New records of the archaic dolphin Agorophius (Mammalia: Cetacea) from the upper Oligocene Chandler Bridge Formation of South Carolina, USA

The stem odontocete Agorophius pygmaeus (Ashley Formation, lower Oligocene, South Carolina; 29.0–26.57 Ma) has been a critical point of comparison for studies of early neocete evolution owing to its early discovery as well as its transitional anatomy relative to archaeocete whales and modern odontocetes. Some time during the late nineteenth century the holotype skull went missing and has never been relocated; supplementary reference specimens have since been recently referred to the species from the Ashley Formation and the overlying Chandler Bridge Formation (upper Oligocene; 24.7–23.5). New crania referable to Agorophius sp. are identifiable to the genus based on several features of the intertemporal region. Furthermore, all published specimens from the Chandler Bridge Formation consistently share larger absolute size and a proportionally shorter exposure of the parietal in the skull roof than specimens from the Ashley Formation (including the holotype). Furthermore, these specimens include well-preserved ethmoid labyrinths and cribriform plates, indicating that Agorophius primitively retained a strong olfactory sense. These new crania suggest that at least two species of Agorophius are present in the Oligocene of South Carolina, revealing a somewhat more complicated taxonomic perspective

The tempo of cetacean cranial evolution

The evolution of cetaceans (whales and dolphins) represents one of the most extreme adaptive transitions known, from terrestrial mammals to a highly specialized aquatic radiation that includes the largest animals alive today. Many anatomical shifts in this transition involve the feeding, respiratory, and sensory structures of the cranium, which we quantified with a high-density, three-dimensional geometric morphometric analysis of 201 living and extinct cetacean species spanning the entirety of their ∼50-million-year evolutionary history. Our analyses demonstrate that cetacean suborders occupy distinct areas of cranial morphospace, with extinct, transitional taxa bridging the gap between archaeocetes (stem whales) and modern mysticetes (baleen whales) and odontocetes (toothed whales). This diversity was obtained through three key periods of rapid evolution: first, the initial evolution of archaeocetes in the early to mid-Eocene produced the highest evolutionary rates seen in cetaceans, concentrated in the maxilla, frontal, premaxilla, and nasal; second, the late Eocene divergence of the mysticetes and odontocetes drives a second peak in rates, with high rates and disparity sustained through the Oligocene; and third, the diversification of odontocetes, particularly sperm whales, in the Miocene (∼18-10 Mya) propels a final peak in the tempo of cetacean morphological evolution. Archaeocetes show the fastest evolutionary rates but the lowest disparity. Odontocetes exhibit the highest disparity, while mysticetes evolve at the slowest pace, particularly in the Neogene. Diet and echolocation have the strongest influence on cranial morphology, with habitat, size, dentition, and feeding method also significant factors impacting shape, disparity, and the pace of cetacean cranial evolution

Low Serum Levels of Soluble Receptor Activator of Nuclear Factor κ B Ligand (sRANKL) Are Associated with Metabolic Dysregulation and Predict Long-Term Mortality in Critically Ill Patients

Soluble receptor activator of nuclear factor κ B ligand (sRANKL) is a member of the tumor necrosis factor receptor superfamily, and therefore, involved in various inflammatory processes. The role of sRANKL in the course of bone remodeling via activation of osteoclasts as well as chronic disease progression has been described extensively. However, the potential functional importance of sRANKL in critically ill or septic patients remained unknown. Therefore, we measured sRANKL serum concentrations in 303 critically ill patients, including 203 patients with sepsis and 100 with non-sepsis critical illness. Results were compared to 99 healthy controls. Strikingly, in critically ill patients sRANKL serum levels were significantly decreased at intensive care unit (ICU) admission (p = 0.011) without differences between sepsis and non-sepsis patients. Inline, sRANKL was correlated with markers of metabolic dysregulation, such as pre-existing diabetes and various adipokines (e.g., adiponectin, leptin receptor). Importantly, overall mortality of critically ill patients in a three-year follow-up was significantly associated with decreased sRANKL serum concentrations at ICU admission (p = 0.038). Therefore, our study suggests sRANKL as a biomarker in critically ill patients which is associated with poor prognosis and overall survival beyond ICU stay

Developmental origin underlies evolutionary rate variation across the placental skull

The placental skull has evolved into myriad forms, from longirostrine whales to globular primates, and with a diverse array of appendages from antlers to tusks. This disparity has recently been studied from the perspective of the whole skull, but the skull is composed of numerous elements that have distinct developmental origins and varied functions. Here, we assess the evolution of the skull's major skeletal elements, decomposed into 17 individual regions. Using a high-dimensional morphometric approach for a dataset of 322 living and extinct eutherians (placental mammals and their stem relatives), we quantify patterns of variation and estimate phylogenetic, allometric and ecological signal across the skull. We further compare rates of evolution across ecological categories and ordinal-level clades and reconstruct rates of evolution along lineages and through time to assess whether developmental origin or function discriminate the evolutionary trajectories of individual cranial elements. Our results demonstrate distinct macroevolutionary patterns across cranial elements that reflect the ecological adaptations of major clades. Elements derived from neural crest show the fastest rates of evolution, but ecological signal is equally pronounced in bones derived from neural crest and paraxial mesoderm, suggesting that developmental origin may influence evolutionary tempo, but not capacity for specialisation. This article is part of the theme issue 'The mammalian skull: development, structure and function'

Developmental origin underlies evolutionary rate variation across the placental skull

The placental skull has evolved into myriad forms, from longirostrine whales to globular primates, and with a diverse array of appendages from antlers to tusks. This disparity has recently been studied from the perspective of the whole skull, but the skull is composed of numerous elements that have distinct developmental origins and varied functions. Here, we assess the evolution of the skull's major skeletal elements, decomposed into 17 individual regions. Using a high-dimensional morphometric approach for a dataset of 322 living and extinct eutherians (placental mammals and their stem relatives), we quantify patterns of variation and estimate phylogenetic, allometric and ecological signal across the skull. We further compare rates of evolution across ecological categories and ordinal-level clades and reconstruct rates of evolution along lineages and through time to assess whether developmental origin or function discriminate the evolutionary trajectories of individual cranial elements. Our results demonstrate distinct macroevolutionary patterns across cranial elements that reflect the ecological adaptations of major clades. Elements derived from neural crest show the fastest rates of evolution, but ecological signal is equally pronounced in bones derived from neural crest and paraxial mesoderm, suggesting that developmental origin may influence evolutionary tempo, but not capacity for specialisation. This article is part of the theme issue 'The mammalian skull: development, structure and function'

Publication trends in the medical informatics literature: 20 years of "Medical Informatics" in MeSH

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to identify publication output, and research areas, as well as descriptively and quantitatively characterize the field of medical informatics through publication trend analysis over a twenty year period (1987–2006).</p> <p>Methods</p> <p>A bibliometric analysis of medical informatics citations indexed in Medline was performed using publication trends, journal frequency, impact factors, MeSH term frequencies and characteristics of citations.</p> <p>Results</p> <p>There were 77,023 medical informatics articles published during this 20 year period in 4,644 unique journals. The average annual article publication growth rate was 12%. The 50 identified medical informatics MeSH terms are rarely assigned together to the same document and are almost exclusively paired with a non-medical informatics MeSH term, suggesting a strong interdisciplinary trend. Trends in citations, journals, and MeSH categories of medical informatics output for the 20-year period are summarized. Average impact factor scores and weighted average impact factor scores increased over the 20-year period with two notable growth periods.</p> <p>Conclusion</p> <p>There is a steadily growing presence and increasing visibility of medical informatics literature over the years. Patterns in research output that seem to characterize the historic trends and current components of the field of medical informatics suggest it may be a maturing discipline, and highlight specific journals in which the medical informatics literature appears most frequently, including general medical journals as well as informatics-specific journals.</p

Connectivity-based parcellation of the human frontal polar cortex

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity

Synaptically-Competent Neurons Derived from Canine Embryonic Stem Cells by Lineage Selection with EGF and Noggin

Pluripotent stem cell lines have been generated in several domestic animal species; however, these lines traditionally show poor self-renewal and differentiation. Using canine embryonic stem cell (cESC) lines previously shown to have sufficient self-renewal capacity and potency, we generated and compared canine neural stem cell (cNSC) lines derived by lineage selection with epidermal growth factor (EGF) or Noggin along the neural default differentiation pathway, or by directed differentiation with retinoic acid (RA)-induced floating sphere assay. Lineage selection produced large populations of SOX2+ neural stem/progenitor cell populations and neuronal derivatives while directed differentiation produced few and improper neuronal derivatives. Primary canine neural lines were generated from fetal tissue and used as a positive control for differentiation and electrophysiology. Differentiation of EGF- and Noggin-directed cNSC lines in N2B27 with low-dose growth factors (BDNF/NT-3 or PDGFαα) produced phenotypes equivalent to primary canine neural cells including 3CB2+ radial progenitors, MOSP+ glia restricted precursors, VIM+/GFAP+ astrocytes, and TUBB3+/MAP2+/NFH+/SYN+ neurons. Conversely, induction with RA and neuronal differentiation produced inadequate putative neurons for further study, even though appropriate neuronal gene expression profiles were observed by RT-PCR (including Nestin, TUBB3, PSD95, STX1A, SYNPR, MAP2). Co-culture of cESC-derived neurons with primary canine fetal cells on canine astrocytes was used to test functional maturity of putative neurons. Canine ESC-derived neurons received functional GABAA- and AMPA-receptor mediated synaptic input, but only when co-cultured with primary neurons. This study presents established neural stem/progenitor cell populations and functional neural derivatives in the dog, providing the proof-of-concept required to translate stem cell transplantation strategies into a clinically relevant animal model

A supermatrix analysis of genomic, morphological, and paleontological data from crown Cetacea

<p>Abstract</p> <p>Background</p> <p>Cetacea (dolphins, porpoises, and whales) is a clade of aquatic species that includes the most massive, deepest diving, and largest brained mammals. Understanding the temporal pattern of diversification in the group as well as the evolution of cetacean anatomy and behavior requires a robust and well-resolved phylogenetic hypothesis. Although a large body of molecular data has accumulated over the past 20 years, DNA sequences of cetaceans have not been directly integrated with the rich, cetacean fossil record to reconcile discrepancies among molecular and morphological characters.</p> <p>Results</p> <p>We combined new nuclear DNA sequences, including segments of six genes (~2800 basepairs) from the functionally extinct Yangtze River dolphin, with an expanded morphological matrix and published genomic data. Diverse analyses of these data resolved the relationships of 74 taxa that represent all extant families and 11 extinct families of Cetacea. The resulting supermatrix (61,155 characters) and its sub-partitions were analyzed using parsimony methods. Bayesian and maximum likelihood (ML) searches were conducted on the molecular partition, and a molecular scaffold obtained from these searches was used to constrain a parsimony search of the morphological partition. Based on analysis of the supermatrix and model-based analyses of the molecular partition, we found overwhelming support for 15 extant clades. When extinct taxa are included, we recovered trees that are significantly correlated with the fossil record. These trees were used to reconstruct the timing of cetacean diversification and the evolution of characters shared by "river dolphins," a non-monophyletic set of species according to all of our phylogenetic analyses.</p> <p>Conclusions</p> <p>The parsimony analysis of the supermatrix and the analysis of morphology constrained to fit the ML/Bayesian molecular tree yielded broadly congruent phylogenetic hypotheses. In trees from both analyses, all Oligocene taxa included in our study fell outside crown Mysticeti and crown Odontoceti, suggesting that these two clades radiated in the late Oligocene or later, contra some recent molecular clock studies. Our trees also imply that many character states shared by river dolphins evolved in their oceanic ancestors, contradicting the hypothesis that these characters are convergent adaptations to fluvial habitats.</p