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  • PMC (PubMed Central)  (38)
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  • 1
    In: PLoS ONE, 2013, Vol.8(8)
    Description: University of Bonn, Institute of Molecular Psychiatry, Bonn, Germany Citation: Schemmer J, Araúzo-Bravo MJ, Haas N, Schäfer S, Weber SN, Becker A, et al. (2013) Correction: Transcription Factor TFAP2C Regulates Major Programs Required for Murine Fetal Germ Cell Maintenance and Haploinsufficiency Predisposes...
    Keywords: Correction
    ISSN: PLoS ONE
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Frontiers in psychology, 2013, Vol.4, pp.316
    Description: Theories of motor-skill acquisition postulate that attentional demands of motor execution decrease with practice. Hence, motor experts should experience less attentional resource conflict when performing a motor task in their domain of expertise concurrently with a demanding cognitive task. We assessed cognitive and motor performance in high-heel experts and novices who were performing a working memory task while walking in gym shoes or high heels on a treadmill. Surprisingly, neither group showed lower working memory performance when walking than when sitting, irrespective of shoe type. However, high-heel experts adapted walking regularity more flexibly to shoe type and cognitive load than novices, by reducing the variability of time spent in the single-support phase of the gait cycle in high heels when cognitively challenged. We conclude that high-heel expertise is associated with more flexible adjustments of movement patterns. Future research should investigate whether a more demanding walking task (e.g., wearing high heels on uneven surfaces and during gait perturbations) results in expertise-related differences in the simultaneous execution of a cognitive task.
    Keywords: Cognition ; Dual-Task ; Expertise ; Gait ; Motor Skills
    ISSN: 1664-1078
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  • 3
    In: PLoS ONE, 2013, Vol.8(8)
    Description: Maintenance and maturation of primordial germ cells is controlled by complex genetic and epigenetic cascades, and disturbances in this network lead to either infertility or malignant aberration. Transcription factor TFAP2C has been described to be essential for primordial germ cell maintenance and to be upregulated in several human germ cell cancers. Using global gene expression profiling, we identified genes deregulated upon loss of Tfap2c in embryonic stem cells and primordial germ cell-like cells. We show that loss of Tfap2c affects many aspects of the genetic network regulating germ cell biology, such as downregulation of maturation markers and induction of markers indicative for somatic differentiation, cell cycle, epigenetic remodeling and pluripotency. Chromatin-immunoprecipitation analyses demonstrated binding of TFAP2C to regulatory regions of deregulated genes ( Sfrp1, Dmrt1 , Nanos3 , c-Kit , Cdk6 , Cdkn1a , Fgf4 , Klf4 , Dnmt3b and Dnmt3l ) suggesting that these genes are direct transcriptional targets of TFAP2C in primordial germ cells. Since Tfap2c deficient primordial germ cell-like cells display cancer related deregulations in epigenetic remodeling, cell cycle and pluripotency control, the Tfap2c -knockout allele was bred onto 129S2/Sv genetic background. There, mice heterozygous for Tfap2c develop with high incidence germ cell cancer resembling human pediatric germ cell tumors. Precursor lesions can be observed as early as E16.5 in developing testes displaying persisting expression of pluripotency markers. We further demonstrate that mice with a heterozygous deletion of the TFAP2C target gene Nanos3 are also prone to develop teratomas. These data highlight TFAP2C as a critical and dose-sensitive regulator of germ cell fate.
    Keywords: Research Article ; Biology ; Medicine
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(5), p.e64544
    Description: C/EBPβ (CCAAT enhancer binding protein) is a transcription factor that plays a crucial role in survival and transformation of ALK+ anaplastic large cell lymphoma (ALCL). The aim of this study was to identify the downstream targets of C/EBPβ...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Environmental Sciences Europe, 2018, Vol.30(1), pp.1-9
    Description: Background Chemical quality of sediment and suspended particulate matter (SPM) is usually assessed by total chemical concentrations ( C total ). However, the freely dissolved concentration ( C free ) is the ecologically more relevant parameter for bioavailability, diffusion and bioaccumulation. In recent studies, equilibrium sampling has been applied to determine C free of hydrophobic organic contaminants (HOCs) in the sediment pore water, whereas such data are missing for SPM. We applied solid-phase micro-extraction to measure and compare C free of PAHs and PCBs in pore water of sediments and SPM sampled along the German part of the river Elbe. Moreover, site-specific distribution ratios were evaluated and C bio,lipid was predicted using C free . Results C free of PAHs remained largely constant while C free of PCBs varied along the Elbe River. The highest C total of PCBs and PAHs were found at Prossen (km 13) and Meißen (km 96). PCB C total even exceeded the environmental quality standard for sediment and SPM in Prossen. Site-specific distribution ratios ( K D ) revealed a stronger sorption for PAHs compared to PCBs, indicating a higher availability of PCBs. Equilibrium partitioning concentrations in lipids ( C lip↔sed ) showed a high correlation with actually measured lipid-normalised concentrations ( C bio,lipid ) in bream. This indicates that PCB bioaccumulation in this benthic fish species is closely linked to the sediment contamination. Conclusions In rivers, SPM functions as a transportation vehicle for HOCs along the stream until it eventually deposits to the sediment. This study demonstrates that due to weaker sorption of PAHs and PCBs to the SPM this matrix poses a higher risk to the aquatic environment compared to the sediment. The prediction of C bio,lipid of PCBs was correct and shows that solid-phase micro-extraction is highly suited to predict lipid concentration, and thus a valuable tool for risk-assessment or sediment management. Electronic supplementary material The online version of this article (10.1186/s12302-018-0159-8) contains supplementary material, which is available to authorized users.
    Keywords: Passive sampling ; SPME ; C free ; HOCs ; SPM ; Sediment ; Elbe River
    ISSN: 2190-4707
    E-ISSN: 2190-4715
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  • 6
    In: Thewes, Verena; Orso, Francesca; Jäger, Richard; Eckert, Dawid; Schäfer, Sabine; Kirfel, Gregor; Garbe, Stephan; Taverna, Daniela; Schorle, Hubert (2010). Interference with activator protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells. BMC Cancer 10 ,
    Description: Background: Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2 alpha and AP-2 gamma is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo-or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods: We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results: We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo-and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo-and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions: Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo-and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference with AP-2 function could increase the sensitivity of tumor cells towards therapeutic intervention.
    Keywords: Tissue Growth-Factor ; Smooth-Muscle-Cells ; Differential Expression ; Mammary-Carcinoma ; Ap-2 Family ; Proliferation ; Overexpression ; Ap-2-Gamma ; Tumor ; Lung
    ISSN: 1471-2407
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  • 7
    Language: English
    In: Frontiers in Human Neuroscience, March 16, 2017
    Description: Neural specificity refers to the degree to which neural representations of different stimuli can be distinguished. Evidence suggests that neural specificity, operationally defined as stimulus-related differences in functional magnetic resonance imaging (fMRI) activation patterns, declines with advancing adult age, and that individual differences in neural specificity are associated with individual differences in fluid intelligence. A growing body of literature also suggests that regular physical activity may help preserve cognitive abilities in old age. Based on this literature, we hypothesized that exercise-induced improvements in fitness would be associated with greater neural specificity among older adults. A total of 52 adults aged 59–74 years were randomly assigned to one of two aerobic-fitness training regimens, which differed in intensity. Participants in both groups trained three times a week on stationary bicycles. In the low-intensity (LI) group, the resistance was kept constant at a low level (10 Watts). In the high-intensity (HI) group, the resistance depended on participants’ heart rate and therefore typically increased with increasing fitness. Before and after the 6-month training phase, participants took part in a functional MRI experiment in which they viewed pictures of faces and buildings. We used multivariate pattern analysis (MVPA) to estimate the distinctiveness of neural activation patterns in ventral visual cortex (VVC) evoked by face or building stimuli. Fitness was also assessed before and after training. In line with our hypothesis, training-induced changes in fitness were positively associated with changes in neural specificity. We conclude that physical activity may protect against age-related declines in neural specificity.
    Keywords: Old Age Cognition -- Physiological Aspects ; Exercise -- Psychological Aspects
    ISSN: 1662-5161
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  • 8
    Language: English
    In: PLoS ONE, 2011, Vol.6(9), p.e23890
    Description: Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. ; Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial, with 5680 participants with a mean age of 75 years, we examined associations of CRP levels and its genetic determinants with cognitive performance and decline over 3.2 years mean follow-up. Higher plasma CRP concentrations were associated with poorer baseline performance on the Stroop test (P = 0.001) and Letter Digit Tests (P0.5). In the prospective analyses, higher CRP concentrations associated with increased rate of decline in the immediate PLT (P = 0.016), but not in other cognitive tests (all p〉0.11). Adjustment for prevalent cardiovascular risk factors and disease did not change the baseline associations nor associations with cognitive decline during follow-up. Four haplotypes of CRP were used and, compared to the common haplotype, carrierships associated strongly with levels of CRP (all P〈0.007). In comparison to strong associations of apolipoprotein E with cognitive measures, associations of CRP haplotypes with such measures were inconsistent. ; Plasma CRP concentrations associate with cognitive performance in part through pathways independent of (risk factors for) cardiovascular disease. However, lifelong exposure to higher CRP levels does not associate with poorer cognitive performance in old age. The current data weaken the argument for a causal role of CRP in cognitive performance, but further study is warranted to draw definitive conclusions.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Public Health And Epidemiology ; Mental Health ; Neurological Disorders ; Biochemistry
    E-ISSN: 1932-6203
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  • 9
    Language: English
    In: BMC Medical Research Methodology, 01 February 2011, Vol.11(1), p.16
    Description: Abstract Background Many research projects in general practice face problems when recruiting patients, often resulting in low recruitment rates and an unknown selection bias, thus limiting their value for health services research. The objective of the study is to evaluate the recruitment performance...
    Keywords: Medicine
    ISSN: 1471-2288
    E-ISSN: 1471-2288
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  • 10
    Language: English
    In: PLoS ONE, 2010, Vol.5(5), p.e10527
    Description: Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda. ; Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100pyar [95% CI 2.82–3.49]); incidence rates at 0–3, 3–6, 6–12 and 12–24 months were 11.25 (9.58–13.21), 6.27 (4.99–7.87), 2.47 (1.87–3.36) and 1.02 (0.80–1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of 〈50 cells/mm (hazard ratio [HR] 1.84 [1.25–2.70],  = 0.002) and male gender (HR 1.68 [1.34–2.11], 〈0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm [IQR; 107, 258, n = 118] vs 209 cells/mm [124, 309, n = 2166],  = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count 〈200 cells/mm: 57.4% vs 46.9%,  = 0.03, and absolute CD4 count 〈200 cells/mm: 30.4 vs 19.9%,  = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%,  = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunogical failure definitions. ; Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm. Incident TB during ART is associated with long-term impairment in immune recovery.
    Keywords: Research Article ; Immunology -- Immune Response ; Virology -- Immunodeficiency Viruses ; Infectious Diseases -- Hiv Infection And Aids ; Public Health And Epidemiology -- Global Health
    E-ISSN: 1932-6203
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