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Biology subjects

Haddad, M.

Publications and source records attributed to Haddad, M..

3 recordsLinked to original sources

Metabotyping of Andean pseudocereals and characterization of emerging mycotoxins

Pseudocereals are best known for three crops derived from the Andes: quinoa (Chenopodium quinoa, Chenopods I), canihua (C. pallidicaule, Chenopods I), and kiwicha (Amaranthus caudatus). Their grains are recognized for their nutritional benefits; however, there is a higher level of polyphenism and the chemical foundation that would rely with such polyphenism has not been thoroughly investigated. Meanwhile, the chemical food safety of pseudocereals remains poorly documented. Here we applied untargeted and targeted metabolomics approach by LC-MS to achieve both: i) a comprehensive chemical mapping of pseudocereal samples collected in the Andes to classify them according to their chemotype; ii) a quantification of their contents in emerging mycotoxins. An inventory of the fungal community was also realized with the aims to better know the filamentous fungi present in these grains and try to parallel this information with the presence of the molecules produced, especially mycotoxins. Metabotyping permitted to add new insights into the chemotaxonomy of pseudocereals, confirming the previously established phylotranscriptomic clades: Chenopods I (clusters quinoa and canihua), and Amaranthaceae s.s. (cluster kiwicha). Moreover, we report for the first time the presence of mycotoxins in pseudocereals. Sixteen samples of Peru (out of 27) and one sample from France (out of one) were contaminated with Beauvericin, an emerging mycotoxin. There were several mycotoxigenic fungi detected, including Aspergillus sp., Penicillium sp., and Alternaria sp., but not Fusaria. Highlights{blacksquare} Twenty-seven grain samples of Andean pseudocereals were profiled by LC-HRMS. {blacksquare}Untargeted metabolomics was used to differentiate varieties from the whole metabolome dataset. {blacksquare}Five mycotoxins were quantify using targeted metabolomics. {blacksquare}Sixteen samples of Peru and one sample from France were contaminated with Beauvericin. {blacksquare}An inventory of the fungal community infesting the Andean pseudocereal samples was documented.

biochemistry↗

Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus dependent manner

Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of the age-related memory impairment remain yet highly debated. Here we showed that fecal microbiota transplantation (FMT) from aged, but not young, animal donors in young mice is sufficient to trigger profound hippocampal alterations including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation and impairment in hippocampus-dependent memory. Furthermore, similar alterations were reported when mice were subjected to an FMT from aged human donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain function, we mapped the vagus nerve (VN)-related neuronal activity patterns and report that aged-mice FM transplanted animals showed a reduction in neuronal activity in the ascending VN output brain structure, both in basal condition and following VN stimulation. Targeted pharmacogenetic manipulation of VN-ascending neurons demonstrated that the decrease in vagal activity is detrimental to hippocampal functions. In contrast, increasing vagal ascending activity alleviated the adverse effects of aged mice FMT on hippocampal functions, and had a pro-mnesic effect in aged mice. Thus, pharmacogenetic VN stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/428594v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@8e668borg.highwire.dtl.DTLVardef@ee5d18org.highwire.dtl.DTLVardef@1220a87org.highwire.dtl.DTLVardef@1e12fe7_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Defective NETs Clearance contributes to sustained FXII Activation in COVID-19-associated Pulmonary Thrombo-Inflammation

BackgroundCoagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. MethodsWe performed proteomic analysis and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We further compared coagulation factor XII (FXII) and DNase activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced Factor XIII (FXII) activation using a chromogenic substrate assay. FindingsFXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients. In agreement with this, plasma FXII activation (FXIIa) was increased in samples from COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially due to impaired NET clearance by extracellular DNases as DNase substitution improved NET dissolution and reduced FXII activation in vitro. InterpretationCollectively, our study supports that the NETs/FXII axis contributes to the pathogenic chain of procoagulant and proinflammatory responses in COVID-19. Targeting both, NETs and FXIIa, could provide a strategy to mitigate COVID-19-induced thrombo-inflammation. FundingThis study was supported by the European Union (840189), the Werner Otto Medical Foundation Hamburg (8/95) and the German Research Foundation (FR4239/1-1, A11/SFB877, B08/SFB841 and P06/KFO306).

molecular biology↗