16 research outputs found

    Characterization of the ubiquitin-like protein Hub1 and its role in pre-mRNA splicing in human cells

    Get PDF

    Characterization of the ubiquitin-like protein Hub1 and its role in pre-mRNA splicing in human cells

    Get PDF

    Eng+ | Ethics For Sustainable Development In Engineering Programmes A Praxis Report Of Tu Berlin’s Think Tank Technology Reflection

    Get PDF
    Many technical universities alike, TU Berlin is in a future-oriented process of programme transformation to invite a holistic perspective on technology which includes critical thinking and ethical reflection. To this end, TU Berlin recently issued a general study guideline calling for an orientation of all programmes toward sustainable development. Accordingly, students should know about the historical, social and cultural contexts of science and technology and learn to reflect on the ethical consequences of their actions. Together with training in good scientific practice, this content should comprise 12 ECTS in each respective BA and MA programme. With only minor integration of this content in the current curricula to date, this transformation presents a significant challenge since courses need to be realigned as well as replaced. To find an answer, TU Berlin’s engineering faculty initiated a think tank in spring 2022, bringing together students, teachers and administration to search for ways of integrating ethics as well as science reflection and technology reflection to foster sustainable development. In our contribution we present a first outcome, namely the integration framework ENG+ for programme design which allows for the incorporation of ethics and strengthening of core values such as diversity, sustainability, and good scientific practice. In the ENG+ framework, we introduce the strategies of advancing and complementing as well as six corresponding measures for integration – emphasising, empowering, embedding, enabling, enriching, and encountering. We explain how they jointly contribute to the overarching ENG+ concept which brings together ethical reflection and sustainable development

    The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells

    Get PDF
    Different from canonical ubiquitin-like proteins, Hub 1 does not form covalent conjugates with substrates but binds proteins non- covalently. In Saccharomyces cerevisiae , Hub 1 associates with spliceosomes and mediates alternative splicing of SRC 1 , without affecting pre-mRNA splicing generally. Human Hub 1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub 1 binds to the spliceosomal protein Snu 66 as in yeast; however, unlike its S. cerevisiae homolog, human Hub 1 is essential for viability. Prolonged in vivo depletion of human Hub 1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe, and consequently cell death by apoptosis. Early consequences of Hub 1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub 1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing

    PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.

    Get PDF
    B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology

    ISSN exercise & sport nutrition review: research & recommendations

    Get PDF
    Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

    On-Surface Synthesis of Porous Carbon Nanoribbons from Polymer Chains

    No full text
    We demonstrate the on-surface synthesis of porous carbon nanoribbons on Ag(111) via a preprogrammed isomerization of conformationally flexible polymer chains followed by dehydrogenation reactions using thermal annealing. The carbon chains are fabricated by polymerization of prochiral 1,3,5-tris­(3-bromophenyl)­benzene (<i>m</i>TBPB) directly on the surface using an Ullmann-type reaction. At room temperature, <i>m</i>TBPB partially self-assembles in halogen-bonded 2D networks, which transform into organometallic chains and rings after debromination. The chain and ring formation is facilitated by conformational switching from a <i>C</i><sub>3<i>h</i></sub> to <i>C<sub>s</sub></i> symmetry of <i>m</i>TBPB via rotation of <i>m</i>-phenylene units. The high conformational selectivity toward <i>C</i><sub><i>s</i></sub>-conformers is templated by the twofold coordination to Ag adatoms. After thermally induced covalent-linking through aryl–aryl coupling, well-ordered nanoporous chains are created. Finally, the rotation of single phenylene units in combination with dehydrogenation cross-linking reactions within the polymer chains leads to the unexpected formation of porous carbon nanoribbons. We unveil the reaction mechanism in a low-temperature scanning tunneling microscopy study and demonstrate that the rotation of <i>m</i>-phenylene units is a powerful design tool to promote structural control in the synthesis of cyclic covalent organic nanostructures on metal surfaces

    Diaspore bank analysis of Baltic coastal waters

    No full text
    <p>The coastal waters are important transition zones for terrestrial nutrient and pollutant runoff and the open Sea. During the last decades, eutrophication has negatively influenced macrophyte communities of the coastal ecosystems, making restoration activities inevitable. This study analysed recent macrophyte vegetation and the reproductive potential through the sediment diaspore reservoir along the German Baltic Sea coastline. Salinity was identified to be the responsible factor for shifts in the macrophyte community with most commonly found species like <i>Stuckenia pectinata</i> or <i>Myriophyllum spicatum</i>. In contrast, the oospores of small charophytes (e.g. <i>Tolypella nidifica</i>) clearly dominated the sediment diaspore bank. The germination rates differed in the recent vegetation composition and the diaspore bank composition with <i>Zannichellia palustris</i> as the dominant species. However, several species not visually detected at the respective sites were represented in the diaspore bank and germinated at a low rate (e.g. <i>Chara contraria</i> and <i>Lamprothamnium papulosum</i>). The maximal germination frequency corresponded to the sediment layer in which diaspore density was the highest (5–15 cm). In conclusion, the germinable diaspores were observed at all sites. Considering the differences between the diaspore composition, recent vegetation and germination success, we have illustrated the potential of the diaspore banks for the restoration of the macrophyte communities after at least mid-term periods of disturbance.</p

    Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling

    Full text link
    Innate-like T cell populations expressing conserved TCRs play critical roles in immunity through diverse developmentally acquired effector functions. Focusing on the prototypical lineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanisms and timing of fate decisions and functional effector differentiation. Utilizing induced expression of the semi-invariant NKT cell TCR on double positive thymocytes, an initially highly synchronous wave of iNKT cell development was triggered by brief homogeneous TCR signaling. After reaching a uniform progenitor state characterized by IL-4 production potential and proliferation, effector subsets emerged simultaneously, but then diverged toward different fates. While NKT17 specification was quickly completed, NKT1 cells slowly differentiated and expanded. NKT2 cells resembled maturing progenitors, which gradually diminished in numbers. Thus, iNKT subset diversification occurs in dividing progenitor cells without acute TCR input but utilizes multiple active cytokine signaling pathways. These data imply a two-step model of iNKT effector differentiation

    Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia.

    No full text
    The Wnt signalling pathway, one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL), is activated in only a subset of patients through somatic mutations. Here we describe alternative, microenvironment-dependent mechanisms of Wnt activation in malignant B cells. We show that tumour cells specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required for the transcription of the complement factor C1q. MSC-derived C1q in turn inhibits Gsk3-β mediated degradation of β-catenin in CLL cells. Additionally, stromal Notch2 activity regulates N-cadherin expression in CLL cells, which interacts with and further stabilises β-catenin. Together, these stroma Notch2-dependent mechanisms induce strong activation of canonical Wnt signalling in CLL cells. Pharmacological inhibition of the Wnt pathway impairs microenvironment-mediated survival of tumour cells. Similarly, inhibition of Notch signalling diminishes survival of stroma-protected CLL cells in vitro and disease engraftment in vivo. Notch2 activation in the microenvironment is a pre-requisite for the activation of canonical Wnt signalling in tumour cells.We would like to express our deepest gratitude to patients who donated blood for research purposes. In particular, we thank Dr Joanna Baxter and her team for enrolling patients in these studies. We are also grateful for the help of Dr Marco Galardini for his bioinformatics support. This work was funded by Cancer Research UK (CRUK; C49940/A17480) and by the Deutsche Forschungsgemeinschaft (DFG, FOR 2033 [projects B3, B6 and B7], I.R. is a senior CRUK fello
    corecore