Métodos para detecção de toxinas e alérgenos de mamona e de pinhão-manso.

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Proteoforms: General Concepts and Methodological Process for Identification

The term proteoform is used to denote all the molecular forms in which the protein product of a single gene can be found. The most frequent processes that lead to transcript modification and the biological implications of these changes observed in the final protein product will be discussed. Proteoforms arising from genetic variations, alternatively spliced RNA transcripts and post-translational modifications will be commented. This chapter will present an evolution of the techniques used to identify the proteoforms and the importance of this identification for understanding of biological processes. This chapter highlights the fundamental concepts in the field of top-down mass spectrometry (TDMS), and provides numerous examples for the use of knowledge obtained from the identification of proteoforms. The identification of mutant proteins is one of the emerging areas of proteogenomics and has the potential to recognize novel disease biomarkers and may point to useful targets for identification of therapeutic approaches

Antihistaminic Treatment, Allergen‐Specific Immunotherapy, and Blockade of IgE as Alternative Allergy Treatments

Allergies mediated by immunoglobulin E (IgE) are the most common immunological hypersensitivity diseases. The prevalence has been continuously increasing in recent decades, and more than 25% of the population is currently affected. Symptoms of allergies can be observed in the skin and respiratory and gastrointestinal tracts, and systemic manifestations include anaphylactic shock. If an allergy is not properly diagnosed and treated, it tends to progress to a severe and chronic debilitating disease. Understanding the mechanisms by which the immune system induces and controls allergic inflammation depends on knowing the structure of several allergens and identifying epitopes, which are critical for the design of new strategies for treating allergies. Strategies for immunotherapy will be reviewed. Allergen‐specific immunotherapy has been used for nearly a century and remains one of the few antigen‐specific treatments for inflammatory diseases. There is a strong rationale for improving the efficacy of allergen‐specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem, including the use of modified allergens, synthetic peptides as vaccines, and alternative strategies for blocking IgE, will be discussed

Current Developments in Allergen-Specific Immunotherapy: A Brief Review

Immunotherapy is a treatment for patients with type I-mediated allergic diseases. Molecular forms of allergen-specific immunotherapy (AIT), based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels, and Treg cell are continuously emerging to improve the efficacy of the treatment, shorten the duration of protocols, and prevent any side effects. This review covers the recent progress in AIT and routes of antigen administration. Classical immunotherapy uses allergen extracts obtained from natural sources. Limitations of the uses of these extracts, such as sensitizations with nonspecific agents, can be avoided using purified components, hypoallergenic recombinant proteins, and vaccines based on peptides (epitopes). However, these molecules have low immunogenicity requiring new carriers or more effective adjuvants. Vaccines based on carrier-bound B-cell epitope-containing peptides and the constructions of allergens coupled to virus-like particles (VLPs) are under evaluation. The possibility of vaccinating with DNA encoding the allergen to obtain an allergen-specific Th1 and IgG response is in development and the success of messenger ribonucleic acid (mRNA) vaccines against severe acute respiratory syndrome Coronavirus 2 must encourage as well the re-exploration of mRNA vaccine platform for innovative AIT

Blocking IgE with L-glutamic acid analogs as an alternative approach to allergy treatment

IgE-mediated allergic diseases have increased in the last decades. The most prevalent allergens from these seeds are Ric c1 and Ric c3, isoforms of 2S albumin. These allergenic proteins cross-react with allergens from peanut, shrimp, fish, corn, gramineous, house dust, and tobacco. The usual allergy treatment employs antihistaminic, immunotherapies and, omalizumab (Xolair)-based anti-IgE therapy. However, antihistaminics relieve symptoms, and the high cost of omalizumab limits its use for continuous treatment. We propose an alternative immunotherapeutic approach, denoted “IgE-blockage” by L-glutamic acid or modified-glutamic acid. Six compounds, D-glutamic acid, L-glutamic acid, N-methyl-L-glutamic acid, N-acetyl-L-glutamic acid, N-(4-nitrobenzoyl)-L-glutamic acid, and N-carbamyl-L-glutamic, were tested as a blocker. To evaluate motor coordination and the sedative/hypnotic activity of L-glutamic acid, a rota-rod test and a thiopental sodium-induced sleeping test were used. The compounds, L-glutamic acid and L-nitrobenzoyl glutamic acid, were the most active compounds to block the interaction of castor allergens with IgE. These compounds also prevent cross-responses with allergens from food sources and inhalants that cross-react with them. In the sleeping test, the groups that received L-glutamic acid at doses of 10 and 30 mg/kg had a sleeping time similar to the vehicle control group. No changes in the animals' behavior were observed and there was no difference between the L-glutamic acid groups and the vehicle control groups in the rota-rod test. L-glutamic acid and L-nitrobenzoyl glutamic acid can used as IgE blocker to prevent allergic diseases. DOI: http://dx.doi.org/10.5281/zenodo.768610

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements