Article
Biochemistry & Molecular Biology
Xiaomeng Liu, Niuben Cao, Xinchan Liu, Yu Deng, Yu Xin, Ruobing Fu, Xirui Xin, Yubo Hou, Weixian Yu
Summary: Circadian rhythms play a crucial role in regulating the body's homeostasis, and circadian rhythm disorders can have detrimental effects on metabolic and immune functions. However, the relationship between circadian rhythm disorders and periodontitis has not been well studied. This research aimed to investigate the role of the circadian rhythm control gene BMAL1 in periodontitis. The results showed that downregulation of BMAL1 in circadian rhythm disorder-induced periodontitis led to significant alveolar bone resorption, increased osteoclast differentiation, upregulation of the inflammatory signaling molecule NF-kappa B, elevated apoptosis and oxidative stress levels in periodontal tissues. This study suggests that BMAL1 is a key regulator in periodontitis exacerbated by circadian rhythm disorders, highlighting a potential avenue for periodontitis treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell Biology
Ueli Schibler
Summary: Mammalian body cells have cell-autonomous and self-sustained circadian oscillators relying on delayed negative feedback loops in gene expression. Transcriptional activation and repression, as well as post-translational mechanisms like phosphorylation and dephosphorylation, play crucial roles in setting the pace of these timekeepers. The study by Klemz and colleagues in Genes & Development demonstrates how dephosphorylation of BMAL1 by protein phosphatase 4 (PPP4) participates in the modulation of circadian timing.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Jiayang Zhang, Chengcheng Liu, Qing Liang, Feng Zheng, Youfei Guan, Guangrui Yang, Lihong Chen
Summary: The study revealed a significant role of the core clock gene Bmal1 in tubulointerstitial fibrosis, possibly mediated through its interaction with Gli2.
Article
Multidisciplinary Sciences
Celia A. McKee, Alexander J. Polino, Melvin W. King, Erik S. Musiek
Summary: The circadian clock is found to play a new role in autophagy and lysosome function, suggesting new directions for studying neurodegeneration. Circadian clock proteins coordinate gene expression programs involved in daily rhythms and cellular processes. The depletion of the core clock protein BMAL1 in astrocytes disrupts circadian function and leads to a unique cell-autonomous activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C. Fiorenza, Irem Kaymak, Anna K. Fritzsche, Erik D. Herzog, Ralf Stanewsky, Achim Kramer
Summary: In organisms with circadian clocks, the post-translational modifications of clock proteins, particularly phosphorylation, play a crucial role in controlling circadian rhythms. Protein phosphatase 4 (PPP4) and its regulatory subunit PPP4R2 have been identified as critical components in mammals and Drosophila, affecting the circadian system by regulating phosphorylation and transactivation activity of CLOCK/BMAL1.
GENES & DEVELOPMENT
(2021)
Article
Immunology
Zainab Taleb, Vania Carmona-Alcocer, Kyle Stokes, Marta Haireek, Huaqing Wang, Stephen M. Collins, Waliul I. Khan, Phillip Karpowicz
Summary: Circadian disruption is associated with increased risk of inflammatory bowel disease (IBD), as shown by studies on mice lacking a functional circadian clock. The severity of colitis in these mice is worsened and their recovery impaired. Inflammation, immune cell infiltration, and epithelial cell proliferation in the colon all exhibit daily rhythms, which are disrupted in mice without a functioning circadian clock. These findings highlight the importance of a functional circadian clock in the colon for inflammation and healing.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zelin Zhang, Jianyong Cheng, Li Yang, Xiaoya Li, Rongmao Hua, Dejun Xu, Zhongliang Jiang, Qingwang Li
Summary: Nicotine induces ferroptosis in testicular cells by downregulating Nrf2 through Bmal1-mediated transcriptional regulation, leading to imbalance of redox state and accumulation of ROS. This study provides a potential mechanism for preventing male reproductive injury caused by smoking or cigarette smoke.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Endocrinology & Metabolism
Yin Jiang, Shiping Li, Wenming Xu, Junjie Ying, Yi Qu, Xiaohui Jiang, Ayuan Zhang, Yan Yue, Ruixi Zhou, Tiechao Ruan, Jinhui Li, Dezhi Mu
Summary: BMAL1 plays a vital role in reproductive physiology, as its knockout results in infertility in mice, with impaired reproductive organs, hormone secretion and signaling, and gonadal steroidogenesis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sang Ah Yi, Ye Ji Jeon, Min Gyu Lee, Ki Hong Nam, Sora Ann, Jaecheol Lee, Jeung-Whan Han
Summary: This study reveals that S6K1 plays a central role in regulating the production of adiponectin, a hormone derived from fat cells that has beneficial effects on metabolism. S6K1 controls adiponectin expression by inducing a transcriptional switch between two transcriptional machineries, BMAL1 and EZH2. Mechanistically, S6K1 induces a suppressive histone code cascade, leading to suppression of adiponectin expression. Upon fasting, inactivation of S6K1 promotes adiponectin expression by inducing a transcriptional switch from EZH2 to BMAL1. These findings provide insights into the regulatory machinery controlling adiponectin production and may guide the development of treatments for metabolic disorders.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Matteo Astone, Roxana E. Oberkersch, Giovanni Tosi, Alberto Biscontin, Massimo M. Santoro
Summary: This study demonstrates that endothelial cells possess an endogenous circadian clock, and core clock genes exhibit robust circadian oscillations. Impairing the function of the circadian clock transcriptional activator BMAL1 leads to angiogenesis defects in both developmental and pathological contexts. BMAL1 regulates endothelial cell cycle progression by binding to the promoters of CCNA1 and CDK1 genes.
CARDIOVASCULAR RESEARCH
(2023)
Article
Medicine, Research & Experimental
Shuai Wang, Yanke Lin, Lu Gao, Zemin Yang, Jingpan Lin, Shujing Ren, Feng Li, Jing Chen, Zhigang Wang, Zhiyong Dong, Pinghua Sun, Baojian Wu
Summary: Growing evidence suggests that circadian clock and obesity are intertwined, but the underlying mechanism is poorly understood. This study investigated the link between circadian clock and obesity, and found that obesity causes perturbance of the circadian clock in white adipose tissue (WAT). Reduced levels of glutamine and methionine in obese WAT were associated with decreased histone acetylation and methylation at the Bmal1 promoter. It was also found that impaired expression of PPAR-gamma in obesity led to downregulation of SLC1A5, resulting in reduced uptake of glutamine and methionine. These findings suggest that PPAR-gamma integrates obesity and adipocyte clock, promoting a vicious cycle between circadian disruption and obesity development.
Article
Multidisciplinary Sciences
Yasuhiro Umemura, Nobuya Koike, Yoshiki Tsuchiya, Hitomi Watanabe, Gen Kondoh, Ryoichiro Kageyama, Kazuhiro Yagita
Summary: Circadian clocks are suppressed during early embryonic stages and pluripotent stem cells in mammals, but gradually emerge during ontogenesis. The expression of CLOCK/BMAL1 affects the oscillation of the segmentation clock, which controls somitogenesis in the early developmental stage.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Gene Ryan Crislip, Stephanie E. Wohlgemuth, Christopher A. Wolff, Miguel A. Gutierrez-Monreal, Collin M. Douglas, Elnaz Ebrahimi, Kit-Yan Cheng, Sarah H. Masten, Dominique Barral, Andrew J. Bryant, Karyn A. Esser, Michelle L. Gumz
Summary: The study found that iMS-BMAL1 KO mice exhibited an aging phenotype with no renal phenotype, and their response to low potassium diet and phase advance in renal function was similar to the control group, indicating that disruption of the clock in skeletal muscle does not lead to significant renal injury.
Article
Psychiatry
Su Been Lee, Jihyun Park, Yongdo Kwak, Young-Un Park, Truong Thi My Nhung, Bo Kyoung Suh, Youngsik Woo, Yeongjun Suh, Eunbyul Cho, Sehyung Cho, Sang Ki Park
Summary: DISC1 plays a crucial role in regulating neuronal activity and circadian rhythm by inhibiting GSK3 beta activity and affecting BMAL1 stability. Deficiency of Disc1 results in decreased expression of circadian genes and disrupted circadian physiology and behaviors in mice.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Baharan Fekry, Aleix Ribas-Latre, Rachel Van Drunen, Rafael Bravo Santos, Samay Shivshankar, Yulin Dai, Zhongming Zhao, Seung-Hee Yoo, Zheng Chen, Kai Sun, Frances M. Sladek, Mamoun Younes, Kristin Eckel-Mahan
Summary: This study reveals the antagonistic effects of HNF4 alpha and BMAL1 in liver disease and HCC. Simultaneous loss of HNF4 alpha and BMAL1 protects against fatty liver and HCC. Furthermore, targeting BMAL1 expression in the absence of HNF4 alpha inhibits HCC growth and progression.
Article
Genetics & Heredity
Lev Prasov, Brenda L. Bohnsack, Antonette S. El Husny, Lam C. Tsoi, Bin Guan, J. Michelle Kahlenberg, Edmundo Almeida, Haitao Wang, Edward W. Cowen, Adriana A. De Jesus, Priyam Jani, Allison C. Billi, Sayoko E. Moroi, Rachael Wasikowski, Izabela Almeida, Luciana N. Almeida, Fernando Kok, Sarah J. Garnai, Shahzad Mian, Marcus Y. Chen, Blake M. Warner, Carlos R. Ferreira, Raphaela Goldbach-Mansky, Sun Hur, Brian P. Brooks, Julia E. Richards, Robert B. Hufnagel, Johann E. Gudjonsson
Summary: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder characterized by features such as juvenile open-angle glaucoma, psoriasiform skin rash, and aortic calcifications. A study identified a novel DDX58 variant, expanding the genotypic spectrum of the disease. Furthermore, detailed ocular and dermatological phenotypes were described for the first time, shedding light on the molecular pathogenesis of SGMRT.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Allergy
Lam C. Tsoi, Matthew T. Patrick, Shao Shuai, Mrinal K. Sarkar, Sunyi Chi, Bethany Ruffino, Allison C. Billi, Xianying Xing, Ranjitha Uppala, Cheng Zang, Joseph Fullmer, Zhi He, Emanual Maverakis, Nehal N. Mehta, Bethany E. Perez White, Spiro Getsios, Yolanda Helfrich, John J. Voorhees, J. Michelle Kahlenberg, Stephan Weidinger, Johann E. Gudjonsson
Summary: This study evaluates the use of baseline molecular expression profiling to assess treatment outcome for patients with psoriasis. The results show a correlation between clinical response and molecular changes, particularly for genes responding to IL-17A/TNF in keratinocytes. Baseline gene expressions in nonlesional skin were found to be the best marker of treatment response, and cytokine gene signatures enriched in baseline nonlesional skin had strong correlations with treatment improvement.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Dermatology
Lam C. Tsoi, Xianying Xing, Enze Xing, Rachael Wasikowski, Shuai Shao, Chang Zeng, Olesya Plazyo, Joseph Kirma, Yanyung Jiang, Allison C. Billi, Mrinal K. Sarkar, Jessica L. Turnier, Ranjitha Uppala, Kathleen M. Smith, Yolanda Helfrich, John J. Voorhees, Emanual Maverakis, Robert L. Modlin, J. Michelle Kahlenberg, Victoria E. Scott, Johann E. Gudjonsson
Summary: This study demonstrates that tape stripping with optimized high-resolution transcriptomic profiling can effectively assess and characterize inflammatory responses in the skin. By comparing different samples and sampling methods, the study shows that tape stripping can capture the transcriptome of the upper layers of the skin, providing insights into the molecular components of the immune amplification pathway in psoriasis. Additionally, the study suggests that nonlesional psoriatic skin exhibits activated, proinflammatory changes, which are not captured by full-thickness skin biopsy transcriptome profiling.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Cell Biology
Filipa Rijo-Ferreira, Joseph S. Takahashi
Summary: Many organisms have evolved timekeeping mechanisms to optimize cellular functions and anticipate environmental changes. Recent research has focused on the interactions between hosts and microbes, with a specific emphasis on how circadian clocks modulate these interactions.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Victoria Acosta-Rodriguez, Filipa Rijo-Ferreira, Mariko Izumo, Pin Xu, Mary Wight-Carter, Carla B. Green, Joseph S. Takahashi
Summary: Research shows that the interval of fasting and circadian alignment of feeding are important factors in extending lifespan under CR; nighttime CR can alleviate inflammation and metabolic pathway damage caused by aging; circadian interventions promote longevity.
Review
Biochemistry & Molecular Biology
Emil Sjulstok Rasmussen, Joseph S. Takahashi, Carla B. Green
Summary: The circadian clock is an intracellular timekeeping device that regulates daily rhythms in the body through a core transcription/translation negative feedback loop and additional interlocking feedback loops. Pharmacological manipulation of the clock may be beneficial for treating various diseases such as jet lag, shift work and sleep disorders, metabolic diseases, and cancer.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Pin Xu, Kazuhiro Shimomura, Changhoon Lee, Xiaofei Gao, Eleanor H. Simpson, Guocun Huang, Chryshanthi M. Joseph, Vivek Kumar, Woo-Ping Ge, Karen S. Pawlowski, Mitchell D. Frye, Said Kourrich, Eric R. Kandel, Joseph S. Takahashi
Summary: Through in vivo mutagenesis screening, researchers identified a mutation in the Kcnc3 gene that leads to spatial learning deficits. Further investigation revealed that this mutation results in the loss of function in voltage-gated potassium channels, affecting conductance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Shuzhang Yang, Shin Yamazaki, Kimberly H. Cox, Yi-Lin Huang, Evan W. Miller, Joseph S. Takahashi
Summary: This study reports the discovery of temperature-sensitive ultradian rhythms in mammalian fibroblasts, which are independent of the cell cycle and circadian clock. These ultradian rhythms are synchronized through cellular coupling and metabolic feedback mechanisms, and play a role in balancing energy demands in cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Dermatology
Alina I. Marusina, Antonio Ji-Xu, Stephanie T. Le, Atrin Toussi, Lam C. Tsoi, Qinyuan Li, Guillaume Luxardi, Jordan Nava, Lauren Downing, Annie R. Leal, Nikolay Y. Kuzminykh, Olga Kruglinskaya, Marie-Charlotte Bruggen, Iannis E. Adamopoulos, Alexander A. Merleev, Johann E. Gudjonsson, Emanual Maverakis
Summary: ERAP1, ERAP2, and LNPEP, which are aminopeptidases, play a role in autoimmune diseases. The expression of ERAP2 is increased while ERAP1 is decreased in psoriasis patients with autoimmune-linked variants of ERAP. Different layers of skin cells show different expression patterns of aminopeptidases, and in psoriasis, basal keratinocytes also express CCL2 and IL-15. In addition, ERAP2-high skin fibroblasts also express more CXCL14.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Letter
Dermatology
Jake R. Saklatvala, Ken B. Hanscombe, Satveer K. Mahil, Lam C. Tsoi, James T. Elder, Jonathan N. Barker, Michael A. Simpson, Catherine H. Smith, Nick Dand
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Henry W. Chen, Jane L. Zhu, Viktor Martyanov, Lam C. Tsoi, Michael E. Johnson, Grant Barber, Dillon Popovich, Jack C. O'Brien, Jennifer Coias, Nika Cyrus, Neeta Malviya, Stephanie Florez-Pollack, Elaine Kunzler, Gregory A. Hosler, Johann E. Gudjonsson, Dinesh Khanna, Michael Whitfield, Heidi T. Jacobe
Summary: Morphea is a skin-directed process characterized by T helper 1 immune-mediated dysregulation, which contrasts with fibrotic signatures and systemic transcriptional changes associated with systemic sclerosis. The similarity between morphea and the inflammatory subset of systemic sclerosis on transcriptional profiling indicates that therapies under development for this subset of systemic sclerosis are also promising for treatment of morphea.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Letter
Dermatology
Kotaro Ogawa, Lam C. Tsoi, Hiroaki Tanaka, Masahiro Kanai, Philip E. Stuart, Rajan P. Nair, Yoshiya Tanaka, Hideki Mochizuki, James T. Elder, Yukinori Okada
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Clinical Neurology
Peter Sguigna, Sabeen Toranian, Lauren M. Tardo, Kyle M. Blackburn, Lindsay A. Horton, Darrel Conger, Ethan Meltzer, R. Nick Hogan, Morgan C. McCreary, Phyllis C. Zee, Joseph S. Takahashi, Benjamin M. Greenberg
Summary: This study investigated the prevalence and causes of excessive daytime sleepiness (EDS) in multiple sclerosis (MS) patients. After excluding patients with sleep disorders, it was found that EDS was not associated with age, sex, disease severity, or optic nerve damage, but was associated with visual dysfunction.
MULTIPLE SCLEROSIS JOURNAL-EXPERIMENTAL TRANSLATIONAL AND CLINICAL
(2023)
Article
Veterinary Sciences
Ikuo Miura, Yoshiaki Kikkawa, Shumpei P. Yasuda, Akiko Shinogi, Daiki Usuda, Vivek Kumar, Joseph S. Takahashi, Masaru Tamura, Hiroshi Masuya, Shigeharu Wakana
Summary: The study investigated single nucleotide polymorphisms (SNPs) available for genetic mapping in substrains of C57BL/6 and BALB/c mice, providing important insights and methods for genetic mapping.
EXPERIMENTAL ANIMALS
(2022)
Article
Medicine, Research & Experimental
Lisa M. Godsel, Quinn R. Roth-Carter, Jennifer L. Koetsier, Lam C. Tsoi, Amber L. Huffine, Joshua A. Broussard, Gillian N. Fitz, Sarah M. Lloyd, Junghun Kweon, Hope E. Burks, Marihan Hegazy, Saki Amagai, Paul W. Harms, Xianying Xing, Joseph Kirma, Jodi L. Johnson, Gloria Urciuoli, Lynn T. Doglio, William R. Swindell, Rajeshwar Awatramani, Eli Sprecher, Xiaomin Bao, Eran Cohen-Barak, Caterina Missero, Johann E. Gudjonsson, Kathleen J. Green
Summary: Research reveals that genetic deficiency of Dsg1 causes a psoriatic-like inflammatory signature, and treatment with targeted therapy significantly improves skin lesions in patients.
JOURNAL OF CLINICAL INVESTIGATION
(2022)