Role of HO/CO in the Control of Peripheral Circulation in Humans

Experimental studies show that the heme oxygenase/carbon monoxide system (HO/CO) plays an important role in the homeostasis of circulation and in the pathophysiology of hypertension. No data are available on its role in the control of peripheral circulation in humans. We evaluated the effects of inhibition of HO with stannous mesoporphyrin IX (SnMP) (200 μM) locally administered by iontophoresis, on human skin blood flow, evaluated by laser-Doppler flowmetry, in the presence and absence of nitric oxide synthase (NOS) inhibition with L-NG-Nitroarginine methyl ester (L-NAME) (100 μM). We also evaluated the effect of HO inhibition on vasodilatation induced by acetylcholine (ACh) and vasoconstriction caused by noradrenaline (NA). SnMP and L-NAME caused a similar 20–25% decrease in skin flow. After nitric oxide (NO) inhibition with L-NAME, HO inhibition with SnMP caused a further 20% decrease in skin perfusion. SnMP decreased vasodilatation induced by ACh by about 70%, while it did not affect vasoconstriction to NA. In conclusion, HO/CO participates in the control of peripheral circulation, independently from NO, and is involved in vasodilatation to ACh

Smart decomposition of cyclic alanine-alanine dipeptide by VUV radiation: a seed for the synthesis of biologically relevant species

A combined experimental and theoretical study shows how the interaction of VUV radiation with cyclo-(alanine-alanine), one of the 2,5-diketopiperazines (DKPs), produces reactive oxazolidinone intermediates. The theoretical simulations reveal that the interaction of these intermediates with other neutral and charged fragments, released in the molecular decomposition, leads either to the reconstruction of the cyclic dipeptide or to the formation of longer linear peptide chains. These results may explain how DKPs could have, on one hand, survived hostile chemical environments and, on the other, provided the seed for amino acid polymerization. Shedding light on the mechanisms of production of such prebiotic building blocks is of paramount importance to understanding the abiotic synthesis of relevant biologically active compoundsThis article is based upon work from COST action CA18212 - Molecular Dynamics in the GAS phase (MD-GAS), supported by COST (European Cooperation in Science and Technology). The authors acknowledge the generous allocation of computer time at the Centro de Computación Cientıfí ca at the Universidad Autonoma de Madrid (CCC-UAM). This work ́ was partially supported by MICINN (Spanish Ministry of Science and Innovation) project PID2019-110091GB-I00, the “Marıa de Maeztu ́ ” (CEX2018-000805-M) Program for Centers of Excellence in R&D, MAECI Italy-Sweden project “Novel molecular tools for the exploration of the nanoworld”, and PRIN 20173B72NB project “Predicting and controlling the fate of biomolecules driven by extreme-ultraviolet radiation”. D.B.-L. acknowledges the FPI grant associated with MICINN project CTQ2016-76061-P. H.Z. acknowledges the Swedish Research Council for the individual project grant with contract no. 2020- 0343

Organic Light-Emitting Transistors in a Smart-Integrated System for Plasmonic-Based Sensing

AbstractThe smart integration of multiple devices in a single functional unit is boosting the advent of compact optical sensors for on‐site analysis. Nevertheless, the development of miniaturized and cost‐effective plasmonic sensors is hampered by the strict angular constraints of the detection scheme, which are fulfilled through bulky optical components. Here, an ultracompact system for plasmonic‐sensing is demonstrated by the smart integration of an organic light‐emitting transistor (OLET), an organic photodiode (OPD), and a nanostructured plasmonic grating (NPG). The potential of OLETs, as planar multielectrode devices with inherent micrometer‐wide emission areas, offers the pioneer incorporation of an OPD onto the source electrode to obtain a monolithic photonic module endowed with light‐emitting and light‐detection characteristics at unprecedented lateral proximity of them. This approach enables the exploitation of the angle‐dependent sensing of the NPG in a miniaturized system based on low‐cost components, in which a reflective detection is enabled by the elegant fabrication of the NPG onto the encapsulation glass of the photonic module. The most effective layout of integration is unraveled by an advanced simulation tool, which allows obtaining an optics‐less plasmonic system able to perform a quantitative detection up to 10−2 RIU at a sensor size as low as 0.1 cm3

Symbolic Implementation of Connectors in BIP

BIP is a component framework for constructing systems by superposing three layers of modeling: Behavior, Interaction, and Priority. Behavior is represented by labeled transition systems communicating through ports. Interactions are sets of ports. A synchronization between components is possible through the interactions specified by a set of connectors. When several interactions are possible, priorities allow to restrict the non-determinism by choosing an interaction, which is maximal according to some given strict partial order. The BIP component framework has been implemented in a language and a tool-set. The execution of a BIP program is driven by a dedicated engine, which has access to the set of connectors and priority model of the program. A key performance issue is the computation of the set of possible interactions of the BIP program from a given state. Currently, the choice of the interaction to be executed involves a costly exploration of enumerative representations for connectors. This leads to a considerable overhead in execution times. In this paper, we propose a symbolic implementation of the execution model of BIP, which drastically reduces this overhead. The symbolic implementation is based on computing boolean representation for components, connectors, and priorities with an existing BDD package

A systematic study of the valence electronic structure of cyclo(Gly–Phe), cyclo(Trp–Tyr) and cyclo(Trp–Trp) dipeptides in the gas phase

The electronic energy levels of cyclo(glycine–phenylalanine), cyclo(tryptophan–tyrosine) and cyclo(tryptophan–tryptophan) dipeptides are investigated with a joint experimental and theoretical approach. Experimentally, valence photoelectron spectra in the gas phase are measured using VUV radiation. Theoretically, we first obtain low-energy conformers through an automated conformer–rotamer ensemble sampling scheme based on tight-binding simulations. Then, different first principles computational schemes are considered to simulate the spectra: Hartree–Fock (HF), density functional theory (DFT) within the B3LYP approximation, the quasi-particle GW correction, and the quantumchemistry CCSD method. Theory allows assignment of the main features of the spectra. A discussion on the role of electronic correlation is provided, by comparing computationally cheaper DFT scheme (and GW) results with the accurate CCSD method

SNAP-25 Single Nucleotide Polymorphisms, Brain Morphology and Intelligence in Children With Borderline Intellectual Functioning: A Mediation Analysis

Borderline intellectual functioning (BIF) is a multifactorial condition in which both genetic and environmental factors are likely to contribute to the clinical outcome. Abnormal cortical development and lower IQ scores were shown to be correlated in BIF children, but the genetic components of this condition and their possible connection with intelligence and brain morphology have never been investigated in BIF. The synaptosomal-associated protein of 25 kD (SNAP-25) is involved in synaptic plasticity, neural maturation, and neurotransmission, affecting intellectual functioning. We investigated SNAP-25 polymorphisms in BIF and correlated such polymorphisms with intelligence and cortical thickness, using socioeconomic status and environmental stress as covariates as a good proxy of the variables that determine intellectual abilities. Thirty-three children with a diagnosis of BIF were enrolled in the study. SNAP-25 polymorphisms rs363050, rs363039, rs363043, rs3746544, and rs1051312 were analyzed by genotyping; cortical thickness was studied by MRI; intelligence was measured using the WISC-III/IV subscales; environmental stressors playing a role in neuropsychiatric development were considered as covariate factors. Results showed that BIF children carrying the rs363043(T) minor allele represented by (CT C TT) genotypes were characterized by lower performance Perceptual Reasoning Index and lower full-scale IQ scores (p = 0.04) compared to those carrying the (CC) genotype. This association was correlated with a reduced thickness of the left inferior parietal cortex (direct effect = 0.44) and of the left supramarginal gyrus (direct effect = 0.56). These results suggest a link between SNAP-25 polymorphism and intelligence with the mediation role of brain morphological features in children with BIF

Gas Phase Oxidation of Carbon Monoxide by Sulfur Dioxide Radical Cation: Reaction Dynamics and Kinetic Trend With the Temperature

Gas phase ion chemistry has fundamental and applicative purposes since it allows the study of the chemical processes in a solvent free environment and represents models for reactions occurring in the space at low and high temperatures. In this work the ion-molecule reaction of sulfur dioxide ion SO2.+ with carbon monoxide CO is investigated in a joint experimental and theoretical study. The reaction is a fast and exothermic chemical oxidation of CO into more stable CO2 by a metal free species, as SO2.+, excited into ro-vibrational levels of the electronic ground state by synchrotron radiation. The results show that the reaction is hampered by the enhancement of internal energy of sulfur dioxide ion and the only ionic product is SO.+. The theoretical approach of variational transition state theory (VTST) based on density functional electronic structure calculations, shows an interesting and peculiar reaction dynamics of the interacting system along the reaction path. Two energy minima corresponding to [SO2–CO].+ and [OS–OCO].+ complexes are identified. These minima are separated by an intersystem crossing barrier which couples the bent 3B2 state of CO2 with C2v symmetry and the 1A1 state with linear D∞h symmetry. The spin and charge reorganization along the minimum energy path (MEP) are analyzed and eventually the charge and spin remain allocated to the SO.+ moiety and the stable CO2 molecule is easily produced. There is no bottleneck that slows down the reaction and the values of the rate coefficient k at different temperatures are calculated with capture theory. A value of 2.95 × 10−10 cm3s−1molecule−1 is obtained at 300 K in agreement with the literature experimental measurement of 3.00 × 10−10 ± 20% cm3s−1molecule−1, and a negative trend with temperature is predicted consistently with the experimental observations

Mycobacterial and Human Ferrous Nitrobindins: Spectroscopic and Reactivity Properties

Structural and functional properties of ferrous Mycobacterium tuberculosis (Mt-Nb) and human (Hs-Nb) nitrobindins (Nbs) were investigated. At pH 7.0 and 25.0 °C, the unliganded Fe(II) species is penta-coordinated and unlike most other hemoproteins no pH-dependence of its coordination was detected over the pH range between 2.2 and 7.0. Further, despite a very open distal side of the heme pocket (as also indicated by the vanishingly small geminate recombination of CO for both Nbs), which exposes the heme pocket to the bulk solvent, their reactivity toward ligands, such as CO and NO, is significantly slower than in most hemoproteins, envisaging either a proximal barrier for ligand binding and/or crowding of H2O molecules in the distal side of the heme pocket which impairs ligand binding to the heme Fe-atom. On the other hand, liganded species display already at pH 7.0 and 25 °C a severe weakening (in the case of CO) and a cleavage (in the case of NO) of the proximal Fe-His bond, suggesting that the ligand-linked movement of the Fe(II) atom onto the heme plane brings about a marked lengthening of the proximal Fe-imidazole bond, eventually leading to its rupture. This structural evidence is accompanied by a marked enhancement of both ligands dissociation rate constants. As a whole, these data clearly indicate that structural-functional relationships in Nbs strongly differ from what observed in mammalian and truncated hemoproteins, suggesting that Nbs play a functional role clearly distinct from other eukaryotic and prokaryotic hemoproteins

Urinary Benzene Biomarkers and DNA Methylation in Bulgarian Petrochemical Workers: Study Findings and Comparison of Linear and Beta Regression Models

Chronic occupational exposure to benzene is associated with an increased risk of hematological malignancies such as acute myeloid leukemia (AML), but the underlying mechanisms are still unclear. The main objective of this study was to investigate the association between benzene exposure and DNA methylation, both in repeated elements and candidate genes, in a population of 158 Bulgarian petrochemical workers and 50 unexposed office workers. Exposure assessment included personal monitoring of airborne benzene at work and urinary biomarkers of benzene metabolism (S-phenylmercapturic acid [SPMA] and trans,trans-muconic acid [t,t-MA]) at the end of the work-shift. The median levels of airborne benzene, SPMA and t,t-MA in workers were 0.46 ppm, 15.5 µg/L and 711 µg/L respectively, and exposure levels were significantly lower in the controls. Repeated-element DNA methylation was measured in Alu and LINE-1, and gene-specific methylation in MAGE and p15. DNA methylation levels were not significantly different between exposed workers and controls (P>0.05). Both ordinary least squares (OLS) and beta-regression models were used to estimate benzene-methylation associations. Beta-regression showed better model specification, as reflected in improved coefficient of determination (pseudo $R^2$) and Akaike’s information criterion (AIC). In beta-regression, we found statistically significant reductions in LINE-1 (−0.15%, P<0.01) and p15 (−0.096%, P<0.01) mean methylation levels with each interquartile range (IQR) increase in SPMA. This study showed statistically significant but weak associations of LINE-1 and p15 hypomethylation with SPMA in Bulgarian petrochemical workers. We showed that beta-regression is more appropriate than OLS regression for fitting methylation data

Electron and ion spectroscopy of Azobenzene in the valence and core shells

Azobenzene is a prototype and building block of a class of molecules of extreme technological interest as molecularphoto-switches. We present a joint experimental and theoretical study of its response to irradiation with light across theUV to X-ray spectrum. The study of valence and inner shell photo-ionization and excitation processes, combined withmeasurement of valence photoelectron-photoion coincidence (PEPICO) and of mass spectra across the core thresholdsprovides a detailed insight onto the site- and state-selected photo-induced processes. Photo-ionization and excita-tion measurements are interpreted via the multi-configurational restricted active space self-consistent field (RASSCF)method corrected by second order perturbation theory (RASPT2). Using static modelling, we demonstrate that thecarbon and nitrogen K edges of Azobenzene are suitable candidates for exploring its photoinduced dynamics thanks tothe transient signals appearing in background-free regions of the NEXAFS and XP