Crossing Paths in Human Renal Cell Carcinoma (hRCC)

Historically, cell-signaling pathways have been studied as the compilation of isolated elements into a unique cascade that transmits extracellular stimuli to the tumor cell nucleus. Today, growing evidence supports the fact that intracellular drivers of tumor progression do not flow in a single linear pathway, but disseminate into multiple intracellular pathways. An improved understanding of the complexity of cancer depends on the elucidation of the underlying regulatory networks at the cellular and intercellular levels and in their temporal dimension. The high complexity of the intracellular cascades causes the complete inhibition of the growth of one tumor cell to be very unlikely, except in cases in which the so-called “oncogene addiction” is known to be a clear trigger for tumor catastrophe, such as in the case of gastrointestinal stromal tumors or chronic myeloid leukemia. In other words, the separation and isolation of the driver from the passengers is required to improve accuracy in cancer treatment. This review will summarize the signaling pathway crossroads that govern renal cell carcinoma proliferation and the emerging understanding of how these pathways facilitate tumor escape. We outline the available evidence supporting the putative links between different signaling pathways and how they may influence tumor proliferation, differentiation, apoptosis, angiogenesis, metabolism and invasiveness. The conclusion is that tumor cells may generate their own crossroads/crosstalk among signaling pathways, thereby reducing their dependence on stimulation of their physiologic pathways.     

Assessment of the bioavailability of toxic and non-toxic arsenic species in seafood samples

Bioavailability of total arsenic, toxic (arsenite, As(III); and arsenate, As(V)), and non-toxic (monomethylarsonic acid, MA; dimethylarsonic acid, DMA; arsenobetaine, AB; and arsenocholine, AC) arsenic species has been assessed in different raw seafood samples (white fish, cold water fish and molluscs) by using an in vitro model that combines simulated gastric and intestinal digestion/dialysis methods. Correlations between arsenic species bioavailability and seafood nutrient contents (fat and protein) have also been established. Total arsenic content in seafood samples, and dialyzable and non-dialyzable fractions, were analyzed by inductively coupled plasma – mass spectrometry (ICP–MS) after a microwave-assisted acid digestion treatment. The determination of the different arsenic species concentrations in the samples (after an optimised matrix solid phase dispersion (MSPD) approach) and in the dialyzable fraction was done by high performance liquid chromatography (HPLC) coupled to ICP-MS as a selective detector. Accuracy of the procedure (total arsenic determination) was assessed by analyzing DORM-2 and BCR-627 certified reference materials. The accuracy of the in vitro procedure was established through a mass-balance study. After statistical evaluation (95% confidence interval), good accuracy of the whole in vitro process, for total arsenic and for arsenic speciation, was observed. High dialyzability percentages for total arsenic and for arsenic species were found (i.e. from 84.6 ± 1.7% to 106 ± 2.6%). Bioavailability of arsenic exhibits a negative correlation with the fat content of the seafood. However, no correlation was observed between the bioavailable fraction of total arsenic and arsenic species and the protein content of the seafood studied.     

The effects of run‐of‐river dam spill on Columbia River microplankton

Dams, increasingly common in riverine systems worldwide, are particularly prevalent on the Columbia River (CR) in the United States. Hydroelectric projects, including both storage and run‐of‐river (i.e., minimal storage) structures, on the mainstem CR highly manage water flow, often by releasing water over (rather than through) dams as “spill.” To test the effects of run‐of‐river dam spill on microplankton abundance and composition, we sampled above and below two dams in the lower CR before and during spill conditions in spring 2016 and during and after spill conditions in late summer 2007. We tested the effects of location (i.e., above vs. below dams), spill condition (i.e., before, during, and after spill), and their interaction on microplankton abundance. Generally, diatoms were most abundant during springtime, whereas cyanobacteria were most abundant in late summer. Most taxa were not significantly different in abundance above and below dams, regardless of spill status; although cyanobacteria abundance was marginally higher below dams in summer 2007 (p = .04). Abundances of all taxa were significantly different between pre‐spill and spill periods in spring 2016, whereas only diatom and flagellate abundances were significantly different between spill and post‐spill periods in summer 2007. We conclude that spill conditions may influence microplankton abundance, but are not likely to affect microplankton communities on either side of run‐of‐river dams on the CR. This is important information for dam managers concerned about ecosystem impacts of spill.     

Effect of Methionine Sulfoxide on the Synthesis and Purification of Aggregation-Prone Peptides

A two-step synthesis for methionine-containing hydrophobic and/or aggregation-prone peptides is presented that takes advantage of the reversibility of methionine oxidation. The use of polar methionine sulfoxide as a building block in solid-phase peptide synthesis improves the synthesis quality and yields the crude peptide, with significantly improved solubility compared to the reduced species. This facilitates the otherwise often laborious peptide purification by high-performance liquid chromatography. The subsequent reduction proceeds quantitatively. This approach has been optimised with the methionine-rich Tar-DNA-binding protein 43 (307–347), but is also more generally applicable, as demonstrated by the syntheses of human calcitonin and two aggregation-prone peptides from the human prion protein.     

Leachability of degradation products from hard chairside reline resins in artificial saliva: Effect of water‐bath post‐polymerization treatment

The effect of a post‐polymerization treatment on the leaching of methacrylic acid (MA) and benzoic acid (BA) from the reline resins [Kooliner (K), New Truliner (N), Ufi Gel hard (U), and Tokuso Rebase Fast (T)] was evaluated. Specimens of each material were divided into two groups: Group C (control) – left untreated; Group WB (water‐bath) – immersion in water at 55 ± 1°C for 10 min. Specimens were placed in artificial saliva at 37 ± 1°C and, after 1‐, 3‐, 5‐, 24‐h and 3‐, 7‐, 14‐, and 30‐day intervals, aliquots were removed and analyzed using high performance liquid chromatography. Data were analyzed by using Wilcoxon, Mann–Whitney or Kruskal–Wallis tests (α = 0.05). At 1 h, the concentration of MA released from U control specimens was higher than those of the other ones, and decreased after 3 h. WB specimens released lower amounts of MA than control specimens only for material U, at the 1‐ and 3‐h periods. For all control specimens, concentrations of leached BA progressively decreased within 5 h and from 24 h to the end. WB specimens released significantly lower amounts of BA than did the control groups. The highest concentration of MA was leached from control specimens of Ufi Gel hard. Water‐bath post‐polymerization treatment caused a significant reduction in elution of BA. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.     

Inhibition of colon adenocarcinoma cell proliferation by flavonols is linked to a G2/M cell cycle block and reduction in cyclin D1 expression

The moderate consumption of red wine has been proposed to reduce the incidence of colorectal cancer. Its anti-cancer action my in part be mediated by the actions of polyphenols on colon cancer epithelial cells. We show that a red wine phenolic (50 μg/ml) extract devoid of anthocyanins (removed to reflect polyphenol bioavailability to the large intestine) and the major red wine flavonols quercetin, myricetin, laricitrin and syringetin (50 μM) are capable of inhibiting the proliferation of colorectal epithelial adenocarcinoma cells. This anti-proliferative activity was partly mediated by the direct cytotoxic actions of flavonols and also their ability to cause a significant cell cycle blockage in G2/M. The anti-proliferative effects induced by flavonols were preceded, in most cases, by a strong and significant reduction of cyclooxygenase-2 (COX-2) and cyclin D1 expression. These results indicate that the observed inverse correlation between colon cancer and a moderate red wine intake may be partly mediated by the actions of red wine flavonols on the growth of cancer cells.     

The effect of climate variations on glulam—an experimental study

Climate variations affect timber structures by causing moisture induced stresses which may lead to cracks in timber members. The paper presents experimentally determined moisture induced stresses that arise perpendicular to the grain of glulam specimens during exposure to 1-dimensional drying and wetting. Although to a certain extent reduced by creep effects, the determined tensile stresses can significantly exceed the characteristic tensile strength of glulam. Additional measurements of moduli of elasticity (E) and hygroexpansion coefficients (α) revealed that these parameters are strongly affected by the geometrical configuration (pith locations) of the specimens. By means of all the parameters determined here, it can be avoided that parameters have to be selected from different literature sources, which introduces large uncertainties into the numerical simulations.