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Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals.

The location of neurons generating the rhythm of breathing in mammals is unknown. By microsection of the neonatal rat brainstem in vitro, a limited region of the ventral medulla (the pre-Bötzinger Complex) that contains neurons essential for rhythmogenesis was identified. Rhythm generation was eliminated by removal of only this region. Medullary slices containing the pre-Bötzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties were identified in this region. Thus, the respiratory rhythm in the mammalian neonatal nervous system may result from a population of conditional bursting pacemaker neurons in the pre-Bötzinger Complex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Evolutionary and preservational constraints on origins of biologic groups: divergence times of eutherian mammals.

Some molecular clock estimates of divergence times of taxonomic groups undergoing evolutionary radiation are much older than the groups' first observed fossil record. Mathematical models of branching evolution are used to estimate the maximal rate of fossil preservation consistent with a postulated missing history, given the sum of species durations implied by early origins under a range of species origination and extinction rates. The plausibility of postulated divergence times depends on origination, extinction, and preservation rates estimated from the fossil record. For eutherian mammals, this approach suggests that it is unlikely that many modern orders arose much earlier than their oldest fossil records.

Animals↗

The promise of comparative genomics in mammals.

Dense genetic maps of human, mouse, and rat genomes that are based on coding genes and on microsatellite and single-nucleotide polymorphism markers have been complemented by precise gene homolog alignment with moderate-resolution maps of livestock, companion animals, and additional mammal species. Comparative genetic assessment expands the utility of these maps in gene discovery, in functional genomics, and in tracking the evolutionary forces that sculpted the genome organization of modern mammalian species.

Animals↗

Relative brain size and metabolism in mammals.

Comparisons of the relation between brain and body weights among extant mammals show that brain sizes have not increased as much as body sizes. Interspecific increases in brain and body size appear to occur at the same rate, however, when the amount of available energy is taken into account. After this adjustment, brains of primates are slightly larger than expected from the overall mammalian data, but primates also use a larger proportion of their total energy reserves for their brains. Analyses of relative brain size must take into account the requirements that the metabolically active brain has for the body.

Animals↗

Running and breathing in mammals.

Mechanical constraints appear to require that locomotion and breathing be synchronized in running mammals. Phase locking of limb and respiratory frequency has now been recorded during treadmill running in jackrabbits and during locomotion on solid ground in dogs, horses, and humans. Quadrupedal species normally synchronize the locomotor and respiratory cycles at a constant ratio of 1:1 (strides per breath) in both the trot and gallop. Human runners differ from quadrupeds in that while running they employ several phase-locked patterns (4:1, 3:1, 2:1, 1:1, 5:2, and 3:2), although a 2:1 coupling ratio appears to be favored. Even though the evolution of bipedal gait has reduced the mechanical constraints on respiration in man, thereby permitting greater flexibility in breathing pattern, it has seemingly not eliminated the need for the synchronization of respiration and body motion during sustained running. Flying birds have independently achieved phase-locked locomotor and respiratory cycles. This hints that strict locomotor-respiratory coupling may be a vital factor in the sustained aerobic exercise of endothermic vertebrates, especially those in which the stresses of locomotion tend to deform the thoracic complex.

Animals↗

Pattern of melatonin secretion mediates transfer of photoperiod information from mother to fetus in mammals.

Studies performed over the past 20 years have revealed that mother rodents can provide photoperiod information to their developing fetuses. In adult mammals, the pattern of pineal melatonin secretion changes in relation to changes in day length, and the melatonin pattern is a key part of the photoperiodic mechanism. Melatonin crosses the placenta, and fetal rodents can respond to the maternal melatonin rhythm. Thus, the mother's melatonin rhythm provides day-length information to the fetus, and this information is used, along with photoperiod information that is obtained after birth, to influence juvenile development. The transfer of photoperiod information from mother to fetus may be part of an adaptive system. When young are born early in the spring or summer breeding season, the increase in day length between the times of fetal and postnatal life results in rapid reproductive maturation, allowing these early-born animals to reproduce later during the same breeding season. In contrast, for young born late in the breeding season, the decrease in photoperiod between fetal and postnatal life results in delayed maturation of the gonads, and reproduction is delayed until the beginning of the next year's breeding season.

Animals↗

Characterization of a novel murine leukemia virus-related subgroup within mammals.

The murine leukemia virus (MuLV)-related retroviruses are one of seven genera which together constitute the family Retroviridae. They are widespread as both endogenous and exogenous agents within vertebrates and have been associated with a variety of malignancies and other disorders. We isolated and characterized 12 endogenous representatives of this genus from a number of mammalian hosts. Subsequent sequence analysis revealed that the isolated viruses cluster into two clearly distinct groups. All of the exogenous MuLV-related retroviruses which have been isolated to date, as well as several endogenous examples, fall into the first group, whereas the second group is represented solely by endogenous representatives, including human endogenous retrovirus type E (HERV.E). The two groups are widespread within mammals, with both often present within one animal species. Despite this, there is no evidence to date that recombination between members of the different groups has occurred. Genetic distances and several other properties of the HERV.E genome suggest that if exogenous members of this subgroup exist, they are likely to have biological properties different from those of the other exogenous viruses of this genus. Several of these viruses are known to have been integrated within their hosts' genomes for a long period of time, and a most recent divergence date for the MuLV and HERV.E subgroups can thus be proposed. This date, approximately 30 million years ago, is the most recent date possible, and it is probable that the actual period of time since their divergence is significantly longer.

Amino Acid Sequence↗

Characterization of murine leukemia virus restriction in mammals.

Restriction of murine leukemia virus (MLV) was examined in cells from a range of mammals. All nonmurine restrictions were saturable blocks to N-tropic MLV infection, and several were prior to reverse transcription. We demonstrate restriction in cells from bat and show that if we express the murine restriction factor Fv1 in human cells, then Fv1, not the human host, defines the stage at which infection is blocked.

Animals↗

Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals.

The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.

Animals↗

Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5.

Only five of the nine subunits of human eukaryotic translation initiation factor 3 (eIF3) have recognizable homologs encoded in the Saccharomyces cerevisiae genome, and only two of these (Prt1p and Tif34p) were identified previously as subunits of yeast eIF3. We purified a polyhistidine-tagged form of Prt1p (His-Prt1p) by Ni2+ affinity and gel filtration chromatography and obtained a complex of approximately 600 kDa composed of six polypeptides whose copurification was completely dependent on the polyhistidine tag on His-Prt1p. All five polypeptides associated with His-Prt1p were identified by mass spectrometry, and four were found to be the other putative homologs of human eIF3 subunits encoded in S. cerevisiae: YBR079c/Tif32p, Nip1p, Tif34p, and YDR429c/Tif35p. The fifth Prt1p-associated protein was eIF5, an initiation factor not previously known to interact with eIF3. The purified complex could rescue Met-tRNAiMet binding to 40S ribosomes in defective extracts from a prt1 mutant or extracts from which Nip1p had been depleted, indicating that it possesses a known biochemical activity of eIF3. These findings suggest that Tif32p, Nip1p, Prt1p, Tif34p, and Tif35p comprise an eIF3 core complex, conserved between yeast and mammals, that stably interacts with eIF5. Nip1p bound to eIF5 in yeast two-hybrid and in vitro protein binding assays. Interestingly, Sui1p also interacts with Nip1p, and both eIF5 and Sui1p have been implicated in accurate recognition of the AUG start codon. Thus, eIF5 and Sui1p may be recruited to the 40S ribosomes through physical interactions with the Nip1p subunit of eIF3.

Animals↗

A mammal-specific exon of WT1 is not required for development or fertility.

The WT1 tumor suppressor gene is a zinc finger-containing transcription factor which is required for development of the kidney and gonads. A mammal-specific alternative splicing event within this gene results in the presence or absence of a 17-amino-acid sequence within the WT1 protein. To determine the function of this sequence in vivo, gene targeting was utilized to specifically eliminate the exon encoding this sequence in mice. Mice lacking WT1 exon 5 develop normally. Adult mice lacking this exon are viable and fertile, and females are capable of lactation.

Alternative Splicing↗

Saccharomyces cerevisiae synthesizes proteins related to the p21 gene product of ras genes found in mammals.

A family of normal vertebrate genes and oncogenes has been called the ras gene family. The name ras was assigned to this gene family based on the species of origin of the viral oncogenes of the rat-derived Harvey and Kirsten murine sarcoma viruses. There are now three known functional members of the ras gene family, and genes homologous to ras genes have been detected in the DNA of a wide variety of mammals and in Drosophila melanogaster. Prior experiments have detected proteins coded for by ras genes in a large number of normal cells, cell lines, and tumors. We report here the detection of ras-related proteins in D. melanogaster, a result predicted by the earlier detection of ras-related genes in the Drosophila genome. We also report for the first time the detection of ras-related proteins in a single-cell eucaryocyte, Saccharomyces cerevisiae. These proteins, approximately 30K in size, are recognized by both a monoclonal antibody which binds to the p21 coded for by mammalian ras genes and a polyclonal rat serum made by transplanting a v-Ha-ras-induced tumor in Osborne-Mendel rats. The p21 of v-Ha-ras and the 30K proteins from S. cerevisiae share methionine-labeled peptides as detected by two-dimensional tryptic peptide maps. The results indicate that S. cerevisiae synthesizes ras-related proteins. A genetic analysis of the function of these proteins for yeast cells may now be possible.

Animals↗

Development of LYNX: a computer application for disease diagnosis and health monitoring in wild mammals, birds and reptiles.

IBM-compatible software has been developed so that quantitative and qualitative haematological and biochemical reference data for over 500 species of mammals, birds and reptiles can be made readily accessible to veterinary surgeons. The LYNX software makes it possible to retrieve these data at different taxonomic levels (species, genera, families, orders and classes) and to select data by age and sex. The data for each variable may be presented in the form of a reference range or as a frequency histogram. Notes describing the variations in blood cell morphology observed in healthy individuals of each species are included in the database. The user's own haematological and biochemical data can also be entered, stored and used.

Animals↗

Guidelines for the interpretation of laboratory findings in birds and mammals with unknown reference ranges: plasma biochemistry.

The results of analyses of plasma samples from healthy and sick adult birds and mammals of a wide range of species were used to calculate reference ranges and clinical ranges for 11 biochemical variables (calcium, sodium, chloride, total protein, albumin, globulin, inorganic phosphate, potassium, bicarbonate, urea and creatinine concentrations) in six mammalian Orders (Primata, Carnivora, Pinnipedia, Proboscidea, Perissodactyla and Artiodactyla) and six avian Orders (Ciconiiformes, Gruiformes, Pelecaniformes, Psittaciformes, Falconiformes and Strigiformes). The patterns of variation between Orders for the different biochemical variables were then used to provide guidelines for the interpretation of plasma biochemistry results in the species in these Orders for which there are no reference data. The observed clinical ranges provide an indication of the potential diagnostic value of each variable.

Animal Diseases↗

Relationship of hepatocyte ploidy levels with body size and growth rate in mammals.

To elucidate possible causes of the elevation of genome number in somatic cells, hepatocyte ploidy levels were measured cytofluorimetrically and related to the organismal parameters (body size, postnatal growth rate, and postnatal development type) in 53 mammalian species. Metabolic scope (ratio of maximal metabolic rate to basal metabolic rate) was also included in 23 species. Body masses ranged 10(5) times, and growth rate more than 30 times. Postnatal growth rate was found to have the strongest effect on the hepatocyte ploidy. At a fixed body mass the growth rate closely correlates (partial correlation analysis) with the cell ploidy level (r = 0.85, P < 10(-6)), whereas at a fixed growth rate body mass correlates poorly with ploidy level (r = -0.38, P < 0.01). The mature young (precocial mammals) of the species have, on average, a higher cell ploidy level than the immature-born (altricial) animals. However, the relationship between precocity of young and cell ploidy levels disappears when the influences of growth rate and body mass are removed. Interspecies variability of the hepatocyte ploidy levels may be explained by different levels of competition between the processes of proliferation and differentiation in cells. In turn, the animal differences in the levels of this competition are due to differences in growth rate. A high negative correlation between the hepatocyte ploidy level and the metabolic scope indicates a low safety margin of organs with a high number of polyploid cells. This fact allows us to challenge a common opinion that increasing ploidy enhances the functional capability of cells or is necessary for cell differentiation. Somatic polyploidy can be considered a "cheap" solution of growth problems that appear when an organ is working at the limit of its capabilities.

Animals↗

Maintenance and regulation of DNA methylation patterns in mammals.

Proper establishment and faithful maintenance of epigenetic information is crucial for the correct development of complex organisms. For mammals, it is now accepted that DNA methylation is an important mechanism for establishing stable heritable epigenetic marks. The distribution of methylation in the genome is not random, and patterns of methylated and unmethylated DNA are well regulated during normal development. The molecular mechanisms by which methylation patterns are established and maintained are complex and just beginning to be understood. In this review, we summarize recent progress in understanding the regulation of mammalian DNA methylation patterns, with an emphasis on the emerging roles of several protein and possible RNA factors. We also revisit the stochastic model of maintenance methylation and discuss its implications for epigenetic fidelity and gene regulation.

Animals↗

A new regulatory interaction suggested by simulations for circadian genetic control mechanism in mammals.

Knowledge of molecular biological systems is increasing at an amazing pace. It is becoming harder to intuitively evaluate the significance of each interaction between the molecules of the complex biological systems. Hence, we need to develop an efficient computational method to explore the biological mechanisms. In this study, we employed a hybrid functional Petri net in order to analyze mammalian circadian genetic control mechanisms, which consists of feedback loops of clock genes and generates endogenous near 24 h rhythms in mammals. We constructed a computational model based on the available biological data, and by using Genomic Object Net, we performed computer simulations of the time courses of clock gene transcription and translation. Although the original model successfully reproduced most of the circadian genetic control mechanisms, two discrepancies remained despite a wide selection of the parameters. We found that addition of a hypothetical path into the original model result in successful simulation of time courses and phase relationships among clock genes. This also demonstrates the usefulness of the hybrid functional Petri net approach to biological systems.

Animals↗

Sphingolipid functions in Saccharomyces cerevisiae: comparison to mammals.

Many roles for sphingolipids have been identified in mammals. Available data suggest that sphingolipids and their intermediates also have diverse roles in Saccharomyces cerevisiae. These roles include signal transduction during the heat stress response, regulation of calcium homeostasis or components in calcium-mediated signaling pathways, regulation of the cell cycle, and functions as components in trafficking of secretory vesicles from the endoplasmic reticulum to the Golgi apparatus and as the lipid moiety in many glycosylphosphatidylinositol-anchored proteins. S. cerevisiae is likely to be the first organism in which all genes involved in sphingolipid metabolism are identified. This information will provide an unprecedented opportunity to determine, for the first time in any organism, how sphingolipid synthesis is regulated. Through the use of both genetic and biochemical techniques, the identification of the complete array of processes regulated by sphingolipid signals is likely to be possible, as is the quantification of the physiological contribution of each.

Animals↗