Article
Multidisciplinary Sciences
Amanda K. Casey, Hillery F. Gray, Suneeta Chimalapati, Genaro Hernandez, Andrew T. Moehlman, Nathan Stewart, Hazel A. Fields, Burak Gulen, Kelly A. Servage, Karoliina Stefanius, Aubrie Blevins, Bret M. Evers, Helmut Kramer, Kim Orth
Summary: Protein homeostasis is crucial for cellular health, and imbalanced unfolded protein response (UPR) can lead to inflammation and cellular damage. The enzyme filamentation induced by cyclic-AMP (Fic) modulates UPR response by posttranslational modification of binding immunoglobulin protein (BiP). Loss of Fic affects vision, UPR activation, and stress recovery. This study highlights the importance of Fic-mediated AMPylation in the mammalian pancreas during physiological stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mercedes Viettri, Jose L. Zambrano, Romel Rosales, Gerson I. Caraballo, Ana Lorena Gutierrez-Escolano, Juan E. Ludert
Summary: The study investigated whether infection with dengue and Zika viruses triggers a Golgi stress response in vertebrate and mosquito cells, showing that these viruses induce expansion of the Golgi complex and activation of the TFE3 pathway.
SCIENTIFIC REPORTS
(2021)
Review
Endocrinology & Metabolism
Yong Zhou, Yang Jin, Yuan Wang, Ruijin Wu
Summary: Endometriosis is a chronic gynecological disease with an unclear cause. Hypoxia is closely related to the occurrence and development of the disease, with hypoxia-inducible factor-1 alpha playing a key role and the unfolded protein response supplementing cell survival under hypoxic stress.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jonathan Turpin, Daed El-Safadi, Gregorie Lebeau, Etienne Frumence, Philippe Despres, Wildriss Viranaicken, Pascale Krejbich-Trotot
Summary: Zika virus manipulates cellular responses to delay apoptosis and optimize virus production; by impairing the expression of CHOP/DDIT3 at a translational level, ZIKV inhibits ER stress-driven apoptosis; ZIKV relies on cellular machinery and the unfolded protein response to complete its viral cycle, posing a threat to human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Plant Sciences
Yao Liu, Yonglun Lv, An Wei, Mujin Guo, Yanjie Li, Jiaojiao Wang, Xinhua Wang, Yan Bao
Summary: This article reviews the unfolded protein response (UPR), one of the systematic strategies used by eukaryotic cells to respond to endoplasmic reticulum (ER) stress. The UPR plays a crucial role not only in stress response, but also in plant growth and development.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Ojore Benedict Valentine Oka, Arvin Shedrach Pierre, Marie Anne Pringle, Wanida Tungkum, Zhenbo Cao, Bethany Fleming, Neil John Bulleid
Summary: The unfolded protein response (UPR) regulates cellular proteostasis by activating and trafficking the ATF6 alpha sensor. After ER stress, ATF6 alpha undergoes a redox switch to form a disulfide bonded dimer, which is then transported to the Golgi for cleavage. Overexpression of ERp18 affects dimer formation and limits Golgi trafficking.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Plant Sciences
Navpreet Kaur, Pramod Kaitheri Kandoth
Summary: This study identified and characterized the tomato bZIP60 (SlbZIP60) and showed that it undergoes splicing in response to ER stress-inducing agent tunicamycin, as well as in certain plant tissues in a physiologically activated manner. SlbZIP60 also responds to environmental stresses, heat, and virus infection.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Kai Huang, Tao Zhang, Wenjun Zhang, Yue Gu, Pan Yu, Lanqing Sun, Zhiwei Liu, Tao Wang, Ying Xu
Summary: Mistimed food intake disrupts circadian rhythms in peripheral tissues and increases the risk of metabolic diseases. This study establishes a 10-generation mouse model to investigate the effects of continuous daytime-restricted feeding (DRF). The results show that mistimed food intake leads to cumulative effects on ER stress sensitivity over generations in mice.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Teresa Borrello, Patricia Santofimia-Castano, Marco Bocchio, Angela Listi, Nicolas Fraunhoffer, Philippe Soubeyran, Eric Chevet, Christopher Pin, Juan Iovanna
Summary: This study uncovers a new role for NUPR1 in the unfolded protein response and the integrated stress response, involving interaction with eIF2 alpha to promote efficient stress response. Loss of NUPR1 leads to sustained eIF2 alpha phosphorylation and slower poststress protein synthesis recovery in cells.
Review
Cell Biology
Md. Sahab Uddin, Wing Shan Yu, Lee Wei Lim
Summary: Alzheimer's disease is characterized by the accumulation of misfolded proteins due to changes in protein homeostasis, possibly stemming from endoplasmic reticulum stress. The unfolded protein response is a critical signaling cascade that helps reduce misfolded proteins, but age-related changes in ER chaperones and enzymes can disrupt this process. The accumulation of misfolded proteins in AD, caused by sustained cellular stress, leads to neurodegeneration and neuronal death.
AGEING RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Yiting Lu, Xiaochun Jiang, Heng Ai, Danting Li, Afrasiyab Khattak, Bei Zhang, Xu Liu, Hualing Zhang, Shoujun Huang
Summary: This study demonstrated the important role of BmUFM1 in the regulation of unfolded protein response and the replication of BmNPV in silkworm. It provides insights into the conjugation machinery of UFM1 and suggests a potential molecular target for BmNPV prevention and silkworm breeding.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Gehan Botrus, Richard M. Miller, Pedro Luiz Serrano Uson Jr, Geoffrey Kannan, Haiyong Han, Daniel D. Von Hoff
Summary: High levels of ER stress and UPR activation are present in pancreatic cancer, leading to adaptive mechanisms and potential apoptosis. This review discusses the mechanisms by which compounds activate the UPR pathways and induce apoptosis, and explores the potential of ER stress inducers for anti-tumor efficacy in pancreatic cancer. A new approach of increasing ER stress and UPR activation to incite apoptotic cell death in pancreatic cancer is hypothesized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Larissa Milano, Clara F. Charlier, Rafaela Andreguetti, Thomas Cox, Eleanor Healing, Marcos P. Thome, Ruan M. Elliott, Leona D. Samson, Jean-Yves Masson, Guido Lenz, Joao Antonio P. Henriques, Axel Nohturfft, Lisiane B. Meira
Summary: The study investigates the effects of the alkylating agent MMS on gene expression in mouse liver using mice deficient in the enzyme Aag. It shows that Aag deficiency leads to a reduction in the cellular stress response induced by alkylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Plant Sciences
June-Sik Kim, Keiichi Mochida, Kazuo Shinozaki
Summary: This review provides an overview of the current knowledge on ER stress sensing, activation, and downstream regulation of the unfolded protein response (UPR). Recent studies have shown that the UPR is also involved in plant growth and development, and it modulates both plant growth and stress tolerance by maintaining ER homeostasis.
Article
Gastroenterology & Hepatology
Michelle M. Cooley, Diana D. H. Thomas, Kali Deans, Yajing Peng, Aurelia Lugea, Stephen J. Pandol, Luigi Puglielli, Guy E. Groblewski
Summary: The study demonstrated that down-regulation of AT-1 during pancreatitis leads to chronic ER stress and pancreatic inflammation. Loss of AT-1 induces activation of unfolded protein response pathways and causes pancreatic disease characterized by intracellular trypsin accumulation, immune cell infiltration, and fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ulla Sovio, Neil Goulding, Nancy McBride, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Debbie A. Lawlor, Gordon C. S. Smith
Article
Microbiology
Francesca Gaccioli, Susanne Lager, Marcus C. de Goffau, Ulla Sovio, Justyna Dopierala, Sungsam Gong, Emma Cook, Andrew Sharkey, Ashley Moffett, Wai Kwong Lee, Christian Delles, Cristina Venturini, Judith Breuer, Julian Parkhill, Sharon J. Peacock, D. Stephen Charnock-Jones, Gordon C. S. Smith
NATURE MICROBIOLOGY
(2020)
Article
Neurosciences
Susanne Lager, Ulla Sovio, Elizabeth Eddershaw, Margaretha W. van der Linden, Cansu Yazar, Emma Cook, Lisa Happerfield, Flora A. Jessop, Neil J. Sebire, D. Stephen Charnock-Jones, Gordon C. S. Smith
JOURNAL OF PHYSIOLOGY-LONDON
(2020)
Article
Biology
Malwina Prater, Russell S. Hamilton, Hong Wa Yung, Andrew M. Sharkey, Paul Robson, N. Erlyani Abd Hamid, Eric Jauniaux, D. Stephen Charnock-Jones, Graham J. Burton, Tereza Cindrova-Davies
Summary: The human placenta undergoes significant changes in gene expression and DNA methylation patterns in response to shifts in nutrition and oxygen concentration during early pregnancy. Early placental cells primarily focus on hormone synthesis and oxygen transport, while later in pregnancy they are more involved in the transport of oxygen, lipids, and other substances.
Review
Obstetrics & Gynecology
Irving L. M. H. Aye, Catherine E. Aiken, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: This article discusses the metabolic basis for placental dysfunction and proposes that alterations in energy metabolism may explain various placental phenotypes in preeclampsia. It also suggests that placental metabolic reprogramming may be associated with severe preeclampsia phenotypes.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2022)
Article
Endocrinology & Metabolism
Ulla Sovio, Neil Goulding, Nancy McBride, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Deborah A. Lawlor, Gordon C. S. Smith
Summary: The study found that a metabolite ratio originally developed for predicting FGR also accurately predicts LGA birth weight and is inversely associated with birth weight across the whole range.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Ulla Sovio, Gemma L. Clayton, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Deborah A. Lawlor, Gordon C. S. Smith
Summary: By analyzing metabolomics, we identified 4 strongly and independently predictive metabolites for gestational diabetes mellitus, which could have clinical utility in screening for the condition.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Correction
Multidisciplinary Sciences
Tim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, D. Stephen Charnock-Jones, Gordon C. S. Smith, Sam Behjati
Article
Biology
Irving L. M. H. Aye, Sungsam Gong, Giulia Avellino, Roberta Barbagallo, Francesca Gaccioli, Benjamin J. Jenkins, Albert Koulman, Andrew J. Murray, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: The function and dysfunction of the placenta differ between sexes, but the mechanisms responsible for this are unknown. This study reveals that differences in polyamine metabolism are associated with the escape from X chromosome inactivation of the gene encoding spermine synthase (SMS), which helps explain some of the sex differences observed in human placenta.
COMMUNICATIONS BIOLOGY
(2022)
Article
Peripheral Vascular Disease
Francesca Gaccioli, Ulla Sovio, Sungsam Gong, Emma Cook, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: This study aimed to investigate the relationship between protein levels of sFLT1 and PlGF in maternal serum and placental tissue lysates. The findings showed that the sFLT1:PlGF ratio is increased in both preeclampsia and FGR, but in preeclampsia, it is primarily driven by increased placental sFLT1 levels, while in FGR, it is primarily driven by decreased placental PlGF levels.
Article
Cell Biology
Giulia Avellino, Ruhi Deshmukh, Stephanie N. Rogers, D. Stephen Charnock-Jones, Gordon C. S. Smith, Saverio Tardito, Irving L. M. H. Aye
Summary: Human trophoblast cultures are important for studying placental development. However, current in vitro studies using commercial media with nonphysiological nutrient levels have unknown effects on trophoblast metabolism and function. This study shows that a physiological medium called Plasmax, which mimics human plasma, improves the proliferation and differentiation of human trophoblast stem cells (hTSCs) compared to standard medium (DMEM-F12). hTSCs cultured in Plasmax-based medium also exhibit altered metabolism and reduced S-adenosylmethionine/S-adenosyl-homocysteine ratio. These findings highlight the importance of the nutritional environment for phenotyping cultured human trophoblasts.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Obstetrics & Gynecology
Ulla Sovio, Francesca Gaccioli, Emma Cook, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: This study aimed to determine the inter-relationships between five first-trimester biomarkers and a range of adverse pregnancy outcomes. The results showed that these biomarkers were associated with fetal growth restriction, preterm birth, and preeclampsia, indicating heterogeneity in the underlying pathophysiological pathways for different types of adverse pregnancy outcomes.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Roshan J. Selvaratnam, Ulla Sovio, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: Consistent exposure to smoking throughout pregnancy is strongly associated with spontaneous preterm birth and fetal growth restriction. High levels of paraxanthine are not independently associated with any of the studied outcomes and are confounded by smoking.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Biochemical Research Methods
Hong Wa Yung, Graham J. Burton, D. Stephen Charnock-Jones
Summary: This article presents a protocol for culturing the endocrine junctional zone of the mouse placenta, allowing the study of placental signals on maternal physiology. The method involves dissecting and separating layers and using serum-free medium for culture.
Article
Obstetrics & Gynecology
Yasmina Al Ghadban, Yuheng Du, D. Stephen Charnock-Jones, Lana X. Garmire, Gordon C. S. Smith, Ulla Sovio
Summary: This study identified and internally validated metabolites predictive of spontaneous preterm birth using multiple machine learning methods and sequential maternal serum samples. A lysolipid was found to be a novel predictor of preterm birth and early term birth.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2023)