Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant.

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Device Management and Data Transport in IoT Networks Based on Visible Light Communication.

LED-based Visible Light Communication (VLC) has been proposed as the IEEE 802.15.7 standard and is regarded as a new wireless access medium in the Internet-of-Things (IoT) environment. With this trend, many works have already been made to improve the performance of VLC. However, the effectively integration of VLC services into IoT networks has not yet been sufficiently studied. In this paper, we propose a scheme for device management and data transport in IoT networks using VLC. Specifically, we discuss how to manage VLC transmitters and receivers, and to support VLC data transmission in IoT networks. The proposed scheme considers uni-directional VLC transmissions from transmitter to receivers for delivery of location-based VLC data. The backward transmission from VLC receivers will be made by using platform server and aggregation agents in the network. For validation and performance analysis, we implemented the proposed scheme with VLC-capable LED lights and open sources of oneM2M. From the experimental results for virtual museum services, we see that the VLC data packets can be exchanged within 590 ms, and the handover between VLC transmitters can be completed within 210 ms in the testbed network.

Age-related change in γH2AX of Drosophila muscle: its significance as a marker for muscle damage and longevity.

Muscle aging is closely related to unhealthy late-life and organismal aging. Recently, the state of differentiated cells was shown to be critical to tissue homeostasis. Thus, understanding how fully differentiated muscle cells age is required for ensuring healthy aging. Adult Drosophila muscle is a useful model for exploring the aging process of fully differentiated cells. In this study, we investigated age-related changes of γH2AX, an indicator of DNA strand breaks, in adult Drosophila muscle to document whether its changes are correlated with muscle degeneration and lifespan. The results demonstrate that γH2AX accumulation increases in adult Drosophila thoracic and leg muscles with age. Analyses of short-, normal-, and long-lived strains indicate that the age-related increase of γH2AX is closely associated with the extent of muscle degeneration, cleaved caspase-3 and poly-ubiquitin aggregates, and longevity. Further analysis of muscle-specific knockdown of heterochromatin protein 1a revealed that the excessive γH2AX accumulation in thoracic and leg muscles induces accelerated degeneration and decreases longevity. These data suggest a strong correlation between age-related muscle damage and lifespan in Drosophila. Our findings indicate that γH2AX may be a reliable biomarker for assessing muscle aging in Drosophila.

Use of silane-functionalized graphene oxide in organic photovoltaic cells and organic light-emitting diodes.

Graphene oxide (GO) and silane-functionalized GO (sGO) sheets obtained through a simple sonication exfoliation method are employed as hole transport layers to improve the efficiency of organic photovoltaic (OPV) cells and organic light-emitting diodes (OLED). GO was functionalized using (3-glycidyl oxypropyl)trimethoxysilane (GPTMS) and triethoxymethylsilane (MTES). The appearance of new peaks in the Fourier-transform infrared spectra of the sGOs indicates the formation of Si-O-C, Si-O-Si, Si-H, and Si-O-C moieties, which provide evidence of the addition of silane to the GO surface. Furthermore, the appearance of Si-O-Si bonds in the synchrotron radiation photoelectron spectra (SRPES) of the MTES-sGO and GPTMS-sGO samples suggests that silane groups were effectively functionalized onto the GO sheets. An OPV cell with GO layers showed a lower performance with a power conversion efficiency (PCE) of 2.06%; in contrast, OPV cells based on GPTMS-sGO and MTES-sGO have PCE values of 3.00 and 3.08%, respectively. The OLED devices based on GPTMS-sGO and MTES-sGO showed a higher maximum luminance efficiency of 13.91 and 12.77 cd A(-1), respectively, than PEDOT:PSS-based devices (12.34 cd A(-1)). The SRPES results revealed that the work functions of GO, GPTMS-sGO, and MTES-sGO were 4.8, 4.9, and 5.0 eV, respectively. Therefore, the increase in the PCE value is attributed to improved band-gap alignment. It is thought that sGO could be used as an interfacial layer in OPV and OLED devices.

Cloning metallothionein gene in Zacco platypus and its potential as an exposure biomarker against cadmium.

Zacco platypus, pale chub, is an indigenous freshwater fish of East Asia including Korea and has many useful characteristics as indicator species for water pollution. While utility of Z. platypus as an experimental species has been recognized, genetic-level information is very limited and warrants extensive research. Metallothionein (MT) is widely used and well-known biomarker for heavy metal exposure in many experimental species. In the present study, we cloned MT in Z. platypus and evaluated its utility as a biomarker for metal exposure. For this purpose, we sequenced complete complementary DNA (cDNA) of MT in Z. platypus and carried out phylogenetic analysis with its sequences. The transcription-level responses of MT gene following the exposure to CdCl2 were also assessed to validate the utility of this gene as an exposure biomarker. Analysis of cDNA sequence of MT gene demonstrated high conformity with those of other fish. MT messenger RNA (mRNA) expression and enzymatic MT content significantly increased following CdCl2 exposure in a concentration-dependent manner. The level of CdCl2 that resulted in significant MT changes in Z. platypus was within the range that was reported from other fish. The MT gene of Z. platypus sequenced in the present study can be used as a useful biomarker for heavy metal exposure in the aquatic environment of Korea and other countries where this freshwater fish species represents the ecosystem.

The neuroprotective effects of α-iso-cubebene on dopaminergic cell death: involvement of CREB/Nrf2 signaling.

As a part of ongoing studies to elucidate pharmacologically active components of Schisandra chinensis, we isolated and studied α-iso-cubebene. The neuroprotective mechanisms of α-iso-cubebene in human neuroblastoma SH-SY5Y cells were investigated. α-Iso-cubebene significantly inhibited cytotoxicity and apoptosis due to 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in dopaminergic SH-SY5Y cells. Pretreatment of cells with α-iso-cubebene reduced intracellular accumulation of ROS and calcium in response to 6-OHDA. The neuroprotective effects of α-iso-cubebene were found to result from protecting the mitochondrial membrane potential. Notably, α-iso-cubebene inhibited the release of apoptosis-inducing factor from the mitochondria into the cytosol and nucleus after 6-OHDA treatment. α-Iso-cubebene also induced the activation of PKA/PKB/CREB/Nrf2 and suppressed 6-OHDA-induced neurotoxicity. α-Iso-cubebene was found to induce phosphorylation of PKA and PKB and activate Nrf2 and CREB signaling pathways in a dose-dependent manner. Additionally, α-iso-cubebene stimulated the expression of the antioxidant response genes NQO1 and HO-1. Finally, α-iso-cubebene-mediated neuroprotective effects were found to be reversible after transfection with CREB and Nrf2 small interfering RNAs.

Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Regulation of intestinal stem cell proliferation by human methyl-CpG-binding protein-2 in Drosophila.

Recent studies have suggested the involvement of epigenetic factors such as methyl-CpG-binding protein-2 (MeCP2) in tumorigenesis. In addition, cancer may represent a stem cell-based disease, suggesting that understanding of stem cell regulation could provide valuable insights into the mechanisms of tumorigenesis. However, the function of epigenetic factors in stem cell regulation in adult tissues remains poorly understood. In the present study, we investigated the role of human MeCP2 (hMeCP2), a bridge factor linked to DNA modification and histone modification, in stem cell proliferation using adult Drosophila midgut, which appears to be an excellent model system to study stem cell biology. Results show that enterocyte (EC)-specific expression of hMeCP2 in adult midgut using an exogenous GAL4/UAS expression system induced intestinal stem cell (ISC) proliferation marked by staining with anti-phospho-histone H3 antibody and BrdU incorporation assays. In addition, hMeCP2 expression in ECs activated extracellular stress-response kinase signals in ISCs. Furthermore, expression of hMeCP2 modulated the distribution of heterochromatin protein-1 in ECs. Our data suggests the hypothesis that the expression of hMeCP2 in differentiated ECs stimulates ISC proliferation, implying a role of MeCP2 as a stem cell regulator.

Ulmus macrocarpa Hance extract modulates intestinal microbiota in healthy adults: a randomized, placebo-controlled clinical trial.

The stem and root bark of Ulmus macrocarpa Hance has been used as traditional pharmacological agent against inflammation related disorders. The objective of this study was to explore the impact of Ulmus macrocarpa Hance extract (UME) on human gut microbiota. A randomized placebo-controlled clinical study was conducted in healthy adults. The study subjects were given 500 mg/day of UME or placebo orally for 4 weeks. Eighty fecal samples were collected at baseline and 4 weeks of UME or placebo intervention. The gut microbiota variation was evaluated by 16S rRNA profiling. The microbial response was highly personalized, and no statistically significant differences was observed in both species richness and abundance. The number of bacterial species identified in study subjects ranged from 86 to 182 species. The analysis for taxonomical changes revealed an increase in Eubacterium ventriosum, Blautia faecis, Ruminococcus gnavus in the UME group. Functional enrichment of bacterial genes showed an increase in primary and secondary bile acid biosynthesis in UME group. Having known from previous studies Eubacterium regulated bile acid homeostasis in protecting gut microbial architecture and immunity, we suggest that UME supplementation might enhance host immunity by modulating gut microbiota. This is the first stage study and forthcoming clinical studies with larger participants are needed to confirm these findings.

Ecological Risk Assessment of Amoxicillin, Enrofloxacin, and Neomycin: Are Their Current Levels in the Freshwater Environment Safe?

Veterinary pharmaceuticals may cause unexpected adverse effects on non-target aquatic species. While these pharmaceuticals were previously identified as priority compounds in ambient water, their ecological risks are relatively unknown. In this study, a series of chronic toxicity tests were conducted for these pharmaceuticals using algae, two cladocerans, and a fish. After a 21-d exposure to amoxicillin, enrofloxacin, and neomycin, no observed effect concentration (NOEC) for the reproduction of Daphnia magna was detected at 27.2, 3.3, and 0.15 mg/L, respectively. For the survival of juvenile Oryzias latipes following the 40-d exposure, NOEC was found at 21.8, 3.2, and 0.87 mg/L, respectively. Based on the results of the chronic toxicity tests and those reported in the literature, predicted no-effect concentrations (PNECs) were determined at 0.078, 4.9, and 3.0 µg/L for amoxicillin, enrofloxacin, and neomycin, respectively. Their hazard quotients (HQs) were less than 1 at their average levels of occurrence in ambient freshwater. However, HQs based on the maximum detected levels of amoxicillin and enrofloxacin were determined at 21.2 and 6.1, respectively, suggesting potential ecological risks. As the potential ecological risks of these veterinary pharmaceuticals at heavily contaminated sites cannot be ignored, hotspot delineation and its management are required.

A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)­directed antibody communities with distinct footprints and competition profiles. Pseudovirion-based neutralization assays reveal spike mutations, individually and clustered together in variants, that affect antibody function among the communities. Key classes of RBD-targeted antibodies maintain neutralization activity against these emerging SARS-CoV-2 variants. These results provide a framework for selecting antibody treatment cocktails and understanding how viral variants might affect antibody therapeutic efficacy.

A Simple and Fast Algorithm for L1-Norm Kernel PCA.

We present an algorithm for L1-norm kernel PCA and provide a convergence analysis for it. While an optimal solution of L2-norm kernel PCA can be obtained through matrix decomposition, finding that of L1-norm kernel PCA is not trivial due to its non-convexity and non-smoothness. We provide a novel reformulation through which an equivalent, geometrically interpretable problem is obtained. Based on the geometric interpretation of the reformulated problem, we present a "fixed-point" type algorithm that iteratively computes a binary weight for each observation. As the algorithm requires only inner products of data vectors, it is computationally efficient and the kernel trick is applicable. In the convergence analysis, we show that the algorithm converges to a local optimal solution in a finite number of steps. Moreover, we provide a rate of convergence analysis, which has been never done for any L1-norm PCA algorithm, proving that the sequence of objective values converges at a linear rate. In numerical experiments, we show that the algorithm is robust in the presence of entry-wise perturbations and computationally scalable, especially in a large-scale setting. Lastly, we introduce an application to outlier detection where the model based on the proposed algorithm outperforms the benchmark algorithms.

A micro opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients.

RATIONALE: Previous studies have demonstrated an association between genetic polymorphisms of the mu opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans. OBJECTIVES: This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects. MATERIALS AND METHODS: Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients]. RESULTS: Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p=0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence. CONCLUSIONS: These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects.

Oligonucleotide array-based detection and genotyping of mollicutes (Acholeplasma, Mycoplasma, and Ureaplasma).

An oligonucleotide array was developed to detect and genotype mollicutes based on the internal transcribed spacer (ITS) sequence. The results of the assay were compared with those of a PCR-RFLP assay. The proposed oligonucleotide array containing 5 genus- and 23 species-specific probes was able to detect Mycoplasma species, including M. penetrans and M. spermatophilum, that were not detected by the PCRRFLP assay. Therefore, the results demonstrated that the proposed oligonucleotide array was effective for the detection and discrimination of 23 species, including an acholeplasma, 21 mycoplasmas, and a ureaplasma, and showed promise as a countermeasure to ensure that biological products are safe and of good quality.

Quality control probes for spot-uniformity and quantitative analysis of oligonucleotide array.

Quality control QC for spot-uniformity is a critical point in fabricating an oligonucleotide array, and quantification of targets is very important in array analysis. We developed two new types of QC probes as a means of confirming the quality of the uniformity of attached probes and the quantification of targets. We compared the signal intensities and fluorescent images of the QC and target-specific probes of arrays containing only target-specific probes and those containing both QC and target-specific probes. In a comparison of quality control methods, it was found that the arrays containing QC probes could check spotuniformity or spot defects during all processes of array fabrication, including after spotting, after washing, and after hybridization. In a comparison of quantification results, the array fabricated by the method using QC probes showed linear and regular results because it was possible to normalize variations in spot size and morphology and amount of attached probe. This method could avoid errors originating in probe concentration and spot morphology because it could be normalized by QC probes. There were significant differences in the signal intensities of all mixtures (P<0.05). This result indicates that the method using QC probes is more useful than the ordinary method for quantification of mixed target. In the quantification of mixed targets, this method could determine a range for mixed targets of various amounts. Our results suggest that methods using QC probes for array fabrication are very useful to the quality control of spots in the fabrication processes of quantitative oligonucleotide arrays.

Gene cloning, purification, and characterization of a cold-adapted lipase produced by Acinetobacter baumannii BD5.

Acinetobacter baumannii BD5 was isolated from waters of Baek-du mountain, and the lipase gene was cloned using a PCR technique. The deduced amino acid sequence of the lipase and lipase chaperone were found to encode proteins of 325 aa and 344 aa with a molecular mass of 35 kDa and 37 kDa, respectively. The lipase gene was cloned and expressed in Escherichia coli BL21 (trxB) as an inclusion body, which was subsequently solubilized by urea, and then purified using Ni-affinity chromatography. After being purified, the lipase was refolded by incubation at 4oC in the presence of a 1:10 molar ratio of lipase:chaperone. The maximal activity of the refolded lipase was observed at a temperature of 35 degrees and pH 8.3 when p-NP caprate (C10) was used as a substrate; however, 28% of the activity observed at 35 degrees was still remaining at 0 degrees . The stability of the purified enzyme at low temperatures indicates that it is a cold-adapted enzyme. The refolded lipase was activated by Ca2+, Mg2+, and Mn2+, whereas Zn2+ and Cu2+ inhibited it. Additionally, 0.1% Tween 20 increased the lipase activity by 33%, but SDS and Triton X-100 inhibited the lipase activity by 40% and 70%, respectively.

Comparison of thyroid hormone disruption potentials by bisphenols A, S, F, and Z in embryo-larval zebrafish.

Several structural analogues of bisphenol A (BPA), e.g., bisphenol F (BPF), bisphenol S (BPS), and bisphenol Z (BPZ), have been used as its substitutes in many applications and consequently detected in the environment, and human specimen such as urine and serum. While BPA has been frequently reported for thyroid hormone disruption in both experimental and epidemiological studies, less is known for the BPA analogues. In the present study, thyroid hormone disrupting effects of BPF, BPS and BPZ, were investigated, and compared with those of BPA, using embryo-larval zebrafish (Danio rerio). At 120 hpf, significant increases in T3 and/or T4 were observed in the larval fish following exposure to BPA, BPF, or BPS. Moreover, transcriptional changes of the genes related to thyroid development (hhex and tg), thyroid hormone transport (ttr) and metabolism (ugt1ab) were observed as well. Thyroid hormone (T4) disruption by BPF was observed even at the concentration (2.0 mg/L) lower than the effective concentration determined for BPA (>2.0 mg/L). Delayed hatching was observed by all tested bisphenols. Our results clearly show that these BPA analogues can disrupt thyroid function of the larval fish, and their thyroid hormone disruption potencies could be even greater than that of BPA. The concentrations which disrupt thyroid function of the larval fish were orders of magnitude higher than those occurring in the ambient environment. However, thyroid hormone disruption by longer term exposure and its consequences in the fish population, deserve further investigation.