Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach.

BACKGROUND: Increasing evidence suggests that the effect of HLA-E on Natural Killer (NK) cell activity can be affected by the nature of the peptides bound to this non-classical, MHC class Ib molecule. However, its reduced cell surface expression, and until recently, the lack of specific monoclonal antibodies hinder studying the peptide-binding specificity HLA-E. RESULTS: An in vitro refolding system was used to assess binding of recombinant HLA-E to either specific peptides or a nonamer random peptide library. Peptides eluted from HLA-E molecules refolded around the nonamer library were then used to determine a binding motif for HLA-E. Hydrophobic and non-charged amino acids were found to predominate along the peptide motif, with a leucine anchor at P9, but surprisingly there was no methionine preference at P2, as suggested by previous studies. CONCLUSIONS: Compared to the results obtained with rat classical class Ia MHC molecules, RT1-A1c and RT1-Au, HLA-E appears to refold around a random peptide library to reduced but detectable levels, suggesting that this molecule's specificity is tight but probably not as exquisite as has been previously suggested. This, and a previous report that it can associate with synthetic peptides carrying a viral sequence, suggests that HLA-E, similar to its mouse counterpart (Qa-1b), could possibly bind peptides different from MHC class I leader peptides and present them to T lymphocytes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Experimental arthritis is dependent on mouse mast cell protease-5

© 2017 by The American Society for Biochemistry and Molecular Biology, Inc. The constitutive heparin+ (HP) mast cells (MCs) in mice express mouseMCprotease (mMCP)-5 and carboxypeptidaseA (mMC-CPA). The amino acid sequence ofmMCP-5is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralisinfected mice. In contrast, the constitutive HP+ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis ofmMCP-5from theMCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wildtype mice in two disease models

Ethnic differences in mental health among incarcerated youths: do Moroccan immigrant boys show less psychopathology than native Dutch boys?

Psychiatric disorders are highly prevalent among incarcerated youth. However, whereas ethnic minority youths are overrepresented in the juvenile justice system, limited research is available on their mental health. In this study, differences in mental health problems between incarcerated adolescents of native Dutch and Moroccan origin, were examined. Child Behavior Checklist and Youth Self-Report scores were compared between incarcerated adolescents of native Dutch and Moroccan origin. Their scores were also compared to those of native Dutch and Moroccan immigrant youths in the general, non-incarcerated population. Native Dutch incarcerated adolescents showed higher levels of various mental health problems than incarcerated adolescents with a Moroccan background. Compared to the general population, incarcerated youths showed higher levels of mental health problems, but this deviation was much larger for native Dutch than for Moroccan immigrant youths. These ethnic differences in mental health problems could not be explained by ethnic differences in socio-economic background and social desirable answering tendencies. Incarcerated youths of Moroccan origin show less psychopathology than incarcerated native Dutch youths, which might be explained by disparities in sentencing procedures

National Origin and Behavioural Problems of Toddlers: The Role of Family Risk Factors and Maternal Immigration Characteristics

In many societies the prevalence of behavioural problems in school-aged children varies by national origin. We examined the association between national origin and behavioural problems in 1½-year-old children. Data on maternal national origin and the Child Behavior Checklist for toddlers (n = 4943) from a population-based cohort in the Netherlands were used. Children from various non-Dutch backgrounds all had a significantly higher mean behavioural problem score. After adjustment for family risk factors, like family income and maternal psychopathology, the differences attenuated, but remained statistically significant. Non-Dutch mothers with immigration risk factors, such as older age at immigration or no good Dutch language skills, reported significantly more behavioural problems in their offspring. In conclusion, the present study indicated more behavioural problems in immigrant toddlers from various backgrounds. Researchers and policymakers aiming to tackle disparities in behavioural problems should take into account that risks associated with national origin are intertwined with unfavourable family and immigration characteristics

Reconsidering the use of rankings in the valuation of health states: a model for estimating cardinal values from ordinal data

BACKGROUND: In survey studies on health-state valuations, ordinal ranking exercises often are used as precursors to other elicitation methods such as the time trade-off (TTO) or standard gamble, but the ranking data have not been used in deriving cardinal valuations. This study reconsiders the role of ordinal ranks in valuing health and introduces a new approach to estimate interval-scaled valuations based on aggregate ranking data. METHODS: Analyses were undertaken on data from a previously published general population survey study in the United Kingdom that included rankings and TTO values for hypothetical states described using the EQ-5D classification system. The EQ-5D includes five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) with three possible levels on each. Rank data were analysed using a random utility model, operationalized through conditional logit regression. In the statistical model, probabilities of observed rankings were related to the latent utilities of different health states, modeled as a linear function of EQ-5D domain scores, as in previously reported EQ-5D valuation functions. Predicted valuations based on the conditional logit model were compared to observed TTO values for the 42 states in the study and to predictions based on a model estimated directly from the TTO values. Models were evaluated using the intraclass correlation coefficient (ICC) between predictions and mean observations, and the root mean squared error of predictions at the individual level. RESULTS: Agreement between predicted valuations from the rank model and observed TTO values was very high, with an ICC of 0.97, only marginally lower than for predictions based on the model estimated directly from TTO values (ICC = 0.99). Individual-level errors were also comparable in the two models, with root mean squared errors of 0.503 and 0.496 for the rank-based and TTO-based predictions, respectively. CONCLUSIONS: Modeling health-state valuations based on ordinal ranks can provide results that are similar to those obtained from more widely analyzed valuation techniques such as the TTO. The information content in aggregate ranking data is not currently exploited to full advantage. The possibility of estimating cardinal valuations from ordinal ranks could also simplify future data collection dramatically and facilitate wider empirical study of health-state valuations in diverse settings and population groups

Exoplanets and SETI

The discovery of exoplanets has both focused and expanded the search for extraterrestrial intelligence. The consideration of Earth as an exoplanet, the knowledge of the orbital parameters of individual exoplanets, and our new understanding of the prevalence of exoplanets throughout the galaxy have all altered the search strategies of communication SETI efforts, by inspiring new "Schelling points" (i.e. optimal search strategies for beacons). Future efforts to characterize individual planets photometrically and spectroscopically, with imaging and via transit, will also allow for searches for a variety of technosignatures on their surfaces, in their atmospheres, and in orbit around them. In the near-term, searches for new planetary systems might even turn up free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor additions and modification

Exploring cross-sectional associations between common childhood illness, housing and social conditions in remote Australian Aboriginal communities

Background:\ud There is limited epidemiological research that provides insight into the complex web of causative and moderating factors that links housing conditions to a variety of poor health outcomes. This study explores the relationship between housing conditions (with a primary focus on the functional state of infrastructure) and common childhood illness in remote Australian Aboriginal communities for the purpose of informing development of housing interventions to improve child health.\ud \ud Methods:\ud Hierarchical multi-level analysis of association between carer report of common childhood illnesses and functional and hygienic state of housing infrastructure, socio-economic, psychosocial and health related behaviours using baseline survey data from a housing intervention study.\ud \ud Results:\ud Multivariate analysis showed a strong independent association between report of respiratory infection and overall functional condition of the house (Odds Ratio (OR) 3.00; 95%CI 1.36-6.63), but no significant association between report of other illnesses and the overall functional condition or the functional condition of infrastructure required for specific healthy living practices. Associations between report of child illness and secondary explanatory variables which showed an OR of 2 or more included: for skin infection - evidence of poor temperature control in the house (OR 3.25; 95%CI 1.06-9.94), evidence of pests and vermin in the house (OR 2.88; 95%CI 1.25-6.60); for respiratory infection - breastfeeding in infancy (OR 0.27; 95%CI 0.14-0.49); for diarrhoea/vomiting - hygienic state of food preparation and storage areas (OR 2.10; 95%CI 1.10-4.00); for ear infection - child care attendance (OR 2.25; 95%CI 1.26-3.99).\ud \ud Conclusion:\ud These findings add to other evidence that building programs need to be supported by a range of other social and behavioural interventions for potential health gains to be more fully realised

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored