Alternaria in food: Ecophysiology, mycotoxin production and toxicology

Alternaria species are common saprophytes or pathogens of a wide range of plants pre- and post-harvest. This review considers the relative importance of Alternaria species, their ecology, competitiveness, production of mycotoxins and the prevalence of the predominant mycotoxins in different food products. The available toxicity data on these toxins and the potential future impacts of Alternaria species and their toxicity in food products pre- and post-harvest are discussed. The growth of Alternaria species is influenced by interacting abiotic factors, especially water activity (a w ), temperature and pH. The boundary conditions which allow growth and toxin production have been identified in relation to different matrices including cereal grain, sorghum, cottonseed, tomato, and soya beans. The competitiveness of Alternaria species is related to their water stress tolerance, hydrolytic enzyme production and ability to produce mycotoxins. The relationship between A. tenuissima and other phyllosphere fungi has been examined and the relative competitiveness determined using both an Index of Dominance (I D ) and the Niche Overlap Index (NOI) based on carbon-utilisation patterns. The toxicology of some of the Alternaria mycotoxins have been studied; however, some data are still lacking. The isolation of Alternaria toxins in different food products including processed products is reviewed. The future implications of Alternaria colonization/infection and the role of their mycotoxins in food production chains pre- and post-harvest are discussed

Investigational drugs for the treatment of diffuse large B-cell lymphoma

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma in adults. 30-40% DLBCL eventually relapse and 10% are primary refractory, posing an unmet clinical need, especially in patients not eligible for hematopoietic stem cell transplant. Knowledge of DLBCL molecular pathogenesis has identified druggable molecular pathways. Surface antigens can be targeted by novel antibodies and innovative cell therapies. Areas covered: This review illuminates those investigational drugs and cell therapies that are currently in early phase clinical trials for the treatment of DLBCL. New small molecules that modulate the pathways involved in the molecular pathogenesis of DLBCL, monospecific and bispecific monoclonal antibodies, drug-immunoconjugates, and cellular therapies are placed under the spotlight. A futuristic perspective concludes the paper. Expert opinion: A precision medicine strategy based on robust molecular predictors of outcome is desirable in the development of investigational small molecules for DLBCL. Novel monoclonal and bispecific antibodies may be offered to (i) relapsed/refractory patients ineligible for CAR-T cells because of comorbidities, and (ii) younger patients before CAR-T cell infusion to reduce a high tumor burden. A focus on the optimal sequencing of the emerging DLBCL drugs is appropriate and necessary

An analytic framework to assess organizational resilience

Background: Resilience Engineering is a paradigm for safety management that focuses on coping with complexity to achieve success, even considering several conflicting goals. Modern socio-technical systems have to be resilient to comply with the variability of everyday activities, the tight-coupled and underspecified nature of work and the nonlinear interactions among agents. At organizational level, resilience can be described as a combination of four cornerstones: monitoring, responding, learning and anticipating. Methods: Starting from these four categories, this paper aims at defining a semi-quantitative analytic framework to measure organizational resilience in complex socio-technical systems, combining the Resilience Analysis Grid (RAG) and the Analytic Hierarchy Process (AHP). Results: This paper presents an approach for defining resilience abilities of an organization, creating a structured domain-dependent framework to define a resilience profile at different levels of abstraction, to identify weaknesses and strengths of the system and thus potential actions to increase system’s adaptive capacity. An illustrative example in an anaesthesia department clarifies the outcomes of the approach. Conclusions: The outcome of the RAG, i.e. a weighted set of probing questions, can be used in different domains, as a support tool in a wider Safety-II oriented managerial action to bring safety management into the core business of the organization

Characterization of small-spored Alternaria from Argentinean crops through a polyphasic approach

Small-spored Alternaria have been isolated from a wide variety of food crops, causing both economic losses and human health risk due to the metabolites produced. Their taxonomy has been discussed widely, but no scientific consensus has been established in this field to date. Argentina is a major exporter of agricultural products, so it is essential to thoroughly understand the physiological behaviour of this pathogen in a food safety context. Thus, the objective of this work was to characterize small-spored Alternaria spp. obtained from tomato fruits, pepper fruits, wheat grains and blueberries from Argentina by a polyphasic approach involving metabolomic and phylogenetic analyses based on molecular and morphological characters. Morphological analysis divided the population studied into three groups; A. arborescens sp.-grp., A. tenuissima sp.-grp., and A. alternata sp.-grp. However, when these characters were simultaneously analysed with molecular data, no clearly separated groups were obtained. Haplotype network and phylogenetic analysis (both Bayesian and maximum parsimony) of a conserved region yielded the same result, suggesting that all isolates belong to the same species. Furthermore, no correlation could be established between morphological species-groups and a metabolite or group of metabolites synthesized. Thus, the whole set of analyses carried out in the present work supports the hypothesis that these small-spored Alternaria isolates from food belong to the same species. Identification at species level through classical morphology or modern molecular techniques does not seem to be a useful tool to predict toxicological risk in food matrices. The detection of any small-spored Alternaria from Section Alternaria (D.P. Lawr., Gannibal, Peever & B.M. Pryor 2013) in food implies a potential toxicological risk.Fil: Da Cruz Cabral, Lucía Mariana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Rodriguero, Marcela Silvina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; ArgentinaFil: Stenglein, Sebastian Alberto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Nielsen, Kristian Fog. Technical University of Denmark; DinamarcaFil: Patriarca, Andrea Rosana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentin

An update on: molecular genetics of high-risk chronic lymphocytic leukemia

ABSTRACTIntroduction: During the past few years, new genomic approaches have elucidated the molecular genetics of chronic lymphocytic leukemia (CLL) to a large extent. As a consequence, specific hi..

Precision Medicine in Systemic Mastocytosis

Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of KIT D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL). More than 80% of patients with SM carry a somatic point mutation of KIT at codon 816, which may be targeted by kinase inhibitors. The presence of additional somatic mutations detected by next generation sequencing analysis may impact prognosis and drive treatment strategy, which ranges from symptomatic drugs in indolent forms to kinase-inhibitors active on KIT. Allogeneic stem cell transplant (SCT) may be considered in selected SM cases. Here, we review the clinical, diagnostic, and therapeutic issues of SM, with special emphasis on the translational implications of SM genetics for a precision medicine approach in clinical practice

Assessing prognosis of chronic lymphocytic leukemia using biomarkers and genetics

Chronic lymphocytic leukemia (CLL) is a clinically and genetically heterogenous disease. Genomic studies have deciphered the pathogenesis of CLL and has allowed the identification of prognostic and..

Targeting p53 in chronic lymphocytic leukemia.

Genomic studies have allowed to identify molecular predictors for chronic lymphocytic leukemia (CLL) treatment tailoring.The review covers the p53 biological pathway, its genetic alterations and clinical implications in CLL, and its druggable targets. The potential therapeutic options forThe key approach to improve CLL outcome is treatment tailoring in individual patients. BCR and BCL2 inhibitors have significantly improved CLL survival, howeve

Phenolic Compounds in Extracts from Eucalyptus globulus Leaves and Calendula officinalis Flowers

Selection of the optimal solvent system for extraction of the phenolics from Eucalyptus globules leaves and Calendula officinalis flowers, determination of the reducing potential and identification of the phenolics in these extracts was performed. The highest content of phenolics was obtained for methanol: water extracts from both sources. All of the Eucalyptus leaf extracts had higher reducing potential than those from the Calendula flowers. Solid-phase purification of the crude extracts removed 57% to 78% of the compounds in the crude extracts. The reducing potential of the purified extracts varied from 0.17 to 2.92 mg caffeic acid/g dry weight. The extracts from Eucalyptus leaves and Calendula flowers both contained chlorogenic acid, rutin and quercetin 3-glucuronide. Ellagic acid derivatives were identified only in the leaves of Eucalyptus, while beside caffeic acid and salicylic acid, quercetin 3-glucuronide, and pinobanksin 3-acetate was found in the Calendula flower extract for the first time.Fil: Dos Santos Ferreira, Cristina Isabel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; ArgentinaFil: Pereyra, A.. University of Ljubljana. Biotechnical Faculty; EsloveniaFil: Patriarca, Andrea Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Micología y Botánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Micología y Botánica; ArgentinaFil: Mazzobre, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polak, T.. University of Ljubljana. Biotechnical Faculty; EsloveniaFil: Abram, V.. University of Ljubljana. Biotechnical Faculty; EsloveniaFil: Buera, Maria del Pilar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Poklar Ulrih, N.. University of Ljubljana. Biotechnical Faculty; Esloveni

The Markov approximation revisited: Inconsistency of the standard quantum Brownian motion model

We revisit the Markov approximation necessary to derive ordinary Brownian motion from a model widely adopted in literature for this specific purpose. We show that this leads to internal inconsistencies, thereby implying that further search for a more satisfactory model is required.Comment: 15 page