Stereotypies in Laboratory Mice — Quantitative and Qualitative Description of the Ontogeny of ‘Wire-gnawing’ and ‘Jumping’ in Zur:ICR and Zur:ICR nu

The ontogeny of two stereotypic patterns, wire-gnawing and jumping, was studied in 24 laboratory mice: six males and six females each of two closely related outbred strains, kept under standard housing conditions, a conventional albino strain (ICR) and a nude, athymic mutant (ICR nu; hereafter: NU). All 24 individuals developed wire-gnawing after weaning at 20 d of age. In ICR one female and in NU five males and three females additionally developed jumping. ICR developed wire-gnawing between the age of 20 and 30 d, in NU jumping started at the age of 20 d, but intense jumping and wire-gnawing comparable to that of ICR did not develop in NU before the age of 40–50 d. Within each strain there was no significant difference between males and females with respect to the development of stereotypic behaviour. By contrast, ICR showed significantly more wire-gnawing but less jumping than NU. Stereotypy level increased with age up to a mean of 10.7 % of total activity in ICR and up to 7.4 % in NU at 100 d of age. However, there was huge inter- and intra-individual variability with respect to all parameters assessed in this study, i.e. total duration, number of bouts and bout length of the two stereotyped patterns. Wire-gnawing developed from outside-directed explorative climbing at the cage lid, whereas the source behaviour pattern (Mason 1991 a, Anim. Behav. 41, 1015–1037) of jumping was outside-directed explorative rearing at the cage wall. At 20 d of age, before the onset of stereotypy development, ICR showed significantly more climbing but less rearing than NU. Physical retardation of NU at weaning may account for decreased climbing ability during early ontogeny, and hence for the retarded development of wire-gnawing. The difference in early experience with either of the two patterns rather than genetic effects may be responsible for the qualitative difference between the strains with respect to the form of later stereotypy.     

Chemical crosslinking of different forms of the simian virus 40 large T antigen using bifunctional reagents

Chemical crosslinking was used for a direct analysis of the different forms of large tumor (T) antigen, the simian virus 40 A gene product. The first subclass, sedimenting at 14-16S, is composed of monomeric to tetrameric units, whereas the second, sedimenting at 5-6S, only contains dimers and monomers of T. The occurrence of oligomeric structures of T in solution which are higher than dimers suggests the possibility of direct binding of such trimers or tetramers to the origin of replication of the viral DNA as an alternative to the formation of these structures by aggregation of bound dimers or monomers after their sliding along the DNA.     

Analysis of the Factors Involved in the Retinoic Acid-Induced Differentiation of a Retinoid-Hypersensitive Embryonal Carcinoma Cell Mutant

Retinoic acid (RA) has been known to play an important role in cellular growth and differentiation as well as in vertebrate development. Many in vitro cell cultures also respond to RA by differentiating. Perhaps the most widely studied of these cultures are embryonal carcinoma (EC) cells. We have used an RA-hypersensitive EC cell mutant, created by retroviral insertion, to analyze the activity of the identifiable components in the RA response pathway. We have analyzed the mRNA expression patterns of the retinoic acid receptors (RARs) α, β, and γ, the retinoid X receptors (RXRs) α, β, and γ, and the cellular retinoic acid binding proteins (CRABPs) I and II. Our results indicate that CRABP I, RAR β, and RAR γ mRNAs are expressed differentially between parent and RA-hypersensitive mutant cells. All three messages are present at higher basal levels and at earlier times after RA addition in the mutant relative to parental cells. All other elements examined are equivalently expressed. Therefore analyses of the expression patterns of CRABPs, RARs, and RXRs in these RA-hypersensitive cells point to the probable importance of CRABP I, RAR β, and RAR γ in the RA induction pathway and also indicate that CRABP II and RXR γ are not likely to be critical elements in the early differentiative response of cells to RA.     

Cosolute modulation of protein oligomerization reactions in the homeostatic timescale

Protein oligomerization processes are widespread and of crucial importance to understand degenerative diseases and healthy regulatory pathways. One particular case is the homo-oligomerization of folded domains involving domain swapping, often found as a part of the protein homeostasis in the crowded cytosol, composed of a complex mixture of cosolutes. Here, we have investigated the effect of a plethora of cosolutes of very diverse nature on the kinetics of a protein dimerization by domain swapping. In the absence of cosolutes, our system exhibits slow interconversion rates, with the reaction reaching the equilibrium within the average protein homeostasis timescale (24–48 h). In the presence of crowders, though, the oligomerization reaction in the same time frame will, depending on the protein's initial oligomeric state, either reach a pure equilibrium state or get kinetically trapped into an apparent equilibrium. Specifically, when the reaction is initiated from a large excess of dimer, it becomes unsensitive to the effect of cosolutes and reaches the same equilibrium populations as in the absence of cosolute. Conversely, when the reaction starts from a large excess of monomer, the reaction during the homeostatic timescale occurs under kinetic control, and it is exquisitely sensitive to the presence and nature of the cosolute. In this scenario (the most habitual case in intracellular oligomerization processes), the effect of cosolutes on the intermediate conformation and diffusion-mediated encounters will dictate how the cellular milieu affects the domain-swapping reaction.     

Description of new species of two genera Dayus Mahmood and Znana Dworakowska from Thailand (Hemiptera: Cicadellidae: Typhlocybinae)

Two genera, Dayus Mahmood, 1967 and Znana Dworakowska, 1994 of the leafhopper tribe Empoascini (Hemiptera: Cicadellidae: Typhlocybinae) are reviewed. One new species of each genus, Dayus furcatus sp. nov. and Znana furca sp. nov., are described from Thailand. A checklist and distribution summary of Dayus Mahmood species is given. Male habitus photos and illustrations of male genitalia of the two new species and notes on allied species are also provided.     

Heptageniidae (Insecta,Ephemeroptera) of Thailand

Nine genera and twenty-two species of heptageniid mayflies from Thailand are defined in this present work as well as one suggested further subgenus, Compsoneuria (Siamoneuria) kovaci (species “incertae sedis”) including some particular characters. Taxonomic remarks, diagnoses, line drawings of key characters, distribution, habitat and biological data, and a larval key to the genera and species are provided. The chorionic eggs of eight genera and eight species were observed and shown using a scanning electron microscope.     

Rare Variants in PLXNA4 and Parkinson’s Disease

Approximately 20% of individuals with Parkinson’s disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.