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1.
Patrizia Vaccino Heinz-Albert Becker Andrea Brandolini Francesco Salamini Benjamin Kilian 《Molecular genetics and genomics : MGG》2009,281(3):289-300
The celiac disease (CD) is an inflammatory condition characterized by injury to the lining of the small-intestine on exposure
to the gluten of wheat, barley and rye. The involvement of gluten in the CD syndrome has been studied in detail in bread wheat,
where a set of “toxic” and “immunogenic” peptides has been defined. For wheat diploid species, information on CD epitopes
is poor. In the present paper, we have adopted a genomic approach in order to understand the potential CD danger represented
by storage proteins in diploid wheat and sequenced a sufficiently large number of cDNA clones related to storage protein genes
of Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides were found. All the classes of storage proteins were shown to contain harmful
sequences. The major conclusion is that einkorn has the full potential to induce the CD syndrome, as already evident for polyploid
wheats. In addition, a complete overview of the storage protein gene arsenal in T. monococcum is provided, including a full-length HMW x-type sequence and two partial HMW y-type sequences.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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The apparent conductance (Kss, in W.m-2.degrees C-1) of a given region of superficial shell (on the thigh, fat + skin) was determined on four nonsweating and nonshivering subjects, resting and exercising (200 W) in water [water temperature (Tw) 22-23 degrees C] Kss = Hss/(Tsf-Tsk) where Hss is the skin-to-water heat flow directly measured by heat flow transducers and Tsf and Tsk are the temperatures of the subcutaneous fat at a known depth below the skin surface and of the skin surface, respectively. The convective heat flow (qc) through the superficial shell was then estimated as qc = (Tsf - Tsk).(Kss - Kss,min), assuming that at rest Kss was minimal (Kss,min) and resting qc = 0. The duration of immersion was set to allow rectal temperature (Tre) to reach approximately 37 degrees C at the end of rest and approximately 38 degrees C at the end of exercise. Except at the highest Tw used, Kss at the start of exercise was always Kss,min and averaged 51 W.m-2.degrees C-1 (range 33-57 W.m-2.degrees C-1) across subjects, and qc was zero. At the end of exercise at the highest Tw used for each subject, Kss averaged 97 W.m-2.degrees C-1 (range 77-108 W.m-2.degrees C-1) and qc averaged 53% (range 48-61%) of Hss (mean Hss = 233 W.m-2).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Paolo d’Errico Marina Boido Antonio Piras Valeria Valsecchi Elena De Amicis Denise Locatelli Silvia Capra Francesco Vagni Alessandro Vercelli Giorgio Battaglia 《PloS one》2013,8(12)
Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients. 相似文献
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Davide Danovi Amos Folarin Sabine Gogolok Christine Ender Ahmed M. O. Elbatsh P?r G. Engstr?m Stefan H. Stricker Sladjana Gagrica Ana Georgian Ding Yu Kin Pong U Kevin J. Harvey Patrizia Ferretti Patrick J. Paddison Jane E. Preston N. Joan Abbott Paul Bertone Austin Smith Steven M. Pollard 《PloS one》2013,8(10)
Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF−/−, or p53−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value. 相似文献
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Summary Previous work has shown that the monoclonal antibody 22/18 identifies progenitor cells (blastemal cells) which depend on the nerve for their division in the early stages of limb regeneration in the newt,Notophthalmus viridescens. This antibody also reacts with cultured cells derived from the newt limb, and the intensity of immunoreactivity appears related to cell density and differentiation into myotubes. We report here that the monoclonal antibody 22/18 recognizes a polypeptide (22/18 antigen) which is intracellular and filamentous. Double staining of cells with 22/18 monoclonal antibody and antibodies against various cytoskeletal components indicates that the epitope is expressed on an intermediate filament component. Although this antibody is specific for blastemal cells in cryostat sections of the regenerating limb, its reactivity on immunoblots is not confined to this tissue. The 22/18 antigen is differentially affected by aldehyde fixatives distinguished by the spacing of their reactive groups. While formaldehyde fixation impairs detection of the antigen, ethylene glycol-bis[succinic acid n-hydroxysuccinimide ester] reveals the antigen in sections of normal and regenerating limbs in a distribution that is consistent with the one obtained from immunoblots. We suggest that the 22/18 monoclonal antibody detects a change in protein conformation, probably related to changes in the physiological state of the cell, that occurs transiently during regeneration and possibly during development. 相似文献
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Effect of cytochalasins on cytosolic-free calcium concentration and phosphoinositide metabolism in leukocytes 总被引:3,自引:0,他引:3
Susan Treves Francesco Di Virgilio Giorgina M. Vaselli Tullio Pozzan 《Experimental cell research》1987,168(2):285-298
Cytochalasins are routinely used to stimulate a variety of functions in eukaryotic cells even though their precise mode of action remains to be elucidated. In the present work we used the fluorescent Ca2+ indicator quin2 to study the effect of various cytochalasins, cytochalasins A, B, C, D, E (CA, CB, CC, CD, CE) and dihydrocytochalasin B (dhCB) on the intracellular Ca2+ concentration ([Ca2+]i) in various types of leukocytes, viz, neutrophils and lymphocytes. In human neutrophils, cytochalasins increase [Ca2+]i mainly by releasing Ca2+ from membrane-bound, intracellular stores. Thus, in order to readily appreciate the effect of cytochalasins on [Ca2+ )i, these cells must be loaded with low intracellular quin2 concentrations. On the other hand, in peripheral blood lymphocytes, splenocytes and thymocytes, the increase in [Ca2+]i is predominantly due to an increased Ca2+ influx from the extracellular medium. In addition, we found that in neutrophils these drugs prolong the increase in [Ca2+]i induced by chemotactic peptides, probably by increasing the cell permeability to Ca2+. Finally, in thymocytes, cytochalasins potentiate the production of inositol phosphates induced by the polyclonal mitogen concanavalin A (conA). 相似文献