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Peas-Mea1-Ppp2r5d overlapping gene complex: a transposon mediated-gene formation in mammals.

Human and mouse MEA1/Mea1 is flanked by two overlapping genes, a novel PEAS/Peas in a head-to-head orientation and PPP2R5D/Ppp2r5d in a tail-to-tail orientation making a Peas-Mea1-Ppp2r5d overlapping gene complex (PMP-complex). Genomic zoo blot analyses and database searching revealed that Mea1 exists only in mammals, while Peas and Ppp2r5d are conserved in eukaryotes. Mea1 and Peas are transcribed from a testis-expressed bidirectional promoter. Mea1-Ppp2r5d overlapping segment (MPOS) contains polyadenylation signals for both genes and shows marked conservation throughout mammals. Furthermore, the MPOS occupies 3'-region of transcripts of both genes is expected to form a clover-like intramolecular structure. Mouse genomic library Screening and database searches identified two MPOS-derived sequences in Odf2 gene and RP23-86H7 cosmid clone, respectively, in which MPOS might be a core segment for the retropositions. Thus, a key role of MPOS, a short transposable element containing polyadenylation signals on both strands, in the formation of the Mea1 during mammalian evolution is suggested.

Animals↗

The influence of non-coding RNAs on allele-specific gene expression in mammals.

Current research has revealed that the influence of RNA molecules on gene expression reaches beyond the realm of protein synthesis back into the nucleus, where it not only dictates the transcriptional activity of genes, but also shapes the chromatin architecture of extensive regions of DNA. Non-coding RNA, in the context of this review, refers to transcripts expressed and processed in the nucleus much like any protein coding gene, but lacking an open reading frame and often transcribed antisense to bona fide protein coding genes. In mammals, these types of transcripts are highly coincident with allele-specific silencing of imprinted genes and have a proven role in dosage compensation via X-inactivation. The biochemistry of how non-coding RNAs regulate transcription is the subject of intense research in both prokaryotic and eukaryotic models. Mechanisms such as RNA interference may have deep phylogenetic roots, but their relevance to imprinting and X-inactivation in mammals has not been proven. The remarkable diversity of non-coding transcription associated with parent-of-origin directed gene silencing hints at an equally diverse assortment of mechanisms.

Alleles↗

Practical uses for ecdysteroids in mammals including humans: an update.

Ecdysteroids are widely used as inducers for gene-switch systems based on insect ecdysteroid receptors and genes of interest placed under the control of ecdysteroid-response elements. We review here these systems, which are currently mainly used in vitro with cultured cells in order to analyse the role of a wide array of genes, but which are expected to represent the basis for future gene therapy strategies. Such developments raise several questions, which are addressed in detail. First, the metabolic fate of ecdysteroids in mammals, including humans, is only poorly known, and the rapid catabolism of ecdysteroids may impede their use as in vivo inducers. A second set of questions arose in fact much earlier with the pioneering "heterophylic" studies of Burdette in the early sixties on the pharmacological effects of ecdysteroids on mammals. These and subsequent studies showed a wide range of effects, most of them being beneficial for the organism (e.g. hypoglycaemic, hypocholesterolaemic, anabolic). These effects are reviewed and critically analysed, and some hypotheses are proposed to explain the putative mechanisms involved. All of these pharmacological effects have led to the development of a wide array of ecdysteroid-containing preparations, which are primarily used for their anabolic and/or "adaptogenic" properties on humans (or horses or dogs). In the same way, increasing numbers of patents have been deposited concerning various beneficial effects of ecdysteroids in many medical or cosmetic domains, which make ecdysteroids very attractive candidates for several practical uses. It may be questioned whether all these pharmacological actions are compatible with the development of ecdysteroid-inducible gene switches for gene therapy, and also if ecdysteroids should be classified among doping substances.

Animals↗

Heterology of mitochondrial DNA from mammals detected by electron microscopic heteroduplex analyses.

Heteroduplex analysis of mitochondrial DNA (mtDNA) from evolutionary closely related mammals (rat vs. mouse, man vs. monkey) are analyzed and compared to heteroduplex analysis of mt-DNA from more distantly related mammals (rat vs. man, rat vs. monkey, mouse vs. man, mouse vs. monkey and man vs. cow). Each analysis is transformed into a heteroduplex map and all maps are aligned to restriction enzyme maps and to genetic maps and where possible compared with the known sequence. We show that early evolutionary changes are seen mainly in URF2, URFA6L, URF6 and the D-loop region. The regions of rRNA, URF1, COI and COIII are generally very conserved regions but areas with some evolutionary activity can be localized. Heteroduplex analysis between distantly related species show much more heterology than do closely related species and the heteroduplex maps between all the distantly related species show a common pattern of heterology. Comparisons between the DNA sequence of mtDNA from man, cow and mouse and the equivalent heteroduplex maps show that base pair homologies higher than 73% are displayed as homologous regions. In the heteroduplex analysis of mtDNA's from more closely related species very few heterologies are displayed at 50% formamide but an increase in formamide concentration to 65-70% demonstrate also in these instances general heterologous regions.

Animals↗

Functional elements of the ribosomal protein L7a (rpL7a) gene promoter region and their conservation between mammals and birds.

The transcriptional initiation sites of the chicken ribosomal protein L7a (rpL7a) gene have been determined and found to occur at three consecutive cytidine residues at the start of a polypyrimidine tract of 8 base pairs (bp). A comparative analysis of the 5' upstream regions of the mouse, human and chicken rpL7a genes identified two sequence elements (Box A and Box B) conserved over the 600 million years of divergent evolution that separate mammals and birds. Only Box A (nts - 56 to - 39) and Box B (nts - 25 to - 4) sequences were detected to bind nuclear factors from mouse nuclear extracts in an analysis of the mouse rpL7a 5' upstream sequence. Box A and Box B bind different nuclear factors and the factor binding to mouse Box A and mouse Box B sequences could be effectively competed by corresponding homologous sequences from the human and chicken rpL7a promoters. These results indicate that elements of the rpL7a promoter region are conserved between mammals and birds. An in vivo analysis of the mouse rpL7a 5' upstream sequence required for efficient transcription identified the 5' border of the minimal promoter region as lying between nts - 50 and - 56. Constructs containing 56 bp of 5' upstream DNA and the first 25 bp rpL7a exon were very efficiently transcribed indicating that sequences within the first intron are not required for gene expression. No sequence similarity was detected between the rpL7a promoter elements and described promoter elements of other eukaryotic ribosomal protein genes.

Animals↗

U21, a novel small nucleolar RNA with a 13 nt. complementarity to 28S rRNA, is encoded in an intron of ribosomal protein L5 gene in chicken and mammals.

Following a search of sequence data bases for intronic sequences exhibiting structural features typical of snoRNAs, we have positively identified by Northern assays and sequence analysis another intron-encoded snoRNA, termed U21. U21 RNA is a 93 nt. long, metabolically stable RNA, present at about 10(4) molecules per HeLa cell. It is encoded in intron 5 of the ribosomal protein L5 gene, both in chicken and in the two mammals studied so far, human and mouse. U21 RNA is devoid of a 5'-trimethyl-cap and is likely to result from processing of intronic RNA. The nucleolar localization of U21 has been established by fluorescence microscopy after in situ hybridization with digoxigenin-labeled oligonucleotide probes. Like most other snoRNAs U21 contains the box C and box D motifs and is precipitated by anti-fibrillarin antibodies. By the presence of a typical 5'-3' terminal stem, U21 appears more particularly related to U14, U15, U16 and U20 intron-encoded snoRNAs. Remarkably, U21 contains a long stretch (13 nt.) of complementarity to a highly conserved sequence in 28S rRNA. Sequence comparisons between chicken and mammals, together with Northern hybridizations with antisense oligonucleotides on cellular RNAs from more distant vertebrates, point to the preferential preservation of this segment of U21 sequence during evolution. Accordingly, this complementarity, which overlaps the complementarity of 28S rRNA to another snoRNA, U18, could reflect an important role of U21 snoRNA in the biogenesis of large ribosomal subunit.

Animals↗

Circadian photosensitive phase and photoperiodic control of testis activity in the mink (Mustela vison Peale and Beauvois), a short-day mammal.

Evidence of a circadian photosensitive phase in male mink, whose annual reproductive cycle is characterized by the recrudescence of testicular development in autumn, was based on the study of testicular response after interrupting the dark period by light breaks (0.5 h) offered at various times. In this mammal, the experimental short days 4L:20D and 8L:16D stimulated testicular growth. Short photoperiods, including a main light period of 3.5 h and an additional 0.5 h light break 7.5 h after the beginning of the main photoperiod, were as effective as 8L:16D in stimulating testicular development. On the other hand, when a 0.5 h light break occurred 11.5 or 15.5 h after the beginning of the main photoperiod, the same inhibiting effect on testicular activity was obtained as for long photoperiods. However, when 0.5 h light breaks were given 19.5 after the beginning of the main light period, some minks recognized, as "dawn", the onset of the shorter of the two light periods offered. Thus our results proved the existence of a special phase in the day cycle in which light inhibited testicular development in the mink which appears to be a short-day animal. One explanation of the difference between long-day and short-day animals would be the following: if for long-day animals exposure to light during the photosensitive phase led to gonadostimulation, in short-day mammals, like mink, it exerted an inhibiting influence on testicular growth.

Animals↗

Refractive state of the eye of a small diurnal mammal: the ground squirrel.

Previous work dealing with the question of whether or not the eyes of small mammals are hyperopic has been restricted largely to the study of nocturnal animals such as the rat. In this study, refractive state of the eye of a small diurnal mammal, the ground squirrel, was measured by retinoscopy and from the electrophysiological response of retinal ganglion cells to grating targets. Both measurements show the squirrel to be emmetropic. We conclude that the refractive state of the eye is not a function of eye size per se, but rather a function of whether the animal is nocturnal or diurnal.

Activity Cycles↗

The angiosomes of the mammals and other vertebrates.

This is a comparative study of the vasculature of the integument and underlying deep tissues of a range of mammals and other vertebrates. The investigation was conducted in the pig, monkey, dog, cat, possum, guinea pig, rat, rabbit, duck, and toad. The results from each are compared not only to each other, but also to previously performed human studies. The arterial network of the fresh animal cadaver was injected with a mixture of lead oxide and gelatin. The vascular anatomy of the skin, deep tissues, and individual muscles was defined by dissection, cutaneous perforator counts, photography, and radiography. A similar pilot study of the venous framework was performed in the pig, dog, and rabbit that included maps of the sites and orientations of the valves. The vasculature of the integument and deep tissues was correlated, and we found that we were able to define angiosomes (composite blocks of tissue supplied by the same source vessel) in each animal. Results revealed a marked dissimilarity of the overlying cutaneous vessels in many cases, yet a striking resemblance of the vascular architecture of the deep tissues. The size and density of the cutaneous perforators bore a close relation to the degree of the skin mobility, being large and sparse where the skin was mobile and smaller and more densely grouped where the integument was tethered or fixed. The cutaneous vasculature of the human resembled that of the monkey closely, was similar to that of the dog, cat, and possum, and was dissimilar to that of the pig, rat, guinea pig, and rabbit. Studies of the amphibian and bird bore many resemblances to those of the mammals. They provided basic concepts regarding modification of the animals' vascular anatomy in response to the functional demands of the species. In each animal, the arteries formed an unbroken network throughout the body. This consisted of anatomic territories linked by anastomotic vessels that were usually of reduced caliber. The pattern of the venous system was almost identical. Valved venous territories were linked by avalvular (oscillating) veins. The common denominator in the vascular system is the capillary bed. Conceptually, the anatomic arrangement of the arteries and veins, reproduced in each species, appears to be a sophisticated mechanism to allow equilibration of flow and pressure arriving at and departing from the capillary bed. The angiosome concept is reinforced by the animal studies. Although this investigation is essentially a detailed pilot study, it embraces many animals commonly used for experimentation and provides a reference atlas of their vasculature.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomy, Comparative↗

Acetylcholine in the corneal epithelium of diurnal and nocturnal mammals.

PURPOSE: To analyze the concentration of acetylcholine (ACh) in the corneal epithelium and aqueous humor of various diurnal and nocturnal mammals. METHODS: The following species were examined: roe deer, cattle, horse, human, moose, sheep, reindeer, wild boar, polecat, lynx, cat, and rat. ACh was determined by liquid chromatography-tandem mass spectrometry. RESULTS: ACh was present in significant amounts in the corneal epithelium of all diurnal mammals, the concentrations varying from one species to the next. By contrast, it was not detected in any of the nocturnal tissue samples. None of the species showed detectable amounts of ACh in the aqueous humor. CONCLUSIONS: The amount of ACh in the corneal epithelium varies from one species to the next, with diurnal species showing significant concentrations and nocturnal species no detectable concentrations.

Acetylcholine↗

The specification of early hematopoiesis in the mammal.

PURPOSE OF REVIEW: A number of interesting surprises has emerged during the past year in the field of early hematopoietic development. This review highlights recent studies that have challenged the prevailing view of embryonic and fetal hematopoiesis in mammals, with a focus on the mouse as a model system. The authors apologize to the many colleagues whose work could not be cited because of space limitations. RECENT FINDINGS: Advances in our understanding of the embryonic origins of hematopoiesis in mammals and in the regulation of primitive and definitive hematopoietic development are discussed. SUMMARY: The ontological relation between primitive (embryonic) and definitive (fetal and adult) hematopoiesis still holds some mysteries for the biologist. Both technical and conceptual breakthroughs have refined our view of how blood cells form at different stages of development. What we learn from the embryo is not only of fundamental interest but may have future applications in the clinic.

Animals↗

Perception of female reproductive state from vocal cues in a mammal species.

While acoustic signalling by males is known to affect male-male competition, mate attraction and the timing of ovulation, the extent to which sexual selection has shaped the evolution of female acoustic signals is poorly understood. Among mammals, experimental evidence indicates that females attract mating partners by using olfactory and visual signals to advertise their reproductive state. Whether or not males ascertain female reproductive state from vocal signals has, however, never been systematically tested. In this study, we use playbacks of recorded vocalizations to demonstrate that male Barbary macaques, Macaca sylvanus, can discriminate between female copulation calls given at different stages of the oestrous cycle, responding more strongly to those given around the time when conception is most likely to occur. Acoustic analysis suggests that the mean dominant frequency of call units and a number of temporal parameters could provide males with the information necessary to discern the proximity of ovulation in this way Our results provide the first experimental evidence that the calls of female mammals may contain information on reproductive state, which males can perceive and use in such a way as to increase their reproductive success.

Animals↗

Modelling population persistence on islands: mammal introductions in the New Zealand archipelago.

Islands are likely to differ in their susceptibility to colonization or invasion due to variation in factors that affect population persistence, including island area, climatic severity and habitat modification. We tested the importance of these factors in explaining the persistence of 164 introductions of six mammal species to 85 islands in the New Zealand archipelago using survival analysis and model selection techniques. As predicted by the theory of stochastic population growth, extinction risk was the greatest in the period immediately following introduction, declining rapidly to low probability by ca 25 years. This suggests that initially small populations were at greatest risk of extinction and that populations which survived for 25 years were likely to persist subsequently for much longer. Islands in the New Zealand archipelago become colder and windier with increasing latitude, and the probability of mammal populations persisting on islands declined steeply with increasing latitude. Hence, our results suggest that climatic suitability was an important determinant of the outcome of these invasions. The form of the relationship between latitude and persistence probability differed among species, emphasizing that the outcome of colonization attempts is species-environment specific.

Animals↗

Rarity of a top predator triggers continent-wide collapse of mammal prey: dingoes and marsupials in Australia.

Top predators in terrestrial ecosystems may limit populations of smaller predators that could otherwise become over abundant and cause declines and extinctions of some prey. It is therefore possible that top predators indirectly protect many species of prey from excessive predation. This effect has been demonstrated in some small-scale studies, but it is not known how general or important it is in maintaining prey biodiversity. During the last 150 years, Australia has suffered the world's highest rate of mammal decline and extinction, and most evidence points to introduced mid-sized predators (the red fox and the feral cat) as the cause. Here, we test the idea that the decline of Australia's largest native predator, the dingo, played a role in these extinctions. Dingoes were persecuted from the beginning of European settlement in Australia and have been eliminated or made rare over large parts of the continent. We show a strong positive relationship between the survival of marsupials and the geographical overlap with high-density dingo populations. Our results suggest that the rarity of dingoes was a critical factor which allowed smaller predators to overwhelm marsupial prey, triggering extinction over much of the continent. This is evidence of a crucial role of top predators in maintaining prey biodiversity at large scales in terrestrial ecosystems and suggests that many remaining Australian mammals would benefit from the positive management of dingoes.

Animals↗

Structure of an excitatory insect-specific toxin with an analgesic effect on mammals from the scorpion Buthus martensii Karsch.

BmK IT-AP is an excitatory insect-specific beta-toxin with analgesic effect from the Chinese scorpion Buthus martensii Karsch (BmK) and consists of 72 residues cross-linked by four disulfide bridges. The crystal structure of BmK IT-AP has been determined at a resolution of 2.6 A by molecular replacement. Compared with the mammal-selective alpha-toxins consisting of 64 residues from the scorpion BmK, the general fold of IT-AP features an additional one-and-a-half turn alpha-helix at the C-terminal residues 59-65 with a shifted disulfide bridge Cys38-Cys64. The extension and 'wiggling' of the C-terminal segment led to a reshaping of the bioactive surface, including the complete destruction of the active site RC comprising the reverse turn (8-12) and C-terminal residues 58-64, the disappearance of an active surface formed by two aromatic residues Trp38 and Tyr42 and the covering of the conserved aromatic cluster Tyr5, Tyr35 and Trp47, which are all critical for the structure and function of mammal-selective alpha-toxins. Bj-xtrIT, the only other excitatory insect-specific toxin whose three-dimensional structure has been determined, is distinct from BmK IT-AP. A functionally important five-residue alpha-helix (alpha0) formed by residues 17-21 in Bj-xtrIT is deleted in BmK IT-AP and helix alpha1 is immediately connected to Cys16 through two residues Leu17 and Phe18. Accordingly, the functional surface of this region in Bj-xtrIT has also been reshaped in IT-AP, which implies subtle differences between BmK IT-AP and Bj-xtrIT in binding to the receptor, although most other critical residues for structure and function adopt almost identical conformations. The crystal structure of IT-AP also forms a sound basis for further study of the structure-function determinants of the analgesic effect.

Amino Acid Sequence↗

Analysis of sex-linked sequences supports a new mammal species in Europe.

European mammals have been the focus of particularly detailed taxonomic studies by traditional morphological methods. However, DNA analyses have the potential to reveal additional, cryptic species. We describe two highly divergent evolutionary lineages within a small Eurasian mammal, the field vole (Microtus agrestis). We show that the two lineages can be detected not only with maternally (mitochondrial DNA), but also with paternally (Y chromosome) and biparentally (X chromosome) inherited DNA sequences. Reciprocal monophyly of all genealogies and their congruent geographical distributions is consistent with reproductive isolation. Our results suggest that the field vole should be reclassified as two separate species.

Animals↗

Restricted mating dispersal and strong breeding group structure in a mid-sized marsupial mammal (Petrogale penicillata).

Ecological genetic studies have demonstrated that spatial patterns of mating dispersal, the dispersal of gametes through mating behaviour, can facilitate inbreeding avoidance and strongly influence the structure of populations, particularly in highly philopatric species. Elements of breeding group dynamics, such as strong structuring and sex-biased dispersal among groups, can also minimize inbreeding and positively influence levels of genetic diversity within populations. Rock-wallabies are highly philopatric mid-sized mammals whose strong dependence on rocky terrain has resulted in series of discreet, small colonies in the landscape. Populations show no signs of inbreeding and maintain high levels of genetic diversity despite strong patterns of limited gene flow within and among colonies. We used this species to investigate the importance of mating dispersal and breeding group structure to inbreeding avoidance within a 'small' population. We examined the spatial patterns of mating dispersal, the extent of kinship within breeding groups, and the degree of relatedness among brush-tailed rock-wallaby breeding pairs within a colony in southeast Queensland. Parentage data revealed remarkably restricted mating dispersal and strong breeding group structuring for a mid-sized mammal. Breeding groups showed significant levels of female kinship with evidence of male dispersal among groups. We found no evidence for inbreeding avoidance through mate choice; however, anecdotal data suggest the importance of life history traits to inbreeding avoidance between first-degree relatives. We suggest that the restricted pattern of mating dispersal and strong breeding group structuring facilitates inbreeding avoidance within colonies. These results provide insight into the population structure and maintenance of genetic diversity within colonies of the threatened brush-tailed rock-wallaby.

Animals↗

Deep genetic subdivision within a continuously distributed and highly vagile marine mammal, the Steller's sea lion (Eumetopias jubatus).

The Steller's sea lion Eumetopias jubatus is an endangered marine mammal that has experienced dramatic population declines over much of its range during the past five decades. Studies using mitochondrial DNA (mtDNA) have shown that an apparently continuous population includes a strong division, yielding two discrete stocks, western and eastern. Based on a weaker split within the western stock, a third Asian stock has also been defined. While these findings indicate strong female philopatry, a recent study using nuclear microsatellite markers found little evidence of any genetic structure, implying extensive paternal gene flow. However, this result was at odds with mark-recapture data, and both sample sizes and genetic resolution were limited. To address these concerns, we increased analytical power by genotyping over 700 individuals from across the species' range at 13 highly polymorphic microsatellite loci. We found a clear phylogenetic break between populations of the eastern stock and those of the western and Asian stocks. However, our data provide little support for the classification of a separate Asian stock. Our findings show that mtDNA structuring is not due simply to female philopatry, but instead reflects a genuine discontinuity within the range, with implications for both the phylogeography and conservation of this important marine mammal.

Animals↗