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We assessed the interactions among the particulate matter (PM) components in generating the reactive oxygen species (ROS) based on a dithiothreitol (DTT) assay. We started with the standard solutions of known redox-active substances, i.e. quinones (9,10-phenanthraquinone, 1,2-naphthoquinone, 1,4-naphthoquinone and 5-hydroxy-1,4-naphthoquinone) and metals [Cu (II), Mn (II) and Fe (II)]. Both DTT consumption and hydroxyl radical (•OH) generation were measured in the DTT assay. The interactions of Fe were additive with quinones in DTT consumption, but strongly synergistic in •OH generation. Cu showed antagonistic interactions with quinones in both DTT consumption and •OH generation. Mn interacted synergistically with quinones in DTT oxidation, but antagonistically in •OH generation. The nature of the interactions of these metals (Fe, Mn and Cu) with ambient humic-like substances (HULIS) resembled to that with quinones, although the intensity of interactions were weaker in DTT consumption than •OH generation. Finally, we demonstrated that the DTT consumption capability of ambient PM can be well explained by HULIS, three transition metals (Fe, Mn and Cu), and their interactions. But, •OH generation involves a contribution (~50 %) from additional compounds (aliphatic species or metals other than Fe, Cu and Mn) present in the hydrophilic PM fraction. The study highlights the need to account for the interactions between organic compounds and metals, while apportioning the relative contributions of chemical components in the PM oxidative potential.

Concepts: Photosynthesis, Oxygen, Iron, Oxidative phosphorylation, Reactive oxygen species, Carbon, Hydrogen peroxide, Chemical compound

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Structural properties of Aβ(16-35) fragment are investigated as a model for the amyloid-β peptide excluding its coil-inducing terminals. Our Replica-Exchange Molecular Dynamics simulations using all-atoms and explicit aqueous solvation widely reduce any structural bias. The principal folding pathway shows direct conversion of coil to β-sheet, without the long proposed helix intermediates. Our PCA analysis indicates that the fragment is also intrinsically disordered, as the full amyloid-β peptide. Thus, the observed folding mechanism lacks free-energy barriers and any peaks in the thermal capacity.

Concepts: Alzheimer's disease, Scientific method, Molecular dynamics, Matter, Concentration, Chemistry, Solutions, Aqueous solution

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Myeloperoxidase (MPO) is a protein present in azurophilic granules, macrophages, and neutrophils that are released into extracellular fluid (ECF) during inflammation. MPO releases hypochlorous acid (HOCL) and other chlorinated species. It is derived from hydrogen peroxide (H2O2) showing response during inflammatory conditions and plays a role in the immune defense against pathogens. MPO may show unwanted effects by indirectly increasing the formation of reactive nitrogen species (RNS), reactive oxygen species (ROS), and tumor necrosis factor alpha (TNF-α) leading to inflammation and oxidative stress. As neuroinflammation is one of the inevitable biological components among most of the neurological disorders, MPO and its receptor may be explored as candidates for future clinical interventions. The purpose of this review is to provide an overview of the pathophysiological characteristics of MPO and further explore the possibilities to target it for clinical use. Targeting MPO is promising and may open an avenue to act as a biomarker for diagnosis with defined risk stratification on patients with various neurological disorders.

Concepts: Immune system, Inflammation, Oxygen, Oxidative stress, Reactive oxygen species, Hydrogen peroxide, Chlorine, Tumor necrosis factor-alpha

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Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is one of the most powerful methods to analyze biomolecules in biological tissues and cells because it provides detailed chemical structure information and chemical images with a high spatial resolution. However, in terms of quantitative analysis, there are issues such as matrix effects that often cause secondary ion intensity changes regardless of the actual concentration in a sample. For instance, the intensity of secondary ions related to peptides is generally suppressed when lipids coexist. Since the evaluation of biomolecules is crucial to understand biological phenomena, it is required to analyze peptides or lipids without matrix effects. Therefore, the mechanism of matrix effects regarding peptides and lipids in TOF-SIMS was investigated in this study. Leu-enkephalin (YGGFL, molecular weight of 555.3 Da) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, C44H84NO8P, molecular weight 785.6 Da) were employed to prepare model samples. Model samples contain different weight ratios of these two molecules. The intensity of secondary ions related to the peptide or the lipid was compared with control samples containing pure leu-enkephalin or DOPC. As a result, it is indicated that the intensity of DOPC related secondary ions is strongly enhanced by coexisting leu-enkephalin, while the intensity of leu-enkephalin related secondary ions is suppressed by coexisting DOPC especially in a low concentration range of the peptide.

Concepts: Protein, Molecular biology, Mass spectrometry, Organism, Molecule, Chemistry, Atom, Ion

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Mitochondria are the energetic, metabolic, redox and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1-5) play an eminent role in the regulation of each of the above aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, while uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δp dissipation decreases superoxide formation dependent on Δp. UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate and malate antiport with phosphate is expected to alter metabolism of cancer cells.

Concepts: DNA, Protein, Metabolism, Adenosine triphosphate, Mitochondrion, RNA, Cellular respiration, Citric acid cycle

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This essay elaborates on Ursula Klein’s methodological concept of “paper tools” by drawing on several examples from the history of the periodic table. Moving from John A. R. Newlands’s “Law of Octaves,” to Dmitrii Mendeleev’s first drafts of his periodic system in 1869, to Mendeleev’s chemical speculations on the place of the ether within his classification, one sees that the ways in which the scientists presented the balance between empirical data and theoretical manipulation proved crucial for the chemical community’s acceptance or rejection of their proposed innovations. This negotiated balance illustrates an underemphasised feature of Klein’s conceptualisation of the ways in which a paper tool generates new knowledge.

Concepts: Chemistry, Chemical element, Periodic table, Germanium, Atomic number, Gallium, Dmitri Mendeleev, History of the periodic table

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GPs undertaking the Induction and Refresher (I&R) Scheme in England spend a period of between 4 weeks and 6 months in placements in a General Practice setting. During this time they have to complete a number of workplace-based assessments, and their Educational Supervisor is required to complete a report which confirms that they have demonstrated an adequate level of competence to enable them to be accepted by NHS England onto the National Medical Performers List without conditions. This report describes a process (using an online survey completed by Educational Supervisors) of reviewing and improving the end-of-placement report forms to make them clearer and easier to use. The word pictures used in the revised forms could be adapted to become a competency framework for members of the primary care workforce.

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The purpose of the present study is to compare results from the 12-item General Functioning Scale (GF-FAD) of the Family Assessment Device (FAD) to a three-item version, the Brief Assessment of Family Functioning Scale (BAFFS), designed to be used when brevity is especially important. We used principal components analysis of the GF-FAD, followed by multiple sample confirmatory factor analyses to test the robustness of the BAFFS in different samples. The BAFFS correlated highly with the GF-FAD, and demonstrated good concurrent validity with another measure of global marital functioning, the Dyadic Adjustment Scale-4 in a help-seeking sample. Like the 12-item version, the BAFFS moderately correlated with an objective, interview-based rating of family functioning, the McMaster Clinical Rating Scale. The BAFFS appears to serve as a good proxy for the GF-FAD when an ultra-brief family assessment measure is needed. Clinical or methodological significance of this article: This article introduces an ultra-brief measure of general family functioning that can easily be used in routine clinical practice. The measure can be used to track change over time, and to get a quick “snap shot” of how family members perceive the general emotional climate in their family.

Concepts: Family, Clinical trial, Psychometrics, Factor analysis, Principal component analysis, 2006 albums, Confirmatory factor analysis, Singular value decomposition

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Tracking newly emergent virulent populations in agroecosystems provides an opportunity to increase our understanding of the co-evolution dynamics of pathogens and their hosts. On the one hand host plants exert selective pressure on pathogen populations, thus dividing them into subpopulations of different virulence, while on the other hand they create an opportunity for secondary contact between the two divergent populations on one tree. The main objectives of the study were to explore whether the previously reported structure between two Venturia inaequalis population types, virulent or avirulent towards Malus x domestica cultivars carrying Rvi6 gene, is maintained or broken several years after the first emergence of new virulent strains in Poland, and to investigate the relationship between ‘new’ and ‘native’ populations derived from the same commercial orchards. For this purpose, we investigated the genetic structure of populations of the apple scab fungus, occurring on apple tree cultivars containing Rvi6, Rvi1 or Rvi17 resistance gene or no resistance at all, based on microsatellite data obtained from 606 strains sampled in 10 orchards composed of various host cultivars.

Concepts: HIV, Bacteria, Biology, Tree, Apple, Orchard, Apple scab, Venturia inaequalis

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The immunoglobulin (Ig) superfamily receptor Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of isoforms via alternative splicing, which is essential for both nervous and immune systems in insects. However, further information is required to develop a comprehensive view of Dscam diversification across the broad spectrum of Chelicerata clades, a basal branch of arthropods and the second largest group of terrestrial animals.

Concepts: Immune system, Protein, Gene expression, Bacteria, Evolution, Insect, Arthropod, Spider