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11.
Christian Fabiansen Mikkel Lykke Anne-Louise Hother J?rgen Koch Ole B?kgaard Nielsen Ingrid Hunter Jens P. Goetze Henrik Friis Thomas Thymann 《PloS one》2015,10(10)
Background
Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.Objective
To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Methods and Results
Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5–7 (p≤0.001). There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2–19.7; p = 0.03). However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0–15.9; p<0.001) in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p<0.001), whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p<0.001) and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025).Conclusions
Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition. 相似文献12.
Mikkel A. J. Kvasnes Torstein Storaas Hans Chr. Pedersen Svein Bjørk Erlend B. Nilsen 《Ecological Research》2010,25(2):367-374
Different species in a given site or population of a given species in different sites may fluctuate in synchrony if they are
affected similarly by factors such as spatially autocorrelated climate, predation, or by dispersal between populations of
one species. We used county wise time series of hunting bag records of four Norwegian tetraonid species covering 24 years
to examine patterns of interspecific and intraspecific synchrony. We estimated synchrony at three spatial scales; national,
regional (consisting of counties with similar climate), and county level. Ecologically related species with overlapping distributions
exhibited strong synchrony across Norway, but there was much variation between the different regions and counties. Regions
with a long coastline to both the North Sea and the Norwegian Ocean exhibited an overall stronger synchrony than those consisting
of more continental areas. Intraspecific synchrony was generally low across all counties, but stronger synchrony between counties
within regions defined by climatic conditions. Synchrony was negatively related to distance between populations in three of
four species. Only the synchrony in willow ptarmigan showed a clear negative relationship with distance, while the other species
had both strong positive and negative correlations at short distances. Strong interspecific synchrony between some species
pairs within regions and weak intraspecific synchrony across counties within regions suggest a stronger synchronizing effect
from environmental factors such as weather or predation and less effect from dispersal. Our results suggest that the complete
tetraonid community is structured by environmental factors affecting the different species similarly and causes widespread
interspecific synchrony. Local factors affecting the population dynamics nevertheless frequently forces neighbouring populations
out of phase. 相似文献
13.
Henrik Lütken James R. Lloyd Mikkel A. Glaring Lone Baunsgaard Kristian Holst Laursen Anna Haldrup Jens Kossmann Andreas Blennow 《Planta》2010,232(5):1127-1139
Two glucanotransferases, disproportionating enzyme 1 (StDPE1) and disproportionating enzyme 2 (StDPE2), were repressed using
RNA interference technology in potato, leading to plants repressed in either isoform individually, or both simultaneously.
This is the first detailed report of their combined repression. Plants lacking StDPE1 accumulated slightly more starch in
their leaves than control plants and high levels of maltotriose, while those lacking StDPE2 contained maltose and large amounts
of starch. Plants repressed in both isoforms accumulated similar amounts of starch to those lacking StDPE2. In addition, they
contained a range of malto-oligosaccharides from maltose to maltoheptaose. Plants repressed in both isoforms had chlorotic
leaves and did not grow as well as either the controls or lines where only one of the isoforms was repressed. Examination
of photosynthetic parameters suggested that this was most likely due to a decrease in carbon assimilation. The subcellular
localisation of StDPE2 was re-addressed in parallel with DPE2 from Arabidopsis thaliana by transient expression of yellow fluorescent protein fusions in tobacco. No translocation to the chloroplasts was observed
for any of the fusion proteins, supporting a cytosolic role of the StDPE2 enzyme in leaf starch metabolism, as has been observed
for Arabidopsis DPE2. It is concluded that StDPE1 and StDPE2 have individual essential roles in starch metabolism in potato and consequently
repression of these disables regulation of leaf malto-oligosaccharides, starch content and photosynthetic activity and thereby
plant growth possibly by a negative feedback mechanism. 相似文献
14.
Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa biofilms
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Haagensen JA Klausen M Ernst RK Miller SI Folkesson A Tolker-Nielsen T Molin S 《Journal of bacteriology》2007,189(1):28-37
During Pseudomonas aeruginosa flow cell biofilm development, the cell population differentiates into a nonmotile subpopulation which forms microcolonies and a migrating subpopulation which eventually colonizes the top of the microcolonies, resulting in the development of mushroom-shaped multicellular structures. The cap-forming subpopulation was found to develop tolerance to membrane-targeting antimicrobial agents, such as the cyclic cationic peptide colistin and the detergent sodium dodecyl sulfate. The stalk-forming subpopulation, on the other hand, was sensitive to the membrane-targeting antibacterial agents. All biofilm-associated cells were sensitive to the antibacterial agents when tested in standard plate assays. A mutation eliminating the production of type IV pili, and hence surface-associated motility, prevented the formation of regular mushroom-shaped structures in the flow cell biofilms, and the development of tolerance to the antimicrobial agents was found to be affected as well. Mutations in genes interfering with lipopolysaccharide modification (pmr) eliminated the biofilm-associated colistin tolerance phenotype. Experiments with a PAO1 strain harboring a pmr-gfp fusion showed that only the cap-forming subpopulation in biofilms treated with colistin expresses the pmr operon. These results suggest that increased antibiotic tolerance in biofilms may be a consequence of differentiation into distinct subpopulations with different phenotypic properties. 相似文献
15.
Jesper Madsen Mikkel Tamstorf Marcel Klaassen Nina Eide Christian Glahder Frank Rigét Helene Nyegaard Fred Cottaar 《Polar Biology》2007,30(11):1363-1372
During four breeding seasons, 2003–2006, we studied the relationship between snow cover and nesting performance in pink-footed
geese (Anser brachyrhynchus) in a key breeding site on Svalbard. Snow cover in late May, i.e., at the time of egg laying of geese, was derived from MODIS
satellite images. Snow cover had a profound cascading effect on reproductive output via the number of nesting pairs and timing
of nesting, which affected nest success, while there was only a tendency for a negative effect on clutch size. Hence, we estimated
a five-fold difference in the number of young produced (to post-hatching) between years with little snow and years with high
snow cover. The results from the study area correlated with whole-population productivity estimates recorded in autumn. Thus,
snow cover derived from MODIS satellite images appears to provide a useful indicator of the breeding conditions in the Arctic. 相似文献
16.
17.
After fertilization, lineage specification is governed by a complicated molecular network in which permissiveness and repression of expression of pluripotency- and differentiation-associated genes are regulated by epigenetic modifications. DNA methylation operates as a very stable repressive mark in this process. In this study, we investigated the relationship between DNA methylation and expression of pluripotency-associated genes (OCT4, NANOG and SOX2), a trophectoderm (TE)-specific gene (ELF5), and genes associated with neural differentiation (SOX2 and VIMENTIN) in porcine Day 10 (E10) epiblast, hypoblast, and TE as well as in epiblast-derived neural progenitor cells (NPCs). We found that OCT4, NANOG, and SOX2 were highly expressed in the epiblast and hypoblast, while VIMENTIN was only highly expressed in the epiblast. Moreover, low expression of OCT4, NANOG, SOX2 and VIMENTIN was noted in the TE. Most CpG sites of OCT4, NANOG, SOX2 and VIMENTIN displayed low methylation levels in the epiblast and hypoblast and, strikingly, also in the TE. Hence, the expression patterns of these genes were not directly related to levels of DNA methylation in the TE in contrast to the situation in the mouse. In contrast, ELF5 was exclusively expressed in the TE and was correspondingly hypomethylated in this tissue. In NPCs, we observed down-regulation of NANOG and OCT4 expression, which correlated with hypermethylation of their promoters, whereas VIMENTIN displayed up-regulation in accordance with hypomethylation of its promoter. In conclusion, DNA methylation is an inconsistently operating epigenetic mechanism in porcine E10 blastocysts, whereas in porcine epiblast-derived NPCs, expression of pluripotency-associated and differentiation genes appear to be regulated by this modification. 相似文献
18.
Oestergaard MZ Inoue M Yoshida S Mahanani WR Gore FM Cousens S Lawn JE Mathers CD;United Nations Inter-Agency Group for Child Mortality Estimation the Child Health Epidemiology Reference Group 《PLoS medicine》2011,8(8):e1001080
Background
Historically, the main focus of studies of childhood mortality has been the infant and under-five mortality rates. Neonatal mortality (deaths <28 days of age) has received limited attention, although such deaths account for about 41% of all child deaths. To better assess progress, we developed annual estimates for neonatal mortality rates (NMRs) and neonatal deaths for 193 countries for the period 1990–2009 with forecasts into the future.Methods and Findings
We compiled a database of mortality in neonates and children (<5 years) comprising 3,551 country-years of information. Reliable civil registration data from 1990 to 2009 were available for 38 countries. A statistical model was developed to estimate NMRs for the remaining 155 countries, 17 of which had no national data. Country consultation was undertaken to identify data inputs and review estimates. In 2009, an estimated 3.3 million babies died in the first month of life—compared with 4.6 million neonatal deaths in 1990—and more than half of all neonatal deaths occurred in five countries of the world (44% of global livebirths): India 27.8% (19.6% of global livebirths), Nigeria 7.2% (4.5%), Pakistan 6.9% (4.0%), China 6.4% (13.4%), and Democratic Republic of the Congo 4.6% (2.1%). Between 1990 and 2009, the global NMR declined by 28% from 33.2 deaths per 1,000 livebirths to 23.9. The proportion of child deaths that are in the neonatal period increased in all regions of the world, and globally is now 41%. While NMRs were halved in some regions of the world, Africa''s NMR only dropped 17.6% (43.6 to 35.9).Conclusions
Neonatal mortality has declined in all world regions. Progress has been slowest in the regions with high NMRs. Global health programs need to address neonatal deaths more effectively if Millennium Development Goal 4 (two-thirds reduction in child mortality) is to be achieved. Please see later in the article for the Editors'' Summary 相似文献19.
Klaus Koefoed Lucilla Steinaa Josefine Nielsen S?derberg Ida Kj?r Helle Jane Jacobsen Per-Johan Meijer John S?rensen Haurum Allan Jensen Michael Kragh Peter Sejer Andersen Mikkel Wandahl Pedersen 《MABS-AUSTIN》2011,3(6):584-595
The epidermal growth factor receptor (EGFR) is frequently dysregulated in human malignancies and a validated target for cancer therapy. Two monoclonal anti-EGFR antibodies (cetuximab and panitumumab) are approved for clinical use. However, the percentage of patients responding to treatment is low and many patients experiencing an initial response eventually relapse. Thus, the need for more efficacious treatments remains. Previous studies have reported that mixtures of antibodies targeting multiple distinct epitopes are more effective than single mAbs at inhibiting growth of human cancer cells in vitro and in vivo. The current work describes the rational approach that led to discovery and selection of a novel anti-EGFR antibody mixture Sym004, which is currently in Phase 2 clinical testing. Twenty-four selected anti-EGFR antibodies were systematically tested in dual and triple mixtures for their ability to inhibit cancer cells in vitro and tumor growth in vivo. The results show that targeting EGFR dependent cancer cells with mixtures of antibodies is superior at inhibiting their growth both in vitro and in vivo. In particular, antibody mixtures targeting non-overlapping epitopes on domain III are efficient and indeed Sym004 is composed of two monoclonal antibodies targeting this domain. The superior growth inhibitory activity of mixtures correlated with their ability to induce efficient EGFR degradation.Key words: EGFR, antibody synergy, functional screening, epitope binning, antibody combinations 相似文献
20.
A semi-continuous magnetic particle-based process for the controlled attachment of PEG (PEGylation) to proteins is described for the first time. Trypsin and 2 kDa mono-activated PEG were used to systematically develop the steps in the process. Proof of concept was shown in a microfluidics system to minimize reagent consumption. Two streams containing (i) 1.2 g/L trypsin and (ii) 4 g/L magnetic adsorbents derivatized with the reversible affinity ligand benzamidine were pumped into a pipe reactor. At the exit, a third solution of activated PEG (0-40 g/L) was introduced and the solutions immediately fed into a second reactor. Upon exiting, the mixture was combined in a third reactor with a fourth stream of free amine groups to stop the reaction (50 mM lysine). The mixture continued into a high-gradient magnetic separator where magnetic supports, with PEGylated trypsin still attached, were captured and washing and elution steps were subsequently carried out. Analysis of the conjugates (with SDS-PAGE & LC-MS) showed that the extent of PEGylation could be controlled by varying the reaction time or PEG concentration. Furthermore, the PEG-conjugates had higher enzyme activity compared to PEGylation of non-immobilized trypsin. 相似文献