We performed sensitivity experiments using an ocean general circulation model at two stages of the Late Ordovician (Caradoc, 454 Ma; Ashgill, 446 Ma) under a range of atmospheric pCO2 values (8–18× PAL; pre-industrial atmospheric level) at high and low sea level.
The model results indicate that the long-term cooling trend during the Late Ordovician can be explained by progressive cooling of the global ocean in response to falling levels of atmospheric pCO2, sea level change, and paleogeographic change. These results also explain the occurrence of low latitude cool-water carbonates in North America.
In all simulations, a drop in sea level led to a reduction in poleward ocean heat transport. This indicates a possible positive feedback that could have enhanced global cooling in response to sea level drop during the Late Ordovician. Alterations in poleward ocean heat transport linked to changes of atmospheric pCO2 also indicate that there is a threshold of 10× PAL, above which ocean current change cannot be responsible for glaciation in the Late Ordovician. Continental drift could explain the observed global cooling trend in the Late Ordovician through a combined poleward ocean heat transport feedback and increased ice-albedo effect if atmospheric pCO2 was low during the entire Late Ordovician.
The model results further indicate that the response of meridional overturning to changes in paleogeography, atmospheric pCO2, and sea level is stronger than the response of surface circulation to these perturbations. Because the overturning circulation is so strong, meridional overturning was the dominant mechanism for described changes in heat transport in the Late Ordovician. 相似文献
Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function
and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal
glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether
depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. 相似文献
Noninvasive functional imaging of tumors can provide valuable early-response biomarkers, in particular, for targeted chemotherapy. Using various experimental tumor models, we have investigated the ability of positron emission tomography (PET) measurements of 2-deoxy-2-[18F]fluoro-glucose (FDG) and 3′-deoxy-3′-[18F]fluorothymidine (FLT) to detect response to the allosteric mammalian target of rapamycin (mTOR) inhibitor everolimus. Tumor models were declared sensitive (murine melanoma B16/BL6 and human lung H596) or relatively insensitive (human colon HCT116 and cervical KB31), according to the IC50 values (concentration inhibiting cell growth by 50%) for inhibition of proliferation in vitro (<10 nM and >1 µM, respectively). Everolimus strongly inhibited growth of the sensitive models in vivo but also significantly inhibited growth of the insensitive models, an effect attributable to its known anti-angiogenic/vascular properties. However, although tumor FDG and FLT uptake was significantly reduced in the sensitive models, it was not affected in the insensitive models, suggesting that endothelial-directed effects could not be detected by these PET tracers. Consistent with this hypothesis, in a well-vascularized orthotopic rat mammary tumor model, other antiangiogenic agents also failed to affect FDG uptake, despite inhibiting tumor growth. In contrast, the cytotoxic patupilone, a microtubule stabilizer, blocked tumor growth, and markedly reduced FDG uptake. These results suggest that FDG/FLT-PET may not be a suitable method for early markers of response to antiangiogenic agents and mTOR inhibitors in which anti-angiogenic/vascular effects predominate because the method could provide false-negative responses. These conclusions warrant clinical testing. 相似文献
Cotyledons of the common bean (Phaseolus vulgaris L.) synthesize large amounts of the reserve protein phaseolin. The polypeptides are synthesized on membrane-bound polysomes, pass through the endoplasmic reticulum (ER) and accumulate in protein bodies. For a study of the biosynthesis and processing of phaseolin, developing cotyledons were labeled with radioactive amino acids, glucosamine and mannose, and isolated fractions (polysomal RNA, polysomes, and rough ER) were used for in vitro protein synthesis. Newly synthesized phaseolin present in the ER of developing cotyledons can be fractioned into four glycopolypeptides by SDS PAGE. In vitro synthesis with polysomal RNA results in the formation of two polypeptides by polysome run-off shows that glycosylation is a co-translational event. The two unglycosylated polypeptides formed by polysome run-off are slightly smaller than the two polypeptides formed by in vitro translation of isolated RNA, indicating that a signal peptide may be present on these polypeptides. Run-off synthesis with rough ER produces a pattern of four polypeptides similar to the one obtained by in vivo labeling. The two abundant glycopolypeptides formed by polysome run-off. This result indicates the existence of a second glycosylation event for the abundant polypeptides. Inhibition of glycosylation by Triton X-100 during chain-completion with rough ER was used to show that these two glycosylation steps normally occur sequentially. Both glycosylation steps are inhibited by tunicamycin. Analysis of carhohydrate to protein ratios of the different polypeptides and of trypsin digests of polypeptides labeled with [(3)H]glucosamine confirmed the conclusion that some glycosylated polypeptides contain two oligosaccharide chains, while others contain only one. An analysis of tryptic peptide maps shows that each of the unglycosylated polypeptides is the precursor for one glycosylated polypeptide with one oligosaccharide chain and one with two oligosaccharide chains. 相似文献
The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units. 相似文献
Intraspecific sequence variation in the D-loop region of mtDNA in white
sturgeon (Acipenser transmontanus), a relict North American fish species,
was examined in 27 individuals from populations of the Columbia and Fraser
rivers. Thirty-three varied nucleotide positions were present in a
462-nucleotide D-loop sequence, amplified using the polymerase chain
reaction. Bootstrapped neighbor-joining and maximum- parsimony trees of
sequences from 19 haplotypes suggest that the two populations have recently
diverged. This is consistent with the hypothesis that the Columbia River, a
Pleistocene refugium habitat, was the source of founders for the Fraser
River after the last glacial recession. On the basis of a divergence time
of 10-12 thousand years ago, the estimated substitution rate of the white
sturgeon D-loop region is 1.1-1.3 x 10(-7) nucleotides/site/year, which is
comparable to rates for hypervariable sequences in the human D-loop region.
Furthermore, the ratio of mean percent nucleotide differences in the D-
loop (2.27%) to that in whole mtDNA (0.54%, as estimated from
restriction-enzyme data) is 4.3, which is similar to the fourfold-to-
fivefold-higher substitution rate estimated for the human D-loop. The high
nucleotide substitution rate of the hypervariable region indicates that the
vertebrate D-loop has potential as a genetic marker in molecular population
studies.
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Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch). Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited. 相似文献