Techniques for estimating genetic admixture and applications to the problem of the origin of the Icelanders and the Ashkenazi Jews

Summary A method is introduced for simultaneously using multiple loci to estimate admixutre and test goodness of fit of the model of admixture. Deviation of observed frequencies from expectation caused by sources of error such as sampling and/or drift is allowed for all loci in all populations. This allows investigation of the effects of different assumptions about sources of error on the estimates. Admixture is then investigated for Icelanders and Ashkenazi Jews. Results indicate that the Icelanders have a large Norse contribution, and that the Jews may have a small to moderate contribution from the European gene pool. There are some indications that ABO and G6PD give abnormal estimates of admixture compared to other loci, and that the Jewish gene pool may be derived from additional populations in addition to the populations considered.     

Prolactin increases the density of striatal dopamine receptors in normal and hypophysectomized male rats

Administration of prolactin to adult male rats, by s.c. injection, significantly increases the density of the striatal dopamine (DA) receptors, without altering the apparent affinity of the receptors for [³H]spiroperidol. Larger doses of prolactin are required to increase the density of the striatal DA receptors in hypophysectomized rates compared to normal rats. These results suggest that prolactin might be the common mediator of the increase in striatal DA receptor density produced by either estrogen or haloperidol administration. Monitoring and/or altering prolactin levels might be informative in neurologic or psychiatric disorders involving striatal DA neurotransmission.     

Changes in amino-terminal sequences of pp60src lead to decreased membrane association and decreased in vivo tumorigenicity

We have suggested previously that the amino-terminal 8 kilodaltons of pp60^src may serve as a structural hydrophobic domain through which pp60^src attaches to plasma membranes. Two isolates of recovered avian sarcoma viruses (rASVs), 1702 and 157, encode pp60^src proteins that have alterations in this amino-terminal region. The rASV 1702 src protein (56 kilodaltons) and the 157 src protein (62.5 kilodaltons) show altered membrane association, and fractionate largely as soluble, cytoplasmic proteins in aqueous buffers, in contrast with the membrane association of more than 80% of the src protein of standard avian sarcoma virus under the identical fractionation procedure. Plasma membranes purified from cells transformed by these rASVs contain less than 10% of the amount of pp60^src found in membranes purified from cells transformed by Rous sarcoma virus or control rASVs. The altered membrane association of these src proteins had little or no effect on the properties of chick embryo fibroblasts transformed in monolayer culture. In contrast, rASV 1702 showed reduced in vivo tumorigenicity compared with Rous sarcoma virus or with other rASVs that encode membrane-associated src proteins. Rous sarcoma virus-induced tumors are malignant, poorly differentiated sarcomas that are lethal to their hosts. rASV 1702 induces a benign, differentiated sarcoma that regresses and is not lethal to its hosts. These data support the role of amino-terminal sequences in the membrane association of pp60^src, and suggest that the amino terminus of pp60^src may have a critical role in the promotion of in vivo tumorigenicity.     

Structure and function of adenovirus type 12 defective virions.

Purified human adenovirus type 12 preparations contain defective virions with a lighter density. These defective virions were isolated, and their biological functions and DNA were characterized. They can induce early and late antigens in infected cells and tumors in newborn hamsters with similar efficiency as complete virions. The majority of the DNA molecules from light virions contain deletions mapping near 16% from the left-hand end of the genome. Mechanisms for the generation of these molecules are discussed.     

Aspects of amino acid requirements for in vitro evagination of imaginal leg discs inDrosophila melanogaster

Summary A method of staging late third instar larvae on the basis of salivary gland morphology is described. Using this technique, we investigated stage related amino acid requirements forDrosophila leg disc evagination in vitro. It was found that the requirement for glutamine lasted longer than that of proline. The staging technique should help in the detailed exploration of the late 3rd instar time period in order to bridge the gap between biochemistry and morphogenesis in the initiation of disc evagination.     

Effect of the TP5 analogue of thymopoietin on the rejection of male skin by aged and thymectomized female mice

Although young adult C3H/HeJ (OH) females do not reject C3H male skin grafts, OH females older than 1 year commonly do so, as also do many thymectomized, young adult C3H females. Therapy With TP5, a synthetic pentapeptide analogue of thymopoietin which has biological properties of the parent molecule, substantially reduced the capacity of aged OH females and of thymectomized, young OH females to reject OH male skin.     

Increase of L-serine dehydratase activity under gluconeogenic conditions in adult-rat hepatocytes cultured on collagen gel/nylon mesh.

Hormonal regulation of L-serine dehydratase [L-serine hydro-lyase (deaminating), EC 4.2.1.13] was studied in primary cultures of adult-rat hepatocytes. The hepatocytes were isolated by collagenase perfusion and maintained in culture on collagen-gel/nylon-mesh substrata. L-Serine dehydratase activity was measured with [14C]threonine as substrate. The enzyme activity in hepatocytes of normal adult rats was low and declined rapidly in culture in L-15 medium containing 0.1 micro M-insulin and even more in the presence of glucose. L-Serine dehydratase activity in hepatocytes of rats with streptozotocin-induced diabetes was initially 20-fold higher than that of normal rats, but fell rapidly to a low value by 4 days in culture. Hormonal regulation of the enzyme activity was manifested by treatment of the cultured hepatocytes with insulin (0.1 micro M), glucagon (0.3 micro M), dexamethasone (10 micro M) and combinations of these hormones. Either glucagon or dexamethasone in the absence of insulin enhanced the activity of L-serine dehydratase, but failed to do so in the presence of insulin. Treatment with both hormones resulted in a 2-3-fold increase in enzyme activity in culture on days 3 and 4. Under conditions in which the enzyme activity was enhanced, glucose production by the cultured hepatocytes was concomitantly increased. Glucose production resulted in part from gluconeogenesis from pyruvate and not entirely from glycogenolysis. The gluconeogenic conditions of culture resulted in a decrease in cellular lipids in the cultured hepatocytes, as evidenced by ultrastructural studies.     

Association of long surface appendages with adherence-related functions of the gram-positive species Actinomyces naeslundii

Electron microscopy of new isolates of gram-positive Actinomyces naeslundii demonstrated long, fragile appendages. Removal of the appendages impaired attachment to epithelial cells and reaggregation, thus implicating them in attachment-related functions.     

Cinnamic acid 4-hydroxylase from gherkin tissues

Homogenates from 4-day-old gherkin cotyledons and hypocotyls fractionated by sucrose density gradient centrifugation contain cinnamic acid 4-hydroxylase activity, the activity being highest in the endoplasmic reticulum fractions. These fractions also contain very low concentrations of cytochrome P₄₅₀. Hydroxylase activity is dependent on NADPH and on molecular oxygen, is optimal at pH 7.5 and is inhibited by carbon monoxide. The enzyme is very sensitive to inhibition by 2-mercaptoethanol, but it is not inhibited by the product, p-coumaric acid. Further, its responses to various potential inhibitors are fairly typical of mixed function oxidases from other sources.