191 research outputs found

    Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

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    Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

    Dietary Profile of Rhinopithecus bieti and Its Socioecological Implications

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    To enhance our understanding of dietary adaptations and socioecological correlates in colobines, we conducted a 20-mo study of a wild group of Rhinopithecus bieti (Yunnan snub-nosed monkeys) in the montane Samage Forest. This forest supports a patchwork of evergreen broadleaved, evergreen coniferous, and mixed deciduous broadleaved/coniferous forest assemblages with a total of 80 tree species in 23 families. The most common plant families by basal area are the predominantly evergreen Pinaceae and Fagaceae, comprising 69% of the total tree biomass. Previous work has shown that lichens formed a consistent component in the monkeys’ diet year-round (67%), seasonally complemented with fruits and young leaves. Our study showed that although the majority of the diet was provided by 6 plant genera (Acanthopanax, Sorbus, Acer, Fargesia, Pterocarya, and Cornus), the monkeys fed on 94 plant species and on 150 specific food items. The subjects expressed high selectivity for uncommon angiosperm tree species. The average number of plant species used per month was 16. Dietary diversity varied seasonally, being lowest during the winter and rising dramatically in the spring. The monkeys consumed bamboo shoots in the summer and bamboo leaves throughout the year. The monkeys also foraged on terrestrial herbs and mushrooms, dug up tubers, and consumed the flesh of a mammal (flying squirrel). We also provide a preliminary evaluation of feeding competition in Rhinopithecus bieti and find that the high selectivity for uncommon seasonal plant food items distributed in clumped patches might create the potential for food competition. The finding is corroborated by observations that the subjects occasionally depleted leafy food patches and stayed at a greater distance from neighboring conspecifics while feeding than while resting. Key findings of this work are that Yunnan snub-nosed monkeys have a much more species-rich plant diet than was previously believed and are probably subject to moderate feeding competition

    Subcellular distribution of nuclear import-defective isoforms of the promyelocytic leukemia protein

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    <p>Abstract</p> <p>Background</p> <p>The promyelocytic leukemia (PML) protein participates in a number of cellular processes, including transcription regulation, apoptosis, differentiation, virus defense and genome maintenance. This protein is structurally organized into a tripartite motif (TRIM) at its N-terminus, a nuclear localization signal (NLS) at its central region and a C-terminus that varies between alternatively spliced isoforms. Most PML splice variants target the nucleus where they define sub-nuclear compartments termed PML nuclear bodies (PML NBs). However, PML variants that lack the NLS are also expressed, suggesting the existence of PML isoforms with cytoplasmic functions. In the present study we expressed PML isoforms with a mutated NLS in U2OS cells to identify potential cytoplasmic compartments targeted by this protein.</p> <p>Results</p> <p>Expression of NLS mutated PML isoforms in U2OS cells revealed that PML I targets early endosomes, PML II targets the inner nuclear membrane (partially due to an extra NLS at its C-terminus), and PML III, IV and V target late endosomes/lysosomes. Clustering of PML at all of these subcellular locations depended on a functional TRIM domain.</p> <p>Conclusions</p> <p>This study demonstrates the capacity of PML to form macromolecular protein assemblies at several different subcellular sites. Further, it emphasizes a role of the variable C-terminus in subcellular target selection and a general role of the N-terminal TRIM domain in promoting protein clustering.</p

    The G-Quadruplex Ligand Telomestatin Impairs Binding of Topoisomerase IIIα to G-Quadruplex-Forming Oligonucleotides and Uncaps Telomeres in ALT Cells

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    In Alternative Lengthening of Telomeres (ALT) cell lines, specific nuclear bodies called APBs (ALT-associated PML bodies) concentrate telomeric DNA, shelterin components and recombination factors associated with telomere recombination. Topoisomerase IIIα (Topo III) is an essential telomeric-associated factor in ALT cells. We show here that the binding of Topo III to telomeric G-overhang is modulated by G-quadruplex formation. Topo III binding to G-quadruplex-forming oligonucleotides was strongly inhibited by telomestatin, a potent and specific G-quadruplex ligand. In ALT cells, telomestatin treatment resulted in the depletion of the Topo III/BLM/TRF2 complex and the disruption of APBs and led to the segregation of PML, shelterin components and Topo III. Interestingly, a DNA damage response was observed at telomeres in telomestatin-treated cells. These data indicate the importance of G-quadruplex stabilization during telomere maintenance in ALT cells. The function of TRF2/Topo III/BLM in the resolution of replication intermediates at telomeres is discussed

    Forest Fruit Production Is Higher on Sumatra Than on Borneo

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    BACKGROUND: Various studies have shown that the population densities of a number of forest vertebrates, such as orangutans, are higher on Sumatra than Borneo, and that several species exhibit smaller body sizes on Borneo than Sumatra and mainland Southeast Asia. It has been suggested that differences in forest fruit productivity between the islands can explain these patterns. Here we present a large-scale comparison of forest fruit production between the islands to test this hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Data on fruit production were collated from Sumatran and Bornean sites. At six sites we assessed fruit production in three forest types: riverine, peat swamp and dryland forests. We compared fruit production using time-series models during different periods of overall fruit production and in different tree size classes. We examined overall island differences and differences specifically for fruiting period and tree size class. The results of these analyses indicate that overall the Sumatran forests are more productive than those on Borneo. This difference remains when each of the three forest types (dryland, riverine, and peat) are examined separately. The difference also holds over most tree sizes and fruiting periods. CONCLUSIONS/SIGNIFICANCE: Our results provide strong support for the hypothesis that forest fruit productivity is higher on Sumatra than Borneo. This difference is most likely the result of the overall younger and more volcanic soils on Sumatra than Borneo. These results contribute to our understanding of the determinants of faunal density and the evolution of body size on both islands

    Reconstructing extreme AMOC events through nudging of the ocean surface: a perfect model approach

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    While the Atlantic Meridional Overturning Circulation (AMOC) is thought to be a crucial component of the North Atlantic climate, past changes in its strength are challenging to quantify, and only limited information is available. In this study, we use a perfect model approach with the IPSL-CM5A-LR model to assess the performance of several surface nudging techniques in reconstructing the variability of the AMOC. Special attention is given to the reproducibility of an extreme positive AMOC peak from a preindustrial control simulation. Nudging includes standard relaxation techniques towards the sea surface temperature and salinity anomalies of this target control simulation, and/or the prescription of the wind-stress fields. Surface nudging approaches using standard fixed restoring terms succeed in reproducing most of the target AMOC variability, including the timing of the extreme event, but systematically underestimate its amplitude. A detailed analysis of the AMOC variability mechanisms reveals that the underestimation of the extreme AMOC maximum comes from a deficit in the formation of the dense water masses in the main convection region, located south of Iceland in the model. This issue is largely corrected after introducing a novel surface nudging approach, which uses a varying restoring coefficient that is proportional to the simulated mixed layer depth, which, in essence, keeps the restoring time scale constant. This new technique substantially improves water mass transformation in the regions of convection, and in particular, the formation of the densest waters, which are key for the representation of the AMOC extreme. It is therefore a promising strategy that may help to better constrain the AMOC variability and other ocean features in the models. As this restoring technique only uses surface data, for which better and longer observations are available, it opens up opportunities for improved reconstructions of the AMOC over the last few decades

    On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosis

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    BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. Recently the "immuno-modulators" methotrexate, azathioprine and 6-MP and the "anti-inflammatory" 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The "immunosuppressants" Cyclosporine A, Rapamycin and Tacrolimus (FK 506) treat a variety of "autoimmune" and "inflammatory" diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth. METHODOLOGY: The effect on radiometric MAP (14)CO(2) growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans (Dominic & UCF 4) or ruminants (ATCC 19698 & 303) and M. avium subspecies avium (ATCC 25291 & 101) are presented as "percent decrease in cumulative GI" (%-DeltacGI.) PRINCIPAL FINDINGS: The positive control clofazimine has 99%-DeltacGI at 0.5 microg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-DeltacGI by 32 microg/ml (Dominic), Rapamycin has 74%-DeltacGI by 64 microg/ml (UCF 4) and Tacrolimus 43%-DeltacGI by 64 microg/ml (UCF 4) CONCLUSIONS: We show heretofore-undescribed inhibition of MAP growth in vitro by "immunosuppressants;" the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some "autoimmune" and "inflammatory" diseases

    A genome-wide association study of marginal zone lymphoma shows association to the HLA region

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    Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10−15) and HLA-B (rs2922994, P=2.43 × 10−9) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility
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