Evolution of the ABPA subunit of androgen-binding protein expressed in the submaxillary glands in New and Old World rodent taxa.

The salivary androgen-binding proteins (ABPs) are members of the secretoglobin gene family present in mammals. Each ABP is a heterodimer assembled as an ABPA subunit encoded by an Abpa gene and linked by disulfide bridges to an ABPBG subunit encoded by an Abpbg gene. The ABP dimers are secreted into the saliva of mice and then transferred to the pelage after grooming and subsequently to the environment allowing an animal to mark territory with a biochemical signal. The putative role of the mouse salivary ABPs is that of pheromones mediating mate selection resulting in assortative mating in the Mus musculus species complex. We focused on comparing patterns of molecular evolution between the Abpa genes expressed in the submaxillary glands of species of New World and Old World muroids. We found that in both sets of rodents the Abpa genes expressed in the submaxillary glands appear to be evolving under a similar evolutionary regime, with relatively high nonsynonymous substitution rates, suggesting that ABP might play a similar biological role in both systems. Thus, ABP could be involved with mate recognition and species isolation in New World as well as Old World muroids.

Tick-borne encephalitis virus, Kyrgyzstan.

Tick-borne encephalitis virus (TBEV) is an emerging pathogen in Europe and Asia. We investigated TBEV in Kyrgyzstan by collecting small mammals and ticks from diverse localities and analyzing them for evidence of TBEV infection. We found TBEV circulating in Kyrgyzstan much farther south and at higher altitudes than previously reported.

Interlobular excretory ducts of mammalian salivary glands: structural and histochemical review.

In the major salivary glands of mammals, excretory ducts (EDs) succeed striated ducts. They are for the most part interlobular in position, although their proximal portions sometimes are on the periphery of a lobule, where they occasionally retain some of the structural features of striated ducts. Based on a survey of a broad range of mammalian species and glands, the predominant tissue type that composes EDs is pseudostratified epithelium. In some species, there is a progression of epithelial types: the proximal EDs are composed of simple cuboidal or columnar epithelium that, in the excurrent direction, usually gives way to the pseudostratified variety. Secretory granules are visible in the apical cytoplasm of the principal cells of the EDs of only a few species, but histochemistry has shown the presence of a variety of glycoproteins in these cells in a spectrum of species. Moreover, the latter methodology has revealed the presence of a variety of oxidative, acid hydrolytic, and transport enzymes in the EDs, showing that, rather than simply acting as a conduit for saliva, these ducts play a metabolically active role in gland function. It is difficult to describe a "typical" mammalian ED because it can vary along its length and interspecific variation does not follow a phylogenetic pattern. Moreover, in contrast to intercalated and striated ducts, ED cellular features do not exhibit a relationship to diet.

Mitochondrial DNA heteroplasmy in laboratory mice experimentally enclosed in the radioactive Chernobyl environment.

Mitochondrial DNA heteroplasmy using the protein-coding cytochrome b (Mtcyb) gene was assessed in laboratory mice (C57BL/6 and BALB/c) exposed to the Chernobyl environment. Subacute to subchronic (30-40 days) exposure resulted in a cumulative radiation dose of 1.2-1.6 Gy ( approximately 0.04 Gy/day). Mice were sampled prior to introduction into the enclosures and again after removal from the enclosures. Nucleotide variation (site heteroplasmy) in 306 pre-exposure Mtcyb gene copies (122400 base pairs) was compared to variation in 354 postexposure gene copies (141600 base pairs). Five mutant copies, each characterized by a single nucleotide substitution, were observed (four in the pre-exposure samples, one in a postexposure sample). The frequencies of mutant gene copies and nucleotide substitutions in pre-exposure and postexposure samples were not significantly different. This suggests that this type of exposure (i.e. low dose rate) does not pose a significant mutation risk to the Mtcyb gene in digit tissue. Furthermore, no significant radiation risk to analogous human tissues may exist when occupational exposures involve low dose rates such as these. Finally, linear, cumulative models of genetic risk currently used to estimate radiation-induced effects are likely to be inappropriate for low-dose-rate exposures and need to be re-evaluated critically.

Exposure to chronic, low-dose rate gamma-radiation at Chornobyl does not induce point mutations in Big Blue mice.

Empirical genetic effects resulting from low-dose rate irradiation and chronic, cumulative exposure are poorly characterized. Expected effects are based on epidemiological studies and downward, linear extrapolations from nonthreshold models derived from acute, high-dose exposures. These extrapolations and their associated risk coefficients have no experimental support, and because of their inherent uncertainty they are the subject of considerable debate. The expectation of deleterious genetic effects resulting from low-dose rate irradiation and chronic exposure is in need of empirical assessment because this type of exposure is typical of those encountered in occupational, residential, and environmental settings. Recent acute low-dose (<10 cGy) studies using cytogenetic and point mutation endpoints indicate that observed effects range from those lower than spontaneous to an increase in the frequency of point mutations. Using the Big Blue assay, we examined the ability of chronic, continuous gamma-irradiation (2.3 x 10(-3) cGy/min) in the Chornobyl environment to induce point mutations. This system has demonstrated a significant point mutation sensitivity (4.5-fold increase) to acute, high-dose (1-3 Gy) gamma-radiation. Mutant frequencies and the mutation spectra were examined in exposed and reference samples of Big Blue mice following 90 days exposure (cumulative absorbed dose = 3 Gy) to the Chornobyl environment. No significant increase in the mutant frequency or bias in the mutational spectrum was observed in exposed individuals. This finding suggests that low-dose rate gamma-irradiation at Chornobyl does not induce point mutations and that cumulative, chronically absorbed doses do not induce the same genetic effects as acute doses of the same magnitude.

The dynamics of two viral infections in a single host population with applications to hantavirus.

An SI epidemic model for a host with two viral infections circulating within the population is developed, analyzed, and numerically simulated. The model is a system of four differential equations which includes a state for susceptible individuals, two states for individuals infected with a single virus, one which is vertically transmitted and the other which is horizontally transmitted, and a fourth state for individuals infected with both viruses. A general growth function with density-dependent mortality is assumed. A special case of this model, where there is no coinfection and total cross immunity, is thoroughly analyzed. Several threshold values are defined which determine establishment of the disease and persistence at equilibrium for one or both of the infections within the host population. The model has applications to a hantavirus and an arenavirus that infect cotton rats. The hantavirus is transmitted horizontally whereas the arenavirus is transmitted vertically. It is shown through analysis and numerical simulations that both diseases can be maintained within a single host population, where individuals can be either infected with both viruses or with a single virus.

Ultrastructure of the submandibular gland of the rare white-winged vampire bat, Diaemus youngi.

The submandibular gland of the white-winged vampire bat, Diaemus youngi, was examined by electron microscopy. Unlike typical submandibular glands, those in Diaemus have only one type of secretory cell in their endpieces, namely, serous cells. These serous cells are conventional in structure, with an extensive rough endoplasmic reticulum, scattered dictyosomes, and numerous secretory granules. The endpiece lumina, as well as intercellular canaliculi, are fitted with numerous microvilli, which also are present on the otherwise unremarkable intercalated duct cells. Striated ducts are of conventional morphology, but have a brush border-like array of microvilli on their luminal surface. These cells resemble those in the submandibular gland of the common vampire bat, Desmodus rotundus. The presence of an abundance of microvilli in the salivary glands in the two vampire bat species (and their absence from chiropteran species that consume other types of diets) is a strong indication that these structures play a significant role in dealing with the problems posed by a sanguivorous diet.

Dietary and flight energetic adaptations in a salivary gland transcriptome of an insectivorous bat.

We hypothesized that evolution of salivary gland secretory proteome has been important in adaptation to insectivory, the most common dietary strategy among Chiroptera. A submandibular salivary gland (SMG) transcriptome was sequenced for the little brown bat, Myotis lucifugus. The likely secretory proteome of 23 genes included seven (RETNLB, PSAP, CLU, APOE, LCN2, C3, CEL) related to M. lucifugus insectivorous diet and metabolism. Six of the secretory proteins probably are endocrine, whereas one (CEL) most likely is exocrine. The encoded proteins are associated with lipid hydrolysis, regulation of lipid metabolism, lipid transport, and insulin resistance. They are capable of processing exogenous lipids for flight metabolism while foraging. Salivary carboxyl ester lipase (CEL) is thought to hydrolyze insect lipophorins, which probably are absorbed across the gastric mucosa during feeding. The other six proteins are predicted either to maintain these lipids at high blood concentrations or to facilitate transport and uptake by flight muscles. Expression of these seven genes and coordinated secretion from a single organ is novel to this insectivorous bat, and apparently has evolved through instances of gene duplication, gene recruitment, and nucleotide selection. Four of the recruited genes are single-copy in the Myotis genome, whereas three have undergone duplication(s) with two of these genes exhibiting evolutionary 'bursts' of duplication resulting in multiple paralogs. Evidence for episodic directional selection was found for six of seven genes, reinforcing the conclusion that the recruited genes have important roles in adaptation to insectivory and the metabolic demands of flight. Intragenic frequencies of mobile- element-like sequences differed from frequencies in the whole M. lucifugus genome. Differences among recruited genes imply separate evolutionary trajectories and that adaptation was not a single, coordinated event.