Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro

The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (ρO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; ρO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it.     

Familial aggregation of blood pressure in 558 adopted children.

Blood pressure was measured in each member of 398 French-Canadian families with at least one adopted child of the same ethnic origin. Measurements were made at home by a nurse, usually with the subject seated. One comparison per family between parents and randomly chosen index children was made, using age- and sex-adjusted scores. The correlation in blood pressure scores between parents and natural children was highly significant (P less than 0.001), at 10.2% for systolic and 13.7% for diastolic in 140 homes with at least one natural child, but the correlation between parents and adopted children was nonsignificant, at 0.81% and 1.0%, in 398 homes with at least one adopted child. The correlation between pairs of natural children was significant (P less than 0.05), at 7.84% for systolic and 8.41% for diastolic, in 80 homes with more than one natural child but nonsignificant, at 0.49% and 1.69%, respectively, for pairs of adopted children in 138 families with more than one adopted child. It is concluded that heredity explains most of the familial resemblance of blood pressure in children.     

Design, synthesis, and characterization of peptide nanostructures having ion channel activity

We report the synthesis and the functional studies of multiple crown alpha-helical peptides designed to form artificial ion channels. The approach combines the versatility of solid phase peptide synthesis, the conformational predictability of peptidic molecules, and the solution synthesis of crown ethers with engineerable ion-binding abilities. Several biophysical methods were employed to characterize the activity and the mode of action of these crown peptide nanostructures. The 21 residue peptides bearing six 21-EC-7 turned out to facilitate the translocation of ions in a similar fashion to natural ion channels.     

Evolutionary dynamics of the glycan shield of the human immunodeficiency virus envelope during natural infection and implications for exposure of the 2G12 epitope

Elucidation of the kinetics of exposure of neutralizing epitopes on the envelope of human immunodeficiency virus type 1 (HIV-1) during the course of infection may provide key information about how HIV escapes the immune system or why its envelope is such a poor immunogen to induce broadly efficient neutralizing antibodies. We analyzed the kinetics of exposure of the epitopes corresponding to the broadly neutralizing human monoclonal antibodies immunoglobulin G1b12 (IgG1b12), 2G12, and 2F5 at the quasispecies level during infection. We studied the antigenicity and sequences of 94 full-length envelope clones present during primary infection and at least 4 years later in four HIV-1 clade B-infected patients. No or only minor exposure differences were observed for the 2F5 and IgG1b12 epitopes between the early and late clones. Conversely, the envelope glycoproteins of the HIV-1 quasispecies present during primary infection did not expose the 2G12 neutralizing epitope, unlike those present after several years in three of the four patients. Sequence analysis revealed major differences at potential N-linked glycosylation sites between early and late clones, particularly at positions known to be important for 2G12 binding. Our study, in natural mutants, confirms that the glycosylation sites N295, N332, and N392 are essential for 2G12 binding. This study demonstrates the relationship between the evolving "glycan shield " of HIV and the kinetics of exposure of the 2G12 epitope during the course of natural infection.     

Influence of a bimodal emergence strategy of a Dipteran host on life-history traits of its main parasitoids

Abstract. 1. Among a great diversity of other strategies, insects have evolved polymodal emergence patterns that can increase survival in the face of annual variations in environmental conditions. Delia radicum L. (Diptera: Anthomyiidae) is a polyvoltine pest that attacks several cultivated cruciferous species. At the time of emergence, most populations show a polymodal emergence of type A (i.e. all individuals that enter diapause in the same year terminate diapause the following growing season, and exhibit a bimodal emergence curve). This results in the occurrence of two sympatric phenotypes, early and late, which differ by the timing of adult emergence in both diapausing and non‐diapausing generations. 2. In Brittany, D. radicum pupae can be heavily parasitised by three parasitoids, Aleochara bilineata Gyll. (Coleoptera: Staphylinidae), Aleochara bipustulata L., and Trybliographa rapae (Hymenoptera: Eucoilidae). As in all parasitoids species, the successful development of both Aleochara species and T. rapae larvae depends mainly on the amount and quality of the food provided by the host. 3. The relationship between early and late host phenotype and (i) the parasitism efficiency, (ii) emergence patterns, and (iii) host selection behaviour were investigated for the three parasitoid species. 4. Depending on parasitoid species and their different parasitism and development mode, the results reveal that host phenotype can influence (i) survival and development time in T. rapae, and (ii) survival in Aleochara species. Aleochara larvae did not appear to discriminate between early and late host pupae on the basis of phenotype, but rather selected them according to their developmental stage. Furthermore, it was discovered that the same phenological strategy occurred in T. rapae and in D. radicum. However, for D. radicum the results indicate that such a strategy has a cost as the longer development time of late host pupae results in a longer period of time favourable for parasitism.     

Impacts of environmental changes on the hydrology and sedimentary processes at the confluence of St. Lawrence tributaries: potential effects on fluvial ecosystems

This study examines the effects of changes in St. Lawrence water levels and in hydrological regimes of two tributaries of the St. Lawrence, the Richelieu and Saint-François Rivers, on the sedimentary dynamics of their confluence in an historical context and in response to projected climate changes. Analysis of historical data indicates that alteration to St. Lawrence mean water levels and spring flood characteristics (duration, timing, and magnitude) have already impacted flow and sediment dynamics at tributary confluences. The major progradation of more than 1.5 km of the sedimentary front of the Saint-François delta into the shallow water of the fluvial Lake Saint-Pierre between 1859 and 2001 is associated with the combined effect of water level reduction in the lake, as a consequence of dredging of the navigation channel, and discharge regulation. High tributary discharges during periods of low water levels in the St. Lawrence have also contributed to accelerated delta front progression. Increases in temperature and changes in the precipitation regime projected for the current century were used into the HSAMI model to obtain hydrological simulations for the tributaries. Results indicate that the greatest hydrological changes will be observed during the winter and spring seasons, a time that is critical for many ecosystems. The mean spring discharge is projected to decrease by 17% for the Richelieu and 40% for the Saint-François by the end of the century. During this season, the frequency of discharge higher than the sediment transport threshold will decrease by 63% for the Saint-François and by 17% for Richelieu when compared to the reference period. However, during winter, the frequency of these high discharges will be four times higher for both rivers. These changes are expected to occur simultaneously with a decrease of the St. Lawrence water levels, a situation that will have significant impacts on sedimentary processes. A hydro-sedimentological modeling approach based on SEDROUT was used to investigate the morphological response of the river beds to the projected changes on the hydrology of St. Lawrence tributaries and to three base level scenarios. Results show that the combined hydrology and base level effects will lead to an increase in sediment supply compared to the current state, and to the extension of accumulation zones. While the effects will vary among the tributaries according to their particular characteristics, the projected increase in sediment supply will modify the extent of freshwater wetlands at the mouth of the St. Lawrence tributaries with feedback effects on local flow and sediment distributions.     

Synthesis and Evaluation of a Series of 2′-Deoxy Analogues of The Antiviral Agent 5,6-Dichloro-2-Isopropylamino-1-(β-L-Ribofuranosyl)-1H-Benzimidazole (1263W94)

Abstract

A series of 2′-deoxy analogues of the antiviral agent 5,6-dichloro-2-isopropylamino-1-(β-L-ribofuranosyl)-1H-benzimidazole (1263W94) were synthesized and evaluated for activity against human cytomegalovirus (HCMV) and for cytotoxicity. The 2-substituents in the benzimidazole moiety correspond to those that were used in the 1263W94 series. In general, as was found in the 1263W94 series, cyclic and branched alkylamino groups were needed for potent activity against HCMV. Three analogues 3a, 3b and 3d were as potent as 1263W94. Further evaluation of two analogues, 3a and 3b, suggested that these 2′-deoxy analogues may act via a novel mechanism of action similar to that of 1263W94. These 2′-deoxy analogues generally lacked cytotoxicity in vitro. Pharmacokinetic parameters in mice and protein binding properties of 3a were quite similar to 1263W94. However, the oral bioavailability of 3a was only half of that observed for 1263W94.     

Diet-induced obesity in rats leads to a decrease in sperm motility

Background  

Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters.