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PubMed2003

Regulation of MAP kinase signaling modules by scaffold proteins in mammals.

The mitogen-activated protein kinase (MAPK) group of serine/threonine protein kinases mediates the response of cells to many extracellular stimuli such as cytokines and growth factors. These protein kinases include the extracellular signal-regulated protein kinases (ERK) and two stress-activated protein kinases (SAPK), the c-Jun N-terminal kinases (JNK), and the p38 MAPK. The enzymes are evolutionarily conserved and are activated by a common mechanism that involves a protein kinase cascade. Scaffold proteins have been proposed to interact with MAPK pathway components to create a functional signaling module and to control the specificity of signal transduction. Here we critically evaluate the evidence that supports a physiologically relevant role of MAPK scaffold proteins in mammals.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The physiological basis of diving to depth: birds and mammals.

There is wide diversity in the animals that dive to depth and in the distribution of their body oxygen stores. A hallmark of animals diving to depth is a substantial elevation of muscle myoglobin concentration. In deep divers, more than 80% of the oxygen store is in the blood and muscles. How these oxygen stores are managed, particularly within muscle, is unclear. The aerobic endurance of four species has now been measured. These measurements provide a standard for other species in which the limits cannot be measured. Diving to depth requires several adaptations to the effects of pressure. In mammals, one adaptation is lung collapse at shallow depths, which limits absorption of nitrogen. Blood N2 levels remain below the threshold for decompression sickness. No such adaptive model is known for birds. There appear to be two diving strategies used by animals that dive to depth. Seals, for example, seldom rely on anaerobic metabolism. Birds, on the other hand, frequently rely on anaerobic metabolism to exploit prey-rich depths otherwise unavailable to them.

Animals↗
PubMed1991

Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals.

In conscious mammals including humans, the neurohumoral and hemodynamic responses to progressive acute hypovolemia have two distinct phases. There is an initial arterial baroreceptor-mediated phase in which the fall in cardiac output is nearly matched by a sympathetically mediated increase in peripheral resistance so that arterial pressure is maintained near normal levels. In most species, adrenal catecholamines and vasopressin contribute little to this phase. Increased renin release appears to augment the sympathetically mediated vasoconstriction. When blood volume has fallen by a critical amount (approximately 30%), a second phase develops abruptly. This phase is characterized by withdrawal of sympathetic vasoconstrictor drive, relative or absolute bradycardia, an increase in release of adrenal catecholamines and vasopressin, and a profound fall in arterial pressure. In rabbits and rats the signal that initiates this phase appears to travel in cardiopulmonary afferents. In dogs and humans its origin is unknown. Central opioidergic and serotonergic mechanisms may be involved.

Acute Disease↗
PubMed1983

Scaling of osmotic regulation in mammals and birds.

Allometric equations provide a means of summarizing and relating the components of renal structure and function in water balance and osmotic regulation. These summary equations also serve as base lines for evaluating adaptations to stressful environments and for comparisons of kidney designs and osmotic strategies of ureotelic mammals and uricotelic birds. Many of the functions can be quantitatively related to the M3/4 scaling of metabolic rates.

Animals↗
PubMed1991

Similar pressure pulse propagation and reflection characteristics in aortas of mammals.

Similar pressure and flow waveforms recorded in mammalian aortas suggest that pulse transmission characteristics may also be similar. We examined the validity of this hypothesis, utilizing allometric equations of pertinent hemodynamic parameters and a model of the arterial system. Results show that both the reflection coefficient and the propagation constant times the aortic length are essentially invariant across the mammalian species investigated. Resolved forward and reflected propagating waves are also similar. These findings suggest that the arterial system in these mammals indeed functions in a similar manner.

Animals↗
PubMed1993

On the nature of the circadian clock in mammals.

The evidence for the essential role of the suprachiasmatic nucleus (SCN) for the generation and maintenance of circadian rhythms in mammals is briefly reviewed. The pharmacology of the phase-response curve is considered and a new circadian measure, the phase-dose-response surface (PDRS), is introduced. The role of neurotransmission, ion fluxes, and non-neuronal cellular elements in the generation and maintenance of circadian rhythmicity is considered. Cell culture of the SCN is proposed as a tool for the functional analysis of clock mechanism. The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock. Finally, the nature of the circadian output signal is analyzed from a phylogenetic viewpoint.

Animals↗
PubMed1994

Relationship between body mass and biomechanical properties of limb tendons in adult mammals.

We investigated the allometric relationship between the mechanical properties of various limb tendons and body mass. The elastic modulus (i.e., stiffness) and hysteresis (i.e., energy dissipation) of digital flexor, ankle extensor, and digital extensor tendons from 18 species of adult quadrupedal mammals ranging in body mass from 0.5 to 545 kg were determined by cyclic tensile testing in vitro. The results show that these elastic properties do not vary significantly among tendons from animals of different body mass, nor do they differ between the digital flexor and ankle extensor tendons (those situated to act as springs during locomotion) and the digital extensor tendons (those not likely to function as springs during locomotion). Consequently, the inherent capability of different limb tendons to store elastic energy, based on their material properties, is the same for large and small animals. The relationship between tendon elastic modulus (E; in GPa) and body mass (Mb; in kg) is described by the allometric equation E = 1.22Mb0.00. The hysteresis (H), as a percentage of total strain energy, is related to body mass as H = 8.89Mb-0.03.

Animals↗
PubMed1994

Temperature and pH effects on Ca2+ sensitivity of cardiac myofibrils: a comparison of trout with mammals.

Active salmonids maintain myocardial contractility at temperatures that are cardioplegic for mammals. We postulated that myofibrillar Ca2+ sensitivity in the trout heart might 1) exhibit lower temperature dependence and/or 2) be greater over the range of physiological temperatures. Temperature-induced changes in intracellular pH may also play a role as alkalosis typically increases calcium affinity of myofibrillar adenosinetriphosphatase (ATPase). Ca2+ sensitivities of ventricular myofibrillar ATPase were determined in rats and in rainbow trout (Oncorhynchus mykiss) over a physiological range of pH and temperatures. Maximal myofibrillar ATPase activities of each species were similar and equally affected by temperature. Trout myofibrillar ATPase lost Ca2+ dependence at 37 degrees C. At constant pH, reduced temperature decreased calcium affinity more in trout (0.35 pCa/10 degrees C) than in rat (0.08-0.16 pCa/10 degrees C). Under alpha-stat conditions, the effects of temperature were reduced in both trout (0.2 pCa/10 degrees C) and rat (no significant effect). Over trout physiological temperatures, Ca2+ sensitivity was greater than rat at 37 degrees C. Qualitatively similar results were observed in studies measuring tension in skinned trout ventricular fibers. One mechanism by which the trout heart is able to maintain contractility at low temperatures is through the inherent higher Ca2+ sensitivity of the contractile element compared with mammalian species.

Adenosine Triphosphatases↗
PubMed2003

Genesis and control of the respiratory rhythm in adult mammals.

The neural mechanisms responsible for respiratory rhythmogenesis in mammals were studied first in vivo in adults and subsequently in vitro in neonates. In vitro data have suggested that the pacemaker neurons are the kernel of the respiratory network. These data are reviewed, and their relevance to adults is discussed.

Age Factors↗
PubMed1998

Regulation of sexual dimorphism in mammals.

Sexual dimorphism in humans has been the subject of wonder for centuries. In 355 BC, Aristotle postulated that sexual dimorphism arose from differences in the heat of semen at the time of copulation. In his scheme, hot semen generated males, whereas cold semen made females (Jacquart, D., and C. Thomasset. Sexuality and Medicine in the Middle Ages, 1988). In medieval times, there was great controversy about the existence of a female pope, who may have in fact had an intersex phenotype (New, M. I., and E. S. Kitzinger. J. Clin. Endocrinol. Metab. 76: 3-13, 1993.). Recent years have seen a resurgence of interest in mechanisms controlling sexual differentiation in mammals. Sex differentiation relies on establishment of chromosomal sex at fertilization, followed by the differentiation of gonads, and ultimately the establishment of phenotypic sex in its final form at puberty. Each event in sex determination depends on the preceding event, and normally, chromosomal, gonadal, and somatic sex all agree. There are, however, instances where chromosomal, gonadal, or somatic sex do not agree, and sexual differentiation is ambiguous, with male and female characteristics combined in a single individual. In humans, well-characterized patients are 46, XY women who have the syndrome of pure gonadal dysgenesis, and a subset of true hermaphrodites are phenotypic men with a 46, XX karyotype. Analysis of such individuals has permitted identification of some of the molecules involved in sex determination, including SRY (sex-determining region Y gene), which is a Y chromosomal gene fulfilling the genetic and conceptual requirements of a testis-determining factor. The purpose of this review is to summarize the molecular basis for syndromes of sexual ambiguity seen in human patients and to identify areas where further research is needed. Understanding how sex-specific gene activity is orchestrated may provide insight into the molecular basis of other cell fate decisions during development which, in turn, may lead to an understanding of aberrant cell fate decisions made in patients with birth defects and during neoplastic change.

Amino Acid Sequence↗
PubMed2001

Challenges for brain repair: insights from adult neurogenesis in birds and mammals.

Adult neurogenesis is a widespread phenomenon occurring in many species, including humans. The functional and therapeutic implications of this form of brain plasticity are now beginning to be realized. Comparative approaches to adult neurogenesis will yield important clues about brain repair. Here, we compare adult neurogenesis in birds and mammals. We review recent studies on the glial identity of stem cells that generate new neurons, the different modes of migration used by the newly generated neurons to reach their destinations, and how these systems respond to experimentally induced cell death. We integrate these findings to address how comparative analysis at the molecular level might be used for brain repair.

Aging↗
PubMed2002

Sex chromosome aneuploidy in wild small mammals.

We describe four examples of the XO condition in wild mammals. One XO house mouse (Mus musculus domesticus) was caught in nature and subsequently gave birth to three litters in captivity, confirming for wild mice the fertility observed for XO laboratory mice. Two other XO house mice were produced from laboratory crosses of wild-caught mice. An immature XO common shrew (Sorex araneus) was caught in nature; this appears to be the first XO recorded in the order Insectivora. We collected data from researchers studying chromosome variation in house mice and common shrews and found an overall incidence of 0.22% sex chromosome aneuploidy in 4608 mice and 0.05% in 6625 shrews. The discrepancy related to a much higher frequency of XO's in mice than shrews. Single XXY and XYY shrews and an XXX mouse have been recorded in nature.

Animals↗
PubMed2003

Turning on the male--SRY, SOX9 and sex determination in mammals.

The decision of the bi-potential gonad to develop into either a testis or ovary is determined by the presence or absence of the Sex-determining Region gene on the Y chromosome (SRY). Since its discovery, almost 13 years ago, the molecular role that SRY plays in initiating the male sexual development cascade has proven difficult to ascertain. While biochemical studies of clinical mutants and mouse genetic models have helped in our understanding of SRY function, no direct downstream targets of SRY have yet been identified. There are, however, a number of other genes of equal importance in determining sexual phenotype, expressed before and after expression of SRY. Of these, one has proven of central importance to mammals and vertebrates, SOX9. This review describes our current knowledge of SRY and SOX9 structure and function in the light of recent key developments.

Animals↗
PubMed2006

Genomic imprinting is a barrier to parthenogenesis in mammals.

Only mammals have relinquished parthenogenesis as a means of producing descendants. Bi-parental reproduction is necessary due to parent-specific epigenetic modification of the genome during gametogenesis, which leads to non-equivalent expression of imprinted genes from the maternal and paternal alleles. However, a series of our work showed that alteration of maternal imprinting by oocyte reconstruction using non-growing oocytes, together with deletion of the H19 gene provide appropriate expression of imprinted genes from the maternal genome. The resulting ng (non-growing)/fg (fully-grown) parthenogenic embryos were developed to term. Here, we discuss how the parthenogenetic embryos survived as normal individuals.

Animals↗
PubMed1993

Inter- and intra-laminar distribution of tectospinal neurons in 23 mammals.

Based on retrograde labeling from the high cervical spinal cord, the inter- and intra-laminar distributions of tectospinal tract (TST) somata within the tectum of 23 mammals and one reptile are described. The results show that TST somata are found only in the intermediate and deep layers. Although more TST somata are usually found in the intermediate layer, there are no useful relationships for predicting the number in one layer given the number in the other. The ratio of numbers of TST somata in the intermediate relative to the deep layer varies widely, from 0:1 (in rabbits) to over 8:1 (in marmosets). Within both layers the majority of TST somata (> 80%) are found in the lateral half of the tectum--the area subversing the lower visual field. In contrast, the variation between temporal and nasal visual fields is adequately accounted for by the animal's 'visual axis'--the azimuth of its field of best vision. In general, the present results uphold the idea that the significance of the TST somata, and perhaps of the tectospinal tract itself, is to be found in directing the head so that the retinal area of best vision can be brought to bear on stimuli either almost outside, or about to pass outside, of the area of best vision. The larger and possibly universal predominance of TST somata subserving the lower visual field suggests that the tectospinal tract may be primarily concerned with adjusting the step dimensions of the forelegs to accommodate obstacles to normal progression.

Animals↗
PubMed1990

The visual pathways of eutherian mammals and marsupials develop according to a common timetable.

Data from cats, ferrets, hamsters, macaques, mice, rabbits and rats concerning the time of occurrence of 26 developmental events involved in the establishment of the retinofugal, geniculocortical, corticogeniculate and corticocollicular pathways were analysed. For each species the timing of developmental events was expressed as a proportion of the period between conception and eye opening ('caecal period'). For 6 of these events, the values for all species fell within a range of 1-5% of the caecal period, the values for 11 other events fell within a range of 6-10% of the caecal period, 4 events had ranges of 11-15% of the caecal period, and only 5 events were spread over more than 15% of the caecal period. The 26 events had an overall mean variation of about 11% of the caecal period, suggesting that the visual pathways of eutherian mammals develop according to a common 'timetable' that is related to the duration of the caecal period. One of the roles of this common timetable may be to assist the establishment of orderly interconnections between the visual centres. Relatively few data are available concerning the timing of developmental events in marsupial visual pathways. However, it is apparent that, during the first half of the caecal period, most events occur much earlier in marsupials than in eutherians, whereas during the second half of the caecal period most events occur at the same stages of the caecal period in both marsupials and eutherians. The accelerated rate of visual development during the first half of the caecal period in marsupials may be related to the precocious development that they undergo prior to their very early birth.

Animals↗
PubMed1984

Folding of the cerebral cortex in mammals. A scaling model.

A model of cortical folding in mammals is presented. The model consists of a cube, superimposed on which are straight close-packed gyri, running the length of the cube. The cortex is represented by a thin layer of constant thickness. It proves possible, by adjusting the length, height, and width of the 'gyri' and the thickness of the 'cortex', to obtain a reasonable fit to the available empirical data (which extend over three to four orders of magnitude in brain weight). The model directs attention to possible features of the macroscopic organization of the mammalian brain which are novel and hitherto unremarked.

Animals↗
PubMed1982

Encephalization in mammals in relation to the size of the cerebral cortex.

A new index of encephalization has been proposed based on a reanalysis of the brain-body weight relationship in mammals. The new index, c, is related to the volume of the whole brain as well as to the surface and volume of the cerebral cortex. From an evolutionary point of view the index-cortex relationship is particularly interesting, since the structure of the brain which contributes most to its evolutionary progression is the cerebral cortex. A theory of corticalization has been developed in which the surface of the cerebral cortex is analyzed into two components, Sb, determined by the size of the animal, and Se, associated with an increase in the information-processing capacity. An analogue division has been performed for the cortical volume. Furthermore, an inquiry has been made into the brain structure which can serve as an estimator of body weight. The medulla oblongata appears to be such a structure.

Animals↗