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281.
Evolution of neoplastic cell lineages in Barrett oesophagus. 总被引:20,自引:0,他引:20
M T Barrett C A Sanchez L J Prevo D J Wong P C Galipeau T G Paulson P S Rabinovitch B J Reid 《Nature genetics》1999,22(1):106-109
It has been hypothesized that neoplastic progression develops as a consequence of an acquired genetic instability and the subsequent evolution of clonal populations with accumulated genetic errors. Accordingly, human cancers and some premalignant lesions contain multiple genetic abnormalities not present in the normal tissues from which the neoplasms arose. Barrett oesophagus (BE) is a premalignant condition which predisposes to oesophageal adenocarcinoma (EA) that can be biopsied prospectively over time because endoscopic surveillance is recommended for early detection of cancer. In addition, oesophagectomy specimens frequently contain the premalignant epithelium from which the cancer arose. Neoplastic progression in BE is associated with alterations in TP53 (also known as p53) and CDKN2A (also known as p16) and non-random losses of heterozygosity (LOH). Aneuploid or increased 4N populations occur in more than 90-95% of EAs, arise in premalignant epithelium and predict progression. We have previously shown in small numbers of patients that disruption of TP53 and CDKN2A typically occurs before aneuploidy and cancer. Here, we determine the evolutionary relationships of non-random LOH, TP53 and CDKN2A mutations, CDKN2A CpG-island methylation and ploidy during neoplastic progression. Diploid cell progenitors with somatic genetic or epigenetic abnormalities in TP53 and CDKN2A were capable of clonal expansion, spreading to large regions of oesophageal mucosa. The subsequent evolution of neoplastic progeny frequently involved bifurcations and LOH at 5q, 13q and 18q that occurred in no obligate order relative to each other, DNA-content aneuploidy or cancer. Our results indicate that clonal evolution is more complex than predicted by linear models. 相似文献
282.
L. Dhers L. Ducassou J.-L. Boucher D. Mansuy 《Cellular and molecular life sciences : CMLS》2017,74(10):1859-1869
Cytochrome P450 2U1 (CYP2U1) exhibits several distinctive characteristics among the 57 human CYPs, such as its presence in almost all living organisms with a highly conserved sequence, its particular gene organization with only five exons, its major location in thymus and brain, and its protein sequence involving an unusually long N-terminal region containing 8 proline residues and an insert of about 20 amino acids containing 5 arginine residues after the transmembrane helix. Few substrates, including fatty acids, N-arachidonoylserotonin (AS), and some drugs, have been reported so far. However, its biological roles remain largely unknown, even though CYP2U1 mutations have been involved in some pathological situations, such as complicated forms of hereditary spastic paraplegia. These data together with its ability to hydroxylate some fatty acids and AS suggest its possible role in lipid metabolism. 相似文献
283.
Sunita A. Ramesh Stephen D. Tyerman Matthew Gilliham Bo Xu 《Cellular and molecular life sciences : CMLS》2017,74(9):1577-1603
The role of γ-aminobutyric acid (GABA) as a signal in animals has been documented for over 60 years. In contrast, evidence that GABA is a signal in plants has only emerged in the last 15 years, and it was not until last year that a mechanism by which this could occur was identified—a plant ‘GABA receptor’ that inhibits anion passage through the aluminium-activated malate transporter family of proteins (ALMTs). ALMTs are multigenic, expressed in different organs and present on different membranes. We propose GABA regulation of ALMT activity could function as a signal that modulates plant growth, development, and stress response. In this review, we compare and contrast the plant ‘GABA receptor’ with mammalian GABAA receptors in terms of their molecular identity, predicted topology, mode of action, and signalling roles. We also explore the implications of the discovery that GABA modulates anion flux in plants, its role in signal transduction for the regulation of plant physiology, and predict the possibility that there are other GABA interaction sites in the N termini of ALMT proteins through in silico evolutionary coupling analysis; we also explore the potential interactions between GABA and other signalling molecules. 相似文献
284.
Isaak Quast Benjamin Peschke Jan D. Lünemann 《Cellular and molecular life sciences : CMLS》2017,74(5):837-847
Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune system. They recognize antigens with high specificity and are indispensable for immunological memory following pathogen exposure or vaccination. The constant, crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity, and antibody-dependent cell-mediated phagocytosis. These functions are regulated by a single N-linked, biantennary glycan of the heavy chain, which resides just below the hinge region, and the presence of specific sugar moieties on the glycan has profound implications on IgG effector functions. Emerging knowledge of how Fc glycans contribute to IgG structure and functions has opened new avenues for the therapeutic exploitation of defined antibody glycoforms in the treatment of cancer and autoimmune diseases. Here, we review recent advances in understanding proinflammatory IgG effector functions and their regulation by Fc glycans. 相似文献
285.
286.
Chung D. Ngo Binh V. Ngo Thuong T. Hoang Thi T.T. Nguyen Hai P. Dang 《Journal of Natural History》2015,49(39-40):2417-2436
We studied the feeding ecology of Eutropis multifasciata in the tropical plains of central Vietnam to understand better the foraging mode, spatiotemporal and sexual variation in dietary composition, and rarefaction curves of prey-taxon richness for males and females. Stomach contents (n = 161) were collected from October 2013 to May 2014 using a nonlethal stomach-flushing technique. A total of 680 food items (624 animal items and 56 plant items) was found in 161 stomachs of skinks, representing 19 unique animal categories. We found that the diet of E. multifasciata is composed mainly of small, sedentary and clumped prey and that this skink specialises on spiders, insect larvae, snails, grasshoppers and crickets (with a combined importance index of 60%). Dietary composition, prey size and total prey volume in E. multifasciata changed between dry and rainy seasons and among regions. The total volume of food items consumed by males was larger than that of females, and the diversity and evenness index of prey categories were larger in males than in females. However, using rarefaction curves revealed that females have the higher prey-taxon richness after points between 130 and 140 prey items for frequency, and between 160 and 170 prey items for number of items, and the differences were not statistically significant. The foraging behaviour of E. multifasciata best fits a ‘widely foraging’ model. 相似文献
287.
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells 总被引:1,自引:0,他引:1
288.
Julie Patenaude Michele D’Elia Claudine Hamelin Jacques Bernier 《Cellular and molecular life sciences : CMLS》2010,67(8):1315-1329
Burn injury causes an immunosuppression associated with suppressed adaptive immune function. Dendritic cells (DCs) are APCs
for which signaling via their Toll-like receptors (TLRs) induces their maturation and activation, which is essential for the
adaptive immune response. In this study, we examined if burn injury alters the TLR activity of splenic DCs. After injury,
we noticed that DC functions were impaired, characterized by a suppressed capacity to prime naive T cells when triggering
the TLR4 signaling cascade using specific ligands (LPS or rHSP60). The observed perturbations on LPS-primed DCs isolated from
burned mice exhibited significantly diminished IL-12p40 production and enhanced IL-10 secretion-associated impairment in mitogen-activated
protein kinase activation. Interestingly, we observed a decrease of TLR4/MD-2 expression on the CD8α+ DC subset that persisted following LPS stimulation. The altered TLR4 expression on LPS-stimulated CD8α+ DCs was associated with reduced capacity to produce IL-12 after stimulation. Our results suggested that TLR4 reactivity on
DCs, especially CD8α+ DCs, is disturbed after burn injury. 相似文献
289.
290.
W.E. Knowles Middleton D.Sc. F.R.S.C. 《Annals of science》2013,70(2):125-141
In 1639–1640 Benedetto Castelli (1577–1643) wrote a treatise on the loadstone which is quite unlike any of its contemporaries. In it are the origins of the notion of elementary magnets sharing a common alignment, the idea that all materials are magnetic in different ways, and the first intimation of the conception of magnetic domains. Castelli did not publish his treatise. Nevertheless his work was noted during his life-time, and may have exerted an influence on the development of magnetic theory in the 17th century. The treatise was published in 1883. Since then, however, it has either been neglected or not appreciated. It deserves being rescued from the neglect of more than three centuries. 相似文献