Compromised Viability Research Articles

Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2).

The human, animal and plant pathogen Fusarium, which contaminates agricultural commodities worldwide, produces numerous secondary metabolites. An example is the thoroughly-investigated deoxynivalenol (DON), which severely impairs gastrointestinal barrier integrity. However, to date, the toxicological profile of other Fusarium-derived metabolites, such as enniatins, beauvericin, moniliformin, apicidin, aurofusarin, rubrofusarin, equisetin and bikaverin, are poorly characterized. Thus we examined their effects—as metabolites alone and as metabolites in combination with DON—on the intestinal barrier function of differentiated intestinal porcine epithelial cells (IPEC-J2) over 72 h. Transepithelial electrical resistance (TEER) was measured at 24-h intervals, followed by evaluation of cell viability using neutral red (NR) assay. Enniatins A, A1, B and B1, apicidin, aurofusarin and beauvericin significantly reduced TEER. Moniliformin, equisetin, bikaverin and rubrofusarin had no effect on TEER. In the case of apicidin, aurofusarin and beauvericin, TEER reductions were further substantiated by the addition of otherwise no-effect DON concentrations. In all cases, viability was unaffected, confirming that TEER reductions were not due to compromised viability. Considering the prevalence of mycotoxin contamination and the diseases associated with intestinal barrier disruption, consumption of contaminated food or feed may have substantial health implications.

Sub-lethal effects of water-based drilling muds on the deep-water sponge Geodia barretti

Offshore oil and gas activities can result in the discharge of large amounts of drilling muds. While these materials have generally been regarded as non-toxic to marine organisms, recent studies have demonstrated negative impacts to suspension feeding organisms. We exposed the arctic-boreal sponge Geodia barretti to the primary particulate components of two water-based drilling muds; barite and bentonite. Sponges were exposed to barite, bentonite and a natural reference sediment at a range of total suspended solid concentrations (TSS = 0, 10, 50 or 100 mg/L) for 12 h after which we measured a suite of biomarker responses (lysosomal membrane stability, lipid peroxidation and glutathione). In addition, we compared biomarker responses, organic energy content and metal accumulation in sponges, which had been continuously or intermittently exposed to suspended barite and natural sediment for 14 d at relevant concentrations (10 and 30 mg TSS/L). Lysosomal membrane stability was reduced in the sponges exposed to barite at 50 and 100 mg TSS/L after just 12 h and at 30 mg TSS/L for both continuous and intermittent exposures over 14 d. Evidence of compromised cellular viability was accompanied by barite analysis revealing concentrations of Cu and Pb well above reference sediments and Norwegian sediment quality guidelines. Metal bioaccumulation in sponge tissues was low and the total organic energy content (determined by the elemental composition of organic tissue) was not affected. Intermittent exposures to barite resulted in less toxicity than continuous exposure to barite. Short term exposures to bentonite did not alter any biomarker responses. This is the first time that these biomarkers have been used to indicate contaminant exposure in an arctic-boreal sponge. Our results illustrate the potential toxicity of barite and the importance of assessments that reflect the ways in which these contaminants are delivered under environmentally realistic conditions.

The purine analogues abacavir and didanosine increase acetaminophen-induced hepatotoxicity by enhancing mitochondrial dysfunction.

NRTIs are essential components of HIV therapy with well-documented, long-term mitochondrial toxicity in hepatic cells, but whose acute effects on mitochondria are unclear. As acetaminophen-induced hepatotoxicity also involves mitochondrial interference, we hypothesized that it would be exacerbated in the context of ART. We evaluated the acute effects of clinically relevant concentrations of the most widely used NRTIs, alone or combined with acetaminophen, on mitochondrial function and cellular viability. The purine analogues abacavir and didanosine produced an immediate and concentration-dependent inhibition of oxygen consumption and complex I and III activity. This inhibition was accompanied by an undermining of mitochondrial function, with increased production of reactive oxygen species and reduction of mitochondrial membrane potential and intracellular ATP levels. However, this interference did not compromise cell survival. Co-administration with concentrations of acetaminophen below those considered hepatotoxic exacerbated the deleterious effects of both compounds on mitochondrial function and compromised cellular viability, showing a clear correlation with diminished glutathione levels. The simultaneous presence of purine analogues and low concentrations of acetaminophen significantly potentiates mitochondrial dysfunction, increasing the risk of liver injury. This new mechanism is relevant given the liver's susceptibility to mitochondrial dysfunction-related toxicity and the tendency of the HIV infection to increase oxidative stress.

Adaptation to sustained nitrogen starvation by Escherichia coli requires the eukaryote-like serine/threonine kinase YeaG.

The Escherichia coli eukaryote-like serine/threonine kinase, encoded by yeaG, is expressed in response to diverse stresses, including nitrogen (N) starvation. A role for yeaG in bacterial stress response is unknown. Here we reveal for the first time that wild-type E. coli displays metabolic heterogeneity following sustained periods of N starvation, with the metabolically active population displaying compromised viability. In contrast, such heterogeneity in metabolic activity is not observed in an E. coli ∆yeaG mutant, which continues to exist as a single and metabolically active population and thus displays an overall compromised ability to survive sustained periods of N starvation. The mechanism by which yeaG acts, involves the transcriptional repression of two toxin/antitoxin modules, mqsR/mqsA and dinJ/yafQ. This, consequently, has a positive effect on the expression of rpoS, the master regulator of the general bacterial stress response. Overall, results indicate that yeaG is required to fully execute the rpoS-dependent gene expression program to allow E. coli to adapt to sustained N starvation and unravels a novel facet to the regulatory basis that underpins adaptive response to N stress.

Surface-engineered graphene navigate divergent biological outcomes toward macrophages.

The "nano-bio" interface profoundly shapes the interaction between cells and nanomaterials and can even decide a cell's fate. As a nascent two-dimensional material, graphene has many unique attributes and is proposed to be a promising candidate for biomedical applications. Thus, for graphene-based applications, it is necessary to clarify how the graphene surface navigates biological outcomes when encountering "janitorial" cells (macrophages). For this purpose, we synthesized nanographene oxide (nGO) and engineered the surface with polyethylene glycol (PEG), bovine serum albumin (BSA), and poly(ether imide) (PEI). In contrast to pristine nGO, decoration with PEG and BSA hindered endocytosis and improved their benignancy toward macrophages. Contrarily, nGO-PEI commenced with favorable endocytosis but then suffered stagnation due to compromised macrophage viability. To unravel the underlying mechanisms regulating these diverse macrophage fates, we built a stepwise analysis. Compared to the others, nGO-PEI tended to interact electrostatically with mitochondria after their cellular internalization. Such an unexpected encounter disrupted the normal potential and integrity of mitochondria and then elicited an alteration in reactive oxygen species and cytochrome c. These responses further initiated the activation of the caspase family and ultimately dictated cells to undergo apoptosis. The advances described above will complement our knowledge of graphene functionality and serve to guide its application in biotechnological applications.

Effect of copper exposure on reproductive ability in the bank vole (Myodes glareolus).

The amount of copper in natural ecosystems is steadily increasing, due to human activities. It accumulates in plants, posing a threat to herbivores. In polluted areas the population density of small rodents is observed to be lower. The decline in rodent numbers may be caused by increased mortality or diminished fertility. This study examined the effect of copper on the reproductive activity of the bank vole (Myodes glareolus), a small rodent which during foraging often wanders into fields where it might be exposed to pollution. The animals were treated with solutions of 0, 150 or 600 ppm Cu. After 12 weeks of exposure the quality and quantity of the male's sperm was tested. To assess morphological development we compared the experimental groups for body weight, the weight of the male's testes and accessory sex glands, the female's uterus, and the number of matured ovary follicles in tested females. At both doses, copper administration led to lower sperm count and caused sperm head anomalies. The higher dose compromised sperm tail membrane integrity, viability and motility. No effect of copper on morphological development was observed in males, and only the lower dose increased testes weight. In females the higher dose had a negative effect on morphological development, and the lower dose increased uterus weight. No effect of copper on ovarian follicle number was found. For the first time, the morphology of the most typical ovarian follicles of the bank vole is presented.

Pyruvate Carboxylase and Pentose Phosphate Fluxes are Reduced in AβPP-PS1 Mouse Model of Alzheimer's Disease: A 13C NMR Study

Although pyruvate dehydrogenase (PDH) is the major pathway of glucose metabolism and source for energy production, pyruvate carboxylase (PC) and pentose phosphate pathway (PPP) account for a significant fraction of glucose oxidation in the mature central nervous system. Flux through the PDH pathway has been reported to be reduced in Alzheimer's disease (AD) patients as well as in animal models of AD. However, fluxes through the PPP and PC pathways have not been explored under conditions of AD. The present study investigates the fluxes of PC and PPP in a 20-month-old AβPP-PS1 mouse model of AD using 13C NMR spectroscopy together with an infusion of [2-13C]glucose. Mice were also administered [1,6-13C2]glucose or [1-13C]glucose for 10 or 90 min, respectively, to investigate PDH flux. AβPP-PS1 mice exhibit a significant reduction in the level of NAA and increase in level of myo-inositol. The flux through PDH was found to be significantly lower in the cerebral cortex (AβPP-PS1 0.39 ± 0.08; control 0.77 ± 0.08 μmol/g/min), hippocampus (AβPP-PS1 0.31 ± 0.04; control 0.64 ± 0.12 μmol/g/min), and striatum (AβPP-PS1 0.34 ± 0.06; control 0.56 ± 0.03 μmol/g/min) of AβPP-PS1 as compared with control mice. The fluxes through PC (AβPP-PS1 0.037 ± 0.006, control 0.079 ± 0.013 μmol/g/min) and PPP (AβPP-PS1 0.024 ± 0.005; control 0.062 ± 0.022 μmol/g/min) were found to be significantly reduced in AβPP-PS1 mice when compared with age-matched controls. The reduction in the fluxes of PC and PPP may lead to a weakened neural defense system of ammonia detoxification and antioxidant reserve in AβPP-PS1 mice, which may be responsible for the compromised neuronal viability and functions in AD.

CMT-associated mutations in glycyl- and tyrosyl-tRNA synthetases exhibit similar pattern of toxicity and share common genetic modifiers in Drosophila

Aminoacyl-tRNA synthetases are ubiquitously expressed proteins that charge tRNAs with their cognate amino acids. By ensuring the fidelity of protein synthesis, these enzymes are essential for the viability of every cell. Yet, mutations in six tRNA synthetases specifically affect the peripheral nerves and cause Charcot–Marie–Tooth (CMT) disease. The CMT-causing mutations in tyrosyl- and glycyl-tRNA synthetases (YARS and GARS, respectively) alter the activity of the proteins in a range of ways (some mutations do not impact charging function, while others abrogate it), making a loss of function in tRNA charging unlikely to be the cause of disease pathology. It is currently unknown which cellular mechanisms are triggered by the mutant enzymes and how this leads to neurodegeneration. Here, by expressing two pathogenic mutations (G240R, P234KY) in Drosophila, we generated a model for GARS-associated neuropathy. We observed compromised viability, and behavioral, electrophysiological and morphological impairment in flies expressing the cytoplasmic isoform of mutant GARS. Their features recapitulated several hallmarks of CMT pathophysiology and were similar to the phenotypes identified in our previously described Drosophila model of YARS-associated neuropathy. Furthermore, CG8316 and CG15599 — genes identified in a retinal degeneration screen to modify mutant YARS, also modified the mutant GARS phenotypes. Our study presents genetic evidence for common mutant-specific interactions between two CMT-associated aminoacyl-tRNA synthetases, lending support for a shared mechanism responsible for the synthetase-induced peripheral neuropathies.

Ceramide Transfer Protein Deficiency Compromises Organelle Function and Leads to Senescence in Primary Cells

Ceramide transfer protein (CERT) transfers ceramide from the endoplasmic reticulum (ER) to the Golgi complex. Its deficiency in mouse leads to embryonic death at E11.5. CERT deficient embryos die from cardiac failure due to defective organogenesis, but not due to ceramide induced apoptotic or necrotic cell death. In the current study we examined the effect of CERT deficiency in a primary cell line, namely, mouse embryonic fibroblasts (MEFs). We show that in MEFs, unlike in mutant embryos, lack of CERT does not lead to increased ceramide but causes an accumulation of hexosylceramides. Nevertheless, the defects due to defective sphingolipid metabolism that ensue, when ceramide fails to be trafficked from ER to the Golgi complex, compromise the viability of the cell. Therefore, MEFs display an incipient ER stress. While we observe that ceramide trafficking from ER to the Golgi complex is compromised, the forward transport of VSVG-GFP protein is unhindered from ER to Golgi complex to the plasma membrane. However, retrograde trafficking of the plasma membrane-associated cholera toxin B to the Golgi complex is reduced. The dysregulated sphingolipid metabolism also leads to increased mitochondrial hexosylceramide. The mitochondrial functions are also compromised in mutant MEFs since they have reduced ATP levels, have increased reactive oxygen species, and show increased glutathione reductase activity. Live-cell imaging shows that the mutant mitochondria exhibit reduced fission and fusion events. The mitochondrial dysfunction leads to an increased mitophagy in the CERT mutant MEFs. The compromised organelle function compromise cell viability and results in premature senescence of these MEFs.

The effect of the essential oils from five different Lippia species on the viability of tumor cell lines

Several Lippia species have been used in folk medicine mainly for gastrointestinal and respiratory diseases. Their biological properties have been partially associated to the terpenoids found in their essential oils. According to the World Health Organization, cancer is the leading cause of death worldwide and is described as a complex group of diseases with several hallmarks. One of its acceptable defining features is the cell proliferation beyond their boundaries forming the tumors. Importantly, some drugs currently available were discovered by the investigation of plant secondary metabolites. Thus, this study aimed to evaluate in vitro cytotoxic effect of the essential oils extracted from five Lippia species against tumor cell lines. The results indicated that mouse colon carcinoma CT26.WT cell line viability was significantly reduced showing an IC50 of 19.05, 30.20 and 36.30μg/ml when treated with the essential oils of L. sidoides, L. salviifolia and L. rotundifolia, respectively. Human lung carcinoma A549 cell line also had a compromised viability to the action of L. alba carvone chemotype essential oil. The tested essential oils did not compromise viability of the normal cell line CHO. These finds suggest that the studied Lippia essential oils might be good candidates for further in-depth studies.

Human Mononuclear Cell Survival and Proliferation is Modulated by Cold Atmospheric Plasma Jet

AbstractCold plasma has become a promising application in the fields of biology and medicine. Its anti‐microbial effects and stimulating properties on eukaryotic cells make plasma an encouraging option in treatment of chronic wounds. Apart from fibroblasts or keratinocytes, immune cells have a major contribution in wound healing. In this study, human peripheral blood mononuclear cells (PBMC) were tested for viability and proliferation after treatment with an atmospheric pressure argon plasma jet. In a treatment time dependent manner compromised viability of PBMC and proliferation of T cells could be shown and was assigned to induced apoptosis. Negligible cell damage was observed after short plasma exposure. Finally, plasma did not cause loss of function and treated but viable T cells retained the ability to proliferate.

Low-Dose γ-Irradiation Affects the Survival of Exposed Daphnia and their Offspring

To analyze the long-term effects of exposure to low-dose γ-irradiation on survival and life span in directly irradiated Daphnia magna and their offspring. One-day-old Daphnia magna were exposed to 10, 100 and 1000 mGy of acute γ-rays. The life-span of irradiated and control animals, as well as their non-exposed progeny was analyzed. Irradiation at dose of 100 and 1000 mGy resulted in a significant decrease in the life span of irradiated Daphnia. The data presented here also show that the survival of non-exposed first-generation offspring of irradiated parents is significantly compromised, thus implying the presence of transgenerational effects. The results of our study show that low-dose irradiation significantly reduces the life-span of directly exposed Daphnia and their first-generation offspring. The observed compromised viability is most likely attributed to non-targeted effects of ionizing radiation.

SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia

AbstractThe Sox4 transcription factor mediates early B-cell differentiation. Compared with normal pre-B cells, SOX4 promoter regions in Ph+ ALL cells are significantly hypomethylated. Loss and gain-of-function experiments identified Sox4 as a critical activator of PI3K/AKT and MAPK signaling in ALL cells. ChIP experiments confirmed that SOX4 binds to and transcriptionally activates promoters of multiple components within the PI3K/AKT and MAPK signaling pathways. Cre-mediated deletion of Sox4 had little effect on normal pre-B cells but compromised proliferation and viability of leukemia cells, which was rescued by BCL2L1 and constitutively active AKT and p110 PI3K. Consistent with these findings, high levels of SOX4 expression in ALL cells at the time of diagnosis predicted poor outcome in a pediatric clinical trial (COG P9906). Collectively, these studies identify SOX4 as a central mediator of oncogenic PI3K/AKT and MAPK signaling in ALL.

Aggressive behavior and employment histories in patients from an internal medicine outpatient clinic

A number of studies have examined the relationships between aggression and various facets of the work environment. However, to our knowledge, the relationship between self-reported aggressive behaviors and corresponding employment histories has never been previously explored. Using a cross-sectional approach and a self-report survey methodology in a consecutive sample of 325 internal medicine outpatients, we examined lifetime histories of 21 aggressive behaviors and 4 employment variables. In both men and women, a higher number of aggressive behaviors correlated with a greater number of different jobs held, greater likelihood of being paid “under the table,” and a greater number of firings. However, only in men was the number of aggressive behaviors related to the percentage of time employed as an adult. According to findings, a history of aggressive behavior appears to be associated with compromised employment viability in adulthood.

Isolation and characterization of living primary astroglial cells using the new GLAST‐specific monoclonal antibody ACSA‐1

Astrocytes show large morphological and functional heterogeneity and are involved in many aspects of neural function. Progress in defining astrocyte subpopulations has been hampered by the lack of a suitable antibody for their direct detection and isolation. Here, we describe a new monoclonal antibody, ACSA-1, which was generated by immunization of GLAST1 knockout mice. The antibody specifically detects an extracellular epitope of the astrocyte-specific L-glutamate/L-aspartate transporter GLAST (EAAT1, Slc1a3). As shown by immunohistochemistry, immunocytochemistry, and flow cytometry, ACSA-1 was cross-reactive for mouse, human, and rat. It labeled virtually all astrocytes positive for GFAP, GS, BLBP, RC2, and Nestin, including protoplastic, fibrous, and reactive astrocytes as well as Bergmann glia, Müller glia, and radial glia. Oligodendrocytes, microglia, neurons, and neuronal progenitors were negative for ACSA-1. Using an immunomagnetic approach, we established a method for the isolation of GLAST-positive cells with high purity. Binding of the antibody to GLAST and subsequent sorting of GLAST-positive cells neither interfered with cellular glutamate transport nor compromised astrocyte viability in vitro. The ACSA-1 antibody is not only a valuable tool to identify and track astrocytes by immunostaining, but also provides the possibility of separation and further analysis of pure astrocytes.

Actinidin, a protease from kiwifruit, induces changes in morphology and adhesion of T84 intestinal epithelial cells

Actinidin belongs to the papain-like family of cysteine proteases and is a major kiwifruit allergen. In this study, the effect of actinidin on cellular morphology and adhesion of T84 intestinal cells was investigated. Both rounding and detachment of T84 cells were observed upon actinidin treatment. The morphological changes and cell desquamation was protease-dependent, as well as time- and concentration-dependent. Changes of intercellular adhesion and adhesion of epithelial cells to collagen upon actinidin treatment could be responsible for the cell rounding and give rise to discontinuous breaches in the epithelial monolayer observed in this study. Actinidin’s action on cell morphology, adhesion and monolayer integrity were not due to compromised viability of T84 epithelial cells, as confirmed by MTT assay and flow cytometric analysis of the cell cycle. Damage to the epithelial monolayer of the intestine induced by actinidin should be further evaluated as an important factor in the development of kiwifruit allergy and other intestinal disorders.

Excorporeal Normothermic Machine Perfusion Resuscitates Pig DCD Livers with Extended Warm Ischemia

The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system. Livers from 12 Yorkshire pigs (20-30 kg) were subjected to either 0 min (WI-0 group, n = 6) or 60 min (WI-60 group, n = 6) of warm ischemia and 2 h of cold storage in UW solution, followed by 4 h of oxygenated sanguineous normothermic machine perfusion. Liver viability and metabolic function were analyzed hourly. Warm ischemic livers showed elevated transaminase levels and reduced ATP concentration. After the start of machine perfusion, transaminase levels stabilized and there was recovery of tissue ATP, coinciding with an increase in bile production. These parameters reached comparable levels to the control group after 1 h of machine perfusion. Histology and gross morphology confirmed recovery of the ischemic allografts. Our data demonstrate that metabolic and functional parameters of livers with extended warm ischemic time (60 min) can be significantly improved using normothermic machine perfusion. We hereby compound the existing body of evidence that machine perfusion is a viable solution for reconditioning marginal organs.

Inclusion of extra perforators – A single and efficient measure to prevent vascular insufficiency in unreliable thoracodorsal artery perforator flaps

The purpose of the study is to establish a clearly defined principle to prevent the vascular insufficiency of thoracodorsal artery perforator flaps, including the criteria to identify unreliable flaps and the measure to improve their viability. The whole project comprised the preliminary study and the major study. In the preliminary study of 42 patients, the intrinsic risk factors associated with the vascular insufficiency of flaps were identified. Using colour Doppler scanning, the linear correlation between colour signal width and external diameter of perforators was demonstrated. Based on the findings, the principle to prevent vascular insufficiency of flaps was established which involved two steps. First was introducing the inclusion criteria to identify the unreliable flaps. Second was including extra perforators as the single measure to improve the viability of unreliable flaps. The principle was applied in the major study of 50 patients to prove its efficacy. In the major study, flap viability was not compromised in the 35 patients without any of the inclusion criteria. At least one of the inclusion criteria was met in the other 15 patients. Three of the 15 unreliable flaps sustained vascular insufficiency. In one patient, only single small-sized perforator was available to support the flap. The principle was disobeyed in the other two patients because of the intertwined relation, and their less dominant perforators were cut to spare the intertwined motor nerves. The rate of compromised flap viability was 2.1% in the 48 patients with complete execution of the principle in comparison with the 16.7% rate in the preliminary study. The inclusion criteria are useful to identify unreliable thoracodorsal artery perforator flaps. Inclusion of extra perforators is a single and efficient measure to prevent vascular insufficiency of unreliable flaps.

N-Acetyl Cysteine Protects TMJ Chondrocytes from Oxidative Stress

Temporomandibular joint (TMJ) inflammation is closely associated with oxidative stress. This study tested the potential of N-acetyl cysteine (NAC), an anti-oxidant amino-acid derivative, in alleviating oxidative stress-related damage in TMJ chondrocytes. The inflammatory condition was simulated by the addition of hydrogen peroxide (H2O2) to TMJ-derived chondrocyte cultures. Exposure to H2O2 decreased the cell population by half within 2 days as a result of induced apoptosis and reduced proliferation. Gene expression of aggrecan and collagen II, as well as glycosaminoglycan production, were reduced by more than 70%. These compromised chondrocyte viability and function were fully restored by the addition of NAC to the cultures. NAC reduced the H2O2-elevated intracellular reactive oxygen species to the normal level and increased cellular glutathione reserves. These results indicate that NAC restores oxidative stress-induced cell death and severe functional impairment in TMJ chondrocytes, and warrant in vivo testing to explore its therapeutic potential as an anti-inflammatory agent.

Metabolomics-Based Discovery of Diagnostic Biomarkers for Onchocerciasis

BackgroundDevelopment of robust, sensitive, and reproducible diagnostic tests for understanding the epidemiology of neglected tropical diseases is an integral aspect of the success of worldwide control and elimination programs. In the treatment of onchocerciasis, clinical diagnostics that can function in an elimination scenario are non-existent and desperately needed. Due to its sensitivity and quantitative reproducibility, liquid chromatography-mass spectrometry (LC-MS) based metabolomics is a powerful approach to this problem.Methodology/Principal FindingsAnalysis of an African sample set comprised of 73 serum and plasma samples revealed a set of 14 biomarkers that showed excellent discrimination between Onchocerca volvulus–positive and negative individuals by multivariate statistical analysis. Application of this biomarker set to an additional sample set from onchocerciasis endemic areas where long-term ivermectin treatment has been successful revealed that the biomarker set may also distinguish individuals with worms of compromised viability from those with active infection. Machine learning extended the utility of the biomarker set from a complex multivariate analysis to a binary format applicable for adaptation to a field-based diagnostic, validating the use of complex data mining tools applied to infectious disease biomarker discovery and diagnostic development.Conclusions/SignificanceAn LC-MS metabolomics-based diagnostic has the potential to monitor the progression of onchocerciasis in both endemic and non-endemic geographic areas, as well as provide an essential tool to multinational programs in the ongoing fight against this neglected tropical disease. Ultimately this technology can be expanded for the diagnosis of other filarial and/or neglected tropical diseases.