A dynamic model for in vivo virus replication

In this paper we present a dynamic model of in vivo virus replication. Kinetic equations are formulated to describe the overall process of replication and then analyzed using a “synergetic” approach. First the importance of a rate-limiting substrate is taken explicitly into account, and secondly the coupling between the processes considered (translation, replication and assembly) is strictly preserved; the analysis itself is carried out in the linear regime. We treat the problems of defective-particle infections, standard-virus infections, inhibition of cellular synthesis, and the case of co-infected cells. The various parameters of the model (initial cellular concentrations, rate constants) are specified using existing experimental data and the full (numerical) consequences of the model are explored in detail and compared directly with experiments by Baltimore, Cole and others on viral systems. Quite surprisingly, the simple model developed in this paper is able to account qualitatively, and occasionally quantitatively, for the behavior observed experimentally for each of the problems cited above.     

Musculoskeletal Symptoms and Risk of Burnout in Child Care Workers — A Cross-Sectional Study

ObjectivesGerman child care workers'' job satisfaction is influenced by the consequences of unfavourable underlying conditions. Child care workers tend to suffer from psychosocial stress, as they feel that their work is undervalued. The objective of the present study is to investigate how the psychosocial factors of the effort-reward imbalance (ERI) model influence musculoskeletal symptoms (MS) and the risk of burnout. To our knowledge this is the first study investigating the association between the factors of the ERI model and MS in child care workers.ConclusionOvercommitment in child care workers is related to MS and risk of burnout. There is also evidence that low control is associated with MS and subjective noise exposure with risk of burnout. Effort-reward imbalance is not related to either outcome. This occupational health risk assessment identifies changeable working factors in different types of facilities.     

Functional changes in brainstem auditory structures in humans suffering from the Chernobyl’ catastrophe

We analyzed the temporal characteristics of short-latency auditory evoked potentials (SL AEP) in people involved in the cleanup work after the Chemobyl’ catastrophe (hereafter, cleanup workers), who now are living within the “clean” territories or remain within the radionuclide-contaminated area (groups 2 and 3, respectively), and in persons who were not involved in the cleanup works but are permanently living within the contaminated zone (group 4). The latencies of the SL AEP were peaks (peak latencies, PL) in all these groups regularly exceeded corresponding values in the control group 1. The increments were mild (several percent) but significant for the waves II–V. The most substantial PL increments were characteristic for group 3. Analysis of the interpeak intervals showed that an increase in the I–III interval provided the greatest contribution to modification of the SL AEP, temporal parameters. The mechanisms of influence of the Chernobyl’ catastrophe-related factors on the brainstem auditory structures are discussed. The data allow us to conclude that functional modifications in the above structures contribute to the hearing change for the worse observed in the people suffering from the Chernobyl’ catastrophe; a prolonged stay within the contaminated territories represents a considerable factor aggravating these changes.     

Regional linkage analysis of the dioxin-inducible P-450 gene family on mouse chromosome 9

The dioxin-inducible P-450 gene family in the C57BL/6N mouse comprises two genes, P1-450 and P3-450. Restriction endonuclease-digested genomic DNA was probed with P1-450 and P3-450 full-length cDNA clones in an attempt to find species-specific fragment length differences between mouse and hamster cell lines and any restriction fragment length polymorphism among four inbred mouse strains. With this Southern blot hybridization technique, PstI fragments were used to distinguish between the mouse and hamster P1-450/P3-450 genes, and PvuII fragments were used to distinguish P3-450 differences between the AKR/J and C57L/J inbred strains. Analysis of nineteen mouse X hamster somatic cell hybrid lines and sixteen AKXL (AKR/J X C57L/J) recombinant inbred lines showed that the P1-450/P3-450 genes are located near the Mpi-1 locus, between the Thy-1 and Pk-3 loci, in the middle portion of mouse chromosome 9.     

Interacting Genes Control Glycerol-3-Phosphate Dehydrogenase Expression in Developing Cerebellum of the Mouse

The cerebellum of BALB/cJ mice has approximately 2.5 times as much glycerol-3-phosphate dehydrogenase (GPDH) as that of C57BL/6J mice. This difference in enzyme levels, which positively correlates with similar differences in the levels of hybridizable GPDH mRNA, is controlled by at least two unlinked regulatory loci and the structural gene, Gdc-1, located on chromosome 15. These regulatory loci, which act predominantly during the second and third weeks of postnatal cerebellar development and differentiation, have been separated from each other in the CXB recombinant inbred strains of mice. One regulatory locus, Gdcr-1, although unlinked to the structural gene, has an allele in BALB/c mice that preferentially enhances expression of the BALB/c structural allele at Gdc-1. The other locus, Gdcr-2, which may or may not be single, enhances GPDH expression at Gdc-1 irrespective of the allele present, as is commonly observed for loci acting from a distance. Measurements of GPDH mRNA in the recombinant inbred mice suggest that these regulatory genes act by modulating mRNA levels. Accordingly, the regulation of GPDH expression in the cerebellum of mice depends on a complex interaction of unlinked regulatory elements with regulatory elements near the structural gene. Furthermore, since the Gdc-1 locus is expressed in virtually every tissue of the mouse except blood and since the observed genetic variation is restricted to the cerebellum, it is likely that other tissues will have their own distinctive genetic mechanisms for modulating Gdc-1 expression.     

Different effects of eubacterial and eukaryotic DNA topoisomerase II inhibitors on chloroplasts ofEuglena gracilis

Inhibitors of eubacterial and eukaryotic DNA topoisomerases type II exhibited different effects on chloroplasts of the flagellateEuglena gracilis. Antibacterial agents (cinoxacin, nalidixic and oxolinic acids, ciprofloxacin, enoxacin, norfloxacin and ofloxacin) from the group of quinolones and coumarins (coumermycin A₁, clorobiocin and novobiocin) — all inhibitors of prokaryotic DNA topoisomerase II — were very potent eliminators of chloroplasts fromE. gracilis. In contrast, antitumor drugs (adriamycin, etoposide, teniposide and mitoxantrone) — antagonists of the eukaryotic counterpart — did not affect these semiautonomous photosynthetic organelles. These findings point out again the close evolutionary relationships between eubacteria and chloroplasts and are in agreement with the hypothesis of an endosymbiotic origin of chloroplasts.     

Analysis of wild-derived mice for Fv-1 and Fv-2 murine leukemia virus restriction loci: a novel wild mouse Fv-1 allele responsible for lack of host range restriction.

Wild-derived mice originally obtained from Asia, Africa, North America, and Europe were typed for in vitro sensitivity to ecotropic murine leukemia viruses and for susceptibility to Friend virus-induced disease. Cell cultures established from some wild mouse populations were generally less sensitive to exogenous virus than were cell cultures from laboratory mice. Wild mice also differed from inbred strains in their in vitro sensitivity to the host range subgroups defined by restriction at the Fv-1 locus. None of the wild mice showed the Fv-1n or Fv-1b restriction patterns characteristic of most inbred strains, several mice resembled the few inbred strains carrying Fv-1nr, and most differed from laboratory mice in that they did not restrict either N- or B-tropic murine leukemia viruses. Analysis of genetic crosses of Mus spretus and Mus musculus praetextus demonstrated that the nonrestrictive phenotype is controlled by a novel allele at the Fv-1 locus, designated Fv-10. The wild mice were also tested for sensitivity to Friend virus complex-induced erythroblastosis to type for Fv-2. Only M. spretus was resistant to virus-induced splenomegaly and did not restrict replication of Friend virus helper murine leukemia virus. Genetic studies confirmed that this mouse carries the resistance allele at Fv-2.