Immunological Basis for the Gender Differences in Murine Paracoccidioides brasiliensis Infection

This study aimed to investigate the immunological mechanisms involved in the gender distinct incidence of paracoccidioidomycosis (pcm), an endemic systemic mycosis in Latin America, which is at least 10 times more frequent in men than in women. Then, we compared the immune response of male and female mice to Paracoccidioides brasiliensis infection, as well as the influence in the gender differences exerted by paracoccin, a P. brasiliensis component with carbohydrate recognition property. High production of Th1 cytokines and T-bet expression have been detected in the paracoccin stimulated cultures of spleen cells from infected female mice. In contrast, in similar experimental conditions, cells from infected males produced higher levels of the Th2 cytokines and expressed GATA-3. Macrophages from male and female mice when stimulated with paracoccin displayed similar phagocytic capability, while fungicidal activity was two times more efficiently performed by macrophages from female mice, a fact that was associated with 50% higher levels of nitric oxide production. In order to evaluate the role of sexual hormones in the observed gender distinction, we have utilized mice that have been submitted to gonadectomy followed by inverse hormonal reconstitution. Spleen cells derived from castrated males reconstituted with estradiol have produced higher levels of IFN-gamma (1291+/-15 pg/mL) and lower levels of IL-10 (494+/-38 pg/mL), than normal male in response to paracoccin stimulus. In contrast, spleen cells from castrated female mice that had been treated with testosterone produced more IL-10 (1284+/-36 pg/mL) and less IFN-gamma (587614 pg/mL) than cells from normal female. In conclusion, our results reveal that the sexual hormones had a profound effect on the biology of immune cells, and estradiol favours protective responses to P. brasiliensis infection. In addition, fungal components, such as paracoccin, may provide additional support to the gender dimorphic immunity that marks P. brasiliensis infection.

Transcriptomic basis for an antiserum against Micrurus corallinus (coral snake) venom

Background: Micrurus corallinus (coral snake) is a tropical forest snake belonging to the family Elapidae. Its venom shows a high neurotoxicity associated with pre- and post-synaptic toxins, causing diaphragm paralysis, which may result in death. In spite of a relatively small incidence of accidents, serum therapy is crucial for those bitten. However, the adequate production of antiserum is hampered by the difficulty in obtaining sufficient amounts of venom from a small snake with demanding breeding conditions. In order to elucidate the molecular basis of this venom and to uncover possible immunogens for an antiserum, we generated expressed sequences tags (ESTs) from its venom glands and analyzed the transcriptomic profile. In addition, their immunogenicity was tested using DNA immunization. Results: A total of 1438 ESTs were generated and grouped into 611 clusters. Toxin transcripts represented 46% of the total ESTs. The two main toxin classes consisted of three-finger toxins (3FTx) (24%) and phospholipases A(2) (PLA(2)s) (15%). However, 8 other classes of toxins were present, including C-type lectins, natriuretic peptide precursors and even high-molecular mass components such as metalloproteases and L-amino acid oxidases. Each class included an assortment of isoforms, some showing evidence of alternative splicing and domain deletions. Five antigenic candidates were selected (four 3FTx and one PLA(2)) and used for a preliminary study of DNA immunization. The immunological response showed that the sera from the immunized animals were able to recognize the recombinant antigens. Conclusion: Besides an improvement in our knowledge of the composition of coral snake venoms, which are very poorly known when compared to Old World elapids, the expression profile suggests abundant and diversified components that may be used in future antiserum formulation. As recombinant production of venom antigens frequently fails due to complex disulfide arrangements, DNA immunization may be a viable alternative. In fact, the selected candidates provided an initial evidence of the feasibility of this approach, which is less costly and not dependent on the availability of the venom.

Dynamic polarizability, Cauchy moments, and the optical absorption spectrum of liquid water: A sequential molecular dynamics/quantum mechanical approach

The dynamic polarizability and optical absorption spectrum of liquid water in the 6-15 eV energy range are investigated by a sequential molecular dynamics (MD)/quantum mechanical approach. The MD simulations are based on a polarizable model for liquid water. Calculation of electronic properties relies on time-dependent density functional and equation-of-motion coupled-cluster theories. Results for the dynamic polarizability, Cauchy moments, S(-2), S(-4), S(-6), and dielectric properties of liquid water are reported. The theoretical predictions for the optical absorption spectrum of liquid water are in good agreement with experimental information.

Electronic properties of liquid ammonia: A sequential molecular dynamics/quantum mechanics approach

The electronic properties of liquid ammonia are investigated by a sequential molecular dynamics/quantum mechanics approach. Quantum mechanics calculations for the liquid phase are based on a reparametrized hybrid exchange-correlation functional that reproduces the electronic properties of ammonia clusters [(NH(3))(n); n=1-5]. For these small clusters, electron binding energies based on Green's function or electron propagator theory, coupled cluster with single, double, and perturbative triple excitations, and density functional theory (DFT) are compared. Reparametrized DFT results for the dipole moment, electron binding energies, and electronic density of states of liquid ammonia are reported. The calculated average dipole moment of liquid ammonia (2.05 +/- 0.09 D) corresponds to an increase of 27% compared to the gas phase value and it is 0.23 D above a prediction based on a polarizable model of liquid ammonia [Deng , J. Chem. Phys. 100, 7590 (1994)]. Our estimate for the ionization potential of liquid ammonia is 9.74 +/- 0.73 eV, which is approximately 1.0 eV below the gas phase value for the isolated molecule. The theoretical vertical electron affinity of liquid ammonia is predicted as 0.16 +/- 0.22 eV, in good agreement with the experimental result for the location of the bottom of the conduction band (-V(0)=0.2 eV). Vertical ionization potentials and electron affinities correlate with the total dipole moment of ammonia aggregates. (c) 2008 American Institute of Physics.

Use of correlated potential harmonic basis functions for the description of the (4)He trimer and small clusters

A correlated many-body basis function is used to describe the (4)He trimer and small helium clusters ((4)HeN) with N = 4-9. A realistic helium dimer potential is adopted. The ground state results of the (4)He dimer and trimer are in close agreement with earlier findings. But no evidence is found for the existence of Efimov state in the trimer for the actual (4)He-(4)He interaction. However, decreasing the potential strength we calculate several excited states of the trimer which exhibit Efimov character. We also solve for excited state energies of these clusters which are in good agreement with Monte Carlo hyperspherical description. (C) 2011 American Institute of Physics. [doi:10.1063/1.3583365]

Experimental and theoretical study of two-photon absorption in nitrofuran derivatives: Promising compounds for photochemotherapy

We report experimental and theoretical studies of the two-photon absorption spectrum of two nitrofuran derivatives: nitrofurantoine, (1-(5-nitro-2-furfurilideneamine)-hidantoine) and quinifuryl, 2-(5`-nitro-2`-furanyl) ethenyl-4-{N-[4`-(N,N-diethylamino)-1`-methylbutyl]carbamoyl} quinoline. Both molecules are representative of a family of 5-nitrofuran-ethenyl-quinoline drugs that have been demonstrated to display high toxicity to various species of transformed cells in the dark. We determine the two-photon absorption cross-section for both compounds, from 560 to 880 nm, which present peak values of 64 GM for quinifuryl and 20 GM for nitrofurantoine (1 GM = 1 x 10(-50) cm(4).s.photon(-1)). Besides, theoretical calculations employing the linear and quadratic response functions were carried out at the density functional theory level to aid the interpretations of the experimental results. The theoretical results yielded oscillator strengths, two-photon transition probabilities, and transition energies, which are in good agreement with the experimental data. A higher number of allowed electronic transitions was identified for quinifuryl in comparison to nitrofurantoine by the theoretical calculations. Due to the planar structure of both compounds, the differences in the two-photon absorption cross-section values are a consequence of their distinct conjugation lengths. (c) 2011 American Institute of Physics. [doi:10.1063/1.3514911]

Theoretical study of one- and two-photon absorption spectra of azoaromatic compounds

In this study, the one- and two-photon absorption spectra of seven azoaromatic compounds (five pseudostilbenes-type and two aminoazobenzenes) were theoretically investigated using the density functional theory combined with the response functions formalism. The equilibrium molecular structure of each compound was obtained at three different levels of theory: Hartree-Fock, density functional theory (DFT), and Moller-Plesset 2. The effect of solvent on the equilibrium structure and the electronic transitions of the compounds were investigated using the polarizable continuum model. For the one-photon absorption, the allowed pi ->pi(*) transition energy showed to be dependent on the molecular structures and the effect of solvent, while the n ->pi(*) and pi ->pi(*)(n) transition energies exhibited only a slight dependence. An inversion between the bands corresponding to the pi ->pi(*) and n ->pi(*) states due to the effect of solvent was observed for the pseudostilbene-type compounds. To characterize the allowed two-photon absorption transitions for azoaromatic compounds, the response functions formalism combined with DFT using the hybrid B3LYP and PBE0 functionals and the long-range corrected CAM-B3LYP functional was employed. The theoretical results support the previous findings based on the three-state model. The model takes into account the ground and two electronic excited states and has already been used to describe and interpret the two-photon absorption spectrum of azoaromatic compounds. The highest energy two-photon allowed transition for the pseudostilbene-type compounds shows to be more effectively affected (similar to 20%) by the torsion of the molecular structure than the lowest allowed transition (similar to 10%). In order to elucidate the effect of the solvent on the two-photon absorption spectra, the lowest allowed two-photon transition (dipolar transition) for each compound was analyzed using a two-state approximation and the polarizable continuum model. The results obtained reveal that the effect of solvent increases drastically the two-photon cross-section of the dipolar transition of the pseudostilbene-type compounds. In general, the features of both one- and two-photon absorption spectra of the azoaromatic compounds are well reproduced by the theoretical calculations.

Adenosine binding to low-molecular-weight purine nucleoside phosphorylase: the structural basis for recognition based on its complex with the enzyme from Schistosoma mansoni

Schistosomes are unable to synthesize purines de novo and depend exclusively on the salvage pathway for their purine requirements. It has been suggested that blockage of this pathway could lead to parasite death. The enzyme purine nucleoside phosphorylase (PNP) is one of its key components and molecules designed to inhibit the low-molecular-weight (LMW) PNPs, which include both the human and schistosome enzymes, are typically analogues of the natural substrates inosine and guanosine. Here, it is shown that adenosine both binds to Schistosoma mansoni PNP and behaves as a weak micromolar inhibitor of inosine phosphorolysis. Furthermore, the first crystal structures of complexes of an LMW PNP with adenosine and adenine are reported, together with those with inosine and hypoxanthine. These are used to propose a structural explanation for the selective binding of adenosine to some LMW PNPs but not to others. The results indicate that transition-state analogues based on adenosine or other 6-amino nucleosides should not be discounted as potential starting points for alternative inhibitors.

Evolutionary dynamics on rugged fitness landscapes: Exact dynamics and information theoretical aspects

The parallel mutation-selection evolutionary dynamics, in which mutation and replication are independent events, is solved exactly in the case that the Malthusian fitnesses associated to the genomes are described by the random energy model (REM) and by a ferromagnetic version of the REM. The solution method uses the mapping of the evolutionary dynamics into a quantum Ising chain in a transverse field and the Suzuki-Trotter formalism to calculate the transition probabilities between configurations at different times. We find that in the case of the REM landscape the dynamics can exhibit three distinct regimes: pure diffusion or stasis for short times, depending on the fitness of the initial configuration, and a spin-glass regime for large times. The dynamic transition between these dynamical regimes is marked by discontinuities in the mean-fitness as well as in the overlap with the initial reference sequence. The relaxation to equilibrium is described by an inverse time decay. In the ferromagnetic REM, we find in addition to these three regimes, a ferromagnetic regime where the overlap and the mean-fitness are frozen. In this case, the system relaxes to equilibrium in a finite time. The relevance of our results to information processing aspects of evolution is discussed.

Theoretical investigation of atomic and electronic structures of Ga(2)O(3)(ZnO)(6)

Transparent conducting oxides (TCO) are widely used in technological applications ranging from photovoltaics to thin-film transparent field-effect transistors. In this work we report a first-principles investigation, based on density-functional theory, of the atomic and electronic properties of Ga(2)O(3)(ZnO)(6) (GZO(6)), which is a promising candidate to be used as host oxide for wide band gap TCO applications. We identify a low-energy configuration for the coherent distribution of the Ga and Zn atoms in the cation positions within the experimentally reported orthorhombic GZO(6) structure. Four Ga atoms are located in four-fold sites, while the remaining 12 Ga atoms in the unit cell form four shared Ga agglomerates (a motif of four atoms). The Zn atoms are distributed in the remaining cation sites with effective coordination numbers from 3.90 to 4.50. Furthermore, we identify the natural formation of twin-boundaries in GZO(6), which can explain the zigzag modulations observed experimentally by high-resolution transmission electron microscopy in GZO(n) (n=9). Due to the intrinsic twin-boundary formation, polarity inversion in the ZnO tetrahedrons is present which is facilitated by the formation of the Ga agglomerates. Our analysis shows that the formation of fourfold Ga sites and Ga agglomerates are stabilized by the electronic octet rule, while the distribution of Ga atoms and the formation of the twin-boundary help alleviate excess strain. Finally we identify that the electronic properties of GZO(6) are essentially determined by the electronic properties of ZnO, i.e., there are slight changes in the band gap and optical absorption properties.

Novel insights into the genomic basis of citrus canker based on the genome sequences of two strains of Xanthomonas fuscans subsp aurantifolii

Background: Citrus canker is a disease that has severe economic impact on the citrus industry worldwide. There are three types of canker, called A, B, and C. The three types have different phenotypes and affect different citrus species. The causative agent for type A is Xanthomonas citri subsp. citri, whose genome sequence was made available in 2002. Xanthomonas fuscans subsp. aurantifolii strain B causes canker B and Xanthomonas fuscans subsp. aurantifolii strain C causes canker C. Results: We have sequenced the genomes of strains B and C to draft status. We have compared their genomic content to X. citri subsp. citri and to other Xanthomonas genomes, with special emphasis on type III secreted effector repertoires. In addition to pthA, already known to be present in all three citrus canker strains, two additional effector genes, xopE3 and xopAI, are also present in all three strains and are both located on the same putative genomic island. These two effector genes, along with one other effector-like gene in the same region, are thus good candidates for being pathogenicity factors on citrus. Numerous gene content differences also exist between the three cankers strains, which can be correlated with their different virulence and host range. Particular attention was placed on the analysis of genes involved in biofilm formation and quorum sensing, type IV secretion, flagellum synthesis and motility, lipopolysacharide synthesis, and on the gene xacPNP, which codes for a natriuretic protein. Conclusion: We have uncovered numerous commonalities and differences in gene content between the genomes of the pathogenic agents causing citrus canker A, B, and C and other Xanthomonas genomes. Molecular genetics can now be employed to determine the role of these genes in plant-microbe interactions. The gained knowledge will be instrumental for improving citrus canker control.

Metastable BrO(2+) and NBr(2+) molecules in the gas phase

The doubly positively charged gas-phase molecules BrO(2+) and NBr(2+) have been produced by prolonged high-current energetic oxygen (17 keV (16)O(-)) ion surface bombardment (ion beam sputtering) of rubidium bromide (RbBr) and of ammonium bromide (NH(4)Br) powdered ionic salt samples, respectively, pressed into indium foil. These novel species were observed at half-integer m/z values in positive ion mass spectra for ion flight times of roughly similar to 12 mu s through a magnetic-sector secondary ion mass spectrometer. Here we present these experimental results and combine them with a detailed theoretical investigation using high level ab initio calculations of the ground states of BrO(2+) and NBr(2+), and a manifold of excited electronic states. NBr(2+) and BrO(2+), in their ground states, are long-lived metastable gas-phase molecules with well depths of 2.73 x 10(4) cm(-1) (3.38 eV) and 1.62 x 10(4) cm(-1) (2.01 eV); their fragmentation channels into two monocations lie 2.31 x 10(3) cm(-1) (0.29 eV) and 2.14 x 10(4) cm(-1) (2.65 eV) below the ground state minimum. The calculated lifetimes for NBr(2+) (v '' < 35) and BrO(2+) (v '' < 18) are large enough to be considered stable against tunneling. For NBr(2+), we predicted R(e) = 3.051 a(0) and omega(e) = 984 cm(-1); for BrO(2+), we obtained 3.033 a(0) and 916 cm(-1), respectively. The adiabatic double ionization energies of BrO and NBr to form metastable BrO(2+) and NBr(2+) are calculated to be 30.73 and 29.08 eV, respectively. The effect of spin-orbit interactions on the low-lying (Lambda + S) states is also discussed. (C) 2011 American Institute of Physics. [doi:10.1063/1.3562121]

The electronic states of SeF: A reinterpretation of the chemiluminescent emission of the reaction of selenium with fluorine

The low-lying doublet and quartet electronic states of the species SeF correlating with the first dissociation channel are investigated theoretically at a high-level of electronic correlation treatment, namely, the complete active space self-consistent field/multireference single and double excitations configuration interaction (CASSCF/MRSDCI) using a quintuple-zeta quality basis set including a relativistic effective core potential for the selenium atom. Potential energy curves for (Lambda+S) states and the corresponding spectroscopic properties are derived that allows for an unambiguous assignment of the only spectrum known experimentally as due to a spin-forbidden X (2)Pi-a (4)Sigma(-) transition, and not a A (2)Pi-X (2)Pi transition as assumed so far. For the bound excited doublets, yet unknown experimentally, this study is the first theoretical characterization of their spectroscopic properties. Also the spin-orbit coupling constant function for the X (2)Pi state is derived as well as the spin-orbit coupling matrix element between the X (2)Pi and a (4)Sigma(-) states. Dipole moment functions and vibrationally averaged dipole moments show SeF to be a very polar species. An overview of the lowest-lying spin-orbit (Omega) states completes this description. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3426315]

The importance of scientific literacy in fostering education for sustainability: Theoretical considerations and preliminary findings from a Brazilian experience

Scientific literacy can be considered as a new demand of post-industrial society. It seems necessary in order to foster education for sustainability throughout students` academic careers. Universities striving to teach sustainability are being challenged to integrate a holistic perspective into a traditional undergraduate curriculum, which aims at specialization. This new integrative, inter- and transdisciplinary epistemological approach is necessary to cultivate autonomous citizenship, i.e., that each citizen be prepared to understand and participate in discussions about the complex contemporary issues posed by post-industrial society. This paper presents an epistemological framework to show the role of scientific literacy in fostering education for sustainability. We present a set of 26 collaborative concept maps (CCmaps) in order to illustrate an instance of theory becoming practice. During a required course for first-year undergraduate students (ACH 0011, Natural Sciences), climate change was presented and discussed in broad perspective by using CCmaps. We present students` CCmaps to show how they use concepts from quantitative and literacy disciplines to deal with the challenges posed by the need of achieving a sustainable development. (C) 2009 Elsevier Ltd. All rights reserved.

Theoretical study on the molecular and electronic properties of some substances used for diabetes mellitus treatment

Diabetes mellitus (DM) is a disease that affects a large number of people, and the number of problems associated with the disease has been increasing in the past few decades. These problems include cardiovascular disorders, blindness and the eventual need to amputate limbs. Therefore, the quality of life for people living with DM is less than it is for healthy people. In several cases, metabolic syndrome (MS), which can be considered a disturbance of the lipid metabolism, is associated with DM. In this work, two drugs used to treat DM, pioglitazone and rosiglitazone, were studied using theoretical methods, and their molecular properties were related to the biological activity of these drugs. From the results, it was possible to correlate the properties of each substance-particularly electronic properties-with the biological interactions that are linked to their pharmacological effects. These results suggest that there are future prospects for designing or developing new drugs based on the correlation between theoretical and experimental properties.