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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before July 31, 2024

      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Genetic and Biological Effects of Sodium-Chloride Cotransporter ( SLC12A3 ) in Diabetic Nephropathy

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          Abstract

          Background/Aims: Solute carrier family 12 member 3 ( SLC12A3) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of SLC12A3 in DN. In this study, we aim to evaluate the genetic effects of the SLC12A3 gene and its Arg913Gln polymorphism with genetic and functional analyses. Methods: We genotyped SLC12A3 genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of slc12a3 in kidney development and progress of DN in zebrafish and db/db mice. Results: We found that SLC12A3 Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of SLC12A3 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage. Slc12a3 mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. Conclusion: The present study provided the first biological and further genetic evidence that SLC12A3 has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease. i 2014 S. Karger AG, Basel

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          Think Small: Zebrafish as a Model System of Human Pathology

          J R Goldsmith, Christian Jobin (2012)
          Although human pathologies have mostly been modeled using higher mammal systems such as mice, the lower vertebrate zebrafish has gained tremendous attention as a model system. The advantages of zebrafish over classical vertebrate models are multifactorial and include high genetic and organ system homology to humans, high fecundity, external fertilization, ease of genetic manipulation, and transparency through early adulthood that enables powerful imaging modalities. This paper focuses on four areas of human pathology that were developed and/or advanced significantly in zebrafish in the last decade. These areas are (1) wound healing/restitution, (2) gastrointestinal diseases, (3) microbe-host interactions, and (4) genetic diseases and drug screens. Important biological processes and pathologies explored include wound-healing responses, pancreatic cancer, inflammatory bowel diseases, nonalcoholic fatty liver disease, and mycobacterium infection. The utility of zebrafish in screening for novel genes important in various pathologies such as polycystic kidney disease is also discussed.
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            TESS: a geometric hashing algorithm for deriving 3D coordinate templates for searching structural databases. Application to enzyme active sites.

            J Thornton, N Borkakoti, Helen Wallace (1997)
            It is well established that sequence templates such as those in the PROSITE and PRINTS databases are powerful tools for predicting the biological function and tertiary structure for newly derived protein sequences. The number of X-ray and NMR protein structures is increasing rapidly and it is apparent that a 3D equivalent of the sequence templates is needed. Here, we describe an algorithm called TESS that automatically derives 3D templates from structures deposited in the Brookhaven Protein Data Bank. While a new sequence can be searched for sequence patterns, a new structure can be scanned against these 3D templates to identify functional sites. As examples, 3D templates are derived for enzymes with an O-His-O "catalytic triad" and for the ribonucleases and lysozymes. When these 3D templates are applied to a large data set of nonidentical proteins, several interesting hits are located. This suggests that the development of a 3D template database may help to identify the function of new protein structures, if unknown, as well as to design proteins with specific functions.
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              Zebrafish as an animal model to study ion homeostasis

              Pung-Pung Hwang, Ming-Yi Chou (2013)
              Zebrafish (Danio rerio) possesses several advantages as an experimental organism, including the applicability of molecular tools, ease of in vivo cellular observation and functional analysis, and rapid embryonic development, making it an emerging model for the study of integrative and regulatory physiology and, in particular, the epithelial transport associated with body fluid ionic homeostasis. Zebrafish inhabits a hypotonic freshwater environment, and as such, the gills (or the skin, during embryonic stages) assume the role of the kidney in body fluid ionic homeostasis. Four types of ionocyte expressing distinct sets of transporters have been identified in these organs: H+-ATPase-rich, Na+-K+-ATPase-rich, Na+-Cl− cotransporter-expressing and K+-secreting cells; these ionocytes perform transepithelial H+ secretion/Na+ uptake/NH4 + excretion, Ca2+ uptake, Na+/Cl− uptake, and K+ secretion, respectively. Zebrafish ionocytes are analogous to various renal tubular cells, in terms of ion transporter expression and function. During embryonic development, ionocyte progenitors develop from epidermal stem cells and then differentiate into different types of ionocyte through a positive regulatory loop of Foxi3a/-3b and other transcription factors. Several hormones, including cortisol, vitamin D, stanniocalcin-1, calcitonin, and isotocin, were found to participate in the control pathways of ionic homeostasis by precisely studying the target ion transport pathways, ion transporters, or ionocytes of the hormonal actions. In conclusion, the zebrafish model not only enhances our understanding of body fluid ion homeostasis and hormonal control in fish but also informs studies on mammals and other animal species, thereby providing new insights into related fields.
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                Author and article information

                Journal
                Journal ID (publisher-id): AJN
                Journal ID (nlm-ta): Am J Nephrol
                Journal ID (doi): 10.1159/issn.0250-8095
                Title: American Journal of Nephrology
                Publisher: S. Karger AG
                ISSN (Print): 0250-8095
                ISSN (Electronic): 1421-9670
                Publication date Subscription-year: 2014
                Publication date (Print): December 2014
                Publication date (Electronic): 14 November 2014
                Volume: 40
                Issue: 5
                Pages: 408-416
                Affiliations
                aRolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; bCardiovascular, Diabetes and Nutrition Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia; cDivision of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
                Author notes
                *Harvest F. Gu, M1:03 Karolinska University Hospital, SE-17176 Stockholm (Sweden), E-Mail harvest.gu@ki.se
                Article
                Publisher ID: 368916 Other ID: Am J Nephrol 2014;40:408-416
                DOI: 10.1159/000368916
                PubMed ID: 25401745
                SO-VID: 7afad16a-039b-4e5c-ab8b-ca08ea686397
                Copyright © © 2014 S. Karger AG, Basel
                License:

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 19 August 2014
                Date accepted : 06 October 2014
                Page count
                Figures: 4, Tables: 3, Pages: 9
                Categories
                Subject: Original Report: Laboratory Investigation

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: SLC12A3,Diabetic nephropathy,Type 2 diabetes
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: SLC12A3, Diabetic nephropathy, Type 2 diabetes

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