Evaluation of the neurovirulence test for mumps vaccines.

Neurovirulence tests in Macaca fascicularis using commercial preparations of different vaccine bulks and a wild-type strain revealed that the test was unable to distinguish mixed from pure populations or a suitable vaccine from a related strain which has been shown to be associated with clinical meningitis. However, the test was able to distinguish a wild-type strain from the vaccine strains successfully. The ability of the test to discriminate between acceptable and unacceptable seeds requires further examination.     

A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids

The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, β-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance.     

Species distribution and <Emphasis Type="Italic">in vitro</Emphasis> antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

Background  

In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis.     

Statistical analysis of the Bacterial Carbohydrate Structure Data Base (BCSDB): Characteristics and diversity of bacterial carbohydrates in comparison with mammalian glycans

Background  

There are considerable differences between bacterial and mammalian glycans. In contrast to most eukaryotic carbohydrates, bacterial glycans are often composed of repeating units with diverse functions ranging from structural reinforcement to adhesion, colonization and camouflage. Since bacterial glycans are typically displayed at the cell surface, they can interact with the environment and, therefore, have significant biomedical importance.     

Consequences of injuries on survival and reproduction of common bottlenose dolphins (Tursiops truncatus) along the west coast of Florida

Accurate identification of human‐induced injuries that lead to death or interfere with reproduction is important for marine mammal management, as deaths exceeding established limits can lead to restrictions on fisheries or vessel operations. The fates of cetaceans last seen swimming with attached gear, particularly in pelagic fisheries, or with vessel strike lacerations, have been difficult to predict. Survival and reproduction data from long‐term research on resident common bottlenose dolphins near Sarasota, Florida were examined relative to consequences of fishing gear ingestion, line entanglements, vessel strikes, and amputations of unknown origins. Fishing hooks embedded in the throat, goosebeak, or esophagus, or line wrapped around the goosebeak, generally lead to death. Multiple, constrictive line wraps around fin insertions can lead to amputation, blood loss, impaired mobility, or infection. Dolphins with ingested gear or severe entanglements may swim away with the gear, but likely die later. Propeller injuries involving only soft tissue were often survivable. Some dolphins survived amputations of the distal ends of fins, and continued to reproduce. As a precautionary approach, dolphins with ingested gear or severe constrictive entanglements should be considered mortalities, but extrapolations of findings from coastal bottlenose dolphins to other cetaceans and different gear must be done with caution.     

Considerations Regarding the Use of Reference Area and Baseline Information in Ecological Risk Assessments

There has been debate in the recent literature as to whether a reference assessment should be included in ecological risk assessments (ERAs) of contaminated sites, and if so, how such an evaluation can be incorporated in a way that aids in decision making. It is our view that an assessment of reference conditions can be useful in the ERA process, for both prospective and retrospective ERAs, given adequate resources and acknowledgement and understanding of the limitations and uncertainties associated with this information. Suggestions and considerations for incorporating reference area information into an ecological risk assessment are discussed.     

Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin

There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs.     

Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen

Background  

Bet v 1 is an important cause of hay fever in northern Europe. Bet v 1 isoforms from the European white birch (Betula pendula) have been investigated extensively, but the allergenic potency of other birch species is unknown. The presence of Bet v 1 and closely related PR-10 genes in the genome was established by amplification and sequencing of alleles from eight birch species that represent the four subgenera within the genus Betula. Q-TOF LC-MS^E was applied to identify which PR-10/Bet v 1 genes are actually expressed in pollen and to determine the relative abundances of individual isoforms in the pollen proteome.