We here show for the first time that small-molecule inhibitors of FGFR, integrins and FAK effectively and selectively abolish L1-stimulated migration and proliferation of glioblastoma-derived cells. Our results suggest that these inhibitors have the potential to reduce the aggressiveness of high-grade gliomas expressing L1.
In schizophrenia, there is a conceptual overlap between depressive and negative symptoms. This study examined the dimensional structure of depressive symptoms and their overlap with negative symptoms in a large sample of older medicated schizophrenia outpatients. Self-reported depression was obtained with the Beck Depression Inventory-II (BDI-II). Three components from this scale (i.e., dysphoria, psychosomatic and regret domains) showed excellent factorability and good consistency. However, adequate construct validity and correlates with outcomes were found for the dysphoria and regret domains, but not for the total score or the psychosomatic domain. Thus, the evaluation of domains within the BDI-II provides a more pure and clinically-relevant assessment of depressed mood in schizophrenia than the use of this scale as a whole.
A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the fl-adrenergic agonist terbutaline and inhibitors of cyclic nucleotide phosphodiesterase. In contrast to the situation in the wild-type clone, synthesis of adenosine 3':5'- (6).Once the independence of the hormone-binding component and adenylate cyclase is assumed, the question of the mechanism of their interaction becomes paramount. Several studies have suggested that the lipid environment is important for this interaction (3,7,8), and it has been proposed that the lipid bilayer may itself act as a "transducer" coupling the receptor and the enzyme (9). Current data also suggest that a guanine-nuAbbreviations: cyclic AMP, adenosine 3':5'-cyclic monophosphate; TRM medium, growth medium containing terbutaline (0.1 mM), R020-1724 (0.03 mM), and 1-methyl-3-isobutylxanthine (0.1 mM); R020-1724, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone; IHYP, iodohydroxybenzylpindolol [hydroxybenzylpindolol is (±)-3-indoloxy-1-(2-p-hydroxybenzylpropyl-2-amino)isopropanol]; UNC, uncoupled phenotype; AC-, adenylate-cyclase-deficient phenotype; Gpp(NH)p, guanyl-5'-yl imidodiphosphate; PGEI, prostaglandin E1. cleotide-binding component may be vitally important for communication between receptors and adenylate cyclase (10).We have attempted to explore the relationship between hormone receptors and adenylate cyclase by genetic manipulation of cultured mammalian cells (11). The S49 lymphoma cell is killed by cyclic AMP or by agents that enhance its accumulation (12), and variant cells can thus be selected that are defective in the hormone-response pathway; adenylate cyclase-deficient clones have been described previously (13). Herein we report the selection and characterization of an S49 lymphoma clone with a phenotype that, to our knowledge, is novel for any adenylate cyclase system: while these cells possess both 3-adrenergic receptors and adenylate cyclase, ,-adrenergic agonists fail to alter enzymatic activity. Interaction between the ligand-binding and the catalytic functions thus appears to be lost, and the response system is permanently uncoupled.MATERIALS AND METHODS Cell Culture and Subcellular Fractionation. Methods for culture of S49 mouse cells have been described. * Growth medium was Dulbecco's modified Eagle's medium supplemented with 7.5-10% heat-inactivated horse serum. We have recently reported techniques for the rapid preparation of a relatively crude but hormone-responsive particulate fraction from these cells (6) and for the preparation of purified membranes in which specific activities of adenylate cyclase and concentrations of the ,B-adrenergic receptor are enriched 20-to 40-fold over those of the homogenate. * Isolation of Variants. It must be admitted that the first isolation of clones with the phenotype to be described (designated as uncoupled, UNC) was the result of relatively uncontrolled "pilot" studies. Wild-type S49 cells were placed in stationary suspension culture in growth medi...
Workplace-based assessment (WBA) serves a critical role in supporting competency-based medical education (CBME) by providing assessment data to inform competency decisions and support learning. Many WBA systems have been developed, but little is known about how to effectively implement WBA. Filling this gap is important for creating suitable and beneficial assessment processes that support large-scale use of CBME. As a step toward filling this gap, the authors describe what is known about WBA implementation and use to identify knowledge gaps and future directions. Method The authors used Arksey and O'Malley's 6-stage scoping review framework to conduct the review, including: (1) identifying the research question; (2) identifying relevant studies; (3) study selection; (4) charting the data; (5) collating, summarizing, and reporting the results; and (6) consulting with relevant stakeholders.
The current era of advanced computing has allowed for the development and implementation of the field of radiomics. In pediatric neuro-oncology, radiomics has been applied in determination of tumor histology, identification of disseminated disease, prognostication, and molecular classification of tumors (i.e., radiogenomics). The field also comes with many challenges, such as limitations in study sample sizes, class imbalance, generalizability of the methods, and data harmonization across imaging centers. The aim of this review paper is two-fold: first, to summarize existing literature in radiomics of pediatric neuro-oncology; second, to distill the themes and challenges of the field and discuss future directions in both a clinical and technical context.
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