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71.
Some leukocyte receptors come in groups of two or more where the partners share ligand(s) but transmit opposite signals. Some
of the ligands, such as MHC class I, are fast evolving, raising the problem of how paired opposing receptors manage to change
in step with respect to ligand binding properties and at the same time conserve opposite signaling functions. An example is
the KLRC (NKG2) family, where opposing variants have been conserved in both rodents and primates. Phylogenetic analyses of
the KLRC receptors within and between the two orders show that the opposing partners have been subject to post-speciation
gene homogenization restricted mainly to the parts of the genes that encode the ligand binding domains. Concerted evolution
similarly restricted is demonstrated also for the KLRI, KLRB (NKR-P1), KLRA (Ly49), and PIR receptor families. We propose
the term merohomogenization for this phenomenon and discuss its significance for the evolution of immune receptors. 相似文献
72.
Grippon S Zhao Q Robinson T Marshall JJ O'Neill RJ Manning H Kennedy G Dunsby C Neil M Halford SE French PM Baldwin GS 《Nucleic acids research》2011,39(7):2593-2603
Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway. As with other DNA glycosylases, the abasic product is potentially more harmful than the initial lesion. Since Mug is known to bind its product tightly, inhibiting enzyme turnover, understanding how Mug binds DNA is of significance when considering how Mug interacts with downstream enzymes in the base-excision repair pathway. We have demonstrated differential binding modes of Mug between its substrate and abasic DNA product using both band shift and fluorescence anisotropy assays. Mug binds its product cooperatively, and a stoichiometric analysis of DNA binding, catalytic activity and salt-dependence indicates that dimer formation is of functional significance in both catalytic activity and product binding. This is the first report of cooperativity in the uracil DNA glycosylase superfamily of enzymes, and forms the basis of product inhibition in Mug. It therefore provides a new perspective on abasic site protection and the findings are discussed in the context of downstream lesion processing and enzyme communication in the base excision repair pathway. 相似文献
73.
- 1 Population density alone is unlikely to be a good predictor of the impacts of deer on their environment. The assessment of management requirements should therefore be based on assessment of deer impacts, alongside estimates of density.
- 2 Both density and impacts need to be monitored at a landscape scale, and there is a need to develop appropriate methodologies that allow managers to consider the current and likely future impact of deer.
- 3 The relevant scale for assessment (and management) varies both with deer species and context of impact, but should always encompass at least the estimated biological range of the population of deer present in an area. Some impacts (e.g. deer–vehicle collisions, and risks of disease transmission) may need to be assessed at a wider regional level.
- 4 In this review we consider various approaches available for assessing: absolute or relative animal abundance; impacts of ungulates on agriculture, forestry, amenity woodlands and other conservation sites; impacts on public safety (e.g. through road traffic accidents) and on humans or livestock through potential spread of disease.
- 5 In each case the advantages and disadvantages of a variety of methods are considered, before recommendations are made for methodologies which are sufficiently accurate, sufficiently robust and sufficiently practical to be favoured in a management context.
- 6 To address impacts at the landscape scale requires management policies that integrate information on both positive and negative impacts of deer in order to ensure appropriate and holistic management. We present a decision‐support framework suitable for use within the UK, using inputs from a variety of possible impact types to assist managers and forewarn of situations where current management may need to be modified.
74.
Yu B Yang M Wong HY Watt RM Song E Zheng BJ Yuen KY Huang JD 《Applied microbiology and biotechnology》2011,91(1):177-188
Live attenuated Salmonella enterica serovar Typhi Ty21a (Ty21a) is an important vaccine strain used in clinical studies for typhoid fever and as a vaccine vector
for the expression of heterologous antigens. To facilitate the use of Ty21a in such studies, it is desirable to develop improved
strategies that enable the stable chromosomal integration and expression of multiple heterologous antigens. The phage λ Red
homologous recombination system has previously been used in various gram-negative bacteria species to mediate the accurate
replacement of regions of chromosomal DNA with PCR-generated ‘targeting cassettes’ that contain flanking regions of shared
homologous DNA sequence. However, the efficiency of λ Red-mediated recombineering in Ty21a is far lower than in Escherichia coli and other Salmonella typhimurium strains. Here, we describe an improved strategy for recombineering-based methods in Ty21a. Our reliable and efficient method
involves the use of linear DNA-targeting cassettes that contain relatively long flanking ‘arms’ of sequence (ca. 1,000 bp)
homologous to the chromosomal target. This enables multiple gene-targeting procedures to be performed on a single Ty21a chromosome
in a straightforward, sequential manner. Using this strategy, we inserted three different influenza antigen expression cassettes
as well as a green fluorescent protein gene reporter into four different loci on the Ty21a chromosome, with high efficiency
and accuracy. Fluorescent microscopy and Western blotting analysis confirmed that strong inducible expression of all four
heterologous genes could be achieved. In summary, we have developed an efficient, robust, and versatile method that may be
used to construct recombinant Ty21a antigen-expressing strains. 相似文献
75.
Jed P. Sparks Subhash Chandra Louis A. Derry Mandayam V. Parthasarathy Carole S. Daugherty Rory Griffin 《Biogeochemistry》2011,104(1-3):237-249
Silicon transport and incorporation into plant tissue is important to both plant physiological function and to the influence plants have on ecosystem silica cycling. However, the mechanisms controlling this transport have only begun to be explored. In this study, we used secondary ion mass spectrometry (SIMS) to image concentrations of Si in root and shoot tissues of annual blue grass (Poa annua L.) and orchard grass (Dactylis glomerata L.) with the goal of identifying control points in the plant silica uptake pathway. In addition, we used SIMS to describe the distributions of germanium (Ge); the element used to trace Si in biogeochemical studies. Within root tissue, Si and Ge were localized in the suberized thick-walled region of endodermal cells, i.e. the proximal side of endodermal cells which is in close association to the casparian strip. In leaves, Si was present in the cell walls, but Ge was barely detectable. The selective localization of Si and Ge in the proximal side of endodermal cell walls of roots suggests transport control is exerted upon Si and Ge by the plant. The absence of Si in most root cell walls and its presence in the cell walls of leaves (in areas outside of the transpiration terminus) suggests modifications in the chemical form of Si to a form that favors Si complexation in the cell walls of leaf tissue. The low abundance of Ge in leaf tissue is consistent with previous studies that suggest preferential transport of Si relative to Ge. 相似文献
76.
Macdonald SJ Dowle MD Harrison LA Shah P Johnson MR Inglis GG Clarke GD Smith RA Humphreys D Molloy CR Amour A Dixon M Murkitt G Godward RE Padfield T Skarzynski T Singh OM Kumar KA Fleetwood G Hodgson ST Hardy GW Finch H 《Bioorganic & medicinal chemistry letters》2001,11(7):895-898
The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616A, are described. 相似文献
77.
Vincent Zecchini Basetti Madhu Roslin Russell Nelma Pértega‐Gomes Anne Warren Edoardo Gaude Joana Borlido Rory Stark Heather Ireland‐Zecchini Roheet Rao Helen Scott Joan Boren Charlie Massie Mohammad Asim Kevin Brindle John Griffiths Christian Frezza Ian G Mills 《The EMBO journal》2014,33(12):1365-1382
78.
79.
Elizabeth du Toit Cari van Schalkwyk Rory Dunbar Karen Jennings Blia Yang David Coetzee Nulda Beyers 《PloS one》2014,9(5)
Background
Few studies have evaluated access to and retention in pre-ART care.Objectives
To evaluate the proportion of People Living With HIV (PLWH) in pre-ART and ART care and factors associated with retention in pre-ART and ART care from a community cohort.Methods
A cross sectional survey was conducted from February – April 2011. Self reported HIV positive, negative or participants of unknown status completed a questionnaire on their HIV testing history, access to pre-ART and retention in pre-ART and ART care.Results
872 randomly selected adults who reported being HIV positive in the ZAMSTAR 2010 prevalence survey were included and revisited. 579 (66%) reconfirmed their positive status and were included in this analysis. 380 (66%) had initiated ART with 357 of these (94%) retained in ART care. 199 (34%) had never initiated ART of whom 186 (93%) accessed pre-ART care, and 86 (43%) were retained in pre-ART care. In a univariable analysis none of the factors analysed were significantly associated with retention in care in the pre-ART group. Due to the high retention in ART care, factors associated with retention in ART care, were not analysed further.Conclusion
Retention in ART care was high; however it was low in pre-ART care. The opportunity exists, if care is better integrated, to engage with clients in primary health care facilities to bring them back to, and retain them in, pre-ART care. 相似文献80.
Christina A. Pacak Peter E. Hammer Allison A. MacKay Rory P. Dowd Kai-Roy Wang Akihiro Masuzawa Bjoern Sill James D. McCully Douglas B. Cowan 《PloS one》2014,9(9)
The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (μCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by μCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while μCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and μCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and μCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label. 相似文献