BRD4 Promotes DNA Repair and Mediates the Formation of TMPRSS2-ERG Gene Rearrangements in Prostate Cancer

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Temperature-dependent development and oviposition models of Illeis koebelei (Coleoptera: Coccinellidae)

The yellow ladybeetle, Illeis koebelei Timberlake, is a potential biological agent for powdery mildew. The objective of this study was to construct development and oviposition models of I. koebelei. Development experiment was conducted at eight temperatures ranging from 15.4 to 39.5?°C. Development rates were well fitted with linear and nonlinear models. Lower developmental thresholds for egg, first instar, second instar, third instar, and fourth instar larva, pre-pupa, pupa, and total immature stage were estimated to be 3.6, 12.7, 12.1, 11.3, 11.3, 12.8, 14.7, and 14.2?°C, respectively. Their respective thermal requirements in degree days (DD) were 86.6, 16.0, 22.5, 30.2, 49.3, 14.5, 43.8 and 217.4, respectively. Survivorship was the highest at 25.1?°C for immatures. Oviposition experiment was conducted at nine temperatures, ranging from 15.4 to 35.3?°C. Mean fecundity ranged from 18.6 eggs at 29.3?°C to 205.3 eggs at 20.3?°C. It was well described by extreme value function. Adult survival and cumulative oviposition rates of I. koebelei were fitted to a sigmoid function and a two-parameter Weibull function, respectively. Findings of this study provide basic information for ecology of I. koebelei. They can be used to optimize environmental conditions for mass-rearing and shipping, comparing optimal occurrence conditions between I. koebelei and powdery mildew, and forecasting phenology and population dynamics of I. koebelei in the fields.     

Analysis of the free fatty acid metabolome in the plasma of patients with systemic lupus erythematosus and fever

Introduction

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with heterogeneous clinical manifestations mediated by immune dysregulation.

Objectives

We aimed to analyze the metabolomic differences in free fatty acids (FFAs) between patients with SLE and healthy controls (HCs).

Methods

In this study, the levels of 24 FFAs, as their tert-butyldimethylsilyl derivatives, in the plasma of 41 patients with SLE and 41 HCs, were investigated using gas chromatography with mass spectrometry in selected-ion monitoring mode.

Results

The results showed that patients with SLE and HCs had significantly different levels of 13 of the 24 FFAs. The levels of myristic, palmitoleic, oleic, and eicosenoic acids were significantly higher, whereas the levels of caproic, caprylic, linoleic, stearic, arachidonic, eicosanoic, behenic, lignoceric, and hexacosanoic acids were significantly lower in patients with SLE, than in the HCs. In the partial-correlation analysis of the FFA profiles and markers of disease activity of SLE, several metabolic markers correlated with SLE disease activity.

Conclusions

Our results provide a comprehensive understanding of the relationship between FFAs and markers of SLE disease activity. Thus, this approach has promising potential for the discovery of metabolic biomarkers of SLE.

     

Association of Periodontitis with the Concentration Levels of Germanium and Tin in Hair

The purpose of this study was to investigate whether or not the concentration levels of certain kinds of trace elements in hair are associated with periodontitis. We studied a total of 109 participants, which are composed of 25 participants with periodontitis and 84 participants without periodontitis. Periodontal conditions were assessed by measuring the periodontal clinical attachment loss and pocket depth, which were determined at six sites of all teeth. Periodontitis was defined according to the criteria of periodontitis proposed by CDC-AAP. The hair samples were washed with acetone, water, and extran (1%v/v), and then aliquots of hair samples were wet-ashed. This sample solution was analyzed by Perkin-Elmer Mass Spectrometer. The odds ratios and 95% confidence intervals of the concentration levels of trace elements for periodontitis were calculated by multivariate logistic regression analysis. After adjusting all confounders, it was found that the higher concentration level of germanium in hair was significantly and positively associated with periodontitis (odds ratio [OR] 7.12; 95% confidential interval [CI] 2.03–25.00). The higher concentration level of tin in hair was significantly and negatively associated with periodontitis (OR 0.27; 95% CI 0.08–0.94). It was concluded that there was a significant relationship between periodontitis and the concentration level of germanium and tin in hair.     

Spermidine/spermine N(1)-acetyltransferase-1 binds to hypoxia-inducible factor-1alpha (HIF-1alpha) and RACK1 and promotes ubiquitination and degradation of HIF-1alpha

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of oxygen homeostasis that controls the expression of genes encoding proteins that play key roles in angiogenesis, erythropoiesis, and glucose/energy metabolism. The stability of the HIF-1alpha subunit is regulated by ubiquitination and proteasomal degradation. In aerobic cells, O(2)-dependent prolyl hydroxylation of HIF-1alpha is required for binding of the von Hippel-Lindau tumor suppressor protein VHL, which then recruits the Elongin C ubiquitin-ligase complex. SSAT2 (spermidine/spermine N-acetyltransferase-2) binds to HIF-1alpha and promotes its ubiquitination/degradation by stabilizing the interaction of VHL and Elongin C. Treatment of cells with heat shock protein HSP90 inhibitors induces the degradation of HIF-1alpha even under hypoxic conditions. HSP90 competes with RACK1 for binding to HIF-1alpha, and HSP90 inhibition leads to increased binding of RACK1, which recruits the Elongin C ubiquitin-ligase complex to HIF-1alpha in an O(2)-independent manner. In this work, we demonstrate that SSAT1, which shares 46% amino acid identity with SSAT2, also binds to HIF-1alpha and promotes its ubiquitination/degradation. However, in contrast to SSAT2, SSAT1 acts by stabilizing the interaction of HIF-1alpha with RACK1. Thus, the paralogs SSAT1 and SSAT2 play complementary roles in promoting O(2)-independent and O(2)-dependent degradation of HIF-1alpha.     

Reducing proteolytic liability of a MMP‐14 inhibitory antibody by site‐saturation mutagenesis

Playing pivotal roles in tumor growth and metastasis, matrix metalloproteinase‐14 (MMP‐14) is an important cancer target. Potent inhibitory Fab 3A2 with therapy‐desired high selectivity has been isolated from a synthetic antibody library carrying long CDR‐H3s. However, like many standard mechanism protease inhibitors, Fab 3A2 can be cleaved by high concentrations of MMP‐14 after extended incubation at acidic pH. Edman sequencing of generated 3A2 fragments indicated that cleavage occurred within its CDR‐H3 between residues N100h (P1) and L100i (P1’). To improve proteolytic stability of 3A2, three positions adjacent to its cleavage site (P1, P1’, and P3’) were subjected to site‐saturation mutagenesis (SSM). Mutations at P1’ (L100i) resulted in loss of inhibition function, while screening of 3A2 Fab mutants at P1 (N100h) or P3’ (A100k) positions identified four clones exhibiting improvements in both stability and inhibition potency. The majority of these mutants with improved stability were substitutions to either hydrophobic (Lue, Trp) or basic residues (Arg, Lys, His). Combinations of these beneficial mutations resulted in a double mutant N100hR/A100kR, which prolonged half‐life twofold with an inhibition potency K_I of 6.6 nM. Enzyme kinetics and competitive ELISA suggested that N100hR/A100kR was a competitive inhibitor overlapping its binding epitope with that of nTIMP‐2. This study demonstrated that site‐directed mutagenesis at or near the cleavage position reduced proteolytic liability of standard mechanism protease inhibitors especially inhibitory antibodies.     

Molecular Basis for the Single-Nucleotide Precision of Primary microRNA Processing

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Laboratory evaluation of floating marine plastic debris as a potential vector for transportation of the harmful benthic dinoflagellate Fukuyoa koreansis

Marine plastic debris (MPD) can significantly impact marine ecosystems because it can function as a dispersal vector for organisms, including toxic and alien species. We performed laboratory experiments to assess the possible function of MPD as a dispersal vector for the harmful epiphytic dinoflagellate Fukuyoa koreansis. Specifically, we monitored growth of these cells under 6 conditions: no MPD (control; with or without agitation), with polyethylene (PE) film (sheet-like MPD; with or without agitation), and with polypropylene (PP) rope (cylindrical MPD; with or without agitation). Growth without agitation was not significantly different between experimental groups (p > 0.05, χ² = 0.228, Kruskal-Wallis test), indicating that the presence of MPDs had no significant effect on growth of F. koreansis under non-agitating conditions. After 15 days, growth without MPD was 25-fold greater without agitation than with agitation (150 ± 42 cells mL^-1 vs. 6 ± 1 cells mL^-1). When grown with both floating MPDs and agitation, 78 ± 1 % of the cells were attached to the MPD, which was 4-times greater than when they were grown without agitation. These results suggest that MPD or another attachment substrate is essential for the growth of F. koreansis in an unstable water mass, and that MPD may provide a habitat or shelter for F. koreansis and thereby function as a dispersal vector for this harmful epiphytic dinoflagellate.