BACKGROUND Fragile X Syndrome (FXS) is a trinucleotide repeat disease that is caused by the expansion of CGG sequences in the 5’ untranslated region of the FMR1 gene. Molecular diagnoses of FXS and other emerging FMR1 disorders typically rely on two tests, PCR and Southern blotting. However, performance or throughput limitations in these methods currently constrain routine testing. METHODS We evaluated a novel FMR1 gene-specific PCR technology with 20 cell line DNA templates and 146 blinded clinical specimens. The CGG repeat number was determined by fragment sizing of PCR amplicons using capillary electrophoresis and compared with the results of FMR1 Southern blotting performed with the same samples. RESULTS The FMR1 PCR accurately detected full mutation alleles up to at least 1300 CGG repeats and comprising >99% GC character. All categories of alleles detected by Southern blot, including 66 specimens with full mutations, were also identified by FMR1 PCR for each of 146 clinical specimens. Since all full mutation alleles in heterozygous female samples were detected by PCR, allele zygosity was reconciled in every case. The PCR reagents also detected a 1% mass fraction of a 940 CGG allele in a background of 99% 23 CGG allele—roughly 5-fold greater sensitivity than Southern blotting. CONCLUSIONS The novel PCR technology can accurately categorize the spectrum of FMR1 alleles, including alleles previously considered too large to amplify, reproducibly detect low abundance full mutation alleles, and correctly infer homozygosity in female specimens, thus greatly reducing the need for sample reflexing to Southern blot.

CD47 is an immunoglobulin that is overexpressed on the surface of many types of cancer cells. CD47 forms a signaling complex with signal-regulatory protein α (SIRPα), enabling the escape of these cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed by various types of solid tumors and to be associated with poor patient prognosis in various types of cancer. A growing number of studies have since demonstrated that inhibiting the CD47-SIRPα signaling pathway promotes the adaptive immune response and enhances the phagocytosis of tumor cells by macrophages. Improved understanding in this field of research could lead to the development of novel and effective anti-tumor treatments that act through the inhibition of CD47 signaling in cancer cells. In this review, we describe the structure and function of CD47, provide an overview of studies that have aimed to inhibit CD47-dependent avoidance of macrophage-mediated phagocytosis by tumor cells, and assess the potential and challenges for targeting the CD47-SIRPα signaling pathway in anti-cancer therapy.

Emerging evidence describe heat shock proteins (HSPs) as critical regulators in normal neural physiological function as well as in cell stress responses. The functions of HSPs represent an enormous and diverse range of cellular activities, far beyond the originally identified role in protein folding and chaperoning. Now understood to be involved in processes such as synaptic transmission, autophagy, ER stress response, protein kinase and cell death signaling as well as protein chaperone and folding, manipulation of HSPs have robust effects on the fate of cells in neurological injury and disease states. The ongoing exploration of multiple HSP superfamilies has underscored the pluripotent nature of HSPs in the cellular context, and demanded the recent restructuring of the nomenclature referring to these families to reflect a re-organization based on structure and function. In keeping with this re-organization, we have first discussed the HSP superfamilies in terms of protein structure, regulation and expression and distribution in the brain. We then explore major cellular functions of HSPs that are relevant to neural physiological states, and from there discuss known and proposed HSP impact on major neurological disease states. This review article presents a three-part discussion on the array of HSPs families relevant to neuronal tissue, their cellular functions, and the exploration of therapeutic targets of these proteins in the context of neurological diseases.