Pathogenic variants carrier screening in New Brunswick: Acadians reveal high carrier frequency for multiple genetic disorders.

Background: Founder populations that have recently undergone important genetic bottlenecks such as French-Canadians and Ashkenazi Jews can harbor some pathogenic variants at a higher carrier rate than the general population, putting them at a higher risk for certain genetic diseases. In these populations, there can be considerable benefit to performing ethnic-based or expanded preconception carrier screening, which can help in the prevention or early diagnosis and management of some genetic diseases. Acadians are descendants of French immigrants who settled in the Atlantic Coast of Canada in the seventeenth century.

Loss of detection of fatty acid-metabolizing proteins in Western blot analyses - Impact of sample heating.

When performing western blots for protein detection using the classical Laemmli method, experimenters often encounter difficulties with the detection of transmembrane proteins involved in lipid or fatty acid metabolism. A crucial phase in sample preparation is heating the samples to 100 °C in a Laemmli sample buffer containing SDS before separation by polyacrylamide gel electrophoresis (PAGE). In the current study, the analysis of several proteins was performed following modifications of the heating step during sample preparation.

Circulating cell-free DNA as potential diagnostic tools for amyotrophic lateral sclerosis.

DNA methylation has garnered much attention in recent years for its diagnostic potential in multiple conditions including cancer and neurodegenerative diseases. Conversely, advances regarding the potential diagnostic relevance of DNA methylation status have been sparse in the field of amyotrophic lateral sclerosis (ALS) even though patients diagnosed with this condition would significantly benefit from improved molecular assays aimed at furthering the current diagnostic and therapeutic options available. This review will provide an overview of the current diagnostic approaches available for ALS diagnosis and discuss the potential clinical usefulness of DNA methylation.

EBF1 drives hallmark B cell gene expression by enabling the interaction of PAX5 with the MLL H3K4 methyltransferase complex.

PAX5 and EBF1 work synergistically to regulate genes that are involved in B lymphocyte differentiation. We used the KIS-1 diffuse large B cell lymphoma cell line, which is reported to have elevated levels of PAX5 expression, to investigate the mechanism of EBF1- and PAX5-regulated gene expression. We demonstrate the lack of expression of hallmark B cell genes, including CD19, CD79b, and EBF1, in the KIS-1 cell line.

The impact of PUFA on cell responses: Caution should be exercised when selecting PUFA concentrations in cell culture.

Polyunsaturated fatty acids (PUFA) are important components of cellular membranes, serving both structural and signaling functions. Investigation of the functional responses of cells to various PUFA often involves cell culture experiments, which can then inform or guide subsequent in vivo and clinical investigations. In this study, human carcinoma and leukemia cell lines (MCF-7, HepG2, THP-1, Jurkat) were incubated for 3 days in the presence of up to 150 μM of exogenous arachidonic or eicosapentaenoic acids.

20-Hydroxy- and 20-carboxy-leukotriene (LT) B downregulate LTB -mediated responses of human neutrophils and eosinophils.

Leukotriene B (LTB ) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB has a short half-life and is rapidly metabolized by leukocytes, notably into 20-OH- and 20-COOH-LTB by neutrophils. Although these LTB metabolites bind to the BLT receptor with high affinity, they activate neutrophils to a much lower extent than LTB .

Polyunsaturated fatty acid elongation and desaturation in activated human T-cells: ELOVL5 is the key elongase.

PUFAs are important constituents of membrane glycerophospholipids. However, changes in the capacities to incorporate and metabolize PUFAs when cells enter the cell cycle have not been thoroughly studied. In this study, differences in the incorporation and metabolism of exogenous PUFAs in resting and proliferating primary human T-cells and in the Jurkat cell line were measured.

On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid.

Alkyne and azide analogs of natural compounds that can be coupled to sensitive tags by click chemistry are powerful tools to study biological processes. Arachidonic acid (AA) is a FA precursor to biologically active compounds. 19-Alkyne-AA (AA-alk) is a sensitive clickable AA analog; however, its use as a surrogate to study AA metabolism requires further evaluation.

Polyunsaturated fatty acid-phospholipid remodeling and inflammation.

Purpose Of Review: To highlight some of the recent advances related to the control of polyunsaturated fatty acid (PUFA) incorporation and remodeling in membrane glycerophospholipids in inflammatory cells.

Recent Findings: Several enzymes have recently been identified that are associated with the control of PUFA incorporation and remodeling into membrane phospholipids and their release. The functional roles of the different enzyme isotypes in the control of PUFA availability for lipid mediator biosynthesis and cell signaling are only now being established.

Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells.

Changes in fatty acid (FA) and glycerophospholipid (GPL) metabolism associated with cell cycle entry are not fully understood. In this study FA-GPL remodeling was investigated in resting and proliferating primary human T cells. Significant changes were measured in the composition and distribution of FAs in GPLs following receptor activation of human T cells.