Resolved Structure Research Articles

Probing single-unit-cell resolved electronic structure modulations in oxide superlattices with standing-wave photoemission

Control of structural couplings at the complex-oxide interfaces is a powerful platform for creating new ultrathin layers with electronic and magnetic properties unattainable in the bulk. However, with the capability to design and control the electronic structure of such buried layers and interfaces at a unit-cell level, a new challenge emerges to be able to probe these engineered emergent phenomena with depth-dependent atomic resolution as well as element- and orbital selectivity. Here, we utilize a combination of core-level and valence-band soft x-ray standing-wave photoemission spectroscopy, in conjunction with scanning transmission electron microscopy, to probe the depth-dependent and single-unit-cell resolved electronic structure of an isovalent manganite superlattice [Eu0.7Sr0.3MnO3/La0.7Sr0.3MnO3]x15 wherein the electronic-structural properties are intentionally modulated with depth via engineered oxygen octahedra rotations/tilts and A-site displacements. Our unit-cell resolved measurements reveal significant transformations in the local chemical and electronic valence-band states, which are consistent with the layer-resolved first-principles theoretical calculations, thus opening the door for future depth-resolved studies of a wide variety of hetero-engineered material systems.

High-resolution photoelectron spectroscopy of the pyridinide isomers

Isomer-specific, high-resolution photoelectron spectra of cryogenically cooled pyridinide anions obtained using slow photoelectron velocity-map imaging are presented. New vibrational structure in the detachment spectrum of para-pyridinide is resolved, and the spectra of meta- and ortho-pyridinide are reported for the first time. These spectra yield electron affinities of 1.4797(5), 1.4473(5), and 0.8669(7) eV for the para-, meta-, and ortho-pyridyl radicals, respectively, as well as a number of vibrational frequencies for each neutral isomer. While most of the resolved structure in all three spectra is readily assigned by comparison to B3LYP/6-311+G* Franck-Condon simulations, the para-pyridinide spectrum shows newly resolved fine structure attributed to anharmonic coupling within the vibrational manifold of the corresponding neutral radical. Isomeric trends in the photoelectron angular distributions are rationalized by approximating the detached anion orbitals as superpositions of s-, p-, and d-like hydrogenic orbitals, based on an application of Sanov’s generalized mixing model [D. Khuseynov et al., J. Chem. Phys. 141, 124312 (2014)]. The presented experimental and theoretical results are used to address the relative energies of the anion and neutral isomers, as well as the site-specific bond dissociation energies of pyridine.

Sensitivity of nocturnal low-level jets to land-use parameters and meteorological quantities

Abstract. The increasing hub height of wind turbines aims at optimizing the wind energy yield at one location and offers the possibility to provide new areas for wind power, for example forests. Inhomogeneous environmental conditions of locations for wind turbines as well as the hub heights of more than 100 m cause challenges for flow models and their potential for wind power assessment. This includes special features of the wind field like low-level jets (LLJs), frequently observed local wind maxima in the nocturnal boundary layer. To characterize the dependencies of LLJs, the micro-scale model HIRVAC2D (HIgh Resolution Vegetation Atmosphere Coupler 2D) is applied in the study. The model HIRVAC2D is capable of modelling different vegetation types by explicitly considering the highly resolved structure of varying plant parameters. Beyond that, the model enables the resolution of temporally variable atmospheric circulation patterns during day- and night-time with typical thermal stratifications. In this way, HIRVAC2D is suitable to capture the nocturnal LLJ development and its characteristics. Results of several HIRVAC2D simulations are presented in order to deduce quantitatively the sensitivity of LLJs to vegetation and model parameters as well as meteorological quantities. It is shown that the geostrophic wind speed is an important criterion for the development of LLJs within a height range between 50 and 300 m. For a geostrophic wind speed of 4 m s−1, a nocturnal LLJ occurs remarkably more frequent as for a wind speed of 10 m s−1. To interpret and evaluate this result regarding possible wind power applications, a frequency distribution of the geostrophic wind speed was calculated over 30 years exemplarily at two locations using the meso-scale model COSMO in climate mode. Additionally, the type of land use has an impact on the height and intensity of LLJs. For a grassland site, the nocturnal LLJ is noticeably more frequent in the considered height range, but with a smaller wind speed and at a lower height above ground in comparison to deciduous or coniferous forests.

95 GHz electron paramagnetic resonance of LiYF4: Nd3+ crystal in parallel orientation

We report the observation of the conventional and pulsed electron paramagnetic resonance (EPR), electron-nuclear double resonance (ENDOR) spectra from 19F and 7Li nuclei on impurity Nd3+ ions in LiYF4 crystal doped with Nd3+ ions in parallel orientation at microwave frequency of ν ≈ 95 GHz (W-band). The resolved structure from the nearby and remote nuclei in spectra is observed. The outcome shows that LiYF4:Nd3+ system can be exploited as a convenient matrix for performing spin manipulations and adjusting quantum computation protocols while ENDOR technique is usable for the investigation of electron-nuclear interaction with the nuclei of the system.

PS921 INACTIVATION OF SH2B3 THROUGH CN‐LOH 12Q IS UNIQUELY ASSOCIATED WITH B‐CELL PRECURSOR ALL WITH IAMP21 OR OTHER CHROMOSOME 21 GAIN

Background:In more than 30% of childhood B‐cell precursor acute lymphoblastic leukaemia (B‐ALL), chromosome 21 sequence is overrepresented through constitutional or acquired aneuploidy or structural rearrangements, exemplified by intrachromosomal amplification of chromosome 21 (iAMP21). How these abnormalities promote B‐ALL remains obscure but a mechanistic link is suggested by the existence of shared co‐occurring abnormalities.Aims:We aimed to identify and characterise acquired genetic abnormalities that cooperate with amplification or aneuploidy of chromosome 21 to promote B‐ALL.Methods:Regions of copy neutral loss of heterozygosity and deletion were defined by analysis of SNP6.0 arrays, methylation arrays were used to assess loss of imprinting. The mutational status of SH2B3 was determined by amplicon sequencing and a homology model based on the resolved structure of the Sh2 domain of Sh2b1 was used to assess the impact of an acquired in‐frame substitution. STAT activation status was determined by flow cytometric immunophenotyping.Results:Analysis of B‐ALL patients with iAMP21, other structural amplifications of chromosome 21 or constitutional or acquired additional whole copies of chromosome 21 (n = 99), revealed recurrent CN‐LOH of 6p, 9p and 12q. In patients without overrepresentation of chromosome 21, CN‐LOH 6p and 9p were also recurrent but intriguingly, CN‐LOH 12q was absent, among our own (n = 203) or published cases (n = 974). Further analysis demonstrated CN‐LOH 12q was not associated with loss of imprinting but with homozygous mutations or deletions of the adaptor protein, SH2B3. In patients without CN‐LOH 12q, bi‐allelic abnormalities of SH2B3 occurred, but only in iAMP21‐ALL, giving an overall incidence of 18% in this sub‐type. Taking into account our own cohort, analysis of archival array data and review of published cases, we conclude that in B‐ALL, SH2B3 abnormalities are invariably bi‐allelic, frequent in iAMP21‐ALL, recurrent but less common in association with acquired aneuploidy 21 but extremely rare in the absence of overrepresentation of chromosome 21. Importantly, as iAMP21 patients are now uniformly treated as high risk, preliminary analysis of 26 patients treated on UKALL97/99 (n = 5) or UKALL2003 (n = 21), linked 12q abnormalities to poor outcome in iAMP21‐ALL (p = 0.03). Homology modelling of an iAMP21‐ALL associated R392W mutation in the SH2 domain of SH2B3 demonstrated loss of critical interactions required for binding and suppression of activated JAK. Further implicating the JAK/STAT pathway as one target for SH2B3 tumour suppressor activity, stimulation with IL7 of iAMP21‐ALL patient derived xenograft cells, with but not without SH2B3 inactivation, resulted in activation of STAT5 though not other STATs.Summary/Conclusion:Although chromosome 21 copy number profiles are highly heterogeneous in iAMP21‐ALL a limited number of candidate oncogenes are consistently amplified, overexpressed and spared from disruption by structural rearrangements. From our data we infer that in iAMP21‐ALL, high expression of one or more of these candidate genes creates strong pressure for loss of SH2B3 function while lower but still elevated expression of the same gene/s, resulting from gain of one or two copies of whole chromosome 21, produces a similar though weaker selective environment. Since JAK/STAT activation is common in B‐ALL without gain of chromosome 21 and given the near‐exclusive association we observed, we are currently exploring the possibility that SH2B3 also interacts with other pathways specifically activated by increased doses of chromosome 21 genes.

Radio jet structures at ∼100 pc and larger scales of the γ-ray-emitting narrow-line Seyfert 1 galaxy PMN J0948+0022

Abstract The narrow-line Seyfert 1 (NLS1) galaxy PMN J0948+0022 is an archetype of γ-ray-emitting NLS1s in active galactic nuclei (AGNs). In this study, we investigate its radio structures using archival data obtained using the Karl G. Jansky Very Large Array (VLA) and the Very Long Baseline Array (VLBA). The new VLA images reveal an outermost radio emission separated by 9.1 arcsec. Its resolved structure and steep spectrum suggest a terminal shock in a radio lobe energized by the jet from the PMN J0948+0022 nucleus. This large-scale radio component is found at almost the same position angle as that of the pc-scale jet, indicating a stable jet direction up to ∼1 Mpc. Its apparent one-sidedness implies a moderate advancing speed (β > 0.27). The kinematic age of <1× 107 yr of the jet activity is consistent with the expected NLS1 phase of ∼107 yr in the AGN lifetime. The VLBA image reveals the jet structure at distances ranging from r = 0.82 milliarcsec to 3.5 milliarcsec, corresponding to approximately 100 pc, where superluminal motions were found. The jet width profile (∝ r1.12) and flux-density profile (∝ r−1.44) depending on the distance r along the jet suggest that the jet kinetic energy is converted to internal energy in this region. The jet is causally connected in a nearly conical streamline, which is supported by ambient pressure at 100 pc scales in the host galaxy of PMN J0948+0022.

Investigation of the WR 11 field at decimeter wavelengths

The massive binary system WR 11 (γ2-Velorum) has recently been proposed as the counterpart of a Fermi source. If this association is correct, this system would be the second colliding wind binary detected in GeV γ-rays. However, the reported flux measurements from 1.4 to 8.64 GHz fail to establish the presence of nonthermal (synchrotron) emission from this source. Moreover, WR 11 is not the only radio source within the Fermi detection box. Other possible counterparts have been identified in archival data, some of which present strong nonthermal radio emission. We conducted arcsec-resolution observations toward WR 11 at very low frequencies (150–1400 MHz) where the nonthermal emission – if existent and not absorbed – is expected to dominate. We present a catalog of more than 400 radio emitters, among which a significant portion are detected at more than one frequency, including limited spectral index information. Twenty-one of these radio emitters are located within the Fermi significant emission. A search for counterparts for this last group pointed at MOST 0808–471; this source is 2′ away from WR 11 and is a promising candidate for high-energy emission, having a resolved structure along 325–1390 MHz. For this source, we reprocessed archive interferometric data up to 22.3 GHz and obtained a nonthermal radio spectral index of − 0.97 ± 0.09. However, multiwavelength observations of this source are required to establish its nature and to assess whether it can produce (part of) the observed γ-rays. WR 11 spectrum follows a spectral index of 0.74 ± 0.03 from 150 to 230 GHz, consistent with thermal emission. We interpret that any putative synchrotron radiation from the colliding-wind region of this relatively short-period system is absorbed in the photospheres of the individual components. Notwithstanding, the new radio data allowed us to derive a mass-loss rate of 2.5 × 10−5 M⊙ yr−1, which, according to the latest models for γ-ray emission in WR 11, would suffice to provide the required kinetic power to feed nonthermal radiation processes.

Electronic transitions of tungsten monosulfide

Electronic transition spectrum of the tungsten monosulfide (WS) molecule in the near infrared region between 725 nm and 885 nm has been recorded using laser ablation/reaction free-jet expansion and laser induced fluorescence spectroscopy. The WS molecule was produced by reacting laser - ablated tungsten atoms with 1% CS2 seeded in argon. Fourteen vibrational bands with resolved rotational structure have been recorded and analyzed, which were organized into six electronic transition systems. Least-squares fit of the measured line positions yielded molecular constants for the electronic states observed. The ground state has been identified to be the X3Σ−(0+) state with bond length, ro, and vibrational frequency, ΔG1/2, determined to be 2.0676 Å and 556.7 cm−1 respectively. Molecular constants and potential energy curves of low-lying Λ-S states and Ω sub-states of the WS molecule have been calculated at the MRCISD + Q level of theory with spin-orbit coupling. Calculated molecular properties of the ground and low-lying electronic states are generally in good agreement with experimental determinations. This work represents the first experimental investigation of the electronic transition spectrum of the WS molecule.

Parametrical study and turbulence analysis of high-speed flows around an open cavity using large eddy simulation

Large eddy simulation is used in this work to simulate the three-dimensional turbulent flow in an open cavity, with special attention paid to the parametrical effect and turbulence analysis. The effect of mesh resolution, the sub-grid model and the advection scheme on the resolved flow structure is discussed in detail. Then, the mechanism of flow-induced pressure fluctuation associated with the primary and secondary vortex in the shear layer is clarified quantitatively and qualitatively. Finally, the turbulent kinetic energy and turbulence production rate, the contribution of three components to total turbulence production rate and the main single contributor are analyzed systematically. The present simulations are performed for two Reynolds numbers and the results show that the flow is more turbulent with the increase in Reynolds number, but the general flow morphology is almost the same. It is expected that the basic founding is useful for understanding such similar flows and will provide some guidelines for controlling the vortex-induced flow instability in engineering applications.

Optical constants of magnetron sputtered Pt thin films with improved accuracy in the N- and O-electronic shell absorption regions

We present an experimental, self-consistent determination of the optical constants (refractive index) of Pt using a combination of photoabsorption and reflectance data in the photon energy range 25–778 eV, which includes the N- and O-shell electronic absorption edges of Pt. We compare our new experimental values with Pt optical constant data sets from the literature. Our Pt optical constant values reveal highly resolved absorption-edge fine structure around the O2,3 and N6,7 edges in both the absorptive and dispersive portions of the refractive index, which were missing in the earlier literature.

Investigations of VO2+ doped SrZn2(PO4)2 nanophosphors by solution combustion synthesis

VO2+ doped SrZn2(PO4)2 nanophosphor is prepared using solution combustion synthesis. The prepared nanophosphor is studied by structural and spectral characterizations XRD, SEM with EDS, TEM, FT-IR, Optical absorption, EPR, and PL. XRD analyses the monoclinic phase of the prepared sample and the crystallite size determined to be in the order below 60 nm. SEM and TEM micrographs show the agglomerated stone-like structures for VO2+ doped SrZn2(PO4)2 nanophosphors. FT-IR spectrum exhibits various vibrational modes for PO43− anionic groups and other related groups. Optical absorption spectrum exhibited characteristic VO2+ bands in visible region and the crystal field and tetragonal field parameters are evaluated as Dq = 1461, Ds = −3035 and Dt = 602 cm−1. EPR spectrum shows well resolved hyperfine octet structure for VO2+ doped nanophosphor. The spin Hamiltonian parameters (g), hyperfine coupling constants (A) are calculated and are satisfying the condition g‖<g⊥<ge and A‖ > A⊥. From Optical and EPR data, VO2+ ions with the host ligands are identified as tetragonal distortion in octahedral site symmetry. PL spectrum illustrates, emission peaks in blue and green regions and its CIE and CCT parameters are evaluated, which are useful in LEDs and lightening devices.

ESR and FT-IR Studies on GeO2 Substituted Lead Vanadate Semiconducting Glass System

A series of Germania-lead-vanadium pentoxide glasses with x=5, 10 and 15 mol% were prepared by melt quenching technique and they were characterized by X-ray diffraction (XRD), Differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) and Electron Spin Resonance (ESR) techniques. X-ray diffraction results reveal that all samples are perfect amorphous in nature. Differential scanning calorimetry results indicate that the substituent GeO2 is replacing PbO in the glass network in such a way that the eutectic composition is maintained. The Fourier Transform Infrared spectra characterized V=O stretching frequency around 968 cm-1 upto 15 mole% and interestingly the Electron Spin Resonance studies did not yield well resolved hyperfine structure due to exchange broadening which varyies with nature of dopant. The Hruby parameter (Kg) for this glass system has been evaluated and reported.

Historical separation and present-day structure of common dolphinfish (Coryphaena hippurus) populations in the Atlantic Ocean and Mediterranean Sea

AbstractThe common dolphinfish (Coryphaena hippurus) is an epipelagic, mid-trophic level, highly migratory species distributed throughout the world’s tropical and subtropical oceans in waters greater than 20°C. Life-history variables, migratory behaviour, and genetic markers have been used to define major stocks in the central Atlantic Ocean and Mediterranean Sea. Here, we used the mitochondrial DNA gene NADH subunit 1 (688 bp) to test for differences between population groups. A total of 103 haplotypes were detected among 203 fish. Gene diversities in samples were large and similar among populations (mean h = 0.932; range 0.894–0.987), but nucleotide diversities varied widely among samples (range π = 0.004–0.034) and appear to reflect population histories. Principal component analysis revealed two large populations groups, and the analysis of molecular variation and pairwise values of ΦST resolved population structure within these groups. Populations in the eastern Atlantic and Mediterranean showed the largest amounts of divergence from one another (ΦCT = 0.331). Adult movement and biophysical barriers to larval dispersal may explain contemporary differences between stocks, but the divergent populations in the Mediterranean Sea are likely due to isolations by cold temperature barriers during Pleistocene glaciations. The geographically large stock groupings require international cooperation in the harvest management and conservation of local dolphinfish populations.

Self-faceting of emulsion droplets as a route to solid icosahedra and other polyhedra

HypothesisTemperature-controlled self-faceting of liquid droplets has been recently discovered in surfactant-stabilized alkane-in-water emulsions. We hypothesize that similar self-faceting may occur in emulsion droplets of UV-polymerizable linear hydrocarbons. We further hypothesize that the faceted droplet shapes can be fixed by UV-initiated polymerization, thus providing a new route towards the production of solid polyhedra. ExperimentsTemperature-induced shape variations were studied by optical microscopy in micron-size emulsion droplets of UV-polymerizable alkyl acrylate. When polymerized, the resultant solid particles’ 3D shape and internal structure were determined by combined scanning electron microscopy (SEM) and focused ion beam (FIB) slicing. The SEM and FIB nanoscale resolution provided a far greater detail imaging than that achievable for the liquid droplets, which could only be studied by optical microscopy, severely limiting their 3D shape determination. FindingsWe demonstrate the formation of solid icosahedra, polyhedral platelets, and rods of hitherto-unreported sizes, well below the 3D-printing resolution (∼20μm). The presence of icosahedral shapes and the absence of any resolvable internal structure at sub-μm length scales, are in line with the surface-freezing-driven mechanism proposed for the faceting phenomenon. Further development of the method presented here may allow large-quantity production of shaped micron- to nano- sized colloidal building blocks for 3D metamaterials and other applications.

Proline- and Arginine-Rich Peptides as Flexible Allosteric Modulators of Human Proteasome Activity.

Proline- and arginine-rich peptide PR11 is an allosteric inhibitor of 20S proteasome. We modified its sequence inter alia by introducing HbYX, RYX, or RHbX C-terminal extensions (Hb, hydrophobic moiety; R, arginine; Y, tyrosine; X, any residue). Consequently, we were able to improve inhibitory potency or to convert inhibitors into strong activators: the former with an aromatic penultimate Hb residue and the latter with the HbYX motif. The PR peptide activator stimulated 20S proteasome in vitro to efficiently degrade protein substrates, such as α-synuclein and enolase, but also activated proteasome in cultured fibroblasts. The positive and negative PR modulators differently influenced the proteasome conformational dynamics and affected opening of the substrate entry pore. The resolved crystal structure showed PR inhibitor bound far from the active sites, at the proteasome outer face, in the pocket used by natural activators. Our studies indicate the opportunity to tune proteasome activity by allosteric regulators based on PR peptide scaffold.

Management implications of highly resolved hierarchical population genetic structure in thinhorn sheep

Patterns of genetic variation of a species can be shaped by events that occur at wide temporal and geographic scales. Geophysical processes, such as continental glaciations, can affect species vicariance at wide scales whereas processes that act at finer scales, such as gene flow between populations, can have more localized effects. Recent studies have shown that contemporary population structure should be interpreted within the context of historical events, such as ice-age vicariance, due to the hierarchical nature of genetic variation found in many species. The thinhorn sheep (Ovis dalli) is a mountain specialist found in northwestern North America, from the Brooks Range in Alaska, east through Yukon to the Mackenzie Mountains of Northwest Territories and south to the Rocky and Coastal Mountains of British Columbia. In this study, we examined the population genetic structure of thinhorn sheep in light of genetic evidence regarding the glacier driven evolution of the two thinhorn sheep subspecies, O. d. dalli and O. d. stonei, using 153 biallelic single-nucleotide polymorphisms genotyped in over 2800 thinhorn rams. We found patterns of genetic variation to be generally consistent with genetic subspecies boundaries at the species-wide level, and mountain range and river valley boundaries at finer scales. By taking in account historical vicariance by conducting hierarchical analyses of population genetic structure, we revealed the presence of three previously unreported Stone’s sheep genetic clusters in the Stikine/Skeena, Cassiar and Rocky Mountains and identified a new geographic range for Stone’s sheep that is much more restricted than currently accepted subspecies maps indicate, and is almost exclusively confined within British Columbia. Our results indicate that contemporary patterns of genetic variation can be influenced by events acting over a range of spatial and temporal scales, and thus the importance of interpreting the findings of present-day genetic structure in light of the phylogeographical history of the species in question.

Spin resolved electronic structure and transport properties of zinc oxide nanoribbon based devices

Employing first principles study, through Density Functional Theory, spin resolved electronic structure and transport behavior of ZnO nanoribbon devices are addressed. Electronic transport properties of both armchair and zigzag ZnO nanoribbon (AZnO and ZZnO, respectively) are investigated using the ZnO and Ni electrodes. Spin dependent electronic properties of these structures are exhibited through the band-structure, transmission and density of states. A spin-asymmetric metallic property and a high spin polarization nearby the Fermi level is found for the ZZnO which can be harnessed to develop a spin-valve device. It is demonstrated that, using either a defect or Ni electrodes in the AZnO, both the electronic transport and magnetic properties of an AZnO based device can be tailored. Current-voltage (I-V) characteristics of the AZnO attached to the Ni electrodes (AZnO-Ni) reveals spin resolved non-ohmic behavior. A pronounced negative differential resistance occurs for both majority and minority current of the AZnO-Ni at certain bias intervals. The induced magnetic moment, spin polarization and other relevant quantities associated with the spin resolved electronic transport are elucidated.

Synthesis, Cyclooxygenase-2 Inhibition, Anti-inflammatory Evaluation and Docking Study of Substituted-N-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole Derivatives.

Non-steroidal anti-inflammatory drugs are widely used for many years, but the chronic use of NSAID's leads to gastric side effects, ulceration and kidney problems. These side effects are due to non-selective inhibition of COX-2 along with COX-1. Therefore, it is imperative to develop novel and selective COX-2 inhibitors. In this paper wehave synthesized a series of novel hybrids comprising of substituted-N- (3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives and screened for the treatment of inflammation. The structures of the obtained compounds were elucidated by elemental and spectral analysis (ATR-FTIR, 1H NMR, 13C NMR, Mass spectroscopy). All of the compounds were evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activity by in vitro enzymatic assay. The compound which showed COX-2 activity (3a - 3e, 3g - 3h, 3k, 3m and 3o) was further screened for in vivo anti-inflammatory activity and ulcerogenic liability. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanism of newly synthesized inhibitors in the active site of COX-2enzyme. The in vitro COX-1 and COX-2 inhibitory studies showed that the synthesized compounds potentially inhibited COX-2 (IC50 = 0.04 - 26.41 µM range) over COX-1 (IC50 = 0.98 - 33.33 µM range). The in vivo studies predicted that compounds 3c (70.9%, 0.6±0.22), 3m (68.1%, 1.9±0.41) and 3o (70.4%, 1.7±0.27) produced more efficacy against carrageenan induced paw edema and less ulcerogenic effect, as compared to standard ibuprofen (65.9%, 2.2±0.44). The results of docking studies were found to be concordant with the biological evaluation studies of the prepared compound. Among all the tested compounds, 2-Chloro-N-(2-(3,4,5-trimethoxyphenyl)- benzo[d]oxazol-5-yl)-benzamide (3c) was the most potent anti-inflammatory agent and has less ulcerogenic potential. This series of compound can be explored more for development of safer and more active anti-inflammatory agents.

Molecular phylogeography and genetic diversity of Angiostrongylus cantonensis and A. malaysiensis (Nematoda: Angiostrongylidae) based on 66-kDa protein gene

Angiostrongylus cantonensis is the main causative agent of human angiostrongyliasis. A sibling species, A. malaysiensis has not been unequivocally incriminated to be involved in human infections. To date, there is only a single report on the application of the partial 66-kDa protein gene sequence for molecular differentiation and phylogeny of Angiostrongylus species. Nucleotide sequences of the 66-kDa protein gene of A. cantonensis and A. malaysiensis from Thailand, as well as those of the laboratory strains of A. cantonensis from Thailand and Hawaii, A. cantonensis from Japan and China, A. malaysiensis from Malaysia, and A. costaricensis from Costa Rica, were used for the reconstruction of phylogenetic tree by the maximum likelihood (ML) method and the haplotypes by the median joining (MJ) network. The ML phylogenetic tree contained two major clades with a full support bootstrap value – (1) A. cantonensis and A. malaysiensis, and (2) A. costaricensis. A. costaricensis was basal to A. cantonensis and A. malaysiensis. The genetic distance between A. cantonensis and A. malaysiensis ranged from p = .82% to p = 3.27%, that between A. cantonensis and A. costaricensis from p = 4.90% to p = 5.31%, and that between A. malaysiensis and A. costaricensis was p = 4.49% to p = 5.71%. Both A. cantonensis and A. malaysiensis possess high 66-kDa haplotype diversity. There was no clear separation of the conspecific taxa of A. cantonensis and A. malaysiensis from different geographical regions. A more intensive and extensive sampling with larger sample size may reveal greater haplotype diversity and a better resolved phylogeographical structure of A. cantonensis and A. malaysiensis.

Molecular dynamics and structure function analysis show that substrate binding and specificity are major forces in the functional diversification of Eqolisins

BackgroundEqolisins are rare acid proteases found in archaea, bacteria and fungi. Certain fungi secrete acids as part of their lifestyle and interestingly these also have many eqolisin paralogs, up to nine paralogs have been recorded. This suggests a process of functional redundancy and diversification has occurred, which was the subject of the research we performed and describe here.ResultsWe identified eqolisin homologs by means of iterative HMMER analysis of the NR database. The identified sequences were scrutinized for which new hallmarks were identified by molecular dynamics simulations of mutants in highly conserved positions, using the structure of an eqolisin that was crystallized in the presence of a transition state inhibitor. Four conserved glycines were shown to be important for functionality. A substitution of W67F is shown to be accompanied by the L105W substitution. Molecular dynamics shows that the W67 binds to the substrate via a π-π stacking and a salt bridge, the latter being stronger in a virtual W67F/L105W double mutant of the resolved structure of Scytalido-carboxyl peptidase-B (PDB ID: 2IFW). Additional problematic mutations are discussed. Upon sequence scrutiny we obtained a set of 233 sequences that was used to reconstruct a Bayesian phylogenetic tree. We identified 14 putative specificity determining positions (SDPs) of which four are explained by mere structural explanations and nine seem to correspond to functional diversification related with substrate binding and specificity. A first sub-network of SDPs is related to substrate specificity whereas the second sub-network seems to affect the dynamics of three loops that are involved in substrate binding.ConclusionThe eqolisins form a small superfamily of acid proteases with nevertheless many paralogs in acidic fungi. Functional redundancy has resulted in diversification related to substrate specificity and substrate binding.