Synthesis and circular dichroism characterization of L-azetidine-2-carboxylic acid cyclic peptides

Several cyclic hemopeptides containing L -azetidine-2-carboxylix acid (Aze)—an imino acid homologous with proline but containing one less methylene group in its cyclic side chain—have been prepared. The peptides reported include (Aze)₂, cyclo(Aze)₃, and cyclo(Aze)₆. The synthesis and spectral characterization of these cyclic peptides are described, and the results discussed in terms of the rigidity and steric constraints attributable to Aze-containing peptides. CD spectra of these materials in several solvents are reported and compared with those of proline analogs; the similarity between the CD spectra of cyclo(Aze)₃ and cyclo (Pro)_3, is noted.     

Circadian and circannual study of the hypophyseal-gonadal axis in healthy young males

Circadian and circannual variations of Testosterone, FSH and LH secretions, other than Oral Body Temperature (OBT) have been studied in four healthy males. OBT showed a constant circadian rhythm with an acrophase located in the afternoon. Plasma Testosterone exhibited both a circadian (acrophase = hr 09,28) and a circannual rhythm (acrophase = 22 february); plasma FSH also showed a circannual rhythm (acrophase = 13 february). By mean chronogram +/- SEM we documented the highest LH levels in December and the lowest in February. These observations would suggest the hypothesis that the winter could be the period in which the hypophysis-gonadal axis in young males exhibits its maximal activity as previously documented for other hormones.     

The nature of protein kinase C activation by physically defined phospholipid vesicles and diacylglycerols

Protein kinase C is activated by a 1,2-sn-diacylglycerol and phospholipid at low calcium concentrations. Of the various phospholipids studied, phosphatidylserine has been shown to be the most effective one and is usually used in assaying the enzyme (Kaibuchi, K., Takai, Y., and Nishizuka, Y. (1981) J. Biol. Chem. 256, 7146-7149). It is shown here that under the conditions of the enzymatic assay, phosphatidylserine does not form typical fluid bilayer structures as seen by electron microscopy and fluorescence polarization. On the other hand, 1:4 phosphatidylserine/phosphatidylcholine bilayer vesicles can be formed which support protein kinase C activation. They have the advantage in that they are characterizable, form physiologically relevant bilayer structures, and are readily and reproducibly formed. In addition, they do not support protein kinase C activation in the absence of added diacylglycerol, a property that makes them invaluable in studying the role of diacylglycerol structure in protein kinase C activation. It is further demonstrated that the rat brain enzyme is activated by 1,2-sn-diolein but not by 2,3-sn-diolein nor 1,3-diolein, demonstrating the high specificity of the kinase toward the glycerol backbone. 1,2-rac-Dielaidin, 1,2-rac-distearin, and 1,2-sn-dipalmitin are all active, which is consistent with the idea that the specificity of protein kinase C is not directed toward the fatty acid side chain of the diacylglycerols.     

Water-Dispersible Three-Dimensional LC-Nanoresonators

Nanolithography techniques enable the fabrication of complex nanodevices that can be used for biosensing purposes. However, these devices are normally supported by a substrate and their use is limited to in vitro applications. Following a top-down procedure, we designed and fabricated composite inductance-capacitance (LC) nanoresonators that can be detached from their substrate and dispersed in water. The multimaterial composition of these resonators makes it possible to differentially functionalize different parts of the device to obtain stable aqueous suspensions and multi-sensing capabilities. For the first time, we demonstrate detection of these devices in an aqueous environment, and we show that they can be sensitized to their local environment and to chemical binding of specific molecular moieties. The possibility to optically probe the nanoresonator resonance in liquid dispersions paves the way to a variety of new applications, including injection into living organisms for in vivo sensing and imaging.     

Enhanced neuronal regeneration by retinoic acid of murine dorsal root ganglia and of fetal murine and human spinal cord in vitro

Summary This study demonstrates that retinoic acid (RA), an active metabolite of vitamin A, can act to enhance regeneration of neurites, at physiologic concentrations, in vitro. Explanted fragments of mouse dorsal root ganglia (DRG) and mouse and human spinal cord (SC) were maintained, in vitro, for periods up to 11 d. Murine DRG neurons were exposed to RA concentrations ranging from 100 μM to 1 nM, whereas neurons within murine and human SC explants were exposed to 10 μM to 10 nM RA. Results show that RA significantly (P<0.001) increases mean neurite length but not neurite number. Specifically, murine DRG neurons showed increases in mean neurite length of 30.7% with individual explants showing increases of up to 133.5%. Murine and human SC showed mean enhancements of 43.4 and 58.1%, respectively, but did so at lower concentrations of RA. The results indicate that RA may play a potentially critical role in neuronal regeneration.     

Effect of sediment elutriate on the chemical composition of Gymnodinium sp. (Dinophyceae). II.

Abstract

The chemical composition of Gymnodinium sp. was studied in cells grown in batch cultures with sediment elutriate, enriched or unenriched with F/2 as the culture medium. The cellular protein, chlorophyll a, nitrogen, carbon and phosphorus content were determined in conjunction with cell density. For the enriched media, a high density of biomass was always measured; differences in cellular composition between control and elutriate cells were not observed and the atomic C:N:P ratios were typical of unstarved phytoplankton. Unenriched media produced different effects on the algal growth, which also affected the biochemical composition of the cells. Relative to the control, some elutriates reduced the algal growth, affected the chemical composition of the cells which showed very high levels of carbon, nitrogen and protein, and resulted in an aberrant morphology. The stimulating growth elutriate affected the chemical composition of the cell in another manner: the greatest effect was a decrease of carbon content, whereas the other compounds remained similar to the control; aberrant forms were not observed.     

Virulence attenuation during an influenza A/H5N1 pandemic

More than 15 years after the first human cases of influenza A/H5N1 in Hong Kong, the world remains at risk for an H5N1 pandemic. Preparedness activities have focused on antiviral stockpiling and distribution, development of a human H5N1 vaccine, operationalizing screening and social distancing policies, and other non-pharmaceutical interventions. The planning of these interventions has been done in an attempt to lessen the cumulative mortality resulting from a hypothetical H5N1 pandemic. In this theoretical study, we consider the natural limitations on an H5N1 pandemic''s mortality imposed by the virus'' epidemiological–evolutionary constraints. Evolutionary theory dictates that pathogens should evolve to be relatively benign, depending on the magnitude of the correlation between a pathogen''s virulence and its transmissibility. Because the case fatality of H5N1 infections in humans is currently 60 per cent, it is doubtful that the current viruses are close to their evolutionary optimum for transmission among humans. To describe the dynamics of virulence evolution during an H5N1 pandemic, we build a mathematical model based on the patterns of clinical progression in past H5N1 cases. Using both a deterministic model and a stochastic individual-based simulation, we describe (i) the drivers of evolutionary dynamics during an H5N1 pandemic, (ii) the range of case fatalities for which H5N1 viruses can successfully cause outbreaks in humans, and (iii) the effects of different kinds of social distancing on virulence evolution. We discuss two main epidemiological–evolutionary features of this system (i) the delaying or slowing of an epidemic which results in a majority of hosts experiencing an attenuated virulence phenotype and (ii) the strong evolutionary pressure for lower virulence experienced by the virus during a period of intense social distancing.     

Behaviour of Listeria monocytogenes in packaged water buffalo mozzarella cheese

Aims: The aim of the study was to evaluate the behaviour of Listeria monocytogenes in the conditioning liquid of packaged water buffalo mozzarella cheese (WBMC). Methods and Results: The conditioning liquid was contaminated with L. monocytogenes, and the contaminated samples were stored at four different storage temperatures: 5 and 10°C for 22 days; 20°C for 9 days; 20°C for 3 days and then at 5°C for 6 days. The results showed that L. monocytogenes concentration decreased when contaminated samples were stored at 5°C. When WBMC was stored at 20°C and at 10°C, L. monocytogenes started to grow after a lag phase of 3 and 10 days, respectively. When samples were stored at variable temperature conditions, L. monocytogenes numbers showed a lag phase of 5 days. Conclusions: Use of a conditioning liquid characterized by acidity and a correct storage temperature is able to counteract pathogen replication during shelf life. A high concentration of lactic acid bacteria was associated with effective control of L. monocytogenes but the role of lactic acid bacteria in WBMC conditioning liquid requires further investigation. Significance and Impact of the Study: According to European regulations, food producers should be able to justify decision‐making on the shelf life assigned to their products, taking into account reasonable storage conditions and use by consumers. The results of the trial yielded information for producers of WBMC and similar cheeses for decision‐making on product shelf life.