Article
Endocrinology & Metabolism
Elizabeth K. M. Johnstone, Mohammed Akli Ayoub, Rebecca J. Hertzman, Heng B. See, Rekhati S. Abhayawardana, Ruth M. Seeber, Kevin D. G. Pfleger
Summary: This study investigated the heteromerization of AT(2) and B-2 receptors in HEK293FT cells. The results demonstrated the functional interaction between these receptors and the differences in signaling, providing important evidence for studying GPCR pharmacology and signaling diversity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Laszlo Sandor Erdelyi, Laszlo Hunyady, Andras Balla
Summary: The diluting and concentrating function of the kidney is regulated by the V2 receptor and antidiuretic hormone, affecting the body's water homeostasis. Mutations of the V2 receptor can lead to X-linked nephrogenic diabetes insipidus or nephrogenic syndrome of inappropriate antidiuresis disease. This review explores potential therapeutic interventions based on recent findings.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Natasha Tatiana Sobol, Luisina Maria Solerno, Brady Beltran, Liliana Vasquez, Giselle Vanina Ripoll, Juan Garona, Daniel Fernando Alonso
Summary: Osteosarcoma, the most common primary bone malignancy, requires novel treatment strategies for improved patient survival. Repurposed agent dDAVP shows potential anti-tumor activity in osteosarcoma by inhibiting AVPR2-expressing cell growth and raising cAMP levels, suggesting a promising therapeutic tool for managing this aggressive cancer. Further preclinical exploration on orthotopic or metastatic models is warranted to confirm its efficacy.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Health Care Sciences & Services
Senthil Selvaraj, Dircea Rodrigues, Navaneethakrishnan Krishnamoorthy, Khalid A. Fakhro, Luis R. Saraiva, Manuel C. Lemos
Summary: In this study, we report a rare case of a female patient with X-linked recessive NDI caused by a novel heterozygous missense mutation in the AVPR2 gene. Through genetic analysis and functional studies, we found that the mutation destabilizes the helical structure of AVPR2, disrupts its membrane localization, and affects downstream signaling pathways upon activation with vasopressin. These defects result in deficient membrane translocation of aquaporin 2, explaining the inability to concentrate urine in this patient.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Endocrinology & Metabolism
Q. Li, D. Tian, J. Cen, L. Duan, W. Xia
Summary: This study investigated the genotype and phenotype of congenital nephrogenic diabetes insipidus caused by AVPR2 mutations in the Chinese population, revealing new mutations and the association between genotype and phenotype.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Laura Szalai, Andras Sziraki, Laszlo Sandor Erdelyi, Kinga Bernadett Kovacs, Miklos Toth, Andras David Toth, Gabor Turu, Dominique Bonnet, Bernard Mouillac, Laszlo Hunyady, Andras Balla
Summary: In this study, a point mutation in the AVPR2 gene of a patient with nephrogenic diabetes insipidus (NDI) was identified, and the impaired function of the mutant receptor was characterized. The mutant receptor was primarily located in the endoplasmic reticulum (ER) and had reduced ability to generate cAMP in response to AVP stimulation. Pretreatment with pharmacochaperones partially restored the receptor's function. Both cell permeant agonists and antagonists can function as pharmacochaperones, providing a potential starting point for developing therapies for patients carrying this mutation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Li Zang, Yuping Gong, Yijun Li, Jingtao Dou, Zhaohui Lyu, Xiaoqing Su, Yawei Zhang, Yiming Mu
Summary: This study investigated novel clinical phenotypic signatures of congenital nephrogenic diabetes insipidus (CNDI) in a Chinese family. A new mutation in the AVPR2 gene was identified as a genetic risk factor for CDNI. Skewed X-chromosome inactivation patterns were observed in female carriers of the mutation.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Chemistry, Organic
Kaoru Funaki, Hidetsugu Tabata, Yusuke Nakazato, Yuka Takahashi, Tomohiko Tasaka, Hideyo Takahashi, Hideaki Natsugari, Tetsuta Oshitari
Summary: By performing the 5N-acylation reaction on 1N-methyl-1,5-benzodiazepin-2ones using (S)-2-phenylpropanoyl and (S)-2-phenylbutanoyl chlorides, the (a1S,a2S,S)-atropisomer (I) was obtained with high diastereoselectivity over the (a1R,a2R,S)-isomer (II). The preferential formation of I can be attributed to the thermodynamically preferable pi-pi stacking interaction between two benzene rings in the benzodiazepine ring and the acyl chloride during the reaction.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Agriculture, Dairy & Animal Science
Farheen Badrealam Khan, Irfa Anwar, Elrashdy M. Redwan, Abdulrasheed Palakkott, Arshida Ashraf, Jaleel Kizhakkayil, Rabah Iratni, Sajid Maqsood, Mohammed Akli Ayoub
Summary: Lactoferrin has been found to have antidiabetic properties by activating insulin receptors and their downstream signaling pathways. This suggests that lactoferrin may be the bioactive component responsible for the antidiabetic properties of camel milk.
JOURNAL OF DAIRY SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Abeda Jamadar, Nidhi Dwivedi, Sijo Mathew, James P. Calvet, Sufi M. Thomas, Reena Rao
Summary: The V2R signaling in ccRCC tumor cells stimulates the activation, migration, and proliferation of cancer-associated fibroblasts. V2R regulates the production of fibroblast-activating factors, some of which are also regulated by YAP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Svetlana Lebedeva, Arus Margaryan, Elena Smolyarchuk, Andrey Nedorubov, Maria Materenchuk, Alexander Tonevitsky, Kerim Mutig
Summary: Diabetic kidney disease is the major cause of chronic kidney disease, and enhanced plasma vasopressin levels have been associated with it. Vasopressin has diuretic effects in the kidneys and adaptive effects in other organs. Overactivation of certain vasopressin receptors can lead to kidney problems and worsen diabetic kidney disease.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
Chloe J. Peach, Laura E. Kilpatrick, Jeanette Woolard, Stephen J. Hill
Summary: VEGF-A is an important mediator of angiogenesis that signals primarily through VEGF receptor 2 (VEGFR2). In this study, researchers investigated the differences in ligand binding kinetics of VEGF-A isoforms in living cells expressing both VEGFR2 and neuropilin-1 (NRP1). They found that despite the selectivity for VEGFR2, one isoform had distinct binding kinetics when interacting with the VEGFR2/NRP1 complex, while the other isoform showed kinetics similar to VEGFR2 alone.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Physiology
Sua Kim, Chor Ho Jo, Gheun-Ho Kim
Summary: This study demonstrates that antipsychotic drugs like haloperidol, sertraline, and carbamazepine can induce nephrogenic syndrome of inappropriate antidiuresis by upregulating vasopressin-2 receptor and aquaporin-2 (AQP2) through cAMP/PKA signaling. Additionally, these drugs also increase AQP2 protein abundance through dephosphorylation at Ser(261) and enhanced transcription.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Carlotta Bon, Ting-Rong Chern, Elena Cichero, Terrence E. O'Brien, Stefano Gustincich, Raul R. Gainetdinov, Stefano Espinoza
Summary: Trace amine-associated receptor 5 (TAAR5) is expressed in the olfactory epithelium and limbic brain regions, and is involved in the regulation of emotional behavior and adult neurogenesis. Two identified mTAAR5 antagonists inhibit TMA-induced cAMP production and downstream signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Physiology
James D. Stockand, Elena V. Mironova, Hong Xiang, Antonio G. Soares, Jorge Contreras, James A. McCormick, Susan B. Gurley, Alan C. Pao
Summary: V2 receptors can increase blood pressure by enhancing ENaC activity, while not affecting AQP2 expression. In the Liddle mouse model, V2 receptor stimulation leads to retention of Na+ and water, resulting in hypertension. These findings highlight the inherent limitation in which the kidney must use ENaC as a pathway to regulate both plasma tonicity and blood pressure.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Letter
Critical Care Medicine
Deborah J. Morris-Rosendahl, Matthew Edwards, Melissa J. McDonnell, Shibu John, Eric W. F. W. Alton, Jane C. Davies, Nicholas J. Simmonds
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2020)
Article
Genetics & Heredity
Mahmoud R. Fassad, Mitali P. Patel, Amelia Shoemark, Thomas Cullup, Jane Hayward, Mellisa Dixon, Andrew Rogers, Sarah Ollosson, Claire Jackson, Patricia Goggin, Robert A. Hirst, Andrew Rutman, James Thompson, Lucy Jenkins, Paul Aurora, Eduardo Moya, Philip Chetcuti, Chris O'Callaghan, Deborah J. Morris-Rosendahl, Christopher M. Watson, Robert Wilson, Siobhan Carr, Woolf Walker, Andreia Pitno, Susana Lopes, Heba Morsy, Walaa Shoman, Luisa Pereira, Carolina Constant, Michael R. Loebinger, Eddie M. K. Chung, Priti Kenia, Nisreen Rumman, Nader Fasseeh, Jane S. Lucas, Claire Hogg, Hannah M. Mitchison
JOURNAL OF MEDICAL GENETICS
(2020)
Article
Genetics & Heredity
Damilola Olubando, Claire Hopton, James Eden, Richard Caswell, N. Thomas, Stephen A. Roberts, Deborah Morris-Rosendahl, Luigi Venetucci, William G. Newman
JOURNAL OF HUMAN GENETICS
(2020)
Article
Respiratory System
Anitha Vijayasingam, Emily Frost, Julie Wilkins, Lise Gillen, Presanna Premachandra, Kate Mclaren, Desmond Gilmartin, Lorenzo Picinali, Alberto Vidal-Diez, Simone Borsci, Melody Zhifang Ni, Wai Y. Tang, Deborah Morris-Rosendahl, Jonny Harcourt, Caroline Elston, N. J. Simmonds, Anand Shah
Article
Respiratory System
Amelia Shoemark, Bruna Rubbo, Marie Legendre, Mahmoud R. Fassad, Eric G. Haarman, Sunayna Best, Irma C. M. Bon, Joost Brandsma, Pierre-Regis Burgel, Gunnar Carlsson, Siobhan B. Carr, Mary Carroll, Matt Edwards, Estelle Escudier, Isabelle Honore, David Hunt, Gregory Jouvion, Michel R. Loebinger, Bernard Maitre, Deborah Morris-Rosendahl, Jean-Francois Papon, Camille M. Parsons, Mitali P. Patel, N. Simon Thomas, Guillaume Thouvenin, Woolf T. Walker, Robert Wilson, Claire Hogg, Hannah M. Mitchison, Jane S. Lucas
Summary: This study used topological data analysis to investigate genotype-phenotype relationships in PCD, revealing that different gene mutations have varying effects on disease severity and presentation, and that cilia ultrastructure and beat pattern defects are closely related to specific causative gene groups.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Review
Genetics & Heredity
Afsoon Sepahzad, Deborah J. Morris-Rosendahl, Jane C. Davies
Summary: The understanding of cystic fibrosis has greatly improved since the discovery of the CFTR gene in 1989, leading to the development of modulator therapies targeted at mutations in CFTR. However, variations in treatment response and disease severity may be influenced by non-CFTR modifiers, highlighting the importance of studying the interaction between genetic and environmental factors. Efforts to personalize care and improve treatment outcomes should focus on understanding the relative influence of genomic versus environmental factors.
Article
Genetics & Heredity
Anne Guimier, Melanie T. Achleitner, Anne Moreau de Bellaing, Matthew Edwards, Loic de Pontual, Kirti Mittal, Kyla E. Dunn, Megan E. Grove, Carolyn J. Tysoe, Clemantine Dimartino, Jessie Cameron, Anil Kanthi, Anju Shukla, Florence van den Broek, Diptendu Chatterjee, Charlotte L. Alston, Charlotte V. Knowles, Laura Brett, Jan A. Till, Tessa Homfray, Paul French, Georgia Spentzou, Noha A. Elserafy, Kate S. Lichkus, Bindu P. Sankaran, Hannah L. Kennedy, Peter M. George, Alexa Kidd, Saskia B. Wortmann, Dianna G. Fisk, Tamara T. Koopmann, Muhammad A. Rafiq, Jason D. Merker, Sumith Parikh, Priyanka Ahimaz, Robert G. Weintraub, Alan S. Ma, Christian Turner, Carolyn J. Ellaway, Liza K. Phillips, David R. Thorburn, Wendy K. Chung, Sajel L. Kana, Ona M. Faye-Petersen, Michelle L. Thompson, Alexandre Janin, Karen McLeod, Ruth McGowan, Robert McFarland, Katta M. Girisha, Deborah J. Morris-Rosendahl, Anna C. E. Hurst, Claire L. S. Turner, Robert M. Hamilton, Robert W. Taylor, Fanny Bajolle, Christopher T. Gordon, Jeanne Amiel, Johannes A. Mayr, Kit Doudney
Summary: Variants in the PPA2 gene lead to heart failure and sudden cardiac arrest at different ages, with significant phenotypic variability within and among families, and some patients may have progressive neurological diseases. Strictly avoiding alcohol intake can prevent cardiac arrest.
GENETICS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Anca Nastase, Amit Mandal, Shir Kiong Lu, Hima Anbunathan, Deborah Morris-Rosendahl, Yu Zhi Zhang, Xiao-Ming Sun, Spyridon Gennatas, Robert C. Rintoul, Matthew Edwards, Alex Bowman, Tatyana Chernova, Tim Benepal, Eric Lim, Anthony Newman Taylor, Andrew G. Nicholson, Sanjay Popat, Anne E. Willis, Marion MacFarlane, Mark Lathrop, Anne M. Bowcock, Miriam F. Moffatt, William O. C. M. Cookson
Summary: The study identified a range of new previously unrecognized genetic deletions and mutations in pleural mesothelioma, which may affect the normal expression of multiple signaling pathways, potentially leading to disease progression and poor prognosis. Additionally, certain drugs showed anti-tumor effects in primary mesothelioma cells.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Respiratory System
Beatrice Cockbain, Deborah Morris-Rosendahl, Adele Corrigan, Matthew David Hind
Article
Cardiac & Cardiovascular Systems
M. Yousuf Salmasi, Deborah Morris-Rosendahl, Omar A. Jarral, Ulrich Rosendahl, George Asimakopoulos, Shahzad Raja, Jose Antonio Aragon-Martin, Anne Child, John Pepper, Aung Oo, Thanos Athanasiou
Summary: This study demonstrates the clinical utility of targeted-genetic sequencing in patients with TAA and establishes a new method for histological characterization of TAA disease. The findings suggest the heterogeneity of TAA microstructure and the potential link between histological appearance and genetic variation.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
M. Yousuf Salmasi, Shehani Alwis, Shabnam Cyclewala, Omar A. Jarral, Heba Mohamed, David Mozalbat, Christoph A. Nienaber, Thanos Athanasiou, Deborah Morris-Rosendahl
Summary: The expansion of genes associated with thoracic aortic aneurysms (TAA) has transformed our understanding of the disease. This progress has led to several clinical benefits, including insights into the non-syndromic hereditary causes of TAA (HTAAD) and improved subclassification of the disease. Additionally, the discovery of deleterious mutations and their impact on aortic phenotype has advanced our understanding of aortic biomechanics and mechanical homeostasis. However, the challenge lies in accurately predicting the risk of thoracic aortic dissection (TAD) based on genotype, which hinders preventive surgery for individuals with normal aortic diameters. Future research should focus on more advanced genetic diagnosis of HTAAD and exploring the diverse pathways involved in its pathophysiology to enhance our understanding of the underlying mechanisms, improve treatment guidelines, and prevent complications.
HELLENIC JOURNAL OF CARDIOLOGY
(2023)
Article
Clinical Neurology
Evelina Carapancea, Marie-Coralie Cornet, Mathieu Milh, Lucrezia De Cosmo, Eric J. Huang, Tiziana Granata, Pasquale Striano, Berten Ceulemans, Anja Stein, Deborah Morris-Rosendahl, Greta Conti, Nipa Mitra, F. Lucy Raymond, David H. Rowitch, Roberta Solazzi, Fabiana Vercellino, Paola De Liso, Gianluca D'Onofrio, Clementina Boniver, Olivier Danhaive, Katherine Carkeek, Vincenzo Salpietro, Sarah Weckhuysen, Marny Fedrigo, Annalisa Angelini, Barbara Castellotti, Damien Lederer, Valerie Benoit, Federico Raviglione, Renzo Guerrini, Robertino Dilena, Maria Roberta Cilio
Summary: BRAT1 encephalopathy is an ultra-rare autosomal recessive neonatal encephalopathy characterized by multifocal myoclonus, microcephaly, hypertonia, and multifocal seizures. Early recognition of BRAT1 encephalopathy is crucial for prompt workup, appropriate management, and genetic counseling.
Editorial Material
Pediatrics
Deborah J. Morris-Rosendahl
PEDIATRIC PULMONOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jesse B. Hayesmoore, Zahurul A. Bhuiyan, Domenico A. Coviello, Desiree du Sart, Matthew Edwards, Maria Iascone, Deborah J. Morris-Rosendahl, Katie Sheils, Marjon van Slegtenhorst, Kate L. Thomson
Summary: Inherited cardiomyopathies and arrhythmias (ICAs) are a prevalent and clinically heterogeneous group of genetic disorders that are associated with increased risk of sudden cardiac death and heart failure. Despite improved understanding of the genetic basis, identifying the causative genotype remains challenging due to genetic and allelic heterogeneity, incomplete/age-related penetrance, and variable expressivity. These recommendations aim to assist clinical laboratories in navigating the challenges of ICAs and improving genetic test provision for this group of disorders.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Neurosciences
Deborah J. Morris-Rosendahl, Marc-Antoine Crocq
DIALOGUES IN CLINICAL NEUROSCIENCE
(2020)