Prenatal screening for neural tube defects: from maternal serum alpha-fetoprotein to ultrasonography.

The two main screening tests during pregnancy are those for chromosomal abnormalities and neural tube defects (NTDs). In particular, for NTDs, measurement of maternal serum alpha-fetoprotein (MSAFP) levels early in the second trimester (15-18 weeks of gestation) has been considered the gold standard screening test for the past 4 decades. However, with remarkable technological advancements and the widespread use of ultrasound during those periods, mid-trimester ultrasonography has gradually replaced the role of measuring MSAFP levels as a screening method for NTDs. This change was initiated more about 10 years ago in some countries, which have issued national guidelines to use mid-trimester ultrasonography instead of measuring MSAFP levels as a prenatal screening method for NTDs. However, no significant changes have occurred in Korea, where second-trimester ultrasonography is routinely performed with high-quality equipment. We aimed to provide information regarding the importance of changing the screening method for NTDs from MSAFP measurement to ultrasonography, and to detail methods of implementing mid-trimester ultrasonography for screening purposes. We also share our experience of operating a prenatal diagnostic program for NTDs without using MSAFP for more than 15 years.

Assessment of acute and chronic toxicity of cyantraniliprole and sulfoxaflor on honey bee (Apis mellifera) larvae.

BACKGROUND: Recently, cyantraniliprole (CYA) and sulfoxaflor (SUL) have been considered as alternatives to neonicotinoid insecticides. In this study, we evaluated the acute and chronic toxicities of CYA and SUL on honey bee (Apis mellifera L.) larvae reared in vitro. RESULTS: In the acute toxicity test, the following test doses were used to determine the median lethal dose (LD50 ): CYA 0.007, 0.014, 0.028, 0.056 and 0.112 µg larva-1 ; SUL 2.5, 5, 10, 20 and 40 µg larva-1 . In the chronic toxicity test, the following test doses were used to determine the LD50 : CYA 0.00512, 0.0128, 0.032, 0.08 and 0.2 µg larva-1 ; SUL 0.0625, 0.125, 0.25, 0.5 and 1.0 µg larva-1 . The acute LD50 values of CYA and SUL were 0.047 and 11.404 µg larva-1 , respectively. Larvae acutely exposed to SUL had significantly lower body weight than controls, but those exposed to CYA showed no difference. The no observed adverse effect level (NOAEL) and LD50 values of the chronic toxicity tests for each insecticide were 0.00512 and 0.064 µg larva-1 for CYA, and 0.0625 µg larva-1 and 0.212 µg larva-1 for SUL, respectively. Larvae chronically exposed to SUL emerged as bees with deformed wings, reaching adult deformation rates of over 50%; however, CYA had no effect on adult deformation. CONCLUSION: Exposure to CYA increased larval mortality but did not cause any adult deformation, whereas SUL exposure increased pupal mortality and caused wing deformation in newly emerged bees. Our study may be useful for the assessment of pesticide toxicity by providing valuable findings on the effects of these insecticides on honey bee larvae. © 2022 Society of Chemical Industry.

Developmental Toxic Effects of Thiram on Developing Zebrafish (Danio rerio) Embryos.

Thiram, an oxidized dimer of dithiocarbamate, has fungicidal and ectoparasiticidal roles. This study aimed to determine the effects of thiram on the development of zebrafish (ZF) embryos. The developmental toxicity test was performed in accordance with the OECD 236 test guidelines, and ZF embryos were subjected to several thiram concentrations and a DMSO (0.01%) control. Subsequently, embryo mortalities and developmental anomalies were evaluated at different hours post fertilization (hpf). Thiram was highly toxic to ZF, with calculated median lethal concentrations (LC50) of thiram at 48 and 96 h as 13.10 ± 2.17 and 8.87 ± 2.09 µg/L, respectively. Thiram-treated embryos/larvae exhibited a variety of deformities, such as abnormal somites, reduced eye pigment, abnormal tail shape, yolk sac edema, hatching defects, and curved spines, with a median effective concentration (EC50) of 3.88 ± 1.23, 5.04 ± 1.82, 6.23 ± 0.92, 5.24 ± 2.22, 1.39 ± 0.25, and 2.60 ± 0.82 µg/L, respectively. Teratogenic index (TI) values ranged from 1.42 to 6.66 for the scored deformities. At 48 hpf, the average heartbeat of the control group was 177.20 ± 5.63 per minute, while the highest thiram-treated group (40 µg/L) was 99.50 ± 18.12 per minute. In addition, cardiac-related issues, such as pericardial edema and abnormal blood flow, were observed in thiram-treated ZF embryos. Overall, these findings suggest that thiram is teratogenic to ZF.

Transcriptome-Based Identification of Genes Responding to the Organophosphate Pesticide Phosmet in Danio rerio.

Organophosphate pesticides (OPPs) are one of the most widely used insecticides. OPPs exert their neurotoxic effects by inhibiting acetylcholine esterase (AChE). Most of the gross developmental abnormalities observed in OPP-treated fish, on the other hand, may not be explained solely by AChE inhibition. To understand the overall molecular mechanisms involved in OPP toxicity, we used the zebrafish (ZF) model. We exposed ZF embryos to an OPP, phosmet, for 96 h, and then analyzed developmental abnormalities and performed whole transcriptome analysis. Phenotypic abnormalities, such as bradycardia, spine curvature, and growth retardation, were observed in phosmet-treated ZF (PTZF). Whole transcriptome analysis revealed 2190 differentially expressed genes (DEGs), with 822 and 1368 significantly up-and downregulated genes, respectively. System process and sensory and visual perception were among the top biological pathways affected by phosmet toxicity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of metabolic pathways, calcium signaling pathway, regulation of actin cytoskeleton, cardiac muscle contraction, drug metabolism-other enzymes, and phototransduction. Quantitative real-time PCR results of six DEGs agreed with the sequencing data expression profile trend. Our findings provide insights into the consequences of phosmet exposure in ZF, as well as an estimate of the potential risk of OPPs to off-target species.

Horizontal Honey-Bee Larvae Rearing Plates Can Increase the Deformation Rate of Newly Emerged Adult Honey Bees.

Rearing honey bee larvae in vitro is an ideal method to study honey bee larval diseases or the toxicity of pesticides on honey bee larvae under standardized conditions. However, recent studies reported that a horizontal position may cause the deformation of emerged bees. Accordingly, the purpose of this study was to evaluate the emergence and deformation rates of honey bee (Apis mellifera ligustica) larvae reared in horizontal and vertical positions. The study was conducted under the same laboratory conditions with three experimental groups, non-capped or capped horizontal plates and capped vertical plates. However, our results demonstrated that the exhibited adult deformation rates of the horizontal plates were significantly higher (27.8% and 26.1%) than those of the vertical plates (11.9%). In particular, the most common symptoms were deformed wings and an abnormal abdomen in the horizontal plates. Additionally, adults reared on horizontal plates were substantially smaller (10.88 and 10.82 mm) than those on vertical plates (11.55 mm). Considering these conclusions, we suggest that a vertical rearing method is more suitable when considering the deformation rates of the control groups to verify the sublethal effects of pesticides on honey bees.

Development of surface water exposure scenarios for risk assessment of pesticides in Korea.

Surface water exposure scenarios used in the risk assessment of Korea's aquatic ecosystems, were developed to represent the 90th percentile pesticide exposure situation as a part of the country's pesticide registration procedure. The scenarios are used to estimate the pesticide concentration in the water of a rice paddy and small streams for three protection goals: (i) mudfish in rice paddies, (ii) the aquatic ecosystem of small streams located near rice paddies, and (iii) the aquatic ecosystem of small streams located near fruit orchards. The scenarios were derived taking into account major exposure routes, such as spray drift, runoff, and drainage. The scenarios were parameterized for appropriate models including the pesticide root zone model (PRZM) and the toxic substances in surface waters model (TOXSWA). A total of 17 pesticide compounds and 28 formulated products were selected to test the risk assessment using the developed scenarios. The simulated predicted environmental concentrations (PECs) fully reflected a) the exposure routes for each protection goal b) the use patterns of the products c) physicochemical properties of the pesticides, and d) meteorological conditions of Korea. However, while assessing the risks for aquatic organisms we observed that for most of the selected pesticides the calculated exposure concentrations were higher than the regulatory acceptable concentration (RAC). To implement the exposure scenarios and models for pesticide authorization in Korea, further research on the RACs is needed. We also recommend studies to develop a higher-tier model and risk-mitigation measures that can be applied to the Korean situation.

Nitrogen Stimulates Microcystis-Dominated Blooms More than Phosphorus in River Conditions That Favor Non-Nitrogen-Fixing Genera.

Despite the implementation of intensive phosphorus reduction measures, periodic outbreaks of cyanobacterial blooms in large rivers remain a problem in Korea, raising the need for more effective solutions to reduce their occurrence. This study sought to evaluate whether phosphorus or nitrogen limitation is an effective approach to control cyanobacterial (Microcystis) blooms in river conditions that favor this non-nitrogen-fixing genus. These conditions include nutrient enrichment, high water temperature, and thermal stratification during summer. Mesocosm bioassays were conducted to investigate the limiting factors for cyanobacterial blooms in a river reach where severe Microcystis blooms occur annually. We evaluated the effect of five different nitrogen (3, 6, 9, 12, and 15 mg/L) and phosphorus (0.01, 0.02, 0.05, 0.1, and 0.2 mg/L) concentrations on algae growth. The results indicate that nitrogen treatments stimulated cyanobacteria (mostly Microcystis aeruginosa) more than phosphorus. Interestingly, phosphorus additions did not stimulate cyanobacteria, although it did stimulate Chlorophyceae and Bacillariophyceae. We conclude that phosphorus reduction might have suppressed the growth of Chlorophyceae and Bacillariophyceae more than that of cyanobacteria; therefore, nitrogen or at least both nitrogen and phosphorus control appears more effective than phosphorus reductions alone for reducing cyanobacteria in river conditions that are favorable for non-nitrogen-fixing genera.

Determination of C-Terminal δ-Catenin Responsible for Inducing Dendritic Morphogenesis.

δ-Catenin induces dendritic morphogenesis in several cells and it was reported that deletion of C-terminal 207 amino acid of δ-catenin completely abolished the dendritic morphogenesis. However, exact domain responsible for inducing dendritic morphogenesis in C-terminus of δ-catenin was not mapped. Here, we report that expression of ΔC47 (lacking 47 amino acid of C-terminus: 1-1200), ΔC77 (lacking 77 amino acid of C-terminus: 1-1170) deletion mutants of δ-catenin induced the dendritic morphogenesis of HEK293T and NIH3T3 cells as full-length δ-catenin did. In agreement with previous report, ΔC207 deletion mutant did not show the dendritic morphogenesis of the cells. Interestingly, introducing 107 amino acid deletion of C-terminus (ΔC107 mutant: 1-1140) and 177 amino acid deletion of C-terminus (ΔC177 mutant: 1-1070) showed limited primary and secondary dendritic process and notable spine-like process formation. These results suggest that 1140-1170 amino acid of C-terminal δ-catenin is required for primary and secondary dendrite-like process formation.