60 research outputs found
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Highly proteolytic bacteria from semi-ripened Chiapas cheese elicit angiotensin-I converting enzyme inhibition and antioxidant activity
Get PDFChiapas cream cheese (CCH) manufacturing process involves a long acid-enzymatic coagulation period of full-fat cow raw milk to achieve an acid and crumbly cheese. These sensorial aspects are related to lactic acid bacteria activity during ripening. Our main objective was to test the hypothesis that CCH contained highly proteolytic strains able to release bioactive compounds upon milk-protein hydrolysis. First, the proteolysis of CCH was evaluated considering the peptide and amino acid profiles of cheese samples collected from Veracruz (AVCH) and Tabasco (HTCH). The angiotensin-converting-enzyme (ACE) inhibitory activity in cheese water-soluble fractions was evaluated. Thereafter, strains from both CCH samples were isolated and selected based on their proteolytic capability, genetic fingerprint differentiation and growth conditions. Finally, a range of activities in vitro were tested in milk fractions fermented with selected strains. CCH showed ACE inhibitory activity: IC50=1.75-2.75 mg/mL. Interestingly, AVCH contains 0.78 g/kg of the antihypertensive γ-aminobutyric acid. Three highly proteolytic strains showed ACE and high antioxidant activities upon milk fermentation. In conclusion, CCH contain proteolytic strains able to release bioactive compounds from milk proteins and potentially useful to produce functional ingredients and foods
Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns
Get PDFMicroRNA expression in formalin fixed paraffin embedded tissue (FFPE) or plasma may add value for cancer management
Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas
Get PDFThe Epstein-Barr virus (EBV)-positive subtype of gastric adenocarcinoma is conventionally identified by in situ hybridization (ISH) for viral nucleic acids, but next-generation sequencing represents a potential alternative. We therefore determined normalized EBV read counts by whole genome, whole exome, mRNA and miRNA sequencing for 295 fresh-frozen gastric tumor samples. Formalin-fixed, paraffin-embedded tissue sections were retrieved for ISH confirmation of 13 high-EBV and 11 low-EBV cases. In pairwise comparisons, individual samples were either concordantly high or concordantly low by all genomic methods for which data were available. Empiric cut-offs of sequencing counts identified 26 (9%) tumors as EBV-positive. EBV-positivity or negativity by molecular testing was confirmed by EBER-ISH in all but one tumor evaluated by both approaches (kappa=0.91). EBV-positive gastric tumors may be accurately identified by quantifying viral sequences in genomic data. Simultaneous analyses of human and viral DNA, mRNA and miRNA could streamline tumor profiling for clinical care and research
<html>Epstein-Barr Virus <i>WZhet</i> DNA Can Induce Lytic Replication in Epithelial Cells in vitro, although <i>WZhet</i> Is Not Detectable in Many Human Tissues in vivo</html>
Get PDFWZhet is a rearranged and partially deleted form of the Epstein-Barr virus (EBV) genome in which the BamH1W region becomes juxtaposed with and activates BZLF1, resulting in constitutive viral replication. We tested whether WZhet induces viral replication in epithelial cells, and we studied its prevalence in a wide range of lesional tissues arising in vivo
A case study using 2019 pre-monsoon snow and stream chemistry in the Khumbu region, Nepal
Get PDFThis case study provides a framework for future monitoring and evidence for human source pollution in the Khumbu region, Nepal. We analyzed the chemical composition (major ions, major/trace elements, black carbon, and stable water isotopes) of pre-monsoon stream water (4300–5250 m) and snow (5200–6665 m) samples collected from Mt. Everest, Mt. Lobuche, and the Imja Valley during the 2019 pre-monsoon season, in addition to a shallow ice core recovered from the Khumbu Glacier (5300 m). In agreement with previous work, pre-monsoon aerosol deposition is dominated by dust originating from western sources and less frequently by transport from southerly air mass sources as demonstrated by evidence of one of the strongest recorded pre-monsoon events emanating from the Bay of Bengal, Cyclone Fani. Elevated concentrations of human-sourced metals (e.g., Pb, Bi, As) are found in surface snow and stream chemistry collected in the Khumbu region. As the most comprehensive case study of environmental chemistry in the Khumbu region, this research offers sufficient evidence for increased monitoring in this watershed and surrounding areas
High levels of Epstein–Barr virus DNA in latently infected gastric adenocarcinoma
Get PDFGastric adenocarcinoma is the second leading cause of cancer death worldwide. Epstein-Barr virus (EBV) is present in the malignant cells of approximately 10% of cases. It is unclear whether EBV is being missed in some gastric adenocarcinomas due to insensitive test methods or partial EBV genome loss. In the current study, we screened 113 gastric adenocarcinomas from low and high incidence regions (United States and Central America) for the presence of EBV using a battery quantitative real-time PCR (Q-PCR) assays targeting disparate segments of the EBV genome (BamH1W, EBNA1, LMP1, LMP2, BZLF1, EBER1) and histochemical stains targeting EBV-encoded RNA (EBER), the latent proteins LMP1 and LMP2, and the lytic proteins BMRF1 and BZLF1. EBV DNA was detected by Q-PCR in 48/75 United States cancers (64%) and in 38/38 Central American cancers (100%), which was a significant differrence. EBER was localized to malignant epithelial cells in 8/48 (17%) United States and 3/38 (8%) Central American cancers. Viral loads were considerably higher for EBER-positive versus EBER-negative cancers (mean 162,986 versus 62 EBV DNA copies per 100,000 cells). A viral load of 2,000 copies per 100,000 cells is recommended as the threshold distinguishing EBER-positive from EBER-negative tumors. One infected cancer selectively failed to amplify the LMP2 gene because of a point mutation, while another cancer had an atypical pattern of Q-PCR positivity suggesting deletion of large segments of the EBV genome. Three different viral latency profiles were observed in the cancers based on constant expression of EBER and focal or variable expression of LMP1 or LMP2, without lytic protein expression. We conclude that EBV DNA levels generally reflect EBER status, and a panel of at least two Q-PCR assays is recommended for sensitive identification of infected cancers
Characteristics of magnetic resonance imaging biomarkers in a natural history study of golden retriever muscular dystrophy
Get PDFAbstractThe goal of this study was to assess whether magnetic resonance imaging (MRI) biomarkers can quantify disease progression in golden retriever muscular dystrophy (GRMD) via a natural history study. The proximal pelvic limbs of ten GRMD and eight normal dogs were scanned at 3, 6, and 9–12months of age. Several MRI imaging and texture analysis biomarkers were quantified in seven muscles. Almost all MRI biomarkers readily distinguished GRMD from control dogs; however, only selected biomarkers tracked with longitudinal disease progression. The biomarkers that performed best were full-length muscle volume and a texture analysis biomarker, termed heterogeneity index. The biceps femoris, semitendinosus and cranial sartorius muscles showed differential progression in GRMD versus control dogs. MRI features in GRMD dogs showed dynamic progression that was most pronounced over the 3- to 6-month period. Volumetric biomarkers and water map values correlated with histopathological features of necrosis/regeneration at 6-months. In conclusion, selected MRI biomarkers (volume and heterogeneity index) in particular muscles (biceps femoris, semitendinosus, and cranial sartorius) adjusted for age effect allow distinction of differential longitudinal progression in GRMD dogs. These biomarkers may be used as surrogate outcome measures in preclinical GRMD trials
Hyperthermia Induces Functional and Molecular Modifications in Cardiac, Smooth and Skeletal Muscle Cells
Get PDFComparative Medicine - OneHealth and Comparative Medicine Poster SessionHyperthermia is used for the treatment of a number of diseases, including muscle injuries, inflammations, tendinitis, and osteoarticular disorder. More recently, hyperthermia has been used as an adjuvant in cancer treatment. Only two studies have shown that hyperthermia leads to hypertrophy in in-vitro models of cardiac and skeletal muscle cells. Functional, biochemical and molecular mechanisms of hyperthermia-induced hypertrophy in muscles remain largely undiscovered. We investigated the effects of mild heat shock (HS) on C2C12 skeletal, HL-1 cardiac and AR-75 smooth muscle cells. Mild HS (20 min 43ºC) induced increases in the cell area in all muscle cells tested. C2C12 cells are a well-accepted model of skeletal muscle fibers, and were selected for complementary studies. First, to biochemically confirm an increase in protein synthesis we measured and found an increase of ~6% in total protein content 24 hrs after HS. Second, we examined potential modifications in calcium (Ca) homeostasis regulation by measuring intracellular Ca. We detected a lower resting level of intracellular Ca and smaller and longer caffeine-induced Ca transients in C2C12 muscle cells 24 hrs after HS. Next, to search for molecular mechanisms involved with HS-induced hypertrophy and calcium homeostasis modifications, mRNA from C2C12 muscle cells was analyzed at different time points after HS (0, 1, 2, and 24 hrs). We used an ABI Step One Plus RT2 PCR Array System and a custom-built 96 gene array. We report for the first time that the expression of key heat-shock, hypertrophy/ metabolic, and Ca+2 signaling genes were altered after HS. Hsp70 and Hsp72 genes were highly expressed (211-1829 fold change) after HS. Also, Myh7 (MHC-I), Myh6, Srf, Ppp3r1 and Pck1 were up-regulated by 2-6 fold change compared with control cells.. Furthermore, a reduction in the expression of RyR and Trdn genes was observed (2- 3.6 fold change) with an associated increase in the expression of IP3R genes (2-4 fold change). These results indicate that hyperthermia modulates not only heat-shock related and hypertrophy genes, but also genes involved with metabolism, apoptosis repression, calcium homeostasis and signaling, and cell homeostasis. Our studies offer an initial exploration of the functional, biochemical and molecular mechanisms that may help explain the beneficially adaptive effects of hyperthermia on muscle function. Our studies shall also prove useful for the refinement of a specific device (EM-Stim) to be employed for the treatment of muscle and bone diseases (See poster by Hatem et al). Importantly, our studies have potential translational applications. By learning how to more precisely use hyperthermia to control specific genes that can improve or treat muscle injuries, musculoskeletal, and cardiovascular diseases, the ensuing benefits shall be unmistakable. Our short and long-term goals are: i) optimize our protocols; ii) test HS in animal models; iii) manipulate expression of promising genes of interest in vitro and in in-vivo animal models; iv) initiate clinical studies to fully translate from the bench to the bed-side
Effectiveness of early detection on breast cancer mortality reduction in Catalonia (Spain)
Get PDFBackground: At present, it is complicated to use screening trials to determine the optimal age intervals and periodicities of breast cancer early detection. Mathematical models are an alternative that has been widely used. The aim of this study was to estimate the effect of different breast cancer early detection strategies in Catalonia (Spain), in terms of breast cancer mortality reduction (MR) and years of life gained (YLG), using the stochastic models developed by Lee and Zelen (LZ).
Methods: We used the LZ model to estimate the cumulative probability of death for a cohort exposed to different screening strategies after T years of follow-up. We also obtained the cumulative probability of death for a cohort with no screening. These probabilities were used to estimate the possible breast cancer MR and YLG by age, period and cohort of birth. The inputs of
the model were: incidence of, mortality from and survival after breast cancer, mortality from other causes, distribution of breast cancer stages at diagnosis and sensitivity of mammography. The outputs were relative breast cancer MR and YLG.
Results: Relative breast cancer MR varied from 20% for biennial exams in the 50 to 69 age interval to 30% for annual exams in the 40 to 74 age interval. When strategies differ in periodicity but not in the age interval of exams, biennial screening achieved almost 80% of the annual screening MR. In contrast to MR, the effect on YLG of extending screening from 69 to 74 years of age was smaller than the effect of extending the screening from 50 to 45 or 40 years.
Conclusion: In this study we have obtained a measure of the effect of breast cancer screening in terms of mortality and years of life gained. The Lee and Zelen mathematical models have been very useful for assessing the impact of different modalities of early detection on MR and YLG in Catalonia (Spain)
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Pulse Jet Mixing Tests With Noncohesive Solids
Get PDFThis report summarizes results from pulse jet mixing (PJM) tests with noncohesive solids in Newtonian liquid conducted during FY 2007 and 2008 to support the design of mixing systems for the Hanford Waste Treatment and Immobilization Plant (WTP). Tests were conducted at three geometric scales using noncohesive simulants. The test data were used to independently develop mixing models that can be used to predict full-scale WTP vessel performance and to rate current WTP mixing system designs against two specific performance requirements. One requirement is to ensure that all solids have been disturbed during the mixing action, which is important to release gas from the solids. The second requirement is to maintain a suspended solids concentration below 20 weight percent at the pump inlet. The models predict the height to which solids will be lifted by the PJM action, and the minimum velocity needed to ensure all solids have been lifted from the floor. From the cloud height estimate we can calculate the concentration of solids at the pump inlet. The velocity needed to lift the solids is slightly more demanding than "disturbing" the solids, and is used as a surrogate for this metric. We applied the models to assess WTP mixing vessel performance with respect to the two perform¬ance requirements. Each mixing vessel was evaluated against these two criteria for two defined waste conditions. One of the wastes was defined by design limits and one was derived from Hanford waste characterization reports. The assessment predicts that three vessel types will satisfy the design criteria for all conditions evaluated. Seven vessel types will not satisfy the performance criteria used for any of the conditions evaluated. The remaining three vessel types provide varying assessments when the different particle characteristics are evaluated. The assessment predicts that three vessel types will satisfy the design criteria for all conditions evaluated. Seven vessel types will not satisfy the performance criteria used for any of the conditions evaluated. The remaining three vessel types provide varying assessments when the different particle characteristics are evaluated. The HLP-022 vessel was also evaluated using 12 m/s pulse jet velocity with 6-in. nozzles, and this design also did not satisfy the criteria for all of the conditions evaluated
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