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Ralph P. Campanale 《The Western journal of medicine》1964,101(6):435-438
Realism introduced in several large scale surprise mock-disaster tests proved to be a real challenge to a disaster-conscious hospital staff that had previously undergone fairly extensive disaster training and testing, utilizing conventional methods.Serious weaknesses, flaws, omissions and deficiencies in disaster capability were dramatically and conclusively revealed by use of what appeared to be a “live” disaster setting with smoke, fire, explosions; adverse weather and light conditions; realistically-simulated “casualites” especially prepared not only to look but to act the part; selected harassment incidents from well-documented disasters, such as utility failures, automobile accident on the main access route, overload of telephone switchboard, and invasion of hospital and disaster site by distraught relatives and the morbidly curious. 相似文献
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ATP-binding cassette (ABC) transporters protect embryos and stem cells from mutagens and pump morphogens that control cell fate and migration. In this study, we measured dynamics of ABC transporter activity during formation of sea urchin embryonic cells necessary for the production of gametes, termed the small micromeres. Unexpectedly, we found small micromeres accumulate 2.32 times more of the ABC transporter substrates calcein-AM, CellTrace RedOrange, BoDipy-verapamil and BoDipy-vinblastine, than any other cell in the embryo, indicating a reduction in multidrug efflux activity. The reduction in small micromere ABC transporter activity is mediated by a pulse of endocytosis occurring 20-60 minutes after the appearance of the micromeres--the precursors of the small micromeres. Treating embryos with phenylarsine oxide, an inhibitor of endocytosis, prevents the reduction of transporter activity. Tetramethylrhodamine dextran and cholera toxin B uptake experiments indicate that micromeres have higher rates of bulk and raft-associated membrane endocytosis during the window of transporter downregulation. We hypothesized that this loss of efflux transport could be required for the detection of developmental signaling molecules such as germ cell chemoattractants. Consistent with this hypothesis, we found that the inhibition of ABCB and ABCC-types of efflux transporters disrupts the ordered distribution of small micromeres to the left and right coelomic pouches. These results point to tradeoffs between signaling and the protective functions of the transporters. 相似文献
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EA Dukhanina TI Lukyanova EA Romanova V Guerriero NV Gnuchev GP Georgiev DV Yashin LP Sashchenko 《Cell cycle (Georgetown, Tex.)》2015,14(22):3635-3643
PGRP-S (Tag7) is an innate immunity protein involved in the antimicrobial defense systems, both in insects and in mammals. We have previously shown that Tag7 specifically interacts with several proteins, including Hsp70 and the calcium binding protein S100A4 (Mts1), providing a number of novel cellular functions. Here we show that Tag7–Mts1 complex causes chemotactic migration of lymphocytes, with NK cells being a preferred target. Cells of either innate immunity (neutrophils and monocytes) or acquired immunity (CD4+ and CD8+ lymphocytes) can produce this complex, which confirms the close connection between components of the 2 branches of immune response. 相似文献
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Tufan G?kirmak Joseph P. Campanale Lauren E. Shipp Gary W. Moy Houchao Tao Amro Hamdoun 《The Journal of biological chemistry》2012,287(52):43876-43883
In this study, we cloned, expressed and functionally characterized Stronglycentrotus purpuratus (Sp) ATP-binding cassette (ABC) transporters. This screen identified three multidrug resistance (MDR) transporters with functional homology to the major types of MDR transporters found in humans. When overexpressed in embryos, the apical transporters Sp-ABCB1a, ABCB4a, and ABCG2a can account for as much as 87% of the observed efflux activity, providing a robust assay for their substrate selectivity. Using this assay, we found that sea urchin MDR transporters export canonical MDR susbtrates such as calcein-AM, bodipy-verapamil, bodipy-vinblastine, and mitoxantrone. In addition, we characterized the impact of nonconservative substitutions in the primary sequences of drug binding domains of sea urchin versus murine ABCB1 by mutation of Sp-ABCB1a and treatment of embryos with stereoisomeric cyclic peptide inhibitors (QZ59 compounds). The results indicated that two substitutions in transmembrane helix 6 reverse stereoselectivity of Sp-ABCB1a for QZ59 enantiomers compared with mouse ABCB1a. This suggests that subtle changes in the primary sequence of transporter drug binding domains could fine-tune substrate specificity through evolution. 相似文献
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We present an efficient computational architecture designed using supervised machine learning model to predict amyloid fibril
forming protein segments, named AmylPepPred. The proposed prediction model is based on bio-physio-chemical properties of
primary sequences and auto-correlation function of their amino acid indices. AmylPepPred provides a user friendly web interface
for the researchers to easily observe the fibril forming and non-fibril forming hexmers in a given protein sequence. We expect that
this stratagem will be highly encouraging in discovering fibril forming regions in proteins thereby benefit in finding therapeutic
agents that specifically aim these sequences for the inhibition and cure of amyloid illnesses.