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991.
While previous research has investigated the ability of animals to learn the spatial and temporal contingencies of biologically significant events (known as time-place learning), this ability has not been studied in humans. Children ranging from 5 to 10 years old were tested on a modified interval time-place learning task using a touchscreen computer. Results demonstrate the children were able to quickly learn both the timing and the sequence of this task. Despite a lack of anticipation on baseline trials, the children continued to follow the spatio-temporal contingencies in probe sessions where these contingencies were removed. Performance on the probe sessions provide strong evidence that the children had learned the spatio-temporal contingencies. Future research is needed to determine what age-related changes in iTPL occur. Furthermore, it is argued that this procedure can be used to extend interval timing in research in children, including, but not limited to, investigation of scalar timing with longer durations than have previously been investigated. 相似文献
992.
Cord F.Stehler Andreas Keller Petra Leidinger Christina Backes Anoop Chandran Jerg Wischhusen Benjamin Meder Eckart Meese 《基因组蛋白质组与生物信息学报(英文版)》2012,10(5):285-294
Co-regulation of genes has been extensively analyzed, however, rather limited knowledge is available on co-regulations within the miRNome. We investigated differential co-expression of microRNAs (miRNAs) based on miRNome profiles of whole blood from 540 individuals. These include patients suffering from different cancer and non-cancer diseases, and unaffected controls. Using hierarchi-cal clustering, we found 9 significant clusters of co-expressed miRNAs containing 2-36 individual miRNAs. Through analyzing multiple sequencing alignments in the clusters, we found that co-expression of miRNAs is associated with both sequence similarity and genomic co-localization. We calculated correlations for all 371,953 pairs of miRNAs for all 540 individuals and identified 184 pairs of miRNAs with high correlation values. Out of these 184 pairs of miRNAs, 16 pairs (8.7%) were differentially co-expressed in unaffected controls, cancer patients and patients with non-cancer diseases. By computing correlated and anti-correlated miRNA pairs, we constructed a network with 184 putative co-regulations as edges and 100 miRNAs as nodes. Thereby, we detected specific clusters of miRNAs with high and low correlation values. Our approach represents the most comprehensive co-regulation analysis based on whole miRNome-wide expression profiling. Our findings further decrypt the interactions of miRNAs in normal and human pathological processes. 相似文献
993.
Graewe S Rankin KE Lehmann C Deschermeier C Hecht L Froehlke U Stanway RR Heussler V 《PLoS pathogens》2011,7(9):e1002224
The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it is released into the bloodstream. The transition to the blood stage was previously shown to involve the packaging of exoerythrocytic merozoites into membrane-surrounded vesicles, called merosomes, which are delivered directly into liver sinusoids. However, it was unclear whether the membrane of these merosomes was derived from the parasite membrane, the parasitophorous vacuole membrane or the host cell membrane. This knowledge is required to determine how phagocytes will be directed against merosomes. Here, we fluorescently label the candidate membranes and use live cell imaging to show that the merosome membrane derives from the host cell membrane. We also demonstrate that proteins in the host cell membrane are lost during merozoite liberation from the parasitophorous vacuole. Immediately after the breakdown of the parasitophorous vacuole membrane, the host cell mitochondria begin to degenerate and protein biosynthesis arrests. The intact host cell plasma membrane surrounding merosomes allows Plasmodium to mask itself from the host immune system and bypass the numerous Kupffer cells on its way into the bloodstream. This represents an effective strategy for evading host defenses before establishing a blood stage infection. 相似文献
994.
The subtidal bivalve Glycymeris glycymeris (L.) exhibits a high degree of respiratory independence in conditions of declining environmental oxygen tension. In contrast to other bivalves previously studied, the index of respiratory independence, decreases with increasing weight specific oxygen consumption indicating that small Glycymeris are better regulators of oxygen consumption than large Glycymeris.The respiratory responses of Glycymeris to hypoxia include a small initial increase in ventilation, brought about by increasing the percentage of time spent pumping and a large increase in oxygen utilization. Heart activity is elevated, principally through a large increase in the amplitude of heart beat, which suggests increased perfusion of the respiratory surfaces. The ventilation : relative perfusion ratio, therefore, declines over the range of oxygen tension that respiratory independence is maintained.The respiratory mechanism of Glycymeris is compared with that previously described for other bivalves and it is concluded that there are no clearcut differences between the respiratory responses to hypoxia of intertidal and subtidal species. 相似文献
995.
996.
Bruylants G Wintjens R Looze Y Redfield C Bartik K 《European biophysics journal : EBJ》2007,37(1):11-18
Protonation/deprotonation equilibria are frequently linked to binding processes involving proteins. The presence of these
thermodynamically linked equilibria affects the observable thermodynamic parameters of the interaction (K
obs, ΔH
obs0). In order to try and elucidate the energetic factors that govern these binding processes, a complete thermodynamic characterisation
of each intrinsic equilibrium linked to the complexation event is needed and should furthermore be correlated to structural
information. We present here a detailed study, using NMR and ITC, of the interaction between α-chymotrypsin and one of its
competitive inhibitors, proflavin. By performing proflavin titrations of the enzyme, at different pH values, we were able
to highlight by NMR the effect of the complexation of the inhibitor on the ionisable residues of the catalytic triad of the
enzyme. Using ITC we determined the intrinsic thermodynamic parameters of the different equilibria linked to the binding process.
The possible driving forces of the interaction between α-chymotrypsin and proflavin are discussed in the light of the experimental
data and on the basis of a model of the complex. This study emphasises the complementarities between ITC and NMR for the study
of binding processes involving protonation/deprotonation equilibria.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
997.
Abdominal obesity in BTBR male mice is associated with peripheral but not hepatic insulin resistance
Flowers JB Oler AT Nadler ST Choi Y Schueler KL Yandell BS Kendziorski CM Attie AD 《American journal of physiology. Endocrinology and metabolism》2007,292(3):E936-E945
Insulin resistance is a common feature of obesity. BTBR mice have more fat mass than most other inbred mouse strains. On a chow diet, BTBR mice have elevated insulin levels relative to the C57BL/6J (B6) strain. Male F1 progeny of a B6 x BTBR cross are insulin resistant. Previously, we reported insulin resistance in isolated muscle and in isolated adipocytes in this strain. Whereas the muscle insulin resistance was observed only in male F1 mice, adipocyte insulin resistance was also present in male BTBR mice. We examined in vivo mechanisms of insulin resistance with the hyperinsulinemic euglycemic clamp technique. At 10 wk of age, BTBR and F1 mice had a >30% reduction in whole body glucose disposal primarily due to insulin resistance in heart, soleus muscle, and adipose tissue. The increased adipose tissue mass and decreased muscle mass in BTBR and F1 mice were negatively and positively correlated with whole body glucose disposal, respectively. Genes involved in focal adhesion, actin cytoskeleton, and inflammation were more highly expressed in BTBR and F1 than in B6 adipose tissue. The BTBR and F1 mice have higher levels of testosterone, which may be related to the pathological changes in adipose tissue that lead to systemic insulin resistance. Despite profound peripheral insulin resistance, BTBR and F1 mice retained hepatic insulin sensitivity. These studies reveal a genetic difference in body composition that correlates with large differences in peripheral insulin sensitivity. 相似文献
998.
Moulakakis C Adam S Seitzer U Schromm AB Leitges M Stamme C 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(7):4480-4491
The pulmonary collectin surfactant protein (SP)-A has a pivotal role in anti-inflammatory modulation of lung immunity. The mechanisms underlying SP-A-mediated inhibition of LPS-induced NF-kappaB activation in vivo and in vitro are only partially understood. We previously demonstrated that SP-A stabilizes IkappaB-alpha, the primary regulator of NF-kappaB, in alveolar macrophages (AM) both constitutively and in the presence of LPS. In this study, we show that in AM and PBMC from IkappaB-alpha knockout/IkappaB-beta knockin mice, SP-A fails to inhibit LPS-induced TNF-alpha production and p65 nuclear translocation, confirming a critical role for IkappaB-alpha in SP-A-mediated LPS inhibition. We identify atypical (a) protein kinase C (PKC) zeta as a pivotal upstream regulator of SP-A-mediated IkappaB-alpha/NF-kappaB pathway modulation deduced from blocking experiments and confirmed by using AM from PKCzeta-/- mice. SP-A transiently triggers aPKCThr(410/403) phosphorylation, aPKC kinase activity, and translocation in primary rat AM. Coimmunoprecipitation experiments reveal that SP-A induces aPKC/p65 binding under constitutive conditions. Together the data indicate that anti-inflammatory macrophage activation via IkappaB-alpha by SP-A critically depends on PKCzeta activity, and thus attribute a novel, stimulus-specific signaling function to PKCzeta in SP-A-modulated pulmonary immune response. 相似文献
999.
Feedback inhibition of pantothenate kinase regulates pantothenol uptake by the malaria parasite 总被引:1,自引:0,他引:1
Lehane AM Marchetti RV Spry C van Schalkwyk DA Teng R Kirk K Saliba KJ 《The Journal of biological chemistry》2007,282(35):25395-25405
To survive, the human malaria parasite Plasmodium falciparum must acquire pantothenate (vitamin B5) from the external medium. Pantothenol (provitamin B5) inhibits parasite growth by competing with pantothenate for pantothenate kinase, the first enzyme in the coenzyme A biosynthesis pathway. In this study we investigated pantothenol uptake by P. falciparum and in doing so gained insights into the regulation of the parasite's coenzyme A biosynthesis pathway. Pantothenol was shown to enter P. falciparum-infected erythrocytes via two routes, the furosemide-inhibited "new permeation pathways" induced by the parasite in the infected erythrocyte membrane (the sole access route for pantothenate) and a second, furosemide-insensitive pathway. Having entered the erythrocyte, pantothenol is taken up by the intracellular parasite via a mechanism showing functional characteristics distinct from those of the parasite's pantothenate uptake mechanism. On reaching the parasite cytosol, pantothenol is phosphorylated and thereby trapped by pantothenate kinase, shown here to be under feedback inhibition control by coenzyme A. Furosemide reduced this inherent feedback inhibition by competing with coenzyme A for binding to pantothenate kinase, thereby increasing pantothenol uptake. 相似文献
1000.
Sidani SM Kirchhoff P Socrates T Stelter L Ferreira E Caputo C Roberts KE Bell RL Egan ME Geibel JP 《The Journal of biological chemistry》2007,282(9):6068-6074
The cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as a multifunctional protein that is involved in Cl(-) secretion, as well as acting as a regulatory protein. In order for acid secretion to take place a complex interaction of transport proteins and channels must occur at the apical pole of the parietal cell. Included in this process is at least one K(+) and Cl(-) channel, allowing for both recycling of K(+) for the H,K-ATPase, and Cl(-) secretion, necessary for the generation of concentrated HCl in the gastric gland lumen. We have previously shown that an ATP-sensitive potassium channel (K(ATP)) is expressed in parietal cells. In the present study we measured secretagogue-induced acid secretion from wild-type and DeltaF508-deficient mice in isolated gastric glands and whole stomach preparations. Secretagogue-induced acid secretion in wild-type mouse gastric glands could be significantly reduced with either glibenclamide or the specific inhibitor CFTR-inh172. In DeltaF508-deficient mice, however, histamine-induced acid secretion was significantly less than in wild-type mice. Furthermore, immunofluorescent localization of sulfonylurea 1 and 2 failed to show expression of a sulfonylurea receptor in the parietal cell, thus further implicating CFTR as the ATP-binding cassette transporter associated with the K(ATP) channels. These results demonstrate a regulatory role for the CFTR protein in normal gastric acid secretion. 相似文献