Discrimination of Sensorimotor EEG (12–15 Hz) Activity: A Comparison of Response, Production, and No-Feedback Training Conditions

The current study was concerned with the discrimination of 12–15 Hz (15μV) surface cortical EEG, recorded over the dominant hemisphere. This EEG bandwidth is sometimes called the SMR (sensorimotor rhythm), and has been associated with seizure reduction. Thirty-six normal subjects were divided into three groups and exposed to three methods of discrimination training: response feedback, production feedback, and no-feedback control. In the initial assessment session, all subjects were asked to detect the presence of SMR by pressing a response button in the absence of feedback. Over the next 4 training sessions, the control group continued without feedback, while the response feedback group received feedback (tone) for correct discriminations, and the production group received feedback for producing the SMR signal. Discrimination performance was assessed during a 15-min no-feedback test period, following each feedback segment. The final session took place two weeks after training had been completed and was the same as session 1. The results showed that both experimental groups improved discrimination accuracy over baseline, and relative to the control group. Performance of the groups at baseline was not significantly different, ranging between 16% and 29% correct. Peak performance during training showed that both experimental groups improved over baseline and relative to the control group, averaging 17%, 43% and 78% correct for the control, response and production feedback groups, respectively. In the final assessment, all groups deteriorated in performance, but the production group remained significantly above baseline levels. No changes in average SMR time or frontal EMG were noted. However, time spent in the occipital alpha bandwidth 8–13 Hz (25μV) did increase in the best discriminators. This may indicate some discrimination of subjective sensations associated with SMR discrimination training.     

A time for learning and a time for sleep: the effect of sleep deprivation on contextual fear conditioning at different times of the day

Study Objectives:

Sleep deprivation negatively affects memory consolidation, especially in the case of hippocampus-dependent memories. Studies in rodents have shown that 5 hours of sleep deprivation immediately following footshock exposure selectively impairs the formation of a contextual fear memory. In these studies, both acquisition and subsequent sleep deprivation were performed in the animals'' main resting phase. However, in everyday life, subjects most often learn during their active phase.

Design:

Here we examined the effects of sleep deprivation on memory consolidation for contextual fear in rats when the task was performed at different times of the day, particularly, at the beginning of the resting phase or right before the onset of the active phase.

Measurements and Results:

Results show that sleep deprivation immediately following training affects consolidation of contextual fear, independent of time of training. However, in the resting phase memory consolidation was impaired by 6 hours of posttraining sleep deprivation, whereas, in the active phase, the impairment was only seen after 12 hours of sleep deprivation. Since rats sleep at least twice as much during the resting phase compared with the active phase, these data suggest that the effect of sleep deprivation depends on the amount of sleep that was lost. Also, control experiments show that effects of sleep deprivation were not related to the amount of stimulation the animals received and were therefore not likely an indirect effect of the sleep-deprivation method.

Conclusion:

These results support the notion that sleep immediately following acquisition, independent of time of day, promotes memory consolidation and that sleep deprivation may disrupt this process depending on the amount of sleep that is lost.

Citation:

Hagewoud R; Whitcomb SN; Heeringa AN; Havekes R; Koolhaas JM; Meerlo P. A time for learning and a time for sleep: the effect of sleep deprivation on contextual fear conditioning at different times of the day. SLEEP 2010;33(10):1315-1322.     

Effect of Interleukin (IL)-12 and IL-15 on Activated Natural Killer (ANK) and Antibody-Dependent Cellular Cytotoxicity (ADCC) in HIV Infection

The ability of IL-12 and IL-15 to enhance natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNCs) from HIV⁺ children and their mothers was investigated. MNCs from HIV⁺ patients were deficient in NK and ADCC activity compared to control MNCs against several target cells. Overnight incubation with IL-15 or IL-12 augmented NK activity of MNCs from both patients and controls, and the combination of IL-12 and IL-15 resulted in the greatest enhancement. ADCC in HIV⁺ patients against gp120-coated CEM.NKR cells or chicken erythrocytes could also be enhanced by IL-2 or IL-15 in overnight cultures. Culturing MNCs with either IL-2 or IL-15 for 1 week increased the NK activity in patients to levels of controls treated with these cytokines. However, the response to the combination of IL-12 and IL-15 was less than that to IL-15 alone in 1-week cultures. Culturing MNCs with IL-2 and IL-15 for 1 week also increased the percentage of CD16⁺/CD56⁺ cells in both patients and controls. Thus, IL-15 can restore the deficient NK activity in patients and may be a candidate for immunomodulative therapy in HIV⁺ patients.     

层粘连蛋白与佛波醇酯对人肝癌细胞粘连和增殖特性的影响

目的:探讨层粘连蛋白(Ln)与佛波醇酯(PMA)对人肝癌细胞粘连和增殖特性的影响及其相关机制,提供肝癌治疗的新线索。方法:体外以人肝癌细胞系(BEL-7402)为靶细胞,在揭示靶细胞是否存在内源性Ln(enLn)表达的同时,利用促癌剂PMA(phorbol-12-myristate-13-acetate)与外源性Ln(exLn)的作用来比较研究enLn及细胞蛋白激酶C-α(cPKC-α)活性表达变化与细胞粘连和增殖特性的关系。结果:靶细胞呈现enLn的阳性表达,exLn能加强其细胞粘连及增殖能力;当PMA作用时,其细胞呈现enLn的更高程度表达,其细胞粘连性亦得到更明显地加强;而仅PMA的单独作用却能使其细胞呈现明显的增殖抑制,但PMA与exLn的共同作用,其细胞增殖力呈现在exLn单独作用得到加强的基础上获得更进一步的加强,显示出了协同效应。并且,PMA的单独作用能下调其细胞cPKC-α的表达,而外源性Ln的作用则能加强其细胞cPKC-α的表达。结论:内、外源性Ln的作用与人肝癌细胞的粘连、增殖密切相关,其与癌细胞的cPKC-α的活性密切关联。抗Ln抗体及PKC的抑制剂的联合应用可提供一条肝癌治疗的可探索新途径。     

The complement regulatory proteins CD55 (decay accelerating factor) and CD59 are expressed on the inner acrosomal membrane of human spermatozoa as well as CD46 (membrane cofactor protein)

The complement regulatory proteins CD55 and CD59 are expressed on the plasma membrane of human spermatozoa, whereas CD46 is only on the inner acrosomal membrane (IAM) which becomes surfaced exposed after the acrosome reaction when sperm assume fertilisation-competence. CD55 & CD59, two glycosylphosphatidylinositol (GPI)-anchored proteins, have been detected previously in some studies also in the acrosomal region of chemically fixed spermatozoa but never demonstrated at this site on unfixed spermatozoa. Dual labelling immunofluorescence and confocal microscopy on fresh unfixed spermatozoa, with minimal subsequent time to fixation, has shown CD55 to be markedly expressed on the IAM, more than on the plasma membrane. However, unlike for CD46, CD55 displayed patchy staining over the acrosome, with some variation between individual spermatozoa. All IAM-associated CD55 was localised within GM1-containing lipid rafts. CD59 was expressed also on the IAM, but in a pronounced granular pattern with more variation observed from one spermatozoa to another. Both CD55 & CD59 were released from the IAM by PI-PLC, demonstrating them to be GPI-anchored. Analysis of acrosome-reacted spermatozoal CD55 by Western blotting revealed a novel single 55 kDa protein lacking significant oligosaccharides susceptible to glycosidases. Antibody-induced membrane rafting and release of CD55 & CD59 in vitro may have influenced previous results. Significant coexpression of CD55 & CD46 on the IAM suggests some functional cooperation at this site.     

HIV-1包膜蛋白2G12和2F5中和表位的改造对假病毒形成及中和活性的影响

目的 研究HIV-1膜蛋白(Env)特定中和表位的改造对功能性假病毒形成及中和活性的影响.方法 采用环形诱变及Dpn I筛选的方法对Env进行定点突变,将2G12和2F5两个中和表位整合入不含该表位的BC亚型的Env上,比较改造对假病毒的形成情况及对2G12和2F5单抗的中和活性的影响.结果 对5株假病毒(BC02、BE03、BC04、BC05和BC12)的Env特定中和表位进行改造,其中BC04和BCl2的2G12表位改造后,不能形成假病毒,BC02、BC03和BC05增加2G12和2F5两个表位后,仍能够形成假病毒,且假病毒滴度较改造前无明显变化,改造后的BC03假病毒较改造前对单抗2G12和2175的中和活性均有所提高,而改造后的BE02和BC05假病毒较改造前对单抗2F5的中和活性增强,而对单抗2G12的中和活性无变化.结论 2G12中和表位部分位点的改造影响假病毒的形成,中和表位的增加能够提高单抗2G12的中和活性,为免疫原的优化提供了新思路.     

Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations

BACKGROUND: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. METHODS: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. RESULTS: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. CONCLUSIONS: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.     

Differential expression of LFA-3, Fas and MHC Class I on Ad5- and Ad12-transformed human cells and their susceptibility to lymphokine-activated killer (LAK) cells

Adenovirus (Ad) E1A is a potent oncogene and has been shown to deregulate the expression of a large number of cellular genes leading to cellular transformation. Here we have analysed the expression of several immunomodulatory molecules on the surface of a set of human cell lines transformed with either Ad12 or Ad5. Human cells transformed with Ad12 demonstrated reduced expression of cell surface LFA-3, Fas and MHC class I when compared to Ad5-transformed cells. Furthermore, Ad12-transformed human cell lines demonstrated greater susceptibility to lysis by lymphokine-activated killer (LAK) cells, compared to Ad5-transformed human cell lines. In contrast, previous studies with rodent cells showed that both Ad5- and Ad12-transformed rat cells were susceptible to LAK cells. Thus, transformation of human cells with Ad5 or Ad12 results in differences in the expression of immunomodulatory molecules on the cell surface and differential recognition of these virus-transformed cells by immune effector cells.     

Differential expression of the cytokine receptors for human interleukin (IL)-12 and IL-18 on lymphocytes of both CD45RA and CD45RO phenotype from tonsils, cord and adult peripheral blood

The objective of this study was to demonstrate the variable expression of cytokine receptors on naive versus memory human CD4+ T cell subpopulations in tonsillar tissue, cord blood and adult blood. We prove that the receptors for both interleukin (IL)-12 and IL-18 are expressed exclusively on memory T cells. This observation was seen not only on the CD45RO+ memory T cells but also on a significant percentage of the CD45RA+, CD62L-, CD27- and CCR7- populations. Furthermore, CD45RA+ CD62L+, CD27+ or CCR7+ CD4+ T cells that expressed IL-12Rbeta1 and IL-18Ralpha did not express CD31, a marker for recent thymic emigrants. We reveal that cord blood lymphocytes do not express IL-12Rbeta1 whereas IL-18Ralpha expression was detected at low levels. Importantly, the IL-12Rbeta2 signalling chain, which is absent in all resting T cells, was up-regulated in both CD45RA+ and CD45RO+ T cells as a result of stimulation with anti-CD3 and anti-CD28 in vitro. This observed up-regulation was, however, restricted to 80% of the total CD4+ population. Finally, a very small proportion of the CD4+ CD45RO+ tonsillar T cells expressed the IL-12 and IL-18 receptors, thereby establishing the differential expression of these receptors between peripheral and tonsillar memory T cell subpopulations.