Article
Ophthalmology
Hang-Jing Wu, Douglas P. Mortlock, Rachel W. Kuchtey, John Kuchtey
Summary: The study demonstrated that Adamts10(G661R/G661R) mice recapitulate the short stature and ocular phenotypes of WMS. The altered fibrillin-1 and fibrillin-2 immunoactivity in the mutant mice suggests that the G661R mutation of Adamts10 perturbs regulation of the fibrillin isotype composition of microfibrils in the mouse eye.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Medicine, General & Internal
Junting Huang, Kailai Nie, Xinpin Lv, Yuting Liu, Guiqi Yang, Junjiang Fu, Longqian Liu, Hongbin Lv
Summary: This case report presents the clinical features and genetic findings of a rare case of Weill-Marchesani syndrome 4 (WMS4). The patient exhibited progressive myopia, thickened lenses, and shorter equatorial diameter, along with brachydactyly and increased intraocular pressure. Genetic testing confirmed the diagnosis of WMS4. During a 3-year follow-up, lens thickness continued to increase and intraocular pressure rose, highlighting the importance of early diagnosis and intervention for better visual outcomes.
FRONTIERS IN MEDICINE
(2023)
Article
Ophthalmology
Dongwei Guo, Liyan Liu, Fengmei Yang, Charlotte Aimee Young, Danying Zheng, Guangming Jin
Summary: This study identified six novel ADAMTS17 mutations in four Weill-Marchesani syndrome probands. These mutations caused significant short stature and possible heart disease in the patients. This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Zerina Balic, Saurav Misra, Belinda Willard, Dieter P. Reinhardt, Suneel S. Apte, Dirk Hubmacher
Summary: ADAMTS proteases play important roles in the biosynthesis and breakdown of ECM molecules, with alternative splicing playing a significant role in regulating their proteolytic activity and cellular localization. This study characterizes the impact of alternative splicing on ADAMTS17, revealing two novel splice variants that affect protease activity through structural changes.
Article
Health Care Sciences & Services
ZhiHong Lin, MinJuan Zhu, HongWei Deng
Summary: Weill-Marchesani syndrome (WMS) is an autosomal inherited connective tissue disease characterized by eye abnormalities and short stature. This case report presented a patient with a WMS-like syndrome due to a mutation in the LTBP2 gene, which has not been previously documented in East Asia.
RISK MANAGEMENT AND HEALTHCARE POLICY
(2021)
Article
Genetics & Heredity
Mojiang Li, Yingshu Li, Huixing Liu, Haiyan Zhou, Wanqin Xie, Qinghua Peng
Summary: This study describes a patient with a homozygous ADAMTSL2 p.Gly656Ser variant, further increasing our understanding of the genotype-phenotype correlation in acromelic dysplasias.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Aviva Levitas, Liam Aspit, Neta Lowenthal, David Shaki, Hanna Krymko, Leonel Slanovic, Ronit Yagev, Ruti Parvari
Summary: Weill-Marchesani syndrome is a rare genetic disorder characterized by short stature, joint stiffness, eye anomalies, and occasionally heart defects. In this study, four patients from one consanguineous family were found to have heart-developed membranes and ocular findings consistent with WMS. Whole exome sequencing identified a homozygous nucleotide change in ADAMTS10 gene, leading to a substitution of tyrosine with histidine. This novel mutation might affect the secretion or function of ADAMTS10, causing the unique presentation of heart abnormalities and their recurrence after surgery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Na Miao, Yao Zhang, Jin-Ying Liao, Lin Zhou, Ji-Cai He, Rong-Qin Yang, Xu-Yang Liu, Li Tang
Summary: This study aimed to explore the phenotype and genotype of Weill-Marchesani syndrome (WMS) in a Chinese family and review related literature. Through medical history, comprehensive ophthalmic examinations, systemic evaluation, and genetic analysis, a homozygous missense mutation in ADAMTS17 gene was identified in three affected siblings, indicating an autosomal recessive inherited manner of WMS. This study expands the knowledge of WMS-associated mutations and deepens understanding of the pathology associated with ADAMTS17 variants.
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Multidisciplinary Sciences
Sarah Stanley, Zerina Balic, Dirk Hubmacher
Summary: Acromelic dysplasias are rare musculoskeletal disorders caused by mutations in genes encoding proteins that cooperate in a biological pathway but have distinct roles in specific tissues. Most affected proteins interact with fibrillin microfibrils and regulate TGF-beta signaling, contributing to musculoskeletal development and homeostasis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Review
Medicine, General & Internal
Mossa N. A. Al Motawa, Manal S. S. Al Shehri, Majed J. Al Buali, Amnah A. M. Al Agnam
Summary: This article studied a rare case of a 9-year-old boy with Weill-Marchesani syndrome, who had bilateral glaucoma, short stature, brachydactyly, and joint stiffness, ultimately confirmed as a homozygous familial variant of the ADAMTS10 gene.
AMERICAN JOURNAL OF CASE REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Vanessa A. Raphtis, Dhruv Sharma, Sichao Wang, Jae Y. Kim, Amanda L. Jacobson, Christine D. Harman, Andras M. Komaromy
Summary: This study revealed a possible relationship between the G661R missense mutation in the ADAMTS10 gene and ocular pulse amplitude (OPA) in a canine model of open-angle glaucoma. Dogs with the mutation displayed higher intraocular pressure (IOP) and lower OPA compared to normal dogs. The findings suggest that OPA may be a valuable clinical tool for assessing ocular stiffness and susceptibility to elevated IOP.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yuki Taniguchi, Toru Akune, Nao Nishida, Go Omori, H. A. Kim, Kazuko Ueno, Taku Saito, Takeshi Oichi, Asako Koike, Akihiko Mabuchi, Hiroyuki Oka, Shigeyuki Muraki, Yasushi Oshima, Hiroshi Kawaguchi, Kozo Nakamura, Katsushi Tokunaga, Sakae Tanaka, Noriko Yoshimura
Summary: Using a genome-wide association study, researchers identified a SNP variant (rs2054564) in the ADAMTS17 gene associated with susceptibility to lumbar spondylosis. Replication analysis in Japanese and Korean cohorts confirmed this association. The study also provided evidence of the involvement of the ADAMTS17-fibrillin network in intervertebral disc function and the role of FBN1 in lumbar spondylosis development.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Dorothy E. Vatner, Marko Oydanich, Jie Zhang, Sara C. Campbell, Stephen F. Vatner
Summary: It has been discovered that mice with RGS14 knockout exhibit enhanced exercise capacity, which is mediated by brown adipose tissue.
Article
Biochemistry & Molecular Biology
Gregory G. Vandenberg, Neal J. Dawson, Alison Head, Graham R. Scott, Angela L. Scott
Summary: Research suggests that mitochondrial dysfunction in astrocytes may contribute to oxidative stress in Fragile X Syndrome, leading to elevated levels of reactive oxygen species, potentially playing a role in the pathology of neurological disorders.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Hang-Jing Wu, Rachel W. Kuchtey, John Kuchtey
Summary: The G661R mutation of ADAMTS10 may be associated with the pathogenesis of glaucoma, leading to blindness through the impairment of RGC function and changes in optic nerve axons. The study also suggests a potential role for ADAMTS10 in regulating TGF8 signaling pathway and modulating cell apoptosis during retinal development.
Article
Chemistry, Physical
Christopher R. Below, Joanna Kelly, Alexander Brown, Jonathan D. Humphries, Colin Hutton, Jingshu Xu, Brian Y. Lee, Celia Cintas, Xiaohong Zhang, Victor Hernandez-Gordillo, Linda Stockdale, Matthew A. Goldsworthy, Joe Geraghty, Lucy Foster, Derek A. O'Reilly, Barbara Schedding, Janet Askari, Jessica Burns, Nigel Hodson, Duncan L. Smith, Catherine Lally, Garry Ashton, David Knight, Aleksandr Mironov, Antonia Banyard, Johannes A. Eble, Jennifer P. Morton, Martin J. Humphries, Linda G. Griffith, Claus Jorgensen
Summary: A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin-integrin interactions in their growth.
Article
Multidisciplinary Sciences
Bodour S. Rajab, Sarah Kassab, Connor D. Stonall, Hussam Daghistani, Stephen Gibbons, Mamas Mamas, David Smith, Aleksandr Mironov, Zainab AlBalawi, Yin Hua Zhang, Florence Baudoin, Min Zi, Sukhpal Prehar, Elizabeth J. Cartwright, Ashraf Kitmitto
Summary: Research reveals that mitochondrial morphology, dynamics and function are dysregulated in the early stages of diabetes, characterized by enlarged mitochondria, irregular shape, increased tubular projections, increased density, decreased complex activity and increased oxygen consumption rate.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Mychel R. P. T. Morais, Pinyuan Tian, Craig Lawless, Syed Murtuza-Baker, Louise Hopkinson, Steven Woods, Aleksandr Mironov, David A. Long, Daniel P. Gale, Telma M. T. Zorn, Susan J. Kimber, Roy Zent, Rachel Lennon
Summary: By studying kidney organoids, we have revealed the complex and dynamic nature of basement membrane assembly, and identified its importance in human development and disease.
Article
Developmental Biology
Jennifer Stables, Emma K. Green, Anuj Sehgal, Omkar L. Patkar, Sahar Keshvari, Isis Taylor, Maisie E. Ashcroft, Kathleen Grabert, Evi Wollscheid-Lengeling, Stefan Szymkowiak, Barry W. McColl, Antony Adamson, Neil E. Humphreys, Werner Mueller, Hana Starobova, Irina Vetter, Sepideh Kiani Shabestari, Matthew M. Blurton-Jones, Kim M. Summers, Katharine M. Irvine, Clare Pridans, David A. Hume
Summary: Amino acid substitutions in the kinase domain of the human CSF1R gene are associated with ALSP. A disease-associated mutation was created in the mouse Csf1r locus to model the human disease. This mutation affected the production of tissue macrophages and microglial cells in the mouse brain.
Article
Biochemistry & Molecular Biology
Christopher A. Smith, Paul A. Humphreys, Nicola Bates, Mark A. Naven, Stuart A. Cain, Mona Dvir-Ginzberg, Susan J. Kimber
Summary: The activation of SIRT1 has a positive impact on the expression of main extracellular matrix (ECM) proteins during human cartilage development, but it also alters ECM composition and suppresses the content of glycosaminoglycans (GAGs). The activation of SIRT1 is associated with increased expression of ECM genes and chondrogenic transcription factors, as well as an interaction with ARID5B. However, the activation of SIRT1 also leads to a decrease in GAGs and down regulation of genes responsible for GAG chain initiation/elongation.
Article
Biochemistry & Molecular Biology
Michael P. Lockhart-Cairns, Stuart A. Cain, Rana Dajani, Ruth Steer, Jennifer Thomson, Yasmene F. Alanazi, Cay M. Kielty, Clair Baldock
Summary: TGF beta superfamily members play essential roles in cellular behavior, and the cross-linking of latent TGF beta binding proteins (LTBPs) with fibrillin can enhance TGF beta activation, influencing cell and tissue function.
Article
Multidisciplinary Sciences
Polly Downton, Fabio Sanna, Robert Maidstone, Toryn M. Poolman, Edward A. Hayter, Suzanna H. Dickson, Nick A. Ciccone, James O. Early, Antony Adamson, David G. Spiller, Devin A. Simpkins, Matthew Baxter, Roman Fischer, Magnus Rattray, Andrew S. I. Loudon, Julie E. Gibbs, David A. Bechtold, David W. Ray
Summary: Chronic inflammation is associated with metabolic dysfunction, with a temporal crosstalk between inflammatory and metabolic processes. Research has shown that arthritis drives changes in lipid metabolism and mitochondrial function, leading to the accumulation of bioactive lipid species.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Timothy J. Mead, Daniel R. Martin, Lauren W. Wang, Stuart A. Cain, Cagri Gulec, Elisabeth Cahill, Joseph Mauch, Dieter Reinhardt, Cecilia Lo, Clair Baldock, Suneel S. Apte, Ernestina Schipani
Summary: This study reveals a proteostatic mechanism contributing to the reduction of fibrillin-2 and dominance of fibrillin-1 during postnatal development. The lack of ADAMTS6 and ADAMTS10 leads to excess fibrillin-2 and impairs skeletal development and signaling. The protease-substrate relationship between ADAMTS6 and fibrillin-2 is established.
Article
Biology
Alex A. Koch, James S. Bagnall, Nicola J. Smyllie, Nicola Begley, Antony D. Adamson, Jennifer L. Fribourgh, David G. Spiller, Qing-Jun Meng, Carrie L. Partch, Korbinian Strimmer, Thomas A. House, Michael H. Hastings, Andrew S. Loudon
Summary: This study develops a quantitative model to explain how a finite pool of BMAL1 protein regulates gene expression at thousands of target sites over daily time scales. By tracking dynamic changes in endogenous labeled proteins in tissues, the researchers determine the contribution of multiple rhythmic processes in coordinating BMAL1 DNA binding. The results also reveal the role of nuclear BMAL1 concentration in determining CLOCK and the mechanism of repression of CLOCK:BMAL1 through interactions with PER2:CRY1 and BMAL1:CRY1.
Article
Multidisciplinary Sciences
Ranjay Jayadev, Mychel R. P. T. Morais, Jamie M. Ellingford, Sandhya Srinivasan, Richard W. Naylor, Craig Lawless, Anna S. Li, Jack F. Ingham, Eric Hastie, Qiuyi Chi, Maryline Fresquet, Nikki-Maria Koudis, Huw B. Thomas, Raymond T. O'Keefe, Emily Williams, Antony Adamson, Helen M. Stuart, Siddharth Banka, Damian Smedley, David R. Sherwood, Rachel Lennon
Summary: By utilizing bioinformatic and in vivo approaches, we have identified a network of proteins involved in basement membrane regulation and function. This study highlights the complexity of basement membranes and their impact on human health.
Article
Biochemistry & Molecular Biology
Fuhui Chen, Sevim B. Gurler, David Novo, Cigdem Selli, Denis G. Alferez, Secil Eroglu, Kyriaki Pavlou, Jingwei Zhang, Andrew H. Sims, Neil E. Humphreys, Antony Adamson, Andrew Campbell, Owen J. Sansom, Cathy Tournier, Robert B. Clarke, Keith Brennan, Charles H. Streuli, Ahmet Ucar
Summary: Breast cancer stem cells (BCSC), responsible for treatment resistance, tumor recurrence, and metastasis, have been hindered by heterogeneity and lack of selective molecular targets. This study identifies RAC1B as a clinically relevant molecular target for BCSC-targeting therapies, highlighting its role in the maintenance of BCSC and their chemoresistance to doxorubicin.
Article
Biochemistry & Molecular Biology
Bali Lee, Christopher Hoyle, Rose Wellens, Jack P. Green, Fatima Martin-Sanchez, Daniel M. Williams, Billie J. Matchett, Paula I. Seoane, Hayley Bennett, Antony Adamson, Gloria Lopez-Castejon, Martin Lowe, David Brough
Summary: Inflammation driven by the NLRP3 inflammasome is triggered by disrupted endosome trafficking, leading to enhanced inflammasome activation and cytokine secretion. These findings provide insight into the spatial activation of the NLRP3 inflammasome and suggest potential therapeutic targets.
Article
Multidisciplinary Sciences
Fleur Talbot, Claire H. Feetham, Jacek Mokrosinski, Katherine Lawler, Julia M. Keogh, Elana Henning, Edson Mendes de Oliveira, Vikram Ayinampudi, Sadia Saeed, Amelie Bonnefond, Mohammed Arslan, Giles S. H. Yeo, Philippe Froguel, David A. Bechtold, Antony Adamson, Neil Humphreys, Ines Barroso, Simon M. Luckman, I. Sadaf Farooqi
Summary: Loss of function variants in the GPR10 gene are found in people with severe obesity, impairing ligand binding and G protein-dependent signaling. Transgenic mice with one of these variants gain excessive weight due to decreased energy expenditure. Targeting GPR10 may be a potential weight-loss therapy.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Polly Downton, James S. Bagnall, Hazel England, David G. Spiller, Neil E. Humphreys, Dean A. Jackson, Pawel Paszek, Michael R. H. White, Antony D. Adamson
Summary: Cells respond to inflammatory stimuli by activating the NF-kappa B signaling pathway, resulting in the oscillatory translocation of p65 and I kappa B alpha proteins. Overexpression of I kappa B alpha reduces target gene expression, while overexpression of p65 partially rescues it. Nuclear accumulation of I kappa B alpha suppresses target gene expression by preventing p65 interaction with promoter binding sites. Modulating the expression levels of both I kappa B alpha and p65 has an anti-inflammatory effect on transcription.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Medicine, Research & Experimental
Mark A. Naven, Leo A. H. Zeef, Shiyang Li, Paul A. Humphreys, Christopher A. Smith, Dharshika Pathiranage, Stuart Cain, Steven Woods, Nicola Bates, Manting Au, Chunyi Wen, Susan J. Kimber, Qing-Jun Meng
Summary: This study utilized a chondrogenic differentiation model on human embryonic stem cells to investigate the activation of the circadian clock in human cartilage. The results demonstrated a differentiation-coupled mechanism in activating the circadian clock during chondrogenic differentiation, showing significant changes in gene expression levels at different stages of differentiation.