对比度检测学习提高猫的视觉对比敏感度

对人的心理学研究结果显示,对比度检测学习可提高学习者对视觉刺激的对比敏感度,但其潜在的神经机制尚不清楚。该研究用二选一（two-alternative forced choice）方法训练3只猫（Felis catus）通过单眼进行对比度检测学习,发现每只猫对视觉刺激的对比敏感度随着训练而显著提高。该学习效果虽然对训练眼有明显的特异性,但部分学习效果可以传递给非训练眼,提示对比度检测学习可能会引起双眼信息汇聚前后的视觉中枢的神经可塑性。另外,猫视觉对比敏感度的提高主要发生在训练刺激的空间频率附近,表明对比度检测学习具有一定的空间频率选择性。该研究结果显示,猫对视觉刺激的对比度检测学习表现出与人类相似的特性,因此可以作为模式动物来研究人类学习诱导的视觉对比敏感度升高的神经机制。     

Individual Variation in Cone Photoreceptor Density in House Sparrows: Implications for Between-Individual Differences in Visual Resolution and Chromatic Contrast

Between-individual variation has been documented in a wide variety of taxa, especially for behavioral characteristics; however, intra-population variation in sensory systems has not received similar attention in wild animals. We measured a key trait of the visual system, the density of retinal cone photoreceptors, in a wild population of house sparrows (Passer domesticus). We tested whether individuals differed from each other in cone densities given within-individual variation across the retina and across eyes. We further tested whether the existing variation could lead to individual differences in two aspects of perception: visual resolution and chromatic contrast. We found consistent between-individual variation in the densities of all five types of avian cones, involved in chromatic and achromatic vision. Using perceptual modeling, we found that this degree of variation translated into significant between-individual differences in visual resolution and the chromatic contrast of a plumage signal that has been associated with mate choice and agonistic interactions. However, there was no evidence for a relationship between individual visual resolution and chromatic contrast. The implication is that some birds may have the sensory potential to perform “better” in certain visual tasks, but not necessarily in both resolution and contrast simultaneously. Overall, our findings (a) highlight the need to consider multiple individuals when characterizing sensory traits of a species, and (b) provide some mechanistic basis for between-individual variation in different behaviors (i.e., animal personalities) and for testing the predictions of several widely accepted hypotheses (e.g., honest signaling).     

视力与视力时间阈值的关系

目的:用计算机控制检测研究视力时间阈值.方法:用pascal语言程序设计视标.视标的大小、显示程序和持续时间由计算机控制.受试者从距离显示器5m处看视标.采用阶梯法测试不同视力受试者的视力时间阈值.结果:检测到约为毫秒级的视力时间阈值.视力1.0组的视力时间阈值平均约为28.10msec,视力1.2组的视力时间阈值平均约为27.90msec,视力1.5组的视力时间阈值平均约为27.80msec.结论:视力与视力时间阈值不成正比,视力好的个体其视力时间阈值不一定短.     

Individual Differences in Inhibitory Control,Not Non-Verbal Number Acuity,Correlate with Mathematics Achievement

Given the well-documented failings in mathematics education in many Western societies, there has been an increased interest in understanding the cognitive underpinnings of mathematical achievement. Recent research has proposed the existence of an Approximate Number System (ANS) which allows individuals to represent and manipulate non-verbal numerical information. Evidence has shown that performance on a measure of the ANS (a dot comparison task) is related to mathematics achievement, which has led researchers to suggest that the ANS plays a critical role in mathematics learning. Here we show that, rather than being driven by the nature of underlying numerical representations, this relationship may in fact be an artefact of the inhibitory control demands of some trials of the dot comparison task. This suggests that recent work basing mathematics assessments and interventions around dot comparison tasks may be inappropriate.     

Screening for Significant Refractive Error Using a Combination of Distance Visual Acuity and Near Visual Acuity

PurposeTo explore the effectiveness of using a series of tests combining near visual acuity (NVA) and distance visual acuity (DVA) for large-scale screenings for significant refractive error (SRE) in primary school children.MethodEach participant underwent DVA, NVA and cycloplegic autorefraction measurements. SREs, including high myopia, high hyperopia and high astigmatism were analyzed. Cycloplegic refraction results were considered to be the gold standard for the comparison of different screening measurements. Receiver-operating characteristic (ROC) curves were constructed to compare the area under the curve (AUC) and the Youden index among DVA, NVA and the series combined tests of DVA and NVA. The efficacies (including sensitivity, specificity, positive predictive value, and negative predictive value) of each test were evaluated. Only the right eye data of each participant were analysed for statistical purpose.ResultA total of 4416 children aged 6 to 12 years completed the study, among which 486 students had right eye SRE (SRE prevalence rate = 11.01%). There was no difference in the prevalence of high hyperopia and high astigmatism among different age groups. However, the prevalence of high myopia significantly increased with the age (χ² = 381.81, p<0.01). High hyperopia was the biggest SRE factor associated with amblyopia（p＜0.01，OR = 167.40, 95% CI: 75.14∼372.94). The DVA test was better than the NVA test for detecting high myopia (Z = 2.71, p<0.01), but the NVA test was better for detecting high hyperopia (Z = 2.35, p = 0.02) and high astigmatism (Z = 4.45, p<0.01). The series combined DVA and NVA test had the biggest AUC and the highest Youden Index for detecting high hyperopia, myopia, astigmatism, as well as all of the SREs (all p<0.01).ConclusionThe series combined DVA and NVA test was more accurate for detecting SREs than either of the two tests alone. This new method could be applied to large-scale SRE screening of children, aged 6 to 12, in areas that are less developed.     

Genetic Control of Individual Differences in Gene-Specific Methylation in Human Brain

We have observed extensive interindividual differences in DNA methylation of 8590 CpG sites of 6229 genes in 153 human adult cerebellum samples, enriched in CpG island “shores” and at further distances from CpG islands. To search for genetic factors that regulate this variation, we performed a genome-wide association study (GWAS) mapping of methylation quantitative trait loci (mQTLs) for the 8590 testable CpG sites. cis association refers to correlation of methylation with SNPs within 1 Mb of a CpG site. 736 CpG sites showed phenotype-wide significant cis association with 2878 SNPs (after permutation correction for all tested markers and methylation phenotypes). In trans analysis of methylation, which tests for distant regulation effects, associations of 12 CpG sites and 38 SNPs remained significant after phenotype-wide correction. To examine the functional effects of mQTLs, we analyzed 85 genes that were with genetically regulated methylation we observed and for which we had quality gene expression data. Ten genes showed SNP-methylation-expression three-way associations—the same SNP simultaneously showed significant association with both DNA methylation and gene expression, while DNA methylation was significantly correlated with gene expression. Thus, we demonstrated that DNA methylation is frequently a heritable continuous quantitatively variable trait in human brain. Unlike allele-specific methylation, genetic polymorphisms mark both cis- and trans-regulatory genetic sites at measurable distances from their CpG sites. Some of the genetically regulated DNA methylation is directly connected with genetically regulated gene expression variation.     

Genetic and Molecular Basis of Individual Differences in Human Umami Taste Perception

Umami taste (corresponds to savory in English) is elicited by L-glutamate, typically as its Na salt (monosodium glutamate: MSG), and is one of five basic taste qualities that plays a key role in intake of amino acids. A particular property of umami is the synergistic potentiation of glutamate by purine nucleotide monophosphates (IMP, GMP). A heterodimer of a G protein coupled receptor, TAS1R1 and TAS1R3, is proposed to function as its receptor. However, little is known about genetic variation of TAS1R1 and TAS1R3 and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human TAS1R1 and TAS1R3, and the functions of TAS1R1/TAS1R3 variants using a heterologous expression system. Our study demonstrated that the TAS1R1-372T creates a more sensitive umami receptor than -372A, while TAS1R3-757C creates a less sensitive one than -757R for MSG and MSG plus IMP, and showed a strong correlation between the recognition thresholds and in vitro dose - response relationships. These results in human studies support the propositions that a TAS1R1/TAS1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity.     

Normal Monocular and Binocular Visual Acuity in Seven-Year-Old Children

The purpose of this study was to obtain age-specific normative data for visual acuity (VA) in sevenyear- old children. The sample included a total of 127 healthy children (mean age 7.53 ± 0.025 years) without ophthalmic disorders. Monocular and binocular VAs were determined to the threshold level at two distances, 5 m and 0.5 m, using eye charts with eight intermediate levels between 1.0 and 2.4 (in the decimal notation system) with widely spaced tumbling Snellen’s E optotypes randomly distributed in four orientations. Since the optotypes were located in lines at intervals that were twice as large as the size of the optotype itself, they could be considered as single stimuli. The normal monocular and binocular VAs were 1.279 ± 0.025 and 1.491 ± 0.028 at 5 m and 1.256 ± 0.024 and 1.388 ± 0.025 m at 0.5 m, respectively (mean ± standard error of mean). Interocular differences in VA are also discussed. Our findings show that the normal VA in seven-yearold children is higher than the clinically accepted norm of 1.0; therefore, VA measurement to the threshold level is necessary for earlier visual disorders to be detected.     

Analysis of Genetic and Non-Genetic Factors Influencing Timing and Time Perception

Performance on different psychophysical tasks measuring the sense of time indicates a large amount of individual variation in the accuracy and precision of timing in the hundredths of milliseconds-to-minutes range. Quantifying factors with an influence on timing is essential to isolating a biological (genetic) contribution to the perception and estimation of time. In the largest timing study to date, 647 participants completed a duration-discrimination task in the sub-second range and a time-production task in the supra-second range. We confirm the stability of a participant’s time sense across multiple sessions and substantiate a modest sex difference on time production. Moreover, we demonstrate a strong correlation between performance on a standardized cognitive battery and performance in both duration-discrimination and time-production tasks; we further show that performance is uncorrelated with age after controlling for general intelligence. Additionally, we find an effect of ethnicity on time sense, with African Americans and possibly Hispanics in our cohort differing in accuracy and precision from other ethnic groups. Finally, a preliminary genome-wide association and exome chip study was performed on 148 of the participants, ruling out the possibility for a single common variant or groups of low-frequency coding variants within a single gene to explain more than ~18% of the variation in the sense of time.     

Photometric Compliance of Tablet Screens and Retro-Illuminated Acuity Charts As Visual Acuity Measurement Devices

Mobile technology is increasingly used to measure visual acuity. Standards for chart-based acuity tests specify photometric requirements for luminance, optotype contrast and luminance uniformity. Manufacturers provide some photometric data but little is known about tablet performance for visual acuity testing. This study photometrically characterised seven tablet computers (iPad, Apple inc.) and three ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity charts with room lights on and off, and compared findings with visual acuity measurement standards. Tablet screen luminance and contrast were measured using nine points across a black and white checkerboard test screen at five arbitrary brightness levels. ETDRS optotypes and adjacent white background luminance and contrast were measured. All seven tablets (room lights off) exceeded the most stringent requirement for mean luminance (≥ 120 cd/m²) providing the nominal brightness setting was above 50%. All exceeded contrast requirement (Weber ≥ 90%) regardless of brightness setting, and five were marginally below the required luminance uniformity threshold (L_min/L_max ≥ 80%). Re-assessing three tablets with room lights on made little difference to mean luminance or contrast, and improved luminance uniformity to exceed the threshold. The three EDTRS charts (room lights off) had adequate mean luminance (≥ 120 cd/m²) and Weber contrast (≥ 90%), but all three charts failed to meet the luminance uniformity standard (L_min/L_max ≥ 80%). Two charts were operating beyond manufacturer’s recommended lamp replacement schedule. With room lights on, chart mean luminance and Weber contrast increased, but two charts still had inadequate luminance uniformity. Tablet computers showed less inter-device variability, higher contrast, and better luminance uniformity than charts in both lights-on and lights-off environments, providing brightness setting was >50%. Overall, iPad tablets matched or marginally out-performed ETDRS charts in terms of photometric compliance with high contrast acuity standards.     

Cigarette Experimentation and the Population Attributable Fraction for Associated Genetic and Non-Genetic Risk Factors

Background

We, and others, have shown that experimenting with cigarettes is a function of both non-genetic and genetic factors. In this analysis we ask: how much of the total risk of experimenting with cigarettes, among those who had not experimented with cigarettes when they enrolled in a prospective cohort, is attributable to genetic factors and to non-genetic factors?

Methods

Participants (N = 1,118 Mexican origin youth), recruited from a large population-based cohort study in Houston, Texas, provided prospective data on cigarette experimentation over three years. Non-genetic data were elicited twice – baseline and follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin and opioid pathways.

Results

In the overall model, the adjusted combined non-genetic PAF was 71.2% and the adjusted combined genetic PAF was 58.5%. Among committed never smokers the adjusted combined non-genetic PAF was 67.0% and the adjusted combined genetic PAF was 53.5%. However, among cognitively susceptible youth, the adjusted combined non-genetic PAF was 52.0% and the adjusted combined genetic PAF was 68.4%.

Conclusions

Our results suggest there may be differences in genotypes between youth who think they will try cigarettes in the future compared to their peers who think they will not and underscore the possibility that the relative influence of genetic vs. non-genetic factors on the uptake of smoking may vary between these two groups of youth.

Impact

A clearer understanding of the relative role of genetic vs. non-genetic factors in the uptake of smoking may have implications for the design of prevention programs.     

Genetic and Non-Genetic Determinants of Raltegravir Penetration into Cerebrospinal Fluid: A Single Arm Pharmacokinetic Study

Background

Antiretroviral drugs vary in their central nervous system penetration, with better penetration possibly conferring neurocognitive benefit during human immunodeficiency virus (HIV) therapy. The efflux transporter gene ABCB1 is expressed in the blood-brain barrier, and an ABCB1 variant (3435C→T) has been reported to affect ABCB1 expression. The integrase inhibitor raltegravir is a substrate for ABCB1. We examined whether ABCB1 3435C→T affects raltegravir disposition into cerebrospinal fluid (CSF), and explored associations with polymorphisms in other membrane transporter genes expressed in the blood-brain barrier.

Methods

Forty healthy, HIV-negative adults of European descent (20 homozygous for ABCB1 3435 C/C, 20 homozygous for 3435 T/T, each group divided equally between males and females) were given raltegravir 400 mg twice daily for 7 days. With the final dose, plasma was collected for pharmacokinetic analysis at 9 timepoints over 12 hours, and CSF collected 4 hours post dose.

Results

The 4-hour CSF concentration correlated more strongly with 2-hour (r²=0.76, P=1.12x10^-11) than 4-hour (r²=0.47, P=6.89x10^-6) single timepoint plasma concentration, and correlated strongly with partial plasma area-under-the-curve values (AUC_0-4h r²=0.86, P=5.15x10^-16). There was no significant association between ABCB1 3435C→T and ratios of CSF-to-plasma AUC or concentration (p>0.05 for each comparison). In exploratory analyses, CSF-to-plasma ratios were not associated with 276 polymorphisms across 16 membrane transporter genes.

Conclusions

Among HIV-negative adults, CSF raltegravir concentrations do not differ by ABCB1 3435C→T genotype but strongly correlate with plasma exposure.

Trial Registration

ClinicalTrials.gov NCT00729924 http://clinicaltrials.gov/show/NCT00729924     

Submaximal Responses in Calcium-triggered Exocytosis Are Explained by Differences in the Calcium Sensitivity of Individual Secretory Vesicles

A graded response to calcium is the defining feature of calcium-regulated exocytosis. That is, there exist calcium concentrations that elicit submaximal exocytotic responses in which only a fraction of the available population of secretory vesicles fuse. The role of calcium-dependent inactivation in defining the calcium sensitivity of sea urchin egg secretory vesicle exocytosis in vitro was examined. The cessation of fusion in the continued presence of calcium was not due to calcium-dependent inactivation. Rather, the calcium sensitivity of individual vesicles within a population of exocytotic vesicles is heterogeneous. Any specific calcium concentration above threshold triggered subpopulations of vesicles to fuse and the size of the subpopulations was dependent upon the magnitude of the calcium stimulus. The existence of multiple, stable subpopulations of vesicles is consistent with a fusion process that requires the action of an even greater number of calcium ions than the numbers suggested by models based on the assumption of a homogeneous vesicle population.