Saccade latency during probability presentation of the visual targets in man

The latent periods of saccadic eye movements in response to peripheral visual stimuli were measured in 8 right-handed healthy subjects using Posner's paradigm "COST-BENEFIT". In 6 subjects, the saccade latency in response to visual target presented in expected location in valid condition was shorter than that in neutral condition ("benefit"). Increase in saccade latency in response to the visual target presented in unexpected location in valid condition versus neutral condition took place only in 4 subjects ("cost"). A decrease in left-directed saccade latency in response to expected target presented in the left hemifield and increase in saccade latency in response to unexpected left target in comparison with analogous right-directed saccades were observed in valid condition. This phenomenon can be explained by the dominance of the right hemisphere in the processes of spatial orientation and "disengage" of attention.     

Synaesthetic colours do not camouflage form in visual search

One of the major issues in synaesthesia research is to identify the level of processing involved in the formation of the subjective colours experienced by synaesthetes: are they perceptual phenomena or are they due to memory and association learning? To address this question, we tested whether the colours reported by a group of grapheme-colour synaesthetes (previously studied in an functional magnetic resonance imaging experiment) influenced them in a visual search task. As well as using a condition where synaesthetic colours should have aided visual search, we introduced a condition where the colours experienced by synaesthetes would be expected to make them worse than controls. We found no evidence for differences between synaesthetes and normal controls, either when colours should have helped them or where they should have hindered. We conclude that the colours reported by our population of synaesthetes are not equivalent to perceptual signals, but arise at a cognitive level where they are unable to affect visual search.     

Short-term visual deprivation does not enhance passive tactile spatial acuity

An important unresolved question in sensory neuroscience is whether, and if so with what time course, tactile perception is enhanced by visual deprivation. In three experiments involving 158 normally sighted human participants, we assessed whether tactile spatial acuity improves with short-term visual deprivation over periods ranging from under 10 to over 110 minutes. We used an automated, precisely controlled two-interval forced-choice grating orientation task to assess each participant's ability to discern the orientation of square-wave gratings pressed against the stationary index finger pad of the dominant hand. A two-down one-up staircase (Experiment 1) or a Bayesian adaptive procedure (Experiments 2 and 3) was used to determine the groove width of the grating whose orientation each participant could reliably discriminate. The experiments consistently showed that tactile grating orientation discrimination does not improve with short-term visual deprivation. In fact, we found that tactile performance degraded slightly but significantly upon a brief period of visual deprivation (Experiment 1) and did not improve over periods of up to 110 minutes of deprivation (Experiments 2 and 3). The results additionally showed that grating orientation discrimination tends to improve upon repeated testing, and confirmed that women significantly outperform men on the grating orientation task. We conclude that, contrary to two recent reports but consistent with an earlier literature, passive tactile spatial acuity is not enhanced by short-term visual deprivation. Our findings have important theoretical and practical implications. On the theoretical side, the findings set limits on the time course over which neural mechanisms such as crossmodal plasticity may operate to drive sensory changes; on the practical side, the findings suggest that researchers who compare tactile acuity of blind and sighted participants should not blindfold the sighted participants.     

Approaches for identifying targets of positive selection

Despite significant advancements in both empirical and theoretical population genetics throughout the past century, fundamental questions about the evolutionary forces that shape genomic diversity remain unresolved. Perhaps foremost among these are the strength and frequency of adaptive evolution. To quantify these parameters, statistical tools are needed that are capable of effectively identifying targets of positive selection throughout the genome in an unbiased manner, and functional approaches are needed that are capable of connecting these identified genotypes with the resulting adaptively significant phenotypes. Here we review recent advancements in both statistical and empirical methodology, and discuss important challenges and opportunities that remain as researchers continue to uncouple the relative importance of stochastic and deterministic factors in the evolution of natural populations.     

Human helper-T-cell function does not require T4 antigen expression

The relationship between immunoregulatory T-cell function and the expression of T-cell subset-specific differentiation antigens was examined using a phenotypically anomalous human T-cell line (TCL), termed H-1. H-1 cells were found to express T11, extremely high levels of T3, but no T4 nor T8 antigen. Despite their lack of T4 antigen expression, H-1 cells could be activated by coculture with pokeweed mitogen (PWM), anti-T3 antibody, or autologous B cells to provide potent help for B-cell differentiation into plaque-forming cells (PFC). In contrast, H-1 cells did not suppress the PFC response triggered by PWM-activated T4+ cells. These results demonstrate that the expression of the T-cell subclass-specific differentiation antigen, T4, is not required for a T cell to become activated and to implement the program for helper function. In addition, enhanced expression of T3 on the T4-, T8-, H-1 cell surface may reflect a compensatory upregulation of the T3/Ti receptor complex on T cells which are deficient in these nonpolymorphic associative recognition structures.     

Visual working memory capacity does not modulate the feature-based information filtering in visual working memory

Background

The limited capacity of visual working memory (VWM) requires us to select the task relevant information and filter out the irrelevant information efficiently. Previous studies showed that the individual differences in VWM capacity dramatically influenced the way we filtered out the distracters displayed in distinct spatial-locations: low-capacity individuals were poorer at filtering them out than the high-capacity ones. However, when the target and distracting information pertain to the same object (i.e., multiple-featured object), whether the VWM capacity modulates the feature-based filtering remains unknown.

Methodology/Principal Findings

We explored this issue mainly based on one of our recent studies, in which we asked the participants to remember three colors of colored-shapes or colored-landolt-Cs while using two types of task irrelevant information. We found that the irrelevant high-discriminable information could not be filtered out during the extraction of VWM but the irrelevant fine-grained information could be. We added 8 extra participants to the original 16 participants and then split the overall 24 participants into low- and high-VWM capacity groups. We found that regardless of the VWM capacity, the irrelevant high-discriminable information was selected into VWM, whereas the irrelevant fine-grained information was filtered out. The latter finding was further corroborated in a second experiment in which the participants were required to remember one colored-landolt-C and a more strict control was exerted over the VWM capacity.

Conclusions/Significance

We conclude that VWM capacity did not modulate the feature-based filtering in VWM.     

Molecular targets in the search for endothelium-protecting compounds

Impairment of endothelial function forms basis for many cardiovascular diseases, therefore today it becomes an independent target for therapeutic action, and the search for new compounds possessing endothelium-protective properties is one of the prospective goals of the pharmacotherapy and medicinal chemistry. An efficient instrument to solve the problem is the use of methods of molecular modeling. Application of the methods is possible only if detailed information on three-dimensional structure and function of molecular targets—receptors and enzymes responsible for signal transduction both inside and outside endothelial cells—is available. In the review we collected the data on the structure and functions of various macromolecules involved in the process of regulation of vascular tone. The structure of endothelial NO-synthase (EC 1.14.13.39) (eNOS) responsible for synthesis of nitrogen oxide and involved in the process of vascular tone regulation is described. The importance of its substrate, L-arginine, from the point of view of eNOS activity regulation is emphasized; the data on structure and functions of L-arginine transport system are presented. Also, various pathways of eNOS activity regulation are described, including activation and competitive inhibition through binding of exogenous substances in its active center and inhibition through caveolin binding at eNOS oxygenase domain among them, as well as regulation by means of phosphorylation of individual eNOS amino acid residues by protein kinases and their dephosphorylation by phosphatases. The importance of membrane receptors of endotheliocytes as targets for substances possessing endothelium-protective activity is emphasized. Receptors of endothelin, thrombocyte activation factor, prostaglandins, bradykinin, histamine, serotonin, and protein kinase-activated receptors are among them. The importance of calcium and potassium ion channels in vessel cells for endothelium protection is emphasized. Finally, the macromolecules discussed in the review are considered as targets in the search for endothelium-protective therapeutic agents by the proposed approaches and methods of molecular modeling.     

Targeted disruption of the murine retinal dehydrogenase gene Rdh12 does not limit visual cycle function

RDH12 codes for a member of the family of short-chain alcohol dehydrogenases/reductases proposed to function in the visual cycle that supplies the chromophore 11-cis retinal to photoreceptor cells. Mutations in RDH12 cause severe and progressive childhood onset autosomal-recessive retinal dystrophy, including Leber congenital amaurosis. We generated Rdh12 knockout mice, which exhibited grossly normal retinal histology at 10 months of age. Levels of all-trans and 11-cis retinoids in dark- and light-adapted animals and scotopic and photopic electroretinogram (ERG) responses were similar to those for the wild type, as was recovery of the ERG response following bleaching, for animals matched for an Rpe65 polymorphism (p.L450M). Lipid peroxidation products and other measures of oxidative stress did not appear to be elevated in Rdh12(-/-) animals. RDH12 was localized to photoreceptor inner segments and the outer nuclear layer in both mouse and human retinas by immunohistochemistry. The present findings, together with those of earlier studies showing only minor functional deficits in mice deficient for Rdh5, Rdh8, or Rdh11, suggest that the activity of any one isoform is not rate limiting in the visual response.     

动物 microRNA 靶基因的筛选与鉴定研究进展

miRNA（microRNA）是一类在生物体内广泛存在的长度约22nt的小分子非编码RNA,其在转录后水平调控靶基因的表达,在生物体生长发育过程中起重要的调控作用。近年来,miRNA的功能研究越来越受到人们的重视,而miRNA功能研究的关键在于其调控靶基因的确定。miRNA主要作用于靶基因mRNA的3’UTR区的结合位点．但由于miRNA和靶基因的作用位点并不完全匹配,没有明显的规律可寻,导致应用传统方法鉴定靶基因十分困难。近年来,人们开发了各种特异的、灵敏度高的高通量miRNA靶基因筛选与鉴定方法,极大地促进了miRNA的功能研究。     

On the manifestations of memory in visual search

Evidence is presented supporting the thesis that performance in visual search tasks is affected by the contribution of memory processes. Three levels of analysis, corresponding to the various time scales present in a typical search experiment, are discussed. Perceptual learning involves the task and stimulus specific improvement seen across blocks of training. Trial-to-trial priming has an influence which extends over 5-8 trials and lasts on the order of 30 s. Within-trial tagging prevents the re-inspection of already attended (or fixated) items. Also at the within-trial level of analysis, parallel accumulation of evidence for target presence/absence or target location inherently involves memory mechanisms. Organizing the various phenomena in this way makes it apparent that the various mechanisms may interact in a causal way. Within-trial tagging may contribute to priming which may contribute to perceptual learning. Recent proposals that visual search is memoryless (amnesic) are discussed and dismissed.     

Non-Advertized does not Mean Concealed: Body Odour Changes across the Human Menstrual Cycle

Females of a number of primate species display their fertile period by behavioural and/or morphological changes. Traditionally, the fertile period in human females has been considered to be concealed. However, this presumption has rarely been tested. One of the possible mechanisms for assessing menstrual cycle phase is through the sense of smell. In this study possible changes in odour across the menstrual cycle were investigated. Samples of body odour were acquired from 12 women (aged 19–27 yr), none of whom were using hormonal contraceptives. Samples were collected using cotton pads worn in the armpit for 24 h, from the menstrual, follicular and luteal cycle phases. Our experimental sample of 42 males (age 19–34 yr) repeatedly rated these odour samples for their intensity, pleasantness, attractiveness and femininity. Raw subjective smell ratings from each man were transformed to z‐scores. Subsequently, these z‐scores were tested by the general linear mixed‐model analysis (PROC MIXED, SAS) with the female's ID nested within the subject's ID as a random factor to account for the repeated measures of the subjects. Significant changes across the cycle were found for ratings of pleasantness [F_(2,689) = 702; p = 0.001], attractiveness [F(2,546) = 6.35; p = 0.002] and intensity [F(2,530) = 3.57; p = 0.028]. Odour from women in the follicular (i.e. fertile) phase was rated as the least intense and the most attractive. Subsequent post hoc analysis revealed significant differences in intensity, pleasantness and attractiveness between the menstrual phase and the follicular phase, and in pleasantness and attractiveness between the menstrual and luteal phases. Significant difference between the follicular and the luteal phase was found only for attractiveness. Our results suggest that men can potentially use smell as a mechanism for monitoring menstrual cycle phase in current or prospective sexual partners. Therefore, the fertile period in humans should be considered non‐advertized, rather than concealed.     

Formulation with an optical brightener does not increase probability of developing resistance to Spodoptera frugiperda nucleopolyhedrovirus in the laboratory

Stilbene-derived optical brighteners can markedly enhance the insecticidal activity of certain baculoviruses. We evaluated the influence of an optical brightener on the rate at which Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) developed resistance to nucleopolyhedrovirus (SfMNPV). Two laboratory colonies of S. frugiperda were inoculated with an LC50 of SfMNPV, in the absence or presence of the optical brightener Tinopal LPW (0.1%), over a period of two and 11 generations, in the first and second experiment, respectively. Compared with the initial susceptibility of the insect colony, resistance ratios of 11- and 12-fold were observed after two generations of treatment with SfMNPV + Tinopal LPW and SfMNPV alone. Similar, but variable degrees of resistance were observed in the long-term experiment with resistance ratios of 8- to 35-fold after seven to 11 generations. The presence of Tinopal LPW alone, or in mixtures with SfMNPV, did not cause any systematic change in insect resistance in either experiment. At the end of the long-term experiment, debilitating effects on pupal weight, adult fecundity, and longevity were observed in the insects exposed to Tinopal LPW alone or in mixtures with SfMNPV, but the pattern of such effects among treatments differed in each generation. We conclude that optical brighteners are unlikely to affect the rate of development of resistance to nucleopolyhedroviruses applied as biological insecticides.     

Human C-reactive protein does not protect against acute lipopolysaccharide challenge in mice

The physiological and pathophysiological functions of C-reactive protein (CRP), the classical acute-phase protein, are not well established, despite many reports of biological effects of CRP in vitro and in model systems in vivo. Limited, small scale experiments have suggested that rabbit and human CRP may both protect mice against lethal toxicity of Gram-negative bacterial LPS. However, in substantial well-controlled studies in C57BL/6 mice challenged with Escherichia coli O111:B4 LPS, we show in this work that significant protection against lethality was conferred neither by an autologous acute-phase response to sterile inflammatory stimuli given to wild-type mice 24 h before LPS challenge, nor by human CRP, whether passively administered or expressed transgenically. Male mice transgenic for human CRP, which mount a major acute-phase response of human CRP after LPS injection, were also not protected against the lethality of LPS from either E. coli O55:B5 or Salmonella typhimurium. Even when the acute-phase human CRP response was actively stimulated in transgenic mice before LPS challenge, no protection against LPS toxicity was observed. Indeed, male mice transgenic for human CRP that were pretreated with casein to stimulate an acute-phase response 24 h before LPS challenge suffered significantly greater mortality than unstimulated human CRP transgenic controls. Rather than being protective in this situation, human CRP may thus have pathogenic proinflammatory effects in vivo.     

Cannabinoids biology: the search for new therapeutic targets

Cannabinoids, in the form of marijuana plant extracts, have been used for thousands of years for a wide variety of medical conditions, ranging from general malaise and mood disorders to more specific ailments, such as pain, nausea, and muscle spasms. The discovery of tetrahydrocannabinol, the active principal in marijuana, and the identification and cloning of two cannabinoid receptors (i.e., CB1 and CB2) has subsequently led to biomedical appreciation for a family of endocannabinoid lipid transmitters. The biosynthesis and catabolism of the endocannabinoids and growing knowledge of their broad physiological roles are providing insight into potentially novel therapeutic targets. Compounds directed at one or more of these targets may allow for cannabinoid-based therapeutics with limited side effects and abuse liability.