Comparative analysis of methods to reduce activation signature gene expression in PBMCs.

Preserving the in vivo cell transcriptome is essential for accurate profiling, yet factors during cell isolation including time ex vivo and temperature induce artifactual gene expression, particularly in stress-responsive immune cells. In this study, we investigated two methods to mitigate ex vivo activation signature gene (ASG) expression in peripheral blood mononuclear cells (PBMCs): transcription and translation inhibitors (TTis) and cold temperatures during isolation. Comparative analysis of PBMCs isolated with TTis revealed reduced ASG expression. However, TTi treatment impaired responsiveness to LPS stimulation in subsequent in vitro experiments. In contrast, cold isolation methods also prevented ASG expression; up to a point where the addition of TTis during cold isolation offered minimal additional advantage. These findings highlight the importance of considering the advantages and drawbacks of different isolation methods to ensure accurate interpretation of PBMC transcriptomic profiles.

Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-dependent neurodegeneration.

The human microbiota is believed to influence health. Microbiome dysbiosis may be linked to neurological conditions like Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. We report the ability of a probiotic bacterial strain in halting neurodegeneration phenotypes. We show that Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of amyotrophic lateral sclerosis and Huntington's disease. Our results show that neuroprotection from L. rhamnosus HA-114 is unique from other L. rhamnosus strains and resides in its fatty acid content. Neuroprotection by L. rhamnosus HA-114 requires acdh-1/ACADSB, kat-1/ACAT1 and elo-6/ELOVL3/6, which are associated with fatty acid metabolism and mitochondrial ß-oxidation. Our data suggest that disrupted lipid metabolism contributes to neurodegeneration and that dietary intervention with L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial ß-oxidation. Our findings encourage the exploration of L. rhamnosus HA-114 derived interventions to modify the progression of neurodegenerative diseases.

Does the adenosine deaminase (ADA) gene confer risk of sleepwalking?

Sleepwalking is a common non-rapid eye movement (NREM) parasomnia and a significant cause of sleep-related injuries. While evidence suggest that the occurrence of this condition is partly determined by genetic factors, its pattern of inheritance remains unclear, and few molecular studies have been conducted. One promising candidate is the adenosine deaminase (ADA) gene. Adenosine and the ADA enzyme play an important role in the homeostatic regulation of NREM sleep. In a single sleepwalking family, genome-wide analysis identified a locus on chromosome 20, where ADA lies. In this study, we examined if variants in the ADA gene were associated with sleepwalking. In total, 251 sleepwalking patients were clinically assessed, and DNA samples were compared to those from 94 unaffected controls. Next-generation sequencing of the whole ADA gene was performed. Bio-informatic analysis enabled the identification of variants and assessed variants enrichment in our cohort compared to controls. We detected 25 different coding and non-coding variants, of which 22 were found among sleepwalkers. None were enriched in the sleepwalking population. However, many missense variants were predicted as likely pathogenic by at least two in silico prediction algorithms. This study involves the largest sleepwalking cohort in which the role of a susceptibility gene was investigated. Our results did not reveal an association between ADA gene and sleepwalking, thus ruling out the possibility of ADA as a major genetic factor for this condition. Future work is needed to identify susceptibility genes.

Estimated prevalence of Niemann-Pick type C disease in Quebec.

Niemann-Pick type C (NP-C) disease is an autosomal recessive disease caused by variants in the NPC1 or NPC2 genes. It has a large range of symptoms depending on age of onset, thus making it difficult to diagnose. In adults, symptoms appear mainly in the form of psychiatric problems. The prevalence varies from 0.35 to 2.2 per 100,000 births depending on the country. The aim of this study is to calculate the estimated prevalence of NP-C in Quebec to determine if it is underdiagnosed in this population. The CARTaGENE database is a unique database that regroups individuals between 40 and 69 years old from metropolitan regions of Quebec. RNA-sequencing data was available for 911 individuals and exome sequencing for 198 individuals. We used a bioinformatic pipeline on those individuals to extract the variants in the NPC1/2 genes. The prevalence in Quebec was estimated assuming Hardy-Weinberg Equilibrium. Two pathogenic variants were used. The variant p.Pro543Leu was found in three heterozygous individuals that share a common haplotype, which suggests a founder French-Canadian pathogenic variant. The variant p.Ile1061Thr was found in two heterozygous individuals. Both variants have previously been reported and are usually associated with infantile onset. The estimated prevalence calculated using those two variants is 0.61:100,000 births. This study represents the first estimate of NP-C in Quebec. The estimated prevalence for NP-C is likely underestimated due to misdiagnosis or missed cases. It is therefore important to diagnose all NP-C patients to initiate early treatment.

Identification and Classification of Rare Variants in NPC1 and NPC2 in Quebec.

Niemann-Pick disease type C (NPC) is a treatable autosomal recessive neurodegenerative condition which leads to a variety of progressive manifestations. Despite most cases being diagnosed at a young age, disease prevalence may be underestimated, especially in adults, and interpretation of NPC1 and NPC2 variants can be difficult. This study aims to identify potential pathogenic variants in a large cohort of healthy individuals and classify their risk of pathogenicity to assist with future interpretation of variants. The CARTaGENE (CaG) cohort was used to identify possible variants of NPC1 and NPC2. Nine-hundred and eleven RNA samples and 198 exome sequencing were screened for genetic variants through a bio-informatic pipeline performing alignment and variant calling. The identified variants were analyzed using annotations for allelic frequency, pathogenicity and conservation scores. The ACMG guidelines were used to classify the variants. These were then compared to existing databases and previous studies of NPC prevalence, including the Tübingen NPC database. Thirty-two distinct variants were identified after running the samples in the RNA-sequencing pipeline, two of which were classified as pathogenic and 21 of which were not published previously. Furthermore, 46 variants were both identified in our population and with the Tübingen database, the majority of which were of uncertain significance. Ten additional variants were found in our exome-sequencing sample. This study of a sample from a population living in Quebec demonstrates a variety of rare variants, some of which were already described in the literature as well as some novel variants. Classifying these variants is arduous given the scarcity of available literature, even so in a population of healthy individuals. Yet using this data, we were able to identify two pathogenic variants within our population and several new variants not previously identified.

Relationship Between Psychosocial Factors, Dietary Intake and Gestational Weight Gain: A Narrative Review.

Inadequate gestational weight gain (GWG), which has reached almost two-thirds of Canadian pregnant women, is associated with several adverse effects both in the mother and her child. The aim of this review was to establish how psychosocial factors, diet and GWG are interrelated during pregnancy. More specifically, it aimed to evaluate how psychosocial factors can impact on diet and, thus, influence GWG. Studies published through May 2017 that examined factors related to GWG were included. Of 3268 non-duplicate titles and abstract, 77 articles underwent full-text review. Regarding dietary intakes, the majority of the included studies demonstrated that a higher caloric intake was associated with an elevated GWG. Also, a negative body image and attitude toward weight gain as well as a poor knowledge of GWG recommendations and inadequate prenatal care is associated with an increased GWG. Only few studies examined altogether the factors included and conclusions about how psychosocial factors can impact on diet and, thus, influence GWG cannot be drawn at this point. In the few studies that evaluated the interrelationships between psychosocial factors, diet and GWG, energy intake was not identified as a mediator of the association between psychosocial factors and GWG. This review highlights the scarcity of findings regarding psychosocial and dietary factors in relation to GWG and the need for high quality prospective cohort studies that will include all these factors to provide a better understanding of how they are interrelated to influence short- and long-term health.