Eutrophication by human activities is increasingly affecting ecosystem functioning and plant community composition. So far, studies mainly focus on the effects of atmospheric nitrogen deposition, surface water eutrophication or soil nutrient accumulation. Groundwater pollution of spring habitats, however, has received much less attention, although numerous papers report groundwater nutrient enrichment worldwide.
View Article and Find Full Text PDFElevated levels of receptor tyrosine kinase-like orphan receptor 1 (RORl) expression are observed in multiple hematological and solid tumors, but not in most of the healthy adult tissues, identifying ROR1 as an attractive target for tumor-specific therapy. Herein we will describe the discovery of macrocyclic peptides as binders of the extracellular Cysteine-Rich Domain (CRD) of human ROR1 via mRNA in vitro selection technology using the PDPS platform, followed by exploration of sidechain SAR of parent macrocycle peptides, fluorescently labeled analogs, and a Peptide Drug Conjugate (PDC). The parent macrocyclic peptides represented by Compound 1 and Compound 14 displayed nanomolar cell-based binding to ROR1 and relatively good internalization in 786-O and MDA-MB-231 tumor cell lines.
View Article and Find Full Text PDFMethods Enzymol
September 2023
Zinc is essential to many important biological processes and the SLC39A family of zinc transporters which help to control zinc levels in cells, are increasingly being implicated in disease states. In order to determine their exact roles in these processes, reliable methods for their successful production are now required. Unfortunately, extensive post-translational modification and temporally specific activation makes visualisation of ZIP family transporters difficult.
View Article and Find Full Text PDFZebrafish are a powerful animal model for small molecule screening. Small molecule treatments of zebrafish embryos usually require that the chorion, an acellular envelope enclosing the embryo, is removed in order for chemical compounds to access the embryo from the bath medium. For large-scale studies requiring hundreds of embryos, manual dechorionation, using forceps, can be a time-consuming and limiting process.
View Article and Find Full Text PDFAquaporins are a family of ubiquitously expressed transmembrane water channels implicated in a broad range of physiological functions. We have previously reported that aquaporin 4 (AQP4) is expressed on T cells and that treatment with a small molecule AQP4 inhibitor significantly delays T cell mediated heart allograft rejection. Using either genetic deletion or small molecule inhibitor, we show that AQP4 supports T cell receptor mediated activation of both mouse and human T cells.
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