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Cold-induced changes in thyroid function in a poikilothermic mammal, the naked mole-rat.

Cold acclimation induces very divergent responses in thyroid function in reptiles and mammals reflective of their different thermoregulatory modes. Naked mole-rats, unlike other small mammals, are unable to effectively employ endothermy and are operatively poikilotherms. We therefore investigated changes in their thyroid status with chronic cold exposure. Under simulated burrow conditions, free thyroxine (T(4); 0.39 +/- 0.09 ng/dl) and thyroid stimulating hormone (TSH; 1.12 +/- 0.56 microIU/ml) levels fell within the reptilian range, one order of magnitude lower than mammalian levels. However, cold induced typical mammalian responses: free T(4) levels (0.55 +/- 0.09 ng/dl) and thyroid follicular cell height were significantly greater. Although TSH levels (1.28 +/- 0.83 microIU/ml) were not significantly elevated, thyrotrophs exhibited ultrastructural signs of increased secretory activity. Low thyroid hormone concentrations may contribute substantially to the unusual thermoregulatory mode exhibited by naked mole-rats.

Adaptation, Physiological↗

Nonrebreathing valve for respiratory measurements in unsedated small mammals.

A nonrebreathing valve for measuring the respiratory volumes and gas exchange of unsedated, trained small mammals is described. The valve was easily fabricated from Plexiglas and latex flaps cut from a surgical glove. It has a low dead space and airflow restance and can be scaled to fit a variety of small mammal species. Ten hamsters were trained to breathe through the valve while expirate was collected. Respiratory frequency, tidal volume, minute volume, O2 uptake, CO2 output, respiratory exchange ratio, and ventilatory equivalent were measured.

Animals↗

Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses.

To investigate whether relevant levels of nasal nitric oxide (NO) are produced in the absence of paranasal sinuses, we studied 17 healthy baboons, mammals without any paranasal sinuses. The animals were anesthetized with ketamine hydrochloride and breathed spontaneously. While the baboons breathed through a face mask (mouths closed) connected to a respirator, NO concentrations in exhaled gas were sampled from the expiratory limb and analyzed by chemiluminescence. While the animals were breathing ambient air, nasal gas was sampled via a thin plastic tube and analyzed for NO concentrations by chemiluminescence. Mean NO concentration in the exhaled gas was 1.00 +/- 0.59 parts/billion, and NO release was 4.28 +/- 2.72 nl/min. A NO concentration of 4.79 +/- 2.08 parts/billion was found in the nasal gas (NO release: 7.18 +/- 3.13 nl/min). An age-dependent increase in nasal NO levels was not observed. Exhaled and nasal NO concentrations in baboons were markedly lower than in mammals with paranasal sinuses, suggesting that paranasal sinuses might be an anatomic requirement for production of relevant nasal NO levels.

Animals↗

Quantitative development of brain and brain structures in birds (galliformes and passeriformes) compared to that in mammals (insectivores and primates).

The brain weight and brain structure volumes of galliform and passeriform birds were calculated and related to body weight. The total brains and 14 brain regions were investigated in order to calculate factors by which these structures in passeriforms exceed those in galliforms in size. The larger passeriform brains have larger telencephala, especially ventral hyperstriata and neostriata. The enlargement of total brain and telencephalon resembles that in primates, compared to insectivores, within mammals. The enlargement of the ventral hyperstriata + neostriata in passeriforms is fundamentally similar to that of the isocortex in mammals: it reflects an expansion of multimodal integrational capacities, as the ventral hyperstriatum and neostriatum are occupied exclusively or primarily by multimodal integrational areas as is the isocortex.

Animals↗

Karyotype stability in marine mammals.

A considerable amount of information is now available on the karyology of the marine mammals, Pinnipedia and Cetacea. This information emanates both from banded and unbanded karyotypes. A majority of the pinnipeds has now been investigated karyologically, and representatives of all extant cetacean families have also been studied. The karyotype stability among the marine mammals has been stressed earlier, and the present discussion emphasizes this point further.

Animals↗

Measurements on the kidneys and vasa recta of various mammals in relation to urine concentrating capacity.

Maximum urine-concentrating capacity (UCC) differs widely among mammals of different species, being very high in some desert species (e.g. kangaroo rats) and very low in freshwater acquatic species (e.g. beaver). In this study, kidneys of 21 species of mammals from widely different habitats were studied in histological sections to determine whether differences in UCC can be attributed to differences in kidney structure. Parameters studied included the ratio of medullary to cortical thickness, the proportional subdivision of the medulla into inner and outer zones, and the dimensions of the vasa recta expressed in terms of the total area and the number of lumens within the vascular bundles. Determinations were made at a level where the size of individual vasa recta bundles has reached a constant maximum size, i.e. in the distal half of the outer zone. A positive correlation was found between the UCC and the ratio of medullary length to cortical thickness. No clear correlation existed between the proportion of the medullary length comprised of outer or inner zones and the UCC, although a trend to higher UCC in animals with relatively longer inner zones was apparent. Thus, it appears that the relative length of the entire medullary region is a major factor determining UCC, but the length of individual medullary zones is of lesser importance. A correlation was also found between the density of vasa recta per cubic millimeter of medullary tissue (the number of lumens regardless of identify in bundles, based on the number counted at the level sampled) and the UCC of the species. Data reported here support the view that UCC can be correlated with two parameters of kidney structure - the length of medulla relative to that of cortex and the density of vasa recta within the outer zone. It is proposed that the anatomical characteristics of the vascular supply to the medulla - that is, the vasa recta - are equally as important for the concentration of urine as is the primary mechanism determined by the characteristics of the loop of Henle and collecting ducts.

Anatomy, Comparative↗

Evidence of constriction of optic nerve axons at the lamina cribrosa in the normotensive eye in humans and other mammals.

The ultrastructure of optic nerve axons was examined in several mammals (human, cat, rat, sheep, ox, pig, guinea pig, rabbit). Human material was obtained from normotensive, glaucoma-free eyes and from eyes with a history of glaucoma and raised intra-ocular pressure (IOP). We describe accumulations of organelles (principally mitochondria) in optic nerve axons where they traverse the lamina cribrosa. Accumulations were most prominent in unmyelinated lengths of axons close to lamellae of the lamina cribrosa. Comparable accumulations were not apparent in axons in the retina or optic nerve, suggesting that axoplasmic flow is constricted at the lamina cribrosa. Accumulations were observed both centrally and peripherally to the lamellae, suggesting that flow is constricted in both ortho- and anterograde directions. Accumulations of organelles were more marked in unmyelinated axons than in adjacent, myelinated axons. In the rabbit, in which most axons are myelinated as they traverse the optic nerve head, organelle accumulations were observed only in a sparse population of unmyelinated axons. In human eyes with a history of raised IOP and glaucoma, the accumulations were abnormally large and frequent and in many axons showed dense-body and fibrillar changes not seen in normotensive eyes. It is suggested that chronic, partial constriction of axoplasmic flow is present at the lamina cribrosa of normotensive eyes in a wide range of mammals, including humans, that the constriction results from the pressure gradient across the lamina cribrosa and that the constriction may be a factor in the many cases of primary glaucoma in which IOP is not raised.

Adult↗

Biology of Toll receptors: lessons from insects and mammals.

Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.

Animals↗

The hormonogenic sites of turtle thyroglobulin and their homology with those of mammals.

Thyroglobulin (Tg) from turtles previously injected with 125I was reduced, alkylated, and digested with trypsin. We purified the resultant peptides on HPLC columns, determined their amino acid sequences and the locations of [125I]T4 and [125I]T3 residues, and compared them with established sequences from humans, cows, rabbits, rats, and guinea pigs. We found five major T4 peptides, three of which were homologous with the major hormonogenic sites A, B, and D of mammalian Tg. Site A, the highly conserved major T4 site in mammals, had substitutions in three residues near the T4 residue and had much less of Tg's newly synthesized T4 than is found in mammalian Tg (25% in turtle vs. 44% in rabbit). Site B contained correspondingly more of Tg's new T4 (42% vs. 24% in rabbit). Turtle Tg contained little [125I]T3, and we did not find site C (Ser-T3/T4-Ser, the major T3 site in guinea pig and rabbit) in turtles, but did find Val-T4, a possible homolog. Site D was quantitatively less important than in mammals. The fifth turtle hormonogenic site, containing 12% of Tg's newly formed T4, had a tyrosyl residue substituted for the phenylalanine at residue 632 in the human sequence. We conclude that Tg's major hormonogenic sites are generally conserved across a considerable evolutionary distance, but that differences in primary structure occur and may contribute to changes in priority of hormone synthesis among these sites.

Alkylation↗

Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals.

Meiosis is a double-division process that is preceded by only one DNA replication event to produce haploid gametes. The defining event in meiosis is prophase I, during which chromosome pairs locate each other, become physically connected, and exchange genetic information. Although many aspects of this process have been elucidated in lower organisms, there has been scant information available until now about the process in mammals. Recent advances in genetic analysis, especially in mice and humans, have revealed many genes that play essential roles in meiosis in mammals. These include cell cycle-regulatory proteins that couple the exit from the premeiotic DNA synthesis to the progression through prophase I, the chromosome structural proteins involved in synapsis, and the repair and recombination proteins that process the recombination events. Failure to adequately repair the DNA damage caused by recombination triggers meiotic checkpoints that result in ablation of the germ cells by apoptosis. These analyses have revealed surprising sexual dimorphism in the requirements of different gene products and a much less stringent checkpoint regulation in females. This may provide an explanation for the 10-fold increase in meiotic errors in females compared with males. This review provides a comprehensive analysis of the use of genetic manipulation, particularly in mice, but also of the analysis of mutations in humans, to elucidate the mechanisms that are required for traverse through prophase I.

Animals↗

Evidence for the use of reflected self-generated seismic waves for spatial orientation in a blind subterranean mammal.

Subterranean mammals like the blind mole-rat (Rodentia: Spalax ehrenbergi) are functionally blind and possess poor auditory sensitivity, limited to low-frequency sounds. Nevertheless, the mole-rat demonstrates extremely efficient ability to orient spatially. A previous field study has revealed that the mole-rat can assess the location, size and density of an underground obstacle, and accordingly excavates the most efficient bypass tunnel to detour around the obstacles. In the present study we used a multidisciplinary approach to examine the possibility that the mole-rat estimates the location and physical properties of underground obstacles using reflected self-generated seismic waves (seismic 'echolocation'). Our field observations revealed that all the monitored mole-rats produced low-frequency seismic waves (250-300 Hz) at intervals of 8+/-5 s (range: 1-13 s) between head drums while digging a bypass to detour an obstacle. Using a computerized simulation model we demonstrated that it is possible for the mole-rat to determine its distance from an obstacle boundary (open ditch or stone) by evaluating the amplitude (intensity) of the seismic wave reflected back to it from the obstacle interface. By evaluating the polarity of the reflected wave the mole-rat could distinguish between air space and solid obstacles. Further, the model showed that the diffracted waves from the obstacle's corners could give the mole-rat precise information on the obstacle size and its relative spatial position. In a behavioural experiment using a special T-maze setup, we tested whether the mole-rat can perceive seismic waves through the somatosensory system and localize the source. The results revealed that the mole-rat is able to detect low frequency seismic waves using only its paws, and in most cases the mole-rats determined accurately the direction of the vibratory source. In a histological examination of the glabrous skin of the mole-rat's paws we identified lamellate corpuscle mechanoreceptors that might be used to detect low frequency seismic waves. The combined findings from these different approaches lead us to suggest that a specialized seismic 'echolocation' system could be used by subterranean mammals to determine the most energy-conserving strategy with which to bypass an obstacle, as well as to estimate their distance from the surface, keeping their tunnels at the optimal depth.

Adaptation, Physiological↗

Seasonal adjustment of energy budget in a large wild mammal, the Przewalski horse (Equus ferus przewalskii) I. Energy intake.

Large ruminants respond to changing plant phenology during winter by decreasing voluntary food intake, increasing gut passage time and utilizing body fat reserves. It is uncertain, however, how other large mammals with a non-ruminant digestive physiology cope with winter forage conditions. Therefore, we investigated seasonality of energy intake in a large herbivorous wild mammal, the Przewalski horse (Equus ferus przewalskii). Throughout all seasons we used the n-alkane method to measure daily dry matter intake (DMI), diet composition and digestion, and determined an index of gut passage time in horses living under close to natural conditions. DMI correlated positively with its content of crude protein and nitrogen-free extract. Independent of these effects, DMI further varied seasonally with a peak in autumn and a nadir in late winter. Fluctuations of DMI corresponded to the annual change in body condition, which decreased during winter while energy reserves were depleted, and increased during the fattening period. Gut passage time varied in the course of the year and was longer during winter when the diet was high in crude fibre. Nevertheless, changes in gut passage time occurred rather independently of changes in forage composition and DMI, suggesting endogenous control for timely adaption of the digestive strategy to meet predictable changes in forage quality.

Animals↗

Locomotory stresses in the limb bones of two small mammals: the ground squirrel and chipmunk.

Peak stresses acting in limb bones should increase with increasing size if the forces acting on the bones increase in direct proportion to the animal's body weight. This is a direct consequence of the scaling of limb bone geometry over a wide range in size in mammals. In addition, recent work has shown that the material strength of bone is similar in large and small animals. If the assumptions in this analysis are correct, large animals would have a lower safety factor to failure than small animals. The purpose of this study was to measure peak stresses acting in the limb bones of small animals during locomotion and compare the results with similar measurements available for larger animals. Locomotory stresses acting in the fore and hindlimb bones of two rodents, the ground squirrel (Spermophilus tridecemlineatus) and chipmunk (Tamais striatus), were calculated using ground force recordings and measurements of limb position taken from high speed x-ray cine films. Peak (compressive) stresses calculated to act in the bones of these animals (-31 to -86 MN/m2) are similar in magnitude to those determined for much larger mammals. The more proximal bones of the fore and hindlimb, the humerus and femur, were found to develop stresses (-31 to -42 MN/m2) significantly lower than those acting in the more distal bones of each limb: the radius, ulna and tibia (-58 to -86 MN/m2). All of the long bones from both species, except their femora, were found to be loaded principally in bending. The caudal cortices of each bone developed a peak compressive stress, whereas the cranial cortices were loaded in tension. Various features of the musculo-skeletal organization and manner of locomotion of these rodents are considered to explain how animals of different size maintain a uniform safety factor to failure.

Animals↗

Receptor specificity of influenza A viruses from sea mammals correlates with lung sialyloligosaccharides in these animals.

The distribution of specific receptors on target organs is a major factor in the host range restriction of influenza A viruses. To assess the correlation between host receptors and the receptor specificity of influenza A viruses from sea mammals, we examined the receptors for influenza A virus in seal and whale lungs. A binding assay using two sialyloligosaccharide (SAalpha2,3Gal and SAalpha2,6Gal)-specific lectins showed that SAalpha2,3Gal, but not SAalpha2,6Gal, was found in both seal and whale lungs. Correspondingly, seal and whale influenza viruses preferentially recognized SAalpha2,3Gal, but not SAalpha2,6Gal. These results indicate that sialyloligosaccharides present at the replication site of influenza A viruses correlate with the receptor recognition of the viruses isolated from sea mammals.

Animals↗

Nitric-oxide-directed synaptic remodeling in the adult mammal CNS.

In adult mammals, learning, memory, and restoration of sensorimotor lost functions imply synaptic reorganization that requires diffusible messengers-mediated communication between presynaptic and postsynaptic structures. A candidate molecule to accomplish this function is the gaseous intercellular messenger nitric oxide (NO), which is involved in synaptogenesis and projection refinement during development; however, the role of NO in synaptic reorganization processes in adulthood remains to be established. In this work, we tested the hypothesis that this free radical is a mediator in the adult mammal CNS synaptic remodeling processes using a model of hypoglossal axonal injury recently developed by us. Axonal injury-induced disconnection of motoneurons from myocytes produces withdrawal of synaptic inputs to motoneurons and concomitant upregulation of the neuronal isoform of NO synthase (NOS-I). After recovery of the neuromuscular function, synaptic coverage is reestablished and NOS-I is downregulated. We also report, by using functional and morphological approaches, that chronic inhibition of the NO/cGMP pathway prevents synaptic withdrawal evoked by axon injury, despite the persistent muscle disconnection. After successful withdrawal of synaptic boutons, inhibition of NO synthesis, but not of cGMP, accelerated the recovery of synaptic coverage, although neuromuscular disconnection was maintained. Furthermore, protein S-nitrosylation was upregulated after nerve injury, and this effect was reversed by NOS-I inhibition. Our results suggest that during synaptic remodeling in the adult CNS, NO acts as a signal for synaptic detachment and inhibits synapse formation by cGMP-dependent and probably S-nitrosylation-mediated mechanisms, respectively. We also suggest a feasible role of NO in neurological disorders coursing with NOS-I upregulation.

Animals↗

Free and solvolysable dehydroepiandrosterone and androsterone in blood of mammals under physiological conditions and following administration of dehydroepiandrosterone.

A gas chromatographic method has been empolyed for the determination of dehydroepiandrosterone (D), androsterone (A), dehydroepiandrosterone sulphate (DS) and androsterone sulphate (AS) in the peripheral blood of human subjects and in various mammals under physiological conditions and after the administration of D or DS. Unconjugated D has been isolated and the resting level determined in the rat, rabbit, dog , sheep, pig and cow, while DS was detectable in the peripheral circulation of the rat, dog and pig. Unconjugated A was present in blood of the rodents and domestic ungulates studied, while the parent sulphate could be demonstrated only in rat, dog, pig and cow. The plasma of lower mammals contained D in higher (0.8-10.9 microng/100 ml) and DS, if any, in lower level (1.5-5.7 microng/100 ml) than the human plasma samples (0.1-2.7 and 86-308 microng/100 ml, respectively). There was a more pronounced increase in D and A than in the DS and AS level in the rat and dog following administration of D. On the contrary, exogenous D hardly affected unconjugated D and appreciably enhanced the DS level in human plasma. The conclusion drawn for human subjects, that D is the metabolically active and DS the reserve hormone, does not seem to be valid for all the animals here studied.

Administration, Oral↗

Stability of the sperm plasma membrane of hibernating bats (Myotis velifer) compared with other mammals.

Previous experiments have established that the long-lived spermatozoa of hibernating bats are resistant to the acrosome reaction and fertilization in vitro conventional techniques. We tested the hypothesis that the membranes of these spermatozoa are more resistant to perturbation than those of other mammals. We exposed them to non-specific bilayer destabilizing agents and abrupt changes in incubation temperature and tested their response by observing their status (motility and viability) after a time interval compared with other mammals (golden hamster, rabbit, human). The results did not support the hypothesis. The inherent longevity of bat spermatozoa may thus be a function of some component other than unique resilience of their plasma membrane.

Animals↗

Phospholipase Czeta, the trigger of egg activation in mammals, is present in a non-mammalian species.

The activation of the egg to begin development into an embryo is triggered by a sperm-induced increase in intracellular egg Ca2+. There has been much controversy about how the sperm induces this fundamental developmental event, but recent studies suggest that, in mammals, egg activation is triggered by a testis-specific phospholipase C: PLCzeta. Since the discovery of PLCzeta, it has been unclear whether its role in triggering egg activation is common to all vertebrates, or is confined to mammals. Here, we demonstrate for the first time that PLCzeta is present in a non-mammalian vertebrate. Using genomic and cDNA databases, we have identified the cDNA encoding a PLCzeta orthologue in the domestic chicken that, like the mammalian isoforms, is a testis-specific gene. The chicken PLCzeta cDNA is 2152 bp in size and encodes an open reading frame of 639 amino acids. When injected into mouse oocytes, chicken PLCzeta cRNA triggers Ca2+ oscillations, indicating that it has functional properties similar to those of mammalian PLCzeta. Our findings suggest that PLCzeta may have a universal role in triggering egg activation in vertebrates.

Amino Acid Sequence↗