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Table of Contents

October 2022 | Volume 5, No. 10

Research Articles

  • Transmembrane protease serine 2 (<em>TMPRSS2</em>) rs75603675, comorbidity, and sex are the primary predictors of COVID-19 severity
    Open Access
    Transmembrane protease serine 2 (TMPRSS2) rs75603675, comorbidity, and sex are the primary predictors of COVID-19 severity

    Gonzalo Villapalos-García, Pablo Zubiaur, Rebeca Rivas-Durán, Pilar Campos-Norte, Cristina Arévalo-Román, Marta Fernández-Rico, Lucio García-Fraile Fraile, Paula Fernández-Campos, Paula Soria-Chacartegui, Sara Fernández de Córdoba-Oñate, Pablo Delgado-Wicke, Elena Fernández-Ruiz, Isidoro González-Álvaro, Jesús Sanz, Francisco Abad-Santos, Ignacio de los Santos

    Gonzalo Villapalos-García ... Ignacio de los Santos

    Published 30 May 2022

    The TMPRSS2 rs75603675 genotype (OR = 0.586), dyslipidemia (OR = 2.289), sex (OR = 0.586), and the Charlson Comorbidity Index (OR = 1.126) were identified as the main predictors of COVID-19 severity in 817 patients who attended Hospital Universitario de La Princesa during March and April 2020.

  • Evolutionary association of receptor-wide amino acids with G protein–coupling selectivity in aminergic GPCRs
    Open Access
    Evolutionary association of receptor-wide amino acids with G protein–coupling selectivity in aminergic GPCRs

    Berkay Selçuk, Ismail Erol, Serdar Durdağı, Ogün Adebali

    Berkay Selçuk ... Ogün Adebali

    Published 25 May 2022

    Evolutionary analyses of aminergic G protein–coupled receptors reveal receptor-wide potential determinants of G protein–coupling selectivity.

  • MET∆14 promotes a ligand-dependent, AKT-driven invasive growth
    Open Access
    MET∆14 promotes a ligand-dependent, AKT-driven invasive growth

    Marina Cerqua, Orsola Botti, Maddalena Arigoni, Noemi Gioelli, Guido Serini, Raffaele Calogero, Carla Boccaccio, Paolo M Comoglio, Dogus M Altintas

    Marina Cerqua ... Dogus M Altintas

    Published 30 May 2022

    The MET oncogene’s most frequent mutation is exon14 deletion. The resulting MET∆14 kinase is not constitutively active but requires HGF. The response to the ligand is stronger and long-lasting, protecting cancer cells from apoptosis and driving invasive growth.

  • Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation
    Open Access
    Axonal transport of Hrs is activity dependent and facilitates synaptic vesicle protein degradation

    Veronica Birdsall, Konner Kirwan, Mei Zhu, Yuuta Imoto, Scott M Wilson, Shigeki Watanabe, Clarissa L Waites

    Veronica Birdsall ... Clarissa L Waites

    Published 30 May 2022

    This study describes an activity-dependent mechanism for transporting ESCRT-0 protein Hrs to synaptic vesicle (SV) pools, facilitating SV protein degradation in response to increased neuronal firing.

  • VDAC1 negatively regulates melanogenesis through the Ca<sup>2+</sup>-calcineurin-CRTC1-MITF pathway
    Open Access
    VDAC1 negatively regulates melanogenesis through the Ca2+-calcineurin-CRTC1-MITF pathway

    Jianli Wang, Juanjuan Gong, Qiaochu Wang, Tieshan Tang, Wei Li

    Jianli Wang ... Wei Li

    Published 1 June 2022

    This study revealed an important and novel role of mitochondrial VDAC1 in regulating melanogenesis in resting melanocytes through a Ca2+-regulated pathway that is independent of the alpha-MSH/UVB pathway.

  • ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis
    Open Access
    ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis

    Jianzhong Zheng, Zhiyuan Shi, Pengbo Yang, Yue Zhao, Wenbin Tang, Shaopei Ye, Zuodong Xuan, Chen Chen, Chen Shao, Qingang Wu, Huimin Sun

    Jianzhong Zheng ... Huimin Sun

    Published 2 June 2022

    The research uncovers a non-canonical role of ERK in TGF-beta-induced EMT, revealing ERK-mediated phosphorylation of Smurf1 is required for its sufficient binding to RhoA and the subsequent RhoA turnover.

  • The intracellular pathogen <em>Francisella tularensis</em> escapes from adaptive immunity by metabolic adaptation
    Open Access
    The intracellular pathogen Francisella tularensis escapes from adaptive immunity by metabolic adaptation

    Kensuke Shibata, Takashi Shimizu, Mashio Nakahara, Emi Ito, Francois Legoux, Shotaro Fujii, Yuka Yamada, Makoto Furutani-Seiki, Olivier Lantz, Sho Yamasaki, Masahisa Watarai, Mutsunori Shirai

    Kensuke Shibata ... Mutsunori Shirai

    Published 6 June 2022

    This study shows that metabolic adaptation allows the intracellular bacterial pathogen Francisella tularensis to escape recognition by the host adaptive immunity.

  • Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage
    Open Access
    Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage

    Moujtaba Y Kasmani, Ashley E Ciecko, Ashley K Brown, Galina Petrova, Jack Gorski, Yi-Guang Chen, Weiguo Cui

    Moujtaba Y Kasmani ... Weiguo Cui

    Published 6 June 2022

    Paired scRNA-seq and scTCR-seq reveals that diabetogenic CD8 T cells in the islets and spleens of NOD mice exhibit phenotypic and clonal heterogeneity despite restricted TCR gene usage. Expression of certain TCR genes correlates with clonal proliferation and effector phenotype.

  • LncRNA <em>RUS</em> shapes the gene expression program towards neurogenesis
    Open Access
    LncRNA RUS shapes the gene expression program towards neurogenesis

    Marius F Schneider, Veronika Müller, Stephan A Müller, Stefan F Lichtenthaler, Peter B Becker, Johanna C Scheuermann

    Marius F Schneider ... Johanna C Scheuermann

    Published 10 June 2022

    The chromatin-associated lncRNA RUS binds in the vicinity to neural differentiation-associated genes and regulates them in a context-dependent manner to enable proper neuron development.

  • Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap
    Open Access
    Estimating intraclonal heterogeneity and subpopulation changes from bulk expression profiles in CMap

    Chiao-Yu Hsieh, Ching-Chih Tu, Jui-Hung Hung

    Chiao-Yu Hsieh ... Jui-Hung Hung

    Published 10 June 2022

    Premnas is a computational framework that provides a new perspective to interpret perturbational data in LINC L1000 CMap by learning an ad hoc subpopulation representation from scRNA-seq and performing the digital cytometry to estimate the abundance of undetermined subpopulations.

  • TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy
    Open Access
    TMBIM5 loss of function alters mitochondrial matrix ion homeostasis and causes a skeletal myopathy

    Li Zhang, Felicia Dietsche, Bruno Seitaj, Liliana Rojas-Charry, Nadina Latchman, Dhanendra Tomar, Rob CI Wüst, Alexander Nickel, Katrin BM Frauenknecht, Benedikt Schoser, Sven Schumann, Michael J Schmeisser, Johannes vom Berg, Thorsten Buch, Stefanie Finger, Philip Wenzel, Christoph Maack, John W Elrod, Jan B Parys, Geert Bultynck, Axel Methner

    Li Zhang ... Axel Methner

    Published 17 June 2022

    TMBIM5 deficiency reduces mitochondrial K+/H+ exchange. Mutation of the channel pore in mice destabilizes the protein and results in increased embryonic lethality and a skeletal myopathy.

  • IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model by <em>Pseudomonas aeruginosa</em>
    Open Access
    IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model by Pseudomonas aeruginosa

    Tania Cebrero-Cangueiro, Gema Labrador-Herrera, Marta Carretero-Ledesma, Soraya Herrera-Espejo, Rocío Álvarez-Marín, Jerónimo Pachón, José Miguel Cisneros, María Eugenia Pachón-Ibáñez

    Tania Cebrero-Cangueiro ... María Eugenia Pachón-Ibáñez

    Published 21 June 2022

    Using polyclonal IgM-enriched immunoglobulin (IgM-IG) as adjuvant therapy to colistin appears useful in the treatment of pneumonia caused by multidrug-resistant strains of P. aeruginosa.

  • Neuropeptide signalling shapes feeding and reproductive behaviours in male <em>Caenorhabditis elegans</em>
    Open Access
    Neuropeptide signalling shapes feeding and reproductive behaviours in male Caenorhabditis elegans

    Matthew J Gadenne, Iris Hardege, Eviatar Yemini, Djordji Suleski, Paris Jaggers, Isabel Beets, William R Schafer, Yee Lian Chew

    Matthew J Gadenne ... Yee Lian Chew

    Published 23 June 2022

    LURY-1 peptides are expressed in distinct cells in different sexes and have sex-specific effects on feeding and mating, providing further evidence for the role of neuromodulators in sexual dimorphism.

  • chromMAGMA: regulatory element-centric interrogation of risk variants
    Open Access
    chromMAGMA: regulatory element-centric interrogation of risk variants

    Robbin Nameki, Anamay Shetty, Eileen Dareng, Jonathan Tyrer, Xianzhi Lin, The Ovarian Cancer Association Consortium, Paul Pharoah, Rosario I Corona, Siddhartha Kar, Kate Lawrenson

    Robbin Nameki ... Kate Lawrenson

    Published 1 July 2022

    chromMAGMA, a pipeline that prioritizes candidate risk regulatory elements and target genes, reveals novel risk-associated genes when applied to epithelial ovarian cancer.

  • The vacuole shapes the nucleus and the ribosomal DNA loop during mitotic delays
    Open Access
    The vacuole shapes the nucleus and the ribosomal DNA loop during mitotic delays

    Emiliano Matos-Perdomo, Silvia Santana-Sosa, Jessel Ayra-Plasencia, Sara Medina-Suárez, Félix Machín

    Emiliano Matos-Perdomo ... Félix Machín

    Published 12 August 2022

    Chromosome structuring and condensation is one of the main features of mitosis. Here, Matos-Perdomo et al show how the nuclear envelope reshapes around the vacuole to give rise to the outstanding ribosomal DNA loop in budding yeast.

  • Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma
    Open Access
    Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma

    Yasuhiro Yamamoto, Ken Kadoya, Mohamad Alaa Terkawi, Takeshi Endo, Kohtarou Konno, Masahiko Watanabe, Satoshi Ichihara, Akira Hara, Kazuo Kaneko, Norimasa Iwasaki, Muneaki Ishijima

    Yasuhiro Yamamoto ... Muneaki Ishijima

    Published 12 August 2022

    Neutrophils accumulate at the epineurium in Wallerian degeneration (WD) and inhibit macrophage infiltration from the epineurium into the parenchyma by releasing neutrophil extracellular traps, resulting in the delay of repair processes in WD.

  • Mitotic H3K9ac is controlled by phase-specific activity of HDAC2, HDAC3, and SIRT1
    Open Access
    Mitotic H3K9ac is controlled by phase-specific activity of HDAC2, HDAC3, and SIRT1

    Shashi Gandhi, Raizy Mitterhoff, Rachel Rapoport, Marganit Farago, Avraham Greenberg, Lauren Hodge, Sharon Eden, Christopher Benner, Alon Goren, Itamar Simon

    Shashi Gandhi ... Itamar Simon

    Published 18 August 2022

    Combination of immunofluorescence, Western blot, and ChIP-seq revealed the interplay between HDAC2, HDAC3, and SIRT1 in H3K9 deacetylation during mitosis of mammalian cells.

  • Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis
    Open Access
    Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis

    William C Simke, Cory P Johnson, Andrew J Hart, Sari Mayhue, P Lucas Craig, Savannah Sojka, Joshua B Kelley

    William C Simke ... Joshua B Kelley

    Published 19 August 2022

    Phosphorylation of the RGS Sst2 alters its subcellular distribution, MAPK localization, and interaction with Kel1, which promotes coordination of polarized growth with completion of cytokinesis.

  • Binding stoichiometry and structural model of the HIV-1 Rev/importin β complex
    Open Access
    Binding stoichiometry and structural model of the HIV-1 Rev/importin β complex

    Didier Spittler, Rose-Laure Indorato, Elisabetta Boeri Erba, Elise Delaforge, Luca Signor, Simon J Harris, Isabel Garcia-Saez, Andrés Palencia, Frank Gabel, Martin Blackledge, Marjolaine Noirclerc-Savoye, Carlo Petosa

    Didier Spittler ... Carlo Petosa

    Published 22 August 2022

    Biochemical, biophysical, and docking studies provide insights into how the HIV-1 regulatory protein Rev is recognized by the nuclear import factor importin beta.

  • Proteasomal down-regulation of the proapoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma
    Open Access
    Proteasomal down-regulation of the proapoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma

    David Romano, Lucía García-Gutiérrez, Nourhan Aboud, David J Duffy, Keith T Flaherty, Dennie T Frederick, Walter Kolch, David Matallanas

    David Romano ... David Matallanas

    Published 29 August 2022

    The loss of MST2 pathway protein expression in BRAF inhibitor resistant melanoma cells is due to ubiquitination and subsequent proteasomal degradation and prevents MST2-mediated apoptosis.

  • Meiotic DNA breaks activate a streamlined phospho-signaling response that largely avoids protein-level changes
    Open Access
    Meiotic DNA breaks activate a streamlined phospho-signaling response that largely avoids protein-level changes

    Funda M Kar, Christine Vogel, Andreas Hochwagen

    Funda M Kar ... Andreas Hochwagen

    Published 1 September 2022

    The meiotic DNA break response is shown to involve a large number of phosphorylation changes and a clearly detectable transcriptional response. By contrast, the meiotic proteome remains remarkably unchanged in response to breaks.

  • HIV-1 infection enhances innate function and <em>TLR7</em> expression in female plasmacytoid dendritic cells
    Open Access
    HIV-1 infection enhances innate function and TLR7 expression in female plasmacytoid dendritic cells

    Flora Abbas, Claire Cenac, Ali Youness, Pascal Azar, Pierre Delobel, Jean-Charles Guéry

    Flora Abbas ... Jean-Charles Guéry

    Published 2 September 2022

    This study shows that the TLR7-driven innate function of pDCs is increased in HIV/ART women and is associated with enhanced expression of the TLR7 locus from both X chromosomes.

  • <em>GhRabA4c</em> coordinates cell elongation via regulating actin filament–dependent vesicle transport
    Open Access
    GhRabA4c coordinates cell elongation via regulating actin filament–dependent vesicle transport

    Xiaoguang Shang, Yujia Duan, Meiyue Zhao, Lijie Zhu, Hanqiao Liu, Qingfei He, Yujia Yu, Weixi Li, Muhammad Waqas Amjid, Yong-Ling Ruan, Wangzhen Guo

    Xiaoguang Shang ... Wangzhen Guo

    Published 6 September 2022

    GhRabA4c is required for cotton fiber cell elongation via functioning in actin filament assembly and bundling, vesicle transport, and deposition of multiple cell wall components.

  • Regulation of Liprin-α phase separation by CASK is disrupted by a mutation in its CaM kinase domain
    Open Access
    Regulation of Liprin-α phase separation by CASK is disrupted by a mutation in its CaM kinase domain

    Debora Tibbe, Pia Ferle, Christoph Krisp, Sheela Nampoothiri, Ghayda Mirzaa, Melissa Assaf, Sumit Parikh, Kerstin Kutsche, Hans-Jürgen Kreienkamp

    Debora Tibbe ... Hans-Jürgen Kreienkamp

    Published 22 September 2022

    Mutations in the human CASK gene cause a neurodevelopmental disorder; we show that CASK regulates condensate formation of Liprin-alpha 2 and that patient mutations in the CaM kinase domain interfere with Liprin binding and regulation of condensate formation.

  • Contribution of the Golgi apparatus in morphogenesis of a virus-induced cytopathic vacuolar system
    Open Access
    Contribution of the Golgi apparatus in morphogenesis of a virus-induced cytopathic vacuolar system

    Ranjan Sengupta, Elaine M Mihelc, Stephanie Angel, Jason K Lanman, Richard J Kuhn, Robert V Stahelin

    Ranjan Sengupta ... Robert V Stahelin

    Published 22 September 2022

    Electron tomography reveals four classes of cytopathic vesicles-II (CPV-II) stemming from the host Golgi apparatus after Venezuelan equine encephalitis virus infection.

Methods

  • Workflow for high-dimensional flow cytometry analysis of T cells from tumor metastases
    Open Access
    Workflow for high-dimensional flow cytometry analysis of T cells from tumor metastases

    Cristina Faccani, Gianluca Rotta, Francesca Clemente, Maya Fedeli, Danilo Abbati, Francesco Manfredi, Alessia Potenza, Achille Anselmo, Federica Pedica, Guido Fiorentini, Chiara Villa, Maria P Protti, Claudio Doglioni, Luca Aldrighetti, Chiara Bonini, Giulia Casorati, Paolo Dellabona, Claudia de Lalla

    Cristina Faccani ... Claudia de Lalla

    Published 3 June 2022

    We describe an improved method for the high-dimensional flow cytometry analysis of conventional and rare unconventional T cells infiltrating tumor liver metastases.

Resources

  • PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system
    Open Access
    PRMT1 is required for the generation of MHC-associated microglia and remyelination in the central nervous system

    Jeesan Lee, Oscar David Villarreal, Yu Chang Wang, Jiannis Ragoussis, Serge Rivest, David Gosselin, Stéphane Richard

    Jeesan Lee ... Stéphane Richard

    Published 15 June 2022

    PRMT1 regulates MHC-associated microglia cluster during de/remyelination.

  • Intestinal single-cell atlas reveals novel lymphocytes in pigs with similarities to human cells
    Open Access
    Intestinal single-cell atlas reveals novel lymphocytes in pigs with similarities to human cells

    Jayne E Wiarda, Julian M Trachsel, Sathesh K Sivasankaran, Christopher K Tuggle, Crystal L Loving

    Jayne E Wiarda ... Crystal L Loving

    Published 22 August 2022

    Single-cell RNA sequencing of porcine ileal lymphocytes reveals similarities to human cells and discovery of porcine intestinal innate lymphoid cells.

Corrections

  • Open Access
    Correction: ESCRT-I fuels lysosomal degradation to restrict TFEB/TFE3 signaling via the Rag-mTORC1 pathway

    Marta Wróbel, Jarosław Cendrowski, Ewelina Szymańska, Malwina Grębowicz-Maciukiewicz, Noga Budick-Harmelin, Matylda Macias, Aleksandra Szybińska, Michał Mazur, Krzysztof Kolmus, Krzysztof Goryca, Michalina Dąbrowska, Agnieszka Paziewska, Michał Mikula, Marta Miączyńska

    Marta Wróbel ... Marta Miączyńska

    Published 7 June 2022
  • Open Access
    Correction: Transmembrane protease serine 2 (TMPRSS2) rs75603675, comorbidity and sex are the primary predictors of Covid-19 severity

    Gonzalo Villapalos-García, Pablo Zubiaur, Rebeca Rivas-Durán, Pilar Campos-Norte, Cristina Arévalo-Román, Marta Fernández-Rico, Lucio García-Fraile Fraile, Paula Fernández-Campos, Paula Soria-Chacartegui, Sara Fernández de Córdoba-Oñate, Pablo Delgado-Wicke, Elena Fernández-Ruiz, Isidoro González-Álvaro, Jesús Sanz, Francisco Abad-Santos, Ignacio de los Santos

    Gonzalo Villapalos-García ... Ignacio de los Santos

    Published 9 June 2022

    We identified an error in the abstract of the article: TPMRSS2 rs75603675 OR is incorrectly indicated. It should read (OR = 2.140) instead of (OR = 0.586).

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Volume 5, No. 10
October 2022
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