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101.
Since the time of Darwin, evolutionary biologists have been fascinated by the spectacular adaptations to insect pollination exhibited by orchids. However, despite being the most diverse plant family on Earth, the Orchidaceae lack a definitive fossil record and thus many aspects of their evolutionary history remain obscure. Here we report an exquisitely preserved orchid pollinarium (of Meliorchis caribea gen. et sp. nov.) attached to the mesoscutellum of an extinct stingless bee, Proplebeia dominicana, recovered from Miocene amber in the Dominican Republic, that is 15-20 million years (Myr) old. This discovery constitutes both the first unambiguous fossil of Orchidaceae and an unprecedented direct fossil observation of a plant-pollinator interaction. By applying cladistic methods to a morphological character matrix, we resolve the phylogenetic position of M. caribea within the extant subtribe Goodyerinae (subfamily Orchidoideae). We use the ages of other fossil monocots and M. caribea to calibrate a molecular phylogenetic tree of the Orchidaceae. Our results indicate that the most recent common ancestor of extant orchids lived in the Late Cretaceous (76-84 Myr ago), and also suggest that the dramatic radiation of orchids began shortly after the mass extinctions at the K/T boundary. These results further support the hypothesis of an ancient origin for Orchidaceae. 相似文献
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Hara MR Kovacs JJ Whalen EJ Rajagopal S Strachan RT Grant W Towers AJ Williams B Lam CM Xiao K Shenoy SK Gregory SG Ahn S Duckett DR Lefkowitz RJ 《Nature》2011,477(7364):349-353
The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term. When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders, and epidemiological studies strongly indicate that chronic stress leads to DNA damage. This stress-induced DNA damage may promote ageing, tumorigenesis, neuropsychiatric conditions and miscarriages. However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates β(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos. Activated β(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of β-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right. Here we elucidate a molecular mechanism by which β-adrenergic catecholamines, acting through both Gs-PKA and β-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, β-arrestin-1 (ARRB1), activated via β(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress, and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress. 相似文献
105.
Immunohistochemical and ultrastructural detection of the secretin cell in the pig intestinal mucosa 总被引:1,自引:0,他引:1
E. Solcia C. Capella P. Vezzadini L. Barbara G. Bussolati 《Cellular and molecular life sciences : CMLS》1972,28(5):549-550
Riassunto Le cellule a secretina vengono identificate con l'immunofluorescenza nella mucosa duodenale e digiunale di maiale facendo uso di antisieri anti-secretina sintetica porcina. Parallele ricerche ultrastrutturali consentono di identificare in un tipo peculiare di cellular endocrina l'equivalente ultrastrutturale della cellular a secretina.
We are much indebted to Dr.M. A. Ondetti (Squibb, New Brunswick) for his generous supply of synthetic secretin and to Dr.S. Ghielmi (Richter, Milano) for his valuable help in immunizing rabbits. 相似文献
We are much indebted to Dr.M. A. Ondetti (Squibb, New Brunswick) for his generous supply of synthetic secretin and to Dr.S. Ghielmi (Richter, Milano) for his valuable help in immunizing rabbits. 相似文献
106.
K. M. Pirke I. Bofilias Barbara Spyra H. Langhammer H. W. Pabst 《Cellular and molecular life sciences : CMLS》1982,38(4):516-517
Summary The average capillary blood flow in the testes was found to be 181 l/min/g testis tissue (n=19) in rats starved for 5 days and 273 l/min/g (n=18, p<0.01) in the control group. Plasma testosterone was significantly decreased in the starved animals (1.00±0.06 ng/ml vs 5.43±0.63 ng/ml). When starved and control rats were stimulated with human chorion gonadotropin, testosterone values in plasma were greatly increased in both groups. The capillary blood flow was not altered. The data indicate that human chorion gonadotropin can stimulate testosterone production in the starved rat without influencing the reduced capillary blood flow. 相似文献
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Oltersdorf T Elmore SW Shoemaker AR Armstrong RC Augeri DJ Belli BA Bruncko M Deckwerth TL Dinges J Hajduk PJ Joseph MK Kitada S Korsmeyer SJ Kunzer AR Letai A Li C Mitten MJ Nettesheim DG Ng S Nimmer PM O'Connor JM Oleksijew A Petros AM Reed JC Shen W Tahir SK Thompson CB Tomaselli KJ Wang B Wendt MD Zhang H Fesik SW Rosenberg SH 《Nature》2005,435(7042):677-681
Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 increase sensitivity to anticancer drugs and enhance in vivo survival. The development of inhibitors of these proteins as potential anti-cancer therapeutics has been previously explored, but obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting a protein-protein interaction. Here, using nuclear magnetic resonance (NMR)-based screening, parallel synthesis and structure-based design, we have discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w, with an affinity two to three orders of magnitude more potent than previously reported compounds. Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models, ABT-737 improves survival, causes regression of established tumours, and produces cures in a high percentage of the mice. 相似文献
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Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis 总被引:1,自引:0,他引:1
Glasson SS Askew R Sheppard B Carito B Blanchet T Ma HL Flannery CR Peluso D Kanki K Yang Z Majumdar MK Morris EA 《Nature》2005,434(7033):644-648
Human osteoarthritis is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multifactorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecan is cleaved at a specific 'aggrecanase' site in human osteoarthritic cartilage; this cleavage can be performed by several members of ADAMTS family of metalloproteases. The relative contribution of individual ADAMTS proteases to cartilage destruction during osteoarthritis has not been resolved. Here we describe experiments with a genetically modified mouse in which the catalytic domain of ADAMTS5 (aggrecanase-2) was deleted. After surgically induced joint instability, there was significant reduction in the severity of cartilage destruction in the ADAMTS5 knockout mice compared with wild-type mice. This is the first report of a single gene deletion capable of abrogating the course of cartilage destruction in an animal model of osteoarthritis. These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis. 相似文献