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The use of superficially porous particles (SPPs) for modern high performance liquid chromatography (HPLC) is now very common. Initially, SPPs rose as an alternative to sub-2-um fully porous particles (FPPs). [...]

The use of superficially porous particles (SPPs) for modern high performance liquid chromatography (HPLC) is now very common. Initially, SPPs rose as an alternative to sub-2-[micro]m fully porous particles (FPPs). In recent years, many column manufacturers have developed 2-[micro]m and smaller SPP-based products. This article investigates the practical utility of these smaller SPP designs., The introduction of modern superficially porous particles (SPPs) by Advanced Materials Development in 2006 revolutionized high performance liquid chromatography (HPLC). Interest in these particles, characterized by a solid core and [...]

Abuse of synthetic opioid prescription painkillers such as fentanyl, along with a rapidly growing list of illicit analogues, is a significant public health problem. In this study, we developed a [...]

Thyroid hormones are essential for the regulation of development and growth in humans and animals. The thyroid gland produces thyroxin (T4) and tri-iodothyronine (T3) and quickly releases these compounds into [...]

Thyroid hormones are essential for the regulation of development and growth in humans and animals. The thyroid gland produces thyroxin (T4) and tri-iodothyronine (T3) and quickly releases these compounds into [...]

The eIF2α (eukaryotic initiation factor-2α) kinase PERK (doublestranded RNA-activated protein kinase-like ER kinase) is essential for the normal function of highly secretory cells in the pancreas and skeletal system, as well as the UPR (unfolded protein response) in mammalian cells. To delineate the regulatory machinery underlying PERK-dependent stress-responses, gene profiling was employed to assess global changes in gene expression in PERK-deficient MEFs (mouse embryonic fibroblasts). Several IE (immediate-early) genes, including c-myc, c-jun, egr-1 (early growth response factor-1), and fra-1 (fos-related antigen-1), displayed PERK-dependent expression in MEFs upon disruption of calcium homoeostasis by inhibiting the ER (endoplasmic reticulum) transmembrane SERCA (sarcoplasmic/ER Ca2+-ATPase) calcium pump. Induction of c-myc and egr-1 by other reagents that elicit the UPR, however, showed variable dependence upon PERK. Induction of c-myc expression by thapsigargin was shown to be linked to key signalling enzymes including PLC (phospholipase C), PI3K (phosphatidylinositol 3-kinase) and p38 MAPK (mitogen-activated protein kinase). Analysis of the phosphorylated status of major components in MAPK signalling pathways indicated that thapsigargin and DTT (dithiothreitol) but not tunicamycin could trigger the PERK-dependent activation of JNK (c-Jun N-terminal kinase) and p38 MAPK. However, activation of JNK and p38 MAPK by non-ER stress stimuli including UV irradiation, anisomycin, and TNF-α (tumour necrosis factor-α) was found to be independent of PERK. PERK plays a particularly important role in mediating the global cellular response to ER stress that is elicited by the depletion of calcium from the ER. We suggest that this specificity of PERK function in the UPR is an extension of the normal physiological function of PERK to act as a calcium sensor in the ER.

Microsomal epoxide hydrolase (EPHX1) catalyzes hydration reactions that determine the cellular disposition of reactive epoxide derivatives. Whereas the previously defined EPHX1 exon 1 sequence (E1) is derived from a promoter proximal to exon 2 of the EPHX1 coding region, in this investigation, we identified an alternative EPHX1 exon 1 sequence, E1-b, originating from a gene promoter localized ∼18.5 kb upstream of exon 2. Northern hybridizations demonstrated that the E1-b variant is widely expressed and that the E1-b promoter functions as the primary driver of EPHX1 expression in human tissues. In contrast, the E1 promoter directs expression only in the liver. To examine the basis for liver-specific usage of the E1 promoter, we identified several potential cis-regulatory elements that included GATA (-110/-105) and hepatocyte nuclear factor 3 (HNF3) (-96/-88) motifs. GATA-4 was the principal GATA family member interacting with its respective motif, whereas both HNF3α and HNF3β were capable of interacting with the HNF3 element. GATA-4 and HNF3α/HNF3β DNA binding complexes were enriched in hepatic cells. Site-directed mutagenesis and transactivation analyses of the E1 promoter revealed that GATA-4 is probably a principal factor that regulates liver-specific expression of the E1 variant, with HNF3α and HNF3β acting to negatively regulate GATA-4 function in hepatic cells.