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Autism spectrum disorder (ASD) and epilepsy are highly comorbid, suggesting potential overlap in genetic etiology, pathophysiology, and neurodevelopmental abnormalities; however, the nature of this relationship remains unclear. This work investigated how two ion channel mutations, one associated with autism (Scn2a-null) and one with epilepsy (Kcna1-null), interact to modify genotype-phenotype relationships in the context of autism. Previous studies have shown that Scn2a
ameliorates epilepsy in Kcna1
mice, improving survival, seizure characteristics, and brain-heart dynamics. Here, we tested the converse, whether Kcna1 deletion modifies ASD-like repetitive and social behaviors in Scn2a
mice.
Mice were bred with various combinations of Kcna1 and Scn2a knockout alleles. Animals were assessed for repetitive behaviors using marble burying, grooming, and nestlet shredding tests and for social behaviors using sociability and social novelty preference tests.
Behavioral testing revealed drastic reductions in all repetitive behaviors in epileptic Kcna1
mice, but relatively normal social interactions. In contrast, mice with partial Kcna1 deletion (Kcna1
) exhibited increased self-grooming and decreased sociability suggestive of ASD-like features similar to those observed in Scn2a
mice. In double-mutant Scn2a
; Kcna1
mice, the two mutations interacted to partially normalize ASD-like behaviors associated with each mutation independently.
Taken together, these findings suggest that Kv1.1 subunits are important in pathways and neural networks underlying ASD and that Kcna1 may be a therapeutic target for treatment of Scn2a-associated ASD.
Taken together, these findings suggest that Kv1.1 subunits are important in pathways and neural networks underlying ASD and that Kcna1 may be a therapeutic target for treatment of Scn2a-associated ASD.Acrylamide is the product of the Maillard reaction, which occurs when starchy, asparagine-rich foods including potato or grain products and coffee are fried, baked, roasted, or heated. Studies in rodents provide evidence that acrylamide is carcinogenic and a male reproductive harmful agent when administered in exceedingly high levels. A 2002 study identified acrylamide in popular consumer food and beverage products, stimulating the European Union (EU) and California to legislate public notice of acrylamide presence in fried and baked foods, and coffee products. The regulatory legislation enacted in the EU and California has scientists working to develop foods and processes aimed at reducing acrylamide formation and advancing rapid and accurate analytical methods for the quantitative and qualitative determination of acrylamide in food and beverage products. The purpose of this review is to survey the studies performed on rodents and humans that identified the potential health impact of acrylamide in the human diet, and provide insight into established and emerging analytical methods used to detect acrylamide in blood, aqueous samples, and food.Brain pericytes regulate diverse aspects of neurovascular development and function, including blood-brain barrier (BBB) induction and maintenance. Primary brain pericytes have been widely employed in coculture-based in vitro models of the BBB, and a method to generate brain pericytes from human pluripotent stem cells (hPSCs) could provide a renewable, genetically tractable source of cells for BBB modeling and studying pericyte roles in development and disease. Here, we describe a protocol to differentiate hPSCs to NG2+ PDGFRβ+ αSMAlow brain pericyte-like cells in 22-25 days through a p75-NGFR+ HNK-1+ neural crest intermediate, which mimics the developmental origin of forebrain pericytes. The resulting brain pericyte-like cells have molecular and functional attributes of brain pericytes. We also provide protocols for maintenance, cryopreservation, and recovery of the neural crest intermediate, and for molecular and functional characterization of the resulting cells. © 2021 Wiley Periodicals LLC. Basic Protocol 1 Differentiation of hPSCs to neural crest Basic Protocol 2 Differentiation of neural crest to brain pericyte-like cells Support Protocol 1 Flow cytometry analysis of neural crest cells Support Protocol 2 Maintenance, cryopreservation, and recovery of neural crest cells Support Protocol 3 Molecular characterization of brain pericyte-like cells Support Protocol 4 Cord formation assay with endothelial cells and brain pericyte-like cells.This article contains detailed synthetic protocols for the preparation of DNA oligonucleotides containing 8-trifluoromethyl-2'-deoxyguanosine (CF3 dG) and their application to observe Z-DNA structure in vitro and in living HeLa cells. First, using a catalytic system consisting of FeSO4 , H2 SO4 , and H2 O2 in DMSO, we achieved a one-step synthesis of CF3 dG through a radical reaction between deoxyguanosine (dG) and CF3 I, with a yield of 45%. We then obtained the 3'-phosphoramidite of CF3 dG through a routine three-step procedure. Next, we employed the CF3 dG phosphoramidite monomer in the synthesis of oligonucleotides on a solid-phase DNA synthesizer. Finally, we used the CF3 dG-modified DNA oligonucleotides to observe Z-DNA structure in vitro and in living HeLa cells through 19 F NMR spectroscopy. © 2021 Wiley Periodicals LLC. Basic Protocol 1 Synthesis of CF3 dG phosphoramidites Basic Protocol 2 Preparation of CF3 dG-modified DNA oligonucleotides Basic Protocol 3 Evaluation of CF3 dG stabilization of Z-DNA structure by CD spectroscopy Basic Protocol 4 Investigation of Z-DNA structure in vitro and in HeLa cells with CF3 dG-modified DNA oligonucleotides and 19 F NMR spectroscopy.Developing a bifunctional water splitting catalyst with high efficiency and low cost are crucial in the electrolysis water industry. Here, we report a rational design and simple preparation method of MoS2 -based bifunctional electrocatalyst on carbon cloth (CC). The optimized P-doped MoS2 @CoP/CC catalyst presents low overpotentials for the hydrogen (HER) and oxygen evolution reactions (OER) of 64 and 282 mV in alkaline solution as well as 72 mV HER overpotential in H2 SO4 at a current density of 10 mA cm-2 . Furthermore, P-MoS2 @CoP/CC as a bifunctional catalyst delivered relatively low cell voltages of 1.83 and 1.97 V at high current densities of 500 and mA cm-2 in 30 % KOH. check details The two-electrode system showed a remarkable stability for 30 h, even outperformed the benchmark RuO2 ||Pt/C catalyst. The excellent electrochemical performance can be credited to the unique microstructure, high surface area, and the synergy between metal species. This study presents a possible alternative for noble metal-based catalysts to overcome the challenges of industrial applications.
Here's my website: https://www.selleckchem.com/products/ide397-gsk-4362676.html
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