👤 Marina Danilenko

Since there is currently no cure for Parkinson's disease, pharmacobiotic approaches based on gut microbiota-capable of producing pharmacologically active compounds-are under development. In this study, we propose LfU21, derived from the strain Show less

Cardiovascular disease (CVD) is the leading cause of mortality in the United States and globally. This review describes changes in CVD lipid and lipoprotein biomarker measurements that occurred in line with the evolution of clinical practice guidelines for CVD risk assessment and treatment. It also discusses the level of comparability of these biomarker measurements in clinical practice. Comparable and reliable measurements are achieved through assay standardization, which not only depends on correct test calibration but also on factors such as analytical sensitivity, selectivity, susceptibility to factors that can affect the analytical measurement process, and the stability of the test system over time. The current status of standardization for traditional and newer CVD biomarkers is discussed, as are approaches to setting and achieving standardization goals for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), lipoprotein(a) (Lp(a)), apolipoproteins (apo) A-I and B, and non-HDL-C. Appropriate levels of standardization for blood lipids are maintained by the Centers for Disease Control and Prevention's (CDC) CVD Biomarkers Standardization Program (CDC CVD BSP) using the analytical performance goals recommended by the National Cholesterol Education Program. The level of measurement agreement that can be achieved is dependent on the characteristics of the analytes and differences in measurement principles between reference measurement procedures and clinical assays. The technical and analytical limitations observed with traditional blood lipids are not observed with apolipoproteins. Additionally, apoB and Lp(a) may more accurately capture CVD risk and residual CVD risk, respectively, than traditional lipids, thus prompting current guidelines to recommend apolipoprotein measurements. This review further discusses CDC's approach to standardization and describes the analytical performance of traditional blood lipids and apoA-I and B observed over the past 11 years. The reference systems for apoA-I and B, previously maintained by a single laboratory, no longer exist, thus requiring the creation of new systems, which is currently underway. This situation emphasizes the importance of a collaborative network of laboratories, such as CDC's Cholesterol Reference Methods Laboratory Network (CRMLN), to ensure standardization sustainability. CDC is supporting the International Federation of Clinical Chemistry and Laboratory Medicine's (IFCC) work to establish such a network for lipoproteins. Ensuring comparability and reliability of CVD biomarker measurements through standardization remains critical for the effective implementation of clinical practice guidelines and for improving patient care. Utilizing experience gained over three decades, CDC CVD BSP will continue to improve the standardization of traditional and emerging CVD biomarkers together with stakeholders. Show less

The RNA binding protein T-STAR was created following a gene triplication 520-610 million years ago, which also produced its two parologs Sam68 and SLM-1. Here we have created a T-STAR null mouse to identify the endogenous functions of this RNA binding protein. Mice null for T-STAR developed normally and were fertile, surprisingly, given the high expression of T-STAR in the testis and the brain, and the known infertility and pleiotropic defects of Sam68 null mice. Using a transcriptome-wide search for splicing targets in the adult brain, we identified T-STAR protein as a potent splicing repressor of the alternatively spliced segment 4 (AS4) exons from each of the Neurexin1-3 genes, and exon 23 of the Stxbp5l gene. T-STAR protein was most highly concentrated in forebrain-derived structures like the hippocampus, which also showed maximal Neurexin1-3 AS4 splicing repression. In the absence of endogenous T-STAR protein, Nrxn1-3 AS4 splicing repression dramatically decreased, despite physiological co-expression of Sam68. In transfected cells Neurexin3 AS4 alternative splicing was regulated by either T-STAR or Sam68 proteins. In contrast, Neurexin2 AS4 splicing was only regulated by T-STAR, through a UWAA-rich response element immediately downstream of the regulated exon conserved since the radiation of bony vertebrates. The AS4 exons in the Nrxn1 and Nrxn3 genes were also associated with distinct patterns of conserved UWAA repeats. Consistent with an ancient mechanism of splicing control, human T-STAR protein was able to repress splicing inclusion of the zebrafish Nrxn3 AS4 exon. Although Neurexin1-3 and Stxbp5l encode critical synaptic proteins, T-STAR null mice had no detectable spatial memory deficits, despite an almost complete absence of AS4 splicing repression in the hippocampus. Our work identifies T-STAR as an ancient and potent tissue-specific splicing regulator that uses a concentration-dependent mechanism to co-ordinately regulate regional splicing patterns of the Neurexin1-3 AS4 exons in the mouse brain. Show less