Hilldickey9519

Benzotriazole UV-stabilizers (BZT-UVs) are commonly used as additives to protect from light-induced degradation in a variety of consumer goods. Despite their widespread presence in aquatic ecosystems, information on the effects of these compounds remain largely unknown. The objectives of the present study were to evaluate the chronic effects of two BZT-UVs alone and in a mixture, 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol (UV-234) and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV-328), in juvenile rainbow trout (Oncorhynchus mykiss) chronically exposed (28-d) through the diet. Chemical analyses of livers from exposed trout suggested liver accumulation and potential metabolism of the two compounds. Hepatic RNA-sequencing analyses revealed specific effects of each compound on gene transcription profiles; UV-234 affected mainly genes involved in cellular metabolism, while UV-328 induced the transcription of ribosomal proteins and down-regulated genes involved in immune responses. Both compounds regulated iron homeostasis genes in an opposite manner. The mixture of both BZT-UVs did not produce significant evidence of additive or synergistic effects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Over the years, ad-hoc procedures were used for designing SNP arrays, but the procedures and strategies varied considerably case by case. Recently, a multiple-objective, local optimization (MOLO) algorithm was proposed to select SNPs for SNP arrays, which maximizes the adjusted SNP information (E score) under multiple constraints, e.g. on MAF, uniformness of SNP locations (U score), the inclusion of obligatory SNPs and the number and size of gaps. In the MOLO, each chromosome is split into equally spaced segments and local optima are selected as the SNPs having the highest adjusted E score within each segment, conditional on the presence of obligatory SNPs. The computation of the adjusted E score, however, is empirical, and it does not scale well between the uniformness of SNP locations and SNP informativeness. In addition, the MOLO objective function does not accommodate the selection of uniformly distributed SNPs. In the present study, we proposed a unified local function for optimally selecting SNPs, as an amendment to the MOLO algorithm. This new local function takes scalable weights between the uniformness and informativeness of SNPs, which allows the selection of SNPs under varied scenarios. The results showed that the weighting between the U and the E scores led to a higher imputation concordance rate than the U score or E score alone. The results from the evaluation of six commercial bovine SNP chips further confirmed this conclusion. © 2020 Stichting International Foundation for Animal Genetics.Microplastics are emerging threat contaminants that have been shown to provide toxic pollutants, either from the environment or from their inherent toxic monomers and additives, a pathway into the aquatic food web. In the present study, the occurrence, abundance, and composition of microplastic load in the surface water of Lake Naivasha (Kenya) was determined. selleck chemicals The surface water physicochemical parameters were measured in situ; microplastic samples were collected using plankton net trawls and treated with H2 O2 to decompose organic matter. The microplastic particles recovered were classified both by visual observation and by attenuated total reflection-Fourier transform infrared spectroscopy. The average microplastic concentration range in surface water was 0.183 ± 0.017 to 0.633 ± 0.067 particles/m2 , with the mean concentration being 0.407 ± 0.135 particles/m2 . Fragments, fibers, and films were identified and were mostly composed of polypropylene, polyethylene, and polyester. We also performed correlational analysis, which showed a strong positive association between microplastic quantity and turbidity, total nitrogen, and total phosphorus in the lake. The high variability in microplastic densities exhibited between the sampled locations was attributed to human activities, water and wastewater intake through rivers and tributaries, and the presence of local wind patterns responsible for the general water circulation. Our assessment adds to the growing documentation of microplastic presence in freshwater ecosystems, and provides a baseline for future monitoring and assessment in sediment and biota of Lake Naivasha and other Kenyan freshwater systems. Environ Toxicol Chem 2020;001-10. © 2020 SETAC.BACKGROUND Oral squamous cell carcinoma (OSCC) ranks as the fifth most frequent cancer worldwide, and the recurrence and migration of OSCC still pose large threats to patients. Long non-coding RNAs (lncRNAs) have recently emerged as crucial players in cancer development, and it is of great significance to understand the regulatory nexus of lncRNAs in OSCC. METHODS Here, we identified a novel lncRNA, RP11-874J12.4, which is ectopically expressed in OSCC and facilitates OSCC. RESULTS RP11-874J12.4 directly binds to and regulates miR-19a-5p. Interestingly, RP11-874J12.4 and miR-19a-5p form a negative regulatory loop that inhibits the expression of miR-19a-5p in OSCC. The expression of an oncogenic transcription factor, EBF1, is unleashed in OSCC due to the low expression of miR-19a-5p, which promotes the growth and migration of OSCC. CONCLUSION Our data illustrate a regulatory axis of RP11-874J12.4/miR-19a-5P/EBF1 and an inhibitory loop with RP11-874J12.4 and miR-19a-5p. These data provide insights into the tumorigenesis of OSCC and the novel drug targets for OSCC. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.The interpretation of sharp force fatality dynamics may be difficult in some cases, but a contribution to analysis of the phenomenon may be provided by case studies. Therefore, the purpose of our study is focused on identifying, in observed sharp force fatalities, reliable parameters that can differentiate a homicidal and suicidal manner of death, with particular reference to criminological parameters. Data derived from sharp force fatality cases in Padua and Venice from 1997 to 2019, anonymized and collected in Excel, included personal, circumstantial, clinical, and psychopathological-criminological data, as well as crime scene investigation, necroscopic, and toxicological data. Statistical analyses were performed using chi-square and Wilcoxon rank-sum tests. Possible predictors of homicide were analyzed by logistic regression. Six parameters (bloodstains distant from the body, clothing lacerations, hesitation/defense wounds, number of injuries, and potential motives) were significantly different in the two groups (p  less then  0.05). An independent statistical association between potential motives explaining the crime (p  less then  0.001; OR 27.533) and homicide on multiple logistic regression analysis was highlighted. The absence of clothing lacerations was inversely related to homicide (p = 0.002, OR 0.092). To the best of our knowledge, this is one of very few Italian studies concerning the differential diagnosis between homicidal and suicidal sharp force fatalities. The dynamics of the event is established in most cases by the integrated evaluation of data from crime scene investigation and the autopsy. Nevertheless, in an atypical scenario, a psychopathological-criminological analysis may provide essential elements, and particular attention should be given to the identification of potential explanatory motives. © 2020 American Academy of Forensic Sciences.Peripheral T-cell lymphomas (PTCL) and natural killer (NK)/T-cell lymphomas (NKTCL) are a heterogeneous group of aggressive malignancies with dismal outcomes and limited treatment options. While the phosphatidylinositol 3-kinase (PIK3) pathway has been shown to be highly activated in many B-cell lymphomas, its therapeutic relevance in PTCL and NKTCL remains unclear. The aim of this study is to investigate the expression of PIK3 and phosphatase and tensin homolog (PTEN) in these subtypes of lymphoma and to identify potential therapeutic targets for clinical testing. Therefore, the expression of PIK3α, PIK3β, PIK3γ, PIK3δ and PTEN was analyzed in 88 cases of PTCL and NKTCL samples by immunohistochemistry. All PTCL and NKTCL samples demonstrated high expression of PIK3 isoforms. In particular, high PIK3α expression was significantly associated with poor survival, even after adjustment for age, International Prognostic Index (IPI) score and anthracycline-based chemotherapy in first line. Notably, copanlisib, a pan-class I inhibitor with predominant activities towards PIK3α and PIK3δ isoforms, effectively inhibited phosphorylation of AKT, 4E-BP-1 and STAT3, causing G0 /G1 cell cycle arrest and resulting in suppression of tumour cell growth in vitro and in vivo. This study provides evidence that targeting the PIK3 pathway, particularly simultaneous inhibition of PIK3α and δ, could be a promising approach for the treatment of PTCL and NKTCL. © 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.The therapy algorithm for severe aplastic anaemia (sAA) is established but moderate AA (mAA), which likely reflects a more diverse pathogenic mechanism, often represents a treatment/management conundrum. A cohort of AA patients (n = 325) was queried for those with non-severe disease using stringent criteria including bone marrow hypocellularity and chronic persistence of moderately depressed blood counts. As a result, we have identified and analyzed pathological and clinical features in 85 mAA patients. Progression to sAA and direct clonal evolution (paroxysmal nocturnal haemoglobinuria/acute myeloid leukaemia; PNH/AML) occurred in 16%, 11% and 1% of mAA cases respectively. Of the mAA patients who received immunosuppressive therapy, 67% responded irrespective of time of initiation of therapy while conservatively managed patients showed no spontaneous remissions. Genomic analysis of mAA identified evidence of clonal haematopoiesis with both persisting and remitting patterns at low allelic frequencies; with more pronounced mutational burden in sAA. Most of the mAA patients have autoimmune pathogenesis similar to those with sAA, but mAA contains a mix of patients with diverse aetiologies. Although progression rates differed between mAA and sAA (P = 0·003), cumulative incidences of mortalities were only marginally different (P = 0·095). Our results provide guidance for diagnosis/management of mAA, a condition for which no current standard of care is established. © 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.Dynamic regulation of the concentration of the natural auxin (IAA) is essential to coordinate most of the physiological and developmental processes and responses to environmental changes. Oxidation of IAA is a major pathway to control auxin concentrations in angiosperms and, along with IAA conjugation, to respond to perturbation of IAA homeostasis. However, these regulatory mechanisms remain poorly investigated in conifers. To reduce this knowledge gap, we investigated the different contributions of the IAA inactivation pathways in conifers. MS-based quantification of IAA metabolites under steady-state conditions and after perturbation was investigated to evaluate IAA homeostasis in conifers. Putative Picea abies GH3 genes (PaGH3) were identified based on a comprehensive phylogenetic analysis including angiosperms and basal land plants. Auxin-inducible PaGH3 genes were identified by expression analysis and their IAA-conjugating activity was explored. Compared to Arabidopsis, oxidative and conjugative pathways differentially contribute to reduce IAA concentrations in conifers.