Use of acyclovir in the prevention of herpes infections after allogenic bone marrow grafts

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.     

Nisin stimulates oxygen consumption by Staphylococcus aureus and Escherichia coli.

Nisin stimulated oxygen consumption by nongrowing, glucose-metabolizing Staphylococcus aureus and Escherichia coli cells, indicating a protonophore mode of action. A similar stimulation in E. coli cells osmotically stressed to disrupt the outer cell membrane confirmed the cytoplasmic membrane as the site of nisin action and showed that nisin uptake was not prevented by the outer membrane.     

Effect of photoperiod and exogenous melatonin on correlates of estrus in the domestic rabbit

It was the purpose of this study to test whether inhibition of estrus in the rabbit by short photoperiod could be simulated by subcutaneous implants of the pineal hormone melatonin. By measuring two non-invasive and readily quantifiable correlates of estrus, emission of the so-called nipple-search pheromone and scent-marking behavior (chinning), it was found that:

1. In intact does kept in stimulatory long photoperiod, melatonin suppressed chinning but had no effect on emission of nipple-search pheromone.
2. In intact, melatonin-treated does which were returned from inhibitory short day to stimulatory long day, chinning remained suppressed, whereas pheromone emission increased as for the vehicle-treated, control does.
3. In ovariectomized does, estradiol administration stimulated both pheromone emission and chinning whereas melatonin failed to suppress these effects.

Thus, although the administration of melatonin had an inhibitory effect on chinning it failed to suppress emission of the nipple-search pheromone and therefore failed to fully simulate the effect of short photoperiod on these two correlates of estrus. Several explanations for this discrepancy are considered, including the possibility that melatonin is not the sole mediary of the photoperiodic response, and that at least in female rabbits, other pineal products may also play a significant role.     

Fluid phase connectivity in an isomorphous, two-component, two-phase phosphatidylcholine bilayer.

Two-dimensional fluid phase connectivity is examined in mixed bilayers of dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine as a function of composition and temperature at constant pressure using fluorescence recovery after photobleaching (FRAP). These isomorphous phospholipid mixtures exhibit nearly ideal mixing behavior. Dilauroyl phosphatidylethanolamine covalently linked through its amino function to NBD is used as the fluorescent probe in this study. These studies show the line of connectivity to be coincident with the line connecting the midpoints of all tie lines in the two-phase region of the phase diagram.     

Development of microsatellite markers for the neotropical tree species Dipteryx alata (Fabaceae)

? Premise of the study: Microsatellite markers were developed for the population genetic analyses of the neotropical tree Dipteryx alata (Fabaceae). ? Methods and Results: Microsatellites were developed from a genomic shotgun library. Polymorphism at each microsatellite loci was analyzed based on 94 individuals from three populations. Eight loci amplified successfully and presented one to 10 alleles, and expected heterozygosities ranged from 0.097 to 0.862. Four loci also amplified in Pterodon emarginatus and presented similar polymorphism. ? Conclusion: The eight microsatellite primer pairs are potentially suitable for population genetic studies and successfully amplified in another Fabaceae species.     

A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.     

Intramembrane client recognition potentiates the chaperone functions of calnexin

One‐third of the human proteome is comprised of membrane proteins, which are particularly vulnerable to misfolding and often require folding assistance by molecular chaperones. Calnexin (CNX), which engages client proteins via its sugar‐binding lectin domain, is one of the most abundant ER chaperones, and plays an important role in membrane protein biogenesis. Based on mass spectrometric analyses, we here show that calnexin interacts with a large number of nonglycosylated membrane proteins, indicative of additional nonlectin binding modes. We find that calnexin preferentially bind misfolded membrane proteins and that it uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by calnexin, and identify sequence motifs within the calnexin TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of calnexin. Together, these data reveal a widespread role of calnexin client recognition in the lipid bilayer, which synergizes with its established lectin‐based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome.