Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis

Adjuvant arthritis (AA) is a chronic disease inducible in rats by immunization with an antigen of Mycobacterium tuberculosis. After the isolation of arthritogenic T-cell lines and clones, it became possible to demonstrate that the critical M. tuberculosis antigen contained an epitope cross-reactive with a self-antigen in joint cartilage. Like AA rats, patients suffering from rheumatoid arthritis demonstrated specific T-lymphocyte reactivity to the M. tuberculosis fraction containing the cross-reactive epitope. To characterize the critical M. tuberculosis epitope we used AA T-cell clones to screen mycobacterial antigens expressed in Escherichia coli and genetically engineered truncated proteins and synthetic peptides. The AA T-cell clones recognized an epitope formed by the amino acids at positions 180-188 in the sequence of a Mycobacterium bovis BCG antigen. Administration of this antigen to rats induced resistance to subsequent attempts to produce AA.     

A multivariate approach to socio-ecological development and endocrine variance in the spotted hyaena, Crocuta crocuta Erxleben.

This investigation of the socio-ecological development and endocrine variance in the spotted hyaena, Crocuta crocuta, illustrates that the complexity of a multivariate endocrine system cannot fully be understood using the concept of a class mean (mu). Any comprehensive investigation of a multivariate endocrine system should also include an analysis of variance (sigma), as it may provide additional insights into the dynamics of an endocrine hypervolume. Mean cortisol concentrations could not differentiate between various social and reproductive categories (MANOVA); however, in males an analysis of variance (principal component analysis) indicated that the contrast between cortisol and androstenedione was the principle axis of variance once the androgen secreting ability had been accounted for. On the other hand, the same contrast was found to be the principal axis of variance in the female sub-sample, suggesting that cortisol may play a significant role in regulating the endocrine dynamics of this species, despite showing little variance in mean values among various social and reproductive categories.     

Heritable variation for aggression as a reflection of individual coping strategies

Evidence is presented in rodents, that individual differences in aggression reflect heritable, fundamentally different, but equally valuable alternative strategies to cope with environmental demands. Generally, aggressive individuals show an active response to aversive situations. In a social setting, they react with flight or escape when defeated; in non-social situations, they react with active avoidance of controllable shocks and with sustained activity during an uncontrollable task. In contrast, non-aggressive individuals generally adopt a passive strategy. In social and non-social aversive situations, they react with immobility and withdrawal. A main aspect of these two alternative strategies is that individuals with an active strategy easily develop routines (intrinsically determined behaviour), and consequently do not react (properly) to 'minor' changes in their environment, whereas in passively reacting animals it is just the other way around (extrinsically determined behaviour). It has become clear that active and passive behavioural strategies represent two different, but equivalent, coping styles. The coping style of the aggressive males is aimed at the removal of themselves from the source of stress or at removal of the stress source itself (i.e. active manipulation). Non-aggressive individuals seem to aim at the reduction of the emotional impact of the stress (i.e. passive confrontation). The success of both coping styles depends upon the variability or stability of the environment. The fact that aggressive males develop routines may contribute to a fast execution of their anticipatory responses, which is necessary for an effective manipulation of events. However, this is only of advantage in predictable (stable) situations, but is maladaptive (e.g. expressed by the development of stress pathologies) when the animal is confronted with the unexpected (variable situations). The flexible behaviour of non-aggressive individuals, depending strongly upon external stimuli, will be of advantage under changing conditions. Studies on wild house mice living under natural conditions show how active and passive coping functions in nature, and how the two types have been brought about by natural selection.     

Real and optimal neural images in early vision.

It has been suggested that the first steps in visual processing strive to compress as much information as possible about the outside world into the limited dynamic range of the visual channels. Here I compare measured neural images with theoretical calculations based on maximizing information, taking into account the statistical structure of natural images. Neural images were obtained by scanning an image while recording from a second-order neuron in the fly visual system. Over a 5.5-log-units-wide range of mean intensities, experiment and theory correspond well. At high mean intensities, redundancy in the image is reduced by spatial and temporal antagonism. At low mean intensities, spatial and temporal low-pass filtering combat noise and increase signal reliability.     

Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A.

We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.     

Deficits in social behavior in autism and their modification by a synthetic adrenocorticotrophic hormone (4–9) analog

When charting the structure of the social behavior of autistic children by means of an ethologically analyzed playroom session, deficits appeared in the reciprocity of eye-contact and in the location of verbal initiatives. These deficits in social behavior were beneficially influenced by treatment with the adrenocorticotrophic hormone (4–9) analog ORG 2766.     

Germline mosaicism and Duchenne muscular dystrophy mutations

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease with an incidence of approximately 1 in 3,500 newborn boys. The DMD locus has a high mutation frequency: one third of the cases is thought to result from a new mutation. Linkage studies using probes to detect restriction fragment length polymorphisms and DNA deletion studies have greatly improved DMD carrier detection and prenatal diagnosis. Here we report on two families in which a pERT87 (DXS164) deletion was transmitted to more than one offspring by women who showed no evidence for the mutation in their own somatic (white blood) cells. We also show that the deletion in both siblings in one of the families is identical, indicating that the deletion must have occurred during mitosis in early germline proliferation, leading to a germline mosaicism. This phenomenon may turn out to be a major factor contributing to the induction of DMD mutations, and has important implications for the counselling of DMD families.