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Allometric scaling of the maximum metabolic rate of mammals: oxygen transport from the lungs to the heart is a limiting step.

BACKGROUND: The maximum metabolic rate (MMR) of mammals is approximately proportional to M(0.9), where M is the mammal's body weight. Therefore, MMR increases with body weight faster than does the basal metabolic rate (BMR), which is approximately proportional to M(0.7). MMR is strongly associated with the capacity of the cardiovascular system to deliver blood to capillaries in the systemic circulation, but properties of this vascular system have not produced an explanation for the scaling of MMR. RESULTS: Here we focus on the pulmonary circulation where resistance to blood flow (impedance) places a limit on the rate that blood can be pumped through the lungs before pulmonary edema occurs. The maximum pressure gradient that does not produce edema determines the maximum rate that blood can flow through the pulmonary veins without compromising the diffusing capacity of oxygen. We show that modeling the pulmonary venous tree as a fractal-like vascular network leads to a scaling equation for maximum cardiac output that predicts MMR as a function of M as well as the conventional power function aM(b) does and that least-squares regression estimates of the equation's slope-determining parameter correspond closely to the value of the parameter calculated directly from Murray's law. CONCLUSION: The assumption that cardiac output at the MMR is limited by pulmonary capillary pressures that produce edema leads to a model that is in agreement with experimental measurements of MMR scaling, and the rate of blood flow in pulmonary veins may be rate-limiting for the pathway of oxygen.

Animals↗

Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals.

BACKGROUND: In mammals, contrary to what is usually assumed, recent evidence suggests that synonymous mutations may not be selectively neutral. This position has proven contentious, not least because of the absence of a viable mechanism. Here we test whether synonymous mutations might be under selection owing to their effects on the thermodynamic stability of mRNA, mediated by changes in secondary structure. RESULTS: We provide numerous lines of evidence that are all consistent with the above hypothesis. Most notably, by simulating evolution and reallocating the substitutions observed in the mouse lineage, we show that the location of synonymous mutations is non-random with respect to stability. Importantly, the preference for cytosine at 4-fold degenerate sites, diagnostic of selection, can be explained by its effect on mRNA stability. Likewise, by interchanging synonymous codons, we find naturally occurring mRNAs to be more stable than simulant transcripts. Housekeeping genes, whose proteins are under strong purifying selection, are also under the greatest pressure to maintain stability. CONCLUSION: Taken together, our results provide evidence that, in mammals, synonymous sites do not evolve neutrally, at least in part owing to selection on mRNA stability. This has implications for the application of synonymous divergence in estimating the mutation rate.

Amino Acid Substitution↗

Measuring fecal glucocorticoid metabolites in mammals and birds: the importance of validation.

In recent years, the noninvasive monitoring of steroid hormone metabolites in feces of mammals and droppings of birds has become an increasingly popular technique. It offers several advantages and has been applied to a variety of species under various settings. However, using this technique to reliably assess an animal's adrenocortical activity is not that simple and straightforward to apply. Because clear differences regarding the metabolism and excretion of glucocorticoid metabolites (GCMs) exist, a careful validation for each species and sex investigated is obligatory. In this review, general analytical issues regarding sample storage, extraction procedures, and immunoassays are briefly discussed, but the main focus lies on experiments and recommendations addressing the validation of fecal GCM measurements in mammals and birds. The crucial importance of scrutinizing the physiological and biological validity of fecal GCM analyses in a given species is stressed. In particular, the relevance of the technique to detect biologically meaningful alterations in adrenocortical activity must be shown. Furthermore, significant effects of the animals' sex, the time of day, season, and different life history stages are discussed, bringing about the necessity to seriously consider possible sex differences as well as diurnal and seasonal variations. Thus, comprehensive information on the animals' biology and stress physiology should be carefully taken into account. Together with an extensive physiological and biological validation, this will ensure that the measurement of fecal GCMs can be used as a powerful tool to assess adrenocortical activity in diverse investigations on laboratory, companion, farm, zoo, and wild animals.

Animals↗

Cloning of a teleost fish glucocorticoid receptor shows that it contains a deoxyribonucleic acid-binding domain different from that of mammals.

In the teleost fish, physiological and biochemical studies suggest that glucocorticoids regulate both salt balance and metabolic activities. In mammals, however, these functions are divided between glucocorticoids and mineralocorticoids. In mammals, separate receptors for these two classes of steroid hormone have been cloned and sequenced. To begin to understand the regulation in fish of the vital processes ascribed to glucocorticoids, we have cloned, sequenced, expressed, and studied the steroid-binding and transcriptional activation capabilities of the rainbow trout (Onchorhynchus mykiss) glucocorticoid receptor. Northern blot analysis shows a single rainbow trout GR messenger RNA species of 7.5 kilobases expressed in gill, intestine, skeletal muscle, kidney, and liver. The trout GR 2274-nucleotide coding sequence provides for a protein of 758 amino acids, with appropriate similarities to mammalian GR, with one striking exception. As in other members of the steroid/thyroid/retinoid receptor family, the DNA-binding domain contains two putative zinc fingers. These have high homology with those of other GRs. However, between the zinc fingers in the trout GR are found 9 more amino acids than are seen in mammalian GRs, raising questions as to the functional form of the fish, as opposed to the mammalian, GR. It has been proposed that as fish appear to use glucocorticoids for both metabolic and salt control, presumably through a single GR, GR would prove to be the evolutionary precursor to mammalian GR and mineralocorticoid receptor (MR). Computer analysis of the known sequences of GRs and MRs, however, suggests that the fish GR did not give rise to the MR of higher animals, but that both subfamilies of receptor arose from some earlier gene.

Amino Acid Sequence↗

A cloned frog vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptor exhibits pharmacological and tissue distribution characteristics of both VPAC1 and VPAC2 receptors in mammals.

Three receptor subtypes for the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been identified in mammals: the PAC1 receptor (PAC1-R) which is selectively activated by PACAP, and two VPAC receptors (VPAC1-R and VPAC2-R), which are equally stimulated by PACAP and VIP. The structures of PACAP and VIP have been well conserved during evolution, but little is known about VIP/PACAP receptors in nonmammalian species. An amphibian VIP/PACAP receptor complementary DNA (cDNA) has been cloned and characterized from a frog (Rana ridibunda) pituitary cDNA library. The predicted protein contains seven putative transmembrane domains and exhibits the highest sequence identity (65%) with the human VPAC1-R. The cloned cDNA was transiently expressed in LLC-PK1 cells, and its pharmacological profile was determined in comparison with the human VPAC1-R. Both PACAP and VIP stimulated cAMP accumulation through the cloned receptor with an EC50 of about 30 nM. In contrast, secretin, at concentrations that stimulate the human VPAC1-R, had no effect on cAMP production. RT-PCR analysis revealed the widespread distribution of this frog VIP/PACAP receptor in peripheral tissues. In situ hybridization histochemistry using a complementary RNA probe showed that the receptor gene is highly expressed in several hypothalamic and thalamic nuclei and to a lesser extent in the pallium and striatum. In the pituitary, the highest messenger RNA levels were detected in the distal lobe. Taken together, these data show that the cloned frog receptor shares several common features with both the VPAC1-R and VPAC2-R of mammals; the frog receptor exhibits the highest sequence identity with mammalian VPAC1-R, but the lack of effect of secretin and the brain distribution of the receptor are reminiscent of the characteristics of the mammalian VPAC2-R. The sequence of the frog receptor should thus prove useful to decipher the structure-activity relationships of the VIP/PACAP receptor family.

Adenylyl Cyclases↗

Sagittal spine movements of small therian mammals during asymmetrical gaits.

Mammalian locomotion is characterized by the use of asymmetrical gaits associated with extensive flexions and extensions of the body axis. Although the impact of sagittal spine movements on locomotion is well known, little information is available on the kinematics of spinal motion. Intervertebral joint movements were studied in two metatherian and three eutherian species during the gallop and halfbound using high-speed cineradiography. Fast-Fourier transformation was used to filter out high frequency digitizing errors and keep the lower frequency sinusoid oscillations that characterize the intervertebral angular movements. Independent of their regional classification as thoracic or lumbar vertebrae, 7+/-1 presacral intervertebral joints were involved in sagittal bending movements. In only one species, no more than five intervertebral joints contributed to the resulting 'pelvic movement'. In general, the trunk region involved in sagittal bending during locomotion did not correspond to the traditional subdivisions of the vertebral column (e.g. as thoracic and lumbar or pre- and postdiaphragmatic region). Therefore, these classifications do not predict the regions involved in spinal oscillations during locomotion. Independent of the gait, maximum flexion of the spine was observed in the interval between the last third of the swing phase and touch-down. This results in a retraction of the pelvis and hindlimbs before touch-down and, we hypothesize, enhances the stability of the system. Maximum extension occurred during the first third of the swing phase (i.e. after lift-off) in all species. In general, the observed timing of dorsoventral oscillations of the spine are in accordance with that observed in other mammals and with activity data of respiratory and epaxial back muscles. Although no strict craniocaudal pattern was observable, the more cranial intervertebral joints tend to flex and extend earlier than the more caudal ones. This is in accordance with the organization and the activation of the paravertebral musculature in mammals. The amplitude of intervertebral joint movements increased caudally, reaching its highest values in the presacral joint. The more intense sagittal bending movements in the caudal intervertebral joints are reflected by the muscle fiber type composition of the back muscles involved. Despite the highly similar amplitude of 'pelvic motion', touch-down and lift-off positions of the pelvis were clearly different between the species with a long, external tail and those with no external tail.

Animals↗

Respiratory and cardiovascular control during diving in birds and mammals.

Recent studies on freely diving birds and mammals indicate that, contrary to the classical hypothesis, the majority of dives are aerobic with minimal cardiovascular adjustments (i.e. bradycardia and selective vasoconstriction). It is postulated that during these aerobic dives the cardiovascular adjustments result from the opposing influences of exercise and the classical diving response, with the bias towards the exercise response. It is envisaged that the active muscles, as well as the brain and heart, are adequately supplied with blood to enable them to metabolize aerobically. Intense mental activity, particularly in carnivores seeking their prey, may also attenuate the classical response. Aerobic dives are usually terminated well before the oxygen stores are depleted, and another dive follows once they have been replenished. In this way a series of dives is performed. Prolonged dives are endured as a result of a shift towards the classical response of bradycardia, presumably more intense vasoconstriction, and anaerobiosis. This may be a form of alarm response, particularly in small animals such as ducks and coypus, or it may be a means of allowing the marine birds and mammals that dive deeply for their food to engage in unusually long hunting expeditions. For those that dive under ice, it may also allow long periods of underwater exploration as well as being a safety mechanism should the animal become disoriented.

Afferent Pathways↗

The relationship between body mass and rate of rewarming from hibernation and daily torpor in mammals.

1. Rewarming rate from torpor and body mass were inversely related in 86 mammals ranging in body mass between 2 and 8500 g. 2. Most of the mammalian taxa investigated showed a similar change of rewarming rate with body mass. Only the insectivores showed a more pronounced increase in rewarming with a decrease in body mass than did the other taxa. The rates of rewarming of marsupials were similar to those of placentals. 3. At low air temperature (Ta), the rate of rewarming of marsupials was not related to body mass, although a strong relationship between the two variables was observed in the same species at high Ta. 4. The slopes relating rewarming rates and body mass of the mammalian groups and taxa analysed here were similar to those obtained earlier for mass-specific basal metabolic rate (BMR) and body mass in mammals, suggesting that the rate of rewarming and BMR are physiologically linked.

Animals↗

Endocrine-disrupting chemicals and climate change: A worst-case combination for arctic marine mammals and seabirds?

The effects of global change on biodiversity and ecosystem functioning encompass multiple complex dynamic processes. Climate change and exposure to endocrine-disrupting chemicals (EDCs) are currently regarded as two of the most serious anthropogenic threats to biodiversity and ecosystems. We should, therefore, be especially concerned about the possible effects of EDCs on the ability of Arctic marine mammals and seabirds to adapt to environmental alterations caused by climate change. Relationships between various organochlorine compounds, necessary such as polychlorinated biphenyls, dichlorophenyldichloroethylene, hexachlorobenzene, and oxychlordane, and hormones in Arctic mammals and seabirds imply that these chemicals pose a threat to endocrine systems of these animals. The most pronounced relationships have been reported with the thyroid hormone system, but effects are also seen in sex steroid hormones and cortisol. Even though behavioral and morphological effects of persistent organic pollutants are consistent with endocrine disruption, no direct evidence exists for such relationships. Because different endocrine systems are important for enabling animals to respond adequately to environmental stress, EDCs may interfere with adaptations to increased stress situations. Such interacting effects are likely related to adaptive responses regulated by the thyroid, sex steroid, and glucocorticosteroid systems.

Animals↗

The use of mammals as sentinels for human exposure to toxic contaminants in the environment.

The use of sentinel species shows the potential to bridge the gap between animal-based and human-based environmental health research. With regard to the assessment of environmental contamination, the use of the terms "indicator," "monitor," and "sentinel" has often been confusing and ambiguous. A set of definitions is proposed as a standard to rectify this situation. The advantages of the use of sentinel species are provided, as well as criteria for sentinel selection, based on species characteristics. The recent use of mammals as sentinels for human exposure to toxic environmental contaminants is reviewed. A tabulated review of mammals proposed as indicators or monitors is included, as these may act as a database for the selection of sentinel species for future research efforts. The complexity and subtlety of factors interacting between an organism and its environment make it imperative that one provide a focused definition of what one wants the sentinel to assess and for what particular aspect of human health. Some examples of how sentinels might be selected for particular research questions are provided. While the potential for sentinel use in the field of environmental health is enormous, future investigators need to choose sentinels carefully, based on well-defined research questions, and confine conclusions drawn to the particular problem the sentinel was chosen to assess.

Animals↗

An investigation of gram-negative tannin-protein complex degrading bacteria in fecal flora of various mammals.

Gram-negative tannin-protein complex degrading bacteria (T-PCDB) were first isolated from animals except for the koala. The occurrence of T-PCDB in feces of 15 species of mammals with different feeding habits was investigated. T-PCDB occurred in 7 of 54 horses but they could not be isolated from other mammals tested. These T-PCDB comprised less than 0.1% of the facultative anaerobic microflora in horse feces and it was much less than that previously reported in koala feces ( > 60%). A total of 7 T-PCDB fecal isolates showed a range of phenotypic diversities. They were all Gram-negative rods of various sizes and shapes including coccoidal rod. Although all produced tannase, no strain showed to have gallate decarboxylase. A total of 23 representative strains belonging to the family Pasteurellaceae were also tested for tannase production. Two strains, Haemophilus actinomycetemcomitans NIAH-10202T and Haemophilus segnis NIAH-10183T which were isolated from human oral cavity were detected positive for tannase.

Animals↗

U.S.-type Babesia microti isolated from small wild mammals in Eastern Hokkaido, Japan.

Our previous report demonstrated that small wild rodents in Japan harbored two types of novel Babesia microti-like parasites (Kobe and Hobetsu types), but not the type widely distributed throughout the temperate zones of North American and Eurasian Continents (U.S. type). In this study, we surveyed small wild mammals collected at various places in the northern part of Japan, seeking for U.S.-type B. microti. A total of 197 small mammals comprising 10 species, Apodemus speciosus, A. argenteus, Clethrionomys rufocanus, C. rutilus, Eothenomys andersoni, Microtus montebelli, Tamias sibiricus, Sorex unguiculatus, S. caecutiens, and Urotrichus talpoides, were examined. Babesia parasites were detected in A. speciosus, C. rufocanus, C. rutilus, M. montebelli, S. unguiculatus, and S. caecutiens by microscopy of blood smears and by PCR targeting babesial nuclear small-subunit rRNA (rDNA) and beta-tubulin genes. Inoculation of their bloods into experimental animals gave rise to 23 parasite isolates, which included 16 from A. speciosus, 4 from C. rufocanus, and 1 each from C. rutilus, M. montebelli and S. unguiculatus. Sequencing analyses of their rDNA and beta-tubulin genes revealed that, of the 23 isolates, 20 and 3 were of Hobetsu and U.S. types, respectively. The U.S.-type B. microti strains isolated in Japan, however, were distinguishable from the isolates in the United States when their beta-tubulin gene sequences and antigen profiles in Western blots were compared. We conclude that U.S.-type B. microti exists in Japan although it has been genetically and antigenically diversified from that distributed in the United States. The results also suggest that not only rodents, but also some insectivores may serve as reservoirs for the agent of human babesiosis.

Animals↗

A comparative histological study on the distribution of striated and smooth muscles and glands in the esophagus of wild birds and mammals.

Musculature and glands of the esophagus in various wild birds and mammals were examined histologically. Cervical and thoracic esophagi of all birds used (mallard, spot-billed duck, Ural owl and Hodgson's hawk-eagle) were comprised of smooth muscle fibers only. In contrast, esophagi of the nutria, Japanese raccoon dog, common raccoon and Japanese marten consisted largely of striated muscle fibers. In the masked palm civet, Japanese macaque and bottlenose dolphin, esophageal muscle layers consisted of both striated and smooth muscle fibers. Esophageal glands were observed except for the nutria and masked palm civet. These results show a wide variety of the structural composition in the esophagus of wild animals, particularly mammals, examined in this study.

Animals↗

A longitudinal study of Escherichia coli strains isolated from captive mammals, birds, and reptiles in Trinidad.

A longitudinal study was conducted of the prevalence and characteristics of Escherichia coli in mammals, birds, and reptiles housed at the Emperor Valley Zoo, Trinidad. During a 6-mo study period, swabs were obtained from fecal samples that were randomly collected from the enclosures of animals from these three taxonomic groups every 3 wk. With snakes, both cloacal and fecal swabs were obtained. Fecal and cloacal swabs were cultured for E. coli on eosin methylene blue agar. The production of mucoid colonies and hemolytic colonies and non-sorbitol fermenter status were identified. The occurrence of O157 strains was determined amongst E. coli isolates that were non-sorbitol fermenters, and the disc diffusion method was used to determine the antibiograms of isolates. The frequency of E. coli isolation was significantly higher in mammals compared with birds and reptiles. Overall, the frequencies of isolation of E. coli from omnivores. herbivores, and carnivores, 87.2%, 70.0%, and 57.3%, respectively, regardless of animal class, were significantly different. Most (99.6%) of the E. coli isolates tested for antibiotic sensitivity exhibited resistance to one or more of the eight antimicrobial agents used. The possession of phenotypic virulence markers by the E. coli isolates studied and the generally high resistance to antimicrobial agents may have health implications for the zoological collection.

Animals↗

Paraspirura bettinae n. sp. from a South African skink with comments on spirurid nematodes from saurians and mammals.

The spirurid nematode, Paraspirura bettinae n. sp., described from Mabuya spilogaster (Scincidae) in South Africa (Molopo Reserve), can be distinguished from the single known species of the genus, Paraspirura mabuyae Sandground, 1936 (also reviewed) by the larger size of the eggs, the shape of the tail of the female, and the smaller body size in both sexes. The cephalic anatomy of Paraspirura spp. does not fit the original description but appears similar to that of spirurid parasites of mammals, Spirura spp. and Protospirura spp. Previous descriptions did not mention the rim and bulges in members of Protospirura. Paraspirura appears close to Protospirura, particularly to Protospirura muricola from the Ethiopian region, but it is distinct because of the persistence of the larval caudal tubercles in the adult stage, the simple right spicule without alae, and the more developed rim and bulges. The species parasitic in saurians may have arisen from Protospirura spp. by capture, or the spirurids of mammals may have been derived from species of Paraspirura and quickly split into a Protospirura line and a more specialized Spirura assemblage.

Animals↗

Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals.

Corticotropin-releasing hormone (CRH) plays multiple roles in vertebrate species. In mammals, it is the major hypothalamic releasing factor for pituitary adrenocorticotropin secretion, and is a neurotransmitter or neuromodulator at other sites in the central nervous system. In non-mammalian vertebrates, CRH not only acts as a neurotransmitter and hypophysiotropin, it also acts as a potent thyrotropin-releasing factor, allowing CRH to regulate both the adrenal and thyroid axes, especially in development. The recent discovery of a family of CRH-like peptides suggests that multiple CRH-like ligands may play important roles in these functions. The biological effects of CRH and the other CRH-like ligands are mediated and modulated not only by CRH receptors, but also via a highly conserved CRH-binding protein (CRH-BP). The CRH-BP has been identified not only in mammals, but also in non-mammalian vertebrates including fishes, amphibians, and birds, suggesting that it is a phylogenetically ancient protein with extensive structural and functional conservation. In this review, we discuss the biochemical properties of the characterized CRH-BPs and the functional roles of the CRH-BP. While much of the in vitro and in vivo data to date support an 'inhibitory' role for the CRH-BP in which it binds CRH and other CRH-like ligands and prevents the activation of CRH receptors, the possibility that the CRH-BP may also exhibit diverse extra- and intracellular roles in a cell-specific fashion and at specific times in development is also discussed.

Adrenal Cortex↗

Role of recA/RAD51 family proteins in mammals.

DNA damage causes chromosomal instability leading to oncogenesis, apoptosis, and severe failure of cell functions. The DNA repair system includes base excision repair, nucleotide excision repair, mismatch repair, translesion replication, non-homologous end-joining, and recombinational repair. Homologous recombination performs the recombinational repair. The RAD51 gene is an ortholog of Esherichia coli recA, and the gene product Rad51 protein plays a central role in the homologous recombination. In mammals, 7 recA-like genes have been identified: RAD51, RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, XRCC3, and DMC1. These genes, with the exception of meiosis-specific DMC1, are essential for development in mammals. Disruption of the RAD51 gene leads to cell death, whereas RAD51L1/B, RAD51L2/C, RAD51L3/D, XRCC2, and XRCC3 genes (RAD51 paralogs) are not essential for viability of cells, but these gene-deficient cells exhibit a similar defective phenotype. Yeast two-hybrid analysis, co-immunoprecipitation, mutation analysis, and domain mapping of Rad51 and Rad51 paralogs have revealed protein-protein interactions among these gene products. Recent investigations have shown that Rad51 paralogs play a role not only in an early step, but also in a late step of homologous recombination. In addition, identification of alternative transcripts of some RAD51 paralogs may reflect the complexity of the homologous recombination system.

Animals↗

Epidemiology of contagious diseases, ecology of mammals, health, management and conservation biology: concluding remarks.

In conclusion to the Proceedings of the Symposium on the Health and management of free-ranging mammals (held in Nancy, France, in 1991), the author presents a review of the literature on the ecology of diseases of wild mammals. This discipline involves the ecology of both pathogens and hosts. The ecology of a pathogen may be considered as a synonym of epidemiology, i.e. the mode of transmission and circulation of parasites, their origin, invasion and persistence. The ecology of the host deals with the outcome of infection within different geographical and time scales: a) the impact on population density and communities within the time scale of the "observer" b) the effect of infection on the co-evolution of hosts and pathogens within the evolutionary time scale. This account is illustrated by numerous examples from field studies, as well as mathematical models, and concludes by examining the effect of pathogens on biodiversity, human health and the health of domestic animals.

Animals↗