Green tea extract supplementation ameliorates CCl4-induced hepatic oxidative stress, fibrosis, and acute-phase protein expression in rat

Background/PurposeWe evaluated the long-term effects of green tea extract (GTE) supplementation on oxidative stress, biliary acute phase protein expression, and liver function in CCl4-induced chronic liver injury.MethodsWe evaluated the antioxidant activity of GTE in comparison with those of vitamin C, vitamin E, and β-carotene in vitro by using an ultrasensitive chemiluminescence analyzer. Chronic liver injury was induced by intraperitoneally administering carbon tetrachloride (CCl4) (1mL/kg body weight, twice weekly) to female Wistar rats for 8 weeks. The effects of low (4mg/kg body weight per day) and high (20mg/kg body weight per day) doses of intragastric GTE on CCl4-induced liver dysfunction and fibrosis were examined by measuring the bile and blood reactive oxygen species levels and biochemical parameters by using Western blot and two-dimensional polyacrylamide gel electrophoresis techniques.ResultsGTE has greater scavenging activity against O2–, H2O2, and Hypochlorous acid (HOCl) in vitro than vitamin C, vitamin E, and β-carotene do. In vivo, CCl4 markedly increased bile and blood reactive oxygen species production, lipid accumulation, number of infiltrated leukocytes, fibrosis, hepatic hydroxyproline content, and plasma alanine aminotransferase and aspartate aminotransferase activities, and reduced plasma albumin levels. Two-dimensional polyacrylamide gel electrophoresis revealed that CCl4 increased the acute-phase expression of six biliary proteins and decreased hepatic B-cell lymphoma 2 (Bcl-2), catalase, and CuZn superoxide dismutase protein expression. GTE supplementation attenuated CCl4-enhanced oxidative stress, levels of biochemical parameters, pathology, and acute-phase protein secretion, and preserved antioxidant/antiapoptotic protein expression.ConclusionGTE supplementation attenuates CCl4-induced hepatic oxidative stress, fibrosis, acute phase protein excretion, and hepatic dysfunction via the antioxidant and antiapoptotic defense mechanisms

Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees

BACKGROUND: Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann–Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. RESULTS: The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence… CONCLUSIONS: The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence

Clinical and molecular characterization of a transmitted reciprocal translocation t(1;12)(p32.1;q21.3) in a family co-segregating with mental retardation, language delay, and microcephaly

<p>Abstract</p> <p>Background</p> <p>Chromosome translocation associated with neurodevelopmental disorders provides an opportunity to identify new disease-associated genes and gain new insight into their function. During chromosome analysis, we identified a reciprocal translocation between chromosomes 1p and 12q, t(1; 12)(p32.1; q21.3), co-segregating with microcephaly, language delay, and severe psychomotor retardation in a mother and her two affected boys.</p> <p>Methods</p> <p>Fluorescence in situ hybridization (FISH), long-range PCR, and direct sequencing were used to map the breakpoints on chromosomes 1p and 12q. A reporter gene assay was conducted in human neuroblastoma (SKNSH) and Chinese hamster ovary (CHO) cell lines to assess the functional implication of the fusion sequences between chromosomes 12 and 1.</p> <p>Results</p> <p>We determined both breakpoints at the nucleotide level. Neither breakpoint disrupted any known gene directly. The breakpoint on chromosome 1p was located amid a gene-poor region of ~ 1.1 Mb, while the breakpoint on chromosome 12q was located ~ 3.4 kb downstream of the ALX1 gene, a homeobox gene. In the reporter gene assay, we discovered that the fusion sequences construct between chromosomes 12 and 1 had a ~ 1.5 to 2-fold increased reporter gene activity compared with the corresponding normal chromosome 12 sequences construct.</p> <p>Conclusion</p> <p>Our findings imply that the translocation may enhance the expression of the ALX1 gene via the position effect and result in the clinical symptoms of this family. Our findings may also expand the clinical phenotype spectrum of ALX1-related human diseases as loss of the ALX1 function was recently reported to result in abnormal craniofacial development.</p

Numerical and experimental study of horizontal pneumatic transportation of spherical and low-aspect-ratio cylindrical particles

The work presented in this paper was carried out as part of the PARDEM project. The overall aim was to quantify the predictive capability of a coupled CFD-DEM approach to simulating the horizontal pneumatic conveying of spherical and low-aspect-ratio non-spherical particles. Carefully controlled experiments were carried out in a 6.5 m long, 0.075 m diameter horizontal conveying line with the aid of the laser Doppler anemometry (LDA). Three different sizes of spherical glass beads, ranging from 0.8 mm to 2 mm and low-aspect-ratio cylindrical shaped particle of size 1 × 1.5 mm were employed. Simulations of the experiments were performed using a two-way coupled computational fluid dynamics and discrete element method (CFD-DEM) implemented in the commercial software FLUENT-EDEM in an Eulerian–Lagrangian framework. Experimental and simulation results of gas and particle velocities for particle laden flow with spherical particles were compared, showing that the CFD-DEM method could capture the experimental trends. However, quantitative discrepancies between simulation and experimental results were observed. Further modelling of low-aspect-ratio cylindrical particles was conducted using a multi-sphere model to represent cylindrical particles in the DEM code. Drag equations were modified in the code to take the effect of particle shape into account. The simulation results of mean axial particle velocity agreed reasonably well with a maximum of 25% discrepancy when compared to experimental measurements using the LDA technique. The discrepancies between simulation and experimental results were attributed to the selected drag model, mesh size and lack of an appropriate mesh interpolation scheme in the selected code

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

Background: Pen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13. Methodology/Principal Findings: Serum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A 148 –E 166) and S22 (A 243 –K 274) were recognized by sera from 90 % and 100 % of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T 261 –K 274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Lower Urinary Tract Symptoms in Female Patients with Rheumatoid Arthritis

Objective: Patients with autoimmune diseases such as systemic lupus erythematosus ( SLE) and Sjogren's syndrome ( SS) are associated with an increased severity of lower urinary tract symptoms ( LUTS). Recent surveys also reveal that rheumatoid arthritis ( RA) is prevalent in patients with interstitial cystitis ( IC). Therefore, we have investigated LUTS in patients with RA. Methods: A total of 198 female patients with RA, aged 40 years or older, from the rheumatology outpatient clinic completed this prospective study. The American Urological Association Symptom Index ( AUASI) score was used to assess the severity of LUTS and the O'Leary-Sant Symptom Index ( ICSI) was used to evaluate IC-like urinary symptoms in these patients, which were compared to those of 679 age-matched controls. The possible associations of clinical parameters with LUTS were also explored. Results: The Mean AUASI score and the percentage of individuals reporting severe LUTS ( AUASI score >= 20) or IC-like urinary symptoms ( ICSI score >= 12) showed no significant differences between the RA and control groups. However, in the RA group multivariate regression analyses identified patients with secondary SS ( n=21) to be associated with a significantly higher AUASI score ( p=0.007) and a higher percentage of severe LUTS ( p= 0.02); these were also significantly higher than those of the control group ( p=0.02 and p=0.01, respectively). Conclusion: Patients with RA have similar urinary complaints when compared to controls . However, those with secondary SS have a greater severity of LUTS, a finding similar to that observed in patients with primary SS