171 research outputs found
The role of oxygen vacancies on the structure and the density of states of iron doped zirconia
In this paper we study, both with theoretical and experimental approach, the
effect of iron doping in zirconia. Combining density functional theory (DFT)
simulations with the experimental characterization of thin films, we show that
iron is in the Fe3+ oxidation state and accordingly that the films are rich in
oxygen vacancies (VO). VO favor the formation of the tetragonal phase in doped
zirconia (ZrO2:Fe) and affect the density of state at the Fermi level as well
as the local magnetization of Fe atoms. We also show that the Fe(2p) and Fe(3p)
energy levels can be used as a marker for the presence of vacancies in the
doped system. In particular the computed position of the Fe(3p) peak is
strongly sensitive to the VO to Fe atoms ratio. A comparison of the theoretical
and experimental Fe(3p) peak position suggests that in our films this ratio is
close to 0.5. Besides the interest in the material by itself, ZrO2:Fe
constitutes a test case for the application of DFT on transition metals
embedded in oxides. In ZrO2:Fe the inclusion of the Hubbard U correction
significantly changes the electronic properties of the system. However the
inclusion of this correction, at least for the value U = 3.3 eV chosen in the
present work, worsen the agreement with the measured photo-emission valence
band spectra.Comment: 24 pages, 8 figure
Extensive counter-ion interactions seen at the surface of subtilisin in an aqueous medium
The extent of protein and counter-ion interactions in solution is still far from being fully described and understood. In low dielectric media there is documented evidence that counter-ions do bind and affect enzymatic activity. However, published crystal structures of macromolecules of biological interest in aqueous solution often do not report the presence of any counter-ions on the surface. The extent of counter-ion interactions within subtilisin in an aqueous medium has been investigated crystallographically using CsCl soak and X-ray wavelength optimised anomalous diffraction at the Cs K-edge. Ten Cs+, as well as six Cl- sites, have been clearly identified, revealing that in aqueous salt solutions ions can bind at defined points around the protein surface. The counter-ions do not generally interact with formal charges on the protein; formally neutral oxygens, mostly backbone carbonyls, mostly coordinate the Cs+ ions. The Cl- ion sites are also found likely to be near positive charges on the protein surface. The presence of counter-ions substantially changes the protein surface electrical charge. The surface charge distribution on a protein is commonly discussed in relation to enzyme function. The correct identification of counter-ions associated with a protein surface is necessary for a proper understanding of an enzyme's function
Transthyretin binding heterogeneity and antiamyloidogenic activity of natural polyphenols and their metabolites
Transthyretin (TTR) is an amyloidogenic protein, the amyloidogenic
potential of which is enhanced by a number of specific
point mutations. The ability to inhibit TTR fibrillogenesis
is known for several classes of compounds, including natural
polyphenols, which protect the native state of TTR by specifically
interacting with its thyroxine binding sites. Comparative
analyses of the interaction and of the ability to protect the TTR
native state for polyphenols, both stilbenoids and flavonoids,
and some of their main metabolites have been carried out. A
main finding of this investigation was the highly preferential
binding of resveratrol and thyroxine, both characterized by negative
binding cooperativity, to distinct sites in TTR, consistent
with the data of x-ray analysis of TTR in complex with both
ligands. Although revealing the ability of the two thyroxine
binding sites of TTR to discriminate between different ligands,
this feature has allowed us to evaluate the interactions of polyphenols
with both resveratrol and thyroxine preferential binding
sites, by using resveratrol and radiolabeled T4 as probes.
Among flavonoids, genistein and apigenin were able to effectively
displace resveratrol from its preferential binding site,
whereas genistein also showed the ability to interact, albeit
weakly, with the preferential thyroxine binding site. Several
glucuronidated polyphenol metabolites did not exhibit significant
competition for resveratrol and thyroxine preferential
binding sites and lacked the ability to stabilize TTR. However,
resveratrol-3-O-sulfate was able to significantly protect the protein
native state. A rationale for the in vitro properties found for
polyphenol metabolites was provided by x-ray analysis of their
complexes with TTR
Inhibition mechanism of urease by Au(III) compounds unveiled by x-ray diffraction analysis
The nickel-dependent enzyme urease is a virulence factor for a large number of critical human pathogens, making this enzyme a potential target of therapeutics for the treatment of resistant bacterial infections. In the search for novel urease inhibitors, five selected coordination and organometallic Au(III) compounds containing N∧N or C∧N and C∧N∧N ligands were tested for their inhibitory effects against Canavalia ensiformis (jack bean) urease. The results showed potent inhibition effects with IC50 values in the nanomolar range. The 2.14 Å resolution crystal structure of Sporosarcina pasteurii urease inhibited by the most effective Au(III) compound [Au(PbImMe)Cl2]PF6 (PbImMe = 1-methyl-2-(pyridin-2-yl)-benzimidazole) reveals the presence of two Au ions bound to the conserved triad αCys322/αHis323/αMet367. The binding of the Au ions to these residues blocks the movement of a flap, located at the edge of the active site channel and essential for enzyme catalysis, completely obliterating the catalytic activity of urease. Overall, the obtained results constitute the basis for the design of new gold complexes as selective urease inhibitors with future antibacterial applications
Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease
The endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer's disease (AD). However, the association between CB1 alterations and the development of AD neuropathology is unclear and often contradictory. In this study, brain CB1 mRNA and CB1 protein levels were analyzed in 3 × Tg-AD mice and compared to wild-type littermates at 2, 6 and 12 months of age, using in-situ hybridization and immunohistochemistry, respectively. Semiquantitative analysis of CB1 expression focused on the prefrontal cortex (PFC), prelimbic cortex, dorsal hippocampus (DH), basolateral amygdala complex (BLA), and ventral hippocampus (VH), all areas with high CB1 densities that are strongly affected by neuropathology in 3 × Tg-AD mice. At 2 months of age, there was no change in CB1 mRNA and protein levels in 3 × Tg-AD mice compared to Non-Tg mice in all brain areas analyzed. However, at 6 and 12 months of age, CB1 mRNA levels were significantly higher in PFC, DH, and BLA, and lower in VH in 3 × Tg-AD mice compared to wild-type littermates. CB1 immunohistochemistry revealed that CB1 protein expression was unchanged in 3 × Tg-AD at 2 and 6 months of age, while a significant decrease in CB1 receptor immunoreactivity was detected in the BLA and DH of 12-month-old 3 × Tg-AD mice, with no sign of alteration in other brain areas. The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD
Mechanical Behavior of PET-G Tooth Aligners Under Cyclic Loading
Invisible aligners are medical devices, which allow repositioning of teeth through a treatment designed by the orthodontists. During this orthodontic treatment, patients use several aligners each for a couple of weeks. The aligner will apply a system of forces on the teeth to shift them to desired position. Since aligners exert forces thanks to their particular shape, it is important that during lifetime's service they do not undergo significant deformations. This research aims to study the mechanical behavior of invisible aligners made by polyethylene terephthalate-glycol (PET-G), which is one of most used the plastic materials to produce such devices. In this study, cyclic compression tests in atmospheric environment (∼25°C) as well as in the presence of saliva (to simulate intraoral environment) were performed. The mechanical behavior of aligners with two different thicknesses (0.75 and 0.88 mm) was studied. In particular, each aligner was subjected to 22500 load cycles from 0 to 50 N. The chosen number of load cycles simulates the average load history to which an aligner is subjected during its lifetime. The tests were performed on a testing machine, using a hard resin dental cast properly fixed to the machine. Analysis of the results shows that the stiffness of the aligners increases during the cyclic test. In particular, a gradual reduction of the crosshead displacement was observed during the test, highlighting the occurrence of cyclic hardening phenomena. It was also found that the aligners show a residual strain recovery after removing the applied load. Moreover, in the analyzed range of load rate, the aligners show a low tendency to accumulate residual strains as loading cycles progress
Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population
BACKGROUND: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; Its prevalence is inferred from autopsy or retrospective arteriographic studies. This study has been conducted on 269 subjects over 50 with hypertension and/or CRF, unrelated to other known causes of renal disease. METHODS: All 269 patients were studied either by color-flow duplex sonography (n = 238) or by renal scintigraphy (n = 224), and 199 of the 269 patients were evaluated using both of these techniques. 40 patients, found to have renal artery stenosis (RAS), were subjected to 3D-contrast enhancement Magnetic Resonance Angiography (MRA) and/or Selective Angiography (SA). An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or SA). RESULTS: Color-duplex sonography, carried out in 238 patients, revealed 49 cases of RAS. MR or SA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography showed a PPV value of 94.3% and NPV of 87.0% while renal scintigraphy, carried out in 224 patients, had a PPV of 72.2% and a NPV of 29.4%. Patients with RAS showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in proteinuria. RAS, based on color-duplex sonography studies, was present in 11% of patients in the age group 50–59, 18% in the 60–69 and 23% at age 70 and above. CONCLUSIONS: A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by RAS and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis
Data collection with a tailored X-ray beam size at 2.69 angstrom wavelength (4.6 keV):sulfur SAD phasing of Cdc23(Nterm)
The capability to reach wavelengths of up to 3.1 Å at the newly established EMBL P13 beamline at PETRA III, the new third-generation synchrotron at DESY in Hamburg, provides the opportunity to explore very long wavelengths to harness the sulfur anomalous signal for phase determination. Data collection at = 2.69 Å (4.6 keV) allowed the crystal structure determination by sulfur SAD phasing of Cdc23, a subunit of the multimeric anaphase-promoting complex (APC/C). At this energy, Cdc23 has an expected Bijvoet ratio <|F|>/<F> of 2.2%, with 282 residues, including six cysteines and five methionine residues, and two molecules in the asymmetric unit (65.4 kDa; 12 Cys and ten Met residues). Selectively illuminating two separate portions of the same crystal with an X-ray beam of 50 µm in diameter allowed crystal twinning to be overcome. The crystals diffracted to 3.1 Å resolution, with unit-cell parameters a = b = 61.2, c = 151.5 Å, and belonged to space group . The refined structure to 3.1 Å resolution has an R factor of 18.7% and an R of 25.9%. This paper reports the structure solution, related methods and a discussion of the instrumentation
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