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Background: Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution. Results: The CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein. Conclusions: The topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus. [ABSTRACT FROM AUTHOR]

Background: Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution. Results: The CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein. Conclusions: The topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a potential drug delivery system. Our current investigation studied the bio-effects of the SF-CSNP uptake by liver cells. In this experiment, the characterizations of SF-CSNPs were measured by particle size analysis and protein assay. The average size of the SF-CSNP was 311.9 ± 10.7 nm, and the average zeta potential was +13.33 ± 0.3 mV. The SF coating on the SF-CSNP was 6.27 ± 0.17 µg/mL. Moreover, using proteomic approaches, several proteins involved in the ubiquitin proteasome pathway were identified by analysis of differential protein expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have demonstrated that the SF-CSNP may be involved in liver cancer cell survival and proliferation. [ABSTRACT FROM AUTHOR]

Background: Comprehensive characterization of the phosphoproteome in living cells is critical in signal transduction research. But the low abundance of phosphopeptides among the total proteome in cells remains an obstacle in mass spectrometry-based proteomic analysis. To provide a solution, an alternative analytic strategy to confidently identify phosphorylated peptides by using the alkaline phosphatase (AP) treatment combined with high-resolution mass spectrometry was provided. While the process is applicable, the key integration along the pipeline was mostly done by tedious manual work. Results: We developed a software toolkit, iPhos, to facilitate and streamline the work-flow of AP-assisted phosphoproteome characterization. The iPhos tookit includes one assister and three modules. The iPhos Peak Extraction Assister automates the batch mode peak extraction for multiple liquid chromatography mass spectrometry (LC-MS) runs. iPhos Module-1 can process the peak lists extracted from the LC-MS analyses derived from the original and dephosphorylated samples to mine out potential phosphorylated peptide signals based on mass shift caused by the loss of some multiples of phosphate groups. And iPhos Module-2 provides customized inclusion lists with peak retention time windows for subsequent targeted LC-MS/MS experiments. Finally, iPhos Module-3 facilitates to link the peptide identifications from protein search engines to the quantification results from pattern-based label-free quantification tools. We further demonstrated the utility of the iPhos toolkit on the data of human metastatic lung cancer cells (CL1-5). Conclusions: In the comparison study of the control group of CL1-5 cell lysates and the treatment group of dasatinib-treated CL1-5 cell lysates, we demonstrated the applicability of the iPhos toolkit and reported the experimental results based on the iPhos-facilitated phosphoproteome investigation. And further, we also compared the strategy with pure DDA-based LC-MS/MS phosphoproteome investigation. The results of iPhos-facilitated targeted LC-MS/MS analysis convey more thorough and confident phosphopeptide identification than the results of pure DDA-based analysis. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis (PD) frequently contributes to peritoneal damage which cannot be easily identified without invasive techniques, implying the urgent need for biomarkers and revealing mechanisms. Chronic glomerulonephritis (CGN) is one of the leading causes of receiving dialysis treatment. Here, we attempted to analyze the peritoneal dialysate collected from CGN patients when they receive continuous ambulatory peritoneal dialysis (CAPD) treatment for the first time and after a year to reveal the protein changes that resulted from PD. Proteins were displayed by two-dimensional gel electrophoresis (2DE). Altered gel spots were digested followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for protein identification. Eight proteins were found to have differential expression levels between two groups. Their differential expressions were validated by Western blots in other sets of peritoneal dialysates. Proteins identified with higher levels in the first-time dialysate suggested their dominant appearance in CGN patients, while those that showed higher levels in peritoneal dialysate collected after one year may result from initial peritoneal inflammation or changes in the permeability of the peritoneum to middle-sized proteins. All the identified proteins may provide a perceptiveness of peritoneal changes caused by PD and may function as potential biomarkers or drug targets. [ABSTRACT FROM AUTHOR]

Background. Since the mechanism of comorbidity and mortality in peritoneal dialysis is unclear, a comparison of peritoneal dialysate and normal peritoneal fluid may provide clues to the biological and pathological processes involved in peritoneal damage. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Phthalates are known to have estrogenic effects in cell models and experimental animals. However, the evidence regarding the effects of phthalates on human reproduction is still limited. We conducted a case–control study to determine whether estrogen-dependent diseases are associated with phthalate exposure and how the glutathione S-transferase M1 (GSTM1; a major detoxification enzyme) genotype modulates the risk. [ABSTRACT FROM PUBLISHER]

To determine the patterns of urinary proteins in bladder cancer subjects using pooled urine from 27 bladder cancer patients. The urine matrix was removed by acetonitrile precipitation followed by molecular weight cutoff. High performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI-MS/MS) was used to analyze the urinary proteome. The candidate protein was validated by western blot. A total of 146 urinary proteins were identified. The protein list was screened using bioinformatic tools, and 11 cancer-related urinary proteins were found to be potential tumor markers for bladder cancer. However, only PLK2 was identified with high confidence. This candidate protein was validated by western blot using urine samples from 14 normal subjects and 10 bladder cancer patients. Statistically significant correlations were detected between PLK2 expression and bladder transitional cell carcinoma (TCC) ( P < 0.05). Urinary PLK2 had a sensitivity of 80% at a specificity of 64% for bladder TCC in the samples tested. Our results demonstrate overexpression of PLK2 in bladder carcinomas, suggesting a possible role of PLK2 in the pathogenesis of bladder carcinomas. However, the small cohort, preliminary results, and lack of subgroup analysis (such as carcinoma in situ, high grade, and stage) in this study prevent us from drawing definitive conclusions about the diagnostic value of PLK2 in these patients. Further studies directed toward a multitude of possible carcinogenic mechanisms of PLK2 in bladder cancer are warranted. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. Analysis of human serum from HCC patients using two-dimensional gel electrophoresis (2DE) combined with nano-high-performance liquid chromatography electrospray ionization tandem mass spectrometry (nano-HPLC–ESI-MS/MS) identified fourteen different proteins differentially expressed between HCC patients and the control group. Twelve proteins were up-regulated and two down-regulated. By using nano-HPLC–MS/MS system to analyze proteome in human serum, 317 proteins were identified, twenty-nine of which to high confidence levels (protein matched at last two unique peptide sequences). Of these twenty-nine proteins, six were present only in HCC patients and may serve as biomarkers for HCC. [ABSTRACT FROM AUTHOR]

Previous studies reported that polychlorinated dibenzo- p -dioxins and dibenzofurans (PCDD/Fs) induced hepatic cytochrome P-4501A1 (CYP1A1). The aim of this study was to examine the interactive influence of CYP1A1 genotypes and PCDD/Fs exposure on liver function profile. PCDD/Fs levels and liver function parameters were determined in serum and correlated with genetic polymorphism of CYP1A1/Msp 1 in 225 human volunteers who had no or minimal occupational exposure to PCDD/F. The results showed that the highest glutamate pyruvate transaminase (GPT) activity levels were found in subjects with homozygous variant CYP1A1/Msp 1, followed by heterozygous variant, and finally homozygous wild type for those individuals whose serum PCDD/Fs levels were higher than 17.4 pg WHO-TEQ/g lipid. Data suggest that GPT activity levels may be modified by interaction of CYP1A1/Msp 1 genotype with dioxin after adjustment for age, alcohol consumption, and history of liver illness. Further studies are needed to characterize the variation in other related genes to verify whether a correlation exists between serum PCDD/Fs levels and adverse health effects. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the proteins involved in the methamphetamine (MA)-induced nigrostriatal dopaminergic toxicity. Infusion of anisomycin into striatum and substantia nigra both abolished the MA-induced striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) depletions, indicating a critical role of local protein synthesis in determining such dopaminergic toxicity. Moreover, local protein synthesis blockade reversed this neurotoxicity via a temperature-independent mechanism. We then employed a proteomic approach, two-dimensional gel electrophoresis (2-DE) in conjunction with mass spectrometry analysis, to identify the protein candidates associated with the MA-induced neurotoxicity. In striatal samples, 2-DE analysis revealed that the intensities of nine protein spots were altered by MA treatment. Mass spectrometry analysis allowed us to identify five proteins, including an up-regulated protein, α-synuclein, and four down-regulated proteins, ATPase, F-actin capping protein β subunit, ubiquitin carboxy-terminal hydrolase/PGP 9.5, and peroxidase. MA-altered expression levels of α-synuclein and ubiquitin carboxy-terminal hydrolase/PGP 9.5 in striata were confirmed by western blotting analysis. Taken together, these results suggest that local up-regulation of α-synuclein and down-regulation of ubiquitin carboxy-terminal hydrolase/PGP 9.5 could be linked to the MA-induced dopaminergic terminal toxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND Maternal hypothyroidism during pregnancy can cause adverse effects in the fetus. Scientific evidence has shown that probable thyroid-like function of some phthalates in vitro and in vivo, and phthalates exposure, can begin in utero. This study investigated the association between phthalate exposure and thyroid hormones in pregnant women. METHODS Serum and spot urine samples were collected from 76 Taiwanese pregnant women at second trimester. Thyroid hormones, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4) and free T4 (FT4) were analysed in serum samples, and five urinary phthalate monoesters, including mono butyl phthalate (MBP), monoethyl phthalate (MEP) and mono ethylhexyl phthalate (MEHP), were measured. RESULTS Urinary MBP, MEP and MEHP, the median levels of which were 81.8, 27.7 and 20.6 ng/ml, respectively, were the predominant substances in the urinary phthalate monoesters. Significant mild negative correlations were found between T4 and urinary MBP (R = −0.248, P 4 and urinary MBP (R = −0.368, P 4 and T4 (FT4: β = −0.110, P 4: β=−0.112, P = 0.003). CONCLUSIONS Exposure to di-n-butyl phthalate (DBP) may affect thyroid activity in pregnant women, but how DBP affects thyroid function is unclear. Further studies are needed to elucidate the mechanism of action and to investigate whether any other factors related to DBP exposure alter the thyroid function. [ABSTRACT FROM AUTHOR]