Mitochondrial Quality Control and Parkinson’s Disease: A Pathway Unfolds

Recent findings from genetic studies suggest that defective mitochondrial quality control may play an important role in the development of Parkinson's disease (PD). Such defects may result in the impairment of neuronal mitochondria, which leads to both synaptic dysfunction and cell death and results in neurodegeneration. Here, we review state-of-the-art knowledge of how pathways affecting mitochondrial quality control might contribute to PD, with a particular emphasis on the molecular mechanisms employed by PTEN-induced putative kinase 1 (PINK1), HtrA2 and Parkin to regulate mitochondrial quality control

Validation and quality assurance applied to goat milk chemical composition: minerals and trace elements measurements

In the present study, quality assurance programmes were implemented to validate and control the analytical methodologies used for the characterization of minerals and trace elements in goat milk from Portuguese breeds. With the exception of chloride that was determined by potentiometric titration, all the other elements were determined by spectroscopic techniques after different sample decomposition: P was measured by ultraviolet-visible molecular absorption spectrometry, Ca, Fe, K, Mg, Mn, Na and Zn by flame atomic absorption spectrometry and Cd, Co, Cr, Cu, Mo, Ni and Pb by electrothermal atomic absorption spectrometry. The methods performance characteristics, namely specificity, limit of detection, limit of quantification, working range, precision and trueness were evaluated. Measurement uncertainty was expressed in terms of precision and trueness. Precision under intralaboratory reproducibility conditions was estimated from triplicate analysis, and the trueness component was estimated in terms of overall recovery using either skim milk powder certified reference materials or spiked samples. The results obtained are discussed on the basis of the performance criteria required by EC regulations to verify when a method is suitable for food control. The methods used for the characterization of minerals and trace elements in goat milk complied with EC requirements since there was no matrix influence, the Horrat values were < 2.0, recoveries were within the interval 1.00 ± 0.10 for minerals and 1.00 ± 0.20 for trace elements and the combined uncertainty of the results were lower than the maximum standard uncertainty calculated using the uncertainty function approach. In relation to the limits of detection and quantification, the limits obtained for Pb were lower than those specified by EC regulation

Insights into the spatial and temporal variability of soil attributes in irrigated farm fields and correlations with management practices: A multivariate statistical approach

The evaluation of the spatial and temporal variability of soil properties can be valuable to improve crop productivity and soil health. A study of soil properties was carried out in southern Portugal, in three farm fields with irrigated annual crops (layers 0–20 cm and 20–40 cm), over three years. Factor Analysis (FA) and Discriminant Analysis (DA) were used to analyze the data. With FA, the observed variables were grouped into a smaller number of latent variables related to soil attributes. Discriminant Analysis was used to classify and identify the most dominant attributes and indicators for the time and space variability of soil parameters. The FA performed for the surface layer included factors related to texture, water and nutrient retention capacity, chemical composition, and soil fertility. In the sub-surface layer, the factor structure was similar, with four factors related to texture, chemical composition, nutrient availability, and soil fertility. The most influential factors and variables in temporal discrimination (sampling dates) in both layers were those related to chemical composition, with electric conductivity as the preponderant indicator. As for the spatial differentiation (fields), the dominant factor in the surface layer was texture, and in the sub-surface layer, nutrient availability. The most important discriminant indicators of spatial variability were fine sand proportion and available potassium, respectively, for the surface and sub-surface layers. The results obtained showed potential for the multidimensional and integrated assessment of patterns of temporal and spatial variation of soil functions from agricultural practices or soil degradation processes

Activation pathway to amino acid adducts

Funding: This work was supported in part by Fundação para a Ciência e a Tecnologia (FCT), Portugal (PTDC/QUI-QUI/113910/2009, RECI/QEQ-MED/0330/2012, UID/QUI/00100/2013 and IF/ 01091/2013/CP1163/CT0001), and by Interagency Agreement Y1ES1027 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute of Environmental Health Sciences/National Toxicology Program. The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. RW, ALG, ILM and SGH thank FCT for postdoctoral and doctoral fellowships (SFRH/BPD/70953/2010, SFRH/BD/72301/2010, SFRH/BD/75426/2010 and SFRH/BD/ 80690/2011, respectively). AMM also acknowledges Programa Operacional Potencial Humano from FCT and the European Social Fund (IF/01091/2013), and the LRI Innovative Science Award. We thank the Portuguese NMR and MS networks (IST nodes) for providing access to the facilities.Nevirapine (NVP) is the non-nucleoside HIV-1 reverse transcriptase inhibitor most commonly used in developing countries, both as a component of combined antiretroviral therapy and to prevent mother-to-child transmission of the virus; however, severe hepatotoxicity and serious adverse cutaneous effects raise concerns about its safety. NVP metabolism yields several phenolic derivatives conceivably capable of undergoing further metabolic oxidation to electrophilic quinoid derivatives prone to react with bionucleophiles and initiate toxic responses. We investigated the ability of two phenolic NVP metabolites, 2-hydroxy-NVP and 3-hydroxy-NVP, to undergo oxidation and subsequent reaction with bionucleophiles. Both metabolites yielded the same ring-contraction product upon oxidation with Frémy's salt in aqueous medium. This is consistent with the formation of a 2,3-NVP-quinone intermediate, which upon stabilization by reduction was fully characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. Additionally, we established that the oxidative activation of 2-hydroxy-NVP involved the transient formation of both the quinone and a quinone-imine, whereas 3-hydroxy-NVP was selectively converted into 2,3-NVP-quinone. The oxidations of 2-hydroxy-NVP and 3-hydroxy-NVP in the presence of the model amino acids ethyl valinate (to mimic the highly reactive N-terminal valine of hemoglobin) and N-acetylcysteine were also investigated. Ethyl valinate reacted with both 2,3-NVP-quinone and NVP-quinone-imine, yielding covalent adducts. By contrast, neither 2,3-NVP-quinone nor NVP-derived quinone-imine reacted with N-acetylcysteine. The product profile observed upon Frémy's salt oxidation of 2-hydroxy-NVP in the presence of ethyl valinate was replicated with myeloperoxidase-mediated oxidation. Additionally, tyrosinase-mediated oxidations selectively yielded 2,3-NVP-quinone-derived products, while quinone-imine-derived products were obtained upon lactoperoxidase catalysis. These observations suggest that the metabolic conversion of phenolic NVP metabolites into quinoid electrophiles is biologically plausible. Moreover, the lack of reaction with sulfhydryl groups might hamper the in vivo detoxification of NVP-derived quinone and quinone-imine metabolites via glutathione conjugation. As a result, these metabolites could be available for reaction with nitrogen-based bionucleophiles (e.g., lysine residues of proteins) ultimately eliciting toxic events.publishersversionpublishe

Are cyanobacteria a nearly immortal source of high market value compounds?

BACKGROUND: When the human population increases, so does the need to explore a wider range of feedstocks and biomasses, such as cyanobacteria. However, a deeper understanding of the growth patterns and pigment production is required to support the selection of the most beneficial species and conditions for industrial production. The growth and pigment production (i.e., chlorophyll a and C-phycocyanin) of three cyanobacterium species were evaluated following a three-fold aim. The first goal was to compare among a species commonly selected for exploitation (Arthrospira platensis) and two alternative species (Anabaena cylindrica and Nostoc muscorum). The second goal was analyzing pigment production in the long-term. The last goal involved comparing different methods (spectrophotometry and fluorimetry) to understand whether there is an appropriate proxy of biomass increase and pigment production that can be used for monitoring purposes. RESULTS: All species showed high longevity and proved capable of growing for more than 100 days without any additional supplementation. However, the maximum quantum yield of PS II (Fv /Fm) revealed that their photosynthetic efficiency varied over time with a clear decrease after 2 months. Pigment analysis showed a heterogeneous pattern during the growth periods of all three species that could only be captured by the parameter Fv /Fm, but the pattern was only present for A. cylindrica and N. muscorum in some stages of the culture period. CONCLUSION: N. muscorum was found to be the best chlorophyll a and C-phycocyanin producer, with the production peaking for all species at defined time periods within the growth profile. © 2022 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).publishe

A tutorial

PM003/2016. Publisher Copyright: © 2022 The Author(s)The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bioinformatics. From (i) sampling to sample treatment; (ii) Matrix-Assisted Laser Desorption Ionization- to Electrospray Ionization -based mass spectrometry; and (iii) from clustering to peptide sequencing; a detailed step-by-step guide is provided and exemplified using SARS-CoV-2 Spike Y839 variant and the variant of concern SARS-CoV-2 Alpha (B.1.1.7 lineage), Influenza B, and Influenza A subtypes AH1N1pdm09 and AH3N2.publishersversionpublishe

How to dissect viral infections and their interplay with the host-proteome by immunoaffinity and mass spectrometry: A tutorial

The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bioinformatics. From (i) sampling to sample treatment; (ii) Matrix-Assisted Laser Desorption Ionization- to Electrospray Ionization -based mass spectrometry; and (iii) from clustering to peptide sequencing; a detailed step-by-step guide is provided and exemplified using SARS-CoV-2 Spike Y839 variant and the variant of concern SARS-CoV-2 Alpha (B.1.1.7 lineage), Influenza B, and Influenza A subtypes AH1N1pdm09 and AH3N2.Highlights: - Immunohistochemistry with magnetic core nanoparticles to isolate viruses. - The use of MALDI-MS for rapid virus detection is explained in detail; - The use of ESI-MS/MS to pinpoint host-patient crosstalk is explained in detail. - The absolute quantitative MS is explained for large-scale protein quantitation.This work received financial support from PT national funds (FCT/MCTES) through the projects UIDB/50006/2020 and UIDP/50006/2020 and from PROTEOMASS Scientific Society through the projects #PM001/2019 and #PM003/2016.info:eu-repo/semantics/publishedVersio