RESUMEN
Seafood fraud is commonly reported on food fraud databases and deceptive practices are highlighted by numerous studies, with impacts on the economy, health and marine conservation. Food fraud assessments are a widely accepted fraud mitigation and prevention activity undertaken to identify possible points of deception within a supply chain. This study aims to understand the food fraud vulnerability of post-harvest seafood supply chains in the UK and determine if there are differences according to commodity, supply chain node, business size and certification status. The SSAFE food fraud vulnerability assessment tool was used to assess 48 fraud factors relating to opportunities, motivations and controls. The analysis found seafood supply chains to have a medium vulnerability to food fraud, with the highest perceived vulnerability in technical opportunities. Certification status was a stronger determinant of vulnerability than any other factor, particularly in the level of controls, a factor that also indicated a higher perceived level of vulnerability in smaller companies and the food service industry. This paper also reviews historic food fraud trends in the sector to provide additional insights and the analysis indicates that certain areas of the supply chain, including uncertified prawn supply chains, salmon supply chains and food service companies, may be at higher risk of food fraud. This study conducts an in-depth examination of food fraud vulnerability relating to the UK and for seafood supply chains and contributes to a growing body of literature identifying areas of vulnerability and resilience to food related criminality within the global food system.
RESUMEN
Synaptotagmin-1 (Syt-1) is a calcium sensing protein that is resident in synaptic vesicles. It is well established that Syt-1 is essential for fast and synchronous neurotransmitter release. However, the role of Ca2+ and phospholipid binding in the function of Syt-1, and ultimately in neurotransmitter release, is unclear. Here, we investigate the binding of Ca2+ to Syt-1, first in the absence of lipids, using native mass spectrometry to evaluate individual binding affinities. Syt-1 binds to one Ca2+ with a KD â¼ 45 µM. Each subsequent binding affinity (n ≥ 2) is successively unfavorable. Given that Syt-1 has been reported to bind anionic phospholipids to modulate the Ca2+ binding affinity, we explored the extent that Ca2+ binding was mediated by selected anionic phospholipid binding. We found that phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and dioleoylphosphatidylserine (DOPS) positively modulated Ca2+ binding. However, the extent of Syt-1 binding to phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) was reduced with increasing [Ca2+]. Overall, we find that specific lipids differentially modulate Ca2+ binding. Given that these lipids are enriched in different subcellular compartments and therefore may interact with Syt-1 at different stages of the synaptic vesicle cycle, we propose a regulatory mechanism involving Syt-1, Ca2+, and anionic phospholipids that may also control some aspects of vesicular exocytosis.
Asunto(s)
Calcio , Fosfolípidos , Sinaptotagmina I , Calcio/metabolismo , Exocitosis/fisiología , Neurotransmisores/metabolismo , Fosfolípidos/metabolismo , Transmisión Sináptica/fisiología , Vesículas Sinápticas/metabolismo , Sinaptotagmina I/metabolismo , Animales , RatasRESUMEN
ABSTRACT: Relapse after CD19-directed chimeric antigen receptor (CAR)-modified T cells remains a substantial challenge. Short CAR T-cell persistence contributes to relapse risk, necessitating novel approaches to prolong durability. CAR T-cell reinfusion (CARTr) represents a potential strategy to reduce the risk of or treat relapsed disease after initial CAR T-cell infusion (CARTi). We conducted a retrospective review of reinfusion of murine (CTL019) or humanized (huCART19) anti-CD19/4-1BB CAR T cells across 3 clinical trials or commercial tisagenlecleucel for relapse prevention (peripheral B-cell recovery [BCR] or marrow hematogones ≤6 months after CARTi), minimal residual disease (MRD) or relapse, or nonresponse to CARTi. The primary endpoint was complete response (CR) at day 28 after CARTr, defined as complete remission with B-cell aplasia. Of 262 primary treatments, 81 were followed by ≥1 reinfusion (investigational CTL019, n = 44; huCART19, n = 26; tisagenlecleucel, n = 11), representing 79 patients. Of 63 reinfusions for relapse prevention, 52% achieved CR (BCR, 15/40 [38%]; hematogones, 18/23 [78%]). Lymphodepletion was associated with response to CARTr for BCR (odds ratio [OR], 33.57; P = .015) but not hematogones (OR, 0.30; P = .291). The cumulative incidence of relapse was 29% at 24 months for CR vs 61% for nonresponse to CARTr (P = .259). For MRD/relapse, CR rate to CARTr was 50% (5/10), but 0/8 for nonresponse to CARTi. Toxicity was generally mild, with the only grade ≥3 cytokine release syndrome (n = 6) or neurotoxicity (n = 1) observed in MRD/relapse treatment. Reinfusion of CTL019/tisagenlecleucel or huCART19 is safe, may reduce relapse risk in a subset of patients, and can reinduce remission in CD19+ relapse.
Asunto(s)
Antígenos CD19 , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Niño , Antígenos CD19/inmunología , Antígenos CD19/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Preescolar , Femenino , Masculino , Receptores Quiméricos de Antígenos/uso terapéutico , Adolescente , Recurrencia , Estudios Retrospectivos , Lactante , Receptores de Antígenos de Linfocitos T/uso terapéutico , Resultado del Tratamiento , Linfocitos T/inmunologíaRESUMEN
Due to complex, valuable, and often extremely opaque supply chains, seafood is a commodity that has experienced a high prevalence of food fraud throughout the entirety of its logistics network. Fraud detection and prevention require an in-depth understanding of food supply chains and their vulnerabilities and risks so that food business operators, regulators, and other stakeholders can implement practical countermeasures. An analysis of historical criminality within a sector, product, or country is an important component and has not yet been conducted for the seafood sector. This study examines reported seafood fraud incidents from the European Union's Rapid Alert System for Food and Feed, Decernis's Food Fraud Database, HorizonScan, and LexisNexis databases between January 01, 2010 and December 31, 2020. Illegal or unauthorized veterinary residues were found to be the most significant issue of concern, with most reports originating from farmed seafood in Vietnam, China, and India. For internationally traded goods, border inspections revealed a significant frequency of reports with fraudulent or insufficient documentation, indicating that deceptive practices are picked up at import or export but are occurring further down the supply chain. Practices such as species adulteration (excluding veterinary residues), species substitution, fishery substitution, catch method fraud, and illegal, unreported, and unregulated fishing were less prevalent in the databases than evidenced in the scientific literature. The analysis demonstrates significant differences in outcomes depending on source and underlines a requirement for a standardized and rigorous dataset through which food fraud can be scrutinized to ensure enforcement, as well as industry and research resources are directed accurately. Practical Application: Levels of historic food fraud in a product, sector, supply chain node or geographic location provide an indication of historic criminality, the methods used and the location of reported frauds. This study provides an overview of historic levels of seafood fraud that can be used to inform seafood fraud prevention and mitigation activities by the food industry, regulators and other stakeholders.