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      Uricase-deficient rats with similarly stable serum uric acid to human’s are sensitive model animals for studying hyperuricemia

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          Abstract

          The aim of this study was to provide a sensitive model animal for studying hyperuricemia. Male uricase-deficient rats, named Kunming-DY rats, were raised for 130 days, or orally administered with purines and other chemicals. Serum uric acid (SUA) in the animals was assayed, and the UA level in their organs and their 24-h excretion was determined. Genes in the jejunum, ileum, kidney and liver related to UA synthesis and transportation were detected by quantitative RNA sequencing. Uricase-deficient rats have a high level of SUA and are sensitive to xanthine, adenosine, inosine, allopurinol, and alcohol. Besides, the high level of SUA in male uricase-deficient rats was stable, much higher than that in wild-type rats but similar to that in men. The distribution pattern of UA in uricase-deficient rats’ organs was different from that in wild-type rats. The kidney, liver, and small intestine were the top three organs where UA distributed, but the UA in the small intestine, colon, lung, thymus, and brain was less affected by uricase deficiency, indicating that these organs are constitutive distribution organs in UA. The 24-h UA excreted by a uricase-deficient rat was about five times higher than that excreted by a wild-type rat. However, the 24-h UA excreted through feces was not significantly changed. Both the urine volume and UA in uricase-deficient rats significantly increased, and more than 90% of UA was excreted via urine. The expression of xanthine dehydrogenase was not upregulated. Some genes of transporter associated with uric acid excretion in the kidney were significantly regulated, though not sufficient to explain the increase in SUA. In conclusion, male uricase-deficient rats’ UA metabolism is similar to that of men. The elevation of SUA in uricase-deficient rats is caused by uricase deficiency, and uricase-deficient rats are a sensitive model for studying hyperuricemia.

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          Transcript assembly and abundance estimation from RNA-Seq reveals thousands of new transcripts and switching among isoforms

          High-throughput mRNA sequencing (RNA-Seq) holds the promise of simultaneous transcript discovery and abundance estimation 1-3 . We introduce an algorithm for transcript assembly coupled with a statistical model for RNA-Seq experiments that produces estimates of abundances. Our algorithms are implemented in an open source software program called Cufflinks. To test Cufflinks, we sequenced and analyzed more than 430 million paired 75bp RNA-Seq reads from a mouse myoblast cell line representing a differentiation time series. We detected 13,692 known transcripts and 3,724 previously unannotated ones, 62% of which are supported by independent expression data or by homologous genes in other species. Analysis of transcript expression over the time series revealed complete switches in the dominant transcription start site (TSS) or splice-isoform in 330 genes, along with more subtle shifts in a further 1,304 genes. These dynamics suggest substantial regulatory flexibility and complexity in this well-studied model of muscle development.
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            SeqKit: A Cross-Platform and Ultrafast Toolkit for FASTA/Q File Manipulation

            FASTA and FASTQ are basic and ubiquitous formats for storing nucleotide and protein sequences. Common manipulations of FASTA/Q file include converting, searching, filtering, deduplication, splitting, shuffling, and sampling. Existing tools only implement some of these manipulations, and not particularly efficiently, and some are only available for certain operating systems. Furthermore, the complicated installation process of required packages and running environments can render these programs less user friendly. This paper describes a cross-platform ultrafast comprehensive toolkit for FASTA/Q processing. SeqKit provides executable binary files for all major operating systems, including Windows, Linux, and Mac OSX, and can be directly used without any dependencies or pre-configurations. SeqKit demonstrates competitive performance in execution time and memory usage compared to similar tools. The efficiency and usability of SeqKit enable researchers to rapidly accomplish common FASTA/Q file manipulations. SeqKit is open source and available on Github at https://github.com/shenwei356/seqkit.
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              Gout

              Gout is a chronic disease caused by monosodium urate (MSU) crystal deposition. Gout typically presents as an acute, self-limiting inflammatory monoarthritis that affects the joints of the lower limb. Elevated serum urate level (hyperuricaemia) is the major risk factor for MSU crystal deposition and development of gout. Although traditionally considered a disorder of purine metabolism, altered urate transport, both in the gut and the kidneys, has a key role in the pathogenesis of hyperuricaemia. Anti-inflammatory agents, such corticosteroids, NSAIDs and colchicine, are widely used for the treatment of gout flare; recognition of the importance of NLRP3 inflammasome activation and bioactive IL-1β release in initiation of the gout flare has led to the development of anti-IL-1β biological therapy for gout flares. Sustained reduction in serum urate levels using urate-lowering therapy is vital in the long-term management of gout, which aims to dissolve MSU crystals, suppress gout flares and resolve tophi. Allopurinol is the first-line urate-lowering therapy and should be started at a low dose, with gradual dose escalation. Low-dose anti-inflammatory therapies can reduce gout flares during initiation of urate-lowering therapy. Models of care, such as nurse-led strategies that focus on patient engagement and education, substantially improve clinical outcomes and now represent best practice for gout management.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: InvestigationRole: Methodology
                Role: Formal analysisRole: Resources
                Role: ConceptualizationRole: Data curationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 March 2022
                2022
                : 17
                : 3
                : e0264696
                Affiliations
                [1 ] The Department of Pharmacology, School of Basic Medicine, Kunming Medical University, Kunming, Yunnan Province, China
                [2 ] The Department of Pathology, School of Basic Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China
                University Medical Center Utrecht, NETHERLANDS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-9006-861X
                Article
                PONE-D-21-37142
                10.1371/journal.pone.0264696
                8893661
                35239728
                ec286270-77bd-4bb5-be05-78862918f4cd
                © 2022 Gao et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 November 2021
                : 15 February 2022
                Page count
                Figures: 8, Tables: 2, Pages: 19
                Funding
                Funded by: Yunnan Provincial Science and Technology Department–Applied Basic Research Joint Special Funds of Kunming Medical University
                Award ID: 202101AY070001-007
                Award Recipient :
                Funded by: the National Natural Science Foundation of China
                Award ID: 81860162
                Award Recipient :
                Funded by: Yunnan Provincial Science and Technology Department–Applied Basic Research Joint Special Funds of Yunnan University of Traditional Chinese Medicine
                Award ID: 202101AZ070001-010
                Award Recipient :
                The work was financially supported by the National Natural Science Foundation of China (No. 81860162), Yunnan Provincial Science and Technology Department–Applied Basic Research Joint Special Funds of Kunming Medical University (202101AY070001-007), and Yunnan Provincial Science and Technology Department–Applied Basic Research Joint Special Funds of Yunnan University of Traditional Chinese Medicine (202101AZ070001-010).
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Uric Acid
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Excretion
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Purines
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Purines
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Urine
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Urine
                Biology and Life Sciences
                Physiology
                Body Fluids
                Urine
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Small Intestine
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Small Intestine
                Research and Analysis Methods
                Chemical Synthesis
                Biology and Life Sciences
                Anatomy
                Liver
                Medicine and Health Sciences
                Anatomy
                Liver
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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