Article
Biochemistry & Molecular Biology
Matthew E. Griffin, Linda C. Hsieh-Wilson
Summary: This primer discusses key methods and recent breakthrough technologies for identifying, monitoring, and manipulating glycans in mammalian systems.
Article
Psychology, Mathematical
Wenyuan Yu, Long Ni, Zijian Zhang, Weiqi Zheng, Ye Liu
Summary: The action representation of man-made tools consists of two types: structural action representation and functional action representation. Functional action representation plays a dominant role in fine-grained object recognition, while it is unclear whether the two types of action representation are involved differently in coarse semantic processing. Three experiments were conducted to investigate this. The results suggest that only functional action information is retrieved during fine-grained object processing, while coarse semantic processing does not require the integration of either structural or functional action information.
PSYCHONOMIC BULLETIN & REVIEW
(2023)
Review
Medicine, Research & Experimental
Lijuan Mao, Wei Wei, Jingyu Chen
Summary: Glucocorticoids (GCs) are steroid hormones that regulate various homeostatic functions in the body through the binding of glucocorticoid receptor (GR). GR signals are biased, with variations in different tissue cells, disease states, and ligands. This bias regulation of GR signaling depends on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly, and intercellular differences. Selective GR agonists and modulators (SEGRAMs) have been developed to bias therapeutic outcomes towards expected effects by influencing GR-mediated gene expression. This paper reviews the bias regulation and mechanism of GR, as well as the progress in drug research.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Environmental Sciences
Fabian Sommer, Bettina Sonntag, Nikolai Rastl, Monika Summerer, Barbara Tartarotti
Summary: Climate warming has various impacts on the Alpine region, particularly on winter sports tourism, leading to the construction of mountain reservoirs for artificial snow making. The planktonic communities in these reservoirs are affected not only by the harsh environmental conditions of the alpine region but also by rapid water level fluctuations. This study focused on ciliates and found that their abundance and community composition in the mountain reservoirs were influenced by local factors like pH, nutrients, water transparency, and crustacean predators.
FRONTIERS IN ENVIRONMENTAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Jacek Jasiecki, Monika Targonska, Anna Janaszak-Jasiecka, Magdalena Chmara, Monika Zuk, Leszek Kalinowski, Krzysztof Waleron, Bartosz Wasag
Summary: Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in the LDL receptor (LDLR) gene, leading to an increased risk of cardiovascular diseases. This study developed a single-cell, kinetic, fluorescent LDL uptake assay to analyze the function of LDLR gene variants. It also established a human cell line with LDLR deficiency and a reporter system for studying LDLR gene transcriptional regulation, which can aid in drug testing for atherosclerosis therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dabin Choi, Wesuk Kang, Soyoon Park, Bomin Son, Taesun Park
Summary: For several decades, excessive glucocorticoids (GCs) have been known to inhibit collagen synthesis and accelerate skin aging, but the molecular mechanisms involved are not well understood. In this study, the researchers identified potential glucocorticoid receptor (GR) target genes that may contribute to the inhibition of collagen synthesis. They confirmed that dexamethasone, a synthetic GC, activates canonical GR signaling in dermal fibroblasts and identified six candidate genes involved in the GC-mediated inhibition of collagen synthesis. This study provides insights into the molecular mechanisms of GC-mediated skin aging and lays the foundation for further research on the biological characteristics of individual GR target genes.
Review
Endocrinology & Metabolism
Nicolas C. Nicolaides
Summary: Glucocorticoid receptors play a crucial role in various cellular processes and physiological functions. Recent studies have shown that the beta isoform of the receptor, GR beta, has important functions in cellular homeostasis and is involved in endocrine physiology and pathophysiology.
Article
Biochemistry & Molecular Biology
Wesuk Kang, Dabin Choi, Jiyun Roh, Yearim Jung, Yoojeong Ha, Suhjin Yang, Taesun Park
Summary: This study examined the role of cyclic adenosine monophosphate (cAMP) in the activation of glucocorticoid receptors (GRs) and its associated mechanisms. The results showed that cAMP enhancement did not affect glucocorticoid signaling under normal conditions, but could modulate it in response to stress. The study also revealed that cAMP upregulation triggers the activation of the extracellular signal-regulated kinase (ERK) pathway, which influences GR translocation and activity. These findings highlight the context-dependent role of cAMP signaling in managing glucocorticoid signaling and its potential therapeutic application in stress-related conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Maud Bagnoud, Jana Remlinger, Sandrine Joly, Marine Massy, Anke Salmen, Andrew Chan, Dimitris Karathanassis, Maria-Eleptheria Evangelopoulos, Robert Hoepner
Summary: The study developed a model to predict resistance to glucocorticoid treatment in multiple sclerosis patients by analyzing the expression of 12 genes in whole blood samples. It was found that patients resistant to glucocorticoids have a transcriptome similar to stable patients, and this model could potentially reduce disability development in patients.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Medicine, General & Internal
Greet Van den Berghe, Arno Teblick, Lies Langouche, Jan Gunst
Summary: The traditional model of increased systemic glucocorticoid availability in response to sepsis and hyperinflammation-induced critical illness has been challenged in recent research, revealing a more complex and time-dependent set of responses. Cortisol production driven by ACTH is only temporarily increased, followed by orchestrated peripheral adaptations to maintain increased cortisol availability for target tissues without the need for continued production, along with changes at target tissues to guide cortisol action according to tissue-specific needs.
Review
Biochemistry & Molecular Biology
Ioanna Kokkinopoulou, Paraskevi Moutsatsou
Summary: Mitochondria play a crucial role in cellular processes beyond energy production, being involved in calcium homeostasis, ROS generation, cell death, thermogenesis, and biosynthesis. Glucocorticoids regulate mitochondrial gene expression and metabolism, with GR directly influencing mitochondrial functions including apoptosis and inflammation. Further studies are needed to fully understand the mechanisms of GR translocation and its impact on mitochondrial processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Sirvan Khalighi, Peronne Joseph, Deepak Babu, Salendra Singh, Thomas LaFramboise, Kishore Guda, Vinay Varadan
Summary: SYSMut is an extendable systems biology platform that can infer the biological consequences of gene mutations by integrating multiomics profiles. It has been used to identify driver genes across 29 cancers and discover new therapeutic targets in head and neck squamous cell cancer.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Forestry
Xiaoni Wu, Xudong Ma, Lianyu Hu, Chunjie Shen, Denggao Fu
Summary: Little is known about the consequences of human activities on species assemblages and biodiversity patterns. Our study in mid-Yunnan, China found that species co-occurrence patterns in man-made forests were non-random, while natural secondary forests had higher values of species diversity, functional diversity, community-weighted means, and soil microbial diversity. In conclusion, our results suggest that naturally recovering forests are better than man-made plantations based on biodiversity patterns.
Article
Cell Biology
Clarissa Silva Martins, Margaret de Castro
Summary: This review summarizes the major factors that influence individual glucocorticoid sensitivity/resistance, highlighting the tissue-specific fine-tuning of GC action.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Rachel M. B. Bell, Elisa Villalobos, Mark Nixon, Allende Miguelez-Crespo, Lee Murphy, Angie Fawkes, Audrey Coutts, Matthew G. F. Sharp, Martha Koerner, Emma Allan, Onno C. Meijer, Rene Houtman, Alex Odermatt, Katharina R. Beck, Scott G. Denham, Patricia Lee, Natalie Z. M. Homer, Brian R. Walker, Ruth A. Morgan
Summary: Carbonyl reductase 1 regulates glucocorticoid and mineralocorticoid receptor activation in adipose tissue, influencing glucose homeostasis in lean mice.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Kelly Van Looveren, Steven Timmermans, Tineke Vanderhaeghen, Charlotte Wallaeys, Marlies Ballegeer, Jolien Souffriau, Melanie Eggermont, Jolien Vandewalle, Lise Van Wyngene, Karolien De Bosscher, Claude Libert
Review
Endocrinology & Metabolism
Karolien De Bosscher, Sofie J. Desmet, Dorien Clarisse, Eva Estebanez-Perpina, Luc Brunsveld
NATURE REVIEWS ENDOCRINOLOGY
(2020)
Article
Medicine, Research & Experimental
Jolien Souffriau, Steven Timmermans, Tineke Vanderhaeghen, Charlotte Wallaeys, Kelly Van Looveren, Lindsy Aelbrecht, Sylviane Dewaele, Jolien Vandewalle, Evy Goossens, Serge Verbanck, Filip Boyen, Melanie Eggermont, Lindsey De Commer, Riet De Rycke, Michiel De Bruyne, Raul Tito, Marlies Ballegeer, Sofie Vandevyver, Tiago Velho, Luis Ferreira Moita, Tino Hochepied, Karolien De Bosscher, Jeroen Raes, Filip Van Immerseel, Rudi Beyaert, Claude Libert
EMBO MOLECULAR MEDICINE
(2020)
Article
Multidisciplinary Sciences
B. Maertens, A. Gagnaire, O. Paerewijck, K. De Bosscher, P. Geldhof
Summary: This study investigated how the intestinal microbiome affects the protective Th17 response against Giardia, finding that antibiotic treatment significantly impacted infection dynamics, reduced protective immune markers, and decreased intestinal motility, resulting in decreased parasite clearance.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Jolien Vandewalle, Steven Timmermans, Ville Paakinaho, Lies Vancraeynest, Liza Dewyse, Tineke Vanderhaeghen, Charlotte Wallaeys, Lise Van Wyngene, Kelly Van Looveren, Louise Nuyttens, Melanie Eggermont, Sylviane Dewaele, Tiago R. Velho, Luis F. Moita, Sebastian Weis, Christoph Sponholz, Leo A. van Grunsven, Mieke Dewerchin, Peter Carmeliet, Karolien De Bosscher, Johan Van de Voorde, Jorma J. Palvimo, Claude Libert
Summary: Defects in the glucocorticoid receptor signaling pathway exacerbate sepsis pathophysiology by reducing lactate clearance and sensitizing mice to lactate-induced toxicity, ultimately leading to lethal vascular collapse.
Editorial Material
Multidisciplinary Sciences
Dorien Clarisse, Karolien De Bosscher
Summary: Research suggests that synthetic glucocorticoids used in combination with chemotherapy for solid malignant tumors may lead to cancer resistance, and proposes a potential escape strategy.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lise Van Wyngene, Tineke Vanderhaeghen, Ioanna Petta, Steven Timmermans, Katrien Corbeels, Bart Van der Schueren, Jolien Vandewalle, Kelly Van Looveren, Charlotte Wallaeys, Melanie Eggermont, Sylviane Dewaele, Leen Catrysse, Geert van Loo, Rudi Beyaert, Roman Vangoitsenhoven, Toshinori Nakayama, Jan Tavernier, Karolien De Bosscher, Claude Libert
Summary: The study demonstrates the essential role of ZBTB32 in glucocorticoid production during starvation response, as ZBTB32(-/-) mice fail to increase GC production. This deficiency in GC synthesis is linked to defective cholesterol import and metabolic adaptation abnormalities, leading to progressive weight gain in ZBTB32(-/-) mice. In conclusion, ZBTB32 interacts with GR to regulate adrenal GC production during metabolic adaptation to starvation.
Review
Pharmacology & Pharmacy
Dorien Clarisse, Lisa Deng, Karolien de Bosscher, Achim Lother
Summary: Mineralocorticoid receptor antagonists are effective therapies for cardiovascular and renal diseases, but their widespread clinical use is limited by the risk of hyperkalaemia. New strategies are needed to selectively target the harmful effects of the mineralocorticoid receptor while preserving its physiological function.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tineke Vanderhaeghen, Steven Timmermans, Deepika Watts, Ville Paakinaho, Melanie Eggermont, Jolien Vandewalle, Charlotte Wallaeys, Lise Van Wyngene, Kelly Van Looveren, Louise Nuyttens, Sylviane Dewaele, Joke Vanden Berghe, Kelly Lemeire, Joey De Backer, Laura Dirkx, Wim Vanden Berghe, Guy Caljon, Bart Ghesquiere, Karolien De Bosscher, Ben Wielockx, Jorma J. Palvimo, Rudi Beyaert, Claude Libert
Summary: The study found that hypoxia impacts the hepatic response of glucocorticoid receptors to dexamethasone in mice, leading to three types of reprogramming of GR: weaker induction of classical GR-responsive genes, induction of specific genes in hypoxia, and activation of a group of genes by the HPA axis under hypoxia. Additionally, hypoxia-induced activation of the HPA axis is associated with GR-dependent lipolysis and ketogenesis.
Article
Biochemistry & Molecular Biology
Steven Timmermans, Nicolette J. D. Verhoog, Kelly Van Looveren, Sylviane Dewaele, Tino Hochepied, Melanie Eggermont, Barbara Gilbert, Anne Boerema-de Munck, Tineke Vanderhaeghen, Joke Vanden Berghe, Natalia Garcia Gonzalez, Jolien Vandewalle, Yehudi Bloch, Mathias Provost, Savvas N. Savvides, Karolien De Bosscher, Wim Declercq, Robbert J. Rottier, Ann Louw, Claude Libert
Summary: The GR(dim/dim) mice with reduced dimerization propensity have helped define the functions of GR monomers and dimers, while the newly generated GR(D+L/D+L) mice exhibit insufficient ligand binding, leading to perinatal lethality.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Kato Bredael, Silke Geurs, Dorien Clarisse, Karolien De Bosscher, Matthias D'hooghe
Summary: Lead optimization involves the fine-tuning of lead compounds to improve their drug-like properties. This literature overview focuses on the use of bioisosteres to replace the carboxylic acid functionality, which is commonly associated with poor pharmacokinetic properties and toxicity. By replacing this functionality, the activity and pharmacokinetic properties of the lead compounds can be maintained or even enhanced.
JOURNAL OF CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Laura Van Moortel, Jonathan Thommis, Brecht Maertens, An Staes, Dorien Clarisse, Delphine De Sutter, Claude Libert, Onno C. Meijer, Sven Eyckerman, Kris Gevaert, Karolien De Bosscher
Summary: In this study, the researchers characterized a set of diverse glucocorticoid receptor ligands and found that monitoring GR Ser211 phosphorylation levels can reliably predict compound effects on endogenous GR target genes.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Luz Andreone, Florencia Fuertes, Carolina Setula, Andres E. Barcala Tabarrozzi, Miranda S. Orellano, Ricardo A. Dewey, Rita Bottino, Karolien De Bosscher, Marcelo J. Perone
Summary: This study suggests that CpdA has therapeutic potential for T1D cellular and animal models. CpdA can improve ER stress, promote the survival and function of beta-cells in a proinflammatory cytokine environment, delay disease onset, and reduce diabetes incidence.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Silke Geurs, Dorien Clarisse, Freya Baele, Jorick Franceus, Tom Desmet, Karolien De Bosscher, Matthias D'hooghe
Summary: In this study, a set of HDAC6-selective inhibitors with low side effects and significant inhibitory activity in the nanomolar range were successfully synthesized using a lean inhibitor strategy.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jacobus C. Buurstede, Susana N. Paul, Karolien De Bosscher, Onno C. Meijer, Jan Kroon
Summary: Glucocorticoids exert their effects by activating the glucocorticoid receptor (GR) throughout the body. This study investigated the interaction between glucocorticoids and androgen signaling in the liver transcriptome. The results showed that a substantial proportion of the hepatic transcriptome is androgen-dependent after chronic exposure, while the effects of glucocorticoids are largely androgen-independent after acute exposure. The study suggests that prolonged glucocorticoid exposure may upregulate androgen receptor expression, leading to androgen dependence not driven by direct interactions between the androgen receptor and glucocorticoid receptor.
