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991.
Priest Pot is an example of the abundant ponds that, collectively, contribute crucially to species diversity. Despite extensive
biological study, little has been reported about the physical framework that supports its ecological richness. This article
elucidates the physical character of Priest Pot’s water column and thus that of similar water bodies. Vertical thermal microstructure
profiles were recorded during summer 2003 and analyzed alongside concurrent meteorological data. During summer stratification,
the thermal structure appeared to be dominated by surface heat fluxes. Surface wind stress, limited by sheltering vegetation,
caused turbulent overturns once a surface mixed layer was present but appeared to contribute little to setting up the thermal
structure. Variations in full-depth mean stratification occurred predominantly over seasonal and ∼5-day time scales, the passage
of atmospheric pressure systems being posited as the cause of the latter. In the uppermost ∼0.5 m, where the stratification
varied at subdaily time scales, turbulence was active (sensu Ivey and Imberger 1991) when this layer was mixed, with dissipation
values ε ∼ 10−8 m2 s−3 and vertical diffusivity KZ = 10−4 — 10−6 m2 s−1. Where the water column was stratified, turbulence was strongly damped by both buoyancy and viscosity, and KZ was an order of magnitude smaller. Vertical transport in the mixed layer occurred via many small overturns (Thorpe scale
r.m.s. and maximum values were typically 0.02 m and 0.10 m, respectively), and seston were fully mixed through the water column. 相似文献
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994.
Helicobacter pylori‐induced Sonic Hedgehog Expression is Regulated by NFκB Pathway Activation: The Use of a Novel In vitro Model to Study Epithelial Response to Infection 下载免费PDF全文
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996.
Jerry W. Marlin Yu-Wen E. Chang Margaret Ober Amy Handy Wenhao Xu Rolf Jakobi 《Mammalian genome》2011,22(5-6):306-317
p21-Activated protein kinase 2 (PAK-2) has both anti- and pro-apoptotic functions depending on its mechanism of activation. Activation of full-length PAK-2 by the monomeric GTPases Cdc42 or Rac stimulates cell survival, whereas caspase activation of PAK-2 to the PAK-2p34 fragment is involved in the apoptotic response. In this study we use functional knockout of PAK-2 and gene replacement with the caspase cleavage-deficient PAK-2D212N mutant to differentiate the biological functions of full-length PAK-2 and caspase-activated PAK-2p34. Knockout of PAK-2 results in embryonic lethality at early stages before organ development, whereas replacement with the caspase cleavage-deficient PAK-2D212N results in viable and healthy mice, indicating that early embryonic lethality is caused by deficiency of full-length PAK-2 rather than lack of caspase activation to the PAK-2p34 fragment. However, deficiency of caspase activation of PAK-2 decreased spontaneous cell death of primary mouse embryonic fibroblasts and increased cell growth at high cell density. In contrast, stress-induced cell death by treatment with the anti-cancer drug cisplatin was not reduced by deficiency of caspase activation of PAK-2, but switched from an apoptotic to a nonapoptotic, caspase-independent mechanism. Homozygous PAK-2D212N primary mouse embryonic fibroblasts that lack the ability to generate the proapoptotic PAK-2p34 show less activation of the effector caspase 3, 6, and 7, indicating that caspase activation of PAK-2 amplifies the apoptotic response through a positive feedback loop resulting in more activation of effector caspases. 相似文献
997.
Karslioglu E Kleinberger JW Salim FG Cox AE Takane KK Scott DK Stewart AF 《Molecular endocrinology (Baltimore, Md.)》2011,25(10):1760-1772
Adult human β-cells replicate slowly. Also, despite the abundance of rodent β-cell lines, there are no human β-cell lines for diabetes research or therapy. Prior studies in four commonly studied rodent β-cell lines revealed that all four lines displayed an unusual, but strongly reproducible, cell cycle signature: an increase in seven G(1)/S molecules, i.e. cyclins A, D3, and E, and cdk1, -2, -4, and -6. Here, we explore the upstream mechanism(s) that drive these cell cycle changes. Using biochemical, pharmacological and molecular approaches, we surveyed potential upstream mitogenic signaling pathways in Ins 1 and RIN cells. We used both underexpression and overexpression to assess effects on rat and human β-cell proliferation, survival and cell cycle control. Our results indicate that cMyc is: 1) uniquely up-regulated among other candidates; 2) principally responsible for the increase in the seven G(1)/S molecules; and, 3) largely responsible for proliferation in rat β-cell lines. Importantly, cMyc expression in β-cell lines, although some 5- to 7-fold higher than normal rat β-cells, is far below the levels (75- to 150-fold) previously associated with β-cell death and dedifferentiation. Notably, modest overexpression of cMyc is able to drive proliferation without cell death in normal rat and human β-cells. We conclude that cMyc is an important driver of replication in the two most commonly employed rat β-cell lines. These studies reverse the current paradigm in which cMyc overexpression is inevitably associated with β-cell death and dedifferentiation. The cMyc pathway provides potential approaches, targets, and tools for driving and sustaining human β-cell replication. 相似文献
998.
Saunders HM Gilis D Rooman M Dehouck Y Robertson AL Bottomley SP 《Protein science : a publication of the Protein Society》2011,20(10):1675-1681
Spinocerebellar Ataxia Type 3 (SCA3) is one of nine polyglutamine (polyQ) diseases that are all characterized by progressive neuronal dysfunction and the presence of neuronal inclusions containing aggregated polyQ protein, suggesting that protein misfolding is a key part of this disease. Ataxin-3, the causative protein of SCA3, contains a globular, structured N-terminal domain (the Josephin domain) and a flexible polyQ-containing C-terminal tail, the repeat-length of which modulates pathogenicity. It has been suggested that the fibrillogenesis pathway of ataxin-3 begins with a non-polyQ-dependent step mediated by Josephin domain interactions, followed by a polyQ-dependent step. To test the involvement of the Josephin domain in ataxin-3 fibrillogenesis, we have created both pathogenic and nonpathogenic length ataxin-3 variants with a stabilized Josephin domain, and have both stabilized and destabilized the isolated Josephin domain. We show that changing the thermodynamic stability of the Josephin domain modulates ataxin-3 fibrillogenesis. These data support the hypothesis that the first stage of ataxin-3 fibrillogenesis is caused by interactions involving the non-polyQ containing Josephin domain and that the thermodynamic stability of this domain is linked to the aggregation propensity of ataxin-3. 相似文献
999.
Bohonak AJ Vandergast AG 《Molecular ecology》2011,20(12):2477–9; authors reply 2480-2477–9; authors reply 2482
In a recent Opinion article in Molecular Ecology, Wang (2010) emphasizes the fact that current patterns of genetic differentiation among populations reflect processes that have acted over temporal scales ranging from contemporary to ancient. He draws a sharp distinction between the fields of phylogeography (as the study of historical processes) and landscape genetics (which he restricts to very recent processes). Wang characterizes DNA sequence data as being inappropriate for the study of contemporary population processes and further states that studies which only include mitochondrial DNA or chloroplast DNA data cannot be considered part of landscape genetics. In this response, we clarify the generally accepted view that DNA sequence data can be analysed with methods that separate contemporary and historical processes. To illustrate this point, we summarize the study of Vandergast et al. (2007), which Wang mischaracterizes as being confused in terms of temporal scale. Although additional focus should be placed on the important issue of correct data interpretation, we disagree strongly with the implication that contemporary and historic processes cannot be separated in the analyses of DNA sequence data. 相似文献
1000.
Lalonde JM Elban MA Courter JR Sugawara A Soeta T Madani N Princiotto AM Kwon YD Kwong PD Schön A Freire E Sodroski J Smith AB 《Bioorganic & medicinal chemistry》2011,19(1):91-101
The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, gold docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. 相似文献