Medicine & Health

Publication Search Results

Now showing 1 - 4 of 4
  • (2006) Lee, Cathryn; Gaeta, Bruno; Malming, H; Bain, Michael; Sewell, William; Collins, Andrew
    Journal Article
    We have used a bioinformatics approach to evaluate the completeness and functionality of the reported human immunoglobulin heavy-chain IGHD gene repertoire. Using the hidden Markov-model-based iHMMune-align program, 1,080 relatively unmutated heavy-chain sequences were aligned against the reported repertoire. These alignments were compared with alignments to 1,639 more highly mutated sequences. Comparisons of the frequencies of gene utilization in the two databases, and analysis of features of aligned IGHD gene segments, including their length, the frequency with which they appear to mutate, and the frequency with which specific mutations were seen, were used to determine the reliability of alignments to the less commonly seen IGHD genes. Analysis demonstrates that IGHD4-23 and IGHD5-24, which have been reported to be open reading frames of uncertain functionality, are represented in the expressed gene repertoire; however, the functionality of IGHD6-25 must be questioned. Sequence similarities make the unequivocal identification of members of the IGHD1 gene family problematic, although all genes except IGHD1-14*01 appear to be functional. On the other hand, reported allelic variants of IGHD2-2 and of the IGHD3 gene family appear to be nonfunctional, very rare, or nonexistent. Analysis also suggests that the reported repertoire is relatively complete, although one new putative polymorphism (IGHD3-10*p03) was identified. This study therefore confirms a surprising lack of diversity in the available IGHD gene repertoire, and restriction of the germline sequence databases to the functional set described here will substantially improve the accuracy of IGHD gene alignments and therefore the accuracy of analysis of the V-D-J junction.

  • (2008) Out, R; Jessup, Wendy; Le Goff, W; Hoekstra, M; Gelissen, Ingrid; Zhao, Yong; Kritharides, Leonard; Chimini, G; Kuiper, J; Chapman, Matthew; Huby, T; Van Berkel, T; Van Eck, M
    Journal Article
    The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.

  • (2008) Out, R; Jessup, Wendy; Le Goff, W; Hoekstra, M; Gelissen, Ingrid; Zhao, Yong; Kritharides, Leonard; Chimini, G; Kuiper, J; Chapman, Matthew; Huby, T; Van Berkel, T; Van Eck, M
    Journal Article

  • (2008) Power, M; Marlon, J; Ortiz, N; Bartlein, P; Harrison, Simon; Mayle, F; Ballouche, A; Bradshaw, R; Carcaillet, C; Cordova, C; Mooney, Scott; Moreno, P; Prentice, I; Thonicke, K; Tinner, W; Whitlock, C; Zhang, Yanling; Zhao, Yong; Ali, Amna; Anderson, Richard; Beer, R; Behling, H; Briles, C; Brown, Katherine; Brunelle, A; Bush, M; Camill, P; Chu, G; Clark, J; Colombaroli, D; Connor, Stuart; Daniau, A; Daniels, M; Dodson, John; Doughty, E; Edwards, Meredith; Finsinger, W; Foster, Douglas; Frechette, J; Gaillard, M; Gavin, D; Gobet, E; Haberle, Simon; Hallett, D; Higuera, P; Hope, G; Horn, S; Inoue, J; Kaltenrieder, P; Kennedy, Liz; Kong, Z; Larsen, C; Long, C; Lynch, Jodi; Lynch, E; McGlone, M; Meeks, S; Mensing, S; Meyer, G; Minckley, T; Mohr, J; Nelson, D; New, J; Newnham, R; Noti, R; Oswald, W; Pierce, J; Richard, P; Rowe, C; Goni, M; Shuman, B; Takahara, H; Toney, J; Turney, C; Urrego-Sanchez, D; Umbanhowar, C; Vandergoes, M; Vanniere, B; Vescovi, E
    Journal Article
    Fire activity has varied globally and continuously since the last glacial maximum (LGM) in response to long-term changes in global climate and shorter-term regional changes in climate, vegetation, and human land use. We have synthesized sedimentary charcoal records of biomass burning since the LGM and present global maps showing changes in fire activity for time slices during the past 21,000 years (as differences in charcoal accumulation values compared to pre-industrial). There is strong broad-scale coherence in fire activity after the LGM, but spatial heterogeneity in the signals increases thereafter. In North America, Europe and southern South America, charcoal records indicate less-than-present fire activity during the deglacial period, from 21,000 to ∼11,000 cal yr BP. In contrast, the tropical latitudes of South America and Africa show greater-than-present fire activity from ∼19,000 to ∼17,000 cal yr BP and most sites from Indochina and Australia show greater-than-present fire activity from 16,000 to ∼13,000 cal yr BP. Many sites indicate greater-than-present or near-present activity during the Holocene with the exception of eastern North America and eastern Asia from 8,000 to ∼3,000 cal yr BP, Indonesia and Australia from 11,000 to 4,000 cal yr BP, and southern South America from 6,000 to 3,000 cal yr BP where fire activity was less than present. Regional coherence in the patterns of change in fire activity was evident throughout the post-glacial period. These complex patterns can largely be explained in terms of large-scale climate controls modulated by local changes in vegetation and fuel load.