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31.
Paul DW Kirk Aviva Witkover Alan Courtney Alexandra M Lewin Robin Wait Michael PH Stumpf Sylvia Richardson Graham P Taylor Charles RM Bangham 《Retrovirology》2011,8(1):1-9
Background
A new subgroup of HIV-1, designated Group P, was recently detected in two unrelated patients of Cameroonian origin. HIV-1 Group P phylogenetically clusters with SIVgor suggesting that it is the result of a cross-species transmission from gorillas. Until today, HIV-1 Group P has only been detected in two patients, and its degree of adaptation to the human host is largely unknown. Previous data have shown that pandemic HIV-1 Group M, but not non-pandemic Group O or rare Group N viruses, efficiently antagonize the human orthologue of the restriction factor tetherin (BST-2, HM1.24, CD317) suggesting that primate lentiviruses may have to gain anti-tetherin activity for efficient spread in the human population. Thus far, three SIV/HIV gene products (vpu, nef and env) are known to have the potential to counteract primate tetherin proteins, often in a species-specific manner. Here, we examined how long Group P may have been circulating in humans and determined its capability to antagonize human tetherin as an indicator of adaptation to humans.Results
Our data suggest that HIV-1 Group P entered the human population between 1845 and 1989. Vpu, Env and Nef proteins from both Group P viruses failed to counteract human or gorilla tetherin to promote efficient release of HIV-1 virions, although both Group P Nef proteins moderately downmodulated gorilla tetherin from the cell surface. Notably, Vpu, Env and Nef alleles from the two HIV-1 P strains were all able to reduce CD4 cell surface expression.Conclusions
Our analyses of the two reported HIV-1 Group P viruses suggest that zoonosis occurred in the last 170 years and further support that pandemic HIV-1 Group M strains are better adapted to humans than non-pandemic or rare Group O, N and P viruses. The inability to antagonize human tetherin may potentially explain the limited spread of HIV-1 Group P in the human population. 相似文献32.
33.
Expression of the mouse alpha-cardiac actin gene in skeletal and cardiac muscle is regulated by enhancers lying 5' to the proximal promoter. Here we report the characterization of a cardiac-specific enhancer located within -2.354/-1.36 kbp of the gene, which is active in cardiocytes but not in C2 skeletal muscle cells. In vivo it directs reporter gene expression to the adult heart, where the proximal promoter alone is inactive. An 85-bp region within the enhancer is highly conserved between human and mouse and contains a central AT-rich site, which is essential for enhancer activity. This site binds myocyte enhancer factor (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts. These results are discussed in the context of MEF2 activity and of the regulation of the alpha-cardiac actin locus. 相似文献
34.
Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells 总被引:18,自引:0,他引:18
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Relaix F Montarras D Zaffran S Gayraud-Morel B Rocancourt D Tajbakhsh S Mansouri A Cumano A Buckingham M 《The Journal of cell biology》2006,172(1):91-102
The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context. 相似文献
35.
Smooth muscle of the dorsal aorta shares a common clonal origin with skeletal muscle of the myotome 总被引:5,自引:0,他引:5
Esner M Meilhac SM Relaix F Nicolas JF Cossu G Buckingham ME 《Development (Cambridge, England)》2006,133(4):737-749
We show that cells of the dorsal aorta, an early blood vessel, and of the myotome, the first skeletal muscle to form within the somite, derive from a common progenitor in the mouse embryo. This conclusion is based on a retrospective clonal analysis, using a nlaacZ reporter targeted to the alpha-cardiac actin gene. A rare intragenic recombination event results in a functional nlacZ sequence, giving rise to clones of beta-galactosidase-positive cells. Periendothelial and vascular smooth muscle cells of the dorsal aorta are the main cell types labelled, demonstrating that these are clonally related to the paraxial mesoderm-derived cells of skeletal muscle. Rare endothelial cells are also seen in some clones. In younger clones, arising from a recent recombination event, myotomal labelling is predominantly in the hypaxial somite, adjacent to labelled smooth muscle cells in the aorta. Analysis of Pax3(GFP/+) embryos shows that these cells are Pax3 negative but GFP positive, with fluorescent cells in the intervening region between the aorta and the somite. This is consistent with the direct migration of smooth muscle precursor cells that had expressed Pax3. These results are discussed in terms of the paraxial mesoderm contribution to the aorta and of the mesoangioblast stem cells that derive from it. 相似文献
36.
Invertebrates have been deployed very successfully in experimental studies of the nervous system and neuromuscular junctions.
Many important discoveries on axonal conduction, synaptic transmission, integrative neurobiology and behaviour have been made
by investigations of these remarkable animals. Their advantages as model organisms for investigations of nervous systems include
(a) the large diameter of neurons, glia and muscle cells of some invertebrates, thereby facilitating microelectrode recordings;
(b) simple nervous systems with few neurons, enhancing the tractability of neuronal circuitry; and (c) well-defined behaviours,
which lend themselves to physiological and genetic dissection. Genetic model organisms such as Drosophila melanogaster and Caenorhabditis elegans have provided powerful genetic approaches to central questions concerning nervous system development, learning and memory
and the cellular and molecular basis of behaviour. The process of attributing function to particular gene products has been
greatly accelerated in recent years with access to entire genome sequences and the application of reverse genetic (e.g. RNA
interference, RNAi) and other post-genome technologies (e.g. microarrays). Studies of many other invertebrates, notably the
honeybee (Apis mellifera), a nudibranch mollusc (Aplysia californica), locusts, lobsters, crabs, annelids and jellyfish have all assisted in the development of major concepts in neuroscience.
The future is equally bright with ease of access to genome-wide reverse genetic technologies, and the development of optical
recordings using voltage and intracellular calcium sensors genetically targeted to selected individual and groups of neurons. 相似文献
37.
HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1 总被引:1,自引:0,他引:1
The ubiquitous tripeptide Gly-Gly-Gln in class 1 polypeptide release factors triggers polypeptide release on ribosomes. The Gln residue in both bacterial and yeast release factors is N5-methylated, despite their distinct evolutionary origin. Methylation of eRF1 in yeast is performed by the heterodimeric methyltransferase (MTase) Mtq2p/Trm112p, and requires eRF3 and GTP. Homologues of yeast Mtq2p and Trm112p are found in man, annotated as an N6-DNA-methyltransferase and of unknown function. Here we show that the human proteins methylate human and yeast eRF1.eRF3.GTP in vitro, and that the MTase catalytic subunit can complement the growth defect of yeast strains deleted for mtq2. 相似文献
38.
Gary R. Buckingham 《BioControl》2001,46(3):363-386
The Australian melaleuca tree, Melaleuca quinquenervia (Cav.) S. T. Blake (Myrtaceae), has naturalized in southern Florida,U.S.A., and is now one of that regions most important weeds.Primarily a weed of wetlands, it also infests neighboring drierareas. Current efforts to restore the South Florida ecosystem arethreatened by the continuing range expansion of melaleuca andother weeds. In an effort to supplement the current chemical andcultural control methods for melaleuca, a search for potentialbiological control agents was begun in Australia in 1986. Thesawfly, Lophyrotoma zonalis, was determined after extensive fieldand laboratory studies to have potential as a biological controlagent. Larvae of L. zonalis eat leaves and occasionally defoliatelarge trees in Australia. Host range studies were conducted in aFlorida quarantine facility with native and cultivated plantspecies. Multi-choice and no-choice oviposition tests wereconducted with 36 species in the Myrtaceae and with 18 species inother families. Larvae developed to prepupae and adults from theeggs oviposited on 23 species of Myrtaceae only on 3 species ofbottlebrushes, Callistemon. Medium-sized larvae were tested forfeeding on bouquets of plant cuttings and on potted plants. Theyare the stage that might wander from defoliated trees. Noticeablefeeding, but much less than on melaleuca, was restricted to theMyrtaceae, except for a few individual larvae that fed on waxmyrtle, Myrica cerifera. Medium-sized larvae became prepupae onlyon Melaleuca decora (73%) and on wax myrtle (10%). However,neither species received eggs in the oviposition tests. Thesestudies confirmed the narrow host range of L. zonalis aspreviously reported from field and laboratory studies inAustralia. 相似文献
39.
40.
Mutants affecting tRNA(Phe) from Escherichia coli. Studies of the suppression of thermosensitive phenylalanyl-tRNA synthetase 总被引:2,自引:0,他引:2
Four mutants of pheV, a gene coding for tRNA(Phe) in Escherichia coli, share the characteristic that when carried in the plasmid pBR322, they lose the capacity of wild-type pheV to complement the thermosensitive defect in a mutant of phenylalanyl-tRNA synthetase. One of these mutants, leading to the change C2----U2 in tRNA(Phe), is expressed about 10-fold lower in transformed cells than wild-type pheV. This mutant, unlike the remaining three (G15----A15, G44----A44, m7G46----A46), can recover the capacity to complement thermosensitivity when carried in a plasmid of higher copy number. The other three mutants, even when expressed at a similar level, remain unable to complement thermosensitivity. A study of charging kinetics suggests that the loss of complementation associated with these mutants is due to an altered interaction with phenylalanyl-tRNA synthetase. The mutant gene pheV (U2), when carried in pBR322, can also recover the capacity to complement thermosensitivity through a second-site mutation outside the tRNA structural gene, in the discriminator region. This mutation, C(-6)----T(-6), restores expression of the mutant U2 to about the level of wild-type tRNA(Phe). 相似文献