Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain

Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the Esr1 gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of Esr2, Gper1, Ahr, Arnt, Cyp19a1, Cyp1a1, and Atg7, and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes.     

CRISPR/Cas9-Based Mutagenesis of Histone H3.1 in Spinal Dynorphinergic Neurons Attenuates Thermal Sensitivity in Mice

Burn injury is a trauma resulting in tissue degradation and severe pain, which is processed first by neuronal circuits in the spinal dorsal horn. We have recently shown that in mice, excitatory dynorphinergic (Pdyn) neurons play a pivotal role in the response to burn-injury-associated tissue damage via histone H3.1 phosphorylation-dependent signaling. As Pdyn neurons were mostly associated with mechanical allodynia, their involvement in thermonociception had to be further elucidated. Using a custom-made AAV9_mutH3.1 virus combined with the CRISPR/cas9 system, here we provide evidence that blocking histone H3.1 phosphorylation at position serine 10 (S10) in spinal Pdyn neurons significantly increases the thermal nociceptive threshold in mice. In contrast, neither mechanosensation nor acute chemonociception was affected by the transgenic manipulation of histone H3.1. These results suggest that blocking rapid epigenetic tagging of S10H3 in spinal Pdyn neurons alters acute thermosensation and thus explains the involvement of Pdyn cells in the immediate response to burn-injury-associated tissue damage.     

Psyllium, not pectin or guar gum, alters lipoprotein and biliary bile acid composition and fecal sterol excretion in the hamster

Different soluble dietary fibers known to alter cholesterol metabolism were fed to golden Syrian hamsters, and their specific impact on lipoproteins, biliary bile acid profile, and fecal sterol excretion was evaluated. Semipurified diets containing 20% fat; 0.12% cholesterol; and 8% of psyllium (PSY); high (hePE) and low (lePE) esterified pectin; or high (hvGG) and low (lvGG) viscous guar gum were fed for 5 wk. Compared to control, PSY caused a significant reduction in plasma cholesterol (2.9±0.5 vs. 5.5±0.5 mmol/L), whereas hePE, lePE, hvGG, or lvGG had no apparent effect on plasma lipids. Hepatic total and esterified cholesterol were substantially decreased with PSY, pectin and guar gum, whereby PSY produced the most pronounced effect. Distinctive changes existed in the bile acid profile related to the different fibers. In contrast to pectin and guar gum, PSY caused a significant increase in the cholate:chenodeoxycholate and the glycine:taurine conjugation ratio. Pectin and guar gum did not alter daily fecal neutral sterol excretion while PSY caused a 90% increase due to a higher fecal output. Daily fecal bile acid excretion and total fecal bile acid concentration were significantly increased by PSY, whereas hePE, lePE, hvGG, and lvGG revealed no or only minor effects. Taken together, the disparate hypocholesterolemic effects of PSY, pectin, and guar gum on cholesterol and bile acid metabolism in the hamster are possibly related to different physicochemical properties, e.g., viscosity and susceptibility to fermentation, affecting the fiber-mediated action in the intestine.     

Isolation and characterization of a major allergen in kiwi fruit

 The isolation of an important allergen in kiwi fruit (Actinidia chinensis) by ion-exchange chromatography (IEC) and micropreparative SDS-PAGE followed by electroelution is reported. The purity of the allergen was analysed by SDS-PAGE and immunoblotting with sera from patients who have an allergy to kiwi. The allergen was shown to have a molecular weight of 43 kDa by SDS-PAGE/immunoblotting and an isoelectric point of approximately 6.9 as estimated by IEC. In accordance with World Health Organization nomenclature, this allergen is called Act c 2. By immunoblot inhibition it was shown that epitopes from different allergens in kiwi fruit are also located on Act c 2. N-terminal amino acid sequencing of 17 amino acid residues did not reveal homology with the major allergens in birch pollen (Bet v 1), apple (Mal d 1) or with other proteins of allergenic plant foods. In addition, the isoelectric point of a 67-kDa allergen in kiwi fruit was estimated to be 7.4 by IEC, but micropreparative isolation of this allergen failed because of its very low content in the fruit. Received: 14 April 1997     

Effectiveness of products from four locally grown plants for the management of Acanthoscelides obtectus (Say) and Zabrotes subfasciatus (Boheman) (both Coleoptera: Bruchidae) in stored beans under laboratory and farm conditions in Northern Tanzania

The effectiveness of whole or powdered leaves (botanicals) from four locally grown plant species applied at a rate of 1.5 kg per 100 kg beans (Phaseolus vulgaris) against Acanthoscelides obtectus and Zabrotes subfasciatus was compared under laboratory and farm conditions. In the laboratory, Chenopodium ambrosioides, applied as powder or as whole leaves, was the most effective, with 100% mortality of adult insects in less than three days and no progeny. Less C. ambrosioides (about 200 g per 100 kg beans) still resulted in 100% mortality within 24 h. Tagetes minuta applied as powder also increased mortality and reduced oviposition and progeny production significantly. The other treatments - T. minuta applied as leaves, and Azadirachta indica or Cupressus lusitanica applied as powder or as whole leaves - had no significant effects upon mortalities, oviposition rate, or progeny production compared with control treatments. When the rate of application was increased to about 8.3 kg per 100 kg beans, there was a slight increase in mortality using T. minuta and A. indica, but not with C. lusitanica. An additional trial with C. ambrosioides from different collections and with plants at different stages of development revealed considerable variations in the efficacy of the treatment.In the on-farm trials, A. indica-seed powder was the most effective treatment, followed respectively by leaf powders of C. ambrosioides, C. lusitanica and T. minuta. All treatments were significantly more effective than the control in reducing the numbers of live insects; they also reduced numbers of damaged beans and maintained germination rates after 5 months of storage. The results of evaluations of the treatments made by farmers just after the trials and five years later are reported.     

Comparison of two sample preparation techniques for sniffing experiments with broccoli (Brassica oleracea var. italica Plenck)

The suitability of the headspace solid phase microextraction (HSSPME) for gas chromatography-olfactometry (GC-O) with aroma extract dilution analysis in comparison to the dynamic head space sampling on a Tenax trap was tested exemplarily by the aroma volatiles of fresh broccoli. A high number of odour sensations in qualitative olfactometry was registered with both sample preparation techniques. The key aroma compounds of the fresh broccoli material are represented by high flavour dilution factors with dynamic head space sampling and headspace SPME. The SPME method has found to be a convenient and fast technique suitable especially for qualitative GC-O. The adsorption selectivity of the fiber and the substance discrimination have to be taken into account for quantitative use like aroma extract dilution analysis.     

Fused calcium zirconate for refractory applications

This article investigates dense CaZrO₃ produced by electric arc melting and compares it to solid state synthesized CaZrO₃. The fused CaZrO₃ had a considerable lower porosity than the solid state synthesized material, however due to evaporation of some CaO during the electric arc melting the stoichiometric ratio of CaO/ZrO₂ was slightly smaller than one, resulting in the formation of cubic ZrO₂ as a second phase. To determine the local phase distribution the materials were investigated with EBSD in addition to integral XRD. The vibration polishing of the ceramics resulted in excellent EBSD patterns. Die pressed cylinders of the fused material led to a porosity as low as 14.3%. The linear thermal expansion coefficient from 25 °C to 1000 °C was 10.45 × 10^?6 K^?1. The cold isostatic pressing of larger crucibles resulted in higher porosity of 15.9–16.5%. The EBSD analysis and the cold isostatic pressed crucibles can be applied in corrosion tests for titanium melts.