Experience-dependent modulation of tonotopic neural responses in human auditory cortex.

Experience-dependent plasticity of receptive fields in the auditory cortex has been demonstrated by electrophysiological experiments in animals. In the present study we used PET neuroimaging to measure regional brain activity in volunteer human subjects during discriminatory classical conditioning of high (8000 Hz) or low (200 Hz) frequency tones by an aversive 100 dB white noise burst. Conditioning-related, frequency-specific modulation of tonotopic neural responses in the auditory cortex was observed. The modulated regions of the auditory cortex positively covaried with activity in the amygdala, basal forebrain and orbitofrontal cortex, and showed context-specific functional interactions with the medial geniculate nucleus. These results accord with animal single-unit data and support neurobiological models of auditory conditioning and value-dependent neural selection.     

Proactive and Reactive Response Inhibition across the Lifespan

One expression of executive control involves proactive preparation for future events, and this contrasts with stimulus driven reactive control exerted in response to events. Here we describe findings from a response inhibition task, delivered using a smartphone-based platform, that allowed us to index proactive and reactive inhibitory self-control in a large community sample (n = 12,496). Change in stop-signal reaction time (SSRT) when participants are provided with advance information about an upcoming trial, compared to when they are not, provides a measure of proactive control while SSRT in the absence of advance information provides a measure of reactive control. Both forms of control rely on overlapping frontostriatal pathways known to deteriorate in healthy aging, an age-related decline that occurs at an accelerated rate in men compared to women. Here we ask whether these patterns of age-related decline are reflected in similar changes in proactive and reactive inhibitory control across the lifespan. As predicted, we observed a decline in reactive control with natural aging, with a greater rate of decline in men compared to women (~10 ms versus ~8 ms per decade of adult life). Surprisingly, the benefit of preparation, i.e. proactive control, did not change over the lifespan and women showed superior proactive control at all ages compared to men. Our results suggest that reactive and proactive inhibitory control partially rely on distinct neural substrates that are differentially sensitive to age-related change.     

Evaluation of Borrelia burgdorferi BbHtrA Protease as a Vaccine Candidate for Lyme Borreliosis in Mice

Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrA^S226A). Although inoculation with either BbHtrA or BbHtrA^S226A produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge.     

Effect of colony morphology variation of <Emphasis Type="Italic">Burkholderia pseudomallei</Emphasis> on intracellular survival and resistance to antimicrobial environments in human macrophages in vitro

Background  

Primary diagnostic cultures from patients with melioidosis demonstrate variation in colony morphology of the causative organism, Burkholderia pseudomallei. Variable morphology is associated with changes in the expression of a range of putative virulence factors. This study investigated the effect of B. pseudomallei colony variation on survival in the human macrophage cell line U937 and under laboratory conditions simulating conditions within the macrophage milieu. Isogenic colony morphology types II and III were generated from 5 parental type I B. pseudomallei isolates using nutritional limitation. Survival of types II and III were compared with type I for all assays.     

Valerie Andersen (1959 2007)

Valérie Andersen formally began her career in oceanographywith a PhD from the Université de Pierre et Marie Curiein 1985. Her thesis (Andersen, 1985a) was centred on the developmentof numerical models of the pelagic food web. However, it wasfirmly based on her experimental studies of salps (Andersen,1985b, 1986, 1989; Andersen and Nival, 1986) and data she gatheredon cruises in the N.W. Mediterranean Sea (Andersen and