@article{11056,
abstract = {Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age-dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ-specific vascular endothelial cells (VECs). Long-living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA-seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin-like-4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established.},
author = {Bersini, Simone and Arrojo e Drigo, Rafael and Huang, Ling and Shokhirev, Maxim N. and HETZER, Martin W},
issn = {2366-7478},
journal = {Advanced Biosystems},
keywords = {General Biochemistry, Genetics and Molecular Biology, Biomedical Engineering, Biomaterials},
number = {5},
publisher = {Wiley},
title = {{Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease}},
doi = {10.1002/adbi.202000044},
volume = {4},
year = {2020},
}
@article{11058,
abstract = {Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.},
author = {Bersini, Simone and Lytle, Nikki K and Schulte, Roberta and Huang, Ling and Wahl, Geoffrey M and HETZER, Martin W},
issn = {2575-1077},
journal = {Life Science Alliance},
keywords = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology},
number = {1},
publisher = {Life Science Alliance},
title = {{Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling}},
doi = {10.26508/lsa.201900623},
volume = {3},
year = {2020},
}
@article{12189,
abstract = {Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that meiotic COs are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation protein modification pathway in Arabidopsis thaliana. Here, we report that in axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the formation of the telomere bouquet is not affected. COs are also redistributed towards subtelomeric chromosomal ends where they frequently form clusters, in contrast to large central regions depleted in recombination. The CO suppressed regions correlate with DNA hypermethylation of transposable elements (TEs) in the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we found axr1-/- affects DNA methylation in a plant, causing hypermethylation in all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic cells but does not restore regular chromosome segregation during meiosis. Collectively, our findings reveal that the neddylation pathway not only regulates hormonal perception and CO distribution but is also, directly or indirectly, a major limiting pathway of TE DNA methylation in somatic cells.},
author = {Christophorou, Nicolas and She, Wenjing and Long, Jincheng and Hurel, Aurélie and Beaubiat, Sébastien and Idir, Yassir and Tagliaro-Jahns, Marina and Chambon, Aurélie and Solier, Victor and Vezon, Daniel and Grelon, Mathilde and Feng, Xiaoqi and Bouché, Nicolas and Mézard, Christine},
issn = {1553-7404},
journal = {PLOS Genetics},
keywords = {Cancer Research, Genetics (clinical), Genetics, Molecular Biology, Ecology, Evolution, Behavior and Systematics},
number = {6},
publisher = {Public Library of Science (PLoS)},
title = {{AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization}},
doi = {10.1371/journal.pgen.1008894},
volume = {16},
year = {2020},
}
@article{14125,
abstract = {Motivation: Recent technological advances have led to an increase in the production and availability of single-cell data. The ability to integrate a set of multi-technology measurements would allow the identification of biologically or clinically meaningful observations through the unification of the perspectives afforded by each technology. In most cases, however, profiling technologies consume the used cells and thus pairwise correspondences between datasets are lost. Due to the sheer size single-cell datasets can acquire, scalable algorithms that are able to universally match single-cell measurements carried out in one cell to its corresponding sibling in another technology are needed.
Results: We propose Single-Cell data Integration via Matching (SCIM), a scalable approach to recover such correspondences in two or more technologies. SCIM assumes that cells share a common (low-dimensional) underlying structure and that the underlying cell distribution is approximately constant across technologies. It constructs a technology-invariant latent space using an autoencoder framework with an adversarial objective. Multi-modal datasets are integrated by pairing cells across technologies using a bipartite matching scheme that operates on the low-dimensional latent representations. We evaluate SCIM on a simulated cellular branching process and show that the cell-to-cell matches derived by SCIM reflect the same pseudotime on the simulated dataset. Moreover, we apply our method to two real-world scenarios, a melanoma tumor sample and a human bone marrow sample, where we pair cells from a scRNA dataset to their sibling cells in a CyTOF dataset achieving 90% and 78% cell-matching accuracy for each one of the samples, respectively.},
author = {Stark, Stefan G and Ficek, Joanna and Locatello, Francesco and Bonilla, Ximena and Chevrier, Stéphane and Singer, Franziska and Aebersold, Rudolf and Al-Quaddoomi, Faisal S and Albinus, Jonas and Alborelli, Ilaria and Andani, Sonali and Attinger, Per-Olof and Bacac, Marina and Baumhoer, Daniel and Beck-Schimmer, Beatrice and Beerenwinkel, Niko and Beisel, Christian and Bernasconi, Lara and Bertolini, Anne and Bodenmiller, Bernd and Bonilla, Ximena and Casanova, Ruben and Chevrier, Stéphane and Chicherova, Natalia and D'Costa, Maya and Danenberg, Esther and Davidson, Natalie and gan, Monica-Andreea Dră and Dummer, Reinhard and Engler, Stefanie and Erkens, Martin and Eschbach, Katja and Esposito, Cinzia and Fedier, André and Ferreira, Pedro and Ficek, Joanna and Frei, Anja L and Frey, Bruno and Goetze, Sandra and Grob, Linda and Gut, Gabriele and Günther, Detlef and Haberecker, Martina and Haeuptle, Pirmin and Heinzelmann-Schwarz, Viola and Herter, Sylvia and Holtackers, Rene and Huesser, Tamara and Irmisch, Anja and Jacob, Francis and Jacobs, Andrea and Jaeger, Tim M and Jahn, Katharina and James, Alva R and Jermann, Philip M and Kahles, André and Kahraman, Abdullah and Koelzer, Viktor H and Kuebler, Werner and Kuipers, Jack and Kunze, Christian P and Kurzeder, Christian and Lehmann, Kjong-Van and Levesque, Mitchell and Lugert, Sebastian and Maass, Gerd and Manz, Markus and Markolin, Philipp and Mena, Julien and Menzel, Ulrike and Metzler, Julian M and Miglino, Nicola and Milani, Emanuela S and Moch, Holger and Muenst, Simone and Murri, Riccardo and Ng, Charlotte KY and Nicolet, Stefan and Nowak, Marta and Pedrioli, Patrick GA and Pelkmans, Lucas and Piscuoglio, Salvatore and Prummer, Michael and Ritter, Mathilde and Rommel, Christian and Rosano-González, María L and Rätsch, Gunnar and Santacroce, Natascha and Castillo, Jacobo Sarabia del and Schlenker, Ramona and Schwalie, Petra C and Schwan, Severin and Schär, Tobias and Senti, Gabriela and Singer, Franziska and Sivapatham, Sujana and Snijder, Berend and Sobottka, Bettina and Sreedharan, Vipin T and Stark, Stefan and Stekhoven, Daniel J and Theocharides, Alexandre PA and Thomas, Tinu M and Tolnay, Markus and Tosevski, Vinko and Toussaint, Nora C and Tuncel, Mustafa A and Tusup, Marina and Drogen, Audrey Van and Vetter, Marcus and Vlajnic, Tatjana and Weber, Sandra and Weber, Walter P and Wegmann, Rebekka and Weller, Michael and Wendt, Fabian and Wey, Norbert and Wicki, Andreas and Wollscheid, Bernd and Yu, Shuqing and Ziegler, Johanna and Zimmermann, Marc and Zoche, Martin and Zuend, Gregor and Rätsch, Gunnar and Lehmann, Kjong-Van},
issn = {1367-4811},
journal = {Bioinformatics},
keywords = {Computational Mathematics, Computational Theory and Mathematics, Computer Science Applications, Molecular Biology, Biochemistry, Statistics and Probability},
number = {Supplement_2},
pages = {i919--i927},
publisher = {Oxford University Press},
title = {{SCIM: Universal single-cell matching with unpaired feature sets}},
doi = {10.1093/bioinformatics/btaa843},
volume = {36},
year = {2020},
}
@article{15036,
abstract = {The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbors. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles, which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshita's postulate, which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed.},
author = {Rosa, Higor Vinícius Dias and Leonardo, Diego Antonio and Brognara, Gabriel and Brandão-Neto, José and D'Muniz Pereira, Humberto and Araújo, Ana Paula Ulian and Garratt, Richard Charles},
issn = {0022-2836},
journal = {Journal of Molecular Biology},
keywords = {Molecular Biology, Structural Biology},
number = {21},
pages = {5784--5801},
publisher = {Elsevier},
title = {{Molecular recognition at septin interfaces: The switches hold the key}},
doi = {10.1016/j.jmb.2020.09.001},
volume = {432},
year = {2020},
}
@article{15037,
abstract = {Protein abundance and localization at the plasma membrane (PM) shapes plant development and mediates adaptation to changing environmental conditions. It is regulated by ubiquitination, a post-translational modification crucial for the proper sorting of endocytosed PM proteins to the vacuole for subsequent degradation. To understand the significance and the variety of roles played by this reversible modification, the function of ubiquitin receptors, which translate the ubiquitin signature into a cellular response, needs to be elucidated. In this study, we show that TOL (TOM1-like) proteins function in plants as multivalent ubiquitin receptors, governing ubiquitinated cargo delivery to the vacuole via the conserved Endosomal Sorting Complex Required for Transport (ESCRT) pathway. TOL2 and TOL6 interact with components of the ESCRT machinery and bind to K63-linked ubiquitin via two tandemly arranged conserved ubiquitin-binding domains. Mutation of these domains results not only in a loss of ubiquitin binding but also altered localization, abolishing TOL6 ubiquitin receptor activity. Function and localization of TOL6 is itself regulated by ubiquitination, whereby TOL6 ubiquitination potentially modulates degradation of PM-localized cargoes, assisting in the fine-tuning of the delicate interplay between protein recycling and downregulation. Taken together, our findings demonstrate the function and regulation of a ubiquitin receptor that mediates vacuolar degradation of PM proteins in higher plants.},
author = {Moulinier-Anzola, Jeanette and Schwihla, Maximilian and De-Araújo, Lucinda and Artner, Christina and Jörg, Lisa and Konstantinova, Nataliia and Luschnig, Christian and Korbei, Barbara},
issn = {1674-2052},
journal = {Molecular Plant},
keywords = {Plant Science, Molecular Biology},
number = {5},
pages = {717--731},
publisher = {Elsevier},
title = {{TOLs function as ubiquitin receptors in the early steps of the ESCRT pathway in higher plants}},
doi = {10.1016/j.molp.2020.02.012},
volume = {13},
year = {2020},
}
@article{15142,
abstract = {Bacteria and archaea employ CRISPR (clustered, regularly, interspaced, short palindromic repeats)-Cas (CRISPR-associated) systems as a type of adaptive immunity to target and degrade foreign nucleic acids. While a myriad of CRISPR-Cas systems have been identified to date, type I-C is one of the most commonly found subtypes in nature. Interestingly, the type I-C system employs a minimal Cascade effector complex, which encodes only three unique subunits in its operon. Here, we present a 3.1 Å resolution cryo-EM structure of the Desulfovibrio vulgaris type I-C Cascade, revealing the molecular mechanisms that underlie RNA-directed complex assembly. We demonstrate how this minimal Cascade utilizes previously overlooked, non-canonical small subunits to stabilize R-loop formation. Furthermore, we describe putative PAM and Cas3 binding sites. These findings provide the structural basis for harnessing the type I-C Cascade as a genome-engineering tool.},
author = {O’Brien, Roisin E. and Santos, Inês C. and Wrapp, Daniel and Bravo, Jack Peter Kelly and Schwartz, Evan A. and Brodbelt, Jennifer S. and Taylor, David W.},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
publisher = {Springer Nature},
title = {{Structural basis for assembly of non-canonical small subunits into type I-C Cascade}},
doi = {10.1038/s41467-020-19785-8},
volume = {11},
year = {2020},
}
@article{15153,
abstract = {Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.},
author = {Fribourgh, Jennifer L and Srivastava, Ashutosh and Sandate, Colby R and Michael, Alicia Kathleen and Hsu, Peter L and Rakers, Christin and Nguyen, Leslee T and Torgrimson, Megan R and Parico, Gian Carlo G and Tripathi, Sarvind and Zheng, Ning and Lander, Gabriel C and Hirota, Tsuyoshi and Tama, Florence and Partch, Carrie L},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing}},
doi = {10.7554/elife.55275},
volume = {9},
year = {2020},
}
@article{10348,
abstract = {The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.},
author = {Pfitzner, Anna-Katharina and Mercier, Vincent and Jiang, Xiuyun and Moser von Filseck, Joachim and Baum, Buzz and Šarić, Anđela and Roux, Aurélien},
issn = {0092-8674},
journal = {Cell},
keywords = {general biochemistry, genetics and molecular biology},
number = {5},
pages = {1140--1155.e18},
publisher = {Elsevier},
title = {{An ESCRT-III polymerization sequence drives membrane deformation and fission}},
doi = {10.1016/j.cell.2020.07.021},
volume = {182},
year = {2020},
}
@article{8402,
abstract = {Background: The mitochondrial pyruvate carrier (MPC) plays a central role in energy metabolism by transporting pyruvate across the inner mitochondrial membrane. Its heterodimeric composition and homology to SWEET and semiSWEET transporters set the MPC apart from the canonical mitochondrial carrier family (named MCF or SLC25). The import of the canonical carriers is mediated by the carrier translocase of the inner membrane (TIM22) pathway and is dependent on their structure, which features an even number of transmembrane segments and both termini in the intermembrane space. The import pathway of MPC proteins has not been elucidated. The odd number of transmembrane segments and positioning of the N-terminus in the matrix argues against an import via the TIM22 carrier pathway but favors an import via the flexible presequence pathway.
Results: Here, we systematically analyzed the import pathways of Mpc2 and Mpc3 and report that, contrary to an expected import via the flexible presequence pathway, yeast MPC proteins with an odd number of transmembrane segments and matrix-exposed N-terminus are imported by the carrier pathway, using the receptor Tom70, small TIM chaperones, and the TIM22 complex. The TIM9·10 complex chaperones MPC proteins through the mitochondrial intermembrane space using conserved hydrophobic motifs that are also required for the interaction with canonical carrier proteins.
Conclusions: The carrier pathway can import paired and non-paired transmembrane helices and translocate N-termini to either side of the mitochondrial inner membrane, revealing an unexpected versatility of the mitochondrial import pathway for non-cleavable inner membrane proteins.},
author = {Rampelt, Heike and Sucec, Iva and Bersch, Beate and Horten, Patrick and Perschil, Inge and Martinou, Jean-Claude and van der Laan, Martin and Wiedemann, Nils and Schanda, Paul and Pfanner, Nikolaus},
issn = {1741-7007},
journal = {BMC Biology},
keywords = {Biotechnology, Plant Science, General Biochemistry, Genetics and Molecular Biology, Developmental Biology, Cell Biology, Physiology, Ecology, Evolution, Behavior and Systematics, Structural Biology, General Agricultural and Biological Sciences},
publisher = {Springer Nature},
title = {{The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments}},
doi = {10.1186/s12915-019-0733-6},
volume = {18},
year = {2020},
}
@article{8568,
abstract = {Aqueous iodine based electrochemical energy storage is considered a potential candidate to improve sustainability and performance of current battery and supercapacitor technology. It harnesses the redox activity of iodide, iodine, and polyiodide species in the confined geometry of nanoporous carbon electrodes. However, current descriptions of the electrochemical reaction mechanism to interconvert these species are elusive. Here we show that electrochemical oxidation of iodide in nanoporous carbons forms persistent solid iodine deposits. Confinement slows down dissolution into triiodide and pentaiodide, responsible for otherwise significant self-discharge via shuttling. The main tools for these insights are in situ Raman spectroscopy and in situ small and wide-angle X-ray scattering (in situ SAXS/WAXS). In situ Raman confirms the reversible formation of triiodide and pentaiodide. In situ SAXS/WAXS indicates remarkable amounts of solid iodine deposited in the carbon nanopores. Combined with stochastic modeling, in situ SAXS allows quantifying the solid iodine volume fraction and visualizing the iodine structure on 3D lattice models at the sub-nanometer scale. Based on the derived mechanism, we demonstrate strategies for improved iodine pore filling capacity and prevention of self-discharge, applicable to hybrid supercapacitors and batteries.},
author = {Prehal, Christian and Fitzek, Harald and Kothleitner, Gerald and Presser, Volker and Gollas, Bernhard and Freunberger, Stefan Alexander and Abbas, Qamar},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
publisher = {Springer Nature},
title = {{Persistent and reversible solid iodine electrodeposition in nanoporous carbons}},
doi = {10.1038/s41467-020-18610-6},
volume = {11},
year = {2020},
}
@article{8592,
abstract = {Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma.},
author = {Tian, Anhao and Kang, Bo and Li, Baizhou and Qiu, Biying and Jiang, Wenhong and Shao, Fangjie and Gao, Qingqing and Liu, Rui and Cai, Chengwei and Jing, Rui and Wang, Wei and Chen, Pengxiang and Liang, Qinghui and Bao, Lili and Man, Jianghong and Wang, Yan and Shi, Yu and Li, Jin and Yang, Minmin and Wang, Lisha and Zhang, Jianmin and Hippenmeyer, Simon and Zhu, Junming and Bian, Xiuwu and Wang, Ying‐Jie and Liu, Chong},
issn = {2198-3844},
journal = {Advanced Science},
keywords = {General Engineering, General Physics and Astronomy, General Materials Science, Medicine (miscellaneous), General Chemical Engineering, Biochemistry, Genetics and Molecular Biology (miscellaneous)},
number = {21},
publisher = {Wiley},
title = {{Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting}},
doi = {10.1002/advs.202001724},
volume = {7},
year = {2020},
}
@article{8744,
abstract = {Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up to now, coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains has remained elusive. Here, we investigate the eye-lens protein γB-crystallin in the ribosomal exit tunnel. Using mass spectrometry, theoretical simulations, dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance and cryo-electron microscopy, we show that thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding.},
author = {Schulte, Linda and Mao, Jiafei and Reitz, Julian and Sreeramulu, Sridhar and Kudlinzki, Denis and Hodirnau, Victor-Valentin and Meier-Credo, Jakob and Saxena, Krishna and Buhr, Florian and Langer, Julian D. and Blackledge, Martin and Frangakis, Achilleas S. and Glaubitz, Clemens and Schwalbe, Harald},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
publisher = {Springer Nature},
title = {{Cysteine oxidation and disulfide formation in the ribosomal exit tunnel}},
doi = {10.1038/s41467-020-19372-x},
volume = {11},
year = {2020},
}
@article{8767,
abstract = {Resources are rarely distributed uniformly within a population. Heterogeneity in the concentration of a drug, the quality of breeding sites, or wealth can all affect evolutionary dynamics. In this study, we represent a collection of properties affecting the fitness at a given location using a color. A green node is rich in resources while a red node is poorer. More colors can represent a broader spectrum of resource qualities. For a population evolving according to the birth-death Moran model, the first question we address is which structures, identified by graph connectivity and graph coloring, are evolutionarily equivalent. We prove that all properly two-colored, undirected, regular graphs are evolutionarily equivalent (where “properly colored” means that no two neighbors have the same color). We then compare the effects of background heterogeneity on properly two-colored graphs to those with alternative schemes in which the colors are permuted. Finally, we discuss dynamic coloring as a model for spatiotemporal resource fluctuations, and we illustrate that random dynamic colorings often diminish the effects of background heterogeneity relative to a proper two-coloring.},
author = {Kaveh, Kamran and McAvoy, Alex and Chatterjee, Krishnendu and Nowak, Martin A.},
issn = {1553-7358},
journal = {PLOS Computational Biology},
keywords = {Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience},
number = {11},
publisher = {Public Library of Science},
title = {{The Moran process on 2-chromatic graphs}},
doi = {10.1371/journal.pcbi.1008402},
volume = {16},
year = {2020},
}
@article{8971,
abstract = {The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Its activation is tightly regulated and involves complex structural rearrangements and actin filament binding, which are yet to be understood. Here, we report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging. This allows us to generate an accurate model of the active Arp2/3 complex in the branch junction and its interaction with actin filaments. Notably, our model reveals a previously undescribed set of interactions of the Arp2/3 complex with the mother filament, significantly different to the previous branch junction model. Our structure also indicates a central role for the ArpC3 subunit in stabilizing the active conformation.},
author = {Fäßler, Florian and Dimchev, Georgi A and Hodirnau, Victor-Valentin and Wan, William and Schur, Florian KM},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
publisher = {Springer Nature},
title = {{Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction}},
doi = {10.1038/s41467-020-20286-x},
volume = {11},
year = {2020},
}
@article{8529,
abstract = {Practical quantum networks require low-loss and noise-resilient optical interconnects as well as non-Gaussian resources for entanglement distillation and distributed quantum computation. The latter could be provided by superconducting circuits but existing solutions to interface the microwave and optical domains lack either scalability or efficiency, and in most cases the conversion noise is not known. In this work we utilize the unique opportunities of silicon photonics, cavity optomechanics and superconducting circuits to demonstrate a fully integrated, coherent transducer interfacing the microwave X and the telecom S bands with a total (internal) bidirectional transduction efficiency of 1.2% (135%) at millikelvin temperatures. The coupling relies solely on the radiation pressure interaction mediated by the femtometer-scale motion of two silicon nanobeams reaching a Vπ as low as 16 μV for sub-nanowatt pump powers. Without the associated optomechanical gain, we achieve a total (internal) pure conversion efficiency of up to 0.019% (1.6%), relevant for future noise-free operation on this qubit-compatible platform.},
author = {Arnold, Georg M and Wulf, Matthias and Barzanjeh, Shabir and Redchenko, Elena and Rueda Sanchez, Alfredo R and Hease, William J and Hassani, Farid and Fink, Johannes M},
issn = {2041-1723},
journal = {Nature Communications},
keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry},
publisher = {Springer Nature},
title = {{Converting microwave and telecom photons with a silicon photonic nanomechanical interface}},
doi = {10.1038/s41467-020-18269-z},
volume = {11},
year = {2020},
}
@article{11059,
abstract = {The genome is packaged and organized nonrandomly within the 3D space of the nucleus to promote efficient gene expression and to faithfully maintain silencing of heterochromatin. The genome is enclosed within the nucleus by the nuclear envelope membrane, which contains a set of proteins that actively participate in chromatin organization and gene regulation. Technological advances are providing views of genome organization at unprecedented resolution and are beginning to reveal the ways that cells co-opt the structures of the nuclear periphery for nuclear organization and gene regulation. These genome regulatory roles of proteins of the nuclear periphery have important influences on development, disease and ageing.},
author = {Buchwalter, Abigail and Kaneshiro, Jeanae M. and HETZER, Martin W},
issn = {1471-0064},
journal = {Nature Reviews Genetics},
keywords = {Genetics (clinical), Genetics, Molecular Biology},
number = {1},
pages = {39--50},
publisher = {Springer Nature},
title = {{Coaching from the sidelines: The nuclear periphery in genome regulation}},
doi = {10.1038/s41576-018-0063-5},
volume = {20},
year = {2019},
}
@article{11060,
abstract = {The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.},
author = {Buchwalter, Abigail and Schulte, Roberta and Tsai, Hsiao and Capitanio, Juliana and HETZER, Martin W},
issn = {2050-084X},
journal = {eLife},
keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
publisher = {eLife Sciences Publications},
title = {{Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress}},
doi = {10.7554/elife.49796},
volume = {8},
year = {2019},
}
@article{11062,
abstract = {Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization.},
author = {Arrojo e Drigo, Rafael and Lev-Ram, Varda and Tyagi, Swati and Ramachandra, Ranjan and Deerinck, Thomas and Bushong, Eric and Phan, Sebastien and Orphan, Victoria and Lechene, Claude and Ellisman, Mark H. and HETZER, Martin W},
issn = {1550-4131},
journal = {Cell Metabolism},
keywords = {Cell Biology, Molecular Biology, Physiology},
number = {2},
pages = {343--351.e3},
publisher = {Elsevier},
title = {{Age mosaicism across multiple scales in adult tissues}},
doi = {10.1016/j.cmet.2019.05.010},
volume = {30},
year = {2019},
}
@article{12190,
abstract = {Meiotic crossover frequency varies within genomes, which influences genetic diversity and adaptation. In turn, genetic variation within populations can act to modify crossover frequency in cis and trans. To identify genetic variation that controls meiotic crossover frequency, we screened Arabidopsis accessions using fluorescent recombination reporters. We mapped a genetic modifier of crossover frequency in Col × Bur populations of Arabidopsis to a premature stop codon within TBP-ASSOCIATED FACTOR 4b (TAF4b), which encodes a subunit of the RNA polymerase II general transcription factor TFIID. The Arabidopsis taf4b mutation is a rare variant found in the British Isles, originating in South-West Ireland. Using genetics, genomics, and immunocytology, we demonstrate a genome-wide decrease in taf4b crossovers, with strongest reduction in the sub-telomeric regions. Using RNA sequencing (RNA-seq) from purified meiocytes, we show that TAF4b expression is meiocyte enriched, whereas its paralog TAF4 is broadly expressed. Consistent with the role of TFIID in promoting gene expression, RNA-seq of wild-type and taf4b meiocytes identified widespread transcriptional changes, including in genes that regulate the meiotic cell cycle and recombination. Therefore, TAF4b duplication is associated with acquisition of meiocyte-specific expression and promotion of germline transcription, which act directly or indirectly to elevate crossovers. This identifies a novel mode of meiotic recombination control via a general transcription factor.},
author = {Lawrence, Emma J. and Gao, Hongbo and Tock, Andrew J. and Lambing, Christophe and Blackwell, Alexander R. and Feng, Xiaoqi and Henderson, Ian R.},
issn = {0960-9822},
journal = {Current Biology},
keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology},
number = {16},
pages = {2676--2686.e3},
publisher = {Elsevier},
title = {{Natural variation in TBP-ASSOCIATED FACTOR 4b controls meiotic crossover and germline transcription in Arabidopsis}},
doi = {10.1016/j.cub.2019.06.084},
volume = {29},
year = {2019},
}