Auditory Discrimination Learning: Role of Working Memory

Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience.     

Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Amphiphilic chitosan-based polymers (Mw < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.     

Investigating the effects of physiological bile acids on GLP-1 secretion and glucose tolerance in normal and GLP-1R(-/-) mice

Physiological secretion of bile acids has previously been linked to the regulation of blood glucose. GLP-1 is an intestinal peptide hormone with important glucose-lowering actions, such as stimulation of insulin secretion and inhibition of glucagon secretion. In this investigation, we assessed the ability of several bile acid compounds to secrete GLP-1 in vitro in STC-1 cells. Bile acids stimulated GLP-1 secretion from 3.3- to 6.2-fold but some were associated with cytolytic effects. Glycocholic and taurocholic acids were selected for in vivo studies in normal and GLP-1R(-/-) mice. Oral glucose tolerance tests revealed that glycocholic acid did not affect glucose excursions. However, taurocholic acid reduced glucose excursions by 40% in normal mice and by 27% in GLP-1R(-/-) mice, and plasma GLP-1 concentrations were significantly elevated 30 min post-gavage. Additional studies used incretin receptor antagonists to probe involvement of GLP-1 and GIP in taurocholic acid-induced glucose lowering. The findings suggest that bile acids partially aid glucose regulation by physiologically enhancing nutrient-induced GLP-1 secretion. However, GLP-1 secretion appears to be only part of the glucose-lowering mechanism and our studies indicate that the other major incretin GIP is not involved.     

Home-range Use by a Large Horde of Wild <Emphasis Type="Italic">Mandrillus sphinx</Emphasis>

The predicted relationship between home-range size and group mass in primates developed by Clutton-Brock and Harvey (1977) has proved extremely robust in describing the use of space by most primate species. However, mandrills (Mandrillus sphinx) are now known to have an extreme group mass in the wild, far larger than that of the species used originally to generate that relationship, and so it was unknown whether this relationship would be robust for this species. We investigated the home-range size and use of a wild horde of ca. 700 mandrills in Lopé National Park, Gabon, using radiotelemetry. The total area the horde used over a 6-yr period [100% minimum convex polygon (MCP)] was 182 km², including 89 km² of suitable forest habitat. Mandrills used gallery forests and isolated forest fragments with high botanical diversity far more intensively that the continuous forest and completely avoided savanna and marsh. Peeled polygons and fixed kernel contours revealed multiple centres of use, with the horde spending more than half its time in <10% of the total documented range, typical of a frugivore using a patchy environment. Home-range size and internal structure varied considerably between years, but total home range fitted the predicted relationship between group mass and home range size, despite being an outlier to the dataset. We discuss the conservation implications of the species’ space requirements, in light of current pressures on land use in their range.     

Description and Bionomics of Mesomermis camdenensis n. sp. (Mermithidae), a Parasite of Black Flies (Simuliidae)

Mesomermis camdenensis n. sp. is described from larvae of Simulium tuberosum (lundstroem) collected in Camden Valley Creek, Washington County, New York. This species possesses a barrel-shaped vagina, vulval flap. two short separate spicules, terminal mouth, six longitudinal chords, six cephalic papillae, large sexually dimorpbic anaphids, an esophagns of uniform width which extends for less than one-third of the body length, and a cone-shaped tail directed ventrally without appendage. Juveniles also are described and illustrated.A detailed morphological comparison with the mermithid M. flumenalis Welch is presented. The most pronounced morphological differences between these species are in the shape of the vulva, juvenile tail, and infective stage. Cross-mating trials support the integrity of the new species.The life cycle of M. camdenensis is closely synchronized with that of its primary host, S. tuberosum larvae. Infected S. tuberosum larvae were first collected in May. Emergence of postparasites from late instars took place from mid-June through mid-October. Sampling data indicate a lower susceptibility to infection among S. venuslum Say larvae.     

Feline model of acute nipah virus infection and protection with a soluble glycoprotein-based subunit vaccine

Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID(50)) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID(50) of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.     

Characterization of neutralizing antibody responses elicited by clade A envelope immunogens derived from early transmitted viruses

The vast majority of studies with candidate immunogens based on the human immunodeficiency virus envelope (Env) have been conducted with Env proteins derived from clade B viruses isolated during chronic infection. Whether non-clade B Env protein immunogens will elicit antibodies with epitope specificities that are similar to those of antibodies elicited by clade B Envs and whether the antibodies elicited by Envs derived from early transmitted viruses will be similar to those elicited by Envs derived from viruses isolated during chronic infection are currently unknown. Here we performed immunizations with four clade A Envs, cloned directly from the peripheral blood of infected individuals during acute infection, which differed in lengths and extents of glycosylation. The antibody responses elicited by these four Envs were compared to each other and to those elicited by a well-characterized clade B Env immunogen derived from the SF162 virus, which was isolated during chronic infection. Only one clade A Env, the one with the fewer glycosylation sites, elicited homologous neutralizing antibodies (NAbs); these did not target the V1, V2, or V3 regions. In contrast, all four clade A Envs elicited anti-V3 NAbs against "easy-to-neutralize" clade B and clade A isolates, irrespective of the variable region length and extent of glycosylation of the Env used as an immunogen. These anti-V3 NAbs did not access their epitopes on homologous and heterologous clade A, or B, neutralization-resistant viruses. The length and extent of glycosylation of the variable regions on the clade A Env immunogens tested did not affect the breadth of the elicited NAbs. Our data also indicate that the development of cross-reactive NAbs against clade A viruses faces similar hurdles to the development of cross-reactive anti-clade B NAbs.