Representation of nonepistatic selection models and analysis of multilocus Hardy-Weinberg equilibrium configurations

Summary The paper develops conditions for the existence and the stability of central equilibria emanating from selection recombination interaction with generalized nonepistatic selection forms operating in multilocus multiallele systems. The selection structure admits a natural representation as simple sums of Kronecker products based on a common set of marginal selection components. A flexible parametrization of the recombination process is introduced leading to a canonical derivation of the transformation equations connecting gamete frequency states over successive generations. Conditions for the existence and stability of multilocus Hardy-Weinberg (H.W.) type equilibria are elaborated for the classical nonepistatic models (multiplicative and additive viability effects across loci) as well as for generalized nonepistatic selection expressions. It is established that the range of recombination distributions maintaining a stable H.W. polymorphic equilibrium is confined to loose linkage in the pure multiplicative case, but is not restricted in the additive model. In the bisexual case we ascertain for the generalized nonepistatic model the stability conditions of a common H.W. polymorphism.This paper was supported in part by NIH Grant GM 10452-14 and NSF Grant MCS 75-23608.     

Loss of net negative surface charge during MLC stimulation of human T lymphocytes: correlation to "stable" E-rosette formation and natural attachment to normal and malignant target cells.

Activation of human blood T lymphocytes in mixed lymphocyte culture (MLC) causes a reduction in the net negative surface charge, as indicated by the reduction in the electrophoretic mobility. Concomitantly, the activated cells acquire new properties, including the ability to form “stable” E rosettes, and attach to normal and malignant cells of the same species (natural attachment (NA)). These properties were found to be expressed by lymphocytes within the low electrophoretic fractions (cells with low negative charge) of the MLC populations. The formation of stable E rosettes and natural attachment capacities of human thymocytes were also found to correlate with the amount of surface negative charge. The slowly migrating (less negative charged) cortical thymocytes, reported earlier as being able to form stable E rosettes, were found also to exhibit NA activity. Medullary thymocytes carrying a high net negative surface charge lack these characteristics. We consider it likely that the reduction of negative charge during activation of peripheral T cells, facilitates cell-to-cell contacts, and thus prepares the (activated) cells to perform cooperative interactions with other cell types, and express the lytic activity of T cells.     

A Point Mutation in the Ethylene-Inducing Xylanase Elicitor Inhibits the β-1-4-Endoxylanase Activity But Not the Elicitation Activity

Ethylene-inducing xylanase (EIX) elicits plant defense responses in certain tobacco (Nicotiana tabacum) and tomato cultivars in addition to its xylan degradation activity. It is not clear, however, whether elicitation occurs by cell wall fragments released by the enzymatic activity or by the xylanase protein interacting directly with the plant cells. We cloned the gene encoding EIX protein and overexpressed it in insect cells. To determine the relationship between the two activities, substitution of amino acids in the xylanase active site was performed. Substitution at glutamic acid-86 or -177 with glutamine (Gln), aspartic acid (Asp), or glycine (Gly) inhibited the β-1-4-endoxylanase activity. Mutants having Asp-86 or Gln-177 also lost the ability to induce the hypersensitive response and ethylene biosynthesis. However, mutants having Gln-86, Gly-86, Asp-177, or Gly-177 retained ability to induce ethylene biosynthesis and the hypersensitive response. Our data show that the xylanase activity of EIX elicitor can be separated from the elicitation process, as some of the mutants lack the former but retain the latter.     

Acute pathophysiological effects of muscle-expressed Dp71 transgene on normal and dystrophic mouse muscle.

products of the dystrophin gene range from the 427-kDa full-length dystrophin to the 70.8-kDa Dp71. Dp427 is expressed in skeletal muscle, where it links the actin cytoskeleton with the extracellular matrix via a complex of dystrophin-associated proteins (DAPs). Dystrophin deficiency disrupts the DAP complex and causes muscular dystrophy in humans and the mdx mouse. Dp71, the major nonmuscle product, consists of the COOH-terminal part of dystrophin, including the binding site for the DAP complex but lacks binding sites for microfilaments. Dp71 transgene (Dp71tg) expressed in mdx muscle restores the DAP complex but does not prevent muscle degeneration. In wild-type (WT) mouse muscle, Dp71tg causes a mild muscular dystrophy. In this study, we tested, using isolated extensor digitorum longus muscles, whether Dp71tg exerts acute influences on force generation and sarcolemmal stress resistance. In WT muscles, there was no effect on isometric twitch and tetanic force generation, but with a cytomegalovirus promotor-driven transgene, contraction with stretch led to sarcolemmal ruptures and irreversible loss of tension. In MDX muscle, Dp71tg reduced twitch and tetanic tension but did not aggravate sarcolemmal fragility. The adverse effects of Dp71 in muscle are probably due to its competition with dystrophin and utrophin (in MDX muscle) for binding to the DAP complex.     

Buckminsterfullerene (C-60 Carbon Allotrope) Inhibits Ethylene Evolution from 1-Aminocyclopropane-1-carboxylic acid (ACC)-treated Shoots of Pea (Pisum sativum), Broadbean (Vicia faba) and Flowers of Carnation (Dianthus caryophyllus)

When applied either in the form of a colloidal solution or inliposomes, buckyballs (C-60—buckminsterfullerene) markedlyreduced ethylene evolution from cut carnation (Dianthus caryophyllus)flowers, as well as pea (Pisum sativum) and broadbean (Viciafaba) foliage treated with ethylene precursor l-aminocyclopropane-l-carboxylicacid (ACC). The liposome preparation was approximately twiceas effective as colloidal solutions. Moreover, upon being incubatedin a closed atmosphere with ethylene, buckyballs induced a significantdepletion of ambient ethylene which was temperature and C-60—concentrationdependent. This mode of C-60 action is attributed to ethyleneadsorption stemming from the vast C-60 surface area, calculatedto be 1317 m² g_-1, and the affinity of its carbon atoms forthe component in the ethylene double bond.Copyright 1993, 1999Academic Press Dainthus caryophyllus, Pisum sativum, Vicia faba, adsorption, ethylene, fullerene     

Potential βPP-processing proteinase activities from alzheimer's and control brain tissues

Fluorogenic peptide substrates designed to encompass the reportedα-secretory and amyloidogenic cleavage sites of the amyloid-β precursor protein (βPP) were used to analyze proteinase activities in brain extracts from control patients and those with Alzheimer's disease (AD). Activity against the secretory substrate atpH 7.5 in control and AD brains produced a major endopeptidase cleavage at the Lys687-Leu688 bond (βPP770 numbering), consistent with theβPP secretase cleavage. Activity in control brains against the amyloidogenic substrate atpH 7.5 produced one cleavage at the Ala673-Glu674 bond, two residues C-terminal to the amyloidogenic Met-Asp site. However, in three of four AD brains, the major cleavage was at the Asp-Ala bond, one residue from the amyloidogenic site. Both endopeptidase and carboxypeptidase activities in AD brains were lower than in control brains. Proteinase activities against the secretory substrate had a major optimum atpH 3.0–4.0 and another atpH 6.0–7.5. Proteinase activities against the amyloidogenic substrate had a major optimum at or belowpH 3.0 and another atpH 6.0. Using both substrates, activities at lowpH were higher in AD brains than in controls, while atpH above 6.5, activities in control brains were higher than in AD. These results indicate that the levels of proteolytic enzymes in AD brains are altered relative to controls.     

Mendelian segregation: a choice between “order” and “chaos”

Research supported in part by a US-Israel Binational Science Foundation grant 85-00021 and by NIH grants GM 28016 and GM 10452