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991.
Jennifer R. Robbins Kasia M. Skrzypczynska Varvara B. Zeldovich Mirhan Kapidzic Anna I. Bakardjiev 《PLoS pathogens》2010,6(1)
Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts—which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin—served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta. 相似文献
992.
26-Hydroxyecdysone is the predominant molting hormone in 24- to 44-hour-old embryonated tobacco hornworm eggs, accounting for approximately 80% of the ecdysones present at this stage of development. This molting hormone was previously shown to be the major ecdysone present in 48- to 64-hour-old embryonated eggs of this insect. During both of these periods of embryonic development in the hornworm 20-hydroxyecdysone is a minor component, in contrast to its presence as the major ecdysone in the hornworm during certain stages of post-embryonic development. 相似文献
993.
The functional significance of the actin binding region at the amino terminus of the cardiac essential myosin light chain (ELC) remains obscure. Previous experiments carried out in vitro indicated that modulation of residues 5-14 could induce an inotropic effect, increasing maximal ATPase activity at submaximal Ca(2+) concentrations (Rarick, H. M., Opgenorth, T. J., von Geldern, T. W., Wu-Wong, J. R., and Solaro, R. J. (1996) J. Biol. Chem. 271, 27039-27043). Using transgenesis, we effected a cardiac-specific replacement of ELC with a protein containing a 10-amino acid deletion at positions 5-14. Both the ventricular (ELC1vDelta5-14) and atrial (ELC1aDelta5-14) isoforms lacking this peptide were stably incorporated into the sarcomere at high efficiencies. Surprisingly when the kinetics of skinned fibers isolated from the ELC1vDelta5-14 or ELC1aDelta5-14 mice were examined, no alterations in either unloaded shortening or maximum shortening velocities were apparent. Myofibrillar Mg(2+)-ATPase activity was also unchanged in these preparations. No significant changes in the fiber kinetics in the cognate compartments were observed when either deletion-containing protein replaced endogenous ELC1v or ELC1a. The data indicate that the previously postulated importance of this region in mediating critical protein interactions between the cardiac ELCs and the carboxyl-terminal residues of actin in vivo should be reassessed. 相似文献
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Phosphodiesterases (PDEs) are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca2+ current (ICa,L) is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP) properties and ICa,L in the sinoatrial node (SAN) and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX) and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on ICa,L in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA), the PDE3 inhibitor milrinone (Mil) and the PDE4 inhibitor rolipram (Rol). In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased ICa,L in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate ICa,L in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased ICa,L in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial ICa,L. In complete contrast, no selective PDE inhibitors increased ICa,L in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium. 相似文献
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999.
Joel Robbins 《The journal of the Royal Anthropological Institute》2013,19(3):447-462
In the 1980s, anthropology set aside a focus on societies defined as radically ‘other’ to the anthropologists' own. There was little consensus at the time, however, about who might replace the other as the primary object of anthropological attention. In important respects, I argue, its replacement has been the suffering subject. Tracing this change, I consider how it addressed key problems of the anthropology of the other, but I also suggest that some strengths of earlier work – particularly some of its unique critical capacities – were lost in the transition. The conclusion considers how recent trends in anthropology might coalesce in a further shift, this one toward an anthropology of the good capable of recovering some of the critical force of an earlier anthropology without taking on its weaknesses. 相似文献
1000.
Robert Tokhunts Samer Singh Tehyen Chu Gisela D'Angelo Valerie Baubet John A. Goetz Zhen Huang Ziqiang Yuan Manuel Ascano Yana Zavros Pascal P. Th��rond Sam Kunes Nadia Dahmane David J. Robbins 《The Journal of biological chemistry》2010,285(4):2562-2568
The hedgehog (HH) family of ligands plays an important instructional role in metazoan development. HH proteins are initially produced as ∼45-kDa full-length proteins, which undergo an intramolecular cleavage to generate an amino-terminal product that subsequently becomes cholesterol-modified (HH-Np). It is well accepted that this cholesterol-modified amino-terminal cleavage product is responsible for all HH-dependent signaling events. Contrary to this model we show here that full-length forms of HH proteins are able to traffic to the plasma membrane and participate directly in cell-cell signaling, both in vitro and in vivo. We were also able to rescue a Drosophila eye-specific hh loss of function phenotype by expressing a full-length form of hh that cannot be processed into HH-Np. These results suggest that in some physiological contexts full-length HH proteins may participate directly in HH signaling and that this novel activity of full-length HH may be evolutionarily conserved. 相似文献