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Duplication and MHC linkage of the CTX family of genes in Xenopus and in mammals.

The effects of whole genome duplications that characterize the evolution of vertebrates have been studied on the gene of the Xenopus thymocyte molecule CTX and its mammalian relatives. CTX, with an extracellular part consisting of one V and one C2 external domain, defines a new subset of the immunoglobulin superfamily and is conserved from amphibians to mammals. The number of CTX loci, their polymorphism, and their genetic linkages have been studied in several Xenopus species and in humans. In the genetically simplest species, X. tropicalis (2n = 20), the unique CTX locus is linked to the MHC. In the polyploid species, all CTX genes, unlike many other immune system genes, have remained in the genome; i.e. there are two CTX loci in the tetraploid species X. laevis (2n = 6) and six CTX loci in the dodecaploid species X. ruwenzoriensis (2n = 108). In X. laevis, one CTX gene is linked to the MHC and the other not, presumably because one set of MHC class I and II has been deleted from the corresponding linkage group. The various mammalian homologues are less related to each other than are the Xenopus CTX genes among each other, and they do not cross-hybridize with each other because they stem from the ancient polyploidization. Some human CTX homologies are on chromosomes 11 and 21, but others are on chromosomes 1, 6 and 19, which contain MHC paralogous regions; this suggests that a very ancient linkage group has been preserved.

Amino Acid Sequence↗

A hypothesis as to the organization of cerebral cortex in the common amniote ancestor of modern reptiles and mammals.

Opinions on the evolutionary origins of mammalian neocortex have divided into two camps: (1) antecedents of the superior neocortex (i.e. occipital, parietal and frontal lobes) and temporal neocortex (i.e. temporal lobe) were present in stem amniotes, and these antecedent regions gave rise to dorsal cortex and dorsal ventricular ridge (DVR), respectively, in living reptiles; (2) the stem amniote antecedent of mammalian superior neocortex gave rise to dorsal cortex in the reptilian lineage, while the stem amniote antecedent of mammal claustrum, endopiriform region and/or basolateral/basomedial amygdala gave rise to DVR in reptiles, with mammalian temporal neocortex being a newly evolved structure with no reptilian homologue. The latter hypothesis has the merit of being more consistent with some current homeobox gene data, but it has the disadvantages of positing that mammalian temporal neocortex arose de novo, and of assuming that the high similarity between DVR and temporal neocortex in the organization of thalamic sensory input and corticostriatal projections and in the topology of sensory areas is coincidental. If one assumes that the antecedent of superior and temporal neocortex in stem amniotes was one continuous field that histologically resembled dorsal cortex in living reptiles, the first hypothesis provides basis for a parsimonious account of the origin of superior and temporal neocortex and their considerable resemblance to dorsal cortex and DVR in reptiles, as well as to Wulst and DVR in birds.

Animals↗

Imprinted genes and the coordination of fetal and postnatal growth in mammals.

A substantial proportion of genes that control fetal growth in placental mammals are imprinted. Imprinted genes can act in fetal tissues to regulate growth by cell proliferation, cell death and the make up of extracellular space. Imprinted growth-promoting genes such as Igf2 probably act predominantly in an endocrine fashion, thus coordinating organ growth with the growth of the organism. In overgrowth and growth deficiency syndromes, however, imprinted growth factors can act by more local mechanisms, resulting in disproportionate growth. In addition to controlling fetal growth directly and thereby determining the nutritional demand of the fetus, imprinted genes can also apparently limit the nutritional supply to the fetus through the placenta. Imprinted genes may also be involved in postnatal growth up to weaning.

Animals↗

Development of the clavicles in birds and mammals.

Clavicles (collar bones) are variably present in mammals. Furculae (wishbones)--which may or may not be homologous with clavicles--are variably present and/or fused in birds and present in theropod dinosaurs. In this overview the development of clavicles and furculae is discussed with special attention to modes of skeletogenesis (whether intramembranous or endochondral), numbers of centres of ossification (one in chick furculae; two in murine clavicles), presence of cartilage (primary in clavicles, secondary in furculae), evidence from experimental analysis and from mutations for dependence of both clavicular and furcular growth on mechanical stimulation, and syndromes and mutations affecting clavicular development leading to both under and over development. J. Exp. Zool. 289:153-161, 2001.

Animals↗

New aspects of glutathione metabolism and translocation in mammals.

An appreciable fraction of the sulphur present in the mammal occurs in the form of glutathione, whose concentration in various tissues ranges from about 0.8 to about 8 mM; the extracellular concentration of glutatione (largely present as the disulphide) is in the micromolecular range. The synthesis of glutathione and its utilization take place by the reactions of the gamma-glutamyl cycle, which include those catalysed by gamma-glutamylcysteine and glutathione synthetases, gamma-glutamyl transpeptidase, cysteinylglycinase, gamma-glutamyl cyclotransferease, and 5-oxoprolinase. gamma-Glutamyl transpeptidase catalyses transpeptidation (with amino acids and dipeptides) and hydrolysis reactions with both blutathione and its disulphide. The transpeptidase is membrane-boudn, apparently to the outer surface of the cell, and is found in certain epithelial cells in anatomical sites that are involved in transport and secretory activities (e.g., renal tubule, jejunal villi, choroid plexus, ciliary body). Evidence that the reactions of the gamma-glutamyl cycle take place in vivo has come from studies with labelled metabolites and selective enzyme inhibitors, and on inborn errors of metabolism associated with specific enzyme deficiencies. Inhibition in vivo of gamma-glutamyl cyclotransferase and 5-oxoprolinase leads, respectively, to decreased and increased renal levels of 5-oxoproline. Administration of a specific inhibitor of gamma-glutamylcysteine synthetase, such as buthionine sulphoximine, leads to a rapid decline in the glutamylcysteine synthetase, such as buthionine sulphoximine, leads to a rapid decline in the glutathione level of the kidney and other tissues, reflecting the appreciable rate of glutathione utilization. When gamma-glutamyl transpeptidase is inhibited in vivo by injection of L- or D-gamma-glutamyl-(o-carboxy)phenylhydrazide, there is extensive glutathionuria and the blood plasma level of glutathione increases. Studies in which inhibitors of glutathione synthesis and transpeptidation were given to mice showed that transport of intracellular glutathione to membrane-bound transpeptidase is a discrete step in the gamma-glutamyl cycle, and that the level of plasma glutatione reflects (a) synthesis of glutathione and its export by liver, muscle, and other tissues and (b) utilization of glutatione by kidney and other tissues. Studies on several lymphoid cell lines show that these cells also actively translocate glutathione out of the cell. A summary scheme is given for the metabolism of glutathione in which glutathione is translocated to the cell membrane where it may be utilized as such or oxidized to glutathione disulphide. Oxidation is inhibited, and transpeptidation is promoted by the presence of amino acids that are substrates of the transpeptidase. Glutathione exported from cells that have membrane-bound transpeptidase may be recovered by the cell transport of gamma-glutamyl amino acids and free amino acids...

Animals↗

Conservation of CGG region in FMR1 gene in mammals.

Only two of the fragile sites found in humans (FRAXA and FRAXE) have been associated with a clinical phenotype. In mentally retarded individuals with cytogenetic expression of FRAXA a CGG repeat in the FMR1 gene is amplified. Fragile sites are found in many animals species. We have analyzed the FRAXA region containing the CGG repeat in several different species by PCR amplification. In most mammals this region could be amplified; the number of copies of the repeat is deduced.

Animals↗

Distribution of caspase-14 in epidermis and hair follicles is evolutionarily conserved among mammals.

Caspase-14, a member of the caspase family of cysteine proteases, is almost exclusively expressed in the epidermis. Studies on human and mouse cells and tissues have implicated caspase-14 in terminal differentiation of epidermal keratinocytes and in the formation of the stratum corneum. Here we investigated evolutionary aspects of the role of caspase-14 by analyzing its distribution in the epidermis and hair follicles of representative species of placental mammals, marsupials, and monotremes. Immunocytochemical staining showed that caspase-14 is consistently expressed in the granular and corneous layer of the epidermis of all mammalian species investigated. Ultrastructural analysis using gold-labeled anticaspase-14 antibodies revealed that caspase-14 is associated preferentially with keratin bundles and amorphous material of keratohyalin granules, but is also present in nuclei of transitional cells of the granular layer and in corneocytes. In hair follicles, caspase-14 was diffusely present in cornifying cells of the outer root sheath, in the companion layer, and, most abundantly, in the inner root sheath of all mammalian species here analyzed. In Henle and Huxley layers of the inner root sheath, labeling was seen in nuclei and, more diffusely, among trichohyalin granules of cornifying cells. In summary, the tissue expression pattern and the intracellular localization of caspase-14 are highly conserved among diverse mammalian species, suggesting that this enzyme is involved in a molecular process that appeared early in the evolution of mammalian skin. The association of caspase-14 with keratohyalin and trichohyalin granules may indicate a specific role of caspase-14 in the maturation of these keratinocyte-specific structures.

Animals↗

Survival and cancer in laboratory mammals exposed to radiofrequency energy.

This article is a review of the effects of radiofrequency (RF) energy on (1). survival and (2). cancer in the same animal populations having survival data. The literature consisted of 18 studies with survival data, and 16 of these have information on cancer. In one study, a significant decrease in lifespan was observed at 6.8 W/kg but not at 2 W/kg. Thermal stress appears to be the causal factor for the effect on lifespan because the higher dose rate, unlike the lower dose rate, was estimated to increase body temperature significantly. The finding that the lower level was without effect is consistent with the results of a number of recent studies showing that long term, low level exposure to RF energy did not affect survival adversely. Many of these recent studies addressed the cancer issue by histopathological analysis of many organs and tissues following exposure up to 2 years, the average lifetime of rats and mice. Some investigations examined the effect of RF fields from mobile phones on brain cancer, including the progression of chemically induced brain cancer. The results demonstrate that RF exposure did not adversely affect cancer incidence at whole body specific absorption rates (SARs) <or=4 W/kg and brain SARs <or=2.3 W/kg. The weight-of-evidence of these 18 studies shows that long term, low level exposure to RF energy does not adversely affect survival and cancer in laboratory mammals.

Animals↗

Helicase homologues maintain cytosine methylation in plants and mammals.

The Arabidopsis DDM1 gene is required for the maintenance of genomic methylation patterns but is a helicase homolog of the SWI2/SNF2 family rather than a DNA methyltransferase. Dennis et al. have shown that disruption of the mouse Lsh gene, the mammalian gene most closely related to DDM1, causes demethylation of the mouse genome. This result suggests that the mechanisms that maintain methylation patterns in the genomes of mammals and flowering plants are more conserved than previously suspected.

Animals↗

Mitochondrial one-carbon metabolism is adapted to the specific needs of yeast, plants and mammals.

In eukaryotes, folate metabolism is compartmentalized between the cytoplasm and organelles. The folate pathways of mitochondria are adapted to serve the metabolism of the organism. In yeast, mitochondria support cytoplasmic purine synthesis through the generation of formate. This pathway is important but not essential for survival, consistent with the flexibility of yeast metabolism. In plants, the mitochondrial pathways support photorespiration by generating serine from glycine. This pathway is essential under photosynthetic conditions and the enzyme expression varies with photosynthetic activity. In mammals, the expression of the mitochondrial enzymes varies in tissues and during development. In embryos, mitochondria supply formate and glycine for purine synthesis, a process essential for survival; in adult tissues, flux through mitochondria can favor serine production. The differences in the folate pathways of mitochondria depending on species, tissues and developmental stages, profoundly alter the nature of their metabolic contribution.

Animals↗

A novel signalling mechanism for generating Ca2+ oscillations at fertilization in mammals.

At fertilization in mammals the sperm activates the egg by triggering a series of oscillations in the intracellular free Ca2+ concentration. The precise sequence of events that occur between sperm-egg contact and the increases in intracellular Ca2+ remains unknown. Here, we discuss recent evidence supporting the hypothesis that a cytosolic sperm protein enters the egg after gamete membrane fusion and triggers Ca2+ oscillations from within the egg cytoplasm. Biochemical studies suggest that there exists a novel sperm protein, named oscillin, that specifically comigrates with Ca2+ oscillation-inducing activity. Oscillin has been immunolocalised to the region of the sperm that first fuses with the egg. The concept of a specific protein that triggers Ca2+ oscillations may have wider physiological significance since sperm oscillin can induce Ca2+ oscillations in somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling system involved in mammalian fertilization may help reveal some fundamental molecular mechanisms responsible for triggering cytoplasmic Ca2+ oscillations.

Animals↗

Biotransformation of terpenoids by mammals, microorganisms, and plant-cultured cells.

This review article summarizes our knowledge of the metabolism of mono- and sesquiterpenoids in mammals, microorganisms, cloned-insect enzymes, and plant-cultured cells. A number of unusual enzymatic reactions and products are reported such as the stereoselective formation of primary alcohols from sterically congested Me2C groups. Such enzymatic processes, including unknown chemical transformations under abiotic conditions, could lead to the discovery of new chemical reactions and might be helpful in the design of new drugs. The transformations of the following mono- and sesquiterpenoids (in alphabetical order) are discussed: (+)-(1R)-aromadendrene (61), (-)-allo-aromadendrene (62), (+/-)-camphene (21), (-)-cis-carane (20), (+)-3-carene (17), (+/-)-carvone (27), (-)-beta-caryophyllene (43), (+)-cedrol (35), cuminaldehyde (25), (+)-curdione (69), (-)-cyclocolorenone (60), (-)-elemol (51), (2E,6E)-farnesol (31), germacrone (67), ginsenol (40), (-)-globulol (63), isoprobotryan-9alpha-ol (82a), juvenile hormone III (33), (+)-ledol (65), (+)-longifolene (46), myrcene (3), (-)-myrtenal (23), (+)-nootkatone (48), patchouli alcohol (37), (-)-perillaldehyde (24), (-)-alpha- and beta-pinene (8 and 9), alpha-santalol (28), (-)-6beta-santonin (83a), 6beta-tetrahydrosantonin (83b), beta-selinene (57), alpha-thujone (26a), beta-thujone (26b), T-2 toxin (87), and valerianol (53).

Animals↗

Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals.

The distribution and size of gap junctions (GJ) in the sensory epithelia of the inner ear have been examined in a reptile (gecko), birds (chicken and owl), and mammals (mouse, guinea pig, gerbil, and bat), and the connexin composition of GJs in the mammalian inner ear has been assessed. Freeze fracture revealed a common pattern of GJ distribution in auditory and vestibular sensory epithelia in the different vertebrate classes. In all these tissues, GJs are numerous, often occupying more than 25% of the plasma membrane area of supporting cells and sometimes composed of more than 100,000 channels. Screening for 12 members of the connexin family in the mammalian inner ear by RT-PCR, Western blotting, and immunohistochemistry revealed four connexin isotypes, cx26, cx30, cx31, and cx43, in the cochlea and three, cx26, cx30, and cx43, in the vestibular organs. With antibodies characterised for their specificity, cx26 and cx30 colocalised in supporting cells of the organ of Corti, in the basal cell region of the stria vascularis, and in type 1 fibrocytes of the spiral ligament. No other connexin was detected in these regions. Cx31 was localised among type 2 fibrocytes below the spiral prominence, a region where cx30 was not expressed and cx26 expression appeared to be low. Cx43 was detected only in the region of "tension fibrocytes" lining the inner aspect of the otic capsule. This suggests separate functional compartments in the cochlea. In addition to cx26 and cx30, cx43 was detected in supporting cells of the vestibular sensory epithelia. Where cx26 and cx30 were colocalised, double immunogold labelling of thin sections showed both cx26 and cx30 evenly distributed in individual GJ plaques, a pattern consistent with the presence of heteromeric connexons. Coimmunoprecipitation of cochlear membrane proteins solubilised with a procedure that preserves the oligomeric structure of connexons confirmed the presence of heteromeric cx26/cx30 connexons. Heteromeric cx26/cx30 connexons may be unique to the inner ear, which could be one factor underlying the non-syndromic character of the deafness caused by mutations in cx26.

Animals↗

Sensory representation in reptilian optic tectum: some comparisons with mammals.

The sensory representations in the tectum of Iguana iguana were studied with electrophysiological recording techniques, and visual, somatic, and auditory cells were found to be represented here. These cells were not equally distributed throughout the tectal laminae. Upper tectal laminae were populated exclusively by visual cells, and deeper laminae were primarily nonvisual. The intermediate laminae had nonvisual, as well as visual, cells. Maps of the visual and somatic representations were constructed, and both representations were topographic and in register with no another. When electrical stimulation was presented via implanted electrodes, orientation responses were evoked that were predictable on the basis of the visuotopic and somatotopic maps. The organizational features of the iguana tectum are strikingly similar to those described in various mammalian species. It is suggested that the pattern of sensory and motor representation used in the midbrain of mammals is an ancient scheme that was retained during the transition from reptilian to mammalian forms more than 180 million years ago.

Acoustic Stimulation↗

Comparative cytoarchitectonic study of Gudden's tegmental nuclei in some mammals.

The structure and location of the dorsal and ventral tegmental nuclei of Gudden were studied in brains of 12 species of mammals. The ventral tegmental nucleus of Gudden is composed of oval or polygonal, medium-sized, well-stained cells, and includes the pars principalis situated ventral to the fasciculus longitudinalis medialis, and the pars suprafascicularis in the central gray matter dorsal to the fasciculus longitudinalis medialis (in the golden hamster, mouse, vole, and house shrew). The dorsal tegmental nucleus of Gudden is situated within the central gray matter. This nucleus includes the pars ventralis, composed of oval or triangular cells, medium-sized but smaller than those of the ventral tegmental nucleus of Gudden, and the pars dorsalis, composed of round, small, and lightly stained cells, and often encapsulated by fibers of the fasciculus longitudinalis dorsalis. The isthmus between the dorsal and ventral tegmental nuclei of Gudden is distinct. In the cat, dog, rat, gerbil, and rabbit, the isthmus stands at the dorsal edge of the fasciculus longitudinalis medialis; in the golden hamster, mouse, vole, and house shrew, within the central gray matter; and in the guinea pig, at the ventral edge of the fasciculus longitudinalis medialis. In the green monkey and man, we could not find a ventral tegmental nucleus of Gudden, and in the house shrew and man, the pars ventralis and pars dorsalis of the dorsal tegmental nucleus of Gudden could not be separated.

Animals↗

The parabigeminogeniculate projection: connectional studies in eight mammals.

Anterograde and retrograde tracing methods have been used to analyze the origin and distribution of parabigeminogeniculate axons in the gray squirrel, the gopher, the rat, the opossum, the cat, the greater bushbaby, the squirrel monkey and the macaque monkey. Our findings reveal that parabigeminogeniculate axons most heavily innervate regions of the lateral geniculate that are also targeted by axons arising from the superior colliculus (tectogeniculate). These geniculate layers and zones of parabigeminal and tectal overlap contain small cells, and in several species are associated with the small W cell retino-geniculocortical pathway. In addition to the dense input to small-celled layers and zones, parabigeminal axons in several species also innervate regions of the lateral geniculate nucleus that are relatively free of tectogeniculate axons and that are associated with the medium (X) and large (Y) cell streams. Finally, our data reveal that the laterality of parabigeminogeniculate pathways varies across mammals, being primarily crossed in the gray squirrel, the gopher, the rat, and the opossum, bilateral in the cat, and primarily ipsilateral in the three primates.

Animals↗

Path integration in mammals.

It is often assumed that navigation implies the use, by animals, of landmarks indicating the location of the goal. However, many animals (including humans) are able to return to the starting point of a journey, or to other goal sites, by relying on self-motion cues only. This process is known as path integration, and it allows an agent to calculate a route without making use of landmarks. We review the current literature on path integration and its interaction with external, location-based cues. Special importance is given to the correlation between observable behavior and the activity pattern of particular neural cell populations that implement the internal representation of space. In mammals, the latter may well be the first high-level cognitive representation to be understood at the neural level.

Animals↗

Comparative patterns of postcranial ontogeny in therian mammals: an analysis of relative timing of ossification events.

Data on the relative sequence of ossification of postcranial elements for eight therian mammals (Myotis lucifugus, Homo sapiens, Rattus norvegicus, Mus musculus, Mesocricetus auratus, Cavia porcellus, Didelphis albiventris, and Sminthopsis macroura) and three outgroups (Chelydra serpentina, Alligator mississippiensis, and Lacerta vivipara) were taken from the literature. For each species, a matrix was constructed in which the relative timing of the onset of ossification in 24 elements was summarized. This resulted in 276 event pairs (characters) for each species. Thirty-three (33.3)% of the characters examined are uniform across all taxa, 16.3% are variable but uninformative in the phylogeny, and 50.4% potentially deliver diagnostic features for clades of two or more taxa. In all species examined, the clavicle is the first bone to appear. Placentalia is not unequivocally diagnosed by the state of any event pair, while Marsupialia has the largest amount of autapomorphies with 18. The acceleration in the timing of ossification of the scapula in relation to the hindlimb in marsupials is most probably causally correlated to movements after birth and during early phases of pre-weaning life. Marsupials are almost unique among amniotes in that the earliest onset of ossification of at least one element among carpals and among tarsals is simultaneous. Three parsimony analyses, each one with a different reptilian taxon as outgroup, were performed using event pairs as characters. In all cases, results were incongruent with the phylogeny of the studied taxa.

Age Factors↗