A search and retrieval framework for the management of copyrighted audiovisual content

This paper presents a search and retrieval framework that enables the management of Intellectual Property in the World Wide Web. This twofold framework helps users to detect digital rights infringements of their copyrighted content. In order to detect possible copyright infringments, first the system crawls the Web to search replicas of user’s images, and later evaluates if the copies have been taken respecting the terms stated by the owner. On the other hand, this framework also helps users in finding something interesting in the Web. It will provide copyrighted content to users according to their preferences and to intellectual property rights integrating search and retrieval with digital rights management tools

The Role of Regulatory T Cells in Cancer

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA

Tumor Cell Phenotype Is Sustained by Selective MAPK Oxidation in Mitochondria

Mitochondria are major cellular sources of hydrogen peroxide (H2O2), the production of which is modulated by oxygen availability and the mitochondrial energy state. An increase of steady-state cell H2O2 concentration is able to control the transition from proliferating to quiescent phenotypes and to signal the end of proliferation; in tumor cells thereby, low H2O2 due to defective mitochondrial metabolism can contribute to sustain proliferation. Mitogen-activated protein kinases (MAPKs) orchestrate signal transduction and recent data indicate that are present in mitochondria and regulated by the redox state. On these bases, we investigated the mechanistic connection of tumor mitochondrial dysfunction, H2O2 yield, and activation of MAPKs in LP07 murine tumor cells with confocal microscopy, in vivo imaging and directed mutagenesis. Two redox conditions were examined: low 1 µM H2O2 increased cell proliferation in ERK1/2-dependent manner whereas high 50 µM H2O2 arrested cell cycle by p38 and JNK1/2 activation. Regarding the experimental conditions as a three-compartment model (mitochondria, cytosol, and nuclei), the different responses depended on MAPKs preferential traffic to mitochondria, where a selective activation of either ERK1/2 or p38-JNK1/2 by co-localized upstream kinases (MAPKKs) facilitated their further passage to nuclei. As assessed by mass spectra, MAPKs activation and efficient binding to cognate MAPKKs resulted from oxidation of conserved ERK1/2 or p38-JNK1/2 cysteine domains to sulfinic and sulfonic acids at a definite H2O2 level. Like this, high H2O2 or directed mutation of redox-sensitive ERK2 Cys214 impeded binding to MEK1/2, caused ERK2 retention in mitochondria and restricted shuttle to nuclei. It is surmised that selective cysteine oxidations adjust the electrostatic forces that participate in a particular MAPK-MAPKK interaction. Considering that tumor mitochondria are dysfunctional, their inability to increase H2O2 yield should disrupt synchronized MAPK oxidations and the regulation of cell cycle leading cells to remain in a proliferating phenotype

Genotoxic potential generated by biomass burning in the Brazilian Legal Amazon by Tradescantia micronucleus bioassay: a toxicity assessment study

<p>Abstract</p> <p>Background</p> <p>The Brazilian Amazon has suffered impacts from non-sustainable economic development, especially owing to the expansion of agricultural commodities into forest areas. The Tangará da Serra region, located in the southern of the Legal Amazon, is characterized by non-mechanized sugar cane production. In addition, it lies on the dispersion path of the pollution plume generated by biomass burning. The aim of this study was to assess the genotoxic potential of the atmosphere in the Tangará da Serra region, using <it>Tradescantia pallida </it>as <it>in situ </it>bioindicator.</p> <p>Methods</p> <p>The study was conducted during the dry and rainy seasons, where the plants were exposed to two types of exposure, active and passive.</p> <p>Results</p> <p>The results showed that in all the sampling seasons, irrespective of exposure type, there was an increase in micronucleus frequency, compared to control and that it was statistically significant in the dry season. A strong and significant relationship was also observed between the increase in micronucleus incidence and the rise in fine particulate matter, and hospital morbidity from respiratory diseases in children.</p> <p>Conclusions</p> <p>Based on the results, we demonstrated that pollutants generated by biomass burning in the Brazilian Amazon can induce genetic damage in test plants that was more prominent during dry season, and correlated with the level of particulates and elevated respiratory morbidity.</p

Kinetics and Ligand-Binding Preferences of Mycobacterium tuberculosis Thymidylate Synthases, ThyA and ThyX

Mycobacterium tuberculosis kills approximately 2 million people each year and presents an urgent need to identify new targets and new antitubercular drugs. Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M. tuberculosis genome contains two putative TS enzymes, a conventional ThyA and a flavin-based ThyX. In M. tuberculosis, both TS enzymes have been implicated as essential for growth, either based on drug-resistance studies or genome-wide mutagenesis screens. To facilitate future small molecule inhibitors against these proteins, a detailed enzymatic characterization was necessary.After cloning, overexpression, and purification, the thymidylate-synthesizing ability of ThyA and ThyX gene products were directly confirmed by HPLC analysis of reaction products and substrate saturation kinetics were established. 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) was a potent inhibitor of both ThyA and ThyX, offering important clues to double-targeting strategies. In contrast, the folate-based 1843U89 was a potent inhibitor of ThyA but not ThyX suggesting that it should be possible to find ThyX-specific antifolates. A turnover-dependent kinetic assay, combined with the active-site titration approach of Ackermann and Potter, revealed that both M. tuberculosis enzymes had very low k(cat) values. One possible explanation for the low catalytic activity of M. tuberculosis ThyX is that its true biological substrates remain to be identified. Alternatively, this slow-growing pathogen, with low demands for TMP, may have evolved to down-regulate TS activities by altering the turnover rate of individual enzyme molecules, perhaps to preserve total protein quantities for other purposes. In many organisms, TS is often used as a part of larger complexes of macromolecules that control replication and DNA repair.Thus, the present enzymatic characterization of ThyA and ThyX from M. tuberculosis provides a framework for future development of cell-active inhibitors and the biological roles of these TS enzymes in M. tuberculosis

A theoretical approach to spot active regions in antimicrobial proteins

Background: Much effort goes into identifying new antimicrobial compounds able to evade the increasing resistance of microorganisms to antibiotics. One strategy relies on antimicrobial peptides, either derived from fragments released by proteolytic cleavage of proteins or designed from known antimicrobial protein regions. Results: To identify these antimicrobial determinants, we developed a theoretical approach that predicts antimicrobial proteins from their amino acid sequence in addition to determining their antimicrobial regions. A bactericidal propensity index has been calculated for each amino acid, using the experimental data reported from a high-throughput screening assay as reference. Scanning profiles were performed for protein sequences and potentially active stretches were identified by the best selected threshold parameters. The method was corroborated against positive and negative datasets. This successful approach means that we can spot active sequences previously reported in the literature from experimental data for most of the antimicrobial proteins examined. Conclusion: The method presented can correctly identify antimicrobial proteins with an accuracy of 85% and a sensitivity of 90%. The method can also predict their key active regions, making this a tool for the design of new antimicrobial drugs

Analysing the eosinophil cationic protein - a clue to the function of the eosinophil granulocyte

Eosinophil granulocytes reside in respiratory mucosa including lungs, in the gastro-intestinal tract, and in lymphocyte associated organs, the thymus, lymph nodes and the spleen. In parasitic infections, atopic diseases such as atopic dermatitis and asthma, the numbers of the circulating eosinophils are frequently elevated. In conditions such as Hypereosinophilic Syndrome (HES) circulating eosinophil levels are even further raised. Although, eosinophils were identified more than hundred years ago, their roles in homeostasis and in disease still remain unclear. The most prominent feature of the eosinophils are their large secondary granules, each containing four basic proteins, the best known being the eosinophil cationic protein (ECP). This protein has been developed as a marker for eosinophilic disease and quantified in biological fluids including serum, bronchoalveolar lavage and nasal secretions. Elevated ECP levels are found in T helper lymphocyte type 2 (atopic) diseases such as allergic asthma and allergic rhinitis but also occasionally in other diseases such as bacterial sinusitis. ECP is a ribonuclease which has been attributed with cytotoxic, neurotoxic, fibrosis promoting and immune-regulatory functions. ECP regulates mucosal and immune cells and may directly act against helminth, bacterial and viral infections. The levels of ECP measured in disease in combination with the catalogue of known functions of the protein and its polymorphisms presented here will build a foundation for further speculations of the role of ECP, and ultimately the role of the eosinophil

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice