{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:28:50Z","timestamp":1788175730204,"version":"build-2803163510"},"reference-count":104,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"WIRES","award":["USYD217760"],"award-info":[{"award-number":["USYD217760"]}]},{"name":"Winifred Violet Scott Charitable Foundation","award":["USYD G218502"],"award-info":[{"award-number":["USYD G218502"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Chlamydiosis is the major infectious disease responsible for significant morbidity and mortality in free-living koalas. Recently, it was reported that 28.5% of koalas infected with chlamydiosis were presented with no overt clinical signs. Identification and quantification of changes in plasma biomarkers\u2019 fluctuations have the potential to enhance <jats:italic>C<\/jats:italic>. <jats:italic>pecorum<\/jats:italic> detection and facilitate the monitoring of therapeutic efficacy of antibiotics to treat this disease in koalas. Therefore, concentrations of the essential amino acid tryptophan, tryptophan\u2019s metabolite kynurenine, and the kynurenine:tryptophan ratio were quantified by high-performance liquid chromatography in the plasma of clinically normal koalas (n = 35), koalas identified with chlamydial disease (n = 35) and koalas that had other non-chlamydial co-morbidities (n = 10). Results showed that there was a significant difference between the clinically normal versus diseased, and clinically normal versus \u2018other\u2019 (both p &lt; 0.001) in kynurenine plasma concentrations and kynurenine:tryptophan ratio; and also between the clinically normal and diseased in tryptophan plasma concentrations (p = 0.001). Proposed reference ranges of tryptophan, kynurenine, and kynurenine:tryptophan ratio in koalas are: 4.27\u201310.4 \u03bcg\/mL, 0.34\u20131.23 \u03bcg\/mL, and 0.05\u20130.22, respectively. Proposed optimal cut-off points to differentiate between clinically normal and diseased are: \u2264 4.75 \u03bcg\/mL (tryptophan), \u2265 0.88 \u03bcg\/mL (kynurenine), and \u2265 0.12 (kynurenine:tryptophan); and \u2264 7.67 \u03bcg\/mL (tryptophan), \u2265 1.18 \u03bcg\/mL (kynurenine), and \u2265 0.16 (kynurenine:tryptophan) to differentiate between released\/recovered and euthanised of the diseased\/\u2018other\u2019 koalas. Significant differences in haematological and biochemical analytes were in the plasma globulins between the clinically normal and diseased koalas (p = 0.01), and in alkaline phosphatase between the clinically normal and \u2018other\u2019 koalas (p = 0.03). Although these potential biomarkers, especially tryptophan, may not be specific for detecting <jats:italic>C<\/jats:italic>. <jats:italic>pecorum<\/jats:italic> from the rest of the population, kynurenine and the kynurenine:tryptophan ratio may have a role in identifying unhealthy koalas from the clinically normal ones, irrespective of the underlying cause.<\/jats:p>","DOI":"10.1371\/journal.pone.0314945","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T18:47:51Z","timestamp":1734634071000},"page":"e0314945","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preliminary analyses of tryptophan, kynurenine, and the kynurenine: Tryptophan ratio in plasma, as potential biomarkers for systemic chlamydial infections in koalas"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6757-9323","authenticated-orcid":true,"given":"Chien-Jung","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kimble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Van Aggelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyne","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Gillett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2343-250X","authenticated-orcid":true,"given":"Jodie","family":"Wakeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merran","family":"Govendir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"issue":"21","key":"pone.0314945.ref001","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222111714","article-title":"Tryptophan: A Unique Role in the Critically Ill.","volume":"22","author":"M Kanova","year":"2021","journal-title":"Int J Mol Sci."},{"key":"pone.0314945.ref002","doi-asserted-by":"crossref","first-page":"1178646917691938","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects.","volume":"10","author":"AA Badawy","year":"2017","journal-title":"Int J Tryptophan Res"},{"issue":"2","key":"pone.0314945.ref003","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0098-2997(83)90005-5","article-title":"Biochemistry of tryptophan in health and disease","volume":"6","author":"DA Bender","year":"1983","journal-title":"Molecular aspects of medicine"},{"key":"pone.0314945.ref004","article-title":"Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention.","volume":"9","author":"AA Badawy","year":"2019","journal-title":"Egypt J Basic Clin Pharmacol"},{"issue":"4","key":"pone.0314945.ref005","doi-asserted-by":"crossref","first-page":"e59749","DOI":"10.1371\/journal.pone.0059749","article-title":"Expression of tryptophan 2, 3-dioxygenase and production of kynurenine pathway metabolites in triple transgenic mice and human Alzheimer\u2019s disease brain","volume":"8","author":"W Wu","year":"2013","journal-title":"PloS one"},{"key":"pone.0314945.ref006","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00726-016-2351-8","article-title":"A review of the immunomodulatory role of dietary tryptophan in livestock and poultry","volume":"49","author":"M Bai","year":"2017","journal-title":"Amino Acids"},{"key":"pone.0314945.ref007","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuropharm.2016.03.013","article-title":"Perez de la Cruz V. Kynurenine pathway metabolites and enzymes involved in redox reactions","volume":"112","author":"D Gonzalez Esquivel","year":"2017","journal-title":"Neuropharmacology"},{"key":"pone.0314945.ref008","first-page":"1","article-title":"The effect of dietary tryptophan levels on oxidative stress of liver induced by diquat in weaned piglets","volume":"5","author":"X Mao","year":"2014","journal-title":"Journal of animal science and biotechnology"},{"key":"pone.0314945.ref009","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cbi.2014.07.009","article-title":"Sensitivity of avian species to the aryl hydrocarbon receptor ligand 6-formylindolo [3, 2-b] carbazole (FICZ).","volume":"221","author":"R Farmahin","year":"2014","journal-title":"Chemico-Biological Interactions"},{"issue":"23","key":"pone.0314945.ref010","doi-asserted-by":"crossref","first-page":"14694","DOI":"10.1073\/pnas.232562899","article-title":"A ligand for the aryl hydrocarbon receptor isolated from lung","volume":"99","author":"J Song","year":"2002","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"13","key":"pone.0314945.ref011","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1016\/S0021-9258(17)30447-7","article-title":"Indoleamine 2,3-dioxygenase. Purification and some properties","volume":"253","author":"T Shimizu","year":"1978","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0314945.ref012","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.gene.2007.04.010","article-title":"Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice","volume":"396","author":"HJ Ball","year":"2007","journal-title":"Gene"},{"key":"pone.0314945.ref013","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4137\/IJTR.S12626","article-title":"The kynurenine pathway in stem cell biology","volume":"6","author":"SP Jones","year":"2013","journal-title":"Int J Tryptophan Res"},{"key":"pone.0314945.ref014","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.3389\/fimmu.2020.01741","article-title":"Intestinal dysbiosis and tryptophan metabolism in autoimmunity","volume":"11","author":"J Brown","year":"2020","journal-title":"Frontiers in immunology"},{"key":"pone.0314945.ref015","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.949603","article-title":"Fine-tuning of regulatory T cells is indispensable for the metabolic steatosis-related hepatocellular carcinoma: A review.","volume":"10","author":"F Riaz","year":"2022","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"pone.0314945.ref016","first-page":"2378","article-title":"The neurobiology of depression\u2014revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms.","author":"PR Albert","year":"2012","journal-title":"The Royal Society"},{"issue":"1","key":"pone.0314945.ref017","first-page":"56","article-title":"Tryptophan\u2013kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later.","volume":"47","author":"GF Oxenkrug","year":"2010","journal-title":"The Israel journal of psychiatry and related sciences."},{"issue":"551","key":"pone.0314945.ref018","doi-asserted-by":"crossref","first-page":"eaax2220","DOI":"10.1126\/scitranslmed.aax2220","article-title":"Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice","volume":"12","author":"S-C Choi","year":"2020","journal-title":"Science translational medicine"},{"key":"pone.0314945.ref019","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/978-1-4684-5952-4_39","article-title":"Implications of interferon-induced tryptophan catabolism in cancer, autoimmune diseases and AIDS.","author":"R Brown","year":"1991","journal-title":"Kynurenine and Serotonin Pathways: Progress in Tryptophan Research."},{"issue":"4","key":"pone.0314945.ref020","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.autrev.2019.02.004","article-title":"Amino acid metabolism as drug target in autoimmune diseases","volume":"18","author":"G Mondanelli","year":"2019","journal-title":"Autoimmunity Reviews"},{"issue":"1","key":"pone.0314945.ref021","doi-asserted-by":"crossref","first-page":"42587","DOI":"10.1038\/srep42587","article-title":"Decline causes of Koalas in South East Queensland, Australia: a 17-year retrospective study of mortality and morbidity.","volume":"7","author":"V Gonzalez-Astudillo","year":"2017","journal-title":"Scientific Reports."},{"key":"pone.0314945.ref022","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.vetmic.2013.02.026","article-title":"Recent advances in understanding the biology, epidemiology and control of chlamydial infections in koalas","volume":"165","author":"A Polkinghorne","year":"2013","journal-title":"Vet Microbiol"},{"issue":"11","key":"pone.0314945.ref023","doi-asserted-by":"crossref","first-page":"e0206471","DOI":"10.1371\/journal.pone.0206471","article-title":"Chlamydia pecorum gastrointestinal tract infection associations with urogenital tract infections in the koala (Phascolarctos cinereus).","volume":"13","author":"S Phillips","year":"2018","journal-title":"PloS one"},{"issue":"1","key":"pone.0314945.ref024","doi-asserted-by":"crossref","first-page":"12670","DOI":"10.1038\/s41598-023-39832-w","article-title":"A retrospective study on antibacterial treatments for koalas infected with Chlamydia pecorum.","volume":"13","author":"CJ Chen","year":"2023","journal-title":"Sci Rep."},{"issue":"4","key":"pone.0314945.ref025","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/IAI.00714-17","article-title":"Characterization of the In Vitro Chlamydia pecorum Response to Gamma Interferon","volume":"86","author":"MM Islam","year":"2018","journal-title":"Infection and Immunity"},{"issue":"12","key":"pone.0314945.ref026","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.1128\/JB.01660-05","article-title":"Molecular mechanism of tryptophan-dependent transcriptional regulation in Chlamydia trachomatis","volume":"188","author":"JC Akers","year":"2006","journal-title":"Journal of bacteriology"},{"issue":"1","key":"pone.0314945.ref027","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1186\/1471-2164-15-667","article-title":"Comparative genomics of koala, cattle and sheep strains of Chlamydia pecorum","volume":"15","author":"NL Bachmann","year":"2014","journal-title":"BMC Genomics"},{"issue":"14","key":"pone.0314945.ref028","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1128\/JB.00454-11","article-title":"Genome sequence of the obligate intracellular animal pathogen Chlamydia pecorum E58","volume":"193","author":"S Mojica","year":"2011","journal-title":"J Bacteriol"},{"issue":"1","key":"pone.0314945.ref029","first-page":"286","article-title":"Tryptophan metabolism in animals: important roles in nutrition and health","volume":"3","author":"K Yao","year":"2011","journal-title":"Front Biosci"},{"key":"pone.0314945.ref030","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4137\/IJTR.S38189","article-title":"Assessment of the Human Kynurenine Pathway: Comparisons and Clinical Implications of Ethnic and Gender Differences in Plasma Tryptophan, Kynurenine Metabolites, and Enzyme Expressions at Baseline and After Acute Tryptophan Loading and Depletion","volume":"9","author":"AA Badawy","year":"2016","journal-title":"Int J Tryptophan Res"},{"issue":"9","key":"pone.0314945.ref031","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0014-827X(03)00140-X","article-title":"Enzyme activities of tryptophan metabolism along the kynurenine pathway in various species of animals","volume":"58","author":"G Allegri","year":"2003","journal-title":"Farmaco"},{"issue":"3","key":"pone.0314945.ref032","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1471-4159.1978.tb07815.x","article-title":"Synthesis and metabolism of L-kynurenine in rat brain","volume":"30","author":"EM G\u00e1l","year":"1978","journal-title":"J Neurochem"},{"key":"pone.0314945.ref033","article-title":"CSF neopterin, quinolinic acid and kynurenine\/tryptophan ratio are biomarkers of active neuroinflammation.","volume":"91","author":"J Yan","year":"2023","journal-title":"eBioMedicine"},{"issue":"9","key":"pone.0314945.ref034","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22094403","article-title":"Kynurenine\/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.","volume":"22","author":"M Mandarano","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0314945.ref035","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.lungcan.2009.05.001","article-title":"Increased serum kynurenine\/tryptophan ratio correlates with disease progression in lung cancer","volume":"67","author":"Y Suzuki","year":"2010","journal-title":"Lung Cancer"},{"issue":"8","key":"pone.0314945.ref036","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20230595","article-title":"The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy","volume":"43","author":"AA Badawy","year":"2023","journal-title":"Biosci Rep"},{"issue":"3","key":"pone.0314945.ref037","doi-asserted-by":"crossref","first-page":"166042","DOI":"10.1016\/j.bbadis.2020.166042","article-title":"Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study","volume":"1867","author":"L Lionetto","year":"2021","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"3","key":"pone.0314945.ref038","doi-asserted-by":"crossref","first-page":"e24257","DOI":"10.1002\/jcla.24257","article-title":"Kynurenine pathway in Coronavirus disease (COVID-19): Potential role in prognosis.","volume":"36","author":"M Cihan","year":"2022","journal-title":"J Clin Lab Anal"},{"key":"pone.0314945.ref039","doi-asserted-by":"crossref","first-page":"132522","DOI":"10.1016\/j.chemosphere.2021.132522","article-title":"Kynurenine to tryptophan ratio as a biomarker of acute stress in fish.","volume":"288","author":"J Wish","year":"2022","journal-title":"Chemosphere"},{"issue":"1\u20132","key":"pone.0314945.ref040","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.applanim.2004.05.004","article-title":"Chronic increase of dietary L-tryptophan decreases gentle feather pecking behaviour","volume":"89","author":"YM van Hierden","year":"2004","journal-title":"Applied Animal Behaviour Science"},{"issue":"6","key":"pone.0314945.ref041","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/mp.2012.77","article-title":"The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner","volume":"18","author":"G Clarke","year":"2013","journal-title":"Mol Psychiatry"},{"issue":"4 Pt 2","key":"pone.0314945.ref042","first-page":"755","article-title":"Kynurenine and its metabolites in the rat with experimental renal insufficiency","volume":"52","author":"D Pawlak","year":"2001","journal-title":"J Physiol Pharmacol"},{"issue":"3","key":"pone.0314945.ref043","doi-asserted-by":"crossref","first-page":"F565","DOI":"10.1152\/ajprenal.2000.279.3.F565","article-title":"Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency","volume":"279","author":"K Saito","year":"2000","journal-title":"Am J Physiol Renal Physiol"},{"issue":"2","key":"pone.0314945.ref044","first-page":"175","article-title":"Peripheral distribution of kynurenine metabolites and activity of kynurenine pathway enzymes in renal failure","volume":"54","author":"D Pawlak","year":"2003","journal-title":"J Physiol Pharmacol"},{"issue":"3","key":"pone.0314945.ref045","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3390\/metabo13030333","article-title":"Association between Tryptophan Metabolism and Inflammatory Biomarkers in Dairy Cows with Ketosis","volume":"13","author":"Z Luo","year":"2023","journal-title":"Metabolites"},{"issue":"6","key":"pone.0314945.ref046","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1111\/rda.13299","article-title":"Tryptophan, kynurenine, kynurenic acid concentrations and indoleamine 2,3-dioxygenase activity in serum and milk of dairy cows with subclinical mastitis caused by coagulase-negative staphylococci","volume":"53","author":"M Bochniarz","year":"2018","journal-title":"Reproduction in Domestic Animals"},{"issue":"5","key":"pone.0314945.ref047","first-page":"632","article-title":"Association of uterine and salpingeal fibrosis with chlamydial hsp60 and hsp10 antigen-specific antibodies in Chlamydia-infected koalas","volume":"12","author":"DP Higgins","year":"2005","journal-title":"Clin Diagn Lab Immunol"},{"key":"pone.0314945.ref048","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/978-1-4615-4709-9_105","article-title":"An HPLC method to determine tryptophan and kynurenine in serum simultaneously","volume":"467","author":"B Widner","year":"1999","journal-title":"Adv Exp Med Biol"},{"key":"pone.0314945.ref049","volume-title":"Bioanalytical method validation and study sample analysis M10","author":"ICH","year":"2022"},{"issue":"5","key":"pone.0314945.ref050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.19080\/OMCIJ.2018.07.555722","article-title":"Limit of Blank (LOB), Limit of Detection (LOD), and Limit of Quantification (LOQ).","volume":"7","author":"M. Taleuzzaman","year":"2018","journal-title":"Organic and Medicinal Chemistry International Journal"},{"key":"pone.0314945.ref051"},{"issue":"2","key":"pone.0314945.ref052","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/cc1473","article-title":"Statistics review 2: samples and populations.","volume":"6","author":"E Whitley","year":"2002","journal-title":"Crit Care."},{"key":"pone.0314945.ref053","volume-title":"An Introduction to Medical Statistics","author":"M. Bland","year":"2015"},{"issue":"Pt 5","key":"pone.0314945.ref054","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1258\/acb.2008.008028","article-title":"Use of routine clinical laboratory data to define reference intervals","volume":"45","author":"B. Shine","year":"2008","journal-title":"Ann Clin Biochem"},{"key":"pone.0314945.ref055","volume-title":"MedCalc Statistical Software","year":"2023"},{"issue":"1","key":"pone.0314945.ref056","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4103\/0301-4738.37595","article-title":"Understanding and using sensitivity, specificity and predictive values.","volume":"56","author":"R Parikh","year":"2008","journal-title":"Indian J Ophthalmol"},{"issue":"1","key":"pone.0314945.ref057","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"WJ Youden","year":"1950","journal-title":"Cancer"},{"issue":"1\u20132","key":"pone.0314945.ref058","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0167-5877(00)00115-X","article-title":"Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests","volume":"45","author":"M Greiner","year":"2000","journal-title":"Prev Vet Med"},{"issue":"5\u20136","key":"pone.0314945.ref059","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jchromb.2010.01.006","article-title":"Optimization of Zn2+-containing mobile phase for simultaneous determination of kynurenine, kynurenic acid and tryptophan in human plasma by high performance liquid chromatography","volume":"878","author":"J Zhao","year":"2010","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"issue":"1\u20132","key":"pone.0314945.ref060","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jad.2006.07.013","article-title":"Kynurenine pathway in major depression: evidence of impaired neuroprotection","volume":"98","author":"AM Myint","year":"2007","journal-title":"J Affect Disord"},{"issue":"3","key":"pone.0314945.ref061","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/clinchem\/48.3.579","article-title":"More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC","volume":"48","author":"A Laich","year":"2002","journal-title":"Clin Chem"},{"issue":"1","key":"pone.0314945.ref062","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0378-4347(95)00341-X","article-title":"Determination of tryptophan and its kynurenine pathway metabolites in human serum by high-performance liquid chromatography with simultaneous ultraviolet and fluorimetric detection","volume":"675","author":"C Herv\u00e9","year":"1996","journal-title":"J Chromatogr B Biomed Appl"},{"issue":"10","key":"pone.0314945.ref063","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/bmc.445","article-title":"Simultaneous determination of tryptophan and kynurenine in serum by HPLC with UV and fluorescence detection","volume":"18","author":"J Vignau","year":"2004","journal-title":"Biomed Chromatogr"},{"issue":"3","key":"pone.0314945.ref064","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.talanta.2011.06.027","article-title":"Determination of neopterin, kynurenine, tryptophan and creatinine in human serum by high throuput HPLC.","volume":"85","author":"L Krcmova","year":"2011","journal-title":"Talanta"},{"issue":"1","key":"pone.0314945.ref065","doi-asserted-by":"crossref","first-page":"7","DOI":"10.4142\/jvs.2013.14.1.7","article-title":"Quantitation of meloxicam in the plasma of koalas (Phascolarctos cinereus) by improved high performance liquid chromatography.","volume":"14","author":"B Kimble","year":"2013","journal-title":"J Vet Sci"},{"issue":"3","key":"pone.0314945.ref066","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3390\/ani12030250","article-title":"Pharmacokinetic Profile of Doxycycline in Koala Plasma after Weekly Subcutaneous Injections for the Treatment of Chlamydiosis.","volume":"12","author":"CJ Chen","year":"2022","journal-title":"Animals"},{"issue":"2","key":"pone.0314945.ref067","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0305-0491(73)90318-0","article-title":"Binding of tryptophan to plasma proteins in several species","volume":"46","author":"RW Fuller","year":"1973","journal-title":"Comp Biochem Physiol B"},{"issue":"1","key":"pone.0314945.ref068","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0003-9861(82)90192-8","article-title":"A comparative study of the binding of l-tryptophan and bilirubin by plasma proteins","volume":"216","author":"FCI Fellows","year":"1982","journal-title":"Archives of Biochemistry and Biophysics"},{"issue":"2","key":"pone.0314945.ref069","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1006\/abbi.1998.0861","article-title":"Species differences in L-tryptophan-kynurenine pathway metabolism: quantification of anthranilic acid and its related enzymes","volume":"358","author":"S Fujigaki","year":"1998","journal-title":"Arch Biochem Biophys"},{"key":"pone.0314945.ref070","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ijid.2019.12.005","article-title":"Neopterin levels and Kyn\/Trp ratios were significantly increased in dengue virus patients and subsequently decreased after recovery","volume":"91","author":"S Geisler","year":"2020","journal-title":"International Journal of Infectious Diseases"},{"issue":"Pt 3","key":"pone.0314945.ref071","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/0004563215583360","article-title":"Reference intervals for plasma-free amino acid in a Japanese population","volume":"53","author":"H Yamamoto","year":"2016","journal-title":"Ann Clin Biochem"},{"issue":"10","key":"pone.0314945.ref072","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0031-9422(00)88697-5","article-title":"Free amino acids in the leaf tissue of Eucalyptus blakelyi","volume":"17","author":"ARP Journet","year":"1978","journal-title":"Phytochemistry"},{"issue":"3","key":"pone.0314945.ref073","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/jn\/121.3.277","article-title":"The importance of alpha-lactalbumin in infant nutrition","volume":"121","author":"WE Heine","year":"1991","journal-title":"J Nutr"},{"key":"pone.0314945.ref074","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.1004545","article-title":"Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics","volume":"13","author":"DA Bizjak","year":"2022","journal-title":"Frontiers in Immunology"},{"issue":"1","key":"pone.0314945.ref075","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0021-9258(19)50967-X","article-title":"The conversion of tryptophan to kynurenine in liver: I. The coupled tryptophan peroxidase-oxidase system forming formylkynurenine","volume":"187","author":"WE Knox","year":"1950","journal-title":"Journal of Biological Chemistry"},{"issue":"3","key":"pone.0314945.ref076","first-page":"327","article-title":"Cytochrome P450 4A, peroxisomal enzymes and nicotinamide cofactors in koala liver","volume":"127","author":"S Ngo","year":"2000","journal-title":"Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology."},{"issue":"3","key":"pone.0314945.ref077","first-page":"351","article-title":"Characterisation of tolbutamide hydroxylase activity in the common brushtail possum, (Trichosurus vulpecula) and koala (Phascolarctos cinereus): inhibition by the eucalyptus terpene 1,8-cineole.","volume":"127","author":"P Liapis","year":"2000","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"issue":"4","key":"pone.0314945.ref078","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1152\/ajplegacy.1970.218.4.1233","article-title":"Standard metabolism, body temperature, and surface areas of Australian marsupials","volume":"218","author":"TJ Dawson","year":"1970","journal-title":"Am J Physiol"},{"issue":"2","key":"pone.0314945.ref079","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/BF00686747","article-title":"The comparative energetics of neotropical marsupials","volume":"125","author":"BK McNab","year":"1978","journal-title":"Journal of comparative physiology"},{"key":"pone.0314945.ref080","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3389\/fpubh.2017.00307","article-title":"Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice.","volume":"5","author":"R Trevethan","year":"2017","journal-title":"Front Public Health."},{"issue":"13","key":"pone.0314945.ref081","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3109\/08958378.2014.955932","article-title":"Screening tests: a review with examples.","volume":"26","author":"LD Maxim","year":"2014","journal-title":"Inhal Toxicol."},{"issue":"4","key":"pone.0314945.ref082","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1128\/jcm.33.4.898-900.1995","article-title":"Detection of Chlamydia trachomatis in urine specimens from women by ligase chain reaction","volume":"33","author":"M Bassiri","year":"1995","journal-title":"Journal of Clinical Microbiology"},{"issue":"5","key":"pone.0314945.ref083","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1086\/514740","article-title":"Screening for Chlamydia trachomatis infection in college women with a polymerase chain reaction assay","volume":"28","author":"RL Cook","year":"1999","journal-title":"Clinical infectious diseases"},{"issue":"5","key":"pone.0314945.ref084","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1128\/JCM.36.5.1300-1304.1998","article-title":"Use of ligase chain reaction with urine versus cervical culture for detection of Chlamydia trachomatis in an asymptomatic military population of pregnant and nonpregnant females attending Papanicolaou smear clinics","volume":"36","author":"CA Gaydos","year":"1998","journal-title":"Journal of clinical microbiology"},{"key":"pone.0314945.ref085","first-page":"160","article-title":"Area under the ROC curve","author":"DW Hosmer","year":"2000","journal-title":"Applied Logistic Regression"},{"issue":"4","key":"pone.0314945.ref086","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.1939-165X.2003.tb00332.x","article-title":"Creatinine in the dog: a review.","volume":"32","author":"JP Braun","year":"2003","journal-title":"Vet Clin Pathol."},{"issue":"18","key":"pone.0314945.ref087","article-title":"Health Assessments of Koalas after Wildfire: A Temporal Comparison of Rehabilitated and Non-Rescued Resident Individuals.","volume":"13","author":"MR Lane","year":"2023","journal-title":"Animals (Basel)."},{"issue":"6","key":"pone.0314945.ref088","first-page":"609","article-title":"Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease.","volume":"35","author":"JG Hashash","year":"2022","journal-title":"Ann Gastroenterol."},{"key":"pone.0314945.ref089","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/B978-012330215-1\/50007-7","volume-title":"Handbook of Toxicologic Pathology (Second Edition).","author":"GS Smith","year":"2002"},{"issue":"4","key":"pone.0314945.ref090","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/clinchem\/41.4.515","article-title":"Significance of low serum alkaline phosphatase activity in a predominantly adult male population","volume":"41","author":"G. Lum","year":"1995","journal-title":"Clin Chem"},{"issue":"12","key":"pone.0314945.ref091","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/0026-0495(74)90027-4","article-title":"Relevance of free tryptophan in serum to tissue tryptophan concentrations","volume":"23","author":"BK Madras","year":"1974","journal-title":"Metabolism"},{"issue":"20","key":"pone.0314945.ref092","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399406000068","article-title":"Tryptophan metabolism in the central nervous system: medical implications","volume":"8","author":"JP Ruddick","year":"2006","journal-title":"Expert Rev Mol Med"},{"issue":"6","key":"pone.0314945.ref093","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-Phase Proteins and Other Systemic Responses to Inflammation.","volume":"340","author":"C Gabay","year":"1999","journal-title":"New England Journal of Medicine"},{"issue":"11","key":"pone.0314945.ref094","first-page":"709","article-title":"Mildly Elevated Liver Transaminase Levels: Causes and Evaluation.","volume":"96","author":"RC Oh","year":"2017","journal-title":"Am Fam Physician"},{"issue":"10","key":"pone.0314945.ref095","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.3390\/ani11102864","article-title":"Physiological Stress in Rescued Wild Koalas (Phascolarctos cinereus) Being Held in a Rehabilitation Sanctuary: A Pilot Study.","volume":"11","author":"R Charalambous","year":"2021","journal-title":"Animals"},{"issue":"8","key":"pone.0314945.ref096","doi-asserted-by":"crossref","first-page":"4750","DOI":"10.1016\/S0021-9258(18)32486-4","article-title":"Transcriptional regulation of the tryptophan oxygenase gene in rat liver by glucocorticoids","volume":"258","author":"U Danesch","year":"1983","journal-title":"J Biol Chem"},{"issue":"5","key":"pone.0314945.ref097","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1210\/endo-117-5-1788","article-title":"A New Glucocorticoid Receptor Species: Relation to Induction of Tryptophan Dioxygenase by Glucocorticoids","volume":"117","author":"T Hirota","year":"1985","journal-title":"Endocrinology"},{"issue":"3","key":"pone.0314945.ref098","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1163\/156856003322315622","article-title":"Diclofenac increases the accumulation of kynurenate following tryptophan pretreatment in the rat: a possible factor contributing to its antihyperalgesic effect","volume":"11","author":"SR Edwards","year":"2003","journal-title":"Inflammopharmacology"},{"issue":"2","key":"pone.0314945.ref099","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1006\/exnr.1996.6365","article-title":"Quinolinate immunoreactivity in experimental rat brain tumors is present in macrophages but not in astrocytes","volume":"144","author":"JR Moffett","year":"1997","journal-title":"Exp Neurol"},{"key":"pone.0314945.ref100","first-page":"113","author":"G Fey","year":"1994"},{"issue":"1","key":"pone.0314945.ref101","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12905-016-0356-9","article-title":"Clinical characteristics of genital chlamydia infection in pelvic inflammatory disease.","volume":"17","author":"ST Park","year":"2017","journal-title":"BMC Womens Health"},{"issue":"2","key":"pone.0314945.ref102","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.mehy.2006.07.031","article-title":"Role of Tryptophan supplementation in the treatment of Chlamydia","volume":"68","author":"M. Singla","year":"2007","journal-title":"Med Hypotheses."},{"issue":"4","key":"pone.0314945.ref103","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1128\/IAI.72.4.1843-1855.2004","article-title":"Chlamydial persistence: beyond the biphasic paradigm","volume":"72","author":"RJ Hogan","year":"2004","journal-title":"Infect Immun"},{"issue":"10","key":"pone.0314945.ref104","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1751-0813.1989.tb09717.x","article-title":"Haematological and biochemical reference values for the koala (Phascolarctos cinereus).","volume":"66","author":"PM Canfield","year":"1989","journal-title":"Aust Vet J."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0314945","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T18:48:21Z","timestamp":1734634101000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0314945"}},"subtitle":[],"editor":[{"given":"Ping","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,19]]},"references-count":104,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0314945","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,19]]}}}