Mechanics of bacteriophage maturation

Capsid maturation with large-scale subunit reorganization occurs in virtually all viruses that use a motor to package nucleic acid into preformed particles. A variety of ensemble studies indicate that the particles gain greater stability during this process, however, it is unknown which material properties of the fragile procapsids change. Using Atomic Force Microscopy-based nano-indentation, we study the development of the mechanical properties during maturation of bacteriophage HK97, a λ-like phage of which the maturation-induced morphological changes are well described. We show that mechanical stabilization and strengthening occurs in three independent ways: (i) an increase of the Young's modulus, (ii) a strong rise of the capsid's ultimate strength, and (iii) a growth of the resistance against material fatigue. The Young's modulus of immature and mature capsids, as determined from thin shell theory, fit with the values calculated using a new multiscale simulation approach. This multiscale calculation shows that the increase in Young's modulus isn't dependent on the crosslinking between capsomers. In contrast, the ultimate strength of the capsids does increase even when a limited number of cross-links are formed while full crosslinking appears to protect the shell against material fatigue. Compared to phage λ, the covalent crosslinking at the icosahedral and quasi threefold axes of HK97 yields a mechanically more robust particle than the addition of the gpD protein during maturation of phage λ. These results corroborate the expected increase in capsid stability and strength during maturation, however in an unexpected intricate way, underlining the complex structure of these self-assembling nanocontainers.     

Parental longevity correlates with offspring’s optimism in two cohorts of community-dwelling older subjects

Dispositional optimism and other positive personality traits have been associated with longevity. Using a familial approach, we investigated the relationship between parental longevity and offspring’s dispositional optimism among community-dwelling older subjects. Parental age of death was assessed using structured questionnaires in two different population-based samples: the Leiden Longevity Study (n = 1,252, 52.2% female, mean age 66 years, SD = 4) and the Alpha Omega Trial (n = 769, 22.8% female, mean age 69 years, SD = 6). Adult offspring’s dispositional optimism was assessed with the Life Orientation Test—Revised (LOT-R). The association between parental age of death and levels of optimism in the offspring was analysed using linear regression analysis within each sample and a meta-analysis for the overall effect. In both samples, the parental mean age of death was positively associated with optimism scores of the offspring. The association remained significant after adjustment for age, gender, living arrangement, body mass index, smoking status, education and self-rated health of the offspring. The pooled B coefficient (increase in LOT-R score per 10-year increase in parental mean age of death) was 0.30 (SE = 0.08, p < 0.001). In conclusion, parental longevity was positively associated with optimism in adult offspring, suggesting a partial linked heritability of longevity and optimism.     

Oral health care utilization in children with disabilities

Objectives

The objectives of this report were to survey the utilization of oral health care in children and adolescents with disabilities over a 7-year period and to compare these data with the utilization pattern of their peers without disabilities. For most countries, these data have not been published in the international literature so far.

Material and methods

The cohort used was the Permanent Sample of Socially Insured Persons, an anonymous representative sample of Belgian residents. The database comprised prospective data on oral and general health care utilization and sociodemographic variables collected from 2002 up to 2008.

Results

Data were available from 326 children and adolescents with and 53,589 without disabilities. Dental attendance rates were low in both subgroups: only 50 % had a dental visit in four or more of the seven observation years. Emergency oral and medical care was recorded significantly more often in children with disabilities whereas radiographs, restorations, and orthodontic assessments and treatments more frequently in children without disabilities.

Conclusion

The present study demonstrated that dental attendance rates in both subgroups were low and that in those who attended, preventive oral health care was only infrequently attested. Further research is needed to elucidate whether the lower number of radiographs and restorations and the higher number of emergency visits observed in the subgroup with disabilities reflect unmet oral treatment needs.

Clinical relevance

Objective data on health care utilization are essential to enable governments and stakeholders to devise appropriate care and to optimize access to care for persons with disabilities.     

Association of midregional proadrenomedullin with coronary artery stenoses, soft atherosclerotic plaques and coronary artery calcium

Midregional proadrenomedullin (MR-proADM) is elevated in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the association of MR-proADM with the grade of coronary artery stenosis, presence of coronary artery soft plaques and coronary artery calcification score (CACS), determined by 64-multislice computed tomography (MSCT) in patients without known prior cardiovascular disease. This retrospective study included 107 patients undergoing MSCT for confirmation (or exclusion) of coronary artery disease. MR-proADM levels were measured in all patients. The assessment of coronary artery stenoses, CACS and soft coronary plaques was made by MSCT using known criteria. The MR-proADM [median (25th–75th percentiles)] level was 0.33 (0.21–0.43)?nmol/l. The MR-proADM level was 0.28 (0.22–0.40)?nmol/l in patients with coronary stenoses ≥50% (n?=?23) versus 0.33 (0.27–0.40)?nmol/l in patients with coronary stenoses <50% (n?=?83, P?=?0.59), 0.33 (0.26–0.40)?nmol/l in patients with soft plaques (n?=?56) versus 0.33 (0.25–0.41)?nmol/l in patients without soft plaques (n?=?50, P?=?0.73) and 0.33 (0.25–0.39)?nmol/l in patients with CACS?<200 (n?=?81) versus 0.32 (0.26–0.44)?nmol/l in patients with CACS?≥200 (n?=?26, P?=?0.77). In multivariate analysis, the MR-proADM level was a significant correlate of coronary artery stenoses [odds ratio (OR)?=?0.93; 95% confidence interval (CI) 0.86–0.99; P?=?0.026] and soft plaques (OR?=?0.94; 95% CI 0.90–0.99; P?=?0.015) but not of CACS (OR?=?0.98; 95% CI 0.93–1.03; P?=?0.36). A decreased MR-proADM level is an independent correlate of the presence of coronary artery disease and of soft atherosclerotic plaques. Patients with decreased MR-proADM levels may need invasive examinations to diagnose more severe forms of coronary artery disease.     

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy

TRACK‐HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3‐Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross‐sectional data from this large well‐characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene‐positive subjects (120 PreHD and 119 early HD) from the TRACK‐HD study were included. Using voxel‐based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti‐saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.