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Table of Contents

February 2024 | Volume 7, No. 2

Research Articles

  • PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells
    Open Access
    PD-L1 regulates inflammatory programs of macrophages from human pluripotent stem cells

    Handi Cao, Yang Xiang, Shihui Zhang, Yiming Chao, Jilong Guo, Theo Aurich, Joshua WK Ho, Yuanhua Huang, Pentao Liu, Ryohichi Sugimura

    Handi Cao ... Ryohichi Sugimura

    Published 10 November 2023

    This study identified the novel role of immune checkpoint PD-L1 in inflammatory programs of macrophages.

  • Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3
    Open Access
    Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

    Pathum Thilakasiri, Ryan N O’Keefe, Sarah Q To, David Chisanga, Moritz F Eissmann, Annalisa LE Carli, Belinda Duscio, David Baloyan, Rhynelle S Dmello, David Williams, John Mariadason, Ashleigh R Poh, Bhupinder Pal, Benjamin T Kile, Joseph HA Vissers, Kieran F Harvey, Michael Buchert, Wei Shi, Matthias Ernst, Ashwini L Chand

    Pathum Thilakasiri ... Ashwini L Chand

    Published 13 November 2023

    The study shows that Yap1 expression correlates with poor outcomes in human gastric cancer and causally contributes to disease progression in mice via cancer cell–intrinsic and –extrinsic mechanisms.

  • Visualization of conformational transition of GRP94 in solution
    Open Access
    Visualization of conformational transition of GRP94 in solution

    Shangwu Sun, Rui Zhu, Mengyao Zhu, Qi Wang, Na Li, Bei Yang

    Shangwu Sun ... Bei Yang

    Published 10 November 2023

    SAXS, nsEM, and HDX-MS reveal that one extended and two compact conformations of GRP94 coexist in solution and that the binding and hydrolysis of ATP only drives the transition between the two compact conformations while leaving the extended population unaffected.

  • Cristae dynamics is modulated in bioenergetically compromised mitochondria
    Open Access
    Cristae dynamics is modulated in bioenergetically compromised mitochondria

    Mathias Golombek, Thanos Tsigaras, Yulia Schaumkessel, Sebastian Hänsch, Stefanie Weidtkamp-Peters, Ruchika Anand, Andreas S Reichert, Arun Kumar Kondadi

    Mathias Golombek ... Arun Kumar Kondadi

    Published 13 November 2023

    Live-cell super-resolution nanoscopy reveals modulation of cristae dynamics in bioenergetically compromised mitochondria demonstrating that cristae morphology and dynamics are intricately connected.

  • DOCK1 insufficiency disrupts trophoblast function and pregnancy outcomes via DUSP4-ERK pathway
    Open Access
    DOCK1 insufficiency disrupts trophoblast function and pregnancy outcomes via DUSP4-ERK pathway

    Yichi Xu, Xiaorui Liu, Weihong Zeng, Yueyue Zhu, Junpeng Dong, Fan Wu, Cailian Chen, Surendra Sharma, Yi Lin

    Yichi Xu ... Yi Lin

    Published 15 November 2023

    This study reveals that decreased DOCK1 in placental villi affects trophoblast function via the DUSP4-ERK pathway, providing insights into adverse pregnancy outcomes.

  • Transgenerational epigenetic effects imposed by neonicotinoid thiacloprid exposure
    Open Access
    Transgenerational epigenetic effects imposed by neonicotinoid thiacloprid exposure

    Ouzna Dali, Shereen D’Cruz, Louis Legoff, Mariam Diba Lahmidi, Celine Heitz, Pierre-Etienne Merret, Pierre-Yves Kernanec, Farzad Pakdel, Fatima Smagulova

    Ouzna Dali ... Fatima Smagulova

    Published 16 November 2023

    We exposed pregnant female mice to neonicotinoid thiacloprid. We observed reproductive defects together with DNA methylation and histone H3K9me3 changes in the third-generation males.

  • Intrinsic deletion at 10q23.31, including the <em>PTEN</em> gene locus, is aggravated upon CRISPR-Cas9–mediated genome engineering in HAP1 cells mimicking cancer profiles
    Open Access
    Intrinsic deletion at 10q23.31, including the PTEN gene locus, is aggravated upon CRISPR-Cas9–mediated genome engineering in HAP1 cells mimicking cancer profiles

    Keyi Geng, Lara G Merino, Raül G Veiga, Christian Sommerauer, Janine Epperlein, Eva K Brinkman, Claudia Kutter

    Keyi Geng ... Claudia Kutter

    Published 20 November 2023

    The unintended 10q23.31 deletion frequency rises in HAP1 cells stressed during CRISPR-Cas9 engineering, leading to aberrant molecular and cellular changes resembling common cancer patient deletions.

  • Chromatin priming elements direct tissue-specific gene activity before hematopoietic specification
    Open Access
    Chromatin priming elements direct tissue-specific gene activity before hematopoietic specification

    Alexander Maytum, Benjamin Edginton-White, Peter Keane, Peter N Cockerill, Jean-Baptiste Cazier, Constanze Bonifer

    Alexander Maytum ... Constanze Bonifer

    Published 21 November 2023

    This study shows that signalling processes prime many enhancer elements at the chromatin level before the expression of their associated genes and that priming is essential for developmental stage-specific dynamic gene activation.

  • Enhancer-driven 3D chromatin domain folding modulates transcription in human mammary tumor cells
    Open Access
    Enhancer-driven 3D chromatin domain folding modulates transcription in human mammary tumor cells

    Silvia Kocanova, Flavien Raynal, Isabelle Goiffon, Betul Akgol Oksuz, Davide Baú, Alain Kamgoué, Sylvain Cantaloube, Ye Zhan, Bryan Lajoie, Marc A Marti-Renom, Job Dekker, Kerstin Bystricky

    Silvia Kocanova ... Kerstin Bystricky

    Published 21 November 2023

    The study shows that estrogen activates transcription within pre-established chromosomal 3D architectures, strengthening enhancer interactions through local accumulation of the estrogen receptor α.

  • Megakaryocytes possess a STING pathway that is transferred to platelets to potentiate activation
    Open Access
    Megakaryocytes possess a STING pathway that is transferred to platelets to potentiate activation

    Firas El-Mortada, Karima Landelouci, Samuel Bertrand-Perron, Félix-Antoine Aubé, Amélie Poirier, Amel Bidias, Georges Jourdi, Mélanie Welman, Michael P Gantier, Justin R Hamilton, Benjamin Kile, Marie Lordkipanidzé, Geneviève Pépin

    Firas El-Mortada ... Geneviève Pépin

    Published 22 November 2023

    This work reveals that megakaryocytes transfer cGAS and STING proteins to platelets during thrombopoiesis and that cGAS stimulation results in the activation and aggregation of platelets, suggesting a new role of cGAS in thromboinflammation.

  • Decline of DNA damage response along with myogenic differentiation
    Open Access
    Decline of DNA damage response along with myogenic differentiation

    Haser H Sutcu, Phoebe Rassinoux, Lise-Marie Donnio, Damien Neuillet, François Vianna, Olivier Gabillot, Pierre-Olivier Mari, Céline Baldeyron, Giuseppina Giglia-Mari

    Haser H Sutcu ... Giuseppina Giglia-Mari

    Published 22 November 2023

    In postmitotic myotubes, DNA repair processes such as Base Excision Repair, and Non-Homologous End Joining are weakened compared with the proliferative precursors myoblasts.

  • Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injury
    Open Access
    Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injury

    Hali Long, Jeffrey D Steimle, Francisco Jose Grisanti Canozo, Jong Hwan Kim, Xiao Li, Yuka Morikawa, Minjun Park, Diwakar Turaga, Iki Adachi, Joshua D Wythe, Md Abul Hassan Samee, James F Martin

    Hali Long ... James F Martin

    Published 27 November 2023

    scRNA-seq uncovers an endothelial cell (EC) subpopulation with immune responsive signatures in cardiac injury. Profiling of human heart failure samples reveals EC-specific immune responsive signatures in adult and pediatric heart failure. ECs can adopt immune responsive signatures during cardiac stress.

  • A dual-targeted drug inhibits cardiac ryanodine receptor Ca<sup>2+</sup> leak but activates SERCA2a Ca<sup>2+</sup> uptake
    Open Access
    A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptake

    Jörg W Wegener, Gyuzel Y Mitronova, Lina ElShareif, Christine Quentin, Vladimir Belov, Tatiana Pochechueva, Gerd Hasenfuss, Lutz Ackermann, Stephan E Lehnart

    Jörg W Wegener ... Stephan E Lehnart

    Published 27 November 2023

    Our study identified a first multi-targeted compound (GM1869) inhibiting RyR2-mediated Ca2+ leak together with activating SERCA2a function that may represent a critical breakthrough for treatment of diastolic Ca2+ leak in heart failure.

  • 2-Hydroxyglutarate modulates histone methylation at specific loci and alters gene expression via Rph1 inhibition
    Open Access
    2-Hydroxyglutarate modulates histone methylation at specific loci and alters gene expression via Rph1 inhibition

    Marios Gavriil, Marco Proietto, Nicole Paczia, Aurelien Ginolhac, Rashi Halder, Elena Valceschini, Thomas Sauter, Carole L Linster, Lasse Sinkkonen

    Marios Gavriil ... Lasse Sinkkonen

    Published 27 November 2023

    This study investigates the genome-wide effects of 2-HG accumulation on chromatin and gene expression and identifies Rph1-dependent and H3K36me3-associated gene repression at silenced loci in yeast.

  • RNA helicase EIF4A1-mediated translation is essential for the GC response
    Open Access
    RNA helicase EIF4A1-mediated translation is essential for the GC response

    Michael Screen, Louise S Matheson, Andrew JM Howden, Douglas Strathdee, Anne E Willis, Martin Bushell, Owen Sansom, Martin Turner

    Michael Screen ... Martin Turner

    Published 27 November 2023

    Conditional mouse knock-out models show that EIF4A1, but not its cofactors EIF4B or EIF4H, is essential in B cells for their development, the GC response, and increased translation after activation.

  • PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development
    Open Access
    PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development

    Gbolahan Bamgbose, Alexei Tulin

    Gbolahan Bamgbose ... Alexei Tulin

    Published 27 November 2023

    PARP-1 fine-tunes gene expression to control energy balance and development by selectively repressing and activating critical genes for developmental progression.

  • Analysis of the indispensable RAD51 cofactor BRCA2 in <em>Naganishia liquefaciens</em>, a Basidiomycota yeast
    Open Access
    Analysis of the indispensable RAD51 cofactor BRCA2 in Naganishia liquefaciens, a Basidiomycota yeast

    Maierdan Palihati, Hiroshi Iwasaki, Hideo Tsubouchi

    Maierdan Palihati ... Hideo Tsubouchi

    Published 28 November 2023

    Identification of the BRCA2 homolog in the Basidiomycota yeast Naganishia liquefaciens reveals the general attributes of fungal BRCA2 and its essential role in Rad51-mediated homologous recombination.

  • Common analysis of direct RNA sequencinG CUrrently leads to misidentification of m<sup>5</sup>C at GCU motifs
    Open Access
    Common analysis of direct RNA sequencinG CUrrently leads to misidentification of m5C at GCU motifs

    Kaylee J Watson, Robin E Bromley, Benjamin C Sparklin, Mark T Gasser, Tamanash Bhattacharya, Jarrett F Lebov, Tyonna Tyson, Nan Dai, Laura E Teigen, Karen T Graf, Jeremy M Foster, Michelle Michalski, Vincent M Bruno, Amelia RI Lindsey, Ivan R Corrêa, Richard W Hardy, Irene LG Newton, Julie C Dunning Hotopp

    Kaylee J Watson ... Julie C Dunning Hotopp

    Published 29 November 2023

    Published predictions of 5-methylcytosine at GCU sites inferred from direct RNA sequencing and the Tombo Alternative Model should be reconsidered unless further validated with orthogonal methods.

  • Proteomic-based stratification of intermediate-risk prostate cancer patients
    Open Access
    Proteomic-based stratification of intermediate-risk prostate cancer patients

    Qing Zhong, Rui Sun, Adel T Aref, Zainab Noor, Asim Anees, Yi Zhu, Natasha Lucas, Rebecca C Poulos, Mengge Lyu, Tiansheng Zhu, Guo-Bo Chen, Yingrui Wang, Xuan Ding, Dorothea Rutishauser, Niels J Rupp, Jan H Rueschoff, Cédric Poyet, Thomas Hermanns, Christian Fankhauser, María Rodríguez Martínez, Wenguang Shao, Marija Buljan, Janis Frederick Neumann, Andreas Beyer, Peter G Hains, Roger R Reddel, Phillip J Robinson, Ruedi Aebersold, Tiannan Guo, Peter J Wild

    Qing Zhong ... Peter J Wild

    Published 4 December 2023

    This study demonstrates the ability of a protein-based signature to risk-stratify prostate cancer patients with Gleason grade groups 2 and 3 and predict the risk of biochemical recurrence.

  • Structural maintenance of chromosomes (SMC) proteins are required for DNA elimination in <em>Paramecium</em>
    Open Access
    Structural maintenance of chromosomes (SMC) proteins are required for DNA elimination in Paramecium

    Fukai Zhang, Sebastian Bechara, Mariusz Nowacki

    Fukai Zhang ... Mariusz Nowacki

    Published 6 December 2023

    This work focuses on two functionally distinct paralogues of SMC4 in Paramecium. SMC4-1 appears to have a classical function as a condensin subunit whereas SMC4-2 is required for developmental DNA elimination process.

  • IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium
    Open Access
    IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium

    Sankhanil Saha, Harini Krishnan, Padinjat Raghu

    Sankhanil Saha ... Padinjat Raghu

    Published 6 December 2023

    This study demonstrates that lithium that is used to treat bipolar disorder acts via IMPA1 to regulate calcium signalling and neuronal excitability.

  • The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors
    Open Access
    The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors

    Santiago Camblor-Perujo, Ebru Ozer Yildiz, Hanna Küpper, Melina Overhoff, Saumya Rastogi, Hisham Bazzi, Natalia L Kononenko

    Santiago Camblor-Perujo ... Natalia L Kononenko

    Published 12 December 2023

    This study reveals a novel role of endocytic adaptor AP-2 in orchestrating centrosome function and cell cycle progression through its interaction with components of the γ-TuRC complex, providing valuable insights for addressing neurodevelopmental and neurodegenerative disorders linked to AP-2 dysfunction.

  • The structural basis for deubiquitination by the fingerless USP-type effector TssM
    Open Access
    The structural basis for deubiquitination by the fingerless USP-type effector TssM

    Thomas Hermanns, Matthias Uthoff, Ulrich Baumann, Kay Hofmann

    Thomas Hermanns ... Kay Hofmann

    Published 13 December 2023

    The structural characterization of the bacterial effector deubiquitinase TssM from Burkholderia pseudomallei, belonging to the USP family, reveals that TssM lacks the canonical “Fingers” subdomain of USP-type deubiquitinases and evolved instead the functionally analog “Littlefinger” loop for ubiquitin binding.

Methods

  • Patient-specific analysis of co-expression to measure biological network rewiring in individuals
    Open Access
    Patient-specific analysis of co-expression to measure biological network rewiring in individuals

    Lanying Wei, Yucui Xin, Mengchen Pu, Yingsheng Zhang

    Lanying Wei ... Yingsheng Zhang

    Published 17 November 2023

    Cosinet has the potential to empower personalized treatment by accurately quantifying the degree of rewiring in individual samples compared with reference conditions using mechanism-related differential co-expression sub-networks.

  • Mitochondria isolated from lipid droplets of white adipose tissue reveal functional differences based on lipid droplet size
    Open Access
    Mitochondria isolated from lipid droplets of white adipose tissue reveal functional differences based on lipid droplet size

    Alexandra J Brownstein, Michaela Veliova, Rebeca Acin-Perez, Frankie Villalobos, Anton Petcherski, Alberto Tombolato, Marc Liesa, Orian S Shirihai

    Alexandra J Brownstein ... Orian S Shirihai

    Published 6 December 2023

    In the current study, we show an optimized protocol using proteolytic treatment that enables the isolation of peridroplet mitochondria (PDM) from white adipose tissue (WAT), revealing a unique function of WAT PDM that depends on the heterogeneity of lipid droplet size.

  • RedRibbon: A new rank–rank hypergeometric overlap for gene and transcript expression signatures
    Open Access
    RedRibbon: A new rank–rank hypergeometric overlap for gene and transcript expression signatures

    Anthony Piron, Florian Szymczak, Theodora Papadopoulou, Maria Inês Alvelos, Matthieu Defrance, Tom Lenaerts, Décio L Eizirik, Miriam Cnop

    Anthony Piron ... Miriam Cnop

    Published 8 December 2023

    RedRibbon is a comparative analysis tool of differential omics analyses to reveal overlapping features between two differential studies, with high performance, accuracy, and simplicity in use.

Resources

  • Mitochondrial phosphoproteomes are functionally specialized across tissues
    Open Access
    Mitochondrial phosphoproteomes are functionally specialized across tissues

    Fynn M Hansen, Laura S Kremer, Ozge Karayel, Isabell Bludau, Nils-Göran Larsson, Inge Kühl, Matthias Mann

    Fynn M Hansen ... Matthias Mann

    Published 20 November 2023

    This study explores tissue-specific mitochondrial proteomes and phosphoproteomes in unprecedented depth, offering valuable insights into mitochondrial organization and specialization.

Corrections

  • Open Access
    Correction: The coenzyme A precursor pantethine enhances antitumor immunity in sarcoma

    Richard Miallot, Virginie Millet, Anais Roger, Romain Fenouil, Catherine Tardivel, Jean-Charles Martin, Fabrice Tranchida, Laetitia Shintu, Paul Berchard, Juliane Sousa Lanza, Bernard Malissen, Sandrine Henri, Sophie Ugolini, Aurélie Dutour, Pascal Finetti, François Bertucci, Jean-Yves Blay, Franck Galland, Philippe Naquet

    Richard Miallot ... Philippe Naquet

    Published 29 November 2023

    VitB5 level becomes limiting in sarcomas. It is regulated by the pantetheinase activity of VNN1. VNN1 expression in sarcomas is associated with better prognosis and immune infiltration. In mice, complementation with pantethine, a vitB5 precursor, boosts antitumor immunity.

  • Correction: LACTB exerts tumor suppressor properties in epithelial ovarian cancer through regulation of Slug
    Open Access
    Correction: LACTB exerts tumor suppressor properties in epithelial ovarian cancer through regulation of Slug

    Valentina Cutano, Jessica Marianne Ferreira Mendes, Sara Escudeiro-Lopes, Susana Machado, Judith Vinaixa Forner, Juan M Gonzales-Morena, Martin Prevorovsky, Viacheslav Zemlianski, Yuxiong Feng, Petra Kralova Viziova, Andrea Hartmanova, Beata Malcekova, Pavel Jakoube, Sonia Iyer, Zuzana Keckesova

    Valentina Cutano ... Zuzana Keckesova

    Published 6 December 2023

    We show the ability of LACTB to function as a tumor suppressor in ovarian cancer through down-regulation of Slug and induction of differentiation.

Reviewer Index

  • Open Access
    2023 Reviewer Index

    Eric Sawey

    Eric Sawey

    Published 16 January 2024

    The LSA Editors thank these scientists for sharing their time and expertise while reviewing manuscripts in 2023. We sincerely appreciate their support.

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Volume 7, No. 2
February 2024
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