Proteomic analysis of peripheral blood mononuclear cells in first episode psychosis - Protein and peptide-centered approaches to elucidate potential diagnostic biomarkers.

Diagnosing patients suffering from psychotic disorders is far from being achieved with molecular support, despite all the efforts to study these disorders from different perspectives. Characterizing the proteome of easily obtainable blood specimens, such as the peripheral blood mononuclear cells (PBMCs), has particular interest in biomarker discovery and generating pathophysiological knowledge. This approach has been explored in psychiatry, and while generating valuable information, it has not translated into meaningful biomarker discovery. In this project, we report the proof-of-concept of a methodology that aims to explore further information obtained with classical proteomics approaches that is easily overlooked. PBMC samples from first-episode psychosis and control subjects were subjected to a SWATH-MS approach, and the classical protein relative quantification was performed, where 389 proteins were found to be important to distinguish the two groups. Individual analysis of the quantified peptides was also performed, highlighting peptides of unchanged proteins that were significantly altered. With the combination of protein- and peptide-centered proteomics approaches, it is possible to highlight that information about proteoforms, namely regulation at the peptide level possibly due to post-translational modifications, is routinely overlooked and that its diagnostic potential should be further explored. SIGNIFICANCE: Our exploratory findings highlight the potential of MS-based proteomics strategies, combining protein- and peptide-centered approaches, to aid clinical decision-making in first-episode psychosis, helping to establish early biomarkers for schizophrenia and other psychotic disorders. Particularly, the less popular peptide-centered approach allows the identification/measurement of overlooked modulated peptides that may have potential biomarker characteristics. The application in parallel of protein- and peptide-centered strategies is transversal to research of other diseases, potentially allowing a more comprehensive characterization of the metabolic/pathophysiological alterations related to a specific disease.

Impact of a legumes diet on the human gut microbiome articulated with fecal and plasma metabolomes: A pilot study.

BACKGROUND & AIMS: Legumes intake is known to be associated with several health benefits the origins of which is still a matter of debate. This paper addresses a pilot small cohort to probe for metabolic aspects of the interplay between legumes intake, human metabolism and gut microbiota. METHODS: Untargeted nuclear magnetic resonance (NMR) metabolomics of blood plasma and fecal extracts was carried out, in tandem with qPCR analysis of feces, to assess the impact of an 8-week pilot legumes diet intervention on the fecal and plasma metabolomes and gut microbiota of 19 subjects. RESULTS: While the high inter-individual variability hindered the detection of statistically significant changes in the gut microbiome, increased fecal glucose and decreased threonine levels were noted. Correlation analysis between the microbiome and fecal metabolome lead to putative hypotheses regarding the metabolic activities of prevalent bacteria groups (Clostridium leptum subgroup, Roseburia spp., and Faecalibacterium prausnitzii). These included elevated fecal glucose as a preferential energy source, the involvement of valerate/isovalerate and reduced protein degradation in gut microbiota. Plasma metabolomics advanced mannose and betaine as potential markers of legume intake and unveiled a decrease in formate and ketone bodies, the latter suggesting improved energy utilization through legume carbohydrates. Amino acid metabolism was also apparently affected, as suggested by lowered urea, histidine and threonine levels. CONCLUSIONS: Despite the high inter-individual gut microbiome variability characterizing the small cohort addressed, combination of microbiological measurements and untargeted metabolomics unveiled several metabolic effects putatively related to legumes intake. If confirmed in larger cohorts, our findings will support the inclusion of legumes in diets and contribute valuable new insight into the origins of associated health benefits.

Magnetoelastic Coupling Evidence by Anisotropic Crossed Thermal Expansion in Magnetocaloric RSrCoFeO6 (R = Sm, Eu) Double Perovskites.

Double perovskite oxides, characterized by their tunable magnetic properties and robust interconnection between the lattice and magnetic degrees of freedom, present an enticing foundation for advanced magnetic refrigeration materials. Herein, we delve into the influence of rare-earth elements on RSrCoFeO6 (R = Sm, Eu) disordered double perovskites by examining their structural, electronic, magnetic, and magnetocaloric properties. Temperature-dependent synchrotron X-ray diffraction analysis confirmed the stability of the orthorhombic phase (Pnma) across a wide temperature range. X-ray photoemission spectroscopy revealed that both Sm and Eu are in the 3+ state, whereas multiple states for Co2+/3+ and Fe3+/4+ are identified. The magnetic investigation and magnetocaloric effect (MCE) analysis brought to light the presence of a long-range antiferromagnetic (AFM) order with a second-order phase transition (SOPT) in both samples. The maximum magnetic entropy change ΔSMmax was approximately 0.9 J/kg K for both samples at applied field 0-7 T, manifesting prominently above Neel temperatures TN ≈ 93 K (Sm) and 84 K (Eu). Nevertheless, different relative cooling powers (RCP) of 112.6 J/kg (Sm) and 95.5 J/kg (Eu) were observed. A detailed analysis of the temperature-dependent lattice parameters shed light on a distinct magnetocaloric effect across the magnetic transition temperature, unveiling an anisotropic thermal expansion [αV = 1.41 × 10-5 K-1 (Sm) and αV = 1.54 × 10-5 K-1 (Eu)] wherein the thermal expansion axial ratio αbSm/αbEu = 0.61 became lower with increasing temperature, which suggests that the Eu sample experiences a greater thermal expansion in the b-axis direction. At the atomic bonding level, the evidence for magnetoelastic coupling around the magnetic transition temperatures TN was found through the anomalies along the average Co/Fe-O bond distance, formal valence, octahedral distortion, as well as an anisotropic lattice expansion.

Elucidating the Magnetoelastic Coupling, Pressure-Dependent Magnetic Behavior, and Anomalous Hall Effect in FexTi2S4 Intercalation Sulfides.

Transition-metal chalcogenides with intercalated layered structures are interesting systems in material physics due to their attractive electronic and magnetic properties, with applications in the fields of magnetic refrigerators, catalysts, and thermoelectrics, among others. In this work, we studied in detail the structural, electronic, and magnetic properties of (Fe,Ti)-based sulfides with formula FexTi2S4 (x = 0.24, 0.32, and 0.42), prepared as polycrystalline materials under high-pressure conditions. They present a layered Heideite-type crystal structure, as assessed by synchrotron X-ray diffraction. A local structure analysis using Fe K-edge extended X-ray-absorption fine structure (EXAFS) data unveiled a conspicuous contraction of the main Fe-S bond in Fe0.24Ti2S4 at the vicinity of the magnetic transition 60-80 K. We suggest that this anomaly is related to magnetoelastic coupling effects. The EXAFS analysis allowed extraction of the Einstein temperatures (θE), i.e., the phonon contribution to the specific heat, for the two bond pairs Fe-S(1) [θE ≈318 K; 290 K (C/T)] and Fe-Ti(1) [θE ≈218 K; 190 K (C/T)]. In addition to the structural and local vibrational measurements, we probed the magnetic properties using magneto-calorimetry, magnetometry under applied pressure, magnetoresistance (MR), and Hall effect measurements. We observed the appearance of a broad peak in the specific heat around 120 K in the x = 0.42 compound that we associated with an antiferromagnetic ordering electronic transition. We found that the antiferromagnetic transition temperature is pressure and composition sensitive and reduces at 1.2 GPa by ∼12 and ∼3 K, for the members with x = 0.24 and x = 0.42, respectively. Similarly, the saturation magnetization in the ordered phase depends on both pressure and iron content, reducing its value by 50, 90, and 30% for x = 0.24, 0.32, and 0.42, respectively. We observed clear jumps in the magnetic hysteresis loops, MR, and anomalous Hall effect (AHE) below 2 K at fields around 2-4 T. We associated this observation with the metamagnetic transitions; from the Berry-curvature a decoupling parameter of SH = 0.12 V-1 is determined. Comparison of the results on the temperature-dependent magnetization, MR, and AHE elucidates a strong inelastic scattering contribution to the AHE at higher temperatures due to the cluster spin-glass phase.

Development of multi-residue gas chromatography coupled with mass spectrometry methodologies for the measurement of 15 chemically different disinfection by-products (DBPs) of emerging concern in drinking water from two different Portuguese water treatment plants.

In water treatment plants (WTPs), chemical agents, such as chlorine and ozone, might react with organic matter and anthropogenic contaminants, forming a high diversity of disinfection by-products (DBPs). Due to the potential toxicological effects, the identification of unregulated DBPs (UR-DBPs) is critical to help water managers in the selection of effective water treatment processes, contributing to improving water safety plans. Given the limited validated analytical methods to detect UR-DBPs, here we developed new multi-residue gas chromatography coupled with mass spectrometry methodologies for the detection and quantification of 15 UR-DBPs, including aldehydes, haloketones (HKs), nitrosamines and alcohols, in drinking water matrices. Solid-phase extraction (SPE), for the nitrosamine group, and solid-phase micro extraction (SPME), for the remaining DBPs, were used as sample preparation methods. The developed methodologies allowed the quantification of target UR-DBPs at trace concentration levels (ng L-1), with method quantification limits (MQLs) ranging from 14.4 ng L-1 to 26.0 ng L-1 (SPE-GC-MS) and 2.3 ng L-1 and 1596 ng L-1 (SPME-GC-MS). The methods were applied to different drinking water matrices, considering distinct delivery points of EPAL - Empresa Portuguesa das Águas Livres WTPs. Overall, the aldehyde group, represented by decanal, nonanal and 2-ethylheaxanal, showed the highest occurrence, followed by HKs and nitrosamines. The results of this study suggested that the formation of these UR-DBPs should be further monitored in WTPs.

Systematic Review and Meta-Analysis of Mass Spectrometry Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Schizophrenia.

Mass spectrometry (MS)-based techniques can be a powerful tool to identify neuropsychiatric disorder biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids of schizophrenia (SCZ) patients to identify disease biomarkers and relevant networks of biological pathways. Following PRISMA guidelines, a search was performed for studies that used MS proteomics approaches to identify proteomic differences between SCZ patients and healthy control groups (PROSPERO database: CRD42021274183). Nineteen articles fulfilled the inclusion criteria, allowing the identification of 217 differentially expressed proteins. Gene ontology analysis identified lipid metabolism, complement and coagulation cascades, and immune response as the main enriched biological pathways. Meta-analysis results suggest the upregulation of FCN3 and downregulation of APO1, APOA2, APOC1, and APOC3 in SCZ patients. Despite the proven ability of MS proteomics to characterize SCZ, several confounding factors contribute to the heterogeneity of the findings. In the future, we encourage the scientific community to perform studies with more extensive sampling and validation cohorts, integrating omics with bioinformatics tools to provide additional comprehension of differentially expressed proteins. The produced information could harbor potential proteomic biomarkers of SCZ, contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.

Systematic Review and Meta-Analysis on MS-Based Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Bipolar Disorder.

Bipolar disorder (BD) is a clinically heterogeneous condition, presenting a complex underlying etiopathogenesis that is not sufficiently characterized. Without molecular biomarkers being used in the clinical environment, several large screen proteomics studies have been conducted to provide valuable molecular information. Mass spectrometry (MS)-based techniques can be a powerful tool for the identification of disease biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids to assess BD biomarkers and identify relevant networks of biological pathways. Following PRISMA guidelines, we searched for studies using MS proteomics to identify proteomic differences between BD patients and healthy controls (PROSPERO database: CRD42021264955). Fourteen articles fulfilled the inclusion criteria, allowing the identification of 266 differentially expressed proteins. Gene ontology analysis identified complement and coagulation cascades, lipid and cholesterol metabolism, and focal adhesion as the main enriched biological pathways. A meta-analysis was performed for apolipoproteins (A-I, C-III, and E); however, no significant differences were found. Although the proven ability of MS proteomics to characterize BD, there are several confounding factors contributing to the heterogeneity of the findings. In the future, we encourage the scientific community to use broader samples and validation cohorts, integrating omics with bioinformatics tools towards providing a comprehensive understanding of proteome alterations, seeking biomarkers of BD, and contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.

Thermal Expansion and Rattling Behavior of Gd-Filled Co4Sb12 Skutterudite Determined by High-Resolution Synchrotron X-ray Diffraction.

In this work, Gd-filled skutterudite GdxCo4Sb12 was prepared using one step method under high pressure in a piston-cylinder-based press at 3.5 GPa and moderate temperature of 800 °C. A detailed structural characterization was performed using synchrotron X-ray diffraction (SXRD), revealing a filling fraction of x = 0.033(2) and an average bond length of 3.3499(3) Å. The lattice thermal expansion accessed via temperature-dependent SXRD led to a precise determination of a Debye temperature of 322(3) K, from the fitting of the unit-cell volume expansion using the second order Grüneisen approximation. This parameter, when evaluated through the mean square displacements of Co and Sb, displayed a value of 265(2) K, meaning that the application of the harmonic Debye theory underestimates the Debye temperature in skutterudites. Regarding the Gd atom, its intrinsic disorder value was ~5× and ~25× higher than those of the Co and Sb, respectively, denoting that Gd has a strong rattling behavior with an Einstein temperature of θE = 67(2) K. As a result, an ultra-low thermal conductivity of 0.89 W/m·K at 773 K was obtained, leading to a thermoelectric efficiency zT of 0.5 at 673 K.

Assessment of Water Quality Parameters and their Seasonal Behaviour in a Portuguese Water Supply System: a 6-year Monitoring Study.

Water quality monitoring is a fundamental tool in the management of freshwater resources. The purpose of monitoring is to provide meaningful quality data for local action planning and catchment-wide decision making. The assessment of water quality is crucial to guarantee the efficient operation of the Water Treatment Plants (WTPs), promoting health conditions and contributing for a more sustainable urban water cycle. In accordance, the objective of this study was to evaluate key target chemical and microbiological water quality parameters, some of them already monitored within Portuguese/EU legal framework and others still not regulated, but with environmental and human heath relevance. A local monitoring database model, using a 6-year period (from 2014 to 2019) of water quality data, regarding water samples collected on representative sampling locations covering the freshwater abstraction sites, conventional WTPs and distribution network was assessed. This work provides new knowledge regarding occurrence and seasonal behaviour for both microbiological and chemical water quality parameters, essential to understand/manage the water supply system. Additionally, relationships between the target variables were also assessed. Particularly, strong correlations were identified between TOC and THMs formation at distribution network (r = 0.69; p ≤ 0.001); nitrates were the water quality parameter that revealed the best correlation between surface water source and treated water (r = 0.81; p ≤ 0.001), suggesting that treatment yield/performance is dependent on surface water load. The local and continuous monitoring of water systems are crucial to implement new approaches to guarantee the best quality of drinking water throughout the supply system.

Enhanced stability in CH3NH3PbI3 hybrid perovskite from mechano-chemical synthesis: structural, microstructural and optoelectronic characterization.

Among the hybrid organic-inorganic perovskites MAPbX3 (MA: methyl-ammonium CH3-NH3+, X = halogen), the triiodide specimen (MAPbI3) is still the material of choice for solar energy applications. Although it is able to absorb light above its 1.6 eV bandgap, its poor stability in humid air atmosphere has been a major drawback for its use in solar cells. However, we discovered that this perovskite can be prepared by ball milling in a straightforward way, yielding specimens with a superior stability. This fact allowed us to take atomic-resolution STEM images for the first time, with sufficient quality to unveil microscopic aspects of this material. We demonstrated full Iodine content, which might be related to the enhanced stability, in a more compact PbI6 framework with reduced unit-cell volume. A structural investigation from neutron powder diffraction (NPD) data of an undeuterated specimen was essential to determine the configuration of the organic MA unit in the 100-298 K temperature range. A phase transition is identified, from the tetragonal structure observed at RT (space group I4/mcm) to an orthorhombic (space group Pnma) phase where the methyl-ammonium organic units are fully localized. Our NPD data reveal that the MA changes are gradual and start before reaching the phase transition. Optoelectronic measurements yield a photocurrent peak at an illumination wavelength of 820 nm, which is redshifted by 30 nm with respect to previously reported measurements on MAPbI3 perovskites synthesized by crystallization from organic solvents.

Bioaugmentation of membrane bioreactor with Achromobacter denitrificans strain PR1 for enhanced sulfamethoxazole removal in wastewater.

Achromobacter denitrificans strain PR1, previously found to harbour specific degradation pathways with high sulfamethoxazole (SMX) degradation rates, was bioaugmented into laboratory-scale membrane bioreactors (MBRs) operated under aerobic conditions to treat SMX-containing real domestic wastewater. Different hydraulic retention times (HRTs), which is related to reaction time and loading rates, were considered and found to affect the SMX removal efficiency. The availability of primary substrates was important in both bioaugmented and non-bioaugmented activated sludge (AS) for cometabolism of SMX. High HRT (24 h) resulted in low food to microorganism ratio (F/M) and low SMX removal, due to substrate limitation. Decrease in HRT from 24 h to 12 h, 6 h and finally 4 h led to gradual increases in primary substrates availability, e.g. organic compounds and ammonia, resulted in increased SMX removal efficiency and degradation rate, and is more favorable for high-rate wastewater treatment processes. After inoculation into the MBRs, the bioaugmentation strain was sustained in the reactor for a maximum of 31 days even though a significant decrease in abundance was observed. The bioaugmented MBRs showed enhanced SMX removal, especially under SMX shock loads compared to the control MBRs. The results of this study indicate that re-inoculation is required regularly after a period of time to maintain the removal efficiency of the target compound.

NMR metabolomics of esca disease-affected Vitis vinifera cv. Alvarinho leaves.

Esca is a destructive disease that affects vineyards leading to important losses in wine production. Information about the response of Vitis vinifera plants to this disease is scarce, particularly concerning changes in plant metabolism. In order to study the metabolic changes in Vitis plants affected by esca, leaves from both infected and non-affected cordons of V. vinifera cv. Alvarinho (collected in the Vinho Verde region, Portugal) were analysed. The metabolite composition of leaves from infected cordons with visible symptoms [diseased leaves (dl)] and from asymptomatic cordons [healthy leaves (hl)] was evaluated by 1D and 2D (1)H-nuclear magnetic resonance (NMR) spectroscopy. Principal component analysis (PCA) of the NMR spectra showed a clear separation between dl and hl leaves, indicating differential compound production due to the esca disease. NMR/PCA analysis allowed the identification of specific compounds characterizing each group, and the corresponding metabolic pathways are discussed. Altogether, the study revealed a significant increase of phenolic compounds in dl, compared with hl, accompanied by a decrease in carbohydrates, suggesting that dl are rerouting carbon and energy from primary to secondary metabolism. Other metabolic alterations detected comprised increased levels of methanol, alanine, and gamma-aminobutyric acid in dl, which might be the result of the activation of other defence mechanisms.