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The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase–12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine–19, granulocyte colony-stimulating factor–3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member–10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored. [ABSTRACT FROM AUTHOR]

The Early Pleistocene archeological site of Fuente Nueva-3 (FN3) preserves some of the oldest evidence of hominin presence in Western Europe, including a huge assemblage of Oldowan tools and evidence of butchering and marrow processing of large mammal bones. Moreover, there is also evidence of the regular presence of carnivores at the site, including a small proportion of bones that show tooth marks, the majority of which can be attributed to the giant, short-faced hyena Pachycrocuta brevirostris, and there are 220 coprolites, most of them from the Upper Archeological Level. In order to identify the defecating agent, we analyze here the coprolites and compare them with other specimens from the literature and with scats from zoo spotted hyenas (Crocuta crocuta). The morphology, color, size, and chemical composition of the FN3 coprolites allow us to attribute them to the hyena P. brevirostris, which is also represented at the site by fossil specimens. In addition, we evaluate the origin of the accumulation of coprolites and discuss on the role played by the scavenging hyenas in the accumulation and modification of the bone remains unearthed at the site, which allows evaluating the contribution of the giant hyena to this Early Pleistocene site. Finally, based on the lithology of layer 5 of the Upper Archeological Level, fine sands and clays deposited in a salt-lake environment, we hypothesize that this layer may have acted as a quicksand where large-sized animals like elephants were trapped and their carcasses lured scavenging carnivores. [ABSTRACT FROM AUTHOR]

Unlabelled: Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL-6-type cytokine expression and regulation by IL-1beta and tumor necrosis factor-alpha (TNF-alpha) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1beta and TNF-alpha. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1beta. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-kappaB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases.Abbreviations: IL-1alpha (interleukin-1alpha); IL-1beta (interleukin-1beta); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); alpha(1)-coll. I (alpha(1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein-2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (complementary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); alpha-MEM (alpha modification of Minimum Essential Medium); and FCS (fetal calf serum). [ABSTRACT FROM AUTHOR]

A morphometric analysis of the skull of the red or lesser panda, Aiulurus fulgens ( Ailuridae), and the giant panda, Ailuropoda melanoleuca (Ursidae), was performed for evaluating the importance of natural selection and phylogenetic constraints in shaping the convergent morphological adaptations of these peculiar carnivores for feeding on bamboo. Principal components and discriminant analyses of landmark data was used in a comparative study across the families Procyonidae, Ursidae and Ailuridae. Skull morphospaces show that major patterns of morphological variation among these arctoid carnivorans correlate with differences in their feeding behavior. More specifically, this study has shown an extreme convergence in skull shape between the two bamboo specialists. Following the most recent molecular and morphological phylogenies, as well as the poor evidence from the fossil record, it seems highly improbable that homology could explain the shared morphology of the giant and red pandas, which lineages diverged ∼40 million years ago. On the contrary, most phylogenetic and paleontological data suggest that convergent or parallel evolution (homoplasy) would be the evolutionary process shaping the common morphological traits of these unusual carnivorans. Therefore, the overall resemblance in skull shape between the giant and red pandas was probably driven by extrinsic factors (natural selection and adaptation for feeding on bamboo) as well as by intrinsic ones (the shared developmental pathway of the carnivoran skull, which posed some biomechanical constraints on the direction of the evolution of pandas). [ABSTRACT FROM AUTHOR]

Patterns of skull shape in Carnivora provide examples of parallel and convergent evolution for similar ecomorphological adaptations. However, although most researchers report on skull homoplasies among hypercarnivorous taxa, evolutionary trends towards herbivory remain largely unexplored. In this study, we analyse the skull of the living herbivorous carnivorans to evaluate the importance of natural selection and phylogenetic legacy in shaping the skulls of these peculiar species. We quantitatively estimated shape variability using geometric morphometrics. A principal components analysis of skull shape incorporating all families of arctoid carnivorans recognized several common adaptations towards herbivory. Ancestral state reconstructions of skull shape and the reconstructed phylogenetic history of morphospace occupation more explicitly reveal the true patterns of homoplasy among the herbivorous carnivorans. Our results indicate that both historical constraints and adaptation have interplayed in the evolution towards herbivory of the carnivoran skull, which has resulted in repeated patterns of biomechanical homoplasy. [ABSTRACT FROM AUTHOR]

The osteotropic interleukin-6 (IL-6) types of cytokines IL-6, IL-11, and leukemia inhibitory factor (LIF), but not oncostatin M, are expressed by human gingival fibroblasts, and their expressions are regulated by IL-1 and tumor necrosis factor-? (TNF-?). In the present study, we investigated whether signaling through Toll-like receptor 2 (TLR2) can affect the expression of these cytokines in human gingival fibroblasts. Lipopolysaccharide (LPS) from P. gingivalis was found to stimulate IL-6 and LIF mRNA and protein, but not IL-11 or OSM mRNA. Using two synthetic ligands acting specifically at TLR2 and siRNA knockdown of TLR2, we demonstrated the importantrole of TLR2 in the stimulation of IL-6 and LIF in gingival fibroblasts. Analysis of these data suggests that signaling through the innate immune system controls the expression of osteotropic cytokines in human gingival fibroblasts. [ABSTRACT FROM AUTHOR]

Relative warp analyses of landmarks describing cranial and mandibular shape are used for investigating patterns of morphological variation among extant bears (Mammalia, Carnivora, Ursidae) indicative of diet and feeding behavior. These patterns are used for deriving inferences about the autecology of two extinct species previously assumed to have had different dietary preferences, the North American giant, short-faced bear Arctodus simus and the Eurasian cave bear Ursus spelaeus. Results reveal a set of shared craniodental traits among the herbivorous bears, including short and vaulted skulls with well-developed zygomatic arches, lateralized orbits and small canines, concave jaws with a highly positioned condyle, large moment arms for the temporalis and masseter muscles, and long cheek teeth. In contrast, those bears that consume animal resources have long skulls with small zygomatic arches, frontalized orbits and well-developed canines, and long jaws with a deep mandibular symphysis, low muscle leverages, a condyle situated at the level of the tooth row and reduced cheek teeth. The craniodental morphology of omnivorous bears is intermediate between those of faunivores and herbivores. This is also the case of the short-faced bear and the cave bear, which suggests that previous reconstructions of the feeding ecology of these extinct species (highly carnivorous for A. simus and herbivorous for U. spelaeus) should be revised. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL- 6-type cytokine expression and regulation by IL-1β and tumor necrosis factor-α (TNF-α) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1β and TNF-α. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1β. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-κB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases. Abbreviations: IL-1α (interleukin-1α); IL-1β (interleukin-1β); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); α (1)-coll. I (α (1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein- 2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (comple mentary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); α-MEM (α modification of Minimum Essential Medium); and FCS (fetal calf serum). [ABSTRACT FROM AUTHOR]

Stable isotopes are useful tools for estimating the relative contribution of different prey to the diet of an extinct predator. Several approaches have been proposed for quantifying these contributions as percentages, but the linear mixing models provide the most reliable estimates. However, these models only yield unique solutions if the number of analyzed isotopes is equal to the number of dietary sources minus one. If stable isotopes from bone collagen ( δ13C, δ15N) are used, this implies that a maximum of three prey must account for the bulk of the predator's diet. Here we show that this requirement holds only for the five extant hypercarnivorous canids and probably also for the cheetah (a cursor) and the lynxes among felids, because for these species the dietary contribution of prey sources in terms of biomass is, on average, equal or higher than 55% for the first, 20% for the second and around 10% for the third. However, five to seven prey species account for the bulk of the diet of most stalking felids and also for those omnivorous canids that are not pack hunters. The conclusion is that the linear mixing models will only provide well-defined solutions using two isotopic ratios in the dietary reconstruction of extinct hypercarnivorous canids, which tend to rely very heavily on only three prey, and probably also in extremely specialized felids with cursorial adaptations or living in temperate habitats. [ABSTRACT FROM AUTHOR]

Hypsodont (i.e. high-crowned) teeth have been interpreted as an indicator of feeding preferences and habitat selection in ungulates. For this reason, the degree of hypsodonty has been used for estimating the diet of ancient taxa and in palaeoenvironmental reconstructions. The goal of this study is to elucidate the relative importance of grass consumption and open habitat foraging in the development of hypsodont teeth, using novel computer techniques of knowledge discovery applied to a dataset of 134 species of artiodactyls and perissodactyls distributed among thirteen families. The results obtained suggest that high-crowned teeth represent an adaptation for feeding in an open habitat, although the minimum threshold of hypsodonty seems to increase with the relative length of the anterior part of the jaw. On the contrary, there is no direct relationship between the degree of hypsodonty and the percentage of grass consumed, except for the correspondence between grazing and dwelling in open habitats. A relatively wide muzzle evidences an adaptation for grass foraging in open and mixed habitats, but there are some non-grazing species from a closed habitat that also show wide muzzles. Thus, the hypsodonty index, combined with the length of the anterior part of the jaw and the width of the muzzle, allows accurate inferences on the ecological preferences of extinct ungulates. [ABSTRACT FROM AUTHOR]

The correlation between body mass and both skeletal and dental measures in living mammals has enabled paleontologists to obtain reliable estimates of body size for extinct species, usually using log-transformed bivariate least-squares regression equations. Multiple regression, however, has rarely been used for estimating the mass of extinct species, although this technique can clearly improve the predictive equations compared with those adjusted by simple regression. However, the use of multiple regression is problematical, because even those functions explaining a high percentage of the variance of the dependent variable (i.e. body mass) can show a rather limited predictive power. After analyzing which factors determine the predictive ability of multiple regression equations, we propose a new set of algorithms that allow the estimation of the body mass of extinct ungulates. These algorithms are finally applied to three Miocene ungulate species, Dinohippus leidyanus, Stenomylus hitchcocki and Aletomeryx scotti. [ABSTRACT FROM AUTHOR]