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  • 1
    Publication Date: 2014-01-08
    Description: The oxidative phosphorylation (OXPHOS) system generates most of the ATP in respiring cells. ATP-depleting conditions, such as hypoxia, trigger responses that promote ATP production. However, how OXPHOS is regulated during hypoxia has yet to be elucidated. In this study, selective measurement of intramitochondrial ATP levels identified the hypoxia-inducible protein G0/G1...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2013-10-02
    Description: Tuite, -Ca 3 (PO 4 ) 2 , is regarded as an important phosphate mineral in the deep mantle playing a crucial role as a host for rare earth elements, large ion lithophile elements, and phosphorus. In this study we report the thermoelastic properties of synthetic -Ca 3 (PO 4 ) 2 at simultaneously high pressures and temperatures of up to 35.4 GPa and 1300 K, respectively, as determined by means of in situ energy-dispersive X-ray diffraction in a large-volume multi-anvil apparatus. The pressure-volume-temperature data obtained for -Ca 3 (PO 4 ) 2 were fitted by the high-temperature Birch-Murnaghan equation of state to yield V 0 = 447.4(4) Å 3 , K T0 = 100.8(18) GPa, K ' T0 = 5.74(13), ( K T / T ) P = –0.020(1) GPa/K, and α T = 3.26(18) x 10 –5 + 1.76(24) x 10 –8 T . In addition, fitting the present data to the Mie-Grüneisen-Debye equation of state gives 0 = 1.35(6), 0 = 944(136) K, and q = 0.37(29). Based on the thermoelastic properties obtained in our study, the density profiles of -Ca 3 (PO 4 ) 2 tuite along typical cold and hot slab geotherms were calculated and are compared with those of the coexisting silicate minerals in subducting mid-ocean ridge basalt.
    Print ISSN: 0003-004X
    Electronic ISSN: 1945-3027
    Topics: Geosciences
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  • 3
    Publication Date: 2015-02-11
    Description: Metformin, a prescribed drug for type 2 diabetes, has been reported to have anti-cancer effects; however, the underlying mechanism is poorly understood. Here we show that this mechanism may be immune-mediated. Metformin enabled normal but not T-cell–deficient SCID mice to reject solid tumors. In addition, it increased the number of...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2015-01-30
    Description: The 2011 moment magnitude ( M w ) 9.0 Tohoku-Oki Japan earthquake occurred in a region where giant megathrust earthquakes were not expected. This earthquake proved the difficulty in assessing seismic hazard by relying mainly on information from historical and instrumental seismicity. To help improve the seismic-hazard assessment for such rare events, we propose a methodology to estimate the slip distribution of future megathrust earthquakes based on a model of interseismic coupling distribution in subduction margins, as well as information of historical earthquakes, and apply the method to the central Peru region, Lima. The slip model obtained from geodetic data represents the large scale features of asperities within the megathrust, which is appropriate for simulation of long-period waves and tsunami modeling. For the simulation of a broadband strong ground motion, we add small scale heterogeneities to the source slip to be able to simulate high frequencies. To achieve this purpose, we propose broadband source models constructed by adding short-wavelength slip distributions obtained from a Von Karman power spectral density function, to the slip model inferred from interseismic geodetic data. Using these slip models and assuming several hypocenter locations, we calculate a set of strong ground motions for Lima and incorporate site effects obtained from microtremors surveys and geotechnical data. Our simulated average pseudospectral accelerations (period 0.3 s) are above for wide areas in Lima, which may be critical in terms of damage of low- to midrise masonry and reinforced concrete buildings, which characterize the majority of buildings in Lima.
    Print ISSN: 0037-1106
    Electronic ISSN: 1943-3573
    Topics: Geosciences , Physics
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  • 5
    Publication Date: 2012-06-20
    Description: The organization of the apical junctional complex and its association with the cytoskeleton is essential for the function of epithelial cells. However, knowledge about the signaling pathways that regulate these processes is still fragmentary. Here we found that ARHGEF11, a member of the RGS-RhoGEF family, associates with tight junctions (TJs) by binding to ZO-1, but not to the highly homologous ZO-2, in polarized epithelial cells. In the early phases of cell–cell contact, ARHGEF11 was located at primordial adherens junctions, and then its localization was altered to TJs as epithelial polarity was established, much like ZO-1. Knockdown of ARHGEF11 reduced the phosphorylation of myosin light chain, retarding the assembly of cell–cell junctions and the development of the paracellular barrier. Furthermore, the simultaneous knockdown of ARHGEF11 and ZO-2 resulted in significant impairment of TJs and of the perijunctional actomyosin ring; similar defects arise when both ZO-1 and ZO-2 are depleted. These results suggest that ARHGEF11 mediates RhoA–myosin light chain signaling pathways at cell–cell junctions, functioning in cooperation with ZO-1, to regulate the paracellular barrier and the organization of the apical junctional complex and perijunctional actomyosin ring of epithelial cells.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2011-09-07
    Description: CD8 T cells play a critical role in protection against viral infections. During effector differentiation, CD8 T cells dramatically change chromatin structure and cellular metabolism, but how energy production increases in response to these epigenetic changes is unknown. We found that loss of basic leucine zipper transcription factor, ATF-like (BATF) inhibited effector CD8 T-cell differentiation. At the late effector stage, BATF was induced by IL-12 and required for IL-12–mediated histone acetylation and survival of effector T cells. BATF, together with c-Jun, transcriptionally inhibited expression of the nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase Sirt1, resulting in increased histone acetylation of the T-bet locus and increased cellular NAD+, which increased ATP production. In turn, high levels of T-bet expression and ATP production promoted effector differentiation and cell survival. These results suggest that BATF promotes effector CD8 T-cell differentiation by regulating both epigenetic remodeling and energy metabolism through Sirt1 expression.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2012-01-05
    Description: Toll like receptors (TLRs) use Toll–IL-1 receptor (TIR) domain-containing adapters, such as myeloid differentiation primary response gene 88 (MyD88) and TIR domain-containing adapter inducing IFN-β (TRIF), to induce activation of transcription factors, including NF-κB, MAP kinases, and IFN regulatory factors. TLR signaling also leads to activation of PI3K, but the molecular mechanism is not understood. Here we have discovered a unique role for B-cell adapter for PI3K (BCAP) in the TLR-signaling pathway. We find that BCAP has a functional N-terminal TIR homology domain and links TLR signaling to activation of PI3K. In addition, BCAP negatively regulates proinflammatory cytokine secretion upon TLR stimulation. In vivo, the absence of BCAP leads to exaggerated recruitment of inflammatory myeloid cells following infections and enhanced susceptibility to dextran sulfate sodium-induced colitis. Our results demonstrate that BCAP is a unique TIR domain-containing TLR signaling adapter crucial for linking TLRs to PI3K activation and regulating the inflammatory response.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2014-07-15
    Description: Predation has led to the evolution of defensive armor in prey species. The dense and long hairs of caterpillars (i.e., lepidopteran larvae) are generally believed to play an important role as a physical defence against predators. However, few studies have been undertaken to investigate how hairs protect caterpillars from a predator’s weapons. To determine the importance of caterpillar hairs as a defensive armor, we observed adults of Calosoma maximowiczi (Carabidae) attacking 5 caterpillar species with different hairiness under laboratory conditions. Carabids used their mandibles to catch caterpillars and thereafter fed on them. Almost all the larvae of 3 smooth species and a short-haired species were easily caught by carabids during their first attack. However, 53.2% of larvae in a long-haired species Lemyra imparilis (Erebidae: Arctiinae) were able to escape from carabid attacks. Even when Lemyra larvae were finally eaten, carabids required a larger number of attacks to catch Lemyra larvae. Dorsal hairs of Lemyra larvae were much longer than the mandible length of carabid adults for any body size, suggesting that the dorsal hairs can function as a physical barrier against carabid attacks. To test the hypothesis, we cut the dorsal hairs of Lemyra larvae shorter than the carabids’ mandibles. Cutting the dorsal hairs of Lemyra larvae resulted in fewer carabid attacks with higher success rates. Therefore, we conclude that long hairs can protect Lemyra larvae from carabid mandibles. This is the first study to clarify the adaptive significance of caterpillar hair length as a morphological defence.
    Print ISSN: 1045-2249
    Electronic ISSN: 1465-7279
    Topics: Biology
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  • 9
    Publication Date: 2001-02-13
    Description: Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated the effects of cycles of food availability (which exert powerful entraining effects on behavior) on the rhythms of gene expression in the liver, lung, and suprachiasmatic nucleus (SCN). We used a transgenic rat model whose tissues express luciferase in vitro. Although rhythmicity in the SCN remained phase-locked to the light-dark cycle, restricted feeding rapidly entrained the liver, shifting its rhythm by 10 hours within 2 days. Our results demonstrate that feeding cycles can entrain the liver independently of the SCN and the light cycle, and they suggest the need to reexamine the mammalian circadian hierarchy. They also raise the possibility that peripheral circadian oscillators like those in the liver may be coupled to the SCN primarily through rhythmic behavior, such as feeding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokkan, K A -- Yamazaki, S -- Tei, H -- Sakaki, Y -- Menaker, M -- MH 56647/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2001 Jan 19;291(5503):490-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Science Foundation Center for Biological Timing and Department of Biology, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904-4328, USA. mm7e@virginia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11161204" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; *Circadian Rhythm ; Corticosterone/blood/pharmacology ; Culture Techniques ; Eating ; Female ; *Food ; *Gene Expression Regulation ; Genes, Reporter ; Liver/*physiology ; Luciferases/genetics ; Lung/physiology ; Male ; Motor Activity ; Organ Specificity ; Rats ; Suprachiasmatic Nucleus/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2000-04-28
    Description: In multicellular organisms, circadian oscillators are organized into multitissue systems which function as biological clocks that regulate the activities of the organism in relation to environmental cycles and provide an internal temporal framework. To investigate the organization of a mammalian circadian system, we constructed a transgenic rat line in which luciferase is rhythmically expressed under the control of the mouse Per1 promoter. Light emission from cultured suprachiasmatic nuclei (SCN) of these rats was invariably and robustly rhythmic and persisted for up to 32 days in vitro. Liver, lung, and skeletal muscle also expressed circadian rhythms, which damped after two to seven cycles in vitro. In response to advances and delays of the environmental light cycle, the circadian rhythm of light emission from the SCN shifted more rapidly than did the rhythm of locomotor behavior or the rhythms in peripheral tissues. We hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamazaki, S -- Numano, R -- Abe, M -- Hida, A -- Takahashi, R -- Ueda, M -- Block, G D -- Sakaki, Y -- Menaker, M -- Tei, H -- MH56647/MH/NIMH NIH HHS/ -- R01 MH056647/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):682-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NSF Center for Biological Timing and Department of Biology, University of Virginia, Charlottesville, VA 22903-2477, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10784453" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Biological Clocks/*physiology ; Cell Cycle Proteins ; Circadian Rhythm/*physiology ; Culture Techniques ; Darkness ; Genes, Reporter ; Light ; Liver/physiology ; Luciferases/genetics/metabolism ; Lung/physiology ; Male ; Mice ; Motor Activity ; Muscle, Skeletal/physiology ; Nuclear Proteins/genetics/physiology ; Period Circadian Proteins ; Promoter Regions, Genetic ; Rats ; Suprachiasmatic Nucleus/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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