Crawling the web: Perceptual learning

Scientist Live turns its eyes to the Web around it and highlights news and research across the Internet. Today we take a look at perceptual learning, HIV vaccines, and diabetes.

BIOLOGY / NEUROSCIENCE 

Perceptual learning of visual features occurs when multiple stimuli are presented in a fixed sequence (temporal patterning), but not when they are presented in random order (roving). This points to the need for proper stimulus coding in order for learning of multiple stimuli to occur. We examined the stimulus coding rules for learning with multiple stimuli. Our results demonstrate that: (1) stimulus rhythm is necessary for temporal patterning to take effect during practice; (2) learning consolidation is subject to disruption by roving up to 4 h after each practice session; (3) importantly, after completion of temporal-patterned learning, performance is undisrupted by extended roving training; (4) roving is ineffective if each stimulus is presented for five or more consecutive trials; and (5) roving is also ineffective if each stimulus has a distinct identity. We propose that for multi-stimulus learning to occur, the brain needs to conceptually "tag" each stimulus, in order to switch attention to the appropriate perceptual template. Stimulus temporal patterning assists in tagging stimuli and switching attention through its rhythmic stimulus sequence.

- Zhang JY, Kuai SG, Xiao LQ, Klein SA, Levi DM, et al. (2008) Stimulus Coding Rules for Perceptual Learning. PLoS Biol 6(8): e197 doi:10.1371/journal.pbio.0060197

 

VIROLOGY 

In April 2006, the National Institute of Allergy and Infectious Disease (NIAID)-funded HIV Vaccine Trials Network and the NIAID Division of AIDS sponsored a workshop at which nonhuman primate (NHP) researchers and clinical trial scientists with HIV vaccine research expertise discussed how to more effectively use NHPs for evaluating HIV-1 vaccine candidates. This workshop precipitated a broad discussion on what types of NHP studies should be targeted in the critical preclinical pathway for HIV-1 vaccine candidates, especially those designed to elicit HIV-1-specific T cell responses. This paper describes the two-stage NHP screening strategy for T cell-based HIV-1 vaccines that emerged from discussions among the authors during the past year and a half. While conceived prior to the recent release of results for the phase IIB trial (STEP Study) of the Merck replication-incompetent adenovirus serotype 5 (Ad5)-HIV gag/pol/nef vaccine, we think the approach outlined below will be particularly useful for preclinical evaluation of vaccine candidates in the current vaccine pipeline for two reasons. First, the proposed strategy will eliminate suboptimal vaccine candidates early in the testing process (i.e., before initiation of phase I clinical trials). Second, the strategy would provide comparative immune response data in NHPs and humans for each promising HIV-1 vaccine product, information that could help the design of future vaccine candidates.

- Morgan C, Marthas M, Miller C, Duerr A, Cheng-Mayer C, et al. (2008) The Use of Nonhuman Primate Models in HIV Vaccine Development. PLoS Med 5(8): e173 doi:10.1371/journal.pmed.0050173

 

GENETICS 

Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.

We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors.

In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations.

Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP.

- Brunner EJ, Kivimäki M, Witte DR, Lawlor DA, Smith GD, et al. (2008) Inflammation, Insulin Resistance, and Diabetes-Mendelian Randomization Using CRP Haplotypes Points Upstream. PLoS Med 5(8): e155 doi:10.1371/journal.pmed.0050155


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