Article
Multidisciplinary Sciences
Richard G. Dorrell, Adrien Villain, Benoit Perez-Lamarque, Guillemette Audren de Kerdrel, Giselle McCallum, Andrew K. Watson, Ouardia Ait-Mohamed, Adriana Alberti, Erwann Corre, Kyle R. Frischkorn, Juan J. Pierella Karlusich, Eric Pelletier, Helene Morlon, Chris Bowler, Guillaume Blanc
Summary: Horizontal gene transfer is an important source of genetic novelty in eukaryotic genomes, particularly in ochrophytes like diatoms. Bacterial HGTs have been identified as the predominant source of recently arrived genes in diatoms, enriching genes encoding secreted proteins and contributing to their evolution. The study provides insights into the frequency, sources, and functional contributions of HGT in algal evolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, General & Internal
Shin Enosawa, Huai-Che Hsu, Yusuke Yanagi, Hitomi Matsunari, Ayuko Uchikura, Hiroshi Nagashima
Summary: To develop novel medical technologies, a genetically engineered ornithine transcarbamylase-deficient (OTCD) pig strain was established and its characteristics and treatment responsiveness were reported. The OTCD pigs were obtained through mating an OTCD carrier female with a wild-type male, with the disease phenotype only appearing in males due to X-linked recessive inheritance. Treatment with nitrogen-scavenging agents based on a clinical protocol significantly extended the survival time of the OTCD pigs.
JOURNAL OF CLINICAL MEDICINE
(2021)
Editorial Material
Surgery
Milad Rezvani, Kathleen M. Campbell, Carlos E. Prada, Anna L. Peters
Summary: Liver transplantation can transfer genetic defects in metabolic pathways, and this case highlights the occurrence of metabolic crisis and early allograft dysfunction due to an acquired argininosuccinate lyase deficiency. The recipient's genetic testing revealed a heterozygous mutation in the ASL gene, which encodes the urea cycle enzyme. Postoperative ischemia/reperfusion injury increased metabolic demand beyond the enzymatic capacity of the allograft. This case emphasizes the importance of considering occult metabolic variants in the allograft during early allograft dysfunction.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Neurosciences
Xiaofan Yu, Peicong Ge, Yuanren Zhai, Wei Liu, Qian Zhang, Xun Ye, Xingju Liu, Rong Wang, Yan Zhang, Jizong Zhao, Dong Zhang
Summary: This study aimed to investigate the association between plasma urea cycle metabolites and the risk of MMD and its subcategories. The study found that plasma ornithine levels are positively associated with the risk of MMD, while levels of arginine, urea, and global arginine bioavailability ratio (GABR) are inversely related to the risk of MMD. Plasma urea cycle metabolites might serve as potential biomarkers for the risk of MMD.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Biotechnology & Applied Microbiology
Mengli Li, Jiufu Qin, Kai Xiong, Bo Jiang, Tao Zhang
Summary: Arginase plays a crucial role in the urea cycle by synthesizing l-ornithine and urea. In addition to its involvement in cell proliferation and collagen formation, it is widely used in food supplements and nutrition products. Arginase also shows potential in treating diseases such as cardiovascular diseases and cancers with high arginase expression.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2022)
Article
Endocrinology & Metabolism
Yuhong Zhao, Yingxi Chen, Ling Wei, Jianhua Ran, Kejian Wang, Shujuan Zhu, Qian Liu
Summary: In this study, it was found that p53 inhibits polyamine metabolism by suppressing the urea cycle, which in turn inhibits glioma progression.
METABOLIC BRAIN DISEASE
(2023)
Article
Physiology
Takahiro Hasumura, Keita Kinoshita, Yoshihiko Minegishi, Noriyasu Ota
Summary: This study aimed to investigate the synergistic effect of tea catechins and low-dose ornithine in activating the urea cycle to reduce blood ammonia levels during exercise. The study used hepatocyte-like cells derived from human-induced pluripotent stem (iPS) cells to assess the effect of tea catechins combined with ornithine on urea cycle activity, and also conducted a human pilot study to validate the synergistic improvement in ammonia metabolism by tea catechins in combination with ornithine.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY
(2023)
Article
Medicine, General & Internal
Xiao-Hui Fu, Yu-Hui Hu, Ian-Xiang Liao, Li Chen, Zhan-Qi Hu, Jia-Lun Wen, Shu-Li Chen
Summary: Liver transplantation can significantly improve neurological impairment caused by OTCD and eliminate the risk of hyperammonemia.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Biochemistry & Molecular Biology
J. Lisa Hoogenboom, Marty Kwok-Shing Wong, Susumu Hyodo, W. Gary Anderson
Summary: In this study, the mechanisms of nitrogen movement across the spiral valve of the cloudy catshark were investigated. The molecular identification of two ammonia transporters (Rhp2 and Rhbg) and a urea transporter (UT) revealed their specific cellular localizations. The mRNA abundance of Rhp2 and UT were found to be influenced by fasting and feeding, indicating their involvement in nitrogen homeostasis in the cloudy catshark.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2023)
Review
Microbiology
Victor M. Hernandez, Alejandra Arteaga, Michael F. Dunn
Summary: Arginase in bacteria plays crucial roles in nitrogen metabolism, stress resistance, and pathogenesis by hydrolyzing l-arginine to produce l-ornithine and urea. This review explores the regulation and functions of the arginase pathway, along with characteristics of related arginine catabolic pathways, emphasizing on the diverse physiological functions and biochemical features of arginases in different bacterial species.
FEMS MICROBIOLOGY REVIEWS
(2021)
Article
Biotechnology & Applied Microbiology
Xin Wei, Miao Zhang, Guang-Yuan Wang, Guang-Lei Liu, Zhen-Ming Chi, Zhe Chi
Summary: In this study, engineered strains of A. pullulans var. aubasidani were found to be suitable for green fumaric acid production. The ornithine-urea cycle was identified as the key pathway for high level fumarate biosynthesis. Genetic modifications and overexpression led to the development of a strain that produced high yields of fumarate. This research is significant for global sustainable development and carbon neutrality.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Toxicology
Brandon J. Sonn, Kennon J. Heard, Susan M. Heard, Angelo D'Alessandro, Kate M. Reynolds, Richard C. Dart, Barry H. Rumack, Andrew A. Monte
Summary: Elevated levels of allantoate and ornithine were found in subjects with ALT elevation in pre-treatment samples, along with significant baseline ALT and alkaline phosphatase levels. These metabolites may be indicative of pathways related to nitrogen release and urea production. Further investigation into metabolic alterations may provide insights into hepatic adaptation mechanisms for various pharmaceuticals.
CLINICAL TOXICOLOGY
(2022)
Review
Endocrinology & Metabolism
Teresa C. Delgado, Javier de las Heras, Maria L. Martinez-Chantar
Summary: This study indicates that nitrogen metabolism is altered in MAFLD, which may contribute to hepatic ammonia accumulation and the progression of fatty liver disease. The authors suggest that regulating the gut-liver axis nitrogenous balance could be an effective therapeutic approach for treating fatty liver disease.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Gastroenterology & Hepatology
Koji Imoto, Masatake Tanaka, Takeshi Goya, Tomomi Aoyagi, Motoi Takahashi, Miho Kurokawa, Shigeki Tashiro, Masaki Kato, Motoyuki Kohjima, Yoshihiro Ogawa
Summary: This study investigated the mechanism of hyperammonemia induced by corticosteroid administration in a mouse model of OTCD. The results showed that corticosteroids induced hyperammonemia in OTCD mice by both muscle catabolism and suppression of gene expressions related to the urea cycle. Early intervention with renal replacement therapy should be considered in corticosteroid-induced UCD patients to prevent brain injuries or fatal outcomes.
BMC GASTROENTEROLOGY
(2022)
Article
Endocrinology & Metabolism
Orna Staretz-Chacham, Suha Daas, Igor Ulanovsky, Ayala Blau, Nira Rostami, Talya Saraf-Levy, Nasser Abu Salah, Yair Anikster, Ehud Banne, Dalit Dar, Elena Dumin, Aviva Fattal-Valevski, Tzipora Falik-Zaccai, Eli Hershkovitz, Sagi Josefsberg, Hatem Khammash, Rimona Keidar, Stanley H. Korman, Yuval Landau, Tally Lerman-Sagie, Dror Mandel, Hanna Mandel, Ronella Marom, Iris Morag, Erez Nadir, Naama Yosha-Orpaz, Ben Pode-Shakked, Elon Pras, Haike Reznik-Wolf, Ann Saada, Reeval Segel, Avraham Shaag, Nava Shaul Lotan, Ronen Spiegel, Galit Tal, Taly Vaisid, Avi Zeharia, Shlomo Almashanu
Summary: Urea cycle disorders, including OTCD, are serious diseases with a wide range of clinical manifestations. Utilizing a new method of screening for OTCD based on the combined measurement of orotic acid and citrulline may improve the early detection of UCDs and differentiate between different types of disorders.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Allergy
Michael P. Horn, Hulda R. Jonsdottir, Daniel Brigger, Lauro Damonti, Franziska Suter-Riniker, Olga Endrich, Tanja K. Froehlich, Martin Fiedler, Carlo R. Largiader, Jonas Marschall, Benjamin Weber, Alexander Eggel, Michael Nagler
Summary: This study evaluated the diagnostic accuracy of various serological testing strategies for COVID-19 in real-life clinical settings. The results showed that different testing methods and antibody subtypes had varying levels of sensitivity and specificity. These findings are important for estimating the infection burden in specific populations and predicting the likelihood of immune protection.
Article
Oncology
Ekaterina Gurevich, Michael Hayoz, Yolanda Aebi, Carlo R. Largiader, Behrouz Mansouri Taleghani, Ulrike Bacher, Thomas Pabst
Summary: This study compared the use of busulfan/melphalan regimen with treosulfan/melphalan regimen in AML patients. The treosulfan/melphalan regimen was found to be safer and more effective, with no neurotoxicity and irreversible alopecia. There was considerable interindividual biovariability in treosulfan serum levels.
Article
Clinical Neurology
Markus Gschwind, Nuria Garcia Segarra, Andre Schaller, Ramona Bolognini, Jean-Marc Nuoffer, Raphael Hourez, Manuel Deprez, Benoit Lhermitte, Philippe Maeder, Christel Tran, Thierry Kuntzer
Summary: This article presents a patient with spastic paraplegia and ataxia, which lasted for 40 years and eventually led to death due to postinfectious lactic acidosis. Various diagnostic methods revealed the patient had a biallelic variant of the NDUFV1 gene, causing necrotizing leukoencephalomyelopathy. This case extends the understanding of NDUFV1 variants and highlights the need for awareness of respiratory chain diseases in adult patients with sudden deteriorating neurological deficits.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haibin Deng, Yanyun Gao, Verdiana Trappetti, Damian Hertig, Darya Karatkevich, Tereza Losmanova, Christian Urzi, Huixiang Ge, Gerrit Adriaan Geest, Remy Bruggmann, Valentin Djonov, Jean-Marc Nuoffer, Peter Vermathen, Nicola Zamboni, Carsten Riether, Adrian Ochsenbein, Ren-Wang Peng, Gregor Jan Kocher, Ralph Alexander Schmid, Patrick Dorn, Thomas Michael Marti
Summary: The study reveals the crucial role of lactate dehydrogenase B (LDHB) in regulating glucose and mitochondrial metabolism, and its impact on the survival and proliferation of non-small cell lung cancer (NSCLC) cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Christian Urzi, Damian Hertig, Christoph Meyer, Sally Maddah, Jean-Marc Nuoffer, Peter Vermathen
Summary: This study demonstrates the potential of using NMR technology to measure intracellular and extracellular metabolite concentrations in living cells, as well as to distinguish between them. The results show that the method is reliable and sensitive in detecting concentration changes of metabolites in intra- and extracellular compartments under different culture media conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Ulrike Muetze, Florian Gleich, Ivo Baric, Mathias Baumgartner, Alberto Burlina, Kimberly A. Chapman, Yin-Hsiu Chien, Elisenda Cortes-Saladelafont, Corinne De Laet, Dries Dobbelaere, Francois Eysken, Matthias Gautschi, Rene Santer, Johannes Haeberle, Clara Joaquin, Daniela Karall, Martin Lindner, Allan M. Lund, Chris Muehlhausen, Elaine Murphy, Dominique Roland, Angeles Ruiz Gomez, Anastasia Skouma, Sarah C. Gruenert, Margreet Wagenmakers, Sven F. Garbade, Stefan Koelker, Nikolas Boy
Summary: This study evaluates the impact of SARS-CoV-2 infections on medical health care and disease outcome in patients with intoxication-type inherited metabolic disorders. The findings indicate that most infected individuals experienced mild symptoms and did not require hospitalization, and no complications specific to inherited metabolic disorders or COVID-19 were observed.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Nutrition & Dietetics
Bigna K. Bolsterli, Eugen Boltshauser, Luigi Palmieri, Johannes Spenger, Michaela Brunner-Krainz, Felix Distelmaier, Peter Freisinger, Tobias Geis, Andrea L. Gropman, Johannes Haberle, Julia Hentschel, Bruno Jeandidier, Daniela Karall, Boris Keren, Annick Klabunde-Cherwon, Vassiliki Konstantopoulou, Raimund Kottke, Francesco M. Lasorsa, Christine Makowski, Cyril Mignot, Ruth O'Gorman Tuura, Vito Porcelli, Rene Santer, Kuntal Sen, Katja Steinbruecker, Steffen Syrbe, Matias Wagner, Andreas Ziegler, Thomas Zoeggeler, Johannes A. Mayr, Holger Prokisch, Saskia B. Wortmann
Summary: Defects in the mitochondrial malate aspartate shuttle system and mitochondrial pyruvate carrier 1 are associated with neurological phenotypes and hepatopathic-neuropsychiatric phenotypes. Ketogenic diets and carbohydrate-restricted/fat-enriched diets are effective interventions. Early (genetic) diagnosis is crucial for initiating proper treatment.
Article
Genetics & Heredity
Nicholas Kueng, Severine Arcioni, Fanny Sandberg, Christian Kuhn, Vanessa Banz, Carlo R. Largiader, Daniel Sidler, Ursula Amstutz
Summary: Liquid biopsy using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma has become a novel approach for allograft monitoring in solid organ transplant recipients. This study compared different dd-cfDNA quantification methods and found that the presented high-throughput sequencing method showed strong correlation with existing methods. Absolute levels of dd-cfDNA in urine may be required for allograft surveillance in stable kidney recipients due to extensive variability of relative amounts.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Cedric Gillich, Dilara Akhoundova, Michael Hayoz, Yolanda Aebi, Carlo R. Largiader, Katja Seipel, Michael Daskalakis, Ulrike Bacher, Thomas Pabst
Summary: Upfront treatment consolidation with TreoMel HDCT and ASCT has promising efficacy and safety in MM patients, achieving a complete response rate of 84% and an OS rate of 83%. Treosulfan pharmacokinetics showed no significant correlation with MM responses, but higher exposure and peak value in female patients were associated with longer hospitalizations.
Article
Oncology
M. de With, A. Sadlon, E. Cecchin, V. Haufroid, F. Thomas, M. Joerger, R. H. N. van Schaik, R. H. J. Mathijssen, C. R. Largiader
Summary: After the release of the EMA recommendations, there was an increase in both genotype and phenotype testing in Europe. Some countries also implemented new local guidelines. Although challenges such as lack of reimbursement and awareness among medical oncologists still existed, the percentage of specialists citing these hurdles decreased after the EMA recommendations.
Article
Genetics & Heredity
Andrea Accogli, Sheng-Jia Lin, Mariasavina Severino, Sung-Hoon Kim, Kevin Huang, Clarissa Rocca, Megan Landsverk, Maha S. Zaki, Almundher Al-Maawali, Varunvenkat M. Srinivasan, Khalid Al-Thihli, G. Bradly Schaefer, Monica Davis, Davide Tonduti, Chiara Doneda, Lara M. Marten, Chris Muehlhausen, Maria Gomez, Eleonora Lamantea, Rafael Mena, Mathilde Nizon, Vincent Procaccio, Amber Begtrup, Aida Telegra, Hong Cui, Heidi L. Schulz, Julia Mohr, Saskia Biskup, Mariana Amina Loos, Hilda Veronica Araoz, Vincenzo Salpietro, Laura Davis Keppen, Manali Chitre, Cassidy Petree, Lucy Raymond, Julie Vogt, Lindsey B. Sawyer, Alice A. Basinger, Signe Vandal Pedersen, Toni S. Pearson, Dorothy K. Grange, Lokesh Lingappa, Paige Mcdunnah, Rita Horvath, Benjamin Cogne, Bertrand Isidor, Andreas Hahn, Karen W. Gripp, Seyed Mehdi Jafarnejad, Elsebet Stergaard, Carlos E. Prada, Daniele Ghezzi, Vykuntaraju K. Gowda, Robert W. Taylor, Nahum Sonenberg, Henry Houlden, Marie Sissler, Gaurav K. Varshney, Reza Maroofian
Summary: This study reports 18 new individuals with biallelic TARS2 variants, who exhibit developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs, and increased blood lactate.
GENETICS IN MEDICINE
(2023)
Article
Infectious Diseases
Peter J. Neyer, Berenger Kabore, Christos T. Nakas, Britta Hartmann, Annelies Post, Salou Diallo, Halidou Tinto, Angelika Hammerer-Lercher, Carlo R. Largiader, Andre J. van der Ven, Andreas R. Huber
Summary: This study investigated the associations between iron homeostasis, inflammation, nutrition, and haemoglobin mutations with asymptomatic malaria infection. The results showed that malnutrition was strongly associated with asymptomatic parasitaemia, and the presence of haemoglobin S mutation could attenuate the infection.
Article
Medicine, General & Internal
Nicholas Kueng, Daniel Sidler, Vanessa Banz, Carlo R. R. Largiader, Charlotte K. Y. Ng, Ursula Amstutz
Summary: This study evaluated the technical biases of single- and double-stranded library preparation methods when applied on cfDNA from plasma and urine, and assessed the proportions of tissue of origin using two deconvolution methods. The results showed that sequencing cfDNA from urine using the double-stranded method resulted in methylation bias and lower global methylation, which were not observed with the single-stranded approach. The deconvolution methods also yielded different results in terms of determining tissue of origin proportions.
Meeting Abstract
Clinical Neurology
E. Wenz, J. Prost, I. Filchenko, J. Warncke, M. Schmidt, C. Largiader, C. Bassetti
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Meeting Abstract
Oncology
Ting Zhang, Alisa Ambrodji, Huixing Huang, Kelly Bouchonville, Amy Etheridge, Remington Schmidt, Jose Cardiel Nunez, Zoey Temesgen, Federico Innocenti, Robert Diasio, Carlo Largiader, Steven M. Offer
