The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as ...sterile wound healing, autoimmunity, cancer, and homeostasis. Here we discuss our current understanding of the regulation of IL-10 production and of the molecular pathways associated with IL-10 responses. In addition to IL-10's classic inhibitory effects on myeloid cells, we also describe the nonclassic roles attributed to this pleiotropic cytokine, including how IL-10 regulates basic processes of neural and adipose cells and how it promotes CD8 T cell activation, as well as epithelial repair. We further discuss its therapeutic potential in the context of different diseases and the outstanding questions that may help develop an effective application of IL-10 in diverse clinical settings.
In high-energy molecular dynamics or Monte Carlo simulations, standard force fields optimized for simulations at ambient temperatures are inadequate. This is largely because their repulsive parts ...have been regarded as not very significant, even well below zero interaction energies. It is, therefore, not obvious which force fields to resort to for simulating hot gases or plasmas. A force field model that uses the electronic densities of noninteracting atoms or molecules within the pair approximation is introduced. We start by deriving a naïve model that neglects any exchange and correlation effects between the electronic clouds and then correct this model by adding a term calibrated from ab initio calculations using the CCSD(T)/cc-pVTZ level of theory. The resulting expression for this term can be regarded as a simple exchange–correlation function. We compare the results for the repulsive part of the potential energy hypersurfaces with the force fields commonly used on some dimers of small molecules.
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IJS, KILJ, NUK, PNG, UL, UM
Secreted autotransporter toxin (Sat) is a 107-kDa serine protease autotransporter of Enterobacteriaceae (SPATE) presenting cytotoxic activity in renal and bladder cells. Further studies have detected ...the Sat-encoding gene (sat) in enteroaggregative Escherichia coli (EAEC) and in E. coli strains isolated from neonatal septicemia and meningitis. Here, we investigated the role of Sat as a cytotoxin of EAEC. Sat was purified from a strain of E. coli harboring sat (DEC/Sat+, O126:H2) and used to raise antibodies in rabbit. The presence of Sat was detected by ELISA in the supernatant of 93.7% of EAEC strains harboring sat and in none lacking the gene. The effect of Sat during infection was investigated in polarized Caco-2 cells infected with Sat-producing EAEC (CV323/77, O125ab:H21). This strain induced intense cell detachment, which was inhibited by PMSF or Sat antiserum. Also, sat transcription and Sat production were detected during infection. Here we demonstrate that Sat is internalized in polarized cells leading to F-actin disruption which preceded cell detachment. A comparative study of the toxin action in cell lines corresponding to the infection sites in which bacteria carrying the sat gene have been isolated was performed. Cells originating from the gastrointestinal tract (Caco-2), urinary (LLC-PK1) and endothelium (HUVEC) were incubated with purified Sat. The time required for observation of cell damage differed according to the cell line. HUVEC cells were more sensitive to Sat than cells derived from urinary and intestinal tracts. The intense activity of Sat on the endothelial cells suggests that Sat could also be a virulence factor for the bacteria in the bloodstream. In addition, this is the first work demonstrating that Sat induces cytotoxic effect during EAEC infection in vitro. The cell damage observed during infection indicates that Sat may be another toxin with cytotoxic role in the EAEC pathogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inspiratory Muscle Training Improves Blood Flow to Resting and Exercising Limbs in Patients With Chronic Heart Failure Gaspar R. Chiappa, Bruno T. Roseguini, Paulo J. C. Vieira, Cristiano N. Alves, ...Angela Tavares, Eliane R. Winkelmann, Elton L. Ferlin, Ricardo Stein, Jorge P. Ribeiro Patients with chronic heart failure (CHF) and inspiratory muscle weakness and healthy volunteers were submitted to inspiratory muscle loading by the addition of inspiratory resistance, while blood flow to the resting calf and exercising forearm were measured. For the patients with CHF, blood flow measurements were made before and after a 4-week program of inspiratory muscle training. In patients with CHF and inspiratory muscle weakness, inspiratory muscle loading resulted in marked reduction of blood flow to resting and exercising limbs. Inspiratory muscle training improved limb blood flow under inspiratory loading in these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dissociative electron transfer in collisions between neutral potassium atoms and neutral ethanol molecules yields mainly OH−, followed by C2H5O−, O−, CH3− and CH2−. The dynamics of negative ions have ...been investigated by recording time‐of‐flight mass spectra in a wide range of collision energies from 17.5 to 350 eV in the lab frame, where the branching ratios show a relevant energy dependence for low/intermediate collision energies. The dominant fragmentation channel in the whole energy range investigated has been assigned to the hydroxyl anion in contrast to oxygen anion from dissociative electron attachment (DEA) experiments. This result shows the relevant role of the electron donor in the vicinity of the temporary negative ion formed allowing access to reactions which are not thermodynamically attained in DEA experiments. The electronic state spectroscopy of such negative ions, was obtained from potassium cation energy loss spectra in the forward scattering direction at 205 eV impact energy, showing a prevalent Feshbach resonance at 9.36±0.10 eV with
σOH*/σCH*
${{\sigma }_{OH}^{^{\ast}}/{\sigma }_{CH}^{^{\ast}}}$
character, while a less pronounced
σOH*
${{\sigma }_{OH}^{^{\ast}}}$
contribution assigned to a shape resonance has been obtained at 3.16±0.10 eV. Quantum chemical calculations for the lowest‐lying unoccupied molecular orbitals in the presence of a potassium atom have been performed to support the experimental findings.
A joint experimental and theoretical investigation on ethanol negative ion formation by charge transfer is reported for the first time. The electronic state spectroscopy of the lowest‐lying anionic states is comprehensively discussed rendering special relevance to the role of the different shape and core‐excited Feshbach resonances, while the fragmentation pattern shows significant differences from dissociative electron attachment experiments.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Histidine is an aromatic amino acid crucial for the biological functioning of proteins and enzymes. When biological matter is exposed to ionising radiation, highly energetic particles interact with ...the surrounding tissue which leads to efficient formation of low‐energy electrons. In the present study, the interaction of low‐energy electrons with gas‐phase histidine is studied at a molecular level in order to extend the knowledge of electron‐induced reactions with amino acids. We report both on the formation of positive ions formed by electron ionisation and negative ions induced by electron attachment. The experimental data were complemented by quantum chemical calculations. Specifically, the free energies for possible fragmentation reactions were derived for the τ and the π tautomer of histidine to get insight into the structures of the formed ions and the corresponding neutrals. We report the experimental ionisation energy of (8.48 ± 0.03) eV for histidine which is in good agreement with the calculated vertical ionisation energy. In the case of negative ions, the dehydrogenated parent anion is the anion with the highest mass observed upon dissociative electron attachment. The comparison of experimental and computational results was also performed in view of a possible thermal decomposition of histidine during the experiments, since the sample was sublimated in the experiment by resistive heating of an oven. Overall, the present study demonstrates the effects of electrons as secondary particles in the chemical degradation of histidine. The reactions induced by those electrons differ when comparing positive and negative ion formation. While for negative ions, simple bond cleav ages prevail, the observed fragment cations exhibit partly restructuring of the molecule during the dissociation process.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Accurate total cross sections (TCS), within 5%, for electron scattering by N2O molecules have been measured with a magnetically confined electron transmission apparatus for impact energies ranging ...from 1 to 200 eV. For higher energies, these measurements have been complemented with our independent atom-based screening corrected additivity rule, including interference (IAM-SCAR + I) method to determine a complete reference TCS data set in the energy range (1–1000 eV). After a critical discussion that includes our calculated integral elastic and ionization cross sections and the theoretical and experimental data available in the literature, a complete set of integral elastic and inelastic (rotational, vibrational, and electronic excitation, ionization and electron attachment) cross sections, consistent with the reference TCS data, have been derived. This update on the N2O collisional database may help to improve the accuracy of radiation-induced transport models.
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Direct and non‐destructive measurements of plant‐water relations of plants exhibiting the Crassulacean acid metabolism (CAM) photosynthetic pathway are seldom addressed, with most findings inferred ...from gas exchange measurements. The main focus of this paper was to study how the water exchange between the chlorenchyma and the hydrenchyma depends on and follows the CAM photosynthetic diel pattern using non‐invasive and continuous methods. Gas exchange and leaf patch clamp pressure probe (LPCP) measurements were performed on Aloe vera (L.) Burm f., a CAM species, and compared to measurements on banana (Musa acuminata Colla), a C3 species. The LPCP output pressure, Pp, of Aloe vera plants follows its diel CAM photosynthetic cycle, reversed to that observed in banana and other C3 species. The four phases of CAM photosynthesis can also be identified in the diel LPCP output pressure, Pp, cycle. The Pp values in Aloe vera are determined by the hydrenchyma turgor pressure, with both parameters being reversely related. A non‐invasive and continuous assessment of the water exchange between the chlorenchyma and the hydrenchyma in CAM plants, namely, by following the changes in the hydrenchyma turgor pressure, is presented. However, showing once more how the LPCP output pressure, Pp, depends on the leaf structure, such an approach can be used to study plant‐water relations in other CAM species with a leaf structure similar to Aloe vera, with the hydrenchyma composing most of the leaf volume.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although generally unnoticed, nearly all crop plants have one or more species of nematodes that feed on their roots, frequently causing tremendous yield losses. The group of sedentary nematodes, ...which are among the most damaging plant-parasitic nematodes, cause the formation of special organs called nematode feeding sites (NFS) in the root tissue. In this review we discuss key metabolic and cellular changes correlated with NFS development, and similarities and discrepancies between different types of NFS are highlighted.
H2O/D2O negative ion time-of-flight mass spectra from electron transfer processes at different collision energies with neutral potassium yield OH–/OD–, O–, and H–/D–. The branching ratios show a ...relevant energy dependence with an important isotope effect in D2O. Electronic state spectroscopy of water has been further investigated by recording potassium cation energy loss spectra in the forward scattering direction at an impact energy of 205 eV (lab frame), with quantum chemical calculations for the lowest-lying unoccupied molecular orbitals in the presence of a potassium atom supporting most of the experimental findings. The DO–D bond dissociation energy has been determined for the first time to be 5.41 ± 0.10 eV. The collision dynamics revealed the character of the singly excited (1b2 –1) molecular orbital and doubly excited states in such K–H2O and K–D2O collisions.
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