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101.
102.
Timm Konold A Robin Sayers Amanda Sach Gemma E Bone Steven van Winden Gerald AH Wells Marion M Simmons Michael J Stack Angus Wear Steve AC Hawkins 《BMC veterinary research》2010,6(1):53
Background
Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. 相似文献103.
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Background
mTOR kinase forms the mTORC1 complex by associating with raptor and other proteins and affects a number of key cell functions. mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn, p70S6K1 phosphorylates a S6 protein of the 40S ribosomal subunit (S6rp) and 4E-BP1, with the latter negatively regulating eukaryotic initiation factor 4E (eIF-4E). MNK1 and MNK2 kinases phosphorylate and augment activity of eIF4E. Rapamycin and its analogs are highly specific, potent, and relatively non-toxic inhibitors of mTORC1. Although mTORC1 activation is present in many types of malignancies, rapamycin-type inhibitors shows relatively limited clinical efficacy as single agents. Initially usually indolent, CTCL displays a tendency to progress to the aggressive forms with limited response to therapy and poor prognosis. Our previous study (M. Marzec et al. 2008) has demonstrated that CTCL cells display mTORC1 activation and short-term treatment of CTCL-derived cells with rapamycin suppressed their proliferation and had little effect on the cell survival.Methods
Cells derived from CTCL were treated with mTORC1 inhibitor rapamycin and MNK inhibitor and evaluated for inhibition of the mTORC1 signaling pathway and cell growth and survival.Results
Whereas the treatment with rapamycin persistently inhibited mTORC1 signaling, it suppressed only partially the cell growth. MNK kinase mediated the eIF4E phosphorylation and inhibition or depletion of MNK markedly suppressed proliferation of the CTCL cells when combined with the rapamycin-mediated inhibition of mTORC1. While MNK inhibition alone mildly suppressed the CTCL cell growth, the combined MNK and mTORC1 inhibition totally abrogated the growth. Similarly, MNK inhibitor alone displayed a minimal pro-apoptotic effect; in combination with rapamycin it triggered profound cell apoptosis.Conclusions
These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of CTCL and other malignancies. 相似文献108.
The late Tortonian – early Messinian shallow marine sands of Cessaniti area (Monte Poro, Vibo Valentia, Southern Italy) yield marine and continental vertebrates. The best represented taxon is the Sirenian Metaxytherium serresii, while the terrestrial mammal assemblage includes a boselafine bovid, an hexaprotodontid hippopotamus, the giraffids Samotherium cf. boissieri and Bohlinia cf. attica, a rhino and the elephantid Stegotetrabelodon syrticus. Until now, the latter was a species with an exclusive Afro-Arabian distribution and the record of Cessaniti is the first outside Afro-Arabia. Our attention is here focused on the occurrence of Samotherium cf. boissieri and Bohlinia cf. attica, both being species well represented in the Pikermian Biome. Although evidences of the distribution of the genus Samotherium in Late Miocene African assemblages are weak, it is reported at several sites, while a new species of Bohlinia reported in Chad is still debated. At Cessaniti, the co-occurrence of two giraffid taxa typical for the Pikermian biome together with a frankly Afro-Arabic species (S. syrticus), further marks the existence of a land connection between the Cessaniti area and North Africa as well as the evidence of a phase of expansion of the Pikermian Biome into the African continent. 相似文献
109.
Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium 下载免费PDF全文
Verónica Lloréns‐Rico Francis J O'Reilly Judith AH Wodke E Besray Unal Eva Yus Sira Martínez Robert J Nichols Tony Ferrar Ana Vivancos Arne Schmeisky Jörg Stülke Vera van Noort Anne‐Claude Gavin Peer Bork Luis Serrano 《Molecular systems biology》2015,11(1)
Identifying all essential genomic components is critical for the assembly of minimal artificial life. In the genome-reduced bacterium Mycoplasma pneumoniae, we found that small ORFs (smORFs; < 100 residues), accounting for 10% of all ORFs, are the most frequently essential genomic components (53%), followed by conventional ORFs (49%). Essentiality of smORFs may be explained by their function as members of protein and/or DNA/RNA complexes. In larger proteins, essentiality applied to individual domains and not entire proteins, a notion we could confirm by expression of truncated domains. The fraction of essential non-coding RNAs (ncRNAs) non-overlapping with essential genes is 5% higher than of non-transcribed regions (0.9%), pointing to the important functions of the former. We found that the minimal essential genome is comprised of 33% (269,410 bp) of the M. pneumoniae genome. Our data highlight an unexpected hidden layer of smORFs with essential functions, as well as non-coding regions, thus changing the focus when aiming to define the minimal essential genome. 相似文献
110.
Martijn AH Oude Voshaar Peter M ten Klooster Erik Taal Eswar Krishnan Mart AFJ van de Laar 《Arthritis research & therapy》2012,14(2):R47-7