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1.
Julia D. I. Meuwese Anouk M. van Loon H. Steven Scholte Philipp B. Lirk Nienke C. C. Vulink Markus W. Hollmann Victor A. F. Lamme 《PloS one》2013,8(11)
Recurrent interactions between neurons in the visual cortex are crucial for the integration of image elements into coherent objects, such as in figure-ground segregation of textured images. Blocking N-methyl-D-aspartate (NMDA) receptors in monkeys can abolish neural signals related to figure-ground segregation and feature integration. However, it is unknown whether this also affects perceptual integration itself. Therefore, we tested whether ketamine, a non-competitive NMDA receptor antagonist, reduces feature integration in humans. We administered a subanesthetic dose of ketamine to healthy subjects who performed a texture discrimination task in a placebo-controlled double blind within-subject design. We found that ketamine significantly impaired performance on the texture discrimination task compared to the placebo condition, while performance on a control fixation task was much less impaired. This effect is not merely due to task difficulty or a difference in sedation levels. We are the first to show a behavioral effect on feature integration by manipulating the NMDA receptor in humans. 相似文献
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Jayne Y. Hehir-Kwa Nienke Wieskamp Caleb Webber Rolph Pfundt Han G. Brunner Christian Gilissen Bert B. A. de Vries Chris P. Ponting Joris A. Veltman 《PLoS computational biology》2010,6(4)
Copy number variants (CNVs) have recently been recognized as a common form of genomic variation in humans. Hundreds of CNVs can be detected in any individual genome using genomic microarrays or whole genome sequencing technology, but their phenotypic consequences are still poorly understood. Rare CNVs have been reported as a frequent cause of neurological disorders such as mental retardation (MR), schizophrenia and autism, prompting widespread implementation of CNV screening in diagnostics. In previous studies we have shown that, in contrast to benign CNVs, MR-associated CNVs are significantly enriched in genes whose mouse orthologues, when disrupted, result in a nervous system phenotype. In this study we developed and validated a novel computational method for differentiating between benign and MR-associated CNVs using structural and functional genomic features to annotate each CNV. In total 13 genomic features were included in the final version of a Naïve Bayesian Tree classifier, with LINE density and mouse knock-out phenotypes contributing most to the classifier''s accuracy. After demonstrating that our method (called GECCO) perfectly classifies CNVs causing known MR-associated syndromes, we show that it achieves high accuracy (94%) and negative predictive value (99%) on a blinded test set of more than 1,200 CNVs from a large cohort of individuals with MR. These results indicate that this classification method will be of value for objectively prioritizing CNVs in clinical research and diagnostics. 相似文献
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Localization of Cell Division Protein FtsQ by Immunofluorescence Microscopy in Dividing and Nondividing Cells of Escherichia coli 总被引:3,自引:0,他引:3 下载免费PDF全文
Nienke Buddelmeijer Mirjam E. G. Aarsman Arend H. J. Kolk Miguel Vicente Nanne Nanninga 《Journal of bacteriology》1998,180(23):6107-6116
The localization of cell division protein FtsQ in Escherichia coli wild-type cells was studied by immunofluorescence microscopy with specific monoclonal antibodies. FtsQ could be localized to the division site in constricting cells. FtsQ could also localize to the division site in ftsQ1(Ts) cells grown at the permissive temperature. A hybrid protein in which the cytoplasmic domain and the transmembrane domain were derived from the γ form of penicillin-binding protein 1B and the periplasmic domain was derived from FtsQ was also able to localize to the division site. This result indicates that the periplasmic domain of FtsQ determines the localization of FtsQ, as has also been concluded by others for the periplasmic domain of FtsN. Noncentral FtsQ foci were found in the area of the cell where the nucleoid resides and were therefore assumed to represent sites where the FtsQ protein is synthesized and simultaneously inserted into the cytoplasmic membrane. 相似文献
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Currently available models describing microbial fuel cell (MFC) polarization curves, do not describe the effect of the presence of toxic components. A bioelectrochemical model combined with enzyme inhibition kinetics, that describes the polarization curve of an MFC-based biosensor, was modified to describe four types of toxicity. To get a stable and sensitive sensor, the overpotential has to be controlled. Simulations with the four modified models were performed to predict the overpotential that gives the most sensitive sensor. These simulations were based on data and parameter values from experimental results under non-toxic conditions. Given the parameter values from experimental results, controlling the overpotential at 250 mV leads to a sensor that is most sensitive to components that influence the whole bacterial metabolism or that influence the substrate affinity constant (Km). Controlling the overpotential at 105 mV is the most sensitive setting for components influencing the ratio of biochemical over electrochemical reaction rate constants (K1), while an overpotential of 76 mV gives the most sensitive setting for components that influence the ratio of the forward over backward biochemical rate constants (K2). The sensitivity of the biosensor was also analyzed for robustness against changes in the model parameters other than toxicity. As an example, the tradeoff between sensitivity and robustness for the model describing changes on K1 (IK1) is presented. The biosensor is sensitive for toxic components and robust for changes in model parameter K2 when overpotential is controlled between 118 and 140 mV under the simulated conditions. 相似文献
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Introduction
Anti-Ro antibodies can be found in the serum of the majority of patients with Sjögren''s syndrome (SS). Immunization with a 60-kDa Ro peptide has been shown to induce SS-like symptoms in mice. The aim of this study was to investigate factors involved in salivary gland (SG) dysfunction after immunization and to test whether the induction of SS could be improved.Methods
Ro60 peptide immunization was tested in Balb/c mice, multiple antigenic peptide (MAP)-Ro60 and Pertussis toxin (PTX) were tested in SJL/J mice. In addition, two injection sites were compared in these two strains: the abdominal area and the tailbase. Each group of mice was tested for a loss of SG function, SG lymphocytic infiltration, anti-Ro and anti-La antibody formation, and cytokine production in cultured cells or homogenized SG extracts.Results
Ro60 peptide immunization in the abdominal area of female Balb/c mice led to impaired SG function, which corresponded with increased Th1 cytokines (IFN-γ and IL-12) systemically and locally in the SG. Moreover, changing the immunization conditions to MAP-Ro60 in the abdominal area, and to lesser extend in the tailbase, also led to impaired SG function in SJL/J mice. As was seen in the Balb/c mice, increased IFN-γ in the SG draining lymph nodes accompanied the SG dysfunction. However, no correlation was observed with anti-MAP-Ro60 antibody titers, and there was no additional effect on disease onset or severity.Conclusions
Effective induction of salivary gland dysfunction after Ro60 peptide immunization depended on the site of injection. Disease induction was not affected by changing the immunization conditions. However, of interest is that the mechanism of action of Ro60 peptide immunization appears to involve an increase in Th1 cytokines, resulting in the induction of SG dysfunction. 相似文献7.
Kranzer K van Schaik N Karmue U Middelkoop K Sebastian E Lawn SD Wood R Bekker LG 《PloS one》2011,6(9):e25244
Objectives
To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV testMethods
A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts. Predictors for previous testing were determined using a binominal model.Results
1,144 (88.0%) of 1,300 randomly selected individuals participated in the study. 71.0% (68.3–73.6) had previously had an HIV test and 37.5% (34.6–40.5) had tested in the past 12 months. Men, migrants and older (>35 years) and younger (<20 years) individuals were less likely to have had a previous HIV test. Overall HIV prevalence was 22.7 (20.3–25.3) with peak prevalence of 41.8% (35.8–47.8) in women aged 25.1–35 years and 37.5% (26.7–48.3) in men aged 25.1–45 years. Prevalence of previously undiagnosed HIV was 10.3% (8.5–12.1) overall and 4.5% (2.3–6.6), 8.0% (CI 3.9–12.0) and 20.0% (13.2–26.8) in individuals who had their most recent HIV test within 1, 1–2 and more than 2 years prior to the survey.Conclusion
The high burden of undiagnosed HIV in individuals who had recently tested underscores the importance of frequent repeat testing at least annually. The high prevalence of previously undiagnosed HIV in individuals reporting a negative test in the 12 months preceding the survey indicates a very high incidence. Innovative prevention strategies are needed. 相似文献8.
Konstantinos Nikopoulos Christian Gilissen Alexander Hoischen C. Erik van Nouhuys Ellen A.W. Blokland Nienke Wieskamp Tim M. Strom Mauk A.D. Tilanus Arijit Mukhopadhyay Hans Scheffer Lies H. Hoefsloot Frans P.M. Cremers Rob W.J. Collin 《American journal of human genetics》2010,86(2):240-247
Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous retinal disorder characterized by abnormal vascularisation of the peripheral retina, often accompanied by retinal detachment. To date, mutations in three genes (FZD4, LRP5, and NDP) have been shown to be causative for FEVR. In two large Dutch pedigrees segregating autosomal-dominant FEVR, genome-wide SNP analysis identified an FEVR locus of ∼40 Mb on chromosome 7. Microsatellite marker analysis suggested similar at risk haplotypes in patients of both families. To identify the causative gene, we applied next-generation sequencing in the proband of one of the families, by analyzing all exons and intron-exon boundaries of 338 genes, in addition to microRNAs, noncoding RNAs, and other highly conserved genomic regions in the 40 Mb linkage interval. After detailed bioinformatic analysis of the sequence data, prioritization of all detected sequence variants led to three candidates to be considered as the causative genetic defect in this family. One of these variants was an alanine-to-proline substitution in the transmembrane 4 superfamily member 12 protein, encoded by TSPAN12. This protein has very recently been implicated in regulating the development of retinal vasculature, together with the proteins encoded by FZD4, LRP5, and NDP. Sequence analysis of TSPAN12 revealed two mutations segregating in five of 11 FEVR families, indicating that mutations in TSPAN12 are a relatively frequent cause of FEVR. Furthermore, we demonstrate the power of targeted next-generation sequencing technology to identify disease genes in linkage intervals. 相似文献
9.
Biermasz NR Pereira AM Frölich M Romijn JA Veldhuis JD Roelfsema F 《American journal of physiology. Endocrinology and metabolism》2004,286(1):E25-E30
Octreotide is a potent somatostatin analog that inhibits growth hormone (GH) release and restricts somatotrope cell growth. The long-acting octreotide formulation Sandostatin LAR is effective clinically in approximately 60% of patients with acromegaly. Tumoral GH secretion in this disorder is characterized by increases in pulse amplitude and frequency, nonpulsatile (basal) release, and irregularity. Whether sustained blockade by octreotide can restore physiological secretion patterns in this setting is unknown. To address this question, we studied seven patients with GH-secreting tumors during chronic receptor agonism. Responses were monitored by sampling blood at 10-min intervals for 24 h, followed by analyses of secretion and regularity by multiparameter deconvolution and approximate entropy (ApEn). The somatostatin agonist suppressed GH secretory-burst mass, nonpulsatile (basal) GH release, and pulsatile secretion, thereby decreasing total GH secretion by 86% (range 70-96%). ApEn decreased from 1.203 +/- 0.129 to 0.804 +/- 0.141 (P = 0.032), denoting greater regularity. None of GH pulse frequency, basal GH secretion rates, or ApEn normalized. In summary, chronic somatostatin agonism is able to repress amplitude-dependent measures of excessive GH secretion in acromegaly. Presumptive tumoral autonomy is inferred by continued elevations of event frequency, overall pattern disruption (irregularity), and nonsuppressible basal GH secretion. 相似文献
10.
Darshini Govindasamy Katharina Kranzer Nienke van Schaik Farzad Noubary Robin Wood Rochelle P. Walensky Kenneth A. Freedberg Ingrid V. Bassett Linda-Gail Bekker 《PloS one》2013,8(11)