Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating

Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant "Gly-loop", the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs

Dengue fever complicated by liver dysfunction due to possible co-infection with hepatitis E in a returning traveller from Cuba

Dengue fever is a mosquito-borne infection that co-circulates with Chikungunya and Zika virus infection in many parts of the world. Dengue virus (DENV) is occasionally responsible for acute hepatitis and a few cases of acute hepatitis due to co-infection with DENV and hepatitis E virus have been described in India. A 37-year-old Cuban woman living in Italy was admitted to our hospital with a presumed arboviral infection upon her return to Italy short after a 15-day trip to her home-country to visit relatives. An acute infection due to DENV serotype 1 was initially diagnosed, following a clinical course characterized by signs of liver dysfunction that were possibly due to co-infection with hepatitis E virus

Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating

Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant “Gly-loop”, the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs

A Plant Gene Encoding One-Heme and Two-Heme Hemoglobins With Extreme Reactivities Toward Diatomic Gases and Nitrite

In plants, symbiotic hemoglobins act as carriers and buffers of O2 in nodules, whereas nonsymbiotic hemoglobins or phytoglobins (Glbs) are ubiquitous in tissues and may perform multiple, but still poorly defined, functions related to O2 and/or nitric oxide (NO). Here, we have identified a Glb gene of the model legume Medicago truncatula with unique properties. The gene, designated MtGlb1-2, generates four alternative splice forms encoding Glbs with one or two heme domains and 215–351 amino acid residues. This is more than double the size of any hemoglobin from plants or other organisms described so far. A combination of molecular, cellular, biochemical, and biophysical methods was used to characterize these novel proteins. RNA-sequencing showed that the four splice variants are expressed in plant tissues. MtGlb1-2 is transcriptionally activated by hypoxia and its expression is further enhanced by an NO source. The gene is preferentially expressed in the meristems and vascular bundles of roots and nodules. Two of the proteins, bearing one or two hemes, were characterized using mutants in the distal histidines of the hemes. The Glbs are extremely reactive toward the physiological ligands O2, NO, and nitrite. They show very high O2 affinities, NO dioxygenase activity (in the presence of O2), and nitrite reductase (NiR) activity (in the absence of O2) compared with the hemoglobins from vertebrates and other plants. We propose that these Glbs act as either NO scavengers or NO producers depending on the O2 tension in the plant tissue, being involved in the fast and fine tuning of NO concentration in the cytosol in response to sudden changes in O2 availability

Degassing and Cycling of Mercury at Nisyros Volcano (Greece)

Nisyros Island (Greece) is an active volcano hosting a high-enthalpy geothermal system. During June 2013, an extensive survey on Hg concentrations in different matrices (fumarolic fluids, atmosphere, soils and plants) was carried out at Lakki Plain, an intra-caldera area affected by widespread soil and fumarolic degassing. Concentrations of gaseous elemental mercury (GEM), H2S and CO2, were simultaneously measured in both the fumarolic emissions and the atmosphere around them. At the same time, 130 samples of top soils and 31 samples of plants (Cistus Creticus and Salvifolius and Erica Arborea and Manipuliflora) were collected for Hg analysis. Mercury concentrations in fumarolic gases ranged from 10,500 to 46,300 ng/m3, while Hg concentrations in the air ranged from high background values in the Lakki Plain caldera (10-36 ng/m3) up to 7100 ng/m3 in the fumarolic areas. Outside the caldera, the concentrations were relatively low (2-5 ng/m3). The positive correlation with both CO2 and H2S in air highlighted the importance of hydrothermal gases as carrier for GEM. On the other hand, soil Hg concentrations (0.023-13.7 µg/g) showed no significant correlations with CO2 and H2S in the soil gases, whereas it showed a positive correlation with total S content and an inverse one with the soil-pH, evidencing the complexity of the processes involving Hg carried by hydrothermal gases while passing through the soil. Total Hg concentrations in plant leaves (0.010-0.112 μg/g) had no direct correlation with soil Hg, with Cistus leaves containing higher values of Hg respect to Erica. Even though GEM concentrations in air within the caldera are sometimes orders of magnitude above the global background, they should not be considered dangerous to human health. Values exceeding the WHO guideline value of 1000 ng/m3 are very rare (<0.1%) and only found very close to the main fumarolic vents, where the access to tourists is prohibited.PublishedID 47835146A. Geochimica per l'ambiente e geologia medicaJCR Journa

Statistical Multifragmentation in Central Au+Au Collisions at 35 MeV/u

Multifragment disintegrations, measured for central Au + Au collisions at E/A = 35 MeV, are analyzed with the Statistical Multifragmentation Model. Charge distributions, mean fragment energies, and two-fragment correlation functions are well reproduced by the statistical breakup of a large, diluted and thermalized system slightly above the multifragmentation threshold.Comment: Latex file, 8 pages + 4 postscript figures available upon request from [email protected]

Multifragment production in Au+Au at 35 MeV/u

Multifragment disintegration has been measured with a high efficiency detection system for the reaction $Au + Au$ at $E/A = 35\ MeV$. From the event shape analysis and the comparison with the predictions of a many-body trajectories calculation the data, for central collisions, are compatible with a fast emission from a unique fragment source.Comment: 9 pages, LaTex file, 4 postscript figures available upon request from [email protected]. - to appear in Phys. Lett.