22 research outputs found

    A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.</p> <p>Methods</p> <p>We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene <it>FANCM </it>(ORs 1.9-2.0, <it>P </it>= 0.003-0.004) and 2 SNPs downstream of the growth hormone gene <it>GH1 </it>(OR 1.6, <it>P </it>= 0.002; OR 0.5, <it>P </it>= 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: <it>MDM2</it>, <it>MPG</it>, <it>FGF2</it>, <it>FGFR3</it>, <it>GNRH2</it>, and <it>IGF1</it>.</p> <p>Conclusions</p> <p>Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.</p

    Chi controlla i controllori? Una rivisitazione del concetto di «top-down» nelle funzioni esecutive e relative implicazioni per lo sviluppo cognitivo tipico e atipico

    No full text
    Classicamente le funzioni esecutive, o controllo cognitivo (CC), sono state associate all’azione top-down di meccanismi di controllo cognitivo che consentono la messa in atto consapevole di comportamento organizzato sulla base di richieste esplicite. Questi meccanismi sono stati tradizionalmente contrapposti a quelli automatici, impliciti e bottom-up dell’apprendimento associativo. Nel presente lavoro si ripercorrono i principali contributi che hanno supportato tale visione teorica per introdurre di seguito la recente «Prospettiva dell’Apprendimento sul Controllo Cognitivo» (Abrahamse et al., 2016), che adotta una visione dimensionale del CC considerato come proprietĂ  emergente del sistema cognitivo, in parte plasmato dalle caratteristiche implicite di regolaritĂ  e contingenza presenti nell’ambiente. All’interno di questa prospettiva i meccanismi impliciti assumono un ruolo centrale nel costruire la capacitĂ  di usare un comportamento finalizzato e consentono una gestione ottimale delle risorse cognitive grazie all’adozione di strategie di controllo reattive e proattive. Infine, vengono discusse le implicazioni di questa nuova corrente teorica per le traiettorie di sviluppo e le possibili applicazioni nella pratica clinica

    Little fast, little slow, should I stay or should I go? Adapting cognitive control to local-global temporal prediction across typical development

    No full text
    Adaptive cognitive control (CC), the ability to adjust goal-directed behavior according to changing environmental demand, can be instantiated bottom-up by implicit knowledge, including temporal predictability of task-relevant events. In S1-S2 tasks, either local (trial-by-trial hazard expectation) or global (block-by-block expectation) temporal information can induce prediction, allowing for proactive action control. Recent developmental evidence showed that adaptive CC based on global temporal prediction emerges earlier than when it is based on the local one only. However, very little is known about how children learn to dynamically adjust behavior on the fly according to changing global predictive information. Addressing this issue is nevertheless crucial to unravel the mechanisms underlying adaptive CC flexibility. Here we used a modified version of the Dynamic Temporal Prediction task to investigate how typically developing younger (6-8 years) and older children (9-11 years), adolescents (12-15 years) and adults (21-31 years) use global prediction to shape adaptive CC over time. Specifically, the short-long percentage of S2 preparatory intervals was manipulated list-wide to create a slow-fast-slow-fast fixed block sequence and test how efficiently the response speed adapted accordingly. Overall, results revealed that in all groups behavioral performance is successfully adjusted as a function of global prediction in the late phase of the task (block 3 to 4). Remarkably, only adolescents and adults exhibit an early adaptation of adaptive CC (block 1 to 2), while children younger than 11 show sluggish ability in inferring implicit changes in global predictive rules. This age-related dissociation suggests that, although being present from an early age, adaptive CC based on global predictive information needs more developmental space to become flexible in an efficient way. In the light of a neuroconstructivist approach, we suggest that bottom-up driven implicit flexibility may represent a key prerequisite for the development of efficient explicit cognitive control

    Adaptive Cognitive Control in Prematurely Born Children: An HD-EEG Investigation

    No full text
    Preterm birth is a neurodevelopmental risk condition often associated with cognitive control (CC) impairment. Recent evidence showed that CC can be implicitly adapted through associative learning. In the present study we investigated the ability to flexibly adjust CC as a function of implicit stimulus-response temporal regularities in preterm (PT; N = 21; mean age 8 ± 1.3 years; gestational age 30 ± 18.5 weeks) and full-term (FT; N = 20; mean age 8 ± 1.3 years) school-age children. All children underwent an HD-EEG recording while undergoing the Dynamic Temporal Prediction (DTP) task, a simple S1-S2 detection task purposely designed to generate local-global temporal predictability of imperative stimuli. The Wisconsin card sorting test (WCST) was administered to measure explicit CC. The PT group showed more premature and slower (DTP) as well as perseverative (WCST) responses than the FT group. Moreover, pre-terms showed poor adaptive CC as revealed by less efficient global response-speed adjustment. This behavioral pattern was mirrored by a reduced and less sensitive to global manipulation anticipatory Contingent Negative Variation (CNV) and by different cortical source recruitment. These findings suggest that implicit CC may be a reliable endophenotypic marker of atypical cognitive development associated with preterm birth

    Functional Fibronectin Adsorption on Aptamer-Doped Chitosan Modulates Cell Morphology by Integrin-Mediated Pathway

    No full text
    A decisive step in cell-biomaterial interaction is represented by the adsorption of proteins at the interface, whose fine control may be useful to trigger proper cell response. To this purpose, we can selectively control protein adsorption on biomaterials by means of aptamers. Aptamers selected to recognize fibronectin dramatically enhance chitosan ability to promote cell proliferation and adhesion, but the underlying biological mechanism remains unknown. We supposed that aptamers contributed to ameliorate the adsorption of fibronectin in an advantageous geometrical conformation for cells, thus regulating their morphology by the proper activation of the integrin-mediated pathway. We investigated this possibility by culturing epithelial cells on chitosan enriched with increasing doses of aptamers in the presence or in the absence of cytoskeleton pharmacological inhibitors. Our results showed that aptamers control cell morphology in a dose dependent manner (p &lt; 0.0001). Simultaneously, when the inhibition of actin polymerization was induced, the control of cell morphology was attenuated (p &lt; 0.0001), while no differences were detected when cells contractility was challenged (p &gt; 0.05). Altogether, our data provide evidence that aptamers contribute to control fibronectin adsorption on biomaterials by preserving its conformation and thus function. Furthermore, our work provides a new insight into a new way to accurately tailor material surface bioactivity
    corecore