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1

Article

Defective cross-presentation of viral antigens in GILT-free mice (2010)

Singh, Reshma ; Cresswell, Peter

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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

DOI: 10.1126/science.1189176

URL: View this record in MEDLINE/PubMed

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2

Article

A disorder of anger and aggression: Children’s perspectives on attention deficit/hyperactivity disorder in the UK (2011)

Singh, Ilina

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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

DOI: 10.1016/j.socscimed.2011.03.049

URL: View record in ScienceDirect (Access to full text may be restricted)

URL: View full text in ScienceDirect

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3

Article

One World, Two Languages: Cross‐Language Semantic Priming in Bilingual Toddlers (2014)

Singh, Leher

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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

DOI: 10.1111/cdev.12133

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4

Article

Role of RAG1 autoubiquitination in V(D)J recombination (2015)

Singh, Samarendra K ; Gellert, Martin

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Language: English

In: Proceedings of the National Academy of Sciences of the United States of America, 14 July 2015, Vol.112(28), pp.8579-83

Description: The variable domains of Ig and T-cell receptor genes in vertebrates are assembled from gene fragments by the V(D)J recombination process. The RAG1-RAG2 recombinase (RAG1/2) initiates this recombination by cutting DNA at the borders of recombination signal sequences (RSS) and their neighboring gene segments. The RAG1 protein is also known to contain a ubiquitin E3 ligase activity, located in an N-terminal region that is not strictly required for the basic recombination reaction but helps to regulate recombination. The isolated E3 ligase domain was earlier shown to ubiquitinate one site in a neighboring RAG1 sequence. Here we show that autoubiquitination of full-length RAG1 at this specific residue (K233) results in a large increase of DNA cleavage by RAG1/2. A mutational block of the ubiquitination site abolishes this effect and inhibits recombination of a test substrate in mouse cells. Thus, ubiquitination of RAG1, which can be promoted by RAG1's own ubiquitin ligase activity, plays a significant role in governing the level of V(D)J recombination activity.

Keywords: Diversification ; Immunoglobulin ; Ubiquitin ; Ubiquitination ; V(D)J Recombination ; Homeodomain Proteins -- Metabolism

ISSN: 00278424

E-ISSN: 1091-6490

DOI: 10.1073/pnas.1510464112

URL: View this record in MEDLINE/PubMed

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5

Article

Chain packing in glassy polymers by natural-abundance 13C-13C spin diffusion using 2D centerband-only detection of exchange (2011)

Singh, Manmilan ; Schaefer, Jacob

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Language: English

In: Journal of the American Chemical Society, 02 March 2011, Vol.133(8), pp.2626-31

Description: The proximities of specific subgroups of nearest-neighbor chains in glassy polymers are revealed by distance-dependent (13)C-(13)C dipolar couplings and spin diffusion. The measurement of such proximities is practical even with natural-abundance levels of (13)C using a 2D version of centerband-only detection of exchange (CODEX). Two-dimensional CODEX is a relaxation-compensated experiment that avoids the problems associated with variations in T(1)(C)'s due to dynamic site heterogeneity in the glass. Isotropic chemical shifts are encoded in the t(1) preparation times before and after mixing, and variations in T(2)'s are compensated by an S(0) reference (no mixing). Data acquisition involves acquisition of an S(0) reference signal on alternate scans, and the active control of power amplifiers, to achieve stability and accuracy over long accumulation times. The model system to calibrate spin diffusion is the polymer itself. For a mixing time of 200 ms, only (13)C-(13)C pairs separated by one or two bonds (2.5 Å) show cross peaks, which therefore identify reference intrachain proximities. For a mixing time of 1200 ms, 5 Å interchain proximities appear. The resulting cross peaks are used in a simple and direct way to compare nonrandom chain packing for two commercial polycarbonates with decidedly different mechanical properties.

Keywords: Polycarboxylate Cement -- Chemistry

ISSN: 00027863

E-ISSN: 1520-5126

DOI: 10.1021/ja109104f

URL: View this record in MEDLINE/PubMed

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6

Article

The unsung heroes of scientific software (2016)

Dalmeet Singh Chawla

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In: Nature, 2016, Vol.529(7584), p.115

Description: For researchers who code, academic norms for tracking the value of their work seem grossly unfair. They can spend hours contributing to software that underpins research, but if that work does not result in the authorship of a research paper and accompanying citations, there is little way to measure its...

Keywords: Code Reuse ; Research ; Software Packages ; Scientists ; Researchers ; Open Access;

ISSN: 0028-0836

E-ISSN: 14764687

DOI: 10.1038/529115a

URL: View this record in Nature

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7

Article

Not robots: children's perspectives on authenticity, moral agency and stimulant drug treatments (2013)

Singh, Ilina

BMJ Publishing Group Ltd and Institute of Medical Ethics

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Language: English

In: Journal of Medical Ethics, 28 June 2013, Vol.39(6), p.359

Description: In this article, I examine children's reported experiences with stimulant drug treatments for attention deficit hyperactivity disorder in light of bioethical arguments about the potential threats of psychotropic drugs to authenticity and moral agency. Drawing on a study that involved over 150 families in the USA and the UK, I show that children are able to report threats to authenticity, but that the majority of children are not concerned with such threats. On balance, children report that stimulants improve their capacity for moral agency, and they associate this capacity with an ability to meet normative expectations. I argue that although under certain conditions stimulant drug treatment may increase the risk of a threat to authenticity, there are ways to minimise this risk and to maximise the benefits of stimulant drug treatment. Medical professionals in particular should help children to flourish with stimulant drug treatments, in good and in bad conditions.

Keywords: Children ; Neuroethics ; Psychiatry ; Psychopharmacology ; Open Access ; Editor'S Choice

ISSN: 0306-6800

ISSN: 03066800

E-ISSN: 1473-4257

E-ISSN: 14734257

DOI: 10.1136/medethics-2011-100224

URL: View this record in BMJ Journals

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8

Article

It's time for a centralized registry of laboratory-acquired infections (2011)

Kamaljit Singh

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In: Nature Medicine, 2011, Vol.17(8), p.919

Description: Accounts of highly infectious laboratory outbreaks should not read like a mystery novel. Sadly, in the absence of integrated reporting systems for laboratory-acquired illnesses, our investigations of such events can resemble a whodunit.

Keywords: Laboratory Infection–Epidemiology ; Laboratory Infection–Prevention & Control ; Registries–Epidemiology ; United States–Epidemiology ; Laboratories ; Infections ; Registration;

ISSN: 1078-8956

E-ISSN: 1546170X

DOI: 10.1038/nm0811-919

URL: View this record in Nature

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9

Article

Evidence in oral health promotion-implications for oral health planning (2012)

Singh, Shenuka

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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

DOI: 10.2105/AJPH.2012.300893

URL: View this record in MEDLINE/PubMed

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10

Article

Publishers take academic networking site to court (2017)

Chawla, Dalmeet Singh

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Language: English

In: Science (New York, N.Y.), 13 October 2017, Vol.358(6360), pp.161

ISSN: 00368075

E-ISSN: 1095-9203

DOI: 10.1126/science.358.6360.161

URL: View this record in MEDLINE/PubMed

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Kooperativer Bibliotheksverbund

Berlin Brandenburg