71 research outputs found

    The evolution of protostome GATA factors: Molecular phylogenetics, synteny, and intron/exon structure reveal orthologous relationships

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    <p>Abstract</p> <p>Background</p> <p>Invertebrate and vertebrate GATA transcription factors play important roles in ectoderm and mesendoderm development, as well as in cardiovascular and blood cell fate specification. However, the assignment of evolutionarily conserved roles to GATA homologs requires a detailed framework of orthologous relationships. Although two distinct classes, GATA123 and GATA456, have been unambiguously recognized among deuterostome GATA genes, it has been difficult to resolve exact orthologous relationships among protostome homologs. Protostome GATA genes are often present in multiple copies within any one genome, and rapidly evolving gene sequences have obscured orthology among arthropod and nematode GATA homologs. In addition, a lack of taxonomic sampling has prevented a stepwise reconstruction of protostome GATA gene family evolution.</p> <p>Results</p> <p>We have identified the complete GATA complement (53 genes) from a diverse sampling of protostome genomes, including six arthropods, three lophotrochozoans, and two nematodes. Reciprocal best hit BLAST analysis suggested orthology of these GATA genes to either the ancestral bilaterian GATA123 or the GATA456 class. Using molecular phylogenetic analyses of gene sequences, together with conserved synteny and comparisons of intron/exon structure, we inferred the evolutionary relationships among these 53 protostome GATA homologs. In particular, we resolved the orthology and evolutionary birth order of all arthropod GATA homologs including the highly divergent <it>Drosophila </it>GATA genes.</p> <p>Conclusion</p> <p>Our combined analyses confirm that all protostome GATA transcription factor genes are members of either the GATA123 or GATA456 class, and indicate that there have been multiple protostome-specific duplications of GATA456 homologs. Three GATA456 genes exhibit linkage in multiple protostome species, suggesting that this gene cluster arose by tandem duplications from an ancestral GATA456 gene. Within arthropods this GATA456 cluster appears orthologous and widely conserved. Furthermore, the intron/exon structures of the arthropod GATA456 orthologs suggest a distinct order of gene duplication events. At present, however, the evolutionary relationship to similarly linked GATA456 paralogs in lophotrochozoans remains unclear. Our study shows how sampling of additional genomic data, especially from less derived and interspersed protostome taxa, can be used to resolve the orthologous relationships within more divergent gene families.</p

    Whole genome duplications and expansion of the vertebrate GATA transcription factor gene family

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    <p>Abstract</p> <p>Background</p> <p>GATA transcription factors influence many developmental processes, including the specification of embryonic germ layers. The GATA gene family has significantly expanded in many animal lineages: whereas diverse cnidarians have only one GATA transcription factor, six GATA genes have been identified in many vertebrates, five in many insects, and eleven to thirteen in <it>Caenorhabditis </it>nematodes. All bilaterian animal genomes have at least one member each of two classes, GATA123 and GATA456.</p> <p>Results</p> <p>We have identified one GATA123 gene and one GATA456 gene from the genomic sequence of two invertebrate deuterostomes, a cephalochordate (<it>Branchiostoma floridae</it>) and a hemichordate (<it>Saccoglossus kowalevskii</it>). We also have confirmed the presence of six GATA genes in all vertebrate genomes, as well as additional GATA genes in teleost fish. Analyses of conserved sequence motifs and of changes to the exon-intron structure, and molecular phylogenetic analyses of these deuterostome GATA genes support their origin from two ancestral deuterostome genes, one GATA 123 and one GATA456. Comparison of the conserved genomic organization across vertebrates identified eighteen paralogous gene families linked to multiple vertebrate GATA genes (GATA paralogons), providing the strongest evidence yet for expansion of vertebrate GATA gene families via genome duplication events.</p> <p>Conclusion</p> <p>From our analysis, we infer the evolutionary birth order and relationships among vertebrate GATA transcription factors, and define their expansion via multiple rounds of whole genome duplication events. As the genomes of four independent invertebrate deuterostome lineages contain single copy GATA123 and GATA456 genes, we infer that the 0R (pre-genome duplication) invertebrate deuterostome ancestor also had two GATA genes, one of each class. Synteny analyses identify duplications of paralogous chromosomal regions (paralogons), from single ancestral vertebrate GATA123 and GATA456 chromosomes to four paralogons after the first round of vertebrate genome duplication, to seven paralogons after the second round of vertebrate genome duplication, and to fourteen paralogons after the fish-specific 3R genome duplication. The evolutionary analysis of GATA gene origins and relationships may inform understanding vertebrate GATA factor redundancies and specializations.</p

    Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT ® nanoparticle formulation against non-small-cell lung cancer brain metastases

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    Particle Replication in Nonwetting Templates (PRINT®) PLGA nanoparticles of docetaxel and acid-labile C2-dimethyl-Si-Docetaxel were evaluated with small molecule docetaxel as treatments for non-small-cell lung cancer brain metastases

    Risks and Benefits of Consumption of Great Lakes Fish

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    Background: Beneficial effects of fish consumption on early cognitive development and cardiovascular health have been attributed to the omega-3 fatty acids in fish and fish oils, but toxic chemicals in fish may adversely affect these health outcomes. Risk–benefit assessments of fish consumption have frequently focused on methylmercury and omega-3 fatty acids, not persistent pollutants such as polychlorinated biphenyls, and none have evaluated Great Lakes fish consumption

    Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer

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    Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. Thi..

    Revisando el papel de los buitres en al interfaz de enfermedades que afectan a humanos, animales salvajes y ganado : una perspectiva africana

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    Vultures are a key component of an effective scavenger guild and have evolved a number of adaptations that allow them to locate and dispose of carcasses quickly and efficiently. The continuing decline of African vultures is threatening the stability of the African scavenger guild, which may result in increased carcass decomposition times and thus, more rapid development of pathogenic bacteria. The absence of competitive regulation by these apex scavengers may also result in changes in the composition of the vertebrate scavenger guild, with an increase in mammalian scavengers giving rise to increased contact rates at carcasses, which may increase the risk of viral disease transmission to humans, livestock, and other wildlife. Although the economic value of vultures in terms of the sanitation services they provide has been evaluated, their contribution to the economics of human health and veterinary care remains to be quantified. Efforts to do so are hampered by lack of data, as well as a number of confounding factors that may mask causality, such as improved disease prevention and surveillance systems. However, the circumstantial nature of the link between vultures and disease prevention should not deter efforts to conserve them, as their regulation of mammalian scavengers and the sanitation services they provide place them firmly within the sphere of One Health, thereby warranting their urgent protection. The restoration of vulture populations and the ecosystem services they provide will benefit the welfare of all humans, but particularly those who are most vulnerable to economic instability and the spillover of disease at the human-wildlife-livestock interface.This review article is a product of an investigation entitled ‘‘There is still time to save Africa’s vultures,’’ hosted and funded by the National Socio-Environmental Synthesis Center (SESYNC) in Annapolis, MD USA.https://bioone.org/journals/journal-of-raptor-researcham2022Zoology and Entomolog

    Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

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    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel
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