Since the first genetically engineered or modified crops or organisms (GMO) were approved for commercial production in 1995, no new GMO has been proven to be a hazard or cause harm to human ...consumers. These modifications have improved crop efficiency, reduced losses to insect pests, reduced losses to viral and microbial plant pathogens and improved drought tolerance. A few have focused on nutritional improvements producing beta carotene in Golden Rice. Regulators in the United States and countries signing the CODEX Alimentarius and Cartagena Biosafety agreements have evaluated human and animal food safety considering potential risks of allergenicity, toxicity, nutritional and anti-nutritional risks. They consider risks for non-target organisms and the environment. There are no cases where post-market surveillance has uncovered harm to consumers or the environment including potential transfer of DNA from the GMO to non-target organisms. In fact, many GMOs have helped improve production, yield and reduced risks from chemical insecticides or fungicides. Yet there are generic calls to label foods containing any genetic modification as a GMO and refusing to allow GM events to be labeled as organic. Many African countries have accepted the Cartagena Protocol as a tool to keep GM events out of their countries while facing food insecurity. The rationale for those restrictions are not rational. Other issues related to genetic diversity, seed production and environmental safety must be addressed. What can be done to increase acceptance of safe and nutritious foods as the population increases, land for cultivation is reduced and energy costs soar?
Fy Protein™ (Nutritional Fungi Protein) is a macro-ingredient produced from the fermentation of the fungal microorganism Fusarium strain flavolapis, isolated from springs in Yellowstone National ...Park. Fy Protein contains all of the essential amino acids plus fiber, fat, carbohydrates, vitamins, and minerals and is developed as an alternative to animal-based protein foods such as meat and dairy.
Fy Protein's nutritional, digestibility, genotoxicity, allergenicity, toxicity, secondary metabolites, and pathogenicity were evaluated. Fy Protein did not show mutagenic or genotoxic potential in in vitro tests. In an allergenicity review, Fy Protein was found to be of low allergenic potential. In a 90-day sub chronic dietary study in rats, administration of Fy Protein did not produce any significant toxicologic manifestations, and the No Observed Adverse Effect Level (NOAEL) was the highest-level fed of 150,000 ppm (15% in the diet). Regulated secondary metabolites from fungi (termed mycotoxins) were non-detectable and below regulated levels using quantitative analytical techniques. A literature review was completed to identify the potential human pathogenicity of Fusarium sp., showing that Fusarium rarely infects humans, with infections seldom developing even in immunocompromised individuals.
The results of these studies confirm that Fy Protein from fermented F. str. flavolapis has low toxicological, genotoxic, pathogenic, and allergenic potential under the conditions tested and anticipated use.
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Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub‐Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but ...also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE‐binding glycans recognized up to 2008 were considered to be “classical” cross‐reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE‐binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose‐alpha‐1,3‐galactose (alpha‐gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha‐gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross‐reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub‐Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.
Papaya ringspot virus biotype-P is a detrimental pathogen of economically important papaya and cucurbits worldwide. The mutation prone feature of this virus perhaps accounts for its geographical ...dissemination. In this study, investigations of the atypical PRSV-P strain was conducted based on phylogenetic, recombination and genetic differentiation analyses considering of it's likely spread across India and Bangladesh. Full length genomic sequences of 38 PRSV isolates and 35 CP gene sequences were subjected to recombination analysis. A total of 61 recombination events were detected in aligned complete PRSV genome sequences. 3 events were detected in complete genome of PRSV strain PK whereas one was in its CP gene sequence. The PRSV-PK appeared to be recombinant of a major parent from Bangladesh. However, the genetic differentiation based on full length genomic sequences revealed less frequent gene flow between virus PRSV-PK and the population from America, India, Colombia, other Asian Countries and Australia. Whereas, frequent gene flow exists between Pakistan and Bangladesh virus populations. These results provided evidence correlating geographical position and genetic distances. We speculate that the genetic variations and evolutionary dynamics of this virus may challenge the resistance developed in papaya against PRSV and give rise to virus lineage because of its atypical emergence where geographic spread is already occurring.
Potential proteins from three novel food sources (Chlorella variabilis, Galdieria sulphuraria, and Fusarium strain flavolapis) were predicted from genomic sequences and were evaluated for potential ...risks of allergic cross-reactivity by comparing the predicted amino acid sequences against the allergens in the www.AllergenOnline.org (AOL) database. The preliminary analysis used CODEX Alimentarius limits of >35% identity over 80 amino acids to evaluate the predicted proteins which include many evolutionarily conserved proteins. Regulators might expect clinical serum IgE tests based on identity matches above the criteria if the proteins were introduced in genetically engineered crops. Some regulators have the same expectations for proteins in novel foods. To address the inequality of extensively conserved sequences, we compared the predicted proteins from curated genomes of 23 highly diverse allergenic species from animals, plants and arthropods as well as humans to AOL sequences and compiled identities. Identity matches greater than CODEX limits (>35% ID over 80 AA) are common for many proteins that are conserved through extensive evolution but are not predictive of published allergy risks based on observed taxonomic cross-reactivity. Therefore, we recommend changes in the allergen databases or methods of identifying matches for risk evaluation of new food sources. Our results provide critical data for redefining allergens in AOL or for providing guidance on more predictive sequence identity matches for risk assessment of possible risks of food allergy.
•Predicting risks of food allergy focuses on possible IgE cross-reactivity.•Allergenic foods contain few clinically important allergen types.•Comparing proteins by sequences can identify possible cross-reactivity.•Allergy databases include many evolutionarily conserved proteins of little risk.•CODEX predictions are designed for single proteins, whole genomes and proteomes are challenging.
Soybean is recognized as a commonly allergenic food, but the identity of important allergens is not well studied. Recently, some global regulatory agencies started requiring quantitative analysis of ...individual allergens, including unproven allergens, as part of the risk assessment for genetically engineered (GE) soybeans. We sought to identify soybean proteins that bind IgE from any of 10 individual soybean-sensitized subjects. Soybean IgE binding proteins were identified by 2-DE immunoblots using sera from four soy-allergic and plasma from six soy-sensitized human subjects. Corresponding spots were excised from stained gels, digested, and analyzed using a quadrupole TOF Synapt G2-S tandem mass spectrometer. Results showed the major IgE binding proteins were subunits of either β-conglycinin (Gly m 5) or glycinin (Gly m 6). Soybean Kunitz trypsin inhibitor (SKTI) was a significant IgE binding protein for four subjects. Soybean agglutinin, seed biotinylated protein (SBP) of 65 kDa, late embryogenesis protein (LEP), and sucrose-binding protein were identified as IgE binding only for soy-sensitized subjects. We conclude that the major soybean allergens are isoforms of Gly m 5, Gly m 6, and possibly SKTI and that requirements for quantitative measurement of proteins that are not clear allergens is not relevant to safety.
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•Subunits of β-conglycinin (Gly m 5) and glycinin (Gly m 6) were major soybean allergens.•Soybean Kunitz trypsin inhibitor (SKTI) was a significant IgE binding protein in four out of ten subjects.•Soy agglutinin, seed biotinylated, late embryogenesis and sucrose-binding proteins bound IgE of soy-sensitized individuals.•Many putative soybean allergens were not detected as IgE binding proteins among the ten subjects.
Scope
Increasingly regulators are demanding evaluation of potential allergenicity of foods prior to marketing. Primary risks are the transfer of allergens or potentially cross‐reactive proteins into ...new foods. AllergenOnline was developed in 2005 as a peer‐reviewed bioinformatics platform to evaluate risks of new dietary proteins in genetically modified organisms (GMO) and novel foods.
Methods and results
The process used to identify suspected allergens and evaluate the evidence of allergenicity was refined between 2010 and 2015. Candidate proteins are identified from the NCBI database using keyword searches, the WHO/IUIS nomenclature database and peer reviewed publications. Criteria to classify proteins as allergens are described. Characteristics of the protein, the source and human subjects, test methods and results are evaluated by our expert panel and archived. Food, inhalant, salivary, venom, and contact allergens are included. Users access allergen sequences through links to the NCBI database and relevant references are listed online. Version 16 includes 1956 sequences from 778 taxonomic‐protein groups that are accepted with evidence of allergic serum IgE‐binding and/or biological activity.
Conclusion
AllergenOnline provides a useful peer‐reviewed tool for identifying the primary potential risks of allergy for GMOs and novel foods based on criteria described by the Codex Alimentarius Commission (2003).
The AllergenOnline database is a risk assessment tool to identify novel proteins in genetically modified organisms or processed foods that might be sufficiently identical to an allergen based on FASTA to suspect potential cross‐reactivity, requiring allergen‐specific serum IgE testing. The AllergenOnline.org is updated annually with sequences associated with published proof of allergy based on pre‐defined criteria as interpreted by a panel of experts. Criteria include definition of protein characteristics, allergic test subjects, IgE binding, and evidence of biological activity (Basophil or in vivo tests).
The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism ...(POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach.
Abstract
The first genetically engineered (GE) food crop (tomato) was introduced in 1995, followed by the successful development and commercial release of maize, soybeans, cotton, canola, potatoes, ...papaya, alfalfa, squash, and sugar beets with specific new genetic traits. Even though the safety of every new GE crop has been evaluated by various regulatory authorities throughout the world prior to its commercial release, the ongoing public debate about the safety of food and feed derived from GE plants has not abated. Such debates often overshadow an important fact that all crops used as human food or animal feed include varieties that have been developed through conventional breeding and selection over hundreds or thousands of years, or through intentional but random mutagenesis. Developing food crops through such breeding practices result in large-scale genomic changes in the resulting crops, and these genomic changes do not undergo molecular characterization. In contrast, new GE crops are developed using well-characterized DNA fragments and the resulting crops are tested and evaluated with much greater scrutiny. This document reviews the safety data and information of GE crops and foods obtained from them.
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