Skytteterrell0963

nd John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.The efficacy of photodynamic therapy (PDT) using aminolevulinic acid (ALA), which is preferentially taken up by cancerous cells and converted to protoporphyrin IX (PpIX), can be substantially improved by pretreating the tumor cells with Vitamin D (Vit D). Vit D is one of several "differentiation-promoting agents" that can promote the preferential accumulation of PpIX within the mitochondria of neoplastic cells, making them better targets for PDT. This article provides a historical overview of how the concept of using combination agents ("neoadjuvants") for PDT evolved, from initial discoveries about neoadjuvant effects of methotrexate and fluorouracil, to later studies to determine how Vitamin D and other agents actually work to augment PDT efficacy. While this review focuses mainly on skin cancer, it includes a discussion about how these concepts may be applied more broadly toward improving PDT outcomes in other types of cancer. This article is protected by copyright. All rights reserved.BACKGROUND AND OBJECTIVES Precision medicine has altered the management of colorectal cancer (CRC). However, the concordance of mutational findings between primary CRC tumors and associated pulmonary metastases (PM) is not well-described. This study aims to determine the concordance of genomic profiles between primary CRC and PM. METHODS Patients treated for colorectal PM at a single institution from 2000 to 2017 were identified. Mutational concordance was defined as either both wild-type or both mutant alleles in lung and colorectal lesion; genes with opposing mutational profiles were reported as discordant. RESULTS Thirty-eight patients met inclusion criteria, among whom KRAS, BRAF, NRAS, MET, RET, and PIK3CA were examined for concordance. High concordance was demonstrated among all evaluated genes, ranging from 86% (KRAS) to 100% concordance (NRAS, RET, and MET). De novo KRAS mutations were detected in the PM of 4 from 35 (11%) patients, 3 of whom had previously received anti-epidermal growth factor receptor (EGFR) therapy. Evaluation of Cohen's κ statistic demonstrated moderate to perfect correlation among evaluated genes. CONCLUSIONS Because high intertumoral genomic homogeneity exists, it may be reasonable to use primary CRC mutational profiles to guide prognostication and targeted therapy for PM. However, the possibility of de novo KRAS-mutant PM should be considered, particularly among patients previously treated with anti-EGFR therapy. © 2020 Wiley Periodicals, Inc.Pharmaceuticals are widely detected in aquatic environments, and their potential risks to aquatic species are of concern because they are designed to be biologically active. Here, we used an in vitro assay, called the transforming growth factor α shedding assay, to measure the biological activities of G protein-coupled receptor (GPCR)-acting pharmaceuticals present in river water and effluents from municipal wastewater treatment plants (WWTPs) in Japan from 2014 to 2016. ML-SI3 cell line Antagonistic activities against angiotensin (AT1), dopamine (D2), adrenergic (β1), acetylcholine (M1) and histamine (H1) receptors were detected in river water, and were stronger downstream than upstream owing to effluent from WWTPs along the river. Ozonation at one WWTP reduced these activities. Concentrations of sulpiride (D2 antagonist) could explain 73% of antagonistic activities against the D2 receptor; those of metoprolol, atenolol and propranolol (β1 antagonists) could explain 16% of activities against the β1 receptor; and those of pirenzepine (M1 antagonist) could explain 15% of activities against the M1 receptor. Therefore, other receptor antagonists also occur. GPCR-acting pharmaceuticals should be given more attention in environmental monitoring and toxicity testing. © 2020 John Wiley & Sons, Ltd.Auxin represents a key plant hormone that functions to shape plant development and growth (Leyser, 2018). The polar transport (PAT) of indole-3-acetic acid (IAA), the major form of auxin in higher plants, is central to the physiological output of this plant hormone. IAA is a weak acid (pKa = 4.58) and according to a prevailing acidic apoplastic pH (pHext ~5.5), the equilibrium for de-protonated (IAA- ) and protonated (IAAH) molecules in the cell wall can be calculated to be about 83% and 17%, respectively (Zazimalova et al., 2010). This article is protected by copyright. All rights reserved.Studies of pulse-type gymnotiform electric fishes have suggested that electric organ discharge waveforms (EODw) allow individuals to discriminate between conspecific and allospecific signals, but few have approached this experimentally. Here we implement a phase-locked playback technique for a syntopic species pair, Brachyhypopomus gauderio and Gymnotus omarorum. Both species respond to changes in stimulus waveform with a transitory reduction in the interpulse interval of their self-generated discharge, providing strong evidence of discrimination. We also document sustained rate changes in response to different EODws, which may suggest recognition of natural waveforms. © 2020 The Fisheries Society of the British Isles.We investigated the interaction between osmotic stress and auxin signaling in leaf growth regulation. Therefore, we grew Arabidopsis thaliana seedlings on agar media supplemented with mannitol to impose osmotic stress and NAA, a synthetic auxin. We performed kinematic analysis and flow-cytometry to quantify the effects on cell division and expansion in the first leaf pair, determined the effects on auxin homeostasis and response (DR5GUS), performed an NGS transcriptome analysis and investigated the response of auxin related mutants. Mannitol inhibited cell division and expansion. NAA increased the effect of mannitol on cell division, but ameliorated its effect on expansion. In proliferating cells, NAA and mannitol increased free IAA levels at the cost of conjugated IAA and stimulated DR5 promotor activity. Transcriptome analysis shows a large overlap between NAA and osmotic stress induced changes, including upregulation of auxin synthesis, conjugation, transport and TIR1 and ARF response genes, but downregulation of Aux/IAA response inhibitors.