Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors

Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain of biological activities when compared with tocopherols. Amongst the most promising therapeutic application, anti-inflammatory potency has been evaluated through the inhibition of various mediators of inflammation. Here, we worked on the isolation of two natural isoforms of garcinoic acid (i.e., δ and γ) from two different sources, respectively, Garcinia kola seeds and Garcinia amplexicaulis bark. We also developed semisynthetic strategies to access the other two non-natural α- and β-garcinoic acid isoforms. In the next stage of our work, microsomal prostaglandin E2 synthase was defined as a target to evaluate the anti-inflammatory potential of the four garcinoic acid isomers. Both dimethylated isoforms, β- and γ-garcinoic acid, exhibited the lowest IC50, 2.8 µM and 2.0 µM, respectively. These results showed that the affinity of tocotrienol analogues to microsomal prostaglandin E2 synthase-1 most probably contributes to the anti-inflammatory potential of this class of derivatives

The Energy Level Shifts, Wave Functions and the Probability Current Distributions for the Bound Scalar and Spinor Particles Moving in a Uniform Magnetic Field

We discuss the equations for the bound one-active electron states based on the analytic solutions of the Schrodinger and Pauli equations for a uniform magnetic field and a single attractive $\delta({\bf r})$-potential. It is vary important that ground electron states in the magnetic field differ essentially from the analogous state of spin-0 particles, whose binding energy was intensively studied more than forty years ago. We show that binding energy equations for spin-1/2 particles can be obtained without using the language of boundary conditions in the $\delta$-potential model developed in pioneering works. We use the obtained equations to calculate the energy level displacements analytically and demonstrate nonlinear dependencies on field intensity. We show that the magnetic field indeed plays a stabilizing role in considered systems in a case of the weak intensity, but the opposite occurs in the case of strong intensity. These properties may be important for real quantum mechanical fermionic systems in two and three dimensions. We also analyze the exact solution of the Pauli equation for an electron moving in the potential field determined by the three-dimensional $\delta$-well in the presence of a strong magnetic field. We obtain asymptotic expressions for this solution for different values of the problem parameters. In addition, we consider electron probability currents and their dependence on the magnetic field. We show that including the spin in the framework of the nonrelativistic approach allows correctly taking the effect of the magnetic field on the electric current into account. The obtained dependencies of the current distribution, which is an experimentally observable quantity, can be manifested directly in scattering processes, for example.Comment: 31 pages, 10 figure

Time and Origin of Cichlid Colonization of the Lower Congo Rapids

Most freshwater diversity is arguably located in networks of rivers and streams, but, in contrast to lacustrine systems riverine radiations, are largely understudied. The extensive rapids of the lower Congo River is one of the few river stretches inhabited by a locally endemic cichlid species flock as well as several species pairs, for which we provide evidence that they have radiated in situ. We use more that 2,000 AFLP markers as well as multilocus sequence datasets to reconstruct their origin, phylogenetic history, as well as the timing of colonization and speciation of two Lower Congo cichlid genera, Steatocranus and Nanochromis. Based on a representative taxon sampling and well resolved phylogenetic hypotheses we demonstrate that a high level of riverine diversity originated in the lower Congo within about 5 mya, which is concordant with age estimates for the hydrological origin of the modern lower Congo River. A spatial genetic structure is present in all widely distributed lineages corresponding to a trisection of the lower Congo River into major biogeographic areas, each with locally endemic species assemblages. With the present study, we provide a phylogenetic framework for a complex system that may serve as a link between African riverine cichlid diversity and the megadiverse cichlid radiations of the East African lakes. Beyond this we give for the first time a biologically estimated age for the origin of the lower Congo River rapids, one of the most extreme freshwater habitats on earth

Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors

<p>Abstract</p> <p>Background</p> <p>We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.</p> <p>Results</p> <p>Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.</p> <p>Conclusion</p> <p>The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.</p

Comprehensive Structural and Substrate Specificity Classification of the Saccharomyces cerevisiae Methyltransferome

Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity

An operational overview of the EXport processes in the ocean from RemoTe sensing (EXPORTS) northeast pacific field deployment

The goal of the EXport Processes in the Ocean from RemoTe Sensing (EXPORTS) field campaign is to develop a predictive understanding of the export, fate, and carbon cycle impacts of global ocean net primary production. To accomplish this goal, observations of export flux pathways, plankton community composition, food web processes, and optical, physical, and biogeochemical (BGC) properties are needed over a range of ecosystem states. Here we introduce the first EXPORTS field deployment to Ocean Station Papa in the Northeast Pacific Ocean during summer of 2018, providing context for other papers in this special collection. The experiment was conducted with two ships: a Process Ship, focused on ecological rates, BGC fluxes, temporal changes in food web, and BGC and optical properties, that followed an instrumented Lagrangian float; and a Survey Ship that sampled BGC and optical properties in spatial patterns around the Process Ship. An array of autonomous underwater assets provided measurements over a range of spatial and temporal scales, and partnering programs and remote sensing observations provided additional observational context. The oceanographic setting was typical of late-summer conditions at Ocean Station Papa: a shallow mixed layer, strong vertical and weak horizontal gradients in hydrographic properties, sluggish sub-inertial currents, elevated macronutrient concentrations and low phytoplankton abundances. Although nutrient concentrations were consistent with previous observations, mixed layer chlorophyll was lower than typically observed, resulting in a deeper euphotic zone. Analyses of surface layer temperature and salinity found three distinct surface water types, allowing for diagnosis of whether observed changes were spatial or temporal. The 2018 EXPORTS field deployment is among the most comprehensive biological pump studies ever conducted. A second deployment to the North Atlantic Ocean occurred in spring 2021, which will be followed by focused work on data synthesis and modeling using the entire EXPORTS data set

ELECTROREFLECTANCE OF IV-VI COMPOUNDS

La modulation par un champ électrique exagère considérablement la structure de la réflectance d'un solide. Outre une plus grande sensibilité, le fait que le paramètre de modulation détruise les symétries, donne, sur ces symétries, des renseignements utiles pour l'identification des points critiques. Les transitions interbandes, les excitations excitoniques, et les interactions entre les porteurs et le réseau peuvent, en principe, être évaluées pour ce qui est de leurs contributions relatives au processus de l'absorption optique. Jusqu'ici, peu de mesures d'électroréflectance ont été faites sur les composés IV-VI. Comme pour tous les autres matériaux, la structure existant dans les mesures optiques statiques se trouve renforcée. On trouve aussi une structure nouvelle qui ne se relie pas à des transitions observées auparavant. Certaines propriétés caractéristiques des IV-VI rendent les mesures et l'interprétation des spectres d'électroréflectance difficiles. Une forte concentration de porteurs de charge amène la compression des régions de charge d'espace qui sont plus petites que la profondeur de pénétration de la lumière réfléchie. Il faut ainsi modifier l'analyse. La forte constante diélectrique déforme la forme de l'onde par l'intermédiaire de retards de phase entre la modulation et la réponse. Les électrolytes faibles non-aqueux nécessaires pour l'infrarouge, en présence de substrats solubles ajoutent des effets parasites de charge d'espace. Tous ces facteurs compliquent l'interprétation qualitative du profil des raies. Au moment présent une analyse de points critiques ne peut être qu'un essai ; cependant, on peut relier certains résultats expérimentaux aux calculs de structure de bande existants. En général, il y a accord. Certains aspects des résultats expérimentaux suggèrent que l'électroréflectance dans les composés IV-VI comme SnTe n'est pas un phénomène dû aux points critiques. Les spectres de la série des cristaux mixtes PbxSn1-xTe changent de façon très nette d'un bout à l'autre de l'échelle des concentrations. Bien qu'elle renforce encore la structure observée par les méthodes optiques statiques, il est possible que l'électroréflectance offre des possibilités limitées, quant aux phénomènes dus aux points critiques, dans des matériaux dégénérés.Electric-field modulation considerably enhances structure in the reflectance of a solid. In addition to the greater sensitivity, the symmetry-breaking effect of the modulation parameter provides symmetry information useful in the identification of critical points. Interband transitions, excitonic excitations and interactions between carriers and lattice can, in principle, be evaluated in their relative contributions to the optical absorption process. The present status of theory and experiment is briefly reviewed in this respect. So far few electroreflectance measurements have been performed on IV-VI compounds. As for all other materials the existing structure in static optical measurements is enhanced. Some new structure does not relate to formerly observed transitions. Properties characteristic for IV-VI compounds make measurements and interpretation of their electroreflectance spectra difficult. A high-carrier concentration results in compressed space-charge layers which are smaller than the penetration depth of the reflected light. This requires a modified analysis. A large dielectric constant distorts the waveform through phase-lags between modulation and response. Weak nonaqueous electrolytes required in the infrared and in the presence of soluble substrates add parasitary space-charge effects. All these factors complicate quantitative line-shape discussions. At present, a critical-point analysis can only be tentative ; however, some of the experimental results can be correlated to existing band-structure calculations and, in general, support their claims. Some features of the experimental results suggest that electroreflectance in degenerate IV-VI compounds, such as SnTe, is not a critical-point phenomenon. Spectra of the mixed-crystal series PbxSn1-xTe change from one type at one end to a markedly different type at the other. Although still enhancing the structure of static optical techniques, electroreflectance is probably restricted as a critical-point phenomenon in these degenerate materials

ELECTROREFLECTANCE

Electroreflectance is the oldest of a growing number of differential reflectance techniques which form the derivative of the joint-density-of-states function by the periodic change of an external parameter such as the electric field. Since this function possesses analytic singularities at critical points, it is possible to lift these key parameters of band structure analysis from the large background absorption caused by non-critical areas of the Brillouin zone. Phase-sensitive synchronous observation of the field-induced reflectance change produces structure which is considerably enhanced compared with static reflectance measurements. This gain in resolution is not the essential feature of the new techniques, however. Some features of electroreflectance are discussed from which information can be derived on the symmetry character of a critical point and its location in the Brillouin zone. Elaborating on the case of silicon, it is pointed out that the interpretation of electroreflectance structure could lead to an expansion of certain aspects of band structure analysis derived from the results of previous static techniques. It is suggested that in the case of interband energy surfaces nearly flat in k-space, as for the 3.4 eV region of silicon, separate interpretation of static reflectance and electroreflectance is required, since the static spectrum may involve extended regions of the Brillouin zone while the derivative spectrum may relate to the critical points. The sensitivity of such a flat interband surface to distortion by changes in external parameters can cause changes in symmetry class and location of critical points.L'électroréflectance est la plus ancienne des techniques de réflectance différentielle, de plus en plus nombreuses, qui donnent la dérivee de la fonction de densité d'états par variation périodique d'un paramètre extérieur, comme le champ électrique. Comme cette fonction présente des singularités analytiques aux points critiques, on peut extraire ces paramètres clefs de la structure des bandes, de la forte absorption de fond due aux parties non critiques de la zone de Brillouin. L'observation synchrone, sensible à la phase, des changements de réflectance produits par le champ donne une structure fortement renforcée par rapport aux mesures de réflectance statiques. Cependant, ce gain en résolution n'est pas l'intérêt essentiel des nouvelles techniques. On discute certains caractères de l'électroréflectance qui peuvent fournir des informations sur la nature de la symétrie d'un point critique, et sa localisation dans la zone de Brillouin. En precisant le cas du silicium, on constate que l'interpretation de la structure d'électroréflectance peut conduire à un développement de certains aspects de l'analyse des structures de bandes, dérivés des résultats des techniques statiques précédentes. On suggère que, dans le cas de surfaces d'énergie interbandes presque plates dans l'espace des k (comme pour la région de 3,4 eV du silicium), des interprétations différentes sont nécessaires pour la réflectance statique et pour l'électroréflectance, puisque le spectre statique peut inclure des régions étendues de la zone de Brillouin, tandis que le spectre dérivé correspond aux points critiques. La sensibilité d'une surface interbande plate à la distorsion par le changement des paramètres externes peut produire des variations de la classe de symétrie et de la position des points critiques