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141.
Objective: The purpose of this study was to determine whether chronic energy deficiency achieved with caloric restriction combined with exercise is associated with changes in the 24‐hour profile of ghrelin in non‐obese, pre‐menopausal women. Research Methods and Procedures: Twelve non‐obese (BMI = 18 to 25 kg/m2), non‐exercising women (age, 18 to 24 years) were randomly assigned to a non‐exercising control group or a diet and exercise group. The 3‐month diet and exercise intervention yielded a daily energy deficit of ?45.7 ± 12.4%. Serial measurements were made of body composition, energy balance, and feelings of fullness. Repeated blood sampling over 24 hours to measure ghrelin occurred before and after the study. Results: Significant decreases in body weight, body fat, and feelings of fullness were observed in only the energy‐deficit group (p < 0.05); significant changes in the following ghrelin features were found in only the deficit group (p < 0.05): elevations in baseline (+353 ± 118 pg/mL), lunch peak (+370 ± 102 pg/mL), dinner peak (+438 ± 149 pg/mL), nocturnal rise (+269 ± 77 pg/mL), and nocturnal peak (+510 ± 143 pg/mL). In addition, we found a larger dinner decline (?197 ± 52 pg/mL) and negative correlations between changes in the ghrelin dinner profile and changes in body weight (R = 0.784), 24‐hour intake (R = 0.67), energy deficiency (R = 0.762), and feelings of fullness (R = 0.648; p < 0.05). Discussion: Changes in ghrelin concentrations across the day after weight loss are closely associated with other physiological adaptations to energy deficiency, further supporting the role of ghrelin as a countermeasure to restore energy balance. 相似文献
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143.
Tien AC Tsai HH Molofsky AV McMahon M Foo LC Kaul A Dougherty JD Heintz N Gutmann DH Barres BA Rowitch DH 《Development (Cambridge, England)》2012,139(14):2477-2487
Expansion of astrocyte populations in the central nervous system is characteristic of evolutionarily more complex organisms. However, regulation of mammalian astrocyte precursor proliferation during development remains poorly understood. Here, we used Aldh1L1-GFP to identify two morphologically distinct types of proliferative astrocyte precursors: radial glia (RG) in the ventricular zone and a second cell type we call an 'intermediate astrocyte precursor' (IAP) located in the mantle region of the spinal cord. Astrogenic RG and IAP cells proliferated in a progressive ventral-to-dorsal fashion in a tight window from embryonic day 13.5 until postnatal day 3, which correlated precisely with the pattern of active ERK signalling. Conditional loss of BRAF function using BLBP-cre resulted in a 20% decrease in astrocyte production, whereas expression of activated BRAFV600E resulted in astrocyte hyperproliferation. Interestingly, BRAFV600E mitogenic effects in astrocytes were restricted, in part, by the function of p16INK4A-p19(ARF), which limited the temporal epoch for proliferation. Together, these findings suggest that astrocyte precursor proliferation involves distinct RG and IAP cells; is subjected to temporal and spatial control; and depends in part on BRAF signalling at early stages of mammalian spinal cord development. 相似文献
144.
Dougherty ER 《BioEssays : news and reviews in molecular, cellular and developmental biology》2012,34(4):277-279
Is a two-fold approach - preliminary studies based on small samples followed by a large-sample study to check reproducibility - in the search for biomarkers really prudent? 相似文献
145.
The enzyme fructose-1,6-bisphosphatase (FBP) is key regulatory point in gluconeogenesis. Mutants of Salmonella enterica lacking purH accumulate 5-amino-4-imidazole carboxamide ribotide (AICAR) and are unable to utilize glycerol as sole carbon and energy sources. The work described here demonstrates this lack of growth is due to inhibition of FBP by AICAR. Mutant alleles of fbp that restore growth on glycerol encode proteins resistant to inhibition by AICAR and the allosteric regulator AMP. This is the first report of biochemical characterization of substitutions causing AMP resistance in a bacterial FBP. Inhibition of FBP activity by AICAR occurs at physiologically relevant concentrations and may represent a form of regulation of gluconeogenic flux in Salmonella enterica. 相似文献
146.
Ahern CA Eastwood AL Lester HA Dougherty DA Horn R 《The Journal of general physiology》2006,128(6):649-657
Open-channel blockers such as tetraethylammonium (TEA) have a long history as probes of the permeation pathway of ion channels. High affinity blockade by extracellular TEA requires the presence of an aromatic amino acid at a position that sits at the external entrance of the permeation pathway (residue 449 in the eukaryotic voltage-gated potassium channel Shaker). We investigated whether a cation-pi interaction between TEA and such an aromatic residue contributes to TEA block using the in vivo nonsense suppression method to incorporate a series of increasingly fluorinated Phe side chains at position 449. Fluorination, which is known to decrease the cation-pi binding ability of an aromatic ring, progressively increased the inhibitory constant K(i) for the TEA block of Shaker. A larger increase in K(i) was observed when the benzene ring of Phe449 was substituted by nonaromatic cyclohexane. These results support a strong cation-pi component to the TEA block. The data provide an empirical basis for choosing between Shaker models that are based on two classes of reported crystal structures for the bacterial channel KcsA, showing residue Tyr82 in orientations either compatible or incompatible with a cation-pi mechanism. We propose that the aromatic residue at this position in Shaker is favorably oriented for a cation-pi interaction with the permeation pathway. This choice is supported by high level ab initio calculations of the predicted effects of Phe modifications on TEA binding energy. 相似文献
147.
The regulation of intracellular calcium by the endoplasmic reticulum (ER) plays a critical role in neuronal function. While the consequences associated with depleting calcium from the ER have been studied in multiple systems, it is not known whether the intrinsic properties of a neuron change in response to such perturbations. In this study, we demonstrate that the depletion of calcium from the ER of hippocampal CA1 pyramidal neurons induces a persistent, perisomatic increase in the density of functional h channels resulting in a reduction in intrinsic excitability and an increase in the optimal response frequency. This form of intrinsic plasticity is dependent on the elevation of cytoplasmic calcium, inositol triphosphate receptors, store-operated calcium channels, and the protein kinase A pathway. We postulate that this form of depletion-induced intrinsic plasticity is a neuroprotective mechanism that reduces excitability after depletion of calcium stores triggered through altered network activity during pathological conditions. 相似文献
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149.
MOTIVATION: A key goal of studying biological systems is to design therapeutic intervention strategies. Probabilistic Boolean networks (PBNs) constitute a mathematical model which enables modeling, predicting and intervening in their long-run behavior using Markov chain theory. The long-run dynamics of a PBN, as represented by its steady-state distribution (SSD), can guide the design of effective intervention strategies for the modeled systems. A major obstacle for its application is the large state space of the underlying Markov chain, which poses a serious computational challenge. Hence, it is critical to reduce the model complexity of PBNs for practical applications. RESULTS: We propose a strategy to reduce the state space of the underlying Markov chain of a PBN based on a criterion that the reduction least distorts the proportional change of stationary masses for critical states, for instance, the network attractors. In comparison to previous reduction methods, we reduce the state space directly, without deleting genes. We then derive stationary control policies on the reduced network that can be naturally induced back to the original network. Computational experiments study the effects of the reduction on model complexity and the performance of designed control policies which is measured by the shift of stationary mass away from undesirable states, those associated with undesirable phenotypes. We consider randomly generated networks as well as a 17-gene gastrointestinal cancer network, which, if not reduced, has a 2(17) × 2(17) transition probability matrix. Such a dimension is too large for direct application of many previously proposed PBN intervention strategies. 相似文献
150.
Blood AJ Iosifescu DV Makris N Perlis RH Kennedy DN Dougherty DD Kim BW Lee MJ Wu S Lee S Calhoun J Hodge SM Fava M Rosen BR Smoller JW Gasic GP Breiter HC;Phenotype Genotype Project on Addiction Mood Disorders 《PloS one》2010,5(11):e13945