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  • 1
    Publication Date: 2014-02-26
    Description: Astronomers and physicists noticed centuries ago that visual spatial resolution is higher for dark than light stimuli, but the neuronal mechanisms for this perceptual asymmetry remain unknown. Here we demonstrate that the asymmetry is caused by a neuronal nonlinearity in the early visual pathway. We show that neurons driven by...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2012-10-03
    Description: An attractive strategy to overcome multidrug resistance in cancer chemotherapy is to suppress P-glycoprotein (P-gp), which is a pump overproduced in cancer cells to remove cytotoxic drugs from cells. In the present study, a Ca2+-permeable channel TRPC5 was found to be overproduced together with P-gp in adriamycin-resistant breast cancer cell...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2018-06-01
    Description: Author(s): R. Wang, Y. J. Jin, J. Z. Zhao, Z. J. Chen, Y. J. Zhao, and H. Xu The interplay between symmetry and magnetization directions in ferromagnetic materials provides an exotic platform to investigate the symmetry-protected topological order. In this work, we propose that unexpected ferromagnetic topological features, such as triple fermions and type-I and type-II Weyl... [Phys. Rev. B 97, 195157] Published Thu May 31, 2018
    Keywords: Electronic structure and strongly correlated systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 4
    Publication Date: 2015-09-25
    Description: Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRs were enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, which was accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2011-02-23
    Description: Point mutations of the NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream effects of mutant IDH1 and IDH2 proteins or of 2HG on cellular metabolism are unknown. We profiled 〉200 metabolites in human oligodendroglioma (HOG) cells to determine the effects of expression of IDH1 and IDH2 mutants. Levels of amino acids, glutathione metabolites, choline derivatives, and tricarboxylic acid (TCA) cycle intermediates were altered in mutant IDH1- and IDH2-expressing cells. These changes were similar to those identified after treatment of the cells with 2HG. Remarkably, N-acetyl-aspartyl-glutamate (NAAG), a common dipeptide in brain, was 50-fold reduced in cells expressing IDH1 mutants and 8.3-fold reduced in cells expressing IDH2 mutants. NAAG also was significantly lower in human glioma tissues containing IDH mutations than in gliomas without such mutations. These metabolic changes provide clues to the pathogenesis of tumors associated with IDH gene mutations.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2015-10-23
    Description: Glycosylation with O -linked β- N -acetylglucosamine ( O -GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O -GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a multiprotein complex that synthesizes ATP from ADP and P i . Here, we found that ATP synthase subunit α (ATP5A) was O -GlcNAcylated at Thr432 and ATP5A O -GlcNAcylation was decreased in the brains of AD patients and transgenic mouse model, as well as Aβ-treated cells. Indeed, Aβ bound to ATP synthase directly and reduced the O -GlcNAcylation of ATP5A by inhibition of direct interaction between ATP5A and mitochondrial O -GlcNAc transferase, resulting in decreased ATP production and ATPase activity. Furthermore, treatment of O -GlcNAcase inhibitor rescued the Aβ-induced impairment in ATP production and ATPase activity. These results indicate that Aβ-mediated reduction of ATP synthase activity in AD pathology results from direct binding between Aβ and ATP synthase and inhibition of O -GlcNAcylation of Thr432 residue on ATP5A.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2015-09-19
    Description: DGCR8 (DiGeorge syndrome critical region gene 8) is essential for primary microRNA (pri-miRNA) processing in the cell nucleus. It specifically combines with Drosha, a nuclear RNase III enzyme, to form the Microprocessor complex (MC) that cleaves pri-miRNA to precursor miRNA (pre-miRNA), which is further processed to mature miRNA by Dicer, a cytoplasmic RNase III enzyme. Increasing evidences suggest that pri-/pre-miRNAs have direct functions in regulation of gene expression, however the underlying mechanism how it is fine-tuned remains unclear. Here we find that DGCR8 is modified by SUMO1 at the major site K 707 , which can be promoted by its ERK-activated phosphorylation. SUMOylation of DGCR8 enhances the protein stability by preventing the degradation via the ubiquitin proteasome pathway. More importantly, SUMOylation of DGCR8 does not alter its association with Drosha, the MC activity and miRNA biogenesis, but rather influences its affinity with pri-miRNAs. This altered affinity of DGCR8 with pri-miRNAs seems to control the direct functions of pri-miRNAs in recognition and repression of the target mRNAs, which is evidently linked to the DGCR8 function in regulation of tumorigenesis and cell migration. Collectively, our data suggest a novel mechanism that SUMOylation of DGCR8 controls direct functions of pri-miRNAs in gene silencing.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2014-09-18
    Description: We study the geometric properties of random multiplicative cascade measures defined on self-similar sets. We show that such measures and their projections and sections are almost surely exact dimensional, generalizing a result of Feng and Hu for self-similar measures. This, together with a compact group extension argument, enables us to generalize Hochman and Shmerkin's theorems on projections of deterministic self-similar measures to these random measures without requiring any separation conditions on the underlying sets. We give applications to self-similar sets and fractal percolation, including new results on projections, $C^1$ -images and distance sets.
    Print ISSN: 0024-6107
    Electronic ISSN: 1469-7750
    Topics: Mathematics
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  • 9
    Publication Date: 2015-01-21
    Description: Large earthquakes in active mountain belts can trigger landslides, which mobilize large volumes of clastic sediment. Delivery of this material to river channels may result in aggradation and flooding, while sediment residing on hillslopes may increase the likelihood of subsequent landslides and debris flows. Despite recognition of these processes, the controls on the residence time of coseismic landslide sediment in river catchments remain poorly understood. Here we assess the residence time of fine-grained (〈0.25 mm) landslide sediment mobilized by the C.E. 2008 M w 7.9 Wenchuan earthquake, China, using daily suspended sediment discharge measured in 16 river catchments from 2006–2012. Following the earthquake, suspended sediment discharge was elevated 3–7 x compared to 2006–2007. However, the total 2008–2012 export (92.5 ± 9.3 Mt from 68,719 km 2 ) was much less than estimates of fine-grained sediment input by coseismic landslides (480 +350/–338 Mt) determined by landslide area-volume scaling and deposit grain-size distributions. We estimate the residence time of fine-grained sediment in the affected river catchments using the post-earthquake rate of sediment export, and find that it ranges from one year to over a century. The first-order variability in fine-sediment residence time is proportional to the areal extent of coseismic landsliding, and is inversely proportional to the frequency of intense runoff events (〉5 mm day –1 ). Together with previous observations from the C.E. 1999 Chi-Chi earthquake in Taiwan, our results demonstrate the importance of landslide density and runoff intensity in setting the duration of earthquake-triggered landslide impacts on river systems.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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  • 10
    Publication Date: 2015-03-07
    Description: Based on the law of physics, known as “Seebeck effect,” a thermoelectric generator (TEG) produces electricity when the temperature differential is applied across the TEG. This article reports a precision method in characterizing TEG modules. A precision instrument is constructed to study thermoelectric conversion in terms of output power and efficiency of TEG modules. The maximum allowable TEG module size is 150 mm, and the preferred size is from 30 mm to 60 mm. During measurements, the highest hot side temperature is 500 °C and the cold side temperature can be adjusted from room temperature to 100 °C. A mechanical structure is developed to control the pressure and parallelism of the clamping force of the TEG on both its hot and cold sides. A heat flux measurement module is installed at its cold side, and the heat flux through TEGs can be measured in position. Finally, the energy conversion efficiency of TEGs is calculated from experimental data of both an output power and a heat flux.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
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