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About the Cover

August 2019 | Volume 2, No. 4

Research Articles

  • Inhibition of host NOX1 blocks tumor growth and enhances checkpoint inhibitor–based immunotherapy
    Open Access
    Inhibition of host NOX1 blocks tumor growth and enhances checkpoint inhibitor–based immunotherapy

    Jimmy Stalin, Sarah Garrido-Urbani, Freddy Heitz, Cédric Szyndralewiez, Stephane Jemelin, Oriana Coquoz, Curzio Ruegg, Beat A Imhof

    Jimmy Stalin ... Beat A Imhof

    Published 27 June 2019

    Blocking NOX1 with the novel small molecule inhibitor GKT771 inhibits tumor growth in mice by targeting tumor lymph/angiogenesis and promoting antitumor immune cells recruitment. GKT771 emerges as a novel and promising anticancer drug worth translating into the clinics.

  • Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology
    Open Access
    Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology

    Vidhya M Ravi, Kevin Joseph, Julian Wurm, Simon Behringer, Nicklas Garrelfs, Paolo d’Errico, Yashar Naseri, Pamela Franco, Melanie Meyer-Luehmann, Roman Sankowski, Mukesch Johannes Shah, Irina Mader, Daniel Delev, Marie Follo, Jürgen Beck, Oliver Schnell, Ulrich G Hofmann, Dieter Henrik Heiland

    Vidhya M Ravi ... Dieter Henrik Heiland

    Published 27 June 2019

    Therapeutically resected, adult brain segments were maintained and characterized for an extended period to study glioblastoma progression and treatment in its almost natural environment.

  • Dietary restriction induces posttranscriptional regulation of longevity genes
    Open Access
    Dietary restriction induces posttranscriptional regulation of longevity genes

    Jarod A Rollins, Dan Shaffer, Santina S Snow, Pankaj Kapahi, Aric N Rogers

    Jarod A Rollins ... Aric N Rogers

    Published 28 June 2019

    By modulating posttranscriptional processes, including RNA editing, miRNA biogenesis, and intron retention, dietary restriction enacts some of its pro-longevity benefits in Caenorhabditis elegans through posttranscriptional regulation of gene expression.

  • The cancer cell proteome and transcriptome predicts sensitivity to targeted and cytotoxic drugs
    Open Access
    The cancer cell proteome and transcriptome predicts sensitivity to targeted and cytotoxic drugs

    Mattias Rydenfelt, Matthew Wongchenko, Bertram Klinger, Yibing Yan, Nils Blüthgen

    Mattias Rydenfelt ... Nils Blüthgen

    Published 28 June 2019

    This study shows that the proteomic and transcriptomic states of cancer cells are more predictive of drug sensitivity than genomic markers for most drugs, both within and across tumor types.

  • Systematic identification of recognition motifs for the hub protein LC8
    Open Access
    Systematic identification of recognition motifs for the hub protein LC8

    Nathan Jespersen, Aidan Estelle, Nathan Waugh, Norman E Davey, Cecilia Blikstad, York-Christoph Ammon, Anna Akhmanova, Ylva Ivarsson, David A Hendrix, Elisar Barbar

    Nathan Jespersen ... Elisar Barbar

    Published 2 July 2019

    LC8 is a eukaryotic hub protein that interacts with multifarious partners; analysis of more than 100 binding/nonbinding sequences led to an algorithm that predicts LC8 partners with 78% accuracy.

  • Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cells
    Open Access
    Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cells

    Katrin Riemschoss, Verena Arndt, Benedetta Bolognesi, Philipp von Eisenhart-Rothe, Shu Liu, Oleksandra Buravlova, Yvonne Duernberger, Lydia Paulsen, Annika Hornberger, André Hossinger, Nieves Lorenzo-Gotor, Sebastian Hogl, Stephan A Müller, Gian Tartaglia, Stefan F Lichtenthaler, Ina M Vorberg

    Katrin Riemschoss ... Ina M Vorberg

    Published 2 July 2019

    This study provides evidence that exogenous proteinaceous seeds can induce protein aggregates that sequester stress granule components independent of stress granule assembly.

  • Human DNA polymerase delta requires an iron–sulfur cluster for high-fidelity DNA synthesis
    Open Access
    Human DNA polymerase delta requires an iron–sulfur cluster for high-fidelity DNA synthesis

    Stanislaw K. Jozwiakowski, Sandra Kummer, Kerstin Gari

    Stanislaw K. Jozwiakowski ... Kerstin Gari

    Published 5 July 2019

    The iron–sulfur cluster in human DNA polymerase delta has an impact on DNA polymerase and exonuclease activities and can hence influence the fidelity of DNA synthesis.

  • Membrane curvature sensing of the lipid-anchored K-Ras small GTPase
    Open Access
    Membrane curvature sensing of the lipid-anchored K-Ras small GTPase

    Hong Liang, Huanwen Mu, Frantz Jean-Francois, Bindu Lakshman, Suparna Sarkar-Banerjee, Yinyin Zhuang, Yongpeng Zeng, Weibo Gao, Ana Maria Zaske, Dwight V Nissley, Alemayehu A Gorfe, Wenting Zhao, Yong Zhou

    Hong Liang ... Yong Zhou

    Published 11 July 2019

    Proteolipid nanoassemblies of K-Ras and lipids in the plasma membrane sense changing membrane curvature architecture and convert mechanical perturbations to mitogenic signaling.

  • PRDM9 forms a trimer by interactions within the zinc finger array
    Open Access
    PRDM9 forms a trimer by interactions within the zinc finger array

    Theresa Schwarz, Yasmin Striedner, Andreas Horner, Karin Haase, Jasmin Kemptner, Nicole Zeppezauer, Philipp Hermann, Irene Tiemann-Boege

    Theresa Schwarz ... Irene Tiemann-Boege

    Published 15 July 2019

    PRDM9 forms a trimer as a soluble protein and in complex with DNA mediated by the ZnF domain. Five ZnFs are already sufficient for multimerization and only one DNA molecule is complexed in the trimer.

  • Stromal fibroblasts induce metastatic tumor cell clusters via epithelial–mesenchymal plasticity
    Open Access
    Stromal fibroblasts induce metastatic tumor cell clusters via epithelial–mesenchymal plasticity

    Yuko Matsumura, Yasuhiko Ito, Yoshihiro Mezawa, Kaidiliayi Sulidan, Yataro Daigo, Toru Hiraga, Kaoru Mogushi, Nadila Wali, Hiromu Suzuki, Takumi Itoh, Yohei Miyagi, Tomoyuki Yokose, Satoru Shimizu, Atsushi Takano, Yasuhisa Terao, Harumi Saeki, Masayuki Ozawa, Masaaki Abe, Satoru Takeda, Ko Okumura, Sonoko Habu, Okio Hino, Kazuyoshi Takeda, Michiaki Hamada, Akira Orimo

    Yuko Matsumura ... Akira Orimo

    Published 22 July 2019

    This study highlights the cellular and molecular mechanisms by which stromal fibroblasts enable human breast cancer cells to form tumor cell clusters and acquire highly invasive and metastatic traits.

  • The miRNA <em>bantam</em> regulates growth and tumorigenesis by repressing the cell cycle regulator <em>tribbles</em>
    Open Access
    The miRNA bantam regulates growth and tumorigenesis by repressing the cell cycle regulator tribbles

    Stephan U Gerlach, Moritz Sander, Shilin Song, Héctor Herranz

    Stephan U Gerlach ... Héctor Herranz

    Published 22 July 2019

    This work identifies the cell cycle regulator tribbles as a target of the miRNA bantam involved in the growth regulatory and oncogenic functions of bantam in Drosophila epithelia.

  • The early-acting glycosome biogenic protein Pex3 is essential for trypanosome viability
    Open Access
    The early-acting glycosome biogenic protein Pex3 is essential for trypanosome viability

    Hiren Banerjee, Barbara Knoblach, Richard A Rachubinski

    Hiren Banerjee ... Richard A Rachubinski

    Published 24 July 2019

    This study reports the identification of trypanosome Pex3, the master regulator of glycosome biogenesis. Trypanosome Pex3 is essential for glycosome assembly and trypanosome viability and is distinct from human Pex3.

  • XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures
    Open Access
    XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures

    Kornelia Ellwanger, Selina Briese, Christine Arnold, Ioannis Kienes, Valentin Heim, Ueli Nachbur, Thomas A Kufer

    Kornelia Ellwanger ... Thomas A Kufer

    Published 26 July 2019

    This study provides evidence that the NOD1/2-associated kinase RIPK2 localizes to detergent insoluble cytosolic complexes upon activation and suggests novel regulatory mechanisms for RIPK2 signaling.

  • Subunit interactions and arrangements in the fission yeast Mis16–Mis18–Mis19 complex
    Open Access
    Subunit interactions and arrangements in the fission yeast Mis16–Mis18–Mis19 complex

    Melanie Korntner-Vetter, Stéphane Lefèvre, Xiao-Wen Hu, Roger George, Martin R Singleton

    Melanie Korntner-Vetter ... Martin R Singleton

    Published 1 August 2019

    A structural study of the fission yeast Mis19 protein, required for centromere establishment, is presented together with data describing its interactions with functional partners Mis16 and Mis18.

  • Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions
    Open Access
    Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions

    Satoshi Konishi, Tomoki Yano, Hiroo Tanaka, Tomoaki Mizuno, Hatsuho Kanoh, Kazuto Tsukita, Toshinori Namba, Atsushi Tamura, Shigenobu Yonemura, Shimpei Gotoh, Hisako Matsumoto, Toyohiro Hirai, Sachiko Tsukita

    Satoshi Konishi ... Sachiko Tsukita

    Published 9 August 2019

    Vinculin in the apical junctional complex maintains the paracellular barrier function specifically for ions, but not for large solutes, by buffering mechanical fluctuations.

  • Kinesin-8B controls basal body function and flagellum formation and is key to malaria transmission
    Open Access
    Kinesin-8B controls basal body function and flagellum formation and is key to malaria transmission

    Mohammad Zeeshan, David JP Ferguson, Steven Abel, Alana Burrrell, Edward Rea, Declan Brady, Emilie Daniel, Michael Delves, Sue Vaughan, Anthony A Holder, Karine G Le Roch, Carolyn A Moores, Rita Tewari

    Mohammad Zeeshan ... Rita Tewari

    Published 13 August 2019

    This comprehensive study describes the key role and real-time dynamics of Plasmodium kinesin-8B in microtubule-based basal body and axoneme assembly during flagellum (male gamete) formation and parasite transmission.

  • MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress
    Open Access
    MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress

    Shun Nagashima, Keisuke Takeda, Nobuhiko Ohno, Satoshi Ishido, Motohide Aoki, Yurika Saitoh, Takumi Takada, Takeshi Tokuyama, Ayumu Sugiura, Toshifumi Fukuda, Nobuko Matsushita, Ryoko Inatome, Shigeru Yanagi

    Shun Nagashima ... Shigeru Yanagi

    Published 15 August 2019

    MITOL deletion in mouse brain impairs the morphology and ER tethering of mitochondria, resulting in enhanced oxidative stress. This study suggests a relationship between morphological abnormalities of mitochondria and developmental disorder.

  • Ncl1-mediated metabolic rewiring critical during metabolic stress
    Open Access
    Ncl1-mediated metabolic rewiring critical during metabolic stress

    Ajay Bhat, Rahul Chakraborty, Khushboo Adlakha, Ganesh Agam, Kausik Chakraborty, Shantanu Sengupta

    Ajay Bhat ... Shantanu Sengupta

    Published 15 August 2019

    Accumulation of cysteine induces translational defects and metabolic rewiring that are abrogated by leucine in a transfer RNA (tRNA) methyltransferase NCL1-dependent manner in yeast.

  • GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
    Open Access
    GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer

    Chun-Chih Tseng, Ramunas Stanciauskas, Pu Zhang, Dennis Woo, Kaijin Wu, Kevin Kelly, Parkash S Gill, Min Yu, Fabien Pinaud, Amy S Lee

    Chun-Chih Tseng ... Amy S Lee

    Published 15 August 2019

    Endoplasmic reticulum chaperone protein GRP78 interacts with CD44v and regulates F-actin integrity, cell adhesion, and cell spreading in breast cancer cells. Targeting cell surface GRP78 by antibodies can reduce CD44v expression.

  • KAP1 is an antiparallel dimer with a functional asymmetry
    Open Access
    KAP1 is an antiparallel dimer with a functional asymmetry

    Giulia Fonti, Maria J Marcaida, Louise C Bryan, Sylvain Träger, Alexandra S Kalantzi, Pierre-Yves JL Helleboid, Davide Demurtas, Mark D Tully, Sergei Grudinin, Didier Trono, Beat Fierz, Matteo Dal Peraro

    Giulia Fonti ... Matteo Dal Peraro

    Published 19 August 2019

    This study reveals the architecture of human KAP1 by integrating molecular modeling with small-angle X-ray scattering and single-molecule experiments. KAP1 dimers feature a structural asymmetry at the C-terminal domains that has functional implications for recruitment of HP1.

  • A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells
    Open Access
    A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells

    Serge Auvin, Harun Öztürk, Yusuf T Abaci, Gisele Mautino, Florence Meyer-Losic, Florence Jollivet, Tarig Bashir, Hugues de Thé, Umut Sahin

    Serge Auvin ... Umut Sahin

    Published 20 August 2019

    A new molecule induces AR sumoylation and degradation resulting in selective growth inhibition in AR-dependent prostate cancer cells, but its activity is blunted by interference with proteasomes.

  • Plasmalogen loss caused by remodeling deficiency in mitochondria
    Open Access
    Plasmalogen loss caused by remodeling deficiency in mitochondria

    Tomohiro Kimura, Atsuko K Kimura, Mindong Ren, Vernon Monteiro, Yang Xu, Bob Berno, Michael Schlame, Richard M Epand

    Tomohiro Kimura ... Richard M Epand

    Published 21 August 2019

    31P NMR unveils cell type–dependent losses of plasmalogen in the chain remodeling–deficient brain, liver, kidney, and lymphoblast in association with aberrant mitochondrial function and morphology.

  • Heterozygous loss of function of <em>IQSEC2</em>/<em>Iqsec2</em> leads to increased activated Arf6 and severe neurocognitive seizure phenotype in females
    Open Access
    Heterozygous loss of function of IQSEC2/Iqsec2 leads to increased activated Arf6 and severe neurocognitive seizure phenotype in females

    Matilda R Jackson, Karagh E Loring, Claire C Homan, Monica HN Thai, Laura Määttänen, Maria Arvio, Irma Jarvela, Marie Shaw, Alison Gardner, Jozef Gecz, Cheryl Shoubridge

    Matilda R Jackson ... Cheryl Shoubridge

    Published 22 August 2019

    We show that the loss of Iqsec2 function in mice recapitulates key aspects of the human phenotype, irrespective of the X-inactivation status of the gene between species. Our understanding of the traditional X-chromosome inheritance with heterozygous female sparing needs revisiting.

Methods

  • De novo prediction of cell-type complexity in single-cell RNA-seq and tumor microenvironments
    Open Access
    De novo prediction of cell-type complexity in single-cell RNA-seq and tumor microenvironments

    Jun Woo, Boris J. Winterhoff, Timothy K. Starr, Constantin Aliferis, Jinhua Wang

    Jun Woo ... Jinhua Wang

    Published 2 July 2019

    This study describes a computational method for determining statistical support to varying levels of heterogeneity provided by single-cell RNA-sequencing data with applications to tumor samples.

  • TAF-ChIP: an ultra-low input approach for genome-wide chromatin immunoprecipitation assay
    Open Access
    TAF-ChIP: an ultra-low input approach for genome-wide chromatin immunoprecipitation assay

    Junaid Akhtar, Piyush More, Steffen Albrecht, Federico Marini, Waldemar Kaiser, Apurva Kulkarni, Leszek Wojnowski, Jean-Fred Fontaine, Miguel A Andrade-Navarro, Marion Silies, Christian Berger

    Junaid Akhtar ... Christian Berger

    Published 22 July 2019

    The authors present a novel method for obtaining chromatin profiles from low cell numbers without prior nuclei isolation. The method is successfully implemented in generating epigenetic profile from 100 cells with high signal-to-noise ratio.

  • Targeted variant detection using unaligned RNA-Seq reads
    Open Access
    Targeted variant detection using unaligned RNA-Seq reads

    Eric Olivier Audemard, Patrick Gendron, Albert Feghaly, Vincent-Philippe Lavallée, Josée Hébert, Guy Sauvageau, Sébastien Lemieux

    Eric Olivier Audemard ... Sébastien Lemieux

    Published 19 August 2019

    This study introduces km, an approach leveraging k-mer decomposition to identify targeted mutations. It can detect single-base mutations, insertions and deletions, as well as fusions. An analysis of over 10,000 RNA-seq samples shows fast mutation detection via km.

  • Reconstructing B-cell receptor sequences from short-read single-cell RNA sequencing with BRAPeS
    Open Access
    Reconstructing B-cell receptor sequences from short-read single-cell RNA sequencing with BRAPeS

    Shaked Afik, Gabriel Raulet, Nir Yosef

    Shaked Afik ... Nir Yosef

    Published 26 August 2019

    BRAPeS is a software for B-cell receptor reconstruction in single cells from very short (25–30 bp) read lengths, which achieves similar success rates and accuracy as applying other methods on long reads.

Correction

  • Open Access
    Correction: The small and large ribosomal subunits depend on each other for stability and accumulation

    Brian Gregory, Nusrat Rahman, Ananth Bommakanti, Md Shamsuzzaman, Mamata Thapa, Alana Lescure, Janice M Zengel, Lasse Lindahl

    Brian Gregory ... Lasse Lindahl

    Published 1 August 2019
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Volume 2, No. 4
August 2019
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