Actions of progesterone on human sperm: A model of non-genomic effects of steroids

Non-genomic actions of steroids have been extensively studied in the last few years. Among these actions, the non-genomic effect of progesterone (P) on human spermatozoa appears to be very promising, in view of the dramatic effect of this steroid on intracellular calcium, activation of tyrosine kinase, and induction of acrosome reaction. We have shown that the ability of spermatozoa to respond to P increases during the process of capacitation and is not counteracted by the P-receptor antagonist RU486 nor by the GABA_A antagonists bicuculline and picrotoxin. We have also shown that P increases tyrosine phosphorylation of a sperm protein of about 97 kDa, suggesting activation of tyrosine kinase(s). In addition, we found that P induces a perturbation of sperm membrane phospholipid metabolism resulting in an increase of synthesis of platelet-activating factor and liberation of arachidonic acid. Results of these biochemical studies indicate that P is able to stimulate several signal transduction pathways in human sperm. We have also investigated responsiveness to P in sperm of oligozoospermic subjects as well as of men undergoing an in vitro fertilization (IVF) program. Our results show that the percentage increases of intracellular calcium and acrosome reaction in response to P is significantly reduced in oligozoospermic men as well as in subjects with reduced fertilization rate. Moreover, in the latter subjects response to P is highly significantly correlated to fertilization rate of oocytes. These studies indicate that a biochemical alteration of sperm in their capacity to respond to P might be responsible for reduced fertilizing ability     

Conformational and kinetic features of the morphine-Mn(II) interaction as probed by nuclear paramagnetic resonance investigations

The nature of binding between manganese ions and morphine was studied using Fourier transform proton nuclear magnetic resonance techniques. Proton relaxation times in the presence of Mn(II) ions were determined together with their temperature dependence. Slow exchange conditions were observed for the NCH₃ group, while fast exchange conditions applied for all the other protons. The rotational correlation time of the complex was approximated by that of the free morphine molecule, as measured by selective and nonselective proton relaxation rate measurements. The distances between the metal ion and proton nuclei of morphine were evaluated on the basis of an association constant, measured from water proton spin-lattice relaxation rate binding studies. The results indicate that the metal binds directly to the two oxydryls with K_ass = 9.7 × 10^?3.The rate constant for the interaction of Mn(II) with the opiate is 2.25 × 10⁴ sec^?1 at 27°C, as determined from the temperature dependence of longitudinal relaxation rate of the NCH₃ group.     

Computer-aided Topological Analysis of the Faujasite Lattice II: Monte Carlo Solution for Zeolite-Y

Abstract

In this paper we extend to the case of Zeolite-Y the topological analysis of the Aluminum distributions of the Faujasite lattice proposed in a previous paper. Here the exact counting of all the inequivalent configurations is complicated by the huge number of possible structures, but the physically relevant distributions can be found by using a Monte Carlo method which turns out to be very efficient. We compare, whenever possible, the Monte Carlo results with the exact countings, and in all these cases we find a perfect agreement. Thus the approach seems to be applicable to the study of every class of Zeolites. In the first two sections the method is introduced, and in the third one the relevant results for the Zeolite-Y are presented and discussed.     

Tópicos y reflexiones sobre la reducción de ingresos hospitalarios: de la evidencia a la práctica

Demographic changes and the economic situation of the recent years have conditioned a turning point in health policies, which have decided to progressively prioritize chronicity care programs. Given that hospital costs were concentrated in attention to patients with chronic diseases, reduction on admissions is now a priority target.     

Distinct Mutants of Retrograde Intraflagellar Transport (IFT) Share Similar Morphological and Molecular Defects

A microtubule-based transport of protein complexes, which is bidirectional and occurs between the space surrounding the basal bodies and the distal part of Chlamydomonas flagella, is referred to as intraflagellar transport (IFT). The IFT involves molecular motors and particles that consist of 17S protein complexes. To identify the function of different components of the IFT machinery, we isolated and characterized four temperature-sensitive (ts) mutants of flagellar assembly that represent the loci FLA15, FLA16, and FLA17. These mutants were selected among other ts mutants of flagellar assembly because they displayed a characteristic bulge of the flagellar membrane as a nonconditional phenotype. Each of these mutants was significantly defective for the retrograde velocity of particles and the frequency of bidirectional transport but not for the anterograde velocity of particles, as revealed by a novel method of analysis of IFT that allows tracking of single particles in a sequence of video images. Furthermore, each mutant was defective for the same four subunits of a 17S complex that was identified earlier as the IFT complex A. The occurrence of the same set of phenotypes, as the result of a mutation in any one of three loci, suggests the hypothesis that complex A is a portion of the IFT particles specifically involved in retrograde intraflagellar movement.     

Metabolic modeling predicts specific gut bacteria as key determinants for Candida albicans colonization levels

Candida albicans is a leading cause of life-threatening hospital-acquired infections and can lead to Candidemia with sepsis-like symptoms and high mortality rates. We reconstructed a genome-scale C. albicans metabolic model to investigate bacterial-fungal metabolic interactions in the gut as determinants of fungal abundance. We optimized the predictive capacity of our model using wild type and mutant C. albicans growth data and used it for in silico metabolic interaction predictions. Our analysis of more than 900 paired fungal–bacterial metabolic models predicted key gut bacterial species modulating C. albicans colonization levels. Among the studied microbes, Alistipes putredinis was predicted to negatively affect C. albicans levels. We confirmed these findings by metagenomic sequencing of stool samples from 24 human subjects and by fungal growth experiments in bacterial spent media. Furthermore, our pairwise simulations guided us to specific metabolites with promoting or inhibitory effect to the fungus when exposed in defined media under carbon and nitrogen limitation. Our study demonstrates that in silico metabolic prediction can lead to the identification of gut microbiome features that can significantly affect potentially harmful levels of C. albicans.Subject terms: Fungi, Infectious diseases, Metagenomics, Gastrointestinal diseases, Microbiome