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101.
Horton R Gibson R Coggill P Miretti M Allcock RJ Almeida J Forbes S Gilbert JG Halls K Harrow JL Hart E Howe K Jackson DK Palmer S Roberts AN Sims S Stewart CA Traherne JA Trevanion S Wilming L Rogers J de Jong PJ Elliott JF Sawcer S Todd JA Trowsdale J Beck S 《Immunogenetics》2008,60(1):1-18
The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised
as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively
annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against
which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC
haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed,
resulted in the identification of >44,000 variations, both substitutions and indels (insertions and deletions), which have
been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence
of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets
revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line)
designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent
builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation
data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource
for future association studies of all MHC-associated diseases and transplant medicine.
Horton and Gibson contributed equally to this work. 相似文献
102.
Dependence of pathogen molecule-induced Toll-like receptor activation and cell function on Neu1 sialidase 总被引:1,自引:0,他引:1
Schammim Ray Amith Preethi Jayanth Susan Franchuk Sarah Siddiqui Volkan Seyrantepe Katrina Gee Sameh Basta Rudi Beyaert Alexey V. Pshezhetsky Myron R. Szewczuk 《Glycoconjugate journal》2009,26(9):1197-1212
The signaling pathways of mammalian Toll-like receptors (TLR) are well characterized, but the initial molecular mechanisms activated following ligand interactions with the receptors remain poorly defined. Here, we show a membrane controlling mechanism that is initiated by ligand binding to TLR-2, -3 and-4 to induce Neu1 sialidase activity within minutes in live primary bone marrow (BM) macrophage cells and macrophage and dendritic cell lines. Central to this process is that Neu1 and not Neu2,-3 and-4 forms a complex with TLR-2,-3 and-4 on the cell surface of naïve macrophage cells. Neuraminidase inhibitors BCX1827, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA), zanamivir and oseltamivir carboxylate have a limited significant inhibition of the LPS-induced sialidase activity in live BMC-2 macrophage cells but Tamiflu (oseltamivir phosphate) completely blocks this activity. Tamiflu inhibits LPS-induced sialidase activity in live BMC-2 cells with an IC50 of 1.2?μM compared to an IC50 of 1015?μM for its hydrolytic metabolite oseltamivir carboxylate. Tamiflu blockage of LPS-induced Neu1 sialidase activity is not affected in BMC-2 cells pretreated with anticarboxylesterase agent clopidogrel. Endotoxin LPS binding to TLR4 induces Neu1 with subsequent activation of NFκB and the production of nitric oxide and pro-inflammatory IL-6 and TNFα cytokines in primary and macrophage cell lines. Hypomorphic cathepsin A mice with a secondary Neu1 deficiency respond poorly to LPS-induced pro-inflammatory cytokines compared to the wild-type or hypomorphic cathepsin A with normal Neu1 mice. Our findings establish an unprecedented mechanism for pathogen molecule-induced TLR activation and cell function, which is critically dependent on Neu1 sialidase activity associated with TLR ligand treated live primary macrophage cells and macrophage and dendritic cell lines. 相似文献
103.
104.
Tom Bongiorno Jacob Kazlow Roman Mezencev Sarah Griffiths Rene Olivares-Navarrete John F. McDonald Zvi Schwartz Barbara D. Boyan Todd C. McDevitt Todd Sulchek 《Journal of biomechanics》2014
Although it has been established that cellular stiffness can change as a stem cell differentiates, the precise relationship between cell mechanics and other phenotypic properties remains unclear. Inherent cell heterogeneity and asynchronous differentiation complicate population analysis; therefore, single-cell analysis was employed to determine how changes in cell stiffness correlate with changes in molecular biomarkers during differentiation. Design of a custom gridded tissue culture dish facilitated single-cell comparisons between cell mechanics and other differentiation biomarkers by enabling sequential measurement of cell mechanics and protein biomarker expression at the single cell level. The Young’s modulus of mesenchymal stem cells was shown not only to decrease during chemically-induced osteoblast differentiation, but also to correlate more closely with the day of differentiation than did the relative expression of the traditional osteoblast differentiation markers, bone sialoprotein and osteocalcin. Therefore, cell stiffness, a measurable property of individual cells, may serve as an improved indicator of single-cell osteoblast differentiation compared to traditional biological markers. Revelation of additional osteoblast differentiation indicators, such as cell stiffness, can improve identification and collection of starting cell populations, with applications to mesenchymal stem cell therapies and stem cell-based tissue engineering. 相似文献
105.
Dale G. Nimmo Sarah Avitabile Sam C. Banks Rebecca Bliege Bird Kate Callister Michael F. Clarke Chris R. Dickman Tim S. Doherty Don A. Driscoll Aaron C. Greenville Angie Haslem Luke T. Kelly Sally A. Kenny Jos J. Lahoz‐Monfort Connie Lee Steven Leonard Harry Moore Thomas M. Newsome Catherine L. Parr Euan G. Ritchie Kathryn Schneider James M. Turner Simon Watson Martin Westbrooke Mike Wouters Matthew White Andrew F. Bennett 《Biological reviews of the Cambridge Philosophical Society》2019,94(3):981-998
Movement is a trait of fundamental importance in ecosystems subject to frequent disturbances, such as fire‐prone ecosystems. Despite this, the role of movement in facilitating responses to fire has received little attention. Herein, we consider how animal movement interacts with fire history to shape species distributions. We consider how fire affects movement between habitat patches of differing fire histories that occur across a range of spatial and temporal scales, from daily foraging bouts to infrequent dispersal events, and annual migrations. We review animal movements in response to the immediate and abrupt impacts of fire, and the longer‐term successional changes that fires set in train. We discuss how the novel threats of altered fire regimes, landscape fragmentation, and invasive species result in suboptimal movements that drive populations downwards. We then outline the types of data needed to study animal movements in relation to fire and novel threats, to hasten the integration of movement ecology and fire ecology. We conclude by outlining a research agenda for the integration of movement ecology and fire ecology by identifying key research questions that emerge from our synthesis of animal movements in fire‐prone ecosystems. 相似文献
106.
107.
108.
Benjamin Zwirzitz Sarah Thalguter Stefanie U. Wetzels Beatrix Stessl Martin Wagner Evelyne Selberherr 《Microbial biotechnology》2022,15(5):1392-1403
Raw meat sausage represents a unique ecological niche rich in nutrients for microbial consumption, making it particularly vulnerable to microbial spoilage. Starter cultures are applied to improve product stability and safety as well as flavour characteristics. However, the influence of starter cultures on microbial community assembly and succession throughout the fermentation process is largely unknown. In particular the effect on the fungal community has not yet been explored. We evaluate the microbiological status of four different raw meat sausages using high-throughput 16S rRNA gene and ITS2 gene sequencing. The objective was to study temporal changes of microbial composition during the fermentation process and to identify potential keystone species that play an important role within the microbial community. Our results suggest that fungi assigned to the species Debaryomyces hansenii and Alternaria alternata play a key role in microbial community dynamics during fermentation. In addition, bacteria related to the starter culture Lactobacillus sakei and the spoilage-associated genera Acinetobacter, Pseudomonas and Psychrobacter are central components of the microbial ecosystem in raw fermented sausages. Elucidating the exact role and interactions of these microorganisms has the potential to have direct impacts on the quality and safety of fermented foods. 相似文献
109.
110.
Sarah A. Cocherell Stephanie N. Chun Dennis E. Cocherell Lisa C. Thompson A. Peter Klimley Joseph J. CechJr. 《Environmental Biology of Fishes》2012,93(1):143-150
In regulated rivers, fluctuating water depths associated with pulsed discharges may strand small fish in side channels and
pools. Quantitative assessments of stranded fish are difficult in field studies (e.g., due to unknown effects of avian and
terrestrial vertebrate predators). To assess such lateral displacement and stranding on juvenile stream fishes, we designed,
constructed, and tested (with three species) a 2 × 1-m, lateral-displacement flume. The flume featured a main channel that
never drained and a raised, wide “floodplain” channel that alternately flooded, with a simulated pulse, and became dewatered.
The floodplain contained four pools, with different shapes and draining capacities, in which fish could become stranded as
the water level subsided. Fish-stranding rates (8%) in this relatively compact laboratory flume, after exposure to simulated
pulsed stream flows, were comparable to those observed in past investigations using larger, artificial streams. 相似文献