Review
Endocrinology & Metabolism
George A. Diaz, Mark Bechter, Stephen D. Cederbaum
Summary: Arginase 1 Deficiency (ARG1-D) is a rare urea cycle disorder that leads to hyperargininemia and neurological disorders. Current treatment methods, such as dietary protein restriction, have limited effectiveness.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Nutrition & Dietetics
Alexander Christian Reisinger, Florian Posch, Gerald Hackl, Gunther Marsche, Harald Sourij, Benjamin Bourgeois, Kathrin Eller, Tobias Madl, Philipp Eller
Summary: Metabolomics using H-1 NMR spectroscopy shows promise for personalized medicine in sepsis, with distinct differences in metabolites between sepsis patients and controls, as well as between septic shock survivors and non-survivors. Branched-chain amino acids (BCAA), including valine, leucine, and isoleucine, were significantly lower in sepsis non-survivors and serve as potential early biomarkers for predicting outcomes in ICU and 28-day mortality.
Article
Pediatrics
Divyani Garg, Sunita Bijarnia-Mahay, Aman Elwadhi, Sandip Ray, Johannes Haberle, Suvasini Sharma
Summary: Argininemia, caused by deficiency of arginase 1 in the urea cycle, can lead to symptoms such as spastic diplegia, cognitive deterioration, and epilepsy. Early recognition is crucial for initiating treatment and providing genetic counseling.
INDIAN JOURNAL OF PEDIATRICS
(2021)
Article
Chemistry, Analytical
Thomas Hankemeier, Luojiao Huang, Nicolas Drouin, Jason Causon, Agnieszka Wegrzyn, Jose Castro-Perez, Ronan Fleming, Amy Harms
Summary: Accurate reconstruction of metabolic pathways is crucial for understanding metabolomics changes and biological processes in diseases. A tracer-based metabolomics strategy using stable isotope labeled precursors can trace pathways by measuring the transformation of metabolites. By quantifying labeled metabolite substructures, a new method achieves simultaneous isotopic labeling information at the intact metabolite and moiety level. This method was applied to trace the fate of labeled atoms in human-induced pluripotent stem cell-derived neurons, revealing the pathway reconstruction of de novo glutathione synthesis and its alteration under oxidative stress and neurodegeneration.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ming Liu, Yiheng Huang, Hongwei Zhang, Dawn Aitken, Michael C. Nevitt, Jason S. Rockel, Jean-Pierre Pelletier, Cora E. Lewis, James Torner, Yoga Raja Rampersaud, Anthony V. Perruccio, Nizar N. Mahomed, Andrew Furey, Edward W. Randell, Proton Rahman, Guang Sun, Johanne Martel-Pelletier, Mohit Kapoor, Graeme Jones, David Felson, Dake Qi, Guangju Zhai
Summary: Obesity is associated with altered amino acid metabolism, and restricting branched-chain amino acids in a high-fat diet can prevent obesity and insulin resistance.
Article
Fisheries
Haolong Li, Muzi Zhang, Haibo Jiang, Yuwen Fan, Xue Li, Rixin Wang, Yunxia Qian, Ming Li
Summary: This study found that ammonia poisoning can lead to oxidative damage, immunosuppression, and inflammation in yellow catfish. Arginase may be an important target of ammonia toxicity, and exogenous arginine supplementation can alleviate the symptoms of ammonia poisoning in yellow catfish.
FISH & SHELLFISH IMMUNOLOGY
(2021)
Review
Nutrition & Dietetics
Xiaonan Zhang, Mengxue Xia, Yingjie Wu, Fang Zhang
Summary: Retinopathy is a major cause of irreversible blindness and vision loss worldwide. Imbalanced nutrients, especially Branched-Chain Amino Acids (BCAAs), play important roles in the development and progression of retinal diseases. This review summarizes the changes in BCAA levels in retinopathy, especially in diabetic retinopathy and aging-related macular disease, as well as the genetics, functions, and mechanisms of BCAAs in the retina and other metabolic tissues. The aim of this review is to provide fundamental knowledge of BCAAs for further research on retina health.
Article
Food Science & Technology
Li Zhu, Siyu He, Ying Lu, Jianhong Gan, Ningping Tao, Xichang Wang, Zaoli Jiang, Yuanxiang Hong, Changhua Xu
Summary: This study comprehensively investigated the changes in metabolic compounds of Chinese traditional fermented soy sauce (CTFSS) associated with fermentation time. The results showed significant changes in formaldehyde nitrogen, total soluble nitrogen, non-salt soluble solids, amino acids, free 5'-nucleotides, and volatile compounds. The study also revealed an opposite trend between volatile compounds and amino acids, indicating a transformation between these two components.
FOOD SCIENCE AND HUMAN WELLNESS
(2022)
Article
Biochemistry & Molecular Biology
Bodhisattwa Banerjee, Iryna Khrystoforova, Baruh Polis, Inbar Ben Zvi, David Karasik
Summary: Living organisms develop evolutionary strategies to cope with stressful events, such as the urea cycle for dealing with ammonia excess and the polyamine stress response. Researches have found that oxidative stress can trigger the expression of specific genes in fish and have specific effects on aging animals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, General & Internal
Jose L. Flores-Guerrero, Margery A. Connelly, Irina Shalaurova, Erwin Garcia, Stephan J. L. Bakker, Robin P. F. Dullaart
Summary: The study found that higher DRI scores were associated with an increased risk of incident hypertension, independent of traditional clinical risk factors. Additionally, the addition of DRI allowed for proper reclassification of 34% of participants.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Penglong Cao, Bing Huang, Mo Hong, Yuxin Jiang, Ran Cao, Chen Chi, Yunfeng Cao, Shijun Li
Summary: Citrulline was consistently associated with diabetic nephropathy risk in two independent cross-sectional studies among Chinese adults, while ornithine, arginine, and the ratio of arginine to ornithine showed no significant association with diabetic nephropathy risk.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Nutrition & Dietetics
Simona Bartova, Francisco Madrid-Gambin, Luis Fernandez, Jerome Carayol, Emmanuelle Meugnier, Berenice Segrestin, Pauline Delage, Nathalie Vionnet, Alexia Boizot, Martine Laville, Hubert Vidal, Santiago Marco, Jorg Hager, Sofia Moco
Summary: This study investigated the effects of grape polyphenol-rich extract supplementation on plasma metabolome during overfeeding in adults. Results showed that the supplementation could counterbalance metabolic markers induced by overfeeding, providing a protective metabolic effect against excessive calorie intake in adults.
FRONTIERS IN NUTRITION
(2022)
Review
Cell Biology
Michaela E. Trautman, Nicole E. Richardson, Dudley W. Lamming
Summary: The proportion of people suffering from age-related diseases is increasing worldwide. Recent research has shown that low protein diets, particularly those low in branched-chain amino acids (BCAAs), can reduce mortality and promote metabolic health and extended lifespan in both humans and rodents. This article discusses the emerging evidence that BCAAs play a crucial role in healthy metabolism and longevity, and explores the physiological and molecular mechanisms behind the benefits of restricting dietary BCAAs. The findings suggest that the quality of protein, specifically the composition of dietary protein, may be a previously overlooked factor in metabolic dysfunction and reducing dietary BCAAs could be a promising new approach to delaying and preventing age-related diseases.
Article
Pharmacology & Pharmacy
Jun-sheng Tian, Hui-liang Zhao, Yao Gao, Qi Wang, Huan Xiang, Xiang-ping Xu, Sheng Huang, Dong-lan Yan, Xue-mei Qin
Summary: Lvjiaobuxue granule has been shown to improve the leukopenia model in 4T1 tumor-bearing mice induced by cyclophosphamide, potentially through regulating the branched-chain amino acid degradation pathway and levels of valine, leucine and isoleucine. Metabolomics studies identified potential biomarkers in the spleen of mice, while integrated analysis of metabolomics and network pharmacology revealed the mechanism of Lvjiaobuxue granule in increasing white blood cells by inhibiting BCAAs degradation pathway. Molecular biology results further supported the importance of BCAAs in improving leukopenia.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Plant Sciences
Ashok Panda, Jaykumar Rangani, Asish Kumar Parida
Summary: The study revealed significant alterations in the metabolite profile of the xero-halophyte Haloxylon salicornicum in response to salinity stress, with amino acids, organic acids, and sugars being predominantly up-regulated. Pathway enrichment analysis identified key biological pathways contributing to salt tolerance in H. salicornicum.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Genetics & Heredity
Alyssa Grygiel, Felicia Ikolo, Raphielle Stephen, Dawnell Bleasdille, Patricia Robbins-Furman, Beverly Nelson, Andrew K. Sobering, Sarah H. Elsea
Summary: The study in Grenada revealed that SCD patients face significant barriers to healthcare and experience negative impacts on their quality of life. Additionally, caregivers of SCD patients also reported experiencing burdens. The findings highlight the importance of further research into specific healthcare delivery barriers and the need for increased education and support for individuals affected by SCD in Grenada and the wider Caribbean community.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Chaya N. Murali, Brady Slater, Salma Musaad, David Cuthbertson, Dianne Nguyen, Alicia Turner, Mahshid Azamian, Laura Tosi, Frank Rauch, V. Reid Sutton, Brendan Lee, Sandesh C. S. Nagamani
Summary: PROMs are increasingly used in clinical trials, with SF-12v2 being a commonly used generic measure. In this study, SF-12v2 was found to be valid in assessing physical HRQoL in adults with OI. However, no correlations were found between mental and physical HRQoL in this population.
Article
Biochemical Research Methods
Lillian R. Thistlethwaite, Varduhi Petrosyan, Xiqi Li, Marcus J. Miller, Sarah H. Elsea, Aleksandar Milosavljevic
Summary: The paper introduces a novel information-theoretic formulation of identifying highly connected subsets within a weighted graph without the need for computationally costly permutation testing. The proposed algorithm, CTD Connect the Dots, uses data compression to detect highly connected subsets within a given set of nodes.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Genetics & Heredity
Runjun D. Kumar, Lindsay C. Burrage, Jan Bartos, Saima Ali, Eric Schmitt, Sandesh C. S. Nagamani, Cynthia LeMons
Summary: This study utilized a gene panel based on massively parallel sequencing to test 10 individuals with clinical or pedigree-based evidence of proximal UCD without molecular confirmation, identifying causal variants in 5 of the individuals. The findings suggest that deep-intronic pathogenic variants may play an important role in causing OTC deficiency.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2021)
Article
Multidisciplinary Sciences
Adam D. Kennedy, Lisa Ford, Bryan Wittmann, Jesse Conner, Jacob Wulff, Matthew Mitchell, Anne M. Evans, Douglas R. Toal
Summary: This study analyzed the effects of different anticoagulants on biochemical levels in blood samples using a global metabolomics platform. The results showed significant differences in biochemical composition, highlighting the importance of consistent additives in clinical metabolomics for assessing small molecule levels.
Article
Genetics & Heredity
John Odom, Hitha Amin, Charul Gijavanekar, Sarah H. Elsea, Stephen Kralik, Javier Chinen, Yuezhen Lin, Amber Meshell Mayfield Yates, Elizabeth Mizerik, Lorraine Potocki, Fernando Scaglia
Summary: Sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) is caused by pathogenic variants in the TRNT1 gene, leading to mitochondrial and cytosolic tRNA processing disorders. In addition to the main symptoms, patients may also exhibit growth hormone deficiency-related hypoglycemia, indicating the complexity and variability of the disease. Metabolomics analysis may provide insights into potential biochemical markers for SIFD.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Peripheral Vascular Disease
Xiqi Li, Aleksandar Milosavljevic, Sarah H. Elsea, Chi Chiu Wang, Fernando Scaglia, Argyro Syngelaki, Kypros H. Nicolaides, Liona C. Poon
Summary: Untargeted metabolomics analysis of plasma samples from high-risk pregnant women before and after aspirin treatment revealed metabolic effects of aspirin and differences potentially associated with treatment response. Aspirin treatment significantly reduces the rate of preterm preeclampsia in high-risk women and the treatment response is significantly linked to internal aspirin exposure levels.
Article
Medicine, General & Internal
Ning Liu, Jing Xiao, Charul Gijavanekar, Kirk L. Pappan, Kevin E. Glinton, Brian J. Shayota, Adam D. Kennedy, Qin Sun, V. Reid Sutton, Sarah H. Elsea
Summary: The study compared the diagnostic rates of traditional metabolic screening and clinical metabolomics, finding that clinical metabolomics had a higher diagnostic rate and could identify a wider variety of inborn errors of metabolism.
Article
Clinical Neurology
Kirt Martin, Alice McConnell, Sarah H. Elsea
Summary: Pathogenic variants in the ALDH5A1 gene lead to SSADH deficiency, with an estimated global prevalence of 1/460,000 and highest carrier frequencies in East Asian and South Asian populations. However, the pan-ethnic carrier frequency for SSADH deficiency may not be fully represented in gnomAD, requiring further analysis to assess the prevalence of this ultra-rare disease.
JOURNAL OF CHILD NEUROLOGY
(2021)
Article
Genetics & Heredity
Giavanna Verdi, Dong Li, Sarah H. Elsea, Beverly Nelson, Elizabeth J. Bhoj, Hakon Hakonarson, Katherine R. Yearwood, Sharmila Upadhya, Sarah Gluschitz, Janice L. Smith, Andrew K. Sobering
Summary: Through international collaboration, we identified a chromosomal abnormality in a boy of Afro-Caribbean descent. The clinical features of this boy suggest the presence of both partial deletion of chromosome 18 and partial duplication of chromosome 5, a combination that has not been described previously.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Biophysics
Neeraja Ravi, Sarah E. Chang, Luis M. Franco, Sandesh C. S. Nagamani, Purvesh Khatri, Paul J. Utz, Shan X. Wang
Summary: Detecting and quantifying the host transcriptional response to influenza virus infection can serve as a real-time diagnostic tool for clinical management. We have developed a novel assay based on the influenza metasignature (IMS) using GMR sensors, which can classify influenza infection based on transcript levels. We also validated the accuracy of a single biomarker in stratifying patients with influenza.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Medicine, Research & Experimental
Jordan Kho, Urszula Polak, Ming-Ming Jiang, John D. Odom, Jill V. Hunter, Saima M. Ali, Lindsay C. Burrage, Sandesh C. S. Nagamani, Robia G. Pautler, Hannah P. Thompson, Akihiko Urayama, Zixue Jin, Brendan Lee
Summary: Nitric oxide (NO) is a critical signaling molecule implicated in neurocognitive diseases. Excessive and insufficient NO production have both been linked to pathology. This study investigates the effects of NO on brain endothelial cells and the blood-brain barrier using a model of NO deficiency. The results suggest that ASL-mediated NO synthesis is necessary for maintaining brain microvascular endothelial cell functions and BBB integrity.
Article
Medicine, Research & Experimental
I-Wen Song, Sandesh Cs Nagamani, Dianne Nguyen, Ingo Grafe, Vernon Reid Sutton, Francis H. Gannon, Elda Munivez, Ming-Ming Jiang, Alyssa Tran, Maegen Wallace, Paul Esposito, Salma Musaad, Elizabeth Strudthoff, Sharon McGuire, Michele Thornton, Vinitha Shenava, Scott Rosenfeld, Shixia Huang, Roman Shypailo, Eric Orwoll, Brendan Lee
Summary: The study found that there is excessive TGF-beta signaling in patients with osteogenesis imperfecta (OI). TGF-beta signaling may be a driver pathogenic mechanism in OI. Anti-TGF-beta therapy could be a potential disease-specific therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Psychology, Developmental
Anusha Gandhi, Dihong Zhou, Joseph Alaimo, Edwin Chon, Michael D. Fountain, Sarah H. Elsea
Summary: Caregivers of children with Smith-Magenis syndrome (SMS), MBD5-associated neurodevelopmental disorder (MAND), and Pitt-Hopkins syndrome (PTHS) were surveyed to assess sleep disturbance and identify specific sleep problems for each disorder. Results showed differences in sleep patterns compared to children with autism spectrum disorder (ASD), with PTHS having significant but less severe sleep disturbances than SMS and MAND. More support, education, and ongoing management of sleep are needed for these individuals due to the complexity of these conditions and challenges of underlying sleep disturbance.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2021)
Article
Genetics & Heredity
Alyssa Grygiel, Felicia Ikolo, Raphielle Stephen, Dawnell Bleasdille, Patricia Robbins-Furman, Beverly Nelson, Andrew K. Sobering, Sarah H. Elsea
Summary: Grenada, a small resource-limited Caribbean country, faces challenges in healthcare access and quality of life for individuals with sickle cell disease (SCD). Findings indicate that both SCD patients and caregivers encounter barriers to healthcare, while adults and children with SCD experience different issues in quality of life.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)