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Table of Contents

October 2023 | Volume 6, No. 10

Research Articles

  • Lsd1 safeguards T-cell development via suppressing endogenous retroelements and interferon responses
    Open Access
    Lsd1 safeguards T-cell development via suppressing endogenous retroelements and interferon responses

    Miaoran Xia, Bingbing Wang, Wujianan Sun, Dengyu Ji, Hang Zhou, Xuefeng Huang, Minghang Yu, Ziyang Su, Ping Chen, Kun Qu, Xi Wang

    Miaoran Xia ... Xi Wang

    Published 10 July 2023

    Bulk and single-cell RNA-seq, combined with ChIP-seq analysis, reveal that the loss of Lsd1 leads to the aberrant depression of endogenous retroelements and subsequent IFN response signaling in thymocytes, which are possible causes of impaired early T cell development.

  • The C-terminal tail of CSNAP attenuates the CSN complex
    Open Access
    The C-terminal tail of CSNAP attenuates the CSN complex

    Maria G Füzesi-Levi, Gili Ben-Nissan, Dina Listov, Yael Fridmann Sirkis, Zvi Hayouka, Sarel Fleishman, Michal Sharon

    Maria G Füzesi-Levi ... Michal Sharon

    Published 17 July 2023

    The study demonstrates inhibition of the COP9 signalosome (CSN) complex by a peptide derived from CSNAP, the smallest CSN subunit. The peptide displaces the endogenous CSNAP subunit from the complex, leading to a CSNAP null phenotype that attenuates CSN activity.

  • Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
    Open Access
    Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior

    Raquel Herrero-Labrador, Joaquín Fernández-Irigoyen, Rebeca Vecino, Candela González-Arias, Karina Ausín, Inmaculada Crespo, Francisco J Fernández Acosta, Vanesa Nieto-Estévez, M José Román, Gertrudis Perea, Ignacio Torres-Alemán, Enrique Santamaría, Carlos Vicario

    Raquel Herrero-Labrador ... Carlos Vicario

    Published 18 July 2023

    A lack of brain-synthesized IGF-I almost completely abrogates hippocampal long-term potentiation (LTP), alters spatial memory and sex-dependent behavior, and produces major changes in the mouse hippocampal proteome.

  • Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions
    Open Access
    Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions

    Valeriia Grudtsyna, Swathi Packirisamy, Tamara C Bidone, Vinay Swaminathan

    Valeriia Grudtsyna ... Vinay Swaminathan

    Published 18 July 2023

    Using fluorescence polarisation microscopy and computational modeling, we find that FA molecules exhibit ECM dependent orientational co-alignment or order. This molecular organizational property in addition to nanoscale localization may explain precise and sensitive decoding of ECM cues.

  • Loss of polarity regulators initiates gasdermin-E-mediated pyroptosis in syncytiotrophoblasts
    Open Access
    Loss of polarity regulators initiates gasdermin-E-mediated pyroptosis in syncytiotrophoblasts

    Khushali Patel, Jasmine Nguyen, Sumaiyah Shaha, Amy Brightwell, Wendy Duan, Ashley Zubkowski, Ivan K Domingo, Meghan Riddell

    Khushali Patel ... Meghan Riddell

    Published 19 July 2023

    Disruption of atypical protein kinase-C isoforms leads to the initiation of pyroptosis, a form of programmed necrosis, in placental syncytiotrophoblasts at the human maternal–fetal interface.

  • Catalytic mechanism of the zinc-dependent MutL endonuclease reaction
    Open Access
    Catalytic mechanism of the zinc-dependent MutL endonuclease reaction

    Kenji Fukui, Tatsuya Yamamoto, Takeshi Murakawa, Seiki Baba, Takashi Kumasaka, Takato Yano

    Kenji Fukui ... Takato Yano

    Published 24 July 2023

    The catalytic mechanism for the DNA cleavage activity of the mismatch repair system endonuclease MutL has been identified, which provides a clue as to how cadmium inhibits its activity.

  • Full-length transcript alterations in human bronchial epithelial cells with <em>U2AF1</em> S34F mutations
    Open Access
    Full-length transcript alterations in human bronchial epithelial cells with U2AF1 S34F mutations

    Cameron M Soulette, Eva Hrabeta-Robinson, Carlos Arevalo, Colette Felton, Alison D Tang, Maximillian G Marin, Angela N Brooks

    Cameron M Soulette ... Angela N Brooks

    Published 24 July 2023

    Using long-read Nanopore cDNA sequencing, this study identifies full-length transcripts associated with U2AF1 S34F mutations revealing effects on translation regulation of specific genes.

  • Reciprocal regulation between the molecular clock and kidney injury
    Open Access
    Reciprocal regulation between the molecular clock and kidney injury

    Carlos Rey-Serra, Jessica Tituaña, Terry Lin, J Ignacio Herrero, Verónica Miguel, Coral Barbas, Anna Meseguer, Ricardo Ramos, Amandine Chaix, Satchidananda Panda, Santiago Lamas

    Carlos Rey-Serra ... Santiago Lamas

    Published 24 July 2023

    The work describes the crosstalk between the circadian rhythm and kidney damage in several mouse genetic models defining that the molecular clock component Cry is important to regulate inflammation, metabolism, and fibrosis.

  • Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops
    Open Access
    Dispersal of PRC1 condensates disrupts polycomb chromatin domains and loops

    Iain Williamson, Shelagh Boyle, Graeme R Grimes, Elias T Friman, Wendy A Bickmore

    Iain Williamson ... Wendy A Bickmore

    Published 24 July 2023

    Endogenous PRC1-mediated chromatin compaction and clustering of polycomb target loci is reversibly perturbed in mESCs by the addition of 1,6 hexanediol, which can disrupt biomolecular condensates.

  • Gene-regulation modules in nonalcoholic fatty liver disease revealed by single-nucleus ATAC-seq
    Open Access
    Gene-regulation modules in nonalcoholic fatty liver disease revealed by single-nucleus ATAC-seq

    Fumihiko Takeuchi, Yi-Qiang Liang, Hana Shimizu-Furusawa, Masato Isono, Mia Yang Ang, Kotaro Mori, Taizo Mori, Eiji Kakazu, Sachiyo Yoshio, Norihiro Kato

    Fumihiko Takeuchi ... Norihiro Kato

    Published 25 July 2023

    This study uncovers cell-type-specific global gene regulation in NAFLD progression, identifying core genes and shedding light on the disease’s molecular mechanisms.

  • Human TLR8 induces inflammatory bone marrow erythromyeloblastic islands and anemia in SLE-prone mice
    Open Access
    Human TLR8 induces inflammatory bone marrow erythromyeloblastic islands and anemia in SLE-prone mice

    Naomi I Maria, Julien Papoin, Chirag Raparia, Zeguo Sun, Rachel Josselsohn, Ailing Lu, Hani Katerji, Mahrukh M Syeda, David Polsky, Robert Paulson, Theodosia Kalfa, Betsy J Barnes, Weijia Zhang, Lionel Blanc, Anne Davidson

    Naomi I Maria ... Anne Davidson

    Published 26 July 2023

    Human TLR8 induces an inflammatory phenotype in BM erythroblastic island central macrophages of lupus-prone Sle1.Yaa mice. Failure to support erythroid precursor adhesion and development induces fatal anemia caused by bone marrow failure followed by hemophagocytosis during stress erythropoiesis.

  • Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis
    Open Access
    Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis

    Lukas A Heger, Nicolas Schommer, Shoichi Fukui, Stijn Van Bruggen, Casey E Sheehy, Long Chu, Sridharan Rajagopal, Dhanalakshmi Sivanandhan, Bruce Ewenstein, Denisa D Wagner

    Lukas A Heger ... Denisa D Wagner

    Published 27 July 2023

    Inhibition of protein arginine deiminase 4 (PAD4), with an orally available inhibitor (JBI-589), prevents the development of hypertrophic cardiomyopathy and diastolic heart failure in murine inflammatory arthritis with reduced neutrophil infiltration, NET deposition, and biomarkers of thromboinflammation in the myocardium.

  • Regulation of hPCL3 isoforms’ ubiquitination by TRIM21 in non-small cell lung cancer progression
    Open Access
    Regulation of hPCL3 isoforms’ ubiquitination by TRIM21 in non-small cell lung cancer progression

    Ye Xu, Wenhong Liu, Xiawei Jiang, Junfeng Li, Qingling Liu, Fang Su, Shanming Ruan, Zhiqian Zhang, Fangfang Tao

    Ye Xu ... Fangfang Tao

    Published 28 July 2023

    hPCL3 isoforms, hPCL3S and hPCL3L, are studied in NSCLC. Elevated expression of both isoforms correlates with poor survival. Inhibiting hPCL3S reduces cell growth, invasion, and migration, suggesting it as a potential therapeutic target.

  • ERK1/2-SOX9/FOXL2 axis regulates ovarian steroidogenesis and favors the follicular–luteal transition
    Open Access
    ERK1/2-SOX9/FOXL2 axis regulates ovarian steroidogenesis and favors the follicular–luteal transition

    Vijay Simha Baddela, Marten Michaelis, Xuelian Tao, Dirk Koczan, Jens Vanselow

    Vijay Simha Baddela ... Jens Vanselow

    Published 2 August 2023

    ERK1/2 negatively regulates estradiol synthesis while positively regulating progesterone production in ovarian granulosa cells via the ERK1/2-SOX9/FOXL2 axis.

  • Basonuclin-2 regulates extracellular matrix production and degradation
    Open Access
    Basonuclin-2 regulates extracellular matrix production and degradation

    Ayla Orang, B Kate Dredge, Chi Yau Liu, Julie M Bracken, Chun-Hsien Chen, Laura Sourdin, Holly J Whitfield, Rachael Lumb, Sarah T Boyle, Melissa J Davis, Michael S Samuel, Philip A Gregory, Yeesim Khew-Goodall, Gregory J Goodall, Katherine A Pillman, Cameron P Bracken

    Ayla Orang ... Cameron P Bracken

    Published 3 August 2023

    Basonuclin-2 (BNC2) is identified as a novel regulator of genes associated with the extracellular matrix and cytokines in fibroblasts. BNC2 is thereby identified as a novel regulator of the tumour microenvironment where its high expression correlates with poor prognosis.

  • PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer
    Open Access
    PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer

    Lara Malik Noureddine, Julien Ablain, Ausra Surmieliova-Garnès, Julien Jacquemetton, Thuy Ha Pham, Elisabetta Marangoni, Anne Schnitzler, Ivan Bieche, Bassam Badran, Olivier Trédan, Nader Hussein, Muriel Le Romancer, Coralie Poulard

    Lara Malik Noureddine ... Coralie Poulard

    Published 3 August 2023

    In triple-negative breast cancer, PRMT5 functions as a master transcriptional coregulator of the glucocorticoid receptor regulating cell migration after dexamethasone treatment. PRMT5 acts in this case as a scaffolding protein independently of its catalytic activity to promote HP1g recruitment.

  • RA-induced prominence-specific response resulted in distinctive regulation of Wnt and osteogenesis
    Open Access
    RA-induced prominence-specific response resulted in distinctive regulation of Wnt and osteogenesis

    Chao Song, Ting Li, Chunlei Zhang, Shufang Li, Songhui Lu, Yi Zou

    Chao Song ... Yi Zou

    Published 4 August 2023

    Early exposure of RA induced altered expressions of Wnt-related genes and subsequent osteogenic differentiation in embryonic mouse craniofacial prominences in a spatiotemporal-dependent manner.

  • Skewed X-inactivation is associated with retinal dystrophy in female carriers of <em>RPGR</em> mutations
    Open Access
    Skewed X-inactivation is associated with retinal dystrophy in female carriers of RPGR mutations

    Muhammad Usman, Christoph Jüschke, Fei Song, Dennis Kastrati, Marta Owczarek-Lipska, Jannis Eilers, Laurenz Pauleikhoff, Clemens Lange, John Neidhardt

    Muhammad Usman ... John Neidhardt

    Published 4 August 2023

    This study shows that skewed X-inactivation modulates the occurrence of Retinitis Pigmentosa in female carriers of RPGR mutations. The findings have implications towards therapeutic interventions.

  • Feto-maternal cholesterol transport regulated by β-Klotho–FGF15 axis is essential for fetal growth
    Open Access
    Feto-maternal cholesterol transport regulated by β-Klotho–FGF15 axis is essential for fetal growth

    Kanako Kobayashi, Kazuko Iwasa, Rika Azuma-Suzuki, Takeshi Kawauchi, Yo-ichi Nabeshima

    Kanako Kobayashi ... Yo-ichi Nabeshima

    Published 4 August 2023

    Inter-tissue communication between β-Klotho in the yolk sac and fibroblast growth factor 15 in the embryo is required to regulate cholesterol supply from maternal blood to embryo through the yolk sac.

  • Generating fast-twitch myotubes in vitro with an optogenetic-based, quantitative contractility assay
    Open Access
    Generating fast-twitch myotubes in vitro with an optogenetic-based, quantitative contractility assay

    Katharina Hennig, David Hardman, David MB Barata, Inês IBB Martins, Miguel O Bernabeu, Edgar R Gomes, William Roman

    Katharina Hennig ... William Roman

    Published 7 August 2023

    We here describe an in vitro contractility assay to control fiber-type composition in muscle cultures.

  • HGF/c-Met/β1-integrin signalling axis induces tunneling nanotubes in A549 lung adenocarcinoma cells
    Open Access
    HGF/c-Met/β1-integrin signalling axis induces tunneling nanotubes in A549 lung adenocarcinoma cells

    Griselda Awanis, Salonee Banerjee, Robert Johnson, Sathuwarman Raveenthiraraj, Aya Elmeligy, Derek Warren, Jelena Gavrilovic, Anastasia Sobolewski

    Griselda Awanis ... Anastasia Sobolewski

    Published 7 August 2023

    Interactions between hepatocyte growth factor (HGF), the c-Met receptor, and β1-integrin induce tunneling nanotubes in A549 cells; paxillin and the downstream MAPK and PI3K pathways and the Arp2/3 complex drive HGF-induced TNT formation.

  • IKBKB reduces huntingtin aggregation by phosphorylating serine 13 via a non-canonical IKK pathway
    Open Access
    IKBKB reduces huntingtin aggregation by phosphorylating serine 13 via a non-canonical IKK pathway

    Cristina Cariulo, Paola Martufi, Margherita Verani, Leticia Toledo-Sherman, Ramee Lee, Celia Dominguez, Lara Petricca, Andrea Caricasole

    Cristina Cariulo ... Andrea Caricasole

    Published 8 August 2023

    Early exposure of RA induced altered expressions of Wnt-related genes and subsequent osteogenic differentiation in embryonic mouse craniofacial prominences in a spatiotemporal-dependent manner.

  • De novo network analysis reveals autism causal genes and developmental links to co-occurring traits
    Open Access
    De novo network analysis reveals autism causal genes and developmental links to co-occurring traits

    Catriona J Miller, Evgeniia Golovina, Joerg S Wicker, Jessie C Jacobsen, Justin M O’Sullivan

    Catriona J Miller ... Justin M O’Sullivan

    Published 8 August 2023

    In this study, we provide a biological argument for looking at an autistic individual’s phenotype as being related to their combined genetic risk for different clusters of traits.

  • Caspase-4 dimerisation and D289 auto-processing elicit an interleukin-1β-converting enzyme
    Open Access
    Caspase-4 dimerisation and D289 auto-processing elicit an interleukin-1β-converting enzyme

    Amy H Chan, Sabrina S Burgener, Kassandra Vezyrgiannis, Xiaohui Wang, Jadie Acklam, Jessica B Von Pein, Malvina Pizzuto, Larisa I Labzin, Dave Boucher, Kate Schroder

    Amy H Chan ... Kate Schroder

    Published 9 August 2023

    The noncanonical inflammasome generates p32/p9 and p34/p9 active caspase-4 species via dimerisation and autocleavage; both species cleave GSDMD to induce pyroptosis, whereas p34/p9 matures IL-1β.

  • High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response
    Open Access
    High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response

    Sandy S Burkart, Darius Schweinoch, Jamie Frankish, Carola Sparn, Sandra Wüst, Christian Urban, Marta Merlo, Vladimir G Magalhães, Antonio Piras, Andreas Pichlmair, Joschka Willemsen, Lars Kaderali, Marco Binder

    Sandy S Burkart ... Marco Binder

    Published 9 August 2023

    This study takes a comprehensive approach to understand the dynamics of the cell-intrinsic response towards virus infection and how viruses actively modulate this.

  • ATP-independent substrate recruitment to proteasomal degradation in mycobacteria
    Open Access
    ATP-independent substrate recruitment to proteasomal degradation in mycobacteria

    Tatjana von Rosen, Monika Pepelnjak, Jan-Philipp Quast, Paola Picotti, Eilika Weber-Ban

    Tatjana von Rosen ... Eilika Weber-Ban

    Published 10 August 2023

    Mycobacterial proteasomes ensure survival during stress by recruiting substrates for degradation via ring-shaped activators. This study elucidates the mechanism of ATP-independent substrate recruitment through the bacterial proteasome activator (Bpa), revealing the determinants for substrate recognition and efficient degradation.

Resources

  • Dissecting morphogenetic apoptosis through a genetic screen in Drosophila
    Open Access
    Dissecting morphogenetic apoptosis through a genetic screen in Drosophila

    Audrey Barbaste, Sonia Schott, Corinne Benassayag, Magali Suzanne

    Audrey Barbaste ... Magali Suzanne

    Published 26 July 2023

    This genetic screen identifies elements of the “morphogenetic apoptosis pathway” potentially involved in the regulation, the orchestration or the impact of the apoptotic process on morphogenesis.

Methods

  • PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cells
    Open Access
    PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cells

    Harshana Rajakaruna, Milie Desai, Jayajit Das

    Harshana Rajakaruna ... Jayajit Das

    Published 28 July 2023

    An experimentally validated protein abundance structured population dynamic model for CAR T cells (PASCAR) that integrates processes from molecules to single cells to cell populations and systematically explores the design space of constitutive and tunable CAR T cells.

  • Refining the genetic risk of breast cancer with rare haplotypes and pattern mining
    Open Access
    Refining the genetic risk of breast cancer with rare haplotypes and pattern mining

    William Letsou, Fan Wang, Wonjong Moon, Cindy Im, Yadav Sapkota, Leslie L Robison, Yutaka Yasui

    William Letsou ... Yutaka Yasui

    Published 4 August 2023

    A closed-pattern mining algorithm helps identify rare, noncontiguous haplotypes underlying breast cancer risk in British women in the UK Biobank.

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Volume 6, No. 10
October 2023
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