Gross rearrangements within the 5''-untranslated region of the picornaviral genomes.

An analysis of reported nucleotide sequences revealed several cases of gross rearrangements in the 5'-untranslated region (5-UTR) of picornaviral genomes. A large (greater than 100 nt) duplication was discovered in a downstream region of poliovirus 5-UTR involved in the translational control. Properties of the poliovirus mutants with large deletions [Kuge and Nomoto (1987) J. Virol. 61, 1478-1487] show that a single copy of the appropriate repeating unit is compatible with a wild type phenotype of the virus. In contrast to poliovirus and another enterovirus genomes, human rhinovirus RNAs contain only a single copy of this repeating unit. Another similarly large repeat was found in an upstream segment of the bovine enterovirus 5-UTR. A comparison of the primary and secondary structures of cardio- and aphthovirus 5-UTRs demonstrated the existence of a large (ca. 250 nucleotides) insertion/deletion in a region preceding the poly(C) tract. The two latter rearrangements appear to involve elements of the viral genome replication machinery. Possible origin as well as evolutionary and functional implications of these structural peculiarities are discussed.     

Age and Sex of Mice Markedly Affect Survival Times Associated with Hyperoxic Acute Lung Injury

Mortality associated with acute lung injury (ALI) remains substantial, with recent estimates of 35–45% similar to those obtained decades ago. Although evidence for sex-related differences in ALI mortality remains equivocal, death rates differ markedly for age, with more than 3-fold increased mortality in older versus younger patients. Strains of mice also show large differences in ALI mortality. To tease out genetic factors affecting mortality, we established a mouse model of differential hyperoxic ALI (HALI) survival. Separate genetic analyses of backcross and F₂ populations generated from sensitive C57BL/6J (B) and resistant 129X1/SvJ (X1) progenitor strains identified two quantitative trait loci (QTLs; Shali1 and Shali2) with strong, equal but opposite, within-strain effects on survival. Congenic lines confirmed these opposing QTL effects, but also retained the low penetrance seen in the 6–12 week X1 control strain. Sorting mice into distinct age groups revealed that ‘age at exposure’ inversely correlated with survival time and explained reduced penetrance of the resistance trait. While B mice were already sensitive by 6 weeks old, X1 mice maintained significant resistance up to 3–4 weeks longer. Reanalysis of F₂ data gave analogous age-related findings, and also supported sex-specific linkage for Shali1 and Shali2. Importantly, we have demonstrated in congenic mice that these age effects on survival correspond with B alleles for Shali1 (6-week old mice more sensitive) and Shali2 (10-week old mice more resistant) placed on the X1 background. Further studies revealed significant sex-specific survival differences in subcongenics for both QTLs. Accounting for age and sex markedly improved penetrance of both QTLs, thereby reducing trait variability, refining Shali1 to <8.5Mb, and supporting several sub-QTLs within the Shali2 interval. Together, these congenics will allow age- and sex-specific studies to interrogate myriad subphenotypes affected during ALI development and progression and identify intermediary injury biomarkers that can predict outcome.     

Effects of Peptide and Non-Peptide Opioids on Protective Reaction of the Cockroach Periplaneta americana in the “Hot Camera”

The ability of morphine, naloxone, and several opioid peptides of the group of beta-casomorphines to change the time of the stay of cockroaches Periplaneta americana in a hot camera (t = 47°C) was studied. It has been shown that the morphine dose ED₅₀ increasing twice the stay amounts to 200 µg/g, while hat of naloxone, to 40, of heptapeptide YPFPGPI, to 440, and of pentapeptide YPFPG, to 420 µg/g. Hexapeptide YPFPGP free of the N-terminal tyrosine had no statistically significant effect on the stay duration. The earlier changes of the stay duration (in 15–60 min after injection; the most pronounced for morphine and naloxone) corresponded to the ability of these drugs to act on the mu-type opioid receptors. The high peptide affinity to the delta-type receptors led to development of the later effects (in 90–150 min after injection; the most pronounced for heptapeptide YPFPGPI). A combined injection of naloxone and heptapeptide lead to the mutual inhibition of their effect: the peptide eliminated the early effect of naloxone on the stay duration, whereas naloxone, the late effects of beta-casomorphine. The obtained results indicate an important role of the endogenous opioid system in control of protective behavior of insects, as well as heterogeneity of the receptor components of the system.     

On the possibility of reflection of Alfvén waves in a curvilinear magnetic field

The propagation of Alfvén waves in a plasma immersed in a curvilinear magnetic field is investigated by using a 2D model. The waves are described by a 1D equation that formally coincides with the equation for the case of a quasi-uniform straight magnetic field with a modified Alfvén velocity that takes into account the longitudinal dependence of the Lame coefficients. It is shown that toroidal and poloidal Alfvén modes depend differently on the magnetic-field geometry. In the case of a 2D plane-parallel configuration of the magnetic field, poloidal modes are efficiently reflected from regions where the magnetic field lines sharply converge or diverge. This effect can result in the formation of open-field-line Alfvén quasi-resonators.     

Molecular mechanisms of attenuation of the Sabin strain of poliovirus type 3

Mutations critical for the central nervous system (CNS) attenuation of the Sabin vaccine strains of poliovirus (PV) are located within the viral internal ribosome entry site (IRES). We examined the interaction of the IRESs of PV type 3 (PV3) and Sabin type 3 (Sabin3) with polypyrimidine tract-binding protein (PTB) and a neural cell-specific homologue, nPTB. PTB and nPTB were found to bind to a site directly adjacent to the attenuating mutation, and binding at this site was less efficient on the Sabin3 IRES than on the PV3 IRES. Translation mediated by the PV3 and Sabin3 IRESs in neurons of the chicken embryo spinal cord demonstrated a translation deficit for the Sabin3 IRES that could be rescued by increasing PTB expression in the CNS. These data suggest that the low levels of PTB available in the CNS, coupled to a reduced binding of PTB on the Sabin3 IRES, leads to its CNS-specific attenuation. This study also demonstrates the use of the chicken embryo to easily investigate translation of RNA within a neuron in the CNS of an intact living organism.     

Rise in the epizootic activity of a natural focus of steppe-type tularemia in Stavropol Territory and its epidemic consequences

One of recurrent autumn and winter rises in the epizootic activity of the steppe-type focus of tularemia in the Stavropol Territory is described. During the tularemia epizooty of 1981-1982 the population of common voles (Microtus arvalis) was very numerous, while the population of house mice (Mus musculus) was comparatively scarce. Francisella tularensis strains were isolated from different species of rodents (Microtus arvalis, Mus musculus, Apodemus sylvanicus, Rattus norvegicus, Lepus, etc.), from fleas and ticks, as well as from environmental objects (well-water, hay). 38 cases of the disease among nonvaccinated persons, mainly in rural areas, were registered. Anginous-bubonic tularemia was the dominant form of the disease. A complex of measures aimed at the detection of tularemia and its liquidation among the population was carried out.