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41.
A change of mind in response to social influence could be driven by informational conformity to increase accuracy, or by normative conformity to comply with social norms such as reciprocity. Disentangling the behavioural, cognitive, and neurobiological underpinnings of informational and normative conformity have proven elusive. Here, participants underwent fMRI while performing a perceptual task that involved both advice-taking and advice-giving to human and computer partners. The concurrent inclusion of 2 different social roles and 2 different social partners revealed distinct behavioural and neural markers for informational and normative conformity. Dorsal anterior cingulate cortex (dACC) BOLD response tracked informational conformity towards both human and computer but tracked normative conformity only when interacting with humans. A network of brain areas (dorsomedial prefrontal cortex (dmPFC) and temporoparietal junction (TPJ)) that tracked normative conformity increased their functional coupling with the dACC when interacting with humans. These findings enable differentiating the neural mechanisms by which different types of conformity shape social changes of mind.When we change our mind in response to other people’s opinion, we may be motivated to be correct or to have a good relationship with others. This fMRI study disentangles the neurobiological underpinnings of these two different motives in the human brain, and shows that the second motive is absent when we interact with computers. 相似文献
42.
Michelle P. Clark Thao Huynh Shringar Rao Liana Mackiewicz Hugh Mason Shahla Romal Michael D. Stutz Sang H. Ahn Linda Earnest Vitina Sozzi Margaret Littlejohn Bang M. Tran Norbert Wiedemann Elizabeth Vincan Joseph Torresi Hans J. Netter Tokameh Mahmoudi Peter Revill Marc Pellegrini Gregor Ebert 《Cell death & disease》2021,12(7)
A major unmet clinical need is a therapeutic capable of removing hepatitis B virus (HBV) genome from the liver of infected individuals to reduce their risk of developing liver cancer. A strategy to deliver such a therapy could utilize the ability to target and promote apoptosis of infected hepatocytes. Presently there is no clinically relevant strategy that has been shown to effectively remove persistent episomal covalently closed circular HBV DNA (cccDNA) from the nucleus of hepatocytes. We used linearized single genome length HBV DNA of various genotypes to establish a cccDNA-like reservoir in immunocompetent mice and showed that clinical-stage orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins can eliminate HBV replication and episomal HBV genome in the liver. Primary human liver organoid models were used to confirm the clinical relevance of these results. This study underscores a clinically tenable strategy for the potential elimination of chronic HBV reservoirs in patients.Subject terms: Target validation, Hepatitis B, Preclinical research, Translational research 相似文献
43.
Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies 总被引:13,自引:0,他引:13
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Bang ML Mudry RE McElhinny AS Trombitás K Geach AJ Yamasaki R Sorimachi H Granzier H Gregorio CC Labeit S 《The Journal of cell biology》2001,153(2):413-427
We describe here a novel sarcomeric 145-kD protein, myopalladin, which tethers together the COOH-terminal Src homology 3 domains of nebulin and nebulette with the EF hand motifs of alpha-actinin in vertebrate Z-lines. Myopalladin's nebulin/nebulette and alpha-actinin-binding sites are contained in two distinct regions within its COOH-terminal 90-kD domain. Both sites are highly homologous with those found in palladin, a protein described recently required for actin cytoskeletal assembly (Parast, M.M., and C.A. Otey. 2000. J. Cell Biol. 150:643-656). This suggests that palladin and myopalladin may have conserved roles in stress fiber and Z-line assembly. The NH(2)-terminal region of myopalladin specifically binds to the cardiac ankyrin repeat protein (CARP), a nuclear protein involved in control of muscle gene expression. Immunofluorescence and immunoelectron microscopy studies revealed that myopalladin also colocalized with CARP in the central I-band of striated muscle sarcomeres. Overexpression of myopalladin's NH(2)-terminal CARP-binding region in live cardiac myocytes resulted in severe disruption of all sarcomeric components studied, suggesting that the myopalladin-CARP complex in the central I-band may have an important regulatory role in maintaining sarcomeric integrity. Our data also suggest that myopalladin may link regulatory mechanisms involved in Z-line structure (via alpha-actinin and nebulin/nebulette) to those involved in muscle gene expression (via CARP). 相似文献
44.
Growth hormone treatment downregulates serum leptin levels in children independent of changes in body mass index 总被引:3,自引:0,他引:3
The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 +/- 2.4 to 28 +/- 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance. 相似文献
45.
We investigated the molecular mechanism of the glucose effect on the regulation of chondrogenesis. Exposure of chick wing bud mesenchymal cells to high concentrations of glucose stimulated chondrogenesis 2–fold to 2.5-fold without affecting cell proliferation. Glucose increased protein levels and the membrane translocation of protein kinase C alpha (PKC), leading to a reduction of extracellular signal-regulated kinase (ERK) phosphorylation. Phosphorylation of p38 was also increased in a PKC-independent manner by glucose treatment. Glucose also increased cell adhesion molecules such as fibronectin, integrin 1, and N-cadherin at early stages and then decreased these adhesion molecules at later stages of chondrogenesis. These alterations in protein level of adhesion molecules and in the phosphorylation of mitogen-activated protein kinases by glucose were blocked by inhibition of PKC or p38 but were synergistically increased by the inhibition of ERK. Therefore, high doses of glucose induce the down-regulation of ERK activity via PKC and the up-regulation of p38 and result in the stimulation of chondrogenesis of chick mesenchymal cells through modulating the expression of adhesion molecules.This work was supported by the Korea Research Foundation (KRF-2000-DP0352) 相似文献
46.
Identification and characterization of a novel angiostatin-binding protein by the display cloning method 总被引:3,自引:0,他引:3
Angiostatin is a potent anti-angiogenic protein. To examine the angiostatin-interacting proteins, we used the display-cloning method with a T7 phage library presenting human cDNAs. The specific T7 phage clone that bound to the immobilized angiostatin was isolated, and a novel gene encoding the displayed polypeptide on the isolated T7 phage was identified. The displayed angiostatin-binding sequence was expressed in E. coli as a soluble protein and purified to homogeneity. This novel angiostatin-binding region interacted specifically to angiostatin with a dissociation constant of 3.4 x 10(-7) M. A sequence analysis showed that the identified sequence was a part of the large ORF of 1,998 amino acids, whose function has not yet been characterized. A Northern analysis indicated that the gene containing the angiostatin-binding sequence was expressed differentially in the developmental stages or cell types. 相似文献
47.
Chang?Jae?Oh Hyoungseok?Lee Ho?Bang?Kim Chung?Sun?AnEmail author 《Journal of Plant Biology》2004,47(3):216-220
We have determined that a nodule-specific cDNA clone (GmCysP1), obtained from a soybean root nodule-specific EST pool, encodes cysteine proteinase. Its amino acid sequence homology, as
well as the conservation of typical motifs and amino acid residues involved in active site formation, shows that GmCysP1 can
be classified as a legumain (C13) family cysteine proteinase, belonging to clan CD. Moreover, based on its expression patterns,GmCysP1 is a nodule-specific cysteine proteinase gene that is possibly associated with nodule development or senescence. Our genomic
Southern analysis also suggests thatGmCysP1 is a member of a multigene family. Therefore, we propose that GmCysP1 is the first to be identified as a nodule-specific
and senescence-related cysteine proteinase that belongs to the legumain family from soybean. 相似文献
48.
Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection ofKlebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetyl-cysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-, IL-1, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-, IL-1, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-, IL-1, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment. 相似文献
49.
The locus ceruleus (LC) contains a high density of angiotensin II (All) receptors. The role of All receptors at the LC in genetic hypertension and organ function is unclear. Spontaneously hypertensive (SHR) rats and Wistar-Kyoto (WKY) rats were studied, and blood pressure of animals was measured using the tail-cuff method. Animals were decapitated and the heart weight (HW) and testicular weight (TW) of animals measured. All receptor binding was carried out by incubating the LC tissue sections with 200 pM [125I]-All receptor ligand, and measured using quantitative autoradiography. Results showed that the HW/BW ratio was significantly higher in SHR rats than WKY rats. However, the TW/BW ratio was higher in SHR rats than WKY rats only at two hypertensive stages, whereas All receptor binding capacity in the LC was also statistically higher in SHR rats than WKY rats. Results indicated that cardiac and testicular hypertrophies were related to higher All receptor binding in the LC of SHR rats, when compared with WKY rats. Interestingly, the literature shows that there is an LC-testes axis. In conclusion, this study indicated that All receptors in the LC are associated with genetic hypertension, and testicular weight could be a reasonable index for essential hypertension. 相似文献
50.
Maiti K Li JH Wang AF Acharjee S Kim WP Im WB Kwon HB Seong JY 《Molecules and cells》2003,16(2):173-179
Recently, we identified three types of non-mammalian gonadotropin-releasing hormone receptors (GnRHR) in the bullfrog (designated bfGnRHR-1-3), and a mammalian type-II GnRHR in green monkey cell lines (denoted gmGnRHR-2). All these receptors responded better to GnRH-II than GnRH-I, while mammalian type-I GnRHR showed greater sensitivity to GnRH-I than GnRH-II. In the present study, we designed new GnRH-II analogs and examined whether they activated or inhibited non-mammalian and mammalian type-II GnRHRs. [D-Ala6]GnRH-II, with D-Ala substituted for Gly6 in GnRH-II, increased inositol phosphate (IP) production in cells stably expressing non-mammalian GnRHRs more effectively than native GnRH-II. However, it exhibited lower activity for mammalian type-I GnRHR than GnRH-I itself. Trptorelix-1, a GnRH-II antagonist, inhibited GnRH-induced IP production in cells expressing non-mammalian GnRHRs more effectively than Cetrorelix, a GnRH-I antagonist. Trptorelix-1, however, had lower potency for mammalian type-I GnRHR than Cetrorelix. Ligand-receptor binding assays revealed that [D-Ala6]GnRH-II and Trptorelix-1 have higher affinities for non-mammalian GnRHRs but lower affinities for mammalian type-I GnRHR than GnRH-II and Cetrorelix, respectively. Moreover, [D-Ala6]GnRH-II and Trptorelix-1 had a higher affinity for gmGnRHR-2 than GnRH-II and Cetrorelix, respectively. These results indicate that [D-Ala6]GnRH-II and Trptorelix-1 are highly effective agonist and antagonist, respectively, for non-mammalian and type-II mammalian GnRHRs. 相似文献