Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Molecular phylogenetic relationships of Metastrongylus nematodes with emphasis on specimens from domestic pigs in Vietnam.

Lungworms of the genus Metastrongylus are parasitic nematodes in the respiratory tract of swine. Although they infect both wild boars and domestic pigs, studies on Metastrongylus infections in wild boars in Europe, the Americas and Africa are numerous, while those in domestic pigs are few. There are several studies analysing the molecular phylogenetic relationships of few individual Metastrongylus species with other nematode taxa, but there are no studies on the phylogenetic relationships of species within the genus Metastrongylus. In Southeast Asia, reports on swine lungworms are extremely scarce and do not include any nucleotide sequence data. Therefore, the aim of the present study is to survey Metastrongylus infection in domestic pigs raised in Dien Bien Province, Northern Vietnam, and to analyse the molecular phylogenetic relationships of Metastrongylus species. Based on morphological and molecular data, we identified two species: Metastrongylus apri and Metastrongylus pudendotectus. The prevalence of the former species was found to be significantly higher than the latter one (24.1% vs. 2.3%). We observed pigs exhibiting a coinfection with the two lungworm species or a single infection with only M. apri. However, we did not observe any pigs being infected with just M. pudendotectus. Vietnamese Metastrongylus specimens showed slight morphological and molecular differences compared to those from other countries. The molecular analyses revealed a close genetic relationship between M. apri and Metastrongylus salmi, while both these species were far distant from M. pudendotectus. The present study highlights the needs for further studies to clarify the morphological features and ecological and phylogenetic relationships of Metastrongylus species at the global scale.

Acute inhibitory effects of clenbuterol on force, Ca²âº transients and action potentials in rat soleus may not involve the ß2-adrenoceptor pathway.

1. Clenbuterol, a ß(2)-adrenoceptor agonist, can have inhibitory and myotoxic effects on slow-twitch muscles. Clenbuterol is lipophilic and may enter into the intracellular compartment, and because of this, it is likely that clenbuterol will have different effects to classical ß(2)-adrenoceptor agonists such as terbutaline. The aim of the present study is to investigate clenbuterol's effect on force, intracellular [Ca(2+)] and electrophysiology, and the role of the ß(2)-adrenoceptor pathway in these effects. 2. Simultaneous measurements of isometric force and [Ca(2+)](i) were made from small bundles of rat soleus muscle fibres in which several superficial fibres had been pressure-injected with the fluorescence Ca(2+) indicator Indo-1. The muscle's electrophysiological response was measured using glass intracellular microelectrodes. 3. The most robust effect of clenbuterol was a concentration- (10-50 µmol/L) and frequency-dependent (10-80 Hz) loss of force and [Ca(2+)](i) maintenance during tetanic stimulation of muscle fibres. None of these effects were reduced in the presence of the ß(2)-antagonist ICI 118551. 4. In addition clenbuterol had a significant effect on muscle electrophysiology, with action potentials measured during tetanic trains being inhibited in a concentration- and frequency-dependent manner. This response was also unchanged by pre-treatment with the ß(2)-antagonist ICI 118551. 5. These results indicate that some of clenbuterol's effects are mediated through a pathway other than the ß(2)-adrenoceptors.