Eatly appreciated the assistance of Yun Zhou and Ning Lu for collecting the water samples. The authors would like to thank the anonymous reviewers and the editor for their comments and suggestions.Application of the New LLE-GC-ECD Method to Field SamplesIn order to validate the optimized method that was developed in this study, drinking water samples were collected and analyzed forPLOS ONE | www.plosone.orgAuthor ContributionsReviewed paper, provided comments and suggestions for revision: XLL XW MRT GSH WDQ. Conceived and designed the experiments: XLL XW GSH WDQ. Performed the experiments: XLL XW WWZ SHJ. Analyzed the data: XLL XW WWZ WDQ. Contributed reagents/Detecting IAA, IF, THM4, and HAA9 in Watermaterials/analysis tools: XLL XW DZ WWZ SHJ. Wrote the paper: XLL XW GSH WDQ.
Lysosomal storage diseases (LSDs) are a heterogeneous collection of over 50 diseases caused by deficiencies in key components of the lysosomal degradation system [1]. Depending on the nature of the lysosomal deficiency, a wide range of metabolites can accumulate including glycans, lipids and proteins, leading to deleterious effects in multiple2013 Elsevier Inc. All rights reserved. Corresponding author. bcrawford@bmrn (B.E. Crawford). **Correspondence to: J.D. Esko, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0687, USA. Fax: +1 858 534 5611. [email protected] (J.D. Esko). Conflict of interest Jillian R. Brown and Brett E. Crawford were employees of Zacharon Pharmaceuticals, Inc. at the time that the paper was written and Roger Lawrence and Jeffrey D. Esko were paid consultants to the company.*Lawrence et al.Pagetissues and organs. LSDs exhibit a great variation in the age of onset and rate of disease progression due to the degree of enzyme deficiency, genotypic modifiers and poorly defined environmental factors. Thus, both severe and attenuated forms of the disease exist, which do not correlate well with genotype. When symptoms are present, most patients begin what has been called a “diagnostic odyssey” to correctly diagnose the disease and to select appropriate treatment [2]. The absence of early diagnosis, especially in infants, can lead to irreversible developmental, neurological, and physiological changes. Thus, there is a great need for simple, reliable biomarkers for early diagnosis. Such biomarkers could also prove useful for monitoring of disease progression and for optimization of therapy.Clindamycin palmitate hydrochloride Mucopolysaccharidoses (MPS) refer to a subset of LSDs in which deficiencies occur in one or more enzymes involved in the degradation of glycosaminoglycans (GAGs) [3].Lusutrombopag Five types of GAGs exist: heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), hyaluronan (HA), and keratan sulfate (KS).PMID:23724934 A family of at least 11 enzymes catalyzes the lysosomal degradation of GAGs, including several glycosidases and sulfatases, an acetyltransferase, and an enzyme required for generating the catalytically active form of all known sulfatases (Table 1). Degradation of the chains occurs in a directional manner by removal or processing of the terminal sugar on the non-reducing end (NRE) of the GAG chain (Fig. 1). Due to the sequential nature of the degradative process, mutations in any enzyme in the pathway result in lysosomal storage of undegraded GAGs, the composition of which depends on the specific enzyme deficiency (Table 1). In addition to the lysosomal enzymes, an extracellular endoglycosidase (heparanase) can cle.