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61.
The effects of selective ibotenate lesions of the complete hippocampus (CHip), the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male rats were assessed on several measures related to energy regulation (i.e., body weight gain, food intake, body adiposity, metabolic activity, general behavioral activity, conditioned appetitive responding). The testing conditions were designed to minimize the nonspecific debilitating effects of these surgeries on intake and body weight. Rats with CHip and VP lesions exhibited significantly greater weight gain and food intake compared with controls. Furthermore, CHip-lesioned rats, but not rats with VP lesions, showed elevated metabolic activity, general activity in the dark phase of the light-dark cycle, and greater conditioned appetitive behavior, compared with control rats without these brain lesions. In contrast, rats with mPFC lesions were not different from controls on any of these measures. These results indicate that hippocampal damage interferes with energy and body weight regulation, perhaps by disrupting higher-order learning and memory processes that contribute to the control of appetitive and consummatory behavior. 相似文献
62.
63.
Action potential duration dispersion and alternans in simulated heterogeneous cardiac tissue with a structural barrier 下载免费PDF全文
Structural barriers to wave propagation in cardiac tissue are associated with a decreased threshold for repolarization alternans both experimentally and clinically. Using computer simulations, we investigated the effects of a structural barrier on the onset of spatially concordant and discordant alternans. We used two-dimensional tissue geometry with heterogeneity in selected potassium conductances to mimic known apex-base gradients. Although we found that the actual onset of alternans was similar with and without the structural barrier, the increase in alternans magnitude with faster pacing was steeper with the barrier--giving the appearance of an earlier alternans onset in its presence. This is consistent with both experimental structural barrier findings and the clinical observation of T-wave alternans occurring at slower pacing rates in patients with structural heart disease. In ionically homogeneous tissue, discordant alternans induced by the presence of the structural barrier arose at intermediate pacing rates due to a source-sink mismatch behind the barrier. In heterogeneous tissue, discordant alternans occurred during fast pacing due to a barrier-induced decoupling of tissue with different restitution properties. Our results demonstrate a causal relationship between the presence of a structural barrier and increased alternans magnitude and action potential duration dispersion, which may contribute to why patients with structural heart disease are at higher risk for ventricular tachyarrhythmias. 相似文献
64.
Willemijn Groenendaal Francis A. Ortega Armen R. Kherlopian Andrew C. Zygmunt Trine Krogh-Madsen David J. Christini 《PLoS computational biology》2015,11(4)
The traditional cardiac model-building paradigm involves constructing a composite model using data collected from many cells. Equations are derived for each relevant cellular component (e.g., ion channel, exchanger) independently. After the equations for all components are combined to form the composite model, a subset of parameters is tuned, often arbitrarily and by hand, until the model output matches a target objective, such as an action potential. Unfortunately, such models often fail to accurately simulate behavior that is dynamically dissimilar (e.g., arrhythmia) to the simple target objective to which the model was fit. In this study, we develop a new approach in which data are collected via a series of complex electrophysiology protocols from single cardiac myocytes and then used to tune model parameters via a parallel fitting method known as a genetic algorithm (GA). The dynamical complexity of the electrophysiological data, which can only be fit by an automated method such as a GA, leads to more accurately parameterized models that can simulate rich cardiac dynamics. The feasibility of the method is first validated computationally, after which it is used to develop models of isolated guinea pig ventricular myocytes that simulate the electrophysiological dynamics significantly better than does a standard guinea pig model. In addition to improving model fidelity generally, this approach can be used to generate a cell-specific model. By so doing, the approach may be useful in applications ranging from studying the implications of cell-to-cell variability to the prediction of intersubject differences in response to pharmacological treatment. 相似文献
65.
Recent horizontal transfer of a mariner transposable element among and between Diptera and Neuroptera 总被引:11,自引:4,他引:7
Transposable elements of the mariner family are widespread among insects
and other invertebrates, and initial analyses of their relationships
indicated frequent occurrence of horizontal transfers between hosts. A
specific PCR assay was used to screen for additional members of the
irritans subfamily of mariners in more than 400 arthropod species.
Phylogenetic analysis of cloned PCR fragments indicated that relatively
recent horizontal transfers had occurred into the lineages of a fruit fly
Drosophila ananassae, the horn fly Haematobia irritans, the African malaria
vector mosquito Anopheles gambiae, and a green lacewing Chrysoperla
plorabunda. Genomic dot-blot analysis revealed that the copy number in
these species varies widely, from about 17,000 copies in the horn fly to
three copies in D. ananassae. Multiple copies were sequenced from genomic
clones from each of these species and four others with related elements.
These sequences confirmed the PCR results, revealing extremely similar
elements in each of these four species (greater than 88% DNA and 95% amino
acid identity). In particular, the consensus sequence of the transposase
gene of the horn fly elements differs by just two base pairs out of 1,044
from that of the lacewing elements. The mosquito lineage has diverged from
the other Diptera for over 200 Myr, and the neuropteran last shared a
common ancestor with them more than 265 Myr ago, so this high similarity
implies that these transposons recently transferred horizontally into each
lineage. Their presence in only the closest relatives in at least the
lacewing lineage supports this hypothesis. Such horizontal transfers
provide an explanation for the evolutionary persistence and widespread
distribution of mariner transposons. We propose that the ability to
transfer horizontally to new hosts before extinction by mutation in the
current host constitutes the primary selective constraint maintaining the
sequence conservation of mariners and perhaps other DNA-mediated elements.
相似文献
66.
In limulus sperm an actin filament bundle 55 mum in length extends from the acrosomal vacuole membrane through a canal in the nucleus and then coils in a regular fashion around the base of the nucleus. The bundle expands systematically from 15 filaments near the acrosomal vacuole to 85 filaments at the basal end. Thin sections of sperm fixed during stages in spermatid maturation reveal that the filament bundle begins to assemble on dense material attached to the acrosomal vacuole membrane. In micrographs fo these early stages in maturation, short bundles are seen extending posteriorly from the dense material. The significance is that these short, developing bundles have about 85 filaments, suggesting that the 85-filament end of the bundle is assembled first. By using filament bundles isolated and incubated in vitro with G actin from muscle, we can determine the end “preferred” for addition of actin monomers during polymerization. The end that would be associated with the acrosomal vacuole membrane, a membrane destined to be continuous with the plasma membrane, is preferred about 10 times over the other, thicker end. Decoration of the newly polymerized portions of the filament bundle with subfragment 1 of myosin reveals that the arrowheads point away from the acrosomal vacuole membrane, as is true of other actin filament bundles attached to membranes. From these observations we conclude that the bundle is nucleated from the dense material associated with the acrosomal vacuole and that monomers are added to the membrane-associated end. As monomers are added at the dense material, the thick first-made end of the filament bundle is pushed down through the nucleus where, upon reaching the base of the nucleus, it coils up. Tapering is brought about by the capping of the peripheral filaments in the bundle. 相似文献
67.
The effects of 18-crown-6 on the synthesis of peptides catalyzed by alpha-chymotrypsin are reported. Lyophilization of the enzyme in the presence of 50 equivalents of 18-crown-6 results in a 425-fold enhanced activity when the reaction between the 2-chloroethylester of N-acetyl-L-phenylalanine and L-phenylalaninamide is carried out in acetonitrile. Addition of crown ether renders the dipeptide synthesis in nonaqueous solvents catalyzed by alpha-chymotrypsin possible on a preparative scale. The acceleration is observed in different solvents and for various peptide precursors. Copyright 1998 John Wiley & Sons, Inc. 相似文献
68.
We report here the structural determination of N-linked oligosaccharides
found on extracellular hemoglobins of the hydrothermal vent tube worm
Riftia pachyptila. Structures were elucidated by a combination of
electrospray ionization tandem mass spectrometry, matrix- assisted laser
desorption/ionization mass spectrometry, normal-phase high performance
liquid chromatography, and exoglycosidase digestion. The sugar chains were
found to consist mainly of high-mannose-type glycans with some structures
partially capped by one or two terminal glucose residues. The present study
represents the first report of the occurrence of glucose capping of
N-linked carbohydrates in a secreted glycoprotein of a metazoan.
Previously, glucose capping has only been described for a membrane-bound
surface glycoprotein from the unicellular parasite Leishmania mexicana
amazonensis.
相似文献
69.
MOTIVATION: Searching a protein sequence database for homologs is a
powerful tool for discovering the structure and function of a sequence. Two
new methods for searching sequence databases have recently been described:
Probabilistic Smith-Waterman (PSW), which is based on Hidden Markov models
for a single sequence using a standard scoring matrix, and a new version of
BLAST (WU-BLAST2), which uses Sum statistics for gapped alignments.
RESULTS: This paper compares and contrasts the effectiveness of these
methods with three older methods (Smith- Waterman: SSEARCH, FASTA and
BLASTP). The analysis indicates that the new methods are useful, and often
offer improved accuracy. These tools are compared using a curated (by Bill
Pearson) version of the annotated portion of PIR 39. Three different
statistical criteria are utilized: equivalence number, minimum errors and
the receiver operating characteristic. For complete-length protein query
sequences from large families, PSW's accuracy is superior to that of the
other methods, but its accuracy is poor when used with partial-length query
sequences. False negatives are twice as common as false positives
irrespective of the search methods if a family-specific threshold score
that minimizes the total number of errors (i.e. the most favorable
threshold score possible) is used. Thus, sensitivity, not selectivity, is
the major problem. Among the analyzed methods using default parameters, the
best accuracy was obtained from SSEARCH and PSW for complete-length
proteins, and the two BLAST programs, plus SSEARCH, for partial-length
proteins.
相似文献
70.
Ghirri P Ladaki C Bartoli A Scirè G Vuerich M Spadoni GL Maiorana A Geremia C Boldrini A Cianfarani S 《Hormone research》2007,67(3):123-131
BACKGROUND/AIMS: Our aim was to investigate glucose homeostasis, insulin sensitivity and insulin-like growth factor (IGF) system status in children born small for gestational age (SGA). METHODS: A case-control study was carried out at birth, infancy and childhood, comparing SGA with children appropriate for gestational age strictly matched for age, gender, pubertal status and body mass index. Ninety newborns, 52 infants, and 68 children were studied. Fasting insulin (I(F)), fasting glucose (G(F)) to I(F) ratio (G(F)/I(F)), the homeostasis model assessment of insulin sensitivity, the quantitative insulin sensitivity check index, insulinogenic index and the triglyceride/high-density lipoprotein-cholesterol ratio were measured. IGF-I, IGF-binding protein-3 and the IGF-I/IGF-binding protein-3 molar ratio were assessed. RESULTS: Glucose concentrations were lower in SGA newborns (p < 0.0001), infants (p = 0.01), and children (p = 0.001). Birth weight correlated with glucose levels at birth (r = 0.59, p < 0.0001), 12 months (r = 0.29, p = 0.04) and childhood (r = 0.44, p < 0.0001). CONCLUSION: Our results provide evidence for a developmental adaptation of glucose metabolism in SGA children leading to reduced glucose concentrations. 相似文献