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(2008)Journal ArticleObjectives: This study assesses interest in genetic testing for gene variations associated with bipolar disorder and associated information needs. Methods: Two hundred individuals (95 unaffected and 105 affected with either bipolar disorder, schizoaffective disorder-manic type, or recurrent major depression) from families with multiple cases of bipolar disorder were assessed, using mailed, self-administered questionnaires. Results: The percentage of participants reporting interest in genetic testing was associated with the degree of certainty with which any test would indicate the development of bipolar disorder. Interest in genetic testing, given a 25% lifetime risk scenario, was lowest (with 77% of participants indicating interest), and highest for the 100% lifetime risk scenario (92%). Eighty percent of participants indicated interest in genetic testing of their own children; of these 30% reported wanting their children tested at birth, and 33% in early childhood. Forty-one percent of participants reported that they would be interested in preimplantation genetic diagnosis, and 54% in prenatal testing. Limitations: The possibility of ascertainment bias cannot be ruled out. Interest in hypothetical genetic testing for bipolar disorder may not necessarily translate into actual utilization. Conclusions: These results indicate that uptake of genetic testing for genotyping for low-risk alleles related to bipolar disorder is likely to be lower than for testing for high-penetrance gene mutations that follow Mendelian inheritance. The discrepancy between the desired age of testing children and the accepted current practice may be a source of distress and conflict for parents and health professionals alike.
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(2008)Journal ArticleLipid droplets (LDs) are emerging cellular organelles that are of crucial importance in cell biology and human diseases. In this study, we present our screen of 4,700 Saccharomyces cerevisiae mutants for abnormalities in the number and morphology of LDs; we identify 17 fld (few LDs) and 116 mld (many LDs) mutants. One of the fld mutants (fld1) is caused by the deletion of YLR404W, a previously uncharacterized open reading frame. Cells lacking FLD1 contain strikingly enlarged (supersized) LDs, and LDs from fld1 Delta cells demonstrate significantly enhanced fusion activities both in vivo and in vitro. Interestingly, the expression of human seipin, whose mutant forms are associated with Berardinelli-Seip congenital lipodystrophy and motoneuron disorders, rescues LD-associated defects in fld1 Delta cells. Lipid profiling reveals alterations in acyl chain compositions of major phospholipids in fld1 Delta cells. These results suggest that an evolutionally conserved function of seipin in phospholipid metabolism and LD formation may be functionally important in human adipogenesis.
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(2008)Journal ArticleThe 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.
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(2008)Journal ArticleFire 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.
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(2008)Journal ArticleTwo-phase composites La0.7Sr0.3MnO3/Ta2O5 are synthesized and their magnetization and low-field magnetoresistance (LFMR) characteristics are investigated. It is found that a small amount of Ta ions enter into LSMO grains near the grain surface region, resulting in the reduction of the cell volume, and consequently, an extra reduction of the saturate magnetization. The paramagnetism-to-ferromagnetism transition temperature, TC, does not show significant change. The LFMR enhancement is observed over a wide range of temperature from 50 to 350K when the second phase material (Ta2O5) is introduced. The magnetic disorder caused by the secondary phase at grain boundaries and the Ta doping effect on the surface of LSMO grains are believed to contribute to the enhanced MR.
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(2008)Journal ArticleThe designers of a large scale video-on-demand system face an optimization problem of deciding how to assign movies to multiple disks (servers) such that the request blocking probability is minimized subject to capacity constraints. To solve this problem, it is essential to develop scalable and accurate analytical means to evaluate the blocking performance of the system for a given file assignment. The performance analysis is made more complicated by the fact that the request blocking probability depends also on how disks are selected to serve user requests for multicopy movies. In this paper, we analyze several efficient resource selection schemes. Numerical results demonstrate that our analysis is scalable and sufficiently accurate to support the task of file assignment optimization in such a system. © 2008 IEEE.
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(2008)Conference Paper
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(2008)Conference Paper