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  • 1
    Language: English
    In: Science (New York, N.Y.), 11 June 2010, Vol.328(5984), pp.1394-8
    Description: Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II-restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I-restricted recognition of such antigens by CD8+ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8+ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8+ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient cross-presentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing.
    Keywords: Cross-Priming ; Antigens, Viral -- Immunology ; Herpes Simplex -- Immunology ; Herpesvirus 1, Human -- Immunology ; Oxidoreductases -- Metabolism ; Viral Envelope Proteins -- Immunology
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 2
    Language: English
    In: Social Science & Medicine, September 2011, Vol.73(6), pp.889-896
    Description: This article investigates the social and moral dimensions of Attention Deficit/Hyperactivity Disorder (ADHD) diagnosis, asking what ADHD means in UK children’s everyday lives, and what children do with this diagnosis. Drawing on interviews with over 150 children, the analysis examines the influence of a UK state school-based culture of aggression on the form and intensity of diagnosed children’s difficulties with behavioral self-control. Diagnosed children’s mobilization of ADHD behaviors and their exploitation of the diagnosis shows how children’s active moral agency can support and compromise cognitive, behavioral and social resilience. The findings support a proposal for a complex sociological model of ADHD diagnosis and demonstrate the relevance of this model for national policy initiatives related to mental health and wellbeing in children. ► In the UK, ADHD is understood to be a disorder of anger and aggression. ► A UK state school-based culture of aggression intensifies children’s difficulty controlling their behavior. ► Children use ADHD diagnosis and symptomatic behaviors to social and moral ends. ► Children rely on friendships to help manage their difficulty with self-control. ► Mental health policy should address the social and moral, as well as the cognitive aspects of ADHD diagnosis.
    Keywords: United Kingdom ; Attention Deficit/Hyperactivity Disorder ; ADHD ; Diagnosis ; Stigma ; Aggression ; Bullying ; Mental Capital ; Children ; Medicine ; Social Sciences (General) ; Public Health
    ISSN: 0277-9536
    E-ISSN: 1873-5347
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  • 3
    In: Child Development, March 2014, Vol.85(2), pp.755-766
    Description: The interconnectedness of bilingual memory remains a topic of great debate. Semantic priming provides a powerful methodological tool with which to investigate this issue in early bilingual toddlers. Semantic priming effects were investigated in 21 bilingual toddlers (2.5 years) within and across each of their languages. Results revealed the first evidence of cross‐language and within‐language semantic priming in bilingual toddlers. However, priming effects were only observed when the prime was presented in the dominant language and were comparable in magnitude within and across languages. Findings point to high interconnectivity across languages; however, there appear to be strong influences of language dominance on semantic facilitation. Findings serve to inform and refine developmental models of bilingual memory.
    Keywords: Toddlers -- Analysis;
    ISSN: 0009-3920
    E-ISSN: 1467-8624
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  • 4
    Language: English
    In: American journal of public health, September 2012, Vol.102(9), pp.e15-8
    Description: I have explored the debates on evidence-based oral health promotion and examined the practicality of promoting oral health care within a whole system (social, cultural, and environmental) approach. The use of evidence-based decision-making in health services and planning is a viable mechanism to identify optimal health benefits; however, barriers to the effective adoption of evidence-based health practice, including barriers that apply to oral health promotion, have been identified. Evidence-based oral health promotion highlights the importance of examining health promotion activities within a defined social context-a departure from the focus on improving study designs and research methods. Thus, the basis for evidence in health activities is grounded in social and organizational systems. This could contribute to sustainable health efforts.
    Keywords: Evidence-Based Medicine -- Standards ; Health Promotion -- Methods ; Oral Health -- Standards
    ISSN: 00900036
    E-ISSN: 1541-0048
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  • 5
    Language: English
    In: Journal of the American College of Cardiology, 26 May 2015, Vol.65(20), pp.2225-2238
    Description: Bleeding avoidance strategies for percutaneous coronary interventions continue to evolve with the availability of newer antiplatelet and anticoagulation therapies. Advances in interventional practices have altered the balance between ischemic and bleeding complications. With the availability of rapidly-acting platelet adenosine diphosphate–receptor antagonists, the need for routine glycoprotein IIb/IIIa inhibitors has diminished. Recent meta-analyses and trials have advanced our knowledge of vascular access and different anticoagulation regimens. Vascular closure devices have long been used for early ambulation; however, more recent results demonstrating lower bleeding complications from observational registries are encouraging. This review synthesizes this information, taking into account changes in the landscape of interventional practice with respect to current bleeding avoidance strategies.
    Keywords: Anticoagulants ; Platelet Aggregation Inhibitors ; Thrombosis ; Vascular closure Devices ; Medicine
    ISSN: 0735-1097
    E-ISSN: 1558-3597
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  • 6
    In: Genes, Chromosomes and Cancer, December 2014, Vol.53(12), pp.999-1007
    Description: Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis. These cancers are deficient in glucocorticoid receptor () expression, and therefore, resistant to glucocorticoids. Overexpression of the both in vivo and in vitro leads to apoptotic cell death suggesting that loss of is favorable for cancer growth. Indeed, the promoter is silenced in SCLC cells by methylation. We now show that treatment of the SCLC cell line (DMS79) cells with the demethylating agent, 5‐aza‐2′‐deoxycytidine (5‐aza), results in significant endogenous re‐expression of both α and the ligand‐independent . The gene has a complex promoter region comprising nine alternative promoters, the proximal seven of which lie within a CpG island. The endogenous re‐expression seen is attributed to the constitutive promoters 1B and 1C and 1J but predominantly 1F, which we show to be heavily methylated in SCLC cells. Flow cytometric analysis using the apoptotic marker, Annexin V, shows that this endogenous re‐expression is sufficient to drive the SCLC cells to apoptosis. Apoptotic induction is specific to re‐expression as cotreatment with 5‐aza and the antagonist, RU486 prevented apoptosis. Of the three functional GR domains (the DNA binding domain, ligand binding domain, and transactivation domain), we identified that the transactivation domain is essential for apoptosis in SCLC. The discovery that endogenous re‐expression of the GR in SCLC cells is sufficient to induce apoptotic cell death by reversing a cancer‐driven DNA methylation effect may lead to the development of novel adjunct therapies. © 2014 Wiley Periodicals, Inc.
    Keywords: Lung Cancer – Analysis ; Methylation – Analysis ; Glucocorticoids – Analysis ; Apoptosis – Analysis ; Steroids (Organic Compounds) – Analysis;
    ISSN: 1045-2257
    E-ISSN: 1098-2264
    E-ISSN: 10916490
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  • 7
    In: Child Development, July 2018, Vol.89(4), pp.e397-e413
    Description: Prior research suggests that bilingualism may endow infants with greater phonological flexibility. This study investigated whether this flexibility facilitates word learning in additional languages ( = 96). Experiment 1 compared 18‐ to 20‐month‐old monolingual (English) and bilingual (English/Mandarin) infants on their ability to learn words distinguished by click consonants from a Southern African language, Ndebele. English–Mandarin bilingual infants were sensitive to Ndebele click contrasts, but monolingual English infants were not. In Experiments 2a and 2b, we investigated whether enhanced bilingual sensitivity extended to analogous nonlinguistic labels: hand claps and finger snaps. Although discriminated by infants, neither group distinguished words labeled by hand claps and finger snaps. Results suggest that bilingual infants' sustained openness to non native contrast may facilitate the uptake of words in distant languages.
    Keywords: Bilingualism ; Infants;
    ISSN: 0009-3920
    E-ISSN: 1467-8624
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  • 8
    Language: English
    In: Nature, September 2018, Vol.561(7723), pp.295-296
    Description: Analysis of thousands of submissions to eLife journal shows that these groups are also under-represented as senior authors and editors. Analysis of thousands of journal submissions at eLife journal shows that these groups are also under-represented as senior authors and editors.
    Keywords: Peer Review ; Periodicals As Topic
    ISSN: 00280836
    E-ISSN: 1476-4687
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  • 9
    Language: English
    In: Science (New York, N.Y.), 25 January 2013, Vol.339(6118), pp.446-8
    Description: The human genome contains ~50 genes that were derived from transposable elements or transposons, and many are now integral components of cellular gene expression programs. The human THAP9 gene is related to the Drosophila P-element transposase. Here, we show that human THAP9 can mobilize Drosophila P-elements in both Drosophila and human cells. Chimeric proteins formed between the Drosophila P-element transposase N-terminal THAP DNA binding domain and the C-terminal regions of human THAP9 can also mobilize Drosophila P elements. Our results indicate that human THAP9 is an active DNA transposase that, although "domesticated," still retains the catalytic activity to mobilize P transposable elements across species.
    Keywords: DNA Transposable Elements ; Transposases -- Genetics
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 10
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 13 December 2016, Vol.113(50), pp.14414-14419
    Description: The number of joints and muscles in a human arm is more than what is required for reaching to a desired point in 3D space. Although previous studies have emphasized how such redundancy and the associated flexibility may play an important role in path planning, control of noise, and optimization of motion, whether and how redundancy might promote motor learning has not been investigated. In this work, we quantify redundancy space and investigate its significance and effect on motor learning. We propose that a larger redundancy space leads to faster learning across subjects. We observed this pattern in subjects learning novel kinematics (visuomotor adaptation) and dynamics (force-field adaptation). Interestingly, we also observed differences in the redundancy space between the dominant hand and nondominant hand that explained differences in the learning of dynamics. Taken together, these results provide support for the hypothesis that redundancy aids in motor learning and that the redundant component of motor variability is not noise.
    Keywords: Minimum-Intervention Principle ; Motor Control ; Motor Noise ; Reaching ; Supervised Learning ; Learning -- Physiology ; Motor Skills -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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