The utility of adenoviral vectors for gene therapy is currently limited due, in part, to the widespread distribution of the cellular receptor for the adenovirus fiber that precludes the targeting of specific cell types. In order to develop a targeted adenovirus, it is therefore necessary both to ablate endogenous viral tropism and to introduce novel tropism. We hypothesized that these two goals could be achieved by employing a neutralizing anti-fiber antibody, or antibody fragment, chemically conjugated to a cell-specific ligand. To test this concept, we chose to target the folate receptor, which is overexpressed on the surface of a variety of malignant cells. Therefore, we conjugated folate to the neutralizing Fab fragment of an anti-fiber monoclonal antibody. This Fab-folate conjugate was complexed with an adenoviral vector carrying the luciferase reporter gene and was shown to redirect adenoviral infection of target cells via the folate receptor at a high efficiency. Furthermore, when complexed with an adenoviral vector carrying the gene for herpes simplex virus thymidine kinase, the Fab-folate conjugate mediated the specific killing of cells that overexpress the folate receptor. This work thus represents the first demonstration of the retargeting of a recombinant adenoviral vector via a non-adenoviral cellular receptor.
Interracial unions and same-sex unions were rare and secretive in the past because U.S. society was organized to suppress such unions. The rise of same-sex and interracial unions in the past few decades suggests changes in the basic structure of U.S. society. Young adults have been marrying later, and single young adults are much less likely to live with their parents. The independence of young adults has reduced parental control over their children's choice of mate. Using microdata from the U.S. Census, this article shows that interracial couples and same-sex couples are more geographically mobile and more urban than same-race married couples. The authors view the geographic mobility of young couples as a proxy for their independence from communities of origin. The results show that nontraditional couples are more geographically mobile even after individual and community attributes are taken into account. Same-sex couples are more likely to be interracial than heterosexual couples, indicating that same-sex and interracial couples are part of a common fabric of family diversification. The article discusses related historical examples and trends.
We present data from a nationally representative 2017 survey of American adults. For heterosexual couples in the United States, meeting online has become the most popular way couples meet, eclipsing meeting through friends for the first time around 2013. Moreover, among the couples who meet online, the proportion who have met through the mediation of third persons has declined over time. We find that Internet meeting is displacing the roles that family and friends once played in bringing couples together.
Morphologic and immunocytochemical studies were conducted to determine the sequence of cellular interactions that occur during the initiation of the fatty streak in the aorta of Watanabe Heritable Hyperlipemic rabbits and comparably hypercholesterolemic fat-fed rabbits. Watanabe rabbits from 3.5 weeks gestation to 2 months of age and fat-fed rabbits from 1 week to 2 months duration of hypercholesterolemia were compared utilizing light microscopic and scanning and transmission microscopic techniques. In both groups of animals, the earliest detectable events were an increase in monocyte adherence and subendothelial migration followed by formation of a single layer of intimal macrophage-derived foam cells. Immunocytochemical studies using macrophage-specific and muscle-actin-specific monoclonal antibodies support the morphologic data which suggests that the early fatty streak in both the Watanabe and fat-fed rabbits is predominantly composed of macrophage-derived foam cells. Thus, the absence of functional low density lipoprotein receptors in the Watanabe rabbit and differences in the distribution of cholesterol among the lipoproteins in the Watanabe and fat-fed rabbits do not appear to alter the initial responses of the cells of the artery wall to chronic hypercholesterolemia.
luse U.S. census data to perform the first large-sample, nationally representative tests of outcomes for children raised by same-sex couples. The results show that children of same-sex couples are as likely to make normal progress through school as the children of most other family structures. Heterosexual married couples are the family type whose children have the lowest rates of grade retention, but the advantage of heterosexual married couples is mostly due to their higher socioeconomic status. Children ofallfamily types (including children ofsame-sex couples) are far more likely to make normal progress through school than are children living in group quarters (such as orphanages and shelters).
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