Optical coherence microscopy for the evaluation of a tissue-engineered artificial cornea

A transparent artificial cornea derived from biological material is the ultimate goal of corneal research. Attempts at artificial corneal constructs produced from synthetic polymers have proved unsuccessful due to lack of biocompatibility and ability to integrate into the tissue. We have designed a corneal model derived from collagenous biological materials that has several advantages: it has low antigenicity and therefore small chance of eliciting an immune reaction, it can be broken down by the body’s own cells and gradually replaced over time by natural materials, and it may contain signaling information for native cells, thereby inducing normal phenotype and behavior. In addition, a transparent corneal model has the potential to be used for testing of novel ophthalmic drugs or gene therapy approaches, eliminating the need for animal testing. We have used an optical coherence microscope (OCM) to evaluate both the structure of our tissue constructs over time in culture and the optical properties of the tissue itself. This imaging technique promises to be an important diagnostic tool in our efforts to understand the influence of mechanical forces, cell phenotype, and soluble factors on the transparency of corneal tissue. From the 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society [September 01-05, 2004, San Francisco, CA] IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS ISBN: 0-7803-8439-

Puberty Predicts Approach But Not Avoidance on the Iowa Gambling Task in a Multinational Sample

According to the dual systems model of adolescent risk taking, sensation seeking and impulse control follow different developmental trajectories across adolescence and are governed by two different brain systems. The authors tested whether different underlying processes also drive age differences in reward approach and cost avoidance. Using a modified Iowa Gambling Task in a multinational, cross‐sectional sample of 3,234 adolescents (ages 9–17; M = 12.87, SD = 2.36), pubertal maturation, but not age, predicted reward approach, mediated through higher sensation seeking. In contrast, age, but not pubertal maturation, predicted increased cost avoidance, mediated through greater impulse control. These findings add to evidence that adolescent behavior is best understood as the product of two interacting, but independently developing, brain systems

Correction to: Age Patterns in Risk Taking Across the World

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Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy.

BACKGROUND: Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction. METHODS: A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. RESULTS: Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p⩽0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. CONCLUSIONS: In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services

Inhibition of HIV virus by neutralizing Vhh attached to dual functional liposomes encapsulating dapivirine

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations

Age Patterns in Risk Taking Across the World

Epidemiological data indicate that risk behaviors are among the leading causes of adolescent morbidity and mortality worldwide. Consistent with this, laboratory-based studies of age differences in risk behavior allude to a peak in adolescence, suggesting that adolescents demonstrate a heightened propensity, or inherent inclination, to take risks. Unlike epidemiological reports, studies of risk taking propensity have been limited to Western samples, leaving questions about the extent to which heightened risk taking propensity is an inherent or culturally constructed aspect of adolescence. In the present study, age patterns in risk-taking propensity (using two laboratory tasks: the Stoplight and the BART) and real-world risk taking (using self-reports of health and antisocial risk taking) were examined in a sample of 5227 individuals (50.7% female) ages 10–30 (M = 17.05 years, SD = 5.91) from 11 Western and non-Western countries (China, Colombia, Cyprus, India, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the US). Two hypotheses were tested: (1) risk taking follows an inverted-U pattern across age groups, peaking earlier on measures of risk taking propensity than on measures of real-world risk taking, and (2) age patterns in risk taking propensity are more consistent across countries than age patterns in real-world risk taking. Overall, risk taking followed the hypothesized inverted-U pattern across age groups, with health risk taking evincing the latest peak. Age patterns in risk taking propensity were more consistent across countries than age patterns in real-world risk taking. Results suggest that although the association between age and risk taking is sensitive to measurement and culture, around the world, risk taking is generally highest among late adolescents

Molecular and biological characterization of the Streptococcal ADP-ribosyltransferase SpyA and ADP-ribosylation of the intermediate filament vimentin

ADP-ribosyltransferases represent an important class of enzymes. These enzymes can be endogenous regulators or toxins, which affect a myriad of cellular processes by the covalent transfer of ADP-ribose, donated from NAD+, onto a substrate protein. SpyA, the first ADP-ribosyltransferase (ADPRT) identified in the human pathogen Streptococcus pyogenes, was found to modify the cytoskeletal protein actin and the intermediate filament vimentin. While ADPRTs have low sequence homology, they share conserved structural motifs, found by mutational analysis to be important to SpyA ADP-ribosylation and general NAD-glycohydrolase activities. Actin is a well-characterized substrate of ADP-ribosylation. Actin-specific bacterial ADPRT toxins universally target a single site on actin, arginine-177. SpyA has a unique ADPRT activity as it targets a novel site of modification of actin, arginine-30. Quantitative comparison of the activity of SpyA on vimentin and actin found vimentin was the preferred substrate for SpyA (k cat, 58.5±3.4 min−1) relative to actin (k cat, 10.1±0.6 min−1) and vimentin was modified at a rate 9.48±1.95 fold faster than actin. Using the novel mass spectrometry method of ADP-ribose marker ion identification, the primary sites of ADP-ribosylation of vimentin were found to be arginine-44, -49 and -63 in the N-terminal regulatory head domain, with several additional secondary sites identified. Because the primary sites are located in the head domain of vimentin, a region responsible for regulation of polymerization via phosphorylation, we investigated the effects of SpyA on vimentin filamentation. Modification of vimentin in vitro was shown to cause a direct defect in polymerization. Additionally, we demonstrated that intoxication of HeLa cells with SpyA resulted in collapse of the vimentin cytoskeleton. We conclude that SpyA modification of vimentin in an important regulatory region has significant functional effects on vimentin assembly. SpyA lacks a traditional binding domain, which mediates the ability of many ADPRTs to translocate across the eukaryotic cell membrane. Though it is currently unknown how SpyA gains entry to the host cell, we present evidence that SpyA associates with the cellular membrane. This interaction appears to be stable when subjected to high ionic conditions but susceptible to treatment with extracellular trypsin suggesting SpyA may be imbedded in the phospholipid bilayer