng, Martina Kron, Valentin H Meissner, Alexander Korte, Stefan Schiele, Helga Schulwitz, Andreas Dinkel, Jürgen E Gschwend, Kathleen Herkommer
BACKGROUND: Due to easy online accessibility of pornography its consumption is popular among adolescents and young adults. Considering recently developed frameworks on the effects of sexual media, we assessed how increased consumption of pornography is associated with the experience of certain aspects of offline and online sexual activity in German medical students. METHODS: Between April 2018 and March 2020 medical students from the Technical University of Munich in Germany were anonymously surveyed with regards to their sexual behavior, consumption of pornography, and use of social media...
July 4, 2022: BMC Public Health
https://read.qxmd.com/read/35590059/acute-lymphoblastic-leukemia-displays-a-distinct-highly-methylated-genome
#26
JOURNAL ARTICLE
Sara Hetzel, Alexandra L Mattei, Helene Kretzmer, Chunxu Qu, Xiang Chen, Yiping Fan, Gang Wu, Kathryn G Roberts, Selina Luger, Mark Litzow, Jacob Rowe, Elisabeth Paietta, Wendy Stock, Elaine R Mardis, Richard K Wilson, James R Downing, Charles G Mullighan, Alexander Meissner
DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data from large cohorts at a genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing across ALL subtypes, leukemia cell lines and healthy hematopoietic cells, and show that unlike most cancers, ALL samples exhibit CpG island hypermethylation but minimal global loss of methylation...
June 2022: Nature Cancer
https://read.qxmd.com/read/35504755/dna-methylation-a-historical-perspective
#27
REVIEW
Alexandra L Mattei, Nina Bailly, Alexander Meissner
In 1925, 5-methylcytosine was first reported in bacteria. However, its biological importance was not intuitive for several decades. After this initial lag, the ubiquitous presence of this methylated base emerged across all domains of life and revealed a range of essential biological functions. Today, we are armed with the knowledge of the key factors that establish, maintain, and remove DNA methylation and have access to a staggering and rapidly growing number of base-resolution methylation maps. Despite this, several fundamental details about the precise role and interpretation of DNA methylation patterns remain under investigation...
July 2022: Trends in Genetics: TIG
https://read.qxmd.com/read/35082151/anomalous-magnetic-noise-in-an-imperfectly-flat-landscape-in-the-topological-magnet-dy-2-ti-2-o-7
#28
JOURNAL ARTICLE
Anjana M Samarakoon, S A Grigera, D Alan Tennant, Alexander Kirste, Bastian Klemke, Peter Strehlow, Michael Meissner, Jonathan N Hallén, Ludovic Jaubert, Claudio Castelnovo, Roderich Moessner
Noise generated by motion of charge and spin provides a unique window into materials at the atomic scale. From temperature of resistors to electrons breaking into fractional quasiparticles, "listening" to the noise spectrum is a powerful way to decode underlying dynamics. Here, we use ultrasensitive superconducting quantum interference device (SQUIDs) to probe the puzzling noise in a frustrated magnet, the spin-ice compound Dy2 Ti2 O7 (DTO), revealing cooperative and memory effects. DTO is a topological magnet in three dimensions-characterized by emergent magnetostatics and telltale fractionalized magnetic monopole quasiparticles-whose real-time dynamical properties have been an enigma from the very beginning...
February 1, 2022: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/34988400/emergence-and-patterning-dynamics-of-mouse-definitive-endoderm
#29
JOURNAL ARTICLE
Maayan Pour, Abhishek Sampath Kumar, Naama Farag, Adriano Bolondi, Helene Kretzmer, Maria Walther, Lars Wittler, Alexander Meissner, Iftach Nachman
The segregation of definitive endoderm (DE) from bipotent mesendoderm progenitors leads to the formation of two distinct germ layers. Dissecting DE commitment and onset has been challenging as it occurs within a narrow spatiotemporal window in the embryo. Here, we employ a dual Bra/Sox17 reporter cell line to study DE onset dynamics. We find Sox17 expression initiates in vivo in isolated cells within a temporally restricted window. In 2D and 3D in vitro models, DE cells emerge from mesendoderm progenitors at a temporally regular, but spatially stochastic pattern, which is subsequently arranged by self-sorting of Sox17 + cells...
January 21, 2022: IScience
https://read.qxmd.com/read/34758323/chromatin-state-barriers-enforce-an-irreversible-mammalian-cell-fate-decision
#30
JOURNAL ARTICLE
M Andrés Blanco, David B Sykes, Lei Gu, Mengjun Wu, Ricardo Petroni, Rahul Karnik, Mathias Wawer, Joshua Rico, Haitao Li, William D Jacobus, Ashwini Jambhekar, Sihem Cheloufi, Alexander Meissner, Konrad Hochedlinger, David T Scadden, Yang Shi
Stem and progenitor cells have the capacity to balance self-renewal and differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions and can increase this output in response to stress or infection. At what point along the spectrum of maturation do progenitors lose capacity for self-renewal and become irreversibly committed to differentiation? Using a system of conditional myeloid development that can be toggled between self-renewal and differentiation, we interrogate determinants of this "point of no return" in differentiation commitment...
November 9, 2021: Cell Reports
https://read.qxmd.com/read/34752748/diverse-epigenetic-mechanisms-maintain-parental-imprints-within-the-embryonic-and-extraembryonic-lineages
#31
JOURNAL ARTICLE
Daniel Andergassen, Zachary D Smith, Helene Kretzmer, John L Rinn, Alexander Meissner
Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to encode allele-specific expression, but how these specific tasks are accomplished at single loci or across chromosomal scales remains incompletely understood. Here, we systematically disrupt essential epigenetic pathways within polymorphic embryos in order to examine canonical and non-canonical genomic imprinting as well as XCI. We find that DNA methylation and Polycomb group repressors are indispensable for autosomal imprinting, albeit at distinct gene sets...
November 8, 2021: Developmental Cell
https://read.qxmd.com/read/34686499/activation-of-notch-and-myc-signaling-via-b-cell-restricted-depletion-of-dnmt3a-generates-a-consistent-murine-model-of-chronic-lymphocytic-leukemia
#32
JOURNAL ARTICLE
Anat Biran, Shanye Yin, Helene Kretzmer, Elisa Ten Hacken, Salma Parvin, Fabienne Lucas, Mohamed Uduman, Catherine Gutierrez, Nathan Dangle, Leah Billington, Fara Faye Regis, Laura Z Rassenti, Arman Mohammad, Gabriela Brunsting Hoffmann, Kristen Stevenson, Mei Zheng, Elizabeth Witten, Stacey M Fernandes, Eugen Tausch, Clare Sun, Stephan Stilgenbauer, Jennifer R Brown, Thomas J Kipps, John C Aster, Andreas Gnirke, Donna S Neuberg, Anthony Letai, Lili Wang, Ruben D Carrasco, Alexander Meissner, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase DNMT3A is a key regulator of DNA methylation. Although DNMT3A somatic mutations in CLL are rare, we found that low DNMT3A expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of Dnmt3a from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5...
December 15, 2021: Cancer Research
https://read.qxmd.com/read/34661365/s3-guideline-management-of-anticoagulants-and-antiplatelet-agents-in-cutaneous-surgery
#33
JOURNAL ARTICLE
Alexander Nast, Hans-Martin Häfner, Andreas Kolk, Jürgen Koscielny, Christian Kunte, Christoph Löser, Markus Meissner, Anna Pokrywka, Steffen Schirmer, Fabian David Scherer, Klaus Strömer, Tino Wetzig, Corinna Dressler
No abstract text is available yet for this article.
October 2021: Journal der Deutschen Dermatologischen Gesellschaft: JDDG
https://read.qxmd.com/read/34661348/s3-leitlinie-umgang-mit-antikoagulanzien-und-thrombozytenaggregationshemmern-bei-operationen-an-der-haut
#34
JOURNAL ARTICLE
Alexander Nast, Hans-Martin Häfner, Andreas Kolk, Jürgen Koscielny, Christian Kunte, Christoph Löser, Markus Meissner, Anna Pokrywka, Steffen Schirmer, Fabian David Scherer, Klaus Strömer, Tino Wetzig, Corinna Dressler
No abstract text is available yet for this article.
October 2021: Journal der Deutschen Dermatologischen Gesellschaft: JDDG
https://read.qxmd.com/read/34601556/rlm-fast-and-simplified-extraction-of-read-level-methylation-metrics-from-bisulfite-sequencing-data
#35
JOURNAL ARTICLE
Sara Hetzel, Pay Giesselmann, Knut Reinert, Alexander Meissner, Helene Kretzmer
Bisulfite sequencing data provide value beyond the straightforward methylation assessment by analyzing single-read patterns. Over the past years, various informative metrics have been established to explore this information. However, limited compatibility with alignment tools, reference genomes or the measurements they provide present a bottleneck for most groups to include this information as standard analysis. To address this, we developed RLM, a fast and scalable tool for the computation of frequently used Read-Level Methylation statistics...
October 2, 2021: Bioinformatics
https://read.qxmd.com/read/34429321/systematic-profiling-of-dnmt3a-variants-reveals-protein-instability-mediated-by-the-dcaf8-e3-ubiquitin-ligase-adaptor
#36
JOURNAL ARTICLE
Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell
Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A ( DNMT3A ) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations...
January 2022: Cancer Discovery
https://read.qxmd.com/read/34413137/dissecting-dual-roles-of-myod-during-lineage-conversion-to-mature-myocytes-and-myogenic-stem-cells
#37
JOURNAL ARTICLE
Masaki Yagi, Fei Ji, Jocelyn Charlton, Simona Cristea, Kathleen Messemer, Naftali Horwitz, Bruno Di Stefano, Nikolaos Tsopoulidis, Michael S Hoetker, Aaron J Huebner, Ori Bar-Nur, Albert E Almada, Masakazu Yamamoto, Anthony Patelunas, David J Goldhamer, Amy J Wagers, Franziska Michor, Alexander Meissner, Ruslan I Sadreyev, Konrad Hochedlinger
The generation of myotubes from fibroblasts upon forced MyoD expression is a classic example of transcription factor-induced reprogramming. We recently discovered that additional modulation of signaling pathways with small molecules facilitates reprogramming to more primitive induced myogenic progenitor cells (iMPCs). Here, we dissected the transcriptional and epigenetic dynamics of mouse fibroblasts undergoing reprogramming to either myotubes or iMPCs using a MyoD-inducible transgenic model. Induction of MyoD in fibroblasts combined with small molecules generated Pax7+ iMPCs with high similarity to primary muscle stem cells...
September 1, 2021: Genes & Development
https://read.qxmd.com/read/34385432/topological-isolation-of-developmental-regulators-in-mammalian-genomes
#38
JOURNAL ARTICLE
Hua-Jun Wu, Alexandro Landshammer, Elena K Stamenova, Adriano Bolondi, Helene Kretzmer, Alexander Meissner, Franziska Michor
Precise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here, we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSCs) that allowed us to identify CTCF loop domains that have highly conserved boundary CTCF sites and show a notable enrichment of individual developmental regulators...
August 12, 2021: Nature Communications
https://read.qxmd.com/read/34337393/chatbots-as-a-tool-to-scale-mentoring-processes-individually-supporting-self-study-in-higher-education
#39
JOURNAL ARTICLE
Alexander Tobias Neumann, Tamar Arndt, Laura Köbis, Roy Meissner, Anne Martin, Peter de Lange, Norbert Pengel, Ralf Klamma, Heinz-Werner Wollersheim
Like most curricula in the humanities and social sciences, the curriculum of pre-service teacher training in educational sciences often includes time-consuming reading and writing tasks, which require high quality support and feedback in a timely manner. A well-known way to provide this support to students is one-to-one mentoring. However, limited time and resources in the German university context require to effectively scale the benefits of individual feedback. The use of scalable technologies to support learning processes seems to be promising, but its development usually requires a deep technical understanding...
2021: Frontiers in artificial intelligence
https://read.qxmd.com/read/34250208/generation-of-mouse-pluripotent-stem-cell-derived-trunk-like-structures-an-in-vitro-model-of-post-implantation-embryogenesis
#40
JOURNAL ARTICLE
Adriano Bolondi, Leah Haut, Seher Ipek Gassaloglu, Polly Burton, Helene Kretzmer, René Buschow, Alexander Meissner, Bernhard G Herrmann, Jesse V Veenvliet
Post-implantation mammalian embryogenesis involves profound molecular, cellular, and morphogenetic changes. The study of these highly dynamic processes is complicated by the limited accessibility of in utero development. In recent years, several complementary in vitro systems comprising self-organized assemblies of mouse embryonic stem cells, such as gastruloids, have been reported. We recently demonstrated that the morphogenetic potential of gastruloids can be further unlocked by the addition of a low percentage of Matrigel as an extracellular matrix surrogate...
June 5, 2021: Bio-protocol
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