Aromatase activity after a short-course of letrozole administration in adult men at sea level and at high altitude (with or without excessive erythrocytosis)

Men living at high altitudes in Peru compared to sea level counterparts have erythrocytosis (hemoglobin 16-21?g/dl) or excessive erythrocytosis (hemoglobin>21?g/dl). High testosterone (T) levels in men at high altitude (HA) were associated with excessive erythrocytosis. High androgen levels could be due to a low aromatase activity or to an elevated rate of conversion from precursors to testosterone. The aim of this study was to evaluate aromatase activity and rate of conversion from precursors to testosterone before and after administration of the aromatase enzyme inhibitor letrozole (5?mg/day) for a 5-day period to men at HA and at sea level (SL). The response to short term aromatase inhibition was assessed in 30 adult men living at sea level, 31 native men at HA with erythrocytosis (Hb 16-21?g/dl), and 35 men at HA with excessive erythrocytosis (Hb>21?g/dl). Serum hormone levels, estradiol/testosterone, testosterone/androstenedione, and testosterone/dehydroepiandrosterone sulfate (DHEAS) ratios were measured. Men with erythrocytosis had lower basal serum T/androstenedione ratios than men with excessive erythrocytosis at HA and men at sea level. Men at HA with excessive erythrocytosis had higher T/DHEAS ratios than men with erythrocytosis and than those at sea level before and after letrozole administration. After letrozole administration, both groups of men at high altitude (with erythrocytosis or with excessive erythrocytosis) showed lower aromatase activities than those at sea level. In conclusion, higher serum testosterone levels in men with excessive erythrocytosis were associated with an increased rate of conversion from DHEAS to testosterone rather than to a lower aromatase activity.     

Difficult macromolecular structures determined using X-ray diffraction techniques

Macromolecular crystallography has been, for the last few decades, the main source of structural information of biological macromolecular systems and it is one of the most powerful techniques for the analysis of enzyme mechanisms and macromolecular interactions at the atomic level. In addition, it is also an extremely powerful tool for drug design. Recent technological and methodological developments in macromolecular X-ray crystallography have allowed solving structures that until recently were considered difficult or even impossible, such as structures at atomic or subatomic resolution or large macromolecular complexes and assemblies at low resolution. These developments have also helped to solve the 3D-structure of macromolecules from twin crystals. Recently, this technique complemented with cryo-electron microscopy and neutron crystallography has provided the structure of large macromolecular machines with great precision allowing understanding of the mechanisms of their function.     

Differential expression of disialic acids in the cerebellum of senile mice

It is known that disialic acids (diSia) are present in the mammalian brain. However, the precise anatomical distribution and the chronology of its expression along life are not well studied yet. It is accepted that the transfer of diSia in the brain is mediated mainly by the enzyme ST8Sia III (α2,8-sialyltransferase III). We studied the expression of diSia glycoepitopes and of the ST8Sia III gene in different structures of the mouse brain at different postnatal stages by immunohistochemistry and real-time polymerase chain reaction, respectively. C57BL/6 mice of different stages were used. Samples of hippocampus, olfactory bulb, cortex and cerebellum were processed for studies of molecular biology and immunohistochemistry. Histological analysis revealed an important decrease in diSia labeling in the senile cerebellum compared with other structures and stages (P???0.001). In concordance with these results, a significant decrease in ST8Sia III gene expression was found in the cerebellum of senile animals (P?相似文献   

Rapid conversion of spirostans into furostan skeletons at room temperature

We report a facile protocol to obtain 22-substituted furostans and pseudosapogenins in high yields from (25R)- and (25S)-sapogenins. This method involves the treatment of the sapogenin with acetic-trifluoroacetic mixed anhydride and BF(3)·OEt(2) at room temperature, followed by the addition of a nucleophile (H(2)O, MeOH or KSeCN). In the case of 22-hydroxyfurostans, they can be transformed to pseudosapogenins by treatment with p-toluensulfonic acid.     

The Epidemiology of Mould Infections in Argentina: Review and Experience

During the last decades, there has been an increasing proportion of patients susceptible to invasive fungal disease (IFD). The epidemiology of IFD varies mainly due to geography, antifungal exposure, and nosocomial reservoirs. We reviewed the Argentinean epidemiology of invasive mold disease (IMD) by analyzing laboratory and clinical data. Invasive mold disease was the second most prevalent IFD following the yeasts, with a prevalence that ranged from 0.98 to 1.31/100,000 population. The majority (60?C85?%) of IMD was caused by hyalohyphomycetes followed by Mucorales (6?C21?%) and phaeohyphomycetes (7?C13?%). The most prevalent genera were Aspergillus (40?C67?% of IMD) followed by Fusarium (10?C14?%). The most prevalent species were A. fumigatus (38?C50?%) followed by A. flavus (27?C43?%). In immunocompromised patients in Argentina the most prevalent agents of IMD are Aspergillus, followed by Fusarium and Mucorales, while the most prevalent Aspergillus species are A. fumigatus followed by A. flavus.     

Satellite surface reflectance improves habitat distribution mapping: a case study on heath and shrub formations in the Cantabrian Mountains (NW Spain)

Aim We aim to map the distribution of four heath and shrub formations constituting habitats of high conservation priority in Europe, whose occurrence is strongly dependent on human activities. Specifically, we assess whether the use of LANDSAT data in habitat distribution modelling may account for land use management, allowing accurate mapping of real distribution patterns. In particular, we explore whether reflectance values may be a better alternative to other remote sensing data traditionally used in modelling approaches (i.e. spectral vegetation indices and classified land cover maps). Finally, we test whether modelling performance is affected by the ecological traits of the dominant species of the target formations. Location Cantabrian Mountains (NW Spain). Methods We generated maps for the four formations (two specialists vs. two generalists) using MaxEnt. First, we ran the models with environmental predictors only (topography, climate, lithology and human disturbances). Then, we compared the advantages of including, in turn, different data derived from LANDSAT imagery: reflectance values (corresponding to different wavelength channels of the multispectral image), a spectral index and a land cover map. We assessed changes in explanatory power and also in the formation’s predicted distribution patterns. Results Formations dominated by specialist species were accurately mapped on a base of environmental variables only, whereas those dominated by generalists were overpredicted. Average mean temperature, southness and distance to urban areas were the variables contributing most in predictions of environmental models. LANDSAT channels increased the accuracy of all models, but mainly those for formations dominated by generalist species. They showed advantages against other remote sensing data traditionally used in modelling approaches. Main conclusions Habitat distribution models allowed accurate mapping of heath and shrub formations. The use of reflectance values as predictors improved the accuracy of the models, particularly for formations dominated by generalist species, supplying environmental information that was otherwise unavailable.     

Phylogenetic analysis of four nuclear protein-encoding genes largely corroborates the traditional classification of Bivalvia (Mollusca)

Revived interest in molluscan phylogeny has resulted in a torrent of molecular sequence data from phylogenetic, mitogenomic, and phylogenomic studies. Despite recent progress, basal relationships of the class Bivalvia remain contentious, owing to conflicting morphological and molecular hypotheses. Marked incongruity of phylogenetic signal in datasets heavily represented by nuclear ribosomal genes versus mitochondrial genes has also impeded consensus on the type of molecular data best suited for investigating bivalve relationships. To arbitrate conflicting phylogenetic hypotheses, we evaluated the utility of four nuclear protein-encoding genes-ATP synthase β, elongation factor-1α, myosin heavy chain type II, and RNA polymerase II-for resolving the basal relationships of Bivalvia. We sampled all five major lineages of bivalves (Archiheterodonta, Euheterodonta [including Anomalodesmata], Palaeoheterodonta, Protobranchia, and Pteriomorphia) and inferred relationships using maximum likelihood and Bayesian approaches. To investigate the robustness of the phylogenetic signal embedded in the data, we implemented additional datasets wherein length variability and/or third codon positions were eliminated. Results obtained include (a) the clade (Nuculanida+Opponobranchia), i.e., the traditionally defined Protobranchia; (b) the monophyly of Pteriomorphia; (c) the clade (Archiheterodonta+Palaeoheterodonta); (d) the monophyly of the traditionally defined Euheterodonta (including Anomalodesmata); and (e) the monophyly of Heteroconchia, i.e., (Palaeoheterodonta+Archiheterodonta+Euheterodonta). The stability of the basal tree topology to dataset manipulation is indicative of signal robustness in these four genes. The inferred tree topology corresponds closely to those obtained by datasets dominated by nuclear ribosomal genes (18S rRNA and 28S rRNA), controverting recent taxonomic actions based solely upon mitochondrial gene phylogenies.     

Production of Fibronectin Binding Protein A at the Surface of Lactococcus lactis Increases Plasmid Transfer In Vitro and In Vivo

Lactococci are noninvasive lactic acid bacteria frequently used as protein delivery vectors and, more recently, as DNA delivery vehicles. We previously showed that Lactococcus lactis (LL) expressing the Fibronectin-Binding Protein A of Staphylococcus aureus (LL-FnBPA+) showed higher internalization rates in vitro in Caco-2 cells than the native (wt) lactococci and were able to deliver a eukaryotic Green Fluorescent Protein (GFP) expression plasmid in 1% of human Caco-2 cells. Here, using the bovine beta-lactoglobulin (BLG), one of the major cow''s milk allergen, and GFP we characterized the potential of LL-FnBPA+ as an in vivo DNA vaccine delivery vehicle. We first showed that the invasive strain LL-FnBPA+ carrying the plasmid pValac:BLG (LL-FnBPA+ BLG) was more invasive than LL-BLG and showed the same invasivity as LL-FnBPA+. Then we demonstrated that the Caco-2 cells, co-incubated with LL-FnBPA+ BLG produced up to 30 times more BLG than the Caco-2 cells co-incubated with the non invasive LL-BLG. Using two different gene reporters, BLG and GFP, and two different methods of detection, EIA and fluorescence microscopy, we showed in vivo that: i) in order to be effective, LL-FnBPA+ required a pre-coating with Fetal Calf Serum before oral administration; ii) plasmid transfer occurred in enterocytes without regard to the strains used (invasive or not); iii) the use of LL-FnBPA+ increased the number of mice producing BLG, but not the level of BLG produced. We thus confirmed the good potential of invasive recombinant lactic acid bacteria as DNA delivery vector in vivo.