Virtual reconstruction of the Canis arnensis type (Canidae, Mammalia) from the Upper Valdarno Basin (Italy, Early Pleistocene).

Taphonomic deformation, whether it be brittle or plastic, is possibly the most influential process hindering the correct understanding of fossil species morphology. This is especially true if the deformation affects type specimens or applies to or obscures taxonomically diagnostic or functionally significant traits. Target Deformation, a recently developed virtual manipulation protocol, was implemented to address this issue by applying landmark-guided restoration of the original, deformed fossils, using undeformed specimens (or parts thereof) of the same species as a reference. The enigmatic Early Pleistocene canid Canis arnensis provides a typical example of a fossil species in dire need of virtual restoration. Its lectotype specimen is heavily deformed and none of the few known skulls are well preserved, obscuring the recognition of its systematic and phylogenetic position. Our results indicate that the algorithm effectively countered the lectotype skull's laterolateral compression and its concomitant rostrocaudal elongation. Morphometrically, comparison of the retrodeformed cranium (IGF 867_W) with other specimens of the same species, and to other fossil and extant canid material, confirms IGF 867_W consistently clusters within C. arnensis variability. Overall, the evidence presented here confirms that Target Deformation provides a powerful tool to better characterize complex taxa like C. arnensis, whose knowledge is severely affected by the state of preservation of its fossil material.

A troodontid dinosaur from the latest Cretaceous of India.

Troodontid dinosaurs share a close ancestry with birds and were distributed widely across Laurasia during the Cretaceous. Hundreds of occurrences of troodontid bones, and their highly distinctive teeth, are known from North America, Europe and Asia. Thus far, however, they remain unknown from Gondwanan landmasses. Here we report the discovery of a troodontid tooth from the uppermost Cretaceous Kallamedu Formation in the Cauvery Basin of South India. This is the first Gondwanan record for troodontids, extending their geographic range by nearly 10,000 km, and representing the first confirmed non-avian tetanuran dinosaur from the Indian subcontinent. This small-bodied maniraptoran dinosaur is an unexpected and distinctly 'Laurasian' component of an otherwise typical 'Gondwanan' tetrapod assemblage, including notosuchian crocodiles, abelisauroid dinosaurs and gondwanathere mammals. This discovery raises the question of whether troodontids dispersed to India from Laurasia in the Late Cretaceous, or whether a broader Gondwanan distribution of troodontids remains to be discovered.

The correlated evolution of Runx2 tandem repeats, transcriptional activity, and facial length in carnivora.

To assess the ability of protein-coding mutations to contribute to subtle, inter-specific morphologic evolution, here, we test the hypothesis that mutations within the protein-coding region of runt-related transcription factor 2 (Runx2) have played a role in facial evolution in 30 species from a naturally evolving group, the mammalian order Carnivora. Consistent with this hypothesis, we find significant correlations between changes in Runx2 glutamine-alanine tandem-repeat ratio, and both Runx2 transcriptional activity and carnivoran facial length. Furthermore, we identify a potential evolutionary mechanism for the correlation between Runx2 tandem repeat ratio and facial length. Specifically, our results are consistent with the Runx2 tandem repeat system providing a flexible genetic mechanism to rapidly change the timing of ossification. These heterochronic changes, in turn, potentially act on existing allometric variation in carnivoran facial length to generate the disparity in adult facial lengths observed among carnivoran species. Our results suggest that despite potentially great pleiotropic effects, changes to the protein-coding regions of genes such as Runx2 do occur and have the potential to affect subtle morphologic evolution across a diverse array of species in naturally evolving lineages.

The effect of high and low dietary crude protein and inulin supplementation on nutrient digestibility, nitrogen excretion, intestinal microflora and manure ammonia emissions from finisher pigs.

A 2 × 2 factorial experiment was performed to investigate the interaction between a high- and low-crude-protein (CP) diet (200 v. 140 g/kg) and inulin supplementation (0 v. 12.5 g/kg) on nutrient digestibility, nitrogen (N) excretion, intestinal microflora, volatile fatty acid (VFA) concentration and manure ammonia emissions from 24 boars (n = 6, 74.0 kg live weight). The diets were formulated to contain similar concentrations of digestible energy and lysine. Pigs offered the high-CP diets had a higher excretion of urinary N (P < 0.001), faecal N (P < 0.01) and total N (P < 0.001) than the pigs offered the low-CP diets. Inulin supplementation increased faecal N excretion (P < 0.05) and decreased the urine N : faeces N ratio (P < 0.05) compared with the inulin-free diets. There was no effect (P > 0.05) of dietary treatment on N retention. There was an interaction (P < 0.05) between dietary CP concentration and inulin supplementation on caecal Enterobacteria spp. Pigs offered the diet containing 200 g/kg of CP plus inulin decreased the population of Enterobacteria spp. compared to those with the inulin-supplemented 140 g/kg CP diet. However, CP level had no significant effect on the population of Enterobacteria spp. in the unsupplemented diets. Inulin supplementation increased caecal Bifidobacteria (P < 0.01) compared with the inulin-free diets. There was no effect of inulin supplementation on VFA concentration or intestinal pH (P > 0.05). Pigs offered the 200 g/kg CP diets had higher (P < 0.05) manure ammonia emissions from 0 to 240 h of storage than pigs offered the 140 g/kg CP. In conclusion, inulin supplementation resulted in an increase in Bifidobacteria concentration and a reduction in Enterobacteria spp. at the high CP level indicating that inulin has the ability to beneficially manipulate gut microflora in a proteolytic environment.

Tempo and mode of evolution in an orthologous Can SINE.

Tempo and mode of nucleotide change were examined in an orthologous carnivoran nuclear repetitive DNA element (Can SINE), and compared with those of the transthyretin intron I (TR-i-I) sequence in which it is embedded, by using a phylogenetic framework. The Can SINE is found in representatives of all living caniform carnivoran families, but no living feliform families. This suggests insertion 40-65 MYA, after the two lineages split, but before the caniform radiation. Despite linkage and a long shared evolutionary history, both parsimony and likelihood analyses showed the Can SINE to be significantly different from TR-i-I in rates of evolution and phylogenetic hypotheses supported. The substitution rate is significantly higher in Can SINE than in TR-i-I, and this is attributable to the tRNA-related region of the insertion. While the incongruence length difference test revealed significant conflict between the Can SINE and TR-i-I partitions, the test was shown to be sensitive to the distribution of homoplasy within partitions. The conflicting phylogenies are likely the result of differences in phylogenetic accuracy (homoplasy distribution) rather than in phylogenetic history (gene trees). The base composition of Can SINE contains a significantly higher GC percentage than TR-i-I. Our results indicate that differences between the two partitions may be the result of homoplasy introduced by an increased substitution rate in the tRNA-related region of Can SINE owing to CpG hypermutability.

Whence the red panda?

The evolutionary history of the red panda (Ailurus fulgens) plays a pivotal role in the higher-level phylogeny of the "bear-like" arctoid carnivoran mammals. Characters from morphology and molecules have provided inconsistent evidence for placement of the red panda. Whereas it certainly is an arctoid, there has been major controversy about whether it should be placed with the bears (ursids), ursids plus pinnipeds (seals, sea lions, walrus), raccoons (procyonids), musteloids (raccoons plus weasels, skunks, otters, and badgers [mustelids]), or as a monotypic lineage of uncertain phylogenetic affinities. Nucleotide sequence data from three mitochondrial genes and one nuclear intron were analyzed, with more complete taxonomic sampling of relevant taxa (arctoids) than previously available in analyses of primary molecular data, to clarify the phylogenetic relationships of the red panda to other arctoid carnivorans. This study provides detailed phylogenetic analyses (both parsimony and maximum-likelihood) of primary character data for arctoid carnivorans, including bootstrap and decay indices for all arctoid nodes, and three statistical tests of alternative phylogenetic hypotheses for the placement of the red panda. Combined phylogenetic analyses reject the hypotheses that the red panda is most closely related to the bears (ursids) or to the raccoons (procyonids). Rather, evidence from nucleotide sequences strongly support placement of the red panda within a broad Musteloidea (sensu lato) clade, including three major lineages (the red panda, the skunks [mephitids], and a clearly monophyletic clade of procyonids plus mustelids [sensu stricto, excluding skunks]). Within the Musteloidea, interrelationships of the three major lineages are unclear and probably are best considered an unresolved trichotomy. These data provide compelling evidence for the relationships of the red panda and demonstrate that small taxonomic sample sizes can result in misleading or possibly erroneous (based on prior modeling, as well as conflict between the results of our analyses of less and more complete data sets) conclusions about phylogenetic relationships and taxonomy.

Phylogeny of the Carnivora (Mammalia): congruence vs incompatibility among multiple data sets.

The purpose of this study was to determine the higher-level phylogenetic relationships among Carnivora, using a conditional data combination (CDC) approach to analyzing multiple data sets. New nucleotide sequences (851 base pairs from intron I of the transthyretin gene) among 22 representatives of the 11 families of Carnivora were generated and analyzed in concert with, and comparison to, other mitochondrial and morphological character data. Conditional data combination analyses of the four independent data sets (transthyretin intron I, cytochrome b, partial 12S rRNA, and morphology) indicate that the phylogenetic results derived from each generally agree, with two exceptions. The first exception, signal heterogeneity in comparisons involving transthyretin and morphology, provides an example where phylogenetic conclusions drawn from total evidence analyses may differ from conclusions drawn from CDC analyses. The second exception demonstrates that while a CDC method may reject the null hypothesis of homogeneity for a particular partition, including that partition in combined analyses, may nevertheless provide an overall increase in phylogenetic signal, in terms of nodal support for most associations, without altering the topology derived from the combined homogeneous data partitions. Phylogenetic reconstruction among the feliform families supports a sister-group relationship between the hyaenas (Hyaenidae) and mongooses (Herpestidae) and places the African palm civet (Nandinia) as basal to all other living Feliformia. Among the caniform families, CDC analyses strongly support the previously enigmatic red panda (Ailurus) as a monotypic lineage that is sister to Musteloidea sensu stricto (mustelids plus procyonids), in addition to pinniped monophyly and a sister-group relationship between the walrus and sea lions.

Recent advances in South American mammalian paleontology.

Recently discovered deposits containing terrestrial mammal fossils, together with multidisciplinary studies of classical sequences, have yielded dramatic insights into the biotic and environmental history of South America. Notable advances include several new fossil primate taxa, an improved chronology of two major immigration events (caviomorph rodents and new world monkeys), documentation of the oldest mammalian faunas dominated by grazing taxa (which suggests that grasslands appeared at least 15 million years earlier than on other continents), evidence of early biogeographical provinciality within South America, and improved sampling of the best known Cenozoic tropical South American paleofauna.

Midodrine treatment for patients with hemodialysis hypotension.

Hypotension is the principal complication of chronic hemodialysis. Autonomic insufficiency is thought to be a primary contributing cause of hemodialysis hypotension. We treated patients who experience hemodialysis hypotension with midodrine, a selective alpha-1 adrenergic pressor agent in an initial effort to assess potential efficacy. Twenty-one patients who experienced severe hypotension during hemodialysis participated in this study. To qualify, patients had to exhibit a fall of > or = 30 mmHg in systolic blood pressure with associated clinical symptoms during hemodialysis. The lowest intra- and post-dialysis blood pressures were monitored for five consecutive hemodialysis treatment periods before receiving midodrine, as a baseline. After the patients were titrated to a maintenance midodrine dose, the lowest intra- and post-dialysis blood pressure data were again collected for five consecutive dialysis treatments. Hemodialysis blood pressures on midodrine treatment were compared to baseline to evaluate the effect of midodrine. Midodrine given at a mean treatment dose of 8 mg (range 2.5-25) significantly increased the mean (+ or - SE) minimal systolic pressure from 93.1 "+ or - " 3.8 to 107.1 + or - 3.2 mmHg (p <0.01) and elevated the mean diastolic pressure from 52.3 + or - 2.9 to 57.9 + or - 2.3 mmHg during hemodialysis. Also, the post-dialysis blood pressures (systolic/diastolic) were significantly increased from 115.6 + or - 3.1/62.3 + or - 2.1 to 129.9 + or - 3.9/68.1 + or - 1.7 mmHg (p <0.01 and 0.05, respectively). No apparent clinical or laboratory abnormalities were observed. Oral midodrine appears to be a safe and effective therapy for the treatment of hemodialysis hypotension.

An Early Miocene anthropoid skull from the Chilean Andes.

Partly because of their poor fossil record, the relationships of neotropical platyrrhine monkeys to other groups of primates and to each other remain perhaps the most poorly known for any major primate clade. Here we report the discovery of a complete platyrrhine skull from the Andes of central Chile, by far the best preserved Tertiary primate cranium from South America. This find, coupled with recent phylogenetic analyses of higher groups of anthropoid primates, has the potential to revise substantially our understanding of platyrrhine interrelationships, indicating, among other points, significant modification to reconstruction of the ancestral platyrrhine morphotype and a likely African origin for New World monkeys. A 40Ar/39Ar radioisotopic date directly associated with the skull indicates an Early Miocene age, marking the first report of South American mammals of this age from outside Argentine Patagonia. Finally, this discovery demonstrates the enormous potential of vastly distributed, but virtually untapped, Andean volcaniclastic deposits to yield further insights into the origin and diversification of South American primates.

Opioid-induced linear running in obese (ob/ob) and lean mice.

Earlier research has shown that opioids stimulate behavioral activation in mice whereas opioid antagonists attenuate this activation. We conducted an experiment to determine the dose-response curve of FK33824, a potent Met-enkephalin analogue. FK33824 produced an unusual form of behavioral activation we called "linear running" in which the mice ran continuously in one direction and were nearly oblivious to environmental stimuli. This may be the kind of running that occurs naturally during migration. Wheel running activity of genetically obese (ob/ob) and lean (C57BL/6J ?/+) mice was measured following the intracerebroventricular infusion of 0.1, 1.0, 10.0 and 100.0 ng of FK33824. The lowest dose did not alter baseline running, whereas the 1.0 and 10.0 ng doses significantly increased running in both genotypes. We found a genotype difference with the highest dose tested, the lean mice ran at baseline levles and displayed ataxia whereas the obese mice continued to show increased running without ataxia. We hypothesize that genetic differences in the enkephalin mechanisms of C57 lean and obese mice are responsible for linear running.

Decreased glucocorticoid binding and receptor activation in brain of genetically diabetic (MDB/MDB) mice.

Binding of [3H]triamcinolone acetonide (TA) to cytosolic receptors and subsequent in vitro activation of glucocorticoid-receptor complexes were studied in whole brain and liver from misty diabetic mice (mdb/mdb) and their control littermates (??/++). Binding was specific for glucocorticoid receptor (GcR) since the specific glucocorticoid, RU26988, was used to compete with [3H]TA for binding. Reduced [3H]TA binding was observed in whole brain and liver in diabetic animals when compared to control animals. Within the brain, binding was significantly (P less than 0.05) decreased in cortex, hippocampus, and hypothalamus. No significant differences in binding were found in the striatum or "midbrain". GcR binding was similar in diabetic and control animals until 2 months of age when overt diabetic symptoms appeared and the GcR binding was lower in diabetic animals. Though GcR from mdb/mdb brain cytosol could be thermally activated, the extent of activation was significantly (P less than 0.05) less than that for controls. These data indicate that GcR in liver and brain cytosol are decreased in mdb/mdb mice and that the GcR available for binding in mdb/mdb brain cytosol appears less capable of undergoing activation and binding to DNA-cellulose than GcR from control brain cytosol. Decreased GcR activation in brain cytosol from mdb/mdb mice was associated with increased dissociation of [3H]TA from the GcR. These results suggest that the decreased negative feedback previously observed in diabetic animals may be due to decreased binding of hormones and a decreased level of activation of hormone bound receptor complexes.

Early eocene vertebrates from baja california: evidence for intracontinental age correlations.

Newly discovered fossils support a Wasatchian (early Eocene) age for the Punta Prieta vertebrate fauna of Baja California and reveal the utility of land mammal ages on a continental scale. Dispersal scenarios for late Paleocene and early Eocene vertebrates usually invoke heterochrony for similar, but geographically separated, faunas or taxa. Such heterochrony is not supported by independent geochronologies or adequate geographic samples.

Serum calcitonin, calcium and thyroxine in young and old Zucker fatty rats (fa/fa).

We determined the serum levels of calcitonin (CT), calcium (Ca), and thyroxine (Ti) in lean (?/+) and fatty (fa/fa) male Zucker rats 10 weeks and 10-12 months of age. The most dramatic finding was a high level of serum CT (3.24 +/- 1.18 ng/ml) in young fatties whereas sera from young leans were all below the limit of assay detection (less than 0.120 ng/ml, p less than 0.01). Young fat rats also had elevated levels of both Ca (11.2 +/- 0.2 vs. 9.7 +/- 0.2 mg/dl, p less than 0.001) and Ti (6.7 +/- 0.48 vs. 4.72 +/- 0.28 micrograms/dl, p less than 0.01). In older animals the mean serum level of CT increased further in the fatties and became readily measurable in leans (5.67 +/- 1.94 vs. 1.49 +/- 0.55, p less than 0.01). Thyroid C-cells, identified immunohistochemically, were abundant in both leans and fatties at this age but were substantially more numerous in the fat rats (p less than 0.001). Calcium levels increased somewhat in the older leans, but still remained higher in the fat rats (p less than 0.05). Thyroxine values were essentially the same for old animals of both genotypes (5.07 +/- 0.61 vs. 5.54 +/- 0.88). Age effects were not significant for any measure in the fat animals, but in the leans there were significant age-related increases in CT (p less than 0.02) and serum Ca (p less than 0.05).

Secretion of calcitonin in the genetically obese Zucker rat (fa/fa).

Previously we found that adult Zucker fatty rats have C-cell hyperplasia and increased thyroidal calcitonin (CT) compared to lean controls. In this study we have evaluated both secretion of CT and responsiveness to CT in order to see whether they, too, were altered. Fat rats and lean littermates, 13-15 months old, were used. CT secretion was provoked by (1) feeding for 2 hr after an 18-hr fast, (2) giving pentagastrin iv, and (3) injecting CaCl2 iv. CT was measured by radioimmunoassay. Responsiveness to CT was examined by giving porcine or salmon CT iv and measuring serum Ca 1-3 hr later. For CT secretion, compared to leans the fat rats showed (1) higher fasting serum Ca and CT and a greater rise in CT after feeding, (2) a similar 5- to 10-fold increase in CT after iv pentagastrin, and (3) a greater rise in both serum Ca and CT at various times between 5 min and 3 hr after iv CaCl2. For CT responsiveness, fat and lean rats were equally responsive to iv CT in terms of the fall in plasma Ca 1-3 hr later. The results show that fat rats can secrete as much or more CT in response to provocative stimuli as lean rats and that they appear normally responsive to injected CT. Therefore, inability to release CT and insensitivity to CT do not underly the C-cell hyperplasia, increased thyroidal CT, and increased circulating CT in the fat rat.

Increased immunoreactive dynorphin and leu-enkephalin in posterior pituitary of obese mice (ob/ob) and super-sensitivity to drugs that act at kappa receptors.

Posterior pituitaries of obese mice (ob/ob) contained significantly more immunoreactive dynorphin (P less than .01) and leu-enkephalin (P less than .01) than their lean littermates. Drinking in obese mice was stimulated by 0.3%, and feeding by 10%, of the dose of ethylketocyclazocine, a kappa receptor agonist, needed to produce extra feeding and drinking in lean mice. Obese mice also showed greater and longer lasting suppression of ingestion after MR-2266, a kappa antagonist, than did lean mice. MR-2266 was much more effective than naloxone in suppressing schedule-induced polydipsia in rats. These results indicate that kappa receptors are involved in feeding and drinking and that obesity is associated with changes in these receptors and their ligands.