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Investigation of risk factors with regard to identifying the requirement for prostate related biopsy throughout sufferers together with damaging MRI.
Increased focus on the development and application of bioavailability-based metal water quality guideline values requires increased understanding of the influence of water chemistry on metal bioavailability and toxicity. Development of empirical models, such as multiple linear regression models, requires the assessment of the influence of individual water quality parameters as toxicity modifying factors. The present study investigated the effect of pH on the lability and toxicity of zinc to a tropical green microalga (Chlorella sp.). Zinc speciation and lability were explored using the Windermere Humic Aqueous Model (WHAM7), ultrafiltration and diffusive gradients in thin-films (DGT). Zinc toxicity increased significantly with increasing pH from pH 6.7 to 8.3, with 50% growth inhibition effect concentrations (EC50) decreasing from 185 to 53 µg.L-1 across the pH range. Linear relationships between DGT-labile zinc and dissolved zinc did not vary across the tested pH range, nor did the linear relationship between dissolved ( less then 0.45 µm) zinc and ultrafiltered ( less then 3 kDa) zinc. Our findings show that zinc toxicity to this freshwater alga is altered as a function of pH across environmentally realistic pH ranges and these toxicity changes could not be explained by zinc speciation and lability as measured by DGT and WHAM7. This article is protected by copyright. All rights reserved.Intraspecific polymorphism in birds, especially plumage colour polymorphism, and the mechanisms that control it are an area of active research in evolutionary biology. The black-headed bulbul (Brachypodius atriceps) is a polymorphic species with two distinct morphs, yellow and grey. This species inhabits the mainland and virtually all continental islands of Southeast Asia where yellow morphs predominate, but on two islands in the Sunda region, Bawean and Maratua, grey morphs are common or exclusive. Here, we generated a high-quality reference genome of a yellow individual and resequenced genomes of multiple individuals of both yellow and grey morphs to study the genetic basis of coloration and population history of the species. Using PCA and STRUCTURE analysis, we found the Maratua Island population (which is exclusively grey) to be distinct from all other B. atriceps populations, having been isolated c. 1.9 million years ago (Ma). In contrast, Bawean grey individuals (a subset of yellow and grey individuals on that island) are embedded within an almost panmictic Sundaic clade of yellow birds. Using FST and dxy to compare variable genomic segments between Maratua and yellow individuals, we located peaks of divergence and identified candidate loci involved in the colour polymorphism. Tests of selection among coding-proteins in high FST regions, however, did not indicate selection on the candidate genes. Overall, we report on some loci that are potentially responsible for the grey/yellow polymorphism in a species that otherwise shows little genetic diversification across most of its range.
Overcoming taxane resistance remains a major clinical challenge in metastatic castrate-resistant prostate cancer (mCRPC). Loss of DNA repair proteins is associated with resistance to anti-microtubule agents. We propose that alterations in DNA damage response (DDR) pathway contribute to taxane resistance, and identification of these alterations may provide a potential therapeutic target to resensitize docetaxel-refractory mCRPC to taxane-based therapy.

Alterations in DDR gene expression in our prostate cancer cell line model of docetaxel-resistance (DU145-DxR) derived from DU-145 cells were determined by DDR pathway-specific polymerase chain reaction array and immunoblotting. The PRKDC gene encoding DNA-PKc (DNA-dependent protein kinase catalytic unit), was noted to be overexpressed and evaluated for its role in docetaxel resistance. Cell viability and clonogenic survival of docetaxel-treated DU145-DxR cells were assessed after pharmacologic inhibition of DNA-PKc with three different inhibitors-NU7441, LTUally, DNA-PKc inhibition did not affect MDR1 activity, indicating that DNA-PKc inhibitors resensitized taxane-resistant cells via an MDR1-independent mechanism.

This study supports a role of DDR genes, particularly, DNA-PKc in promoting resistance to taxanes in mCRPC. Targeting prostatic DNA-PKc may provide a novel strategy to restore taxane sensitivity in taxane-refractory mCRPC.
This study supports a role of DDR genes, particularly, DNA-PKc in promoting resistance to taxanes in mCRPC. Targeting prostatic DNA-PKc may provide a novel strategy to restore taxane sensitivity in taxane-refractory mCRPC.
To further advance the understanding of the species-rich, economically and ecologically important angiosperm order Myrtales in the rosid clade, comprising nine families, approximately 400 genera and almost 14,000 species occurring on all continents (except Antarctica), we tested the Angiosperms353 probe kit.

We combined high-throughput sequencing and target enrichment with the Angiosperms353 probe kit to evaluate a sample of 485 species across 305 genera (76% of all genera in the order).

Results provide the most comprehensive phylogenetic hypothesis for the order to date. Relationships at all ranks, such as the relationship of the early-diverging families, often reflect previous studies, but gene conflict is evident, and relationships previously found to be uncertain often remain so. Technical considerations for processing HTS data are also discussed.

High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.
High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.We studied biotic ligand model (BLM) predictions of toxicity of nickel (Ni) and zinc (Zn) in natural waters from Illinois and Minnesota USA which had combinations of pH, hardness, and dissolved organic carbon (DOC) more extreme than 99.7% of waters in a nationwide database. We conducted 7-d chronic tests with Ceriodaphnia dubia, and 96-hr acute test and 14-d chronic tests with Neocloeon triangulifer, and estimated LC50s and EC20s for both species. Toxicity of Ni and Zn to both species differed among test waters by factors from 8 (Zn tests with C. dubia) to 35 (Zn tests with N. triangulifer). For both species and metals, tests with Minnesota waters (low pH and hardness, high DOC) showed lower toxicity than Illinois waters (high pH, high hardness, low DOC). Recalibration of the Ni BLM to be more responsive to pH-related changes improved predictions of Ni toxicity, especially for C. iCARM1 dubia. We compared several input data scenarios for the Zn BLM, which generally had minor effects on Model Performance Scores (MPS).
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