Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies

) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification. (sister taxon to Phalacrocoracidae). These relationships are invariant when ‘backbone’ constraints based on recent avian phylogenies are imposed.Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several “stem fossil + crown family” clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny

High prevalence of Trichomonas gallinae in wild columbids across western and southern Europe

Avian trichomonosis is known as a widespread disease in columbids and passerines, and recent findings have highlighted the pathogenic character of some lineages found in wild birds. Trichomonosis can affect wild bird populations including endangered species, as has been shown for Mauritian pink pigeons Nesoenas mayeri in Mauritius and suggested for European turtle doves Streptopelia turtur in the UK. However, the disease trichomonosis is caused only by pathogenic lineages of the parasite Trichomonas gallinae. Therefore, understanding the prevalence and distribution of both potentially pathogenic and non-pathogenic T. gallinae lineages in turtle doves and other columbids across Europe is relevant to estimate the potential impact of the disease on a continental scale

The FGFR4-G388R Polymorphism Promotes Mitochondrial STAT3 Serine Phosphorylation to Facilitate Pituitary Growth Hormone Cell Tumorigenesis

Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Mesozoic retroposons reveal parrots as the closest living relatives of passerine birds

The relationships of passerines (such as the well-studied zebra finch) with non-passerine birds is one of the great enigmas of avian phylogenetic research, because decades of extensive morphological and molecular studies yielded highly inconsistent results between and within data sets. Here we show the first application of the virtually homoplasy-free retroposon insertions to this controversy. Our study examined ~200,000 retroposon-containing loci from various avian genomes and retrieved 51 markers resolving early bird phylogeny. Among these, we obtained statistically significant evidence that parrots are the closest and falcons the second-closest relatives of passerines, together constituting the Psittacopasserae and the Eufalconimorphae, respectively. Our new and robust phylogenetic framework has substantial implications for the interpretation of various conclusions drawn from passerines as model organisms. This includes insights of relevance to human neuroscience, as vocal learning (that is, birdsong) probably evolved in the psittacopasseran ancestor, >30 million years earlier than previously assumed

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

Tumor classification: molecular analysis meets Aristotle

BACKGROUND: Traditionally, tumors have been classified by their morphologic appearances. Unfortunately, tumors with similar histologic features often follow different clinical courses or respond differently to chemotherapy. Limitations in the clinical utility of morphology-based tumor classifications have prompted a search for a new tumor classification based on molecular analysis. Gene expression array data and proteomic data from tumor samples will provide complex data that is unobtainable from morphologic examination alone. The growing question facing cancer researchers is, "How can we successfully integrate the molecular, morphologic and clinical characteristics of human cancer to produce a helpful tumor classification?" DISCUSSION: Current efforts to classify cancers based on molecular features ignore lessons learned from millennia of experience in biological classification. A tumor classification must include every type of tumor and must provide a unique place for each tumor within the classification. Groups within a classification inherit the properties of their ancestors and impart properties to their descendants. A classification was prepared grouping tumors according to their histogenetic development. The classification is simple (reducing the complexity of information received from the molecular analysis of tumors), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. The clinical and research value of this historical approach to tumor classification is discussed. SUMMARY: This manuscript reviews tumor classification and provides a new and comprehensive classification for neoplasia that preserves traditional nomenclature while incorporating information derived from the molecular analysis of tumors. The classification is provided as an open access XML document that can be used by cancer researchers to relate tumor classes with heterogeneous experimental and clinical tumor databases

Vectors Based on Modified Vaccinia Ankara Expressing Influenza H5N1 Hemagglutinin Induce Substantial Cross-Clade Protective Immunity

New highly pathogenic H5N1 influenza viruses are continuing to evolve with a potential threat for an influenza pandemic. So far, the H5N1 influenza viruses have not widely circulated in humans and therefore constitute a high risk for the non immune population. The aim of this study was to evaluate the cross-protective potential of the hemagglutinins of five H5N1 strains of divergent clades using a live attenuated modified vaccinia Ankara (MVA) vector vaccine.The replication-deficient MVA virus was used to express influenza hemagglutinin (HA) proteins. Specifically, recombinant MVA viruses expressing the HA genes of the clade 1 virus A/Vietnam/1203/2004 (VN/1203), the clade 2.1.3 virus A/Indonesia/5/2005 (IN5/05), the clade 2.2 viruses A/turkey/Turkey/1/2005 (TT01/05) and A/chicken/Egypt/3/2006 (CE/06), and the clade 2.3.4 virus A/Anhui/1/2005 (AH1/05) were constructed. These experimental live vaccines were assessed in a lethal mouse model. Mice vaccinated with the VN/1203 hemagglutinin-expressing MVA induced excellent protection against all the above mentioned clades. Also mice vaccinated with the IN5/05 HA expressing MVA induced substantial protection against homologous and heterologous AH1/05 challenge. After vaccination with the CE/06 HA expressing MVA, mice were fully protected against clade 2.2 challenge and partially protected against challenge of other clades. Mice vaccinated with AH1/05 HA expressing MVA vectors were only partially protected against homologous and heterologous challenge. The live vaccines induced substantial amounts of neutralizing antibodies, mainly directed against the homologous challenge virus, and high levels of HA-specific IFN-γ secreting CD4 and CD8 T-cells against epitopes conserved among the H5 clades and subclades.The highest level of cross-protection was induced by the HA derived from the VN/1203 strain, suggesting that pandemic H5 vaccines utilizing MVA vector technology, should be based on the VN/1203 hemagglutinin. Furthermore, the recombinant MVA-HA-VN, as characterized in the present study, would be a promising candidate for such a vaccine

Strong mitochondrial DNA support for a Cretaceous origin of modern avian lineages

<p>Abstract</p> <p>Background</p> <p>Determining an absolute timescale for avian evolutionary history has proven contentious. The two sources of information available, paleontological data and inference from extant molecular genetic sequences (colloquially, 'rocks' and 'clocks'), have appeared irreconcilable; the fossil record supports a Cenozoic origin for most modern lineages, whereas molecular genetic estimates suggest that these same lineages originated deep within the Cretaceous and survived the K-Pg (Cretaceous-Paleogene; formerly Cretaceous-Tertiary or K-T) mass-extinction event. These two sources of data therefore appear to support fundamentally different models of avian evolution. The paradox has been speculated to reflect deficiencies in the fossil record, unrecognized biases in the treatment of genetic data or both. Here we attempt to explore uncertainty and limit bias entering into molecular divergence time estimates through: (i) improved taxon (<it>n </it>= 135) and character (<it>n = </it>4594 bp mtDNA) sampling; (ii) inclusion of multiple cladistically tested internal fossil calibration points (<it>n </it>= 18); (iii) correction for lineage-specific rate heterogeneity using a variety of methods (<it>n </it>= 5); (iv) accommodation of uncertainty in tree topology; and (v) testing for possible effects of episodic evolution.</p> <p>Results</p> <p>The various 'relaxed clock' methods all indicate that the major (basal) lineages of modern birds originated deep within the Cretaceous, although temporal intraordinal diversification patterns differ across methods. We find that topological uncertainty had a systematic but minor influence on date estimates for the origins of major clades, and Bayesian analyses assuming fixed topologies deliver similar results to analyses with unconstrained topologies. We also find that, contrary to expectation, rates of substitution are not autocorrelated across the tree in an ancestor-descendent fashion. Finally, we find no signature of episodic molecular evolution related to either speciation events or the K-Pg boundary that could systematically mislead inferences from genetic data.</p> <p>Conclusion</p> <p>The 'rock-clock' gap has been interpreted by some to be a result of the vagaries of molecular genetic divergence time estimates. However, despite measures to explore different forms of uncertainty in several key parameters, we fail to reconcile molecular genetic divergence time estimates with dates taken from the fossil record; instead, we find strong support for an ancient origin of modern bird lineages, with many extant orders and families arising in the mid-Cretaceous, consistent with previous molecular estimates. Although there is ample room for improvement on both sides of the 'rock-clock' divide (e.g. accounting for 'ghost' lineages in the fossil record and developing more realistic models of rate evolution for molecular genetic sequences), the consistent and conspicuous disagreement between these two sources of data more likely reflects a genuine difference between estimated ages of (i) stem-group origins and (ii) crown-group morphological diversifications, respectively. Further progress on this problem will benefit from greater communication between paleontologists and molecular phylogeneticists in accounting for error in avian lineage age estimates.</p