Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to Coxsackievirus B3-induced myocarditis

Several mouse strains are susceptible to immunopathic myocarditis after infection with Coxsackievirus B3 (CB3). This disease is associated with autoantibodies that are directed against myosin. In this study we characterized sera from CB3-infected mice for their reactivity with three different myosin isoforms (heart, skeletal muscle, and brain myosins) and for autoantibody isotype by using an ELISA. Competitive inhibition assays and absorption studies with various myosins demonstrated the presence of two autoantibody populations in sera of susceptible A.CA and A.SW mice. The first was specific for cardiac myosin and was mainly IgG. The second antibody population cross-reacted with heart, skeletal muscle, and brain myosin and was mainly IgM. B10.PL/SgSf and B10.A/SgSf mice, which do not develop immunopathic myocarditis, produced only the IgM autoantibody population cross-reactive with all three myosin isoforms. Because the heart-specific myosin autoantibodies were found exclusively in the mouse strains that developed immunopathic myocarditis, they can be considered a serologic marker for autoimmune heart disease.     

Effect of Endotoxin on Serum Zinc Concentrations in the Rat

Serum zinc concentrations decreased significantly in a dose-dependent response after endotoxin administration in the rat. The reproducibility and sensitivity of the biological response offer a potential bioassay of endotoxin.     

Duplication of chromosome 10p: confirmation of regional assignments of platelet-type phosphofructokinase.

A proband, clinically thought to have trisomy 10p, was found to have an inverted duplication of 10p [46, XY, inv dup(10)(qter----p15.3::p15.3----p 11.1:)]. The phenotypic findings and cytogenetic observations were supported by relevant biochemical studies. The activity of phosphofructokinase (platelet-type; PFKP), previously localized to 10p, and hexokinase-I (HKI), putatively on 10p, demonstrated 153% and 149% of control activity in the proband's fibroblasts. These gene-dosage effects confirmed the clinical and cytogenetic observations as well as the localization of HKI to 10p. Additionally, phosphofructokinase (PFK) and hexokinase (HK), which are control points in the glycolytic pathway, were shown to be syntenic.     

Genetic factors controlling the susceptibility to experimental autoimmune thyroiditis in inbred rat strains

CDF (high responder) rats were crossed with SHR (low responder) rats to study genetic factors influencing susceptibility to experimental autoimmune thyroiditis (EAT). F1 hybrid rats showed intermediate susceptibility to thyroiditis. Gene segregation patterns of F2 and backcross rats demonstrated that the immune response to rat thyroglobulin (RaTg) is under polygenic control. A main factor controlling immune response to RaTg is associated with the X chromosome. Females of CDF and SHR rats produced higher levels of antibody, suggesting that antibody production to RaTg is a sex-influenced trait. Different genetic control mechanisms are evident in autoantibody production and thyroid lesions. No evidence of linkage of an immune response gene to RaTg to the major histocompatibility complex of the rat (RT1) was observed.     

Cytoplasmic filaments and cellular wound healing in amoeba proteus

The flexibility and self-healing properties of animal cell surface membranes are well known. These properties have been best exploited in various micrurgical studies on living cells (2, 3), especially in amoebae (7, 20). During nuclear transplantation in amoebae, the hole in the membrane through which a nucleus passes can have a diameter of 20-30 μm, and yet such holes are quickly sealed, although some cytoplasm usually escapes during the transfer. While enucleating amoebae in previous studies, we found that if a very small portion of a nucleus was pushed through the membrane and exposed to the external medium, the amoeba expelled such a nucleus on its own accord. When this happened, a new membrane appeared to form around the embedded portion of the nucleus and no visible loss of cytoplasm occurred during nuclear extrusion. In the present study, we examined amoebae that were at different stages of expelling partially exposed nuclei, to follow the sequence of events during the apparent new membrane formation. Unexpectedly, we found that a new membrane is not formed around the nucleus from inside but a hole is sealed primarily by a constriction of the existing membrane, and that cytoplasmic filaments are responsible for the prevention of the loss of cytoplasm.     

Testing the extreme value domain of attraction for distributions of beneficial fitness effects

In modeling evolutionary genetics, it is often assumed that mutational effects are assigned according to a continuous probability distribution, and multiple distributions have been used with varying degrees of justification. For mutations with beneficial effects, the distribution currently favored is the exponential distribution, in part because it can be justified in terms of extreme value theory, since beneficial mutations should have fitnesses in the extreme right tail of the fitness distribution. While the appeal to extreme value theory seems justified, the exponential distribution is but one of three possible limiting forms for tail distributions, with the other two loosely corresponding to distributions with right-truncated tails and those with heavy tails. We describe a likelihood-ratio framework for analyzing the fitness effects of beneficial mutations, focusing on testing the null hypothesis that the distribution is exponential. We also describe how to account for missing the smallest-effect mutations, which are often difficult to identify experimentally. This technique makes it possible to apply the test to gain-of-function mutations, where the ancestral genotype is unable to grow under the selective conditions. We also describe how to pool data across experiments, since we expect few possible beneficial mutations in any particular experiment.