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Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals.

The commitment complex is the first defined step in the yeast (S. cerevisiae) splicing pathway. It contains U1 snRNP as well as Mud2p, which resembles human U2AF65. In a genetic screen, we identified the yeast gene MSL-5, which is a novel commitment complex component. Genetic and biochemical criteria indicate a direct interaction between Msl5p and both Mud2p and the U1 snRNP protein Prp40p. This defines a bridge between the two ends of the intron. Msl5p (renamed BBP for branchpoint bridging protein) has a mammalian ortholog, the splicing factor SF1. Our results show that SF1 interacts strongly with human U2AF65, and that SF1 is a bona fide E complex component. This implies that aspects of these novel cross-intron protein-protein interactions are conserved between yeast and mammals.

Animals↗

Metabolic fuels and reproduction in female mammals.

A complete reproductive cycle of ovulation, conception, pregnancy, and lactation is one of the most energetically expensive activities that a female mammal can undertake. A reproductive attempt at a time when calories are not sufficiently available can result in a reduced return on the maternal energetic investment or even in the death of the mother and her offspring. Numerous physiological and behavioral mechanisms link reproduction and energy metabolism. Reproductive attempts may be interrupted or deferred when food is scarce or when other physiological processes, such as thermoregulation or fattening, make extraordinary energetic demands. Food deprivation suppresses both ovulation and estrous behavior. The neural mechanisms controlling pulsatile release of gonadotropin-releasing hormone (GnRH) and, consequently, luteinizing hormone secretion and ovarian function appear to respond to minute-to-minute changes in the availability of metabolic fuels. It is not clear whether GnRH-secreting neurons are able to detect the availability of metabolic fuels directly or whether this information is relayed from detectors elsewhere in the brain. Although pregnancy is less affected by fuel availability, both lactational performance and maternal behaviors are highly responsive to the energy supply. When a reproductive attempt is made, changes in hormone secretion have dramatic effects on the partitioning and utilization of metabolic fuels. During ovulatory cycles and pregnancy, the ovarian steroids, estradiol and progesterone, induce coordinated changes in the procurement, ingestion, metabolism, storage, and expenditure of metabolic fuels. Estradiol can act in the brain to alter regulatory behaviors, such as food intake and voluntary exercise, as well as adenohypophyseal and autonomic outputs. At the same time, ovarian hormones act on peripheral tissues such as adipose tissue, muscle, and liver to influence the metabolism, partitioning and storage of metabolic fuels. During lactation, the peptide hormones, prolactin and growth hormone, rather than estradiol and progesterone, are the principal hormones controlling partitioning and utilization of metabolic fuels. The interactions between metabolic fuels and reproduction are reciprocal, redundant, and ubiquitous; both behaviors and physiological processes play vital roles. Although there are species differences in the particular physiological and behavioral mechanisms mediating nutrition-reproduction interactions, two findings are consistent across species: 1) Reproductive physiology and behaviors are sensitive to the availability of oxidizable metabolic fuels. 2) When reproductive attempts are made, ovarian hormones play a major role in the changes in ingestion, partitioning, and utilization of metabolic fuels.

Animals↗

Functional sex differences ('sexual diergism') of central nervous system cholinergic systems, vasopressin, and hypothalamic-pituitary-adrenal axis activity in mammals: a selective review.

Sexual dimorphism of the mammalian central nervous system (CNS) has been widely documented. Morphological sex differences in brain areas underlie sex differences in function. To distinguish sex differences in physiological function from underlying sexual dimorphisms, we use the term, sexual diergism, to encompass differences in function between males and females. Whereas the influence of sex hormones on CNS morphological characteristics and function of the hypothalamic-pituitary-gonadal axis has been well-documented, little is known about sexual diergism of CNS control of the hypothalamic-pituitary-adrenal (HPA) axis. Many studies have been conducted on both men and women but have not reported comparisons between them, and many animal studies have used males or females, but not both. From a diergic standpoint, the CNS cholinergic system appears to be more responsive to stress and other stimuli in female than in male mammals; but from a dimorphic standpoint, it is anatomically larger, higher in cell density, and more stable with age in males than in females. Dimorphism often produces diergism, but age, hormones, environment and genetics contribute differentially. This review focuses on the sexual diergism of CNS cholinergic and vasopressinergic systems and their relationship to the HPA axis, with resulting implications for the study of behavior, disease, and therapeutics.

Acetylcholine↗

A transcutaneous wire interface for small mammals using an expanded PTFE patch.

The objective of this paper is to provide the reader with a method of surgical implantation of a transcutaneous wire interface for chronic instrumentation of small mammals, utilizing a non-bioreactive expanded polytetrafluoroethylene (ePTFE) material (W.L. Gore and Associates, Inc., Flagstaff, AZ). We describe the implant assembly, as well as details of the surgical implantation, which will facilitate successful data acquisition. EMG signal from the implant is of a high quality during both rest and activity of the animal and the signal quality is maintained up to at least 7 weeks post-implantation without any sign of infection or other adverse reaction. This represents an improvement in the viability of long-term physiological signal collection via a surgically implanted back plug.

Animals↗

Sound localization and delay lines--do mammals fit the model?

The current dominant model of binaural sound localization proposes that the lateral position of a sound source is determined by the position of maximal activation within an array of binaural coincidence-detector neurons that are tuned to different interaural time differences (ITDs). The tuning of a neuron for an ITD is determined by the difference in axonal conduction delay from each ear--the so-called "delay line" hypothesis. Although studies in birds appear to support this model, recent evidence from mammals suggests that the model does not provide accurate descriptions of how ITDs are encoded in the mammalian auditory brainstem or of how ITD-sensitive neurons contribute to mammalian sound localization.

Animals↗

The epigenetic basis of gender in flowering plants and mammals.

What makes a sperm male or an egg female, and how can we tell? A gamete's gender could be defined in many ways, such as the sex of the individual or organ that produced it, its cellular morphology, or its behaviour at fertilization. In flowering plants and mammals, however, there is an extra dimension to the gender of a gamete--due to parental imprinting, some of the genes it contributes to the next generation will have different expression patterns depending on whether they were maternally or paternally transmitted. The non-equivalence of gamete genomes, along with natural and experimental modification of imprinting, reveal a level of sexual identity that we describe as 'epigender'. In this paper, we explore epigender in the life history of plants and animals, and its significance for reproduction and development.

Animals↗

Oxygen sensors in the organism: examples of regulation under altitude hypoxia in mammals.

Oxygen sensing is a determinant function of mammals, especially humans, to maintain their activity under acute or chronic exposure to hypoxia. True O2 sensors (chemoreceptors, erythropoietin secreting cells) are involved in regulation loops, which aim to restore O2 availability to the cells. Pseudo O2 sensors are cells activated by the lack of oxygen but not clearly involved in regulation processes. Potassium channels in the carotid bodies have been suspected to be O2 sensitive and could mediate the chemosensitivity to hypoxia. Na,K-ATPase related ion transport in alveolar pneumocytes could be sensitive to O2 availability and regulate the flux of water and sodium in the alveolar space. Signal transduction in G-protein-dependent receptor systems is modified in hypoxia, such as in cardiac beta-receptors and adenosinergic and muscarinic receptors. Recent studies have provided some evidence to the possible role of hypoxia inducible factors (HIF-1) in the regulation of protein synthesis at the transcriptional level. Similarities between O2-sensing mechanisms in erythropoiesis and in the synthesis of vascular endothelial growth factor were recently evidenced. Both genes are upregulated in hypoxia. However, the precise structure (heme-linked enzyme?) of all these O2-sensitive sites is not known, either in the erythropoietic system or in the chemoreceptor function. An adequate balance between hypoxia-induced upregulation and downregulation processes is necessary for optimal survival in a hypoxic environment.

Altitude↗

Glucose kinetics of the Virginia opossum: possible implications for predicting glucose turnover in mammals.

Primed continuous infusions of 6-3H-glucose, respirometry and measurements of nitrogen excretion were carried out in adult Virginia opossums (Didelphis virginiana). Our goals were to determine resting glucose turnover rate, to establish the relative importance of this oxidative fuel in the energy budget of this species, to assess whether metabolic rate is a better predictor of glucose turnover rate than body mass and to demonstrate that glucose kinetics can be measured in the opossum for future use of this animal model in studies of mammalian glucoregulation. Results show that the resting glucose turnover rate of opossums averages 17.5 +/- 0.9 mumol/kg.min (n = 9), that 31% of total glucose flux is oxidized and that glucose oxidation represents 9% of their metabolic rate. An allometric equation predicting glucose turnover rate from body mass for placental mammals overestimates the measured turnover rate of this marsupial by 30%, suggesting that turnover rate is better predicted from metabolic rate than from body mass. Finally, this study demonstrates that the Virginia opossum is a convenient model to study glucose metabolism in vivo, and we propose that the very rapid aging characteristics of this species should be exploited to investigate the effects of aging on glucose homeostasis.

Aging↗

The vestibular system as a model of sensorimotor transformations. A combined in vivo and in vitro approach to study the cellular mechanisms of gaze and posture stabilization in mammals.

To understand the cellular mechanisms underlying behaviours in mammals, the respective contributions of the individual properties characterizing each neuron, as opposed to the properties emerging from the organization of these neurons in functional networks, have to be evaluated. This requires the use, in the same species, of various in vivo and in vitro experimental preparations. The present review is meant to illustrate how such a combined in vivo in vitro approach can be used to investigate the vestibular-related neuronal networks involved in gaze and posture stabilization, together with their plasticity, in the adult guinea-pig. Following first a general introduction on the vestibular system, the second section describes various in vivo experiments aimed at characterizing gaze and posture stabilization in that species. The third and fourth parts of the review deal with the combined in vivo-in vitro investigations undertaken to unravel the physiological and pharmacological properties of vestibulo-ocular and vestibulo-spinal networks, together with their functional implications. In particular, we have tried to use the central vestibular neurons as examples to illustrate how the preparation of isolated whole brain can be used to bridge the gap between the results obtained through in vitro, intracellular recordings on slices and those collected in vivo, in the behaving animal.

Animals↗

Serologic survey of trichinellosis in wild mammals kept in a Mexico City Zoo.

A serologic survey of Trichinella infection was carried out to determine the prevalence of this parasitosis among wild mammals kept in captivity at the Chapultepec Zoo. This was prompted by the necropsy finding of a heavy Trichinella infection in a Canadian polar bear (Ursus maritimus) that had been kept at the Zoo for more than 11 years. The parasites recovered were identified as T. nativa (T2). A serologic study based on ELISA and Western blot analysis was performed in serum samples from two polar bears (U. maritimus), six wolves (Canis lupus); nine foxes (Urocyon cinereoargenteus); seven coyotes (Canis latrans); nine jaguars (Panthera onca); ten lions (Panthera leo); 11 tigers (Panthera tigris); six panthers (Panthera pardus); eight leopards (Panthera pardus); two lynxes (Lynx rufus); five pumas (Felis concolor); one yagouaroundi (Felis yagouaroundi); and one ocelot (Felis pardalis). In these assays, 25% and 27% of the samples studied were positive using total muscle larva extract from T. nativa (T2) or T. spiralis (T1), respectively. When T. spiralis (T1) excretory/secretory products or surface/stichosomal antigens were used, 15 and 13% positivity was obtained respectively. The reactivity rates obtained among the different groups varied from 11 to 83%, wolves having the highest infection rate. Western blot analysis of positive ELISA sera showed an antigenic recognition pattern characteristic of animals infected with Trichinella.

Animals↗

Gonadotropin-releasing hormone containing neurons and olfactory fibers during development: from lamprey to mammals.

Gonadotropin releasing-hormone (GnRH) regulates the hypothalamo-pituitary-gonadal axis in all vertebrates. The vast majority of GnRH neurons are thought to be derived from progenitor cells in medial olfactory placodes. Several antibodies and lectins that recognize cell surface carbohydrates have been useful for delineating the migratory pathway from the olfactory placodes and vomeronasal organ, through the nasal compartment, and across the cribriform plate into the brain. In rats, alpha-galactosyl-linked glycoconjugates (immunoreactive with the CC2 monoclonal antibody) are expressed on fibers along the GnRH migration pathway and approximately 10% of the GnRH neuronal population. In lamprey, the alpha-galactosyl binding lectin, Grifonia simplicifolia-I (GS-1), identifies cells and fibers of the developing olfactory system. In contrast to the CC2 immunoreactive GnRH neurons in rats, the GS-1 does not label a subpopulation of presumptive GnRH neurons in lamprey. Results from these and other experiments suggest that GnRH neurons in developing lamprey do not originate within the olfactory placode, but rather within proliferative zones of the diencephalon. However, the overlap of olfactory- and GnRH-containing fibers from prolarval stages to metamorphosis, suggest that olfactory stimuli may play a major role in the regulation of GnRH secretion in lamprey throughout life. By contrast, olfactory fibers are directly relevant to the migration of GnRH neurons from the olfactory placodes in mammalian species. Primary interactions between olfactory fibers and GnRH neurons are likely transient in mammals, and so in later life olfactory modulation of GnRH secretion is likely to be indirect.

Aging↗

Cytokines during early pregnancy of mammals: a review.

This article reviews the function of cytokines during early pregnancy of mammals including the human species. Investigations concerning conceptus and other secretory proteins, their meaning for maternal recognition and maintenance of pregnancy, fetal and placental growth and differentiation, adhesion, invasion and implantation are discussed, and differences between laboratory rodents, carnivores, artiodactyls, horses and human beings elucidated and summarized. Finally topics that might be of interest for further research are emphasized.

Animals↗

Use of high-performance liquid chromatography for the estimation of polychlorinated biphenyls and p,p-DDE residues in marine mammals.

We present a screening technique for the detection of polychlorinated biphenyls (PCBs) and p,p-DDE residue levels in marine mammal blubber using high-performance liquid chromatography (HPLC). This method modifies the standard extraction and clean-up methods for organochlorines for use with HPLC and uses a method of chemical derivatization to separate and semi-quantify the two organochlorines with HPLC.

Adipose Tissue↗

Cellular distribution of the calcium-binding proteins parvalbumin, calbindin, and calretinin in the neocortex of mammals: phylogenetic and developmental patterns.

The three calcium-binding proteins parvalbumin, calbindin, and calretinin are found in morphologically distinct classes of inhibitory interneurons as well as in some pyramidal neurons in the mammalian neocortex. Although there is a wide variability in the qualitative and quantitative characteristics of the neocortical subpopulations of calcium-binding protein-immunoreactive neurons in mammals, most of the available data show that there is a fundamental similarity among the mammalian species investigated so far, in terms of the distribution of parvalbumin, calbindin, and calretinin across the depth of the neocortex. Thus, calbindin- and calretinin-immunoreactive neurons are predominant in layers II and III, but are present across all cortical layers, whereas parvalbumin-immunoreactive neurons are more prevalent in the middle and lower cortical layers. These different neuronal populations have well defined regional and laminar distribution, neurochemical characteristics and synaptic connections, and each of these cell types displays a particular developmental sequence. Most of the available data on the development, distribution and morphological characteristics of these calcium-binding proteins are from studies in common laboratory animals such as the rat, mouse, cat, macaque monkey, as well as from postmortem analyses in humans, but there are virtually no data on other species aside of a few incidental reports. In the context of the evolution of mammalian neocortex, the distribution and morphological characteristics of calcium-binding protein-immunoreactive neurons may help defining taxon-specific patterns that may be used as reliable phylogenetic traits. It would be interesting to extend such neurochemical analyses of neuronal subpopulations to other species to assess the degree to which neurochemical specialization of particular neuronal subtypes, as well as their regional and laminar distribution in the cerebral cortex, may represent sets of derived features in any given mammalian order. This could be particularly interesting in view of the consistent differences in neurochemical typology observed in considerably divergent orders such as cetaceans and certain families of insectivores and metatherians, as well as in monotremes. The present article provides an overview of calcium-binding protein distribution across a large number of representative mammalian species and a review of their developmental patterns in the species where data are available. This analysis demonstrates that while it is likely that the developmental patterns are quite consistent across species, at least based on the limited number of species for which ontogenetic data exist, the distribution and morphology of calcium-binding protein-containingneurons varies substantially among mammalian orders and that certain species show highly divergent patterns compared to closely related taxa. Interestingly, primates, carnivores, rodents and tree shrews appear closely related on the basis of the observed patterns, marsupials show some affinities with that group, whereas prototherians have unique patterns. Our findings also support the relationships of cetaceans and ungulates, and demonstrates possible affinities between carnivores and ungulates, as well as the existence of common, probably primitive, traits in cetaceans and insectivores.

Animals↗

Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals.

Changes in plasma nitrite concentration in the human forearm circulation have recently been shown to reflect acute changes in endothelial nitric oxide synthase (eNOS)-activity. Whether basal plasma nitrite is a general marker of constitutive NOS-activity in vivo is yet unclear. Due to the rapid metabolism of nitrite in blood and the difficulties in its analytical determination literature data on levels of nitrite in mammals are largely inconsistent. We hypothesized that constitutive NOS-activity in the circulatory system is relatively uniform throughout the mammalian kingdom. If true, this should result in comparable systemic plasma nitrite levels in different species. Using three different analytical approaches we determined plasma nitrite concentration to be in a nanomolar range in a variety of species: humans (305 +/- 23 nmol/l), monkeys (367 +/- 62 nmol/l), minipigs (319 +/- 24 nmol/l), dogs (305 +/- 50 nmol/l), rabbits (502 +/- 21 nmol/l), guinea pigs (412 +/- 44 nmol/l), rats (191 +/- 43 nmol/l), and mice (457 +/- 51 nmol/l). Application of different NOS-inhibitors in humans, minipigs, and dogs decreased NOS-activity and thereby increased vascular resistance. This was accompanied by a significant, up to 80%, decrease in plasma nitrite concentration. A comparison of plasma nitrite concentrations between eNOS(-/-) and NOS-inhibited wild-type mice revealed that 70 +/- 5% of plasma nitrite is derived from eNOS. These results provide evidence for a uniform constitutive vascular NOS-activity across mammalian species.

Animals↗

Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain.

We have cloned and characterized the mouse cDNA of a third mammalian homolog of the Drosophila period gene and designated it mPer3. The mPER3 protein shows approximately 37% amino acid identity with mPER1 and mPER2 proteins. The three mammalian PER proteins share several regions of sequence homology, and each contains a protein dimerization PAS domain. mPer3 RNA levels oscillate in the suprachiasmatic nuclei (SCN) and eyes. In the SCN, mPer3 RNA levels are not acutely altered by light exposure at different times during subjective night. This contrasts with the acute induction by light of mPer1 and mPer2 RNA levels during early and late subjective night. mPer3 is widely expressed in tissues outside of brain. In liver, skeletal muscle, and testis, mPer RNAs exhibit prominent, synchronous circadian oscillations. The results highlight the differential light responses among the three mammalian Per genes in the SCN and raise the possibility of circadian oscillators in mammals outside of brain and retina.

Animals↗

Does Hebbian synaptic plasticity explain learning-induced sensory plasticity in adult mammals?

Over the last decade, a large number of studies have demonstrated that sensory systems undergo functional reorganizations in adult mammals. In the auditory system, highly specific reorganizations were observed during learning situations in which a particular tone frequency predicts the occurrence of an aversive event. After a brief overview of the specific receptive field changes observed after associative learning in cortical and thalamic neurons, I will raise the question concerning whether or not Hebbian synaptic plasticity adequately accounts for these data. The required conditions for Hebbian synaptic plasticity to act do not seem to be met in situations in which learning-induced receptive field plasticity occurs. This analysis points out the weakness of the traditional Hebbian scheme to provide realistic bases for learning-induced neuronal plasticity and stresses the need to look for other potential mechanisms involving neuromodulators.

Animals↗