234 results match your criteria: "Biocenter of the University[Affiliation]"

NEAT1 promotes genome stability via mA methylation-dependent regulation of CHD4.

Genes Dev

October 2024

Mildred Scheel Early Career Center for Cancer Research (Mildred-Scheel-Nachwuchszentrum [MSNZ]) Würzburg, University Hospital Würzburg, 97080 Würzburg, Germany;

Long noncoding (lnc)RNAs emerge as regulators of genome stability. The nuclear-enriched abundant transcript 1 (NEAT1) is overexpressed in many tumors and is responsive to genotoxic stress. However, the mechanism that links NEAT1 to DNA damage response (DDR) is unclear.

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Nono induces Gadd45b to mediate DNA repair.

Life Sci Alliance

August 2024

Mildred Scheel Early Career Center for Cancer Research (Mildred-Scheel-Nachwuchszentrum, MSNZ) Würzburg, University Hospital Würzburg, Würzburg, Germany

RNA-binding proteins are frequently deregulated in cancer and emerge as effectors of the DNA damage response (DDR). The non-POU domain-containing octamer-binding protein NONO/p54 is a multifunctional RNA-binding protein that not only modulates the production and processing of mRNA, but also promotes the repair of DNA double-strand breaks (DSBs). Here, we investigate the impact of deletion in the murine KP ( , ) cell-based lung cancer model.

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Article Synopsis
  • DNA damage from ionizing irradiation prompts a transcriptional response that suppresses gene expression while increasing the production of antisense transcripts known as PROMPTs.* -
  • Using mNET-seq, the study found that PROMPTs are transcribed by a specific form of RNA polymerase II that is phosphorylated at the Y1P residue, which is linked to key protein interactions and transcriptional pausing.* -
  • The research highlights that Y1P-dependent PROMPTs help recruit PRC2 to chromatin, and disrupting these PROMPTs or PRC2 results in the loss of transcriptional repression, indicating their crucial role in managing gene expression after DNA damage.*
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Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts.

Nucleic Acids Res

April 2024

Mildred Scheel Early Career Center for Cancer Research (Mildred-Scheel-Nachwuchszentrum, MSNZ) Würzburg, University Hospital Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.

RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood.

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Pheromone of grouped female mice impairs genome stability in male mice through stress-mediated pathways.

Sci Rep

October 2023

Department of Genetics and Biotechnology, Saint-Petersburg State University, Universitetskaya Emb., 7-9, Saint Petersburg, Russia, 199034.

Population density is known to affect the health and survival of many species, and is especially important for social animals. In mice, living in crowded conditions results in the disruption of social interactions, chronic stress, and immune and reproductive suppression; however, the underlying mechanisms remain unclear. Here, we investigated the role of chemosignals in the regulation of mouse physiology and behavior in response to social crowding.

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Interleukin-4 (IL-4) plays a key role in atopic diseases. It coordinates T-helper cell differentiation to subtype 2, thereby directing defense toward humoral immunity. Together with Interleukin-13, IL-4 further induces immunoglobulin class switch to IgE.

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Developing protein structure figures.

Trends Biochem Sci

March 2023

Department of Therapeutic Discovery, Amgen Research, Amgen Inc., South San Francisco, CA, USA. Electronic address:

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Proximity Labeling of Nuclear and Nucleolar Proteins by a Stably Expressed, DNA Damage-Responsive NONO-APEX2 Fusion Protein.

Front Mol Biosci

June 2022

Mildred Scheel Early Career Center for Cancer Research (Mildred-Scheel-Nachwuchszentrum, MSNZ), University Hospital Würzburg, Würzburg, Germany.

Cellular stress can induce DNA lesions that threaten the stability of genes. The DNA damage response (DDR) recognises and repairs broken DNA to maintain genome stability. Intriguingly, components of nuclear paraspeckles like the non-POU domain containing octamer-binding protein (NONO) participate in the repair of DNA double-strand breaks (DSBs).

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Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation. A long appreciated, yet undefined relationship exists between the lytic-latent switch and viral non-coding RNAs. Here we identify viral microRNA (miRNA)-mediated inhibition of host miRNA processing as a cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defences and drive the switch from latent to lytic virus infection.

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To counteract insect decline, it is essential to understand the underlying causes, especially for key pollinators such as nocturnal moths whose ability to orientate can easily be influenced by ambient light conditions. These comprise natural light sources as well as artificial light, but their specific relevance for moth orientation is still unknown. We investigated the influence of moonlight on the reproductive behavior of privet hawkmoths (Sphinx ligustri) at a relatively dark site where the Milky Way was visible while the horizon was illuminated by distant light sources and skyglow.

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Compartment-Specific Proximity Ligation Expands the Toolbox to Assess the Interactome of the Long Non-Coding RNA NEAT1.

Int J Mol Sci

April 2022

Mildred Scheel Early Career Center for Cancer Research (Mildred-Scheel-Nachwuchszentrum, MSNZ), University Hospital Würzburg, Josef-Schneider Str. 2, 97080 Würzburg, Germany.

The nuclear paraspeckle assembly transcript 1 (NEAT1) locus encodes two long non-coding (lnc)RNA isoforms that are upregulated in many tumours and dynamically expressed in response to stress. NEAT1 transcripts form ribonucleoprotein complexes with numerous RNA-binding proteins (RBPs) to assemble paraspeckles and modulate the localisation and activity of gene regulatory enzymes as well as a subset of messenger (m)RNA transcripts. The investigation of the dynamic composition of NEAT1-associated proteins and mRNAs is critical to understand the function of NEAT1.

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Many vaccine candidates with promising results in preclinical testing fail in human trials. New complex human tissue models have the potential to improve the predictability of vaccine safety and efficacy in human clinical trials.

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Commuting to Work: Nucleolar Long Non-Coding RNA Control Ribosome Biogenesis from Near and Far.

Noncoding RNA

July 2021

Mildred Scheel Early Career Center for Cancer Research (Mildred-Scheel-Nachwuchszentrum, MSNZ), University Hospital Würzburg, Josef-Schneider Str. 2, 97080 Würzburg, Germany.

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism.

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TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis.

Cell Rep

June 2021

Institut für Genetik, Rheinische Friedrich-Wilhelms Universität Bonn, 53115 Bonn, Germany; Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. Electronic address:

The activity of the SMN complex in promoting the assembly of pre-mRNA processing UsnRNPs correlates with condensation of the complex in nuclear Cajal bodies. While mechanistic details of its activity have been elucidated, the molecular basis for condensation remains unclear. High SMN complex phosphorylation suggests extensive regulation.

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Poly-l-lysine Glycoconjugates Inhibit DC-SIGN-mediated Attachment of Pandemic Viruses.

ChemMedChem

August 2021

Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.

The C-type lectin receptor DC-SIGN mediates interactions with envelope glycoproteins of many viruses such as SARS-CoV-2, ebola, and HIV and contributes to virus internalization and dissemination. In the context of the recent SARS-CoV-2 pandemic, involvement of DC-SIGN has been linked to severe cases of COVID-19. Inhibition of the interaction between DC-SIGN and viral glycoproteins has the potential to generate broad spectrum antiviral agents.

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Article Synopsis
  • The study investigated the clinical characteristics and genetic variations associated with the DHX30-related neurodevelopmental disorder, especially focusing on new missense variants in the gene.
  • Researchers collected clinical and genetic data from affected individuals via social media, collaboration networks, and analyzed the effects of these variants on cellular functions and development using various experimental models, including zebrafish.
  • Findings revealed that individuals with missense variants presented with severe developmental issues, while those with variants leading to milder haploinsufficiency showed less severe symptoms, suggesting the presence of two distinct clinical subtypes based on the type and location of the genetic variants.
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Eukaryotic cells determine the protein output of their genetic program by regulating mRNA transcription, localization, translation and turnover rates. This regulation is accomplished by an ensemble of RNA-binding proteins (RBPs) that bind to any given mRNA, thus forming mRNPs. Poly(A) binding proteins (PABPs) are prominent members of virtually all mRNPs that possess poly(A) tails.

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Mild proteasomal stress improves photosynthetic performance in Arabidopsis chloroplasts.

Nat Commun

April 2020

Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3a, 06120, Halle, Saale, Germany.

The proteasome is an essential protein-degradation machinery in eukaryotic cells that controls protein turnover and thereby the biogenesis and function of cell organelles. Chloroplasts import thousands of nuclear-encoded precursor proteins from the cytosol, suggesting that the bulk of plastid proteins is transiently exposed to the cytosolic proteasome complex. Therefore, there is a cytosolic equilibrium between chloroplast precursor protein import and proteasomal degradation.

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The gene of encodes a highly abundant 47 kDa synaptic vesicle-associated protein. null mutants show defects in synaptic plasticity and larval olfactory associative learning but the molecular function of Sap47 at the synapse is unknown. We demonstrate that Sap47 modulates the phosphorylation of another highly abundant conserved presynaptic protein, synapsin.

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Background/aims: Free amino acids (FAAs) and urea, present inside the corneocytes, can be important indicators of skin condition. However, due to the lack of a standard extraction protocol for FAAs from corneocytes, conflicting research results have been reported. Therefore, the purpose of this study was (1) to standardize the extraction protocol and (2) to investigate FAA profiles in healthy young and healthy old volunteers, as well as in psoriasis and atopic dermatitis patients.

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We present the results of a DNA barcoding pipeline that was established as part of the German-Indonesian IndobioSys project - Indonesian Biodiversity Information System. Our data release provides the first large-scale diversity assessment of Indonesian coleoptera obtained by canopy fogging. The project combined extensive fieldwork with databasing, DNA barcode based species delineation and the release of results in collaboration with Indonesian counterparts, aimed at supporting further analyses of the data.

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Vascular Endothelial Growth Factor, from Basic Research to Clinical Applications.

Int J Mol Sci

November 2018

Biomolecular Research, Paul Scherrer Institute, 5232 Villigen, Switzerland.

Judah Folkman's landmark discovery in the 1970s showing that tumors, growing beyond a few millimeters in diameter, depend on de novo vascularization triggered by specific growth factors released by tumor cells encountering hypoxia [...

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Basement membranes (BMs) are specialized sheets of extracellular matrix that outline epithelial cell layers, muscle fibers, blood vessels, and peripheral nerves. A well-documented histological hallmark of progressing diabetes is a major increase in vascular BM thickness. In order to investigate whether this structural change is accompanied by a change in the protein composition, we compared the proteomes of retinal vascular BMs from diabetic and non-diabetic donors by using LC-MS/MS.

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The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new protocol for the diagnosis and treatment of childhood renal tumours, the UMBRELLA SIOP-RTSG 2016 (the UMBRELLA protocol), to continue international collaboration in the treatment of childhood renal tumours. This protocol will support integrated biomarker and imaging research, focussing on assessing the independent prognostic value of genomic changes within the tumour and the volume of the blastemal component that survives preoperative chemotherapy. Treatment guidelines for Wilms tumours in the UMBRELLA protocol include recommendations for localized, metastatic, and bilateral disease, for all age groups, and for relapsed disease.

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