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31.
Context
Mathematical models may help the analysis of biological systems by providing estimates of otherwise un-measurable quantities such as concentrations and fluxes. The variability in such systems makes it difficult to translate individual characteristics to group behavior. Mixed effects models offer a tool to simultaneously assess individual and population behavior from experimental data. Lipoproteins and plasma lipids are key mediators for cardiovascular disease in metabolic disorders such as diabetes mellitus type 2. By the use of mathematical models and tracer experiments fluxes and production rates of lipoproteins may be estimated.Results
We developed a mixed effects model to study lipoprotein kinetics in a data set of 15 healthy individuals and 15 patients with type 2 diabetes. We compare the traditional and the mixed effects approach in terms of group estimates at various sample and data set sizes.Conclusion
We conclude that the mixed effects approach provided better estimates using the full data set as well as with both sparse and truncated data sets. Sample size estimates showed that to compare lipoprotein secretion the mixed effects approach needed almost half the sample size as the traditional method. 相似文献32.
Stephanie J. Culler Kevin G. Hoff Rodger B. Voelker J. Andrew Berglund Christina D. Smolke 《Nucleic acids research》2010,38(15):5152-5165
Despite the critical role of pre-mRNA splicing in generating proteomic diversity and regulating gene expression, the sequence composition and function of intronic splicing regulatory elements (ISREs) have not been well elucidated. Here, we employed a high-throughput in vivo Screening PLatform for Intronic Control Elements (SPLICE) to identify 125 unique ISRE sequences from a random nucleotide library in human cells. Bioinformatic analyses reveal consensus motifs that resemble splicing regulatory elements and binding sites for characterized splicing factors and that are enriched in the introns of naturally occurring spliced genes, supporting their biological relevance. In vivo characterization, including an RNAi silencing study, demonstrate that ISRE sequences can exhibit combinatorial regulatory activity and that multiple trans-acting factors are involved in the regulatory effect of a single ISRE. Our work provides an initial examination into the sequence characteristics and function of ISREs, providing an important contribution to the splicing code. 相似文献
33.
Christian Andersson Ekaterina Petrova Kris Berglund Ulrika Rova 《Bioprocess and biosystems engineering》2010,33(6):711-718
During dual-phase fermentations using Escherichia coli engineered for succinic acid production, the productivity and viable cell concentration decrease as the concentration of
succinic acid increases. The effects of succinic acid on the fermentation kinetics, yield, and cell viability were investigated
by resuspending cells in fresh media after selected fermentation times. The cellular succinic acid productivity could be restored,
but cell viability continuously decreased throughout the fermentations by up to 80% and subsequently the volumetric productivity
was reduced. Omitting complex nutrients in the resuspension media had no significant effect on cellular succinate productivity
and yield, although the viable cell concentration and thus the volumetric productivity was reduced by approximately 20%. By
resuspending the cells, the amount of succinate produced during a 100-h fermentation was increased by more than 60%. The results
demonstrate that by product removal succinic acid productivity can be maintained at high levels for extended periods of time. 相似文献
34.
Biomimetic polysaccharide nanocomposites of high cellulose content and high toughness 总被引:3,自引:0,他引:3
Plant cell walls combine mechanical stiffness, strength and toughness despite a highly hydrated state. Inspired by this, a nanostructured cellulose network is combined with an almost viscous polysaccharide matrix in the form of a 50/50 amylopectin-glycerol blend. Homogeneous films with a microfibrillated cellulose (MFC) nanofiber content in the range of 10-70 wt % are successfully cast. Characterization is carried out by dynamic mechanical analysis, field-emission scanning electron microscopy, X-ray diffraction, and mercury density measurements. The MFC is well dispersed and predominantly oriented random-in-the-plane. High tensile strength is combined with high modulus and very high work of fracture in the nanocomposite with 70 wt % MFC. The reasons for this interesting combination of properties include nanofiber and matrix properties, favorable nanofiber-matrix interaction, good dispersion, and the ability of the MFC network to maintain its integrity to a strain of at least 8%. 相似文献
35.
36.
Rossi J Balthasar N Olson D Scott M Berglund E Lee CE Choi MJ Lauzon D Lowell BB Elmquist JK 《Cell metabolism》2011,13(2):195-204
Melanocortin-4 receptor (MC4R) mutations cause dysregulation of energy balance and hyperinsulinemia. We have used mouse models to study the physiological roles of extrahypothalamic MC4Rs. Re-expression of MC4Rs in cholinergic neurons (ChAT-Cre, loxTB MC4R mice) modestly reduced body weight gain without altering food intake and was sufficient to normalize energy expenditure and attenuate hyperglycemia and hyperinsulinemia. In contrast, restoration of MC4R expression in brainstem neurons including those in the dorsal motor nucleus of the vagus (Phox2b-Cre, loxTB MC4R mice) was sufficient to attenuate hyperinsulinemia, while the hyperglycemia and energy balance were not normalized. Additionally, hepatic insulin action and insulin-mediated suppression of hepatic glucose production were improved in ChAT-Cre, loxTB MC4R mice. These findings suggest that MC4Rs expressed by cholinergic neurons regulate energy expenditure and hepatic glucose production. Our results also provide further evidence of the dissociation in pathways mediating the effects of melanocortins on energy balance and glucose homeostasis. 相似文献
37.
Brodersen J Rodriguez-Gil JL Jönsson M Hansson LA Brönmark C Nilsson PA Nicolle A Berglund O 《PloS one》2011,6(10):e24022
The predicted global warming may affect freshwater systems at several organizational levels, from organism to ecosystem. Specifically, in temperate regions, the projected increase of winter temperatures may have important effects on the over-winter biology of a range of organisms and especially for fish and other ectothermic animals. However, temperature effects on organisms may be directed strongly by resource availability. Here, we investigated whether over-winter loss of biomass and lipid content of juvenile roach (Rutilus rutilus) was affected by the physiologically relatively small (2-5 °C) changes of winter temperatures predicted by the Intergovernmental Panel on Climate Change (IPCC), under both natural and experimental conditions. This was investigated in combination with the effects of food availability. Finally, we explored the potential for a correlation between lake temperature and resource levels for planktivorous fish, i.e., zooplankton biomass, during five consecutive winters in a south Swedish lake. We show that small increases in temperature (+2 °C) affected fish biomass loss in both presence and absence of food, but negatively and positively respectively. Temperature alone explained only a minor part of the variation when food availability was not taken into account. In contrast to other studies, lipid analyses of experimental fish suggest that critical somatic condition rather than critical lipid content determined starvation induced mortality. Our results illustrate the importance of considering not only changes in temperature when predicting organism response to climate change but also food-web interactions, such as resource availability and predation. However, as exemplified by our finding that zooplankton over-winter biomass in the lake was not related to over-winter temperature, this may not be a straightforward task. 相似文献
38.
A comparative description of mitochondrial DNA differentiation in selected avian and other vertebrate genera 总被引:13,自引:1,他引:13
Levels of mitochondrial DNA (mtDNA) sequence divergence between species
within each of several avian (Anas, Aythya, Dendroica, Melospiza, and
Zonotrichia) and nonavian (Lepomis and Hyla) vertebrate genera were
compared. An analysis of digestion profiles generated by 13-18 restriction
endonucleases indicates little overlap in magnitude of mtDNA divergence for
the avian versus nonavian taxa examined. In 55 interspecific comparisons
among the avian congeners, the fraction of identical fragment lengths (F)
ranged from 0.26 to 0.96 (F = 0.46), and, given certain assumptions, these
translate into estimates of nucleotide sequence divergence (p) ranging from
0.007 to 0.088; in 46 comparisons among the fish and amphibian congeners, F
values ranged from 0.00 to 0.36 (F = 0.09), yielding estimates of P greater
than 0.070. The small mtDNA distances among avian congeners are associated
with protein-electrophoretic distances (D values) less than approximately
0.2, while the mtDNA distances among assayed fish and amphibian congeners
are associated with D values usually greater than 0.4. Since the
conservative pattern of protein differentiation previously reported for
many avian versus nonavian taxa now appears to be paralleled by a
conservative pattern of mtDNA divergence, it seems increasingly likely that
many avian species have shared more recent common ancestors than have their
nonavian taxonomic counterparts. However, estimates of avian divergence
times derived from mtDNA- and protein-calibrated clocks cannot readily be
reconciled with some published dates based on limited fossil remains. If
the earlier paleontological interpretations are valid, then protein and
mtDNA evolution must be somewhat decelerated in birds. The empirical and
conceptual issues raised by these findings are highly analogous to those in
the long-standing debate about rates of molecular evolution and times of
separation of ancestral hominids from African apes.
相似文献
39.
Jennifer W. Hill Carol F. Elias Makoto Fukuda Kevin W. Williams Eric D. Berglund William L. Holland You-Ree Cho Jen-Chieh Chuang Yong Xu Michelle Choi Danielle Lauzon Charlotte E. Lee Roberto Coppari James A. Richardson Jeffrey M. Zigman Streamson Chua Philipp E. Scherer Bradford B. Lowell Jens C. Brüning Joel K. Elmquist 《Cell metabolism》2010,11(4):286-297
40.
In order to function in vivo, tissue engineered blood vessels (TEBVs) must encumber pulsatile blood flow and withstand hemodynamic pressures for long periods of time. To date TEBV mechanical assessment has typically relied on single time point burst and/or uniaxial tensile testing to gauge the strengths of the constructs. This study extends this analysis to include creep and stepwise stress relaxation viscoelastic testing methodologies. TEBV models exhibiting diverse mechanical behaviors as a result of different architectures ranging from reconstituted collagen gels to hybrid constructs reinforced with either untreated or glutaraldhyde-crosslinked collagen supports were evaluated after 8 and 23 days of in vitro culturing. Data were modeled using three and four-parameter linear viscoelastic mathematical representations and compared to porcine carotid arteries. While glutaraldhyde-treated hybrid TEBVs exhibited the largest overall strengths and toughness, uncrosslinked hybrid samples exhibited time-dependent behaviors most similar to native arteries. These findings emphasize the importance of viscoelastic characterization when evaluating the mechanical performance of TEBVs. Limits of testing methods and modeling systems are presented and discussed. 相似文献