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Sample records for cross-seeding mimics cross-species

  1. Crossing species boundaries.

    PubMed

    Robert, Jason Scott; Baylis, Françoise

    2003-01-01

    This paper critically examines the biology of species identity and the morality of crossing species boundaries in the context of emerging research that involves combining human and nonhuman animals at the genetic or cellular level. We begin with the notion of species identity, particularly focusing on the ostensible fixity of species boundaries, and we explore the general biological and philosophical problem of defining species. Against this backdrop, we survey and criticize earlier attempts to forbid crossing species boundaries in the creation of novel beings. We do not attempt to establish the immorality of crossing species boundaries, but we conclude with some thoughts about such crossings, alluding to the notion of moral confusion regarding social and ethical obligations to novel interspecies beings.

  2. Mimic nets.

    PubMed

    Johnson, G E

    1993-01-01

    This paper introduces techniques to train feedforward nets to automate ranking and classification tasks. The techniques are denoted mimic nets since the nets can always mimic self-consistent training data. The mimic nets are constructed not for any neurological analogy, but for computational ease and purposeful utility. Mimic nets are designed for problems requiring sensible extrapolation from noiseless training data, and errorless recall of the training data. Linear programming algorithms are utilized to train the net to exactly mimic the expert in all training situations, to identify efficacious features, and to assess the training data. The number of nodes and the number of connections, the structure of the mimic net, are adapted together with weights in the net. The existence of a mimic net for every consistent set of training data is demonstrated.

  3. Cross-species transmission of CWD prions.

    PubMed

    Kurt, Timothy D; Sigurdson, Christina J

    2016-01-01

    Prions cause fatal neurodegenerative diseases in humans and animals and can be transmitted zoonotically. Chronic wasting disease (CWD) is a highly transmissible prion disease of wild deer and elk that affects cervids over extensive regions of the United States and Canada. The risk of cross-species CWD transmission has been experimentally evaluated in a wide array of mammals, including non-human primates and mouse models expressing human cellular prion protein. Here we review the determinants of cross-species CWD transmission, and propose a model that may explain a structural barrier for CWD transmission to humans. PMID:26809254

  4. Polymorphic cross-seeding amyloid assemblies of amyloid-β and human islet amyloid polypeptide.

    PubMed

    Zhang, Mingzhen; Hu, Rundong; Chen, Hong; Chang, Yung; Ma, Jie; Liang, Guizhao; Mi, Jingyan; Wang, Yaru; Zheng, Jie

    2015-09-21

    Epidemiological studies have shown that the development of Alzheimer's disease (AD) is associated with type 2 diabetes (T2D), but it still remains unclear how AD and T2D are connected. Heterologous cross-seeding between the causative peptides of Aβ and hIAPP may represent a molecular link between AD and T2D. Here, we computationally modeled and simulated a series of cross-seeding double-layer assemblies formed by Aβ and hIAPP peptides using all-atom and coarse-gained molecular dynamics (MD) simulations. The cross-seeding Aβ-hIAPP assemblies showed a wide range of polymorphic structures via a combination of four β-sheet-to-β-sheet interfaces and two packing orientations, focusing on a comparison of different matches of β-sheet layers. Two cross-seeding Aβ-hIAPP assemblies with different interfacial β-sheet packings exhibited high structural stability and favorable interfacial interactions in both oligomeric and fibrillar states. Both Aβ-hIAPP assemblies displayed interfacial dehydration to different extents, which in turn promoted Aβ-hIAPP association depending on interfacial polarity and geometry. Furthermore, computational mutagenesis studies revealed that disruption of interfacial salt bridges largely disfavor the β-sheet-to-β-sheet association, highlighting the importance of salt bridges in the formation of cross-seeding assemblies. This work provides atomic-level information on the cross-seeding interactions between Aβ and hIAPP, which may be involved in the interplay between these two disorders. PMID:26283068

  5. Polymorphic cross-seeding amyloid assemblies of amyloid-β and human islet amyloid polypeptide.

    PubMed

    Zhang, Mingzhen; Hu, Rundong; Chen, Hong; Chang, Yung; Ma, Jie; Liang, Guizhao; Mi, Jingyan; Wang, Yaru; Zheng, Jie

    2015-09-21

    Epidemiological studies have shown that the development of Alzheimer's disease (AD) is associated with type 2 diabetes (T2D), but it still remains unclear how AD and T2D are connected. Heterologous cross-seeding between the causative peptides of Aβ and hIAPP may represent a molecular link between AD and T2D. Here, we computationally modeled and simulated a series of cross-seeding double-layer assemblies formed by Aβ and hIAPP peptides using all-atom and coarse-gained molecular dynamics (MD) simulations. The cross-seeding Aβ-hIAPP assemblies showed a wide range of polymorphic structures via a combination of four β-sheet-to-β-sheet interfaces and two packing orientations, focusing on a comparison of different matches of β-sheet layers. Two cross-seeding Aβ-hIAPP assemblies with different interfacial β-sheet packings exhibited high structural stability and favorable interfacial interactions in both oligomeric and fibrillar states. Both Aβ-hIAPP assemblies displayed interfacial dehydration to different extents, which in turn promoted Aβ-hIAPP association depending on interfacial polarity and geometry. Furthermore, computational mutagenesis studies revealed that disruption of interfacial salt bridges largely disfavor the β-sheet-to-β-sheet association, highlighting the importance of salt bridges in the formation of cross-seeding assemblies. This work provides atomic-level information on the cross-seeding interactions between Aβ and hIAPP, which may be involved in the interplay between these two disorders.

  6. GENOMIC APPROACHES FOR CROSS-SPECIES EXTRAPOLATION IN TOXICOLOGY

    EPA Science Inventory

    The latest tools for investigating stress in organisms, genomic technologies provide great insight into how different organisms respond to environmental conditions. However, their usefulness needs testing, verification, and codification. Genomic Approaches for Cross-Species Extra...

  7. Cross-species cloning: influence of cytoplasmic factors on development.

    PubMed

    Sun, Yong-Hua; Zhu, Zuo-Yan

    2014-06-01

    It is widely accepted that the crosstalk between naive nucleus and maternal factors deposited in the egg cytoplasm before zygotic genome activation is crucial for early development. This crosstalk may also exert some influence on later development. It is interesting to clarify the relative roles of the zygotic genome and the cytoplasmic factors in development. Cross-species nuclear transfer (NT) between two distantly related species provides a unique system to study the relative role and crosstalk between egg cytoplasm and zygotic nucleus in development. In this review, we will summarize the recent progress of cross-species NT, with emphasis on the cross-species NT in fish and the influence of cytoplasmic factors on development. Finally, we conclude that the developmental process and its evolution should be interpreted in a systemic way, rather than in a way that solely focuses on the role of the nuclear genome.

  8. CROSS-SPECIES DOSE EXTRAPOLATION FOR DIESEL EMISSIONS

    EPA Science Inventory

    Models for cross-species (rat to human) dose extrapolation of diesel emission were evaluated for purposes of establishing guidelines for human exposure to diesel emissions (DE) based on DE toxicological data obtained in rats. Ideally, a model for this extrapolation would provide...

  9. MULTIPLE SOLVENT EXPOSURE IN HUMANS: CROSS-SPECIES EXTRAPOLATIONS

    EPA Science Inventory

    Multiple Solvent Exposures in Humans:
    Cross-Species Extrapolations
    (Future Research Plan)

    Vernon A. Benignus1, Philip J. Bushnell2 and William K. Boyes2

    A few solvents can be safely studied in acute experiments in human subjects. Data exist in rats f...

  10. Cross-Seeding Interaction between β-Amyloid and Human Islet Amyloid Polypeptide.

    PubMed

    Hu, Rundong; Zhang, Mingzhen; Chen, Hong; Jiang, Binbo; Zheng, Jie

    2015-10-21

    Alzheimer's disease (AD) and type 2 diabetes (T2D) are two common protein misfolding diseases. Increasing evidence suggests that these two diseases may be correlated with each other via cross-sequence interactions between β-amyloid peptide (Aβ) associated with AD and human islet amyloid polypeptide (hIAPP) associated with T2D. However, little is known about how these two peptides work and how they interact with each other to induce amyloidogenesis. In this work, we study the effect of cross-sequence interactions between Aβ and hIAPP peptides on hybrid amyloid structures, conformational changes, and aggregation kinetics using combined experimental and simulation approaches. Experimental results confirm that Aβ and hIAPP can interact with each other to aggregate into hybrid amyloid fibrils containing β-sheet-rich structures morphologically similar to pure Aβ and hIAPP. The cross-seeding of Aβ and hIAPP leads to the coexistence of both a retarded process at the initial nucleation stage and an accelerated process at the fibrillization stage, in conjunction with a conformational transition from random structures to α-helix to β-sheet. Further molecular dynamics simulations reveal that Aβ and hIAPP oligomers can efficiently cross-seed each other via the association of two highly similar U-shaped β-sheet structures; thus, conformational compatibility between Aβ and hIAPP aggregates appears to play a key role in determining barriers to cross-seeding. The cross-seeding effects in this work may provide new insights into the molecular mechanisms of interactions between AD and T2D.

  11. Toward a cross-species understanding of empathy

    PubMed Central

    Panksepp, Jaak; Panksepp, Jules B.

    2013-01-01

    Although signs of empathy have now been well documented in non-human primates, only during the past few years have systematic observations suggested that a primal form of empathy exists in rodents. Thus, the study of empathy in animals has started in earnest. Here we review recent studies indicating that rodents are able to share states of fear, and highlight how affective neuroscience approaches to the study of primary-process emotional systems can help to delineate how primal empathy is constituted in mammalian brains. Cross-species evolutionary approaches to understanding the neural circuitry of emotional ‘contagion’ or ‘resonance’ between nearby animals, together with the underlying neurochemistries, may help to clarify the origins of human empathy. PMID:23746460

  12. [Cross-species Transmission of Avian Leukosis Virus Subgroup J].

    PubMed

    Shen, Yanwei; He, Menglian; Zhang, Ji; Zhao, Manda; Wang, Guihua; Cheng, Ziqiang

    2016-01-01

    Avian leukosis virus subgroup J (ALV-J) is an avian retrovirus that can induce myelocytomas. A high-frequency mutation in gene envelope endows ALV-J with the potential for cross-species transmission. We wished to ascertain if the ALV-J can spread across species under selection pressure in susceptible and resistant hosts. First, we inoculated (in turn) two susceptible host birds (specific pathogen-free (SPF) chickens and turkeys). Then, we inoculated three resistant hosts (pheasants, quails and ducks) to detect the viral shedding, pathologic changes, and genetic evolution of different isolates. We found that pheasants and quails were infected under the selective pressure that accumulates stepwise in different hosts, and that ducks were not infected. Infection rates for SPF chickens and turkeys were 100% (16/16), whereas those for pheasants and quails were 37.5% (6/16) and 11.1% (3/27). Infected hosts showed immune tolerance, and inflammation and tissue damage could be seen in the liver, spleen, kidneys and cardiovascular system. Non-synonymous mutation and synonymous ratio (NS/S) analyses revealed the NS/S in hypervariable region (hr) 2 of pheasants and quails was 2.5. That finding suggested that mutation of isolates in pheasants and quails was induced by selective pressure from the resistant host, and that the hr2 region is a critical domain in cross-species transmission of ALV-J. Sequencing showed that ALV-J isolates from turkeys, pheasants and quails had moved away from the original virus, and were closer to the ALV-J prototype strain HPRS-103. However, the HPRS-103 strain cannot infect pheasants and quails, so further studies are needed. PMID:27295883

  13. [Cross-species Transmission of Avian Leukosis Virus Subgroup J].

    PubMed

    Shen, Yanwei; He, Menglian; Zhang, Ji; Zhao, Manda; Wang, Guihua; Cheng, Ziqiang

    2016-01-01

    Avian leukosis virus subgroup J (ALV-J) is an avian retrovirus that can induce myelocytomas. A high-frequency mutation in gene envelope endows ALV-J with the potential for cross-species transmission. We wished to ascertain if the ALV-J can spread across species under selection pressure in susceptible and resistant hosts. First, we inoculated (in turn) two susceptible host birds (specific pathogen-free (SPF) chickens and turkeys). Then, we inoculated three resistant hosts (pheasants, quails and ducks) to detect the viral shedding, pathologic changes, and genetic evolution of different isolates. We found that pheasants and quails were infected under the selective pressure that accumulates stepwise in different hosts, and that ducks were not infected. Infection rates for SPF chickens and turkeys were 100% (16/16), whereas those for pheasants and quails were 37.5% (6/16) and 11.1% (3/27). Infected hosts showed immune tolerance, and inflammation and tissue damage could be seen in the liver, spleen, kidneys and cardiovascular system. Non-synonymous mutation and synonymous ratio (NS/S) analyses revealed the NS/S in hypervariable region (hr) 2 of pheasants and quails was 2.5. That finding suggested that mutation of isolates in pheasants and quails was induced by selective pressure from the resistant host, and that the hr2 region is a critical domain in cross-species transmission of ALV-J. Sequencing showed that ALV-J isolates from turkeys, pheasants and quails had moved away from the original virus, and were closer to the ALV-J prototype strain HPRS-103. However, the HPRS-103 strain cannot infect pheasants and quails, so further studies are needed.

  14. A brief history of cross-species organ transplantation

    PubMed Central

    2012-01-01

    Cross-species transplantation (xenotransplantation) offers the prospect of an unlimited supply of organs and cells for clinical transplantation, thus resolving the critical shortage of human tissues that currently prohibits a majority of patients on the waiting list from receiving transplants. Between the 17th and 20th centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the 19th century from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into aged men whose “zest for life” was deteriorating, believing that the hormones produced by the testis would rejuvenate his patients. Following the pioneering surgical work of Carrel, who developed the technique of blood vessel anastomosis, numerous attempts at nonhuman primate organ transplantation in patients were carried out in the 20th century. In 1963–1964, when human organs were not available and chronic dialysis was not yet in use, Reemtsma transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 hours. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992, he obtained patient survival for 70 days following a baboon liver transplant. With the advent of genetic engineering and cloning technologies, pigs are currently available with a number of different manipulations that protect their tissues from the human immune response, resulting in increasing pig graft survival in nonhuman primate models. Genetically modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant. PMID:22275786

  15. Deadly viral syndrome mimics.

    PubMed

    Lowenstein, Robert

    2004-11-01

    Upper respiratory tract infections (ie, "the common cold") have several hundred causes, the most common of which include rhino-virus, coronavirus, and respiratory syncytial virus. The clinical presentation varies with symptoms. Every emergency department, no matter what the demographics, cares for patients with this constellation of symptoms. Emergency physicians examine, diagnose, and treat these disorders frequently. With increasing burdens being placed on emergency physicians, it is possible to assume a diagnosis of upper respiratory tract infection without generating a complete differential diagnosis. The challenge is to identify and recognize the distinctions between an innocuous upper respiratory tract infection and a life-threatening disease "mimic" or entities. This article discusses some of these life-threatening mimics.

  16. Lesion mimic mutants

    PubMed Central

    Moeder, Wolfgang

    2008-01-01

    Over the last decade a substantial number of lesion mimic mutants (LMM) have been isolated and a growing number of the genes have been cloned. It is now becoming clear that these mutants are valuable tools to dissect various aspects of programmed cell death (PCD) and pathogen resistance pathways in plants. Together with other forward genetics approaches LMMs shed light on the PCD machinery in plant cells and revealed important roles for sphingolipids, Ca2+ and chloroplast-derived porphyrin-metabolites during cell death development. PMID:19513227

  17. Amyotrophic lateral sclerosis mimic syndromes

    PubMed Central

    Ghasemi, Majid

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) misdiagnosis has many broad implications for the patient and the neurologist. Potentially curative treatments exist for certain ALS mimic syndromes, but delay in starting these therapies may have an unfavorable effect on outcome. Hence, it is important to exclude similar conditions. In this review, we discuss some of the important mimics of ALS. PMID:27326363

  18. Enzyme Mimics: Advances and Applications.

    PubMed

    Kuah, Evelyn; Toh, Seraphina; Yee, Jessica; Ma, Qian; Gao, Zhiqiang

    2016-06-13

    Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. PMID:27062126

  19. Antimicrobial activities of squalamine mimics.

    PubMed

    Kikuchi, K; Bernard, E M; Sadownik, A; Regen, S L; Armstrong, D

    1997-07-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and fungi. Some had little or no hemolytic activity. The hydrophobicity of the sterol backbone and the length and the cationic charge of the side chains appeared to be critical determinants of activity. One of the squalamine mimics, SM-7, was bactericidal against Escherichia coli, Pseudomonas aeruginosa, and S. aureus; its activity was decreased by divalent or monovalent cations and by bovine serum albumin. Subinhibitory concentrations of SM-7 markedly enhanced the antimicrobial activity of rifampin against gram-negative rods. These results suggest that the compounds may disrupt an outer membrane of gram-negative rods. Squalamine mimics are a new class of broad-spectrum antimicrobial agents. The antagonism of their activity by serum and albumin and their hemolytic properties may limit their use as systemic agents. The squalamine mimics, because of their potencies, broad spectra of antimicrobial activity, and potential for systemic toxicity, appear to be good candidates for development as topical antimicrobial agents. PMID:9210661

  20. New roles for microRNAs in cross-species communication.

    PubMed

    Liang, Hongwei; Zen, Ke; Zhang, Junfeng; Zhang, Chen-Yu; Chen, Xi

    2013-03-01

    Communication between cells ensures coordinated behavior. In prokaryotes, this signaling is typically referred to as quorum sensing, whereas in eukaryotic cells, communication occurs through hormones. In recent years, reports have shown that small noncoding RNAs, called microRNAs (miRNAs), can be transmitted from one species to another, inducing signal interference in distant species, even in a cross-kingdom manner. This new mode of cross-species communication might mediate symbiotic and pathogenic relationships between various organisms (e.g., microorganisms and their hosts). Here, we discuss several recent studies concerning miRNA-mediated cross-species gene regulation.

  1. CROSS-SPECIES EVALUATION OF ENDOCRINE DISRUPTING EFFECTS OF LEAD (Pb) on MATURATION AND DEVELOPMENT

    EPA Science Inventory

    In a cross-species evaluation conducted in support of the review of the US EPA National Ambient Air Quality Standards (NAAQS) for Lead (Pb), findings from epidemiologic, toxicological and ecological disciplines were used in a weight of evidence approach to evaluate reproductive a...

  2. EMERGING MOLECULAR AND COMPUTATIONAL APPROACHES FOR CROSS-SPECIES EXTRAPLATIONS: A WORKSHOP SUMMARY REPORT

    EPA Science Inventory

    Benson, W.H., R.T. Di Giulio, J.C. Cook, J. Freedman, R.L. Malek, C. Thompson and D. Versteeg. In press. Emerging Molecular and Computational Approaches for Cross-Species Extrapolations: A Workshop Summary Report (Abstract). To be presented at the SETAC Fourth World Congress, 14-...

  3. The ReproGenomics Viewer: an integrative cross-species toolbox for the reproductive science community

    PubMed Central

    Darde, Thomas A.; Sallou, Olivier; Becker, Emmanuelle; Evrard, Bertrand; Monjeaud, Cyril; Le Bras, Yvan; Jégou, Bernard; Collin, Olivier; Rolland, Antoine D.; Chalmel, Frédéric

    2015-01-01

    We report the development of the ReproGenomics Viewer (RGV), a multi- and cross-species working environment for the visualization, mining and comparison of published omics data sets for the reproductive science community. The system currently embeds 15 published data sets related to gametogenesis from nine model organisms. Data sets have been curated and conveniently organized into broad categories including biological topics, technologies, species and publications. RGV's modular design for both organisms and genomic tools enables users to upload and compare their data with that from the data sets embedded in the system in a cross-species manner. The RGV is freely available at http://rgv.genouest.org. PMID:25883147

  4. Ontology-based cross-species integration and analysis of Saccharomyces cerevisiae phenotypes

    PubMed Central

    2012-01-01

    Ontologies are widely used in the biomedical community for annotation and integration of databases. Formal definitions can relate classes from different ontologies and thereby integrate data across different levels of granularity, domains and species. We have applied this methodology to the Ascomycete Phenotype Ontology (APO), enabling the reuse of various orthogonal ontologies and we have converted the phenotype associated data found in the SGD following our proposed patterns. We have integrated the resulting data in the cross-species phenotype network PhenomeNET, and we make both the cross-species integration of yeast phenotypes and a similarity-based comparison of yeast phenotypes across species available in the PhenomeBrowser. Furthermore, we utilize our definitions and the yeast phenotype annotations to suggest novel functional annotations of gene products in yeast. PMID:23046642

  5. Ontology-based cross-species integration and analysis of Saccharomyces cerevisiae phenotypes.

    PubMed

    Gkoutos, Georgios V; Hoehndorf, Robert

    2012-09-21

    Ontologies are widely used in the biomedical community for annotation and integration of databases. Formal definitions can relate classes from different ontologies and thereby integrate data across different levels of granularity, domains and species. We have applied this methodology to the Ascomycete Phenotype Ontology (APO), enabling the reuse of various orthogonal ontologies and we have converted the phenotype associated data found in the SGD following our proposed patterns. We have integrated the resulting data in the cross-species phenotype network PhenomeNET, and we make both the cross-species integration of yeast phenotypes and a similarity-based comparison of yeast phenotypes across species available in the PhenomeBrowser. Furthermore, we utilize our definitions and the yeast phenotype annotations to suggest novel functional annotations of gene products in yeast.

  6. Vocal learning in Grey parrots: A brief review of perception, production, and cross-species comparisons.

    PubMed

    Pepperberg, Irene M

    2010-10-01

    This chapter briefly reviews what is known-and what remains to be understood-about Grey parrot vocal learning. I review Greys' physical capacities-issues of auditory perception and production-then discuss how these capacities are used in vocal learning and can be recruited for referential communication with humans. I discuss cross-species comparisons where applicable and conclude with a description of recent research that integrates issues of reference, production and perception.

  7. Enzyme sequence similarity improves the reaction alignment method for cross-species pathway comparison

    SciTech Connect

    Ovacik, Meric A.; Androulakis, Ioannis P.

    2013-09-15

    Pathway-based information has become an important source of information for both establishing evolutionary relationships and understanding the mode of action of a chemical or pharmaceutical among species. Cross-species comparison of pathways can address two broad questions: comparison in order to inform evolutionary relationships and to extrapolate species differences used in a number of different applications including drug and toxicity testing. Cross-species comparison of metabolic pathways is complex as there are multiple features of a pathway that can be modeled and compared. Among the various methods that have been proposed, reaction alignment has emerged as the most successful at predicting phylogenetic relationships based on NCBI taxonomy. We propose an improvement of the reaction alignment method by accounting for sequence similarity in addition to reaction alignment method. Using nine species, including human and some model organisms and test species, we evaluate the standard and improved comparison methods by analyzing glycolysis and citrate cycle pathways conservation. In addition, we demonstrate how organism comparison can be conducted by accounting for the cumulative information retrieved from nine pathways in central metabolism as well as a more complete study involving 36 pathways common in all nine species. Our results indicate that reaction alignment with enzyme sequence similarity results in a more accurate representation of pathway specific cross-species similarities and differences based on NCBI taxonomy.

  8. Initial description of a quantitative, cross-species (chimpanzee-human) social responsiveness measure

    PubMed Central

    Marrus, Natasha; Faughn, Carley; Shuman, Jeremy; Petersen, Steve; Constantino, John; Povinelli, Daniel; Pruett, John R.

    2011-01-01

    Objective Comparative studies of social responsiveness, an ability that is impaired in autistic spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. Method We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimp SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n=29) with the Chimp SRS and typical and autistic spectrum disorder (ASD) human children (n=20) with the XSRS. Results The Chimp SRS demonstrated strong inter-rater reliability at the three sites (ranges for individual ICCs: .534–.866 and mean ICCs: .851–.970). As has been observed in humans, exploratory principal components analysis of Chimp SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r=.976, p=.001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. Conclusion Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) humans and chimpanzees. PMID:21515200

  9. Strain conformation controls the specificity of cross-species prion transmission in the yeast model.

    PubMed

    Grizel, Anastasia V; Rubel, Aleksandr A; Chernoff, Yury O

    2016-07-01

    Transmissible self-assembled fibrous cross-β polymer infectious proteins (prions) cause neurodegenerative diseases in mammals and control non-Mendelian heritable traits in yeast. Cross-species prion transmission is frequently impaired, due to sequence differences in prion-forming proteins. Recent studies of prion species barrier on the model of closely related yeast species show that colocalization of divergent proteins is not sufficient for the cross-species prion transmission, and that an identity of specific amino acid sequences and a type of prion conformational variant (strain) play a major role in the control of transmission specificity. In contrast, chemical compounds primarily influence transmission specificity via favoring certain strain conformations, while the species origin of the host cell has only a relatively minor input. Strain alterations may occur during cross-species prion conversion in some combinations. The model is discussed which suggests that different recipient proteins can acquire different spectra of prion strain conformations, which could be either compatible or incompatible with a particular donor strain. PMID:27565563

  10. Cross-Species Network Analysis Uncovers Conserved Nitrogen-Regulated Network Modules in Rice1[OPEN

    PubMed Central

    Obertello, Mariana; Shrivastava, Stuti; Katari, Manpreet S.; Coruzzi, Gloria M.

    2015-01-01

    In this study, we used a cross-species network approach to uncover nitrogen (N)-regulated network modules conserved across a model and a crop species. By translating gene network knowledge from the data-rich model Arabidopsis (Arabidopsis thaliana) to a crop, rice (Oryza sativa), we identified evolutionarily conserved N-regulatory modules as targets for translational studies to improve N use efficiency in transgenic plants. To uncover such conserved N-regulatory network modules, we first generated an N-regulatory network based solely on rice transcriptome and gene interaction data. Next, we enhanced the network knowledge in the rice N-regulatory network using transcriptome and gene interaction data from Arabidopsis and new data from Arabidopsis and rice plants exposed to the same N treatment conditions. This cross-species network analysis uncovered a set of N-regulated transcription factors (TFs) predicted to target the same genes and network modules in both species. Supernode analysis of the TFs and their targets in these conserved network modules uncovered genes directly related to N use (e.g. N assimilation) and to other shared biological processes indirectly related to N. This cross-species network approach was validated with members of two TF families in the supernode network, BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTOR1-TGA and HYPERSENSITIVITY TO LOW PI-ELICITED PRIMARY ROOT SHORTENING1 (HRS1)/HRS1 Homolog family, which have recently been experimentally validated to mediate the N response in Arabidopsis. PMID:26045464

  11. A portable expression resource for engineering cross-species genetic circuits and pathways

    PubMed Central

    Kushwaha, Manish; Salis, Howard M.

    2015-01-01

    Genetic circuits and metabolic pathways can be reengineered to allow organisms to process signals and manufacture useful chemicals. However, their functions currently rely on organism-specific regulatory parts, fragmenting synthetic biology and metabolic engineering into host-specific domains. To unify efforts, here we have engineered a cross-species expression resource that enables circuits and pathways to reuse the same genetic parts, while functioning similarly across diverse organisms. Our engineered system combines mixed feedback control loops and cross-species translation signals to autonomously self-regulate expression of an orthogonal polymerase without host-specific promoters, achieving nontoxic and tuneable gene expression in diverse Gram-positive and Gram-negative bacteria. Combining 50 characterized system variants with mechanistic modelling, we show how the cross-species expression resource's dynamics, capacity and toxicity are controlled by the control loops' architecture and feedback strengths. We also demonstrate one application of the resource by reusing the same genetic parts to express a biosynthesis pathway in both model and non-model hosts. PMID:26184393

  12. Dissection of a Ciona regulatory element reveals complexity of cross-species enhancer activity.

    PubMed

    Chen, Wei-Chung; Pauls, Stefan; Bacha, Jamil; Elgar, Greg; Loose, Matthew; Shimeld, Sebastian M

    2014-06-15

    Vertebrate genomes share numerous conserved non-coding elements, many of which function as enhancer elements and are hypothesised to be under evolutionary constraint due to a need to be bound by combinations of sequence-specific transcription factors. In contrast, few such conserved elements can be detected between vertebrates and their closest invertebrate relatives. Despite this lack of sequence identity, cross-species transgenesis has identified some cases where non-coding DNA from invertebrates drives reporter gene expression in transgenic vertebrates in patterns reminiscent of the expression of vertebrate orthologues. Such instances are presumed to reflect the presence of conserved suites of binding sites in the regulatory regions of invertebrate and vertebrate orthologues, such that both regulatory elements can correctly interpret the trans-activating environment. Shuffling of binding sites has been suggested to lie behind loss of sequence conservation; however this has not been experimentally tested. Here we examine the underlying basis of enhancer activity for the Ciona intestinalis βγ-crystallin gene, which drives expression in the lens of transgenic vertebrates despite the Ciona lineage predating the evolution of the lens. We construct an interactive gene regulatory network (GRN) for vertebrate lens development, allowing network interactions to be robustly catalogued and conserved network components and features to be identified. We show that a small number of binding motifs are necessary for Ciona βγ-crystallin expression, and narrow down the likely factors that bind to these motifs. Several of these overlap with the conserved core of the vertebrate lens GRN, implicating these sites in cross species function. However when we test these motifs in a transgenic vertebrate they prove to be dispensable for reporter expression in the lens. These results show that current models depicting cross species enhancer function as dependent on conserved binding

  13. N-Terminal Extensions Retard Aβ42 Fibril Formation but Allow Cross-Seeding and Coaggregation with Aβ42.

    PubMed

    Szczepankiewicz, Olga; Linse, Björn; Meisl, Georg; Thulin, Eva; Frohm, Birgitta; Sala Frigerio, Carlo; Colvin, Michael T; Jacavone, Angela C; Griffin, Robert G; Knowles, Tuomas; Walsh, Dominic M; Linse, Sara

    2015-11-25

    Amyloid β-protein (Aβ) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the aggregation process. Until recently, naturally occurring amyloid β-protein (Aβ) variants were believed to begin at or after the canonical β-secretase cleavage site within the amyloid β-protein precursor. However, N-terminally extended forms of Aβ (NTE-Aβ) were recently discovered and may contribute to Alzheimer's disease. Here, we have used thioflavin T fluorescence to study the aggregation kinetics of Aβ42 variants with N-terminal extensions of 5-40 residues, and transmission electron microscopy to analyze the end states. We find that all variants form amyloid fibrils of similar morphology as Aβ42, but the half-time of aggregation (t1/2) increases exponentially with extension length. Monte Carlo simulations of model peptides suggest that the retardation is due to an underlying general physicochemical effect involving reduced frequency of productive molecular encounters. Indeed, global kinetic analyses reveal that NTE-Aβ42s form fibrils via the same mechanism as Aβ42, but all microscopic rate constants (primary and secondary nucleation, elongation) are reduced for the N-terminally extended variants. Still, Aβ42 and NTE-Aβ42 coaggregate to form mixed fibrils and fibrils of either Aβ42 or NTE-Aβ42 catalyze aggregation of all monomers. NTE-Aβ42 monomers display reduced aggregation rate with all kinds of seeds implying that extended termini interfere with the ability of monomers to nucleate or elongate. Cross-seeding or coaggregation may therefore represent an important contribution in the in vivo formation of assemblies believed to be important in disease. PMID:26535489

  14. Frequent cross-species transmission of parvoviruses among diverse carnivore hosts.

    PubMed

    Allison, Andrew B; Kohler, Dennis J; Fox, Karen A; Brown, Justin D; Gerhold, Richard W; Shearn-Bochsler, Valerie I; Dubovi, Edward J; Parrish, Colin R; Holmes, Edward C

    2013-02-01

    Although parvoviruses are commonly described in domestic carnivores, little is known about their biodiversity in nondomestic species. A phylogenetic analysis of VP2 gene sequences from puma, coyote, gray wolf, bobcat, raccoon, and striped skunk revealed two major groups related to either feline panleukopenia virus ("FPV-like") or canine parvovirus ("CPV-like"). Cross-species transmission was commonplace, with multiple introductions into each host species but, with the exception of raccoons, relatively little evidence for onward transmission in nondomestic species. PMID:23221559

  15. Frequent cross-species transmission of parvoviruses among diverse carnivore hosts

    USGS Publications Warehouse

    Allison, Andrew B.; Kohler, Dennis J.; Fox, Karen A.; Brown, Justin D.; Gerhold, Richard W.; Shearn-Bochsler, Valerie I.; Dubovi, Edward J.; Parrish, Colin R.; Holmes, Edward C.

    2013-01-01

    Although parvoviruses are commonly described in domestic carnivores, little is known about their biodiversity in nondomestic species. A phylogenetic analysis of VP2 gene sequences from puma, coyote, gray wolf, bobcat, raccoon, and striped skunk revealed two major groups related to either feline panleukopenia virus (“FPV-like”) or canine parvovirus (“CPV-like”). Cross-species transmission was commonplace, with multiple introductions into each host species but, with the exception of raccoons, relatively little evidence for onward transmission in nondomestic species.

  16. Frequent Cross-Species Transmission of Parvoviruses among Diverse Carnivore Hosts

    PubMed Central

    Allison, Andrew B.; Kohler, Dennis J.; Fox, Karen A.; Brown, Justin D.; Gerhold, Richard W.; Shearn-Bochsler, Valerie I.; Dubovi, Edward J.; Parrish, Colin R.

    2013-01-01

    Although parvoviruses are commonly described in domestic carnivores, little is known about their biodiversity in nondomestic species. A phylogenetic analysis of VP2 gene sequences from puma, coyote, gray wolf, bobcat, raccoon, and striped skunk revealed two major groups related to either feline panleukopenia virus (“FPV-like”) or canine parvovirus (“CPV-like”). Cross-species transmission was commonplace, with multiple introductions into each host species but, with the exception of raccoons, relatively little evidence for onward transmission in nondomestic species. PMID:23221559

  17. What makes us human (Homo sapiens)? The challenge of cognitive cross-species comparison.

    PubMed

    Boesch, Christophe

    2007-08-01

    Two major theoretical approaches have dominated the quest for uniquely human cognitive abilities: a developmentalist approach stressing the importance of environmental and social conditions, and a predominant approach in experimental and comparative psychology, the deterministic approach suggesting the effect of environmental and social conditions to be minimal. As a consequence, most claims of human cognitive uniqueness are based on comparisons of White middle class Westerner humans (Homo sapiens) with captive chimpanzees (Pan troglodytes). However, humans are much more than only White middle class Westerners, and chimpanzees are much more than only captives. A review of some data available on different populations of humans and chimpanzees reveals that only the predictions of the developmentalist approach are supported. In addition, systematic biases are too often introduced in experiment protocols when comparing humans with apes that further cast doubts on cross-species comparisons. The author argues that only with consideration of within-species population differences in the cognitive domains and the use of well-matched cross-species experimental procedures will an objective understanding of the different cognitive abilities between species emerge. This will require a shift in the theoretical approach adopted by many in experimental and comparative psychology.

  18. Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

    PubMed Central

    Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A.; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H.; Ching, Grace; Nguyen, Tran N.; Nicholas, Courtney; Thomas, Valencia D.; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A.; Abbas, Hussein A.; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R.; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N.; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P.; Wheeler, David A.; Hawk, Ernest T.; Flores, Elsa R.; Tsai, Kenneth Y.

    2016-01-01

    Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

  19. Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.

    PubMed

    Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H; Ching, Grace; Nguyen, Tran N; Nicholas, Courtney; Thomas, Valencia D; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A; Abbas, Hussein A; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P; Wheeler, David A; Hawk, Ernest T; Flores, Elsa R; Tsai, Kenneth Y

    2016-01-01

    Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

  20. Differentially expressed genes identified by cross-species microarray in the blind cavefish Astyanax.

    PubMed

    Strickler, Allen G; Jeffery, William R

    2009-03-01

    Changes in gene expression were examined by microarray analysis during development of the eyed surface dwelling (surface fish) and blind cave-dwelling (cavefish) forms of the teleost Astyanax mexicanus De Filippi, 1853. The cross-species microarray used surface and cavefish RNA hybridized to a DNA chip prepared from a closely related species, the zebrafish Danio rerio Hamilton, 1822. We identified a total of 67 differentially expressed probe sets at three days post-fertilization: six upregulated and 61 downregulated in cavefish relative to surface fish. Many of these genes function either in eye development and/or maintenance, or in programmed cell death. The upregulated probe set showing the highest mean fold change was similar to the human ubiquitin specific protease 53 gene. The downregulated probe sets showing some of the highest fold changes corresponded to genes with roles in eye development, including those encoding gamma crystallins, the guanine nucleotide binding proteins Gnat1 and Gant2, a BarH-like homeodomain transcription factor, and rhodopsin. Downregulation of gamma-crystallin and rhodopsin was confirmed by in situ hybridization and immunostaining with specific antibodies. Additional downregulated genes encode molecules that inhibit or activate programmed cell death. The results suggest that cross-species microarray can be used for identifying differentially expressed genes in cavefish, that many of these genes might be involved in eye degeneration via apoptotic processes, and that more genes are downregulated than upregulated in cavefish, consistent with the predominance of morphological losses over gains during regressive evolution.

  1. Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways.

    PubMed

    Das, Jishnu; Vo, Tommy V; Wei, Xiaomu; Mellor, Joseph C; Tong, Virginia; Degatano, Andrew G; Wang, Xiujuan; Wang, Lihua; Cordero, Nicolas A; Kruer-Zerhusen, Nathan; Matsuyama, Akihisa; Pleiss, Jeffrey A; Lipkin, Steven M; Yoshida, Minoru; Roth, Frederick P; Yu, Haiyuan

    2013-05-21

    The fission yeast Schizosaccharomyces pombe has more metazoan-like features than the budding yeast Saccharomyces cerevisiae, yet it has similarly facile genetics. We present a large-scale verified binary protein-protein interactome network, "StressNet," based on high-throughput yeast two-hybrid screens of interacting proteins classified as part of stress response and signal transduction pathways in S. pombe. We performed systematic, cross-species interactome mapping using StressNet and a protein interactome network of orthologous proteins in S. cerevisiae. With cross-species comparative network studies, we detected a previously unidentified component (Snr1) of the S. pombe mitogen-activated protein kinase Sty1 pathway. Coimmunoprecipitation experiments showed that Snr1 interacted with Sty1 and that deletion of snr1 increased the sensitivity of S. pombe cells to stress. Comparison of StressNet with the interactome network of orthologous proteins in S. cerevisiae showed that most of the interactions among these stress response and signaling proteins are not conserved between species but are "rewired"; orthologous proteins have different binding partners in both species. In particular, transient interactions connecting proteins in different functional modules were more likely to be rewired than conserved. By directly testing interactions between proteins in one yeast species and their corresponding binding partners in the other yeast species with yeast two-hybrid assays, we found that about half of the interactions that are traditionally considered "conserved" form modified interaction interfaces that may potentially accommodate novel functions. PMID:23695164

  2. Synthetic Peptides as Protein Mimics

    PubMed Central

    Groß, Andrea; Hashimoto, Chie; Sticht, Heinrich; Eichler, Jutta

    2016-01-01

    The design and generation of molecules capable of mimicking the binding and/or functional sites of proteins represents a promising strategy for the exploration and modulation of protein function through controlled interference with the underlying molecular interactions. Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites because such peptides can be generated as exact copies of protein fragments, as well as in diverse chemical modifications, which includes the incorporation of a large range of non-proteinogenic amino acids as well as the modification of the peptide backbone. Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their utility for biological applications. This article reviews recent advances by this and other laboratories in the use of synthetic protein mimics to modulate protein function, as well as to provide building blocks for synthetic biology. PMID:26835447

  3. COLOMBOS v3.0: leveraging gene expression compendia for cross-species analyses

    PubMed Central

    Moretto, Marco; Sonego, Paolo; Dierckxsens, Nicolas; Brilli, Matteo; Bianco, Luca; Ledezma-Tejeida, Daniela; Gama-Castro, Socorro; Galardini, Marco; Romualdi, Chiara; Laukens, Kris; Collado-Vides, Julio; Meysman, Pieter; Engelen, Kristof

    2016-01-01

    COLOMBOS is a database that integrates publicly available transcriptomics data for several prokaryotic model organisms. Compared to the previous version it has more than doubled in size, both in terms of species and data available. The manually curated condition annotation has been overhauled as well, giving more complete information about samples’ experimental conditions and their differences. Functionality-wise cross-species analyses now enable users to analyse expression data for all species simultaneously, and identify candidate genes with evolutionary conserved expression behaviour. All the expression-based query tools have undergone a substantial improvement, overcoming the limit of enforced co-expression data retrieval and instead enabling the return of more complex patterns of expression behaviour. COLOMBOS is freely available through a web application at http://colombos.net/. The complete database is also accessible via REST API or downloadable as tab-delimited text files. PMID:26586805

  4. Microsatellite loci in the tiger shark and cross-species amplification using pyrosequencing technology.

    PubMed

    Mendes, Natália J; Cruz, Vanessa P; Ashikaga, Fernando Y; Camargo, Sâmia M; Oliveira, Claudio; Piercy, Andrew N; Burgess, George H; Coelho, Rui; Santos, Miguel N; Mendonça, Fernando F; Foresti, Fausto

    2016-01-01

    The tiger shark (Galeocerdo cuvier) has a global distribution in tropical and warm temperate seas, and it is caught in numerous fisheries worldwide, mainly as bycatch. It is currently assessed as near threatened by the International Union for Conservation of Nature (IUCN) Red List. In this study, we identified nine microsatellite loci through next generation sequencing (454 pyrosequencing) using 29 samples from the western Atlantic. The genetic diversity of these loci were assessed and revealed a total of 48 alleles ranging from 3 to 7 alleles per locus (average of 5.3 alleles). Cross-species amplification was successful at most loci for other species such as Carcharhinus longimanus, C. acronotus and Alopias superciliosus. Given the potential applicability of genetic markers for biological conservation, these data may contribute to the population assessment of this and other species of sharks worldwide. PMID:27635306

  5. Hepacivirus cross-species transmission and the origins of the hepatitis C virus.

    PubMed

    Pybus, Oliver G; Thézé, Julien

    2016-02-01

    Just 5 years ago the hepatitis C virus (HCV) - a major cause of liver disease infecting >3% of people worldwide - was the sole confirmed member of the Hepacivirus genus. Since then, genetically-diverse hepaciviruses have been isolated from bats, dogs, cows, horses, primates and rodents. Here we review current information on the hepaciviruses and speculate on the zoonotic origins of the viruses in humans, horses and dogs. Recent and direct cross-species transmission from horses to dogs appears plausible, but the zoonotic origins of HCV in humans remain opaque. Mechanical transmission by biting insects, notably tabanids, could, in theory, connect all three host species. Much further work is needed to understand the transmission and zoonotic potential of hepaciviruses in natural populations.

  6. Cross-species transmission and emergence of novel viruses from birds.

    PubMed

    Chan, Jasper Fuk-Woo; To, Kelvin Kai-Wang; Chen, Honglin; Yuen, Kwok-Yung

    2015-02-01

    Birds, the only living member of the Dinosauria clade, are flying warm-blooded vertebrates displaying high species biodiversity, roosting and migratory behavior, and a unique adaptive immune system. Birds provide the natural reservoir for numerous viral species and therefore gene source for evolution, emergence and dissemination of novel viruses. The intrusions of human into natural habitats of wild birds, the domestication of wild birds as pets or racing birds, and the increasing poultry consumption by human have facilitated avian viruses to cross species barriers to cause zoonosis. Recently, a novel adenovirus was exclusively found in birds causing an outbreak of Chlamydophila psittaci infection among birds and humans. Instead of being the primary cause of an outbreak by jumping directly from bird to human, a novel avian virus can be an augmenter of another zoonotic agent causing the outbreak. A comprehensive avian virome will improve our understanding of birds' evolutionary dynamics.

  7. Serologic survey for cross-species pathogens in urban coyotes (Canis latrans), Colorado, USA.

    PubMed

    Malmlov, Ashley; Breck, Stewart; Fry, Tricia; Duncan, Colleen

    2014-10-01

    Abstract As coyotes (Canis latrans) adapt to living in urban environments, the opportunity for cross-species transmission of pathogens may increase. We investigated the prevalence of antibodies to pathogens that are either zoonotic or affect multiple animal species in urban coyotes in the Denver metropolitan area, Colorado, USA, in 2012. We assayed for antibodies to canine parvovirus-2, canine distemper virus, rabies virus, Toxoplasma gondii, Yersinia pestis, and serotypes of Leptospira interrogans. Overall, 84% of the animals had antibodies to canine parvovirus-2, 44% for canine distemper virus, 20% for T. gondii (IgG), 28% for Y. pestis, and 4% for L. interrogans serotype Grippotyphosa. No neutralizing antibodies were detected to rabies virus, T. gondii (IgM), or L. interrogans serotypes other than Grippotyphosa. With 88% of animals exposed to at least one pathogen, our results suggest that coyotes may serve as important reservoirs and sentinels for etiologic agents.

  8. Cross-species fostering affects meat preferences of wild house mice.

    PubMed

    Wuensch, K L

    1993-10-01

    Wild-strain male house mice were fostered at birth onto conspecifics, deer mice, or domestic Norway rats. In adulthood, their flesh-eating preferences were tested by allowing them to feed from freshly asphyxiated conspecifics and either deer mice or rats. The mice ate significantly more conspecific flesh than contraspecific flesh, except when the flesh offered was that of the contraspecies upon which the mouse had been fostered at birth. The failure of cross-species-fostered mice to discriminate between their own species and their foster species in flesh-preference tests is attributed to their having learned early in life to respond to the foster species in the same way they normally respond to conspecifics, that is, by approaching them, investigating them, and, when finding them dead, feeding upon them. PMID:8189209

  9. Hepatitis B virus lineages in mammalian hosts: Potential for bidirectional cross-species transmission

    PubMed Central

    Bonvicino, Cibele R; Moreira, Miguel A; Soares, Marcelo A

    2014-01-01

    The hepatitis B virus (HBV) is a cosmopolitan infectious agent currently affecting over 350 million people worldwide, presently accounting for more than two billion infections. In addition to man, other hepatitis virus strains infect species of several mammalian families of the Primates, Rodentia and Chiroptera orders, in addition to birds. The mounting evidence of HBV infection in African, Asian and neotropical primates draws attention to the potential cross-species, zoonotic transmission of these viruses to man. Moreover, recent evidence also suggests the humans may also function as a source of viral infection to other mammals, particularly to domestic animals like poultry and swine. In this review, we list all evidence of HBV and HBV-like infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species. PMID:24976704

  10. Cross-Species Application of SNP Chips is Not Suitable for Identifying Runs of Homozygosity.

    PubMed

    Shafer, Aaron B A; Miller, Joshua M; Kardos, Marty

    2016-03-01

    Cross-species application of single-nucleotide polymorphism (SNP) chips is a valid, relatively cost-effective alternative to the high-throughput sequencing methods generally required to obtain a genome-wide sampling of polymorphisms. Kharzinova et al. (2015) examined the applicability of SNP chips developed in domestic bovids (cattle and sheep) to a semi-wild cervid (reindeer). The ancestors of bovids and cervids diverged between 20 and 30 million years ago (Hassanin and Douzery 2003; Bibi et al. 2013). Empirical work has shown that for a SNP chip developed in a bovid and applied to a cervid species, approximately 50% genotype success with 1% of the loci being polymorphic is expected (Miller et al. 2012). The genotyping of Kharzinova et al. (2015) follows this pattern; however, these data are not appropriate for identifying runs of homozygosity (ROH) and can be problematic for estimating linkage disequilibrium (LD) and we caution readers in this regard.

  11. Microsatellite loci in the tiger shark and cross-species amplification using pyrosequencing technology

    PubMed Central

    Mendes, Natália J.; Cruz, Vanessa P.; Ashikaga, Fernando Y.; Camargo, Sâmia M.; Oliveira, Claudio; Piercy, Andrew N.; Burgess, George H.; Coelho, Rui; Santos, Miguel N.; Foresti, Fausto

    2016-01-01

    The tiger shark (Galeocerdo cuvier) has a global distribution in tropical and warm temperate seas, and it is caught in numerous fisheries worldwide, mainly as bycatch. It is currently assessed as near threatened by the International Union for Conservation of Nature (IUCN) Red List. In this study, we identified nine microsatellite loci through next generation sequencing (454 pyrosequencing) using 29 samples from the western Atlantic. The genetic diversity of these loci were assessed and revealed a total of 48 alleles ranging from 3 to 7 alleles per locus (average of 5.3 alleles). Cross-species amplification was successful at most loci for other species such as Carcharhinus longimanus, C. acronotus and Alopias superciliosus. Given the potential applicability of genetic markers for biological conservation, these data may contribute to the population assessment of this and other species of sharks worldwide. PMID:27635306

  12. Microsatellite loci in the tiger shark and cross-species amplification using pyrosequencing technology

    PubMed Central

    Mendes, Natália J.; Cruz, Vanessa P.; Ashikaga, Fernando Y.; Camargo, Sâmia M.; Oliveira, Claudio; Piercy, Andrew N.; Burgess, George H.; Coelho, Rui; Santos, Miguel N.; Foresti, Fausto

    2016-01-01

    The tiger shark (Galeocerdo cuvier) has a global distribution in tropical and warm temperate seas, and it is caught in numerous fisheries worldwide, mainly as bycatch. It is currently assessed as near threatened by the International Union for Conservation of Nature (IUCN) Red List. In this study, we identified nine microsatellite loci through next generation sequencing (454 pyrosequencing) using 29 samples from the western Atlantic. The genetic diversity of these loci were assessed and revealed a total of 48 alleles ranging from 3 to 7 alleles per locus (average of 5.3 alleles). Cross-species amplification was successful at most loci for other species such as Carcharhinus longimanus, C. acronotus and Alopias superciliosus. Given the potential applicability of genetic markers for biological conservation, these data may contribute to the population assessment of this and other species of sharks worldwide.

  13. Karyotyping of Brachypodium pinnatum (2n = 18) chromosomes using cross-species BAC-FISH.

    PubMed

    Wolny, Elzbieta; Fidyk, Wojciech; Hasterok, Robert

    2013-04-01

    Identification of individual chromosomes in a complement is usually a difficult task in the case of most plant species, especially for those with small, numerous, and morphologically uniform chromosomes. In this paper, we demonstrate that the landmarks produced by cross-species fluorescence in situ hybridisation (FISH) of Brachypodium distachyon derived bacterial artificial chromosome (BAC) clones can be used for discrimination of Brachypodium pinnatum (2n = 18) chromosomes. Selected sets of clones were hybridised in several sequential experiments performed on exactly the same chromosome spreads, using reprobing of cytological preparations. Analysis of the morphometric features of B. pinnatum chromosomes was performed to establish their total length, the position of centromeres, and the position of BAC-based landmarks in relation to the centromere, thereby enabling their effective karyotyping, which is a prerequisite for more complex study of the grass genome structure and evolution at the cytomolecular level. PMID:23706077

  14. Cross-Species Application of SNP Chips is Not Suitable for Identifying Runs of Homozygosity.

    PubMed

    Shafer, Aaron B A; Miller, Joshua M; Kardos, Marty

    2016-03-01

    Cross-species application of single-nucleotide polymorphism (SNP) chips is a valid, relatively cost-effective alternative to the high-throughput sequencing methods generally required to obtain a genome-wide sampling of polymorphisms. Kharzinova et al. (2015) examined the applicability of SNP chips developed in domestic bovids (cattle and sheep) to a semi-wild cervid (reindeer). The ancestors of bovids and cervids diverged between 20 and 30 million years ago (Hassanin and Douzery 2003; Bibi et al. 2013). Empirical work has shown that for a SNP chip developed in a bovid and applied to a cervid species, approximately 50% genotype success with 1% of the loci being polymorphic is expected (Miller et al. 2012). The genotyping of Kharzinova et al. (2015) follows this pattern; however, these data are not appropriate for identifying runs of homozygosity (ROH) and can be problematic for estimating linkage disequilibrium (LD) and we caution readers in this regard. PMID:26774056

  15. Serologic survey for cross-species pathogens in urban coyotes (Canis latrans), Colorado, USA.

    PubMed

    Malmlov, Ashley; Breck, Stewart; Fry, Tricia; Duncan, Colleen

    2014-10-01

    Abstract As coyotes (Canis latrans) adapt to living in urban environments, the opportunity for cross-species transmission of pathogens may increase. We investigated the prevalence of antibodies to pathogens that are either zoonotic or affect multiple animal species in urban coyotes in the Denver metropolitan area, Colorado, USA, in 2012. We assayed for antibodies to canine parvovirus-2, canine distemper virus, rabies virus, Toxoplasma gondii, Yersinia pestis, and serotypes of Leptospira interrogans. Overall, 84% of the animals had antibodies to canine parvovirus-2, 44% for canine distemper virus, 20% for T. gondii (IgG), 28% for Y. pestis, and 4% for L. interrogans serotype Grippotyphosa. No neutralizing antibodies were detected to rabies virus, T. gondii (IgM), or L. interrogans serotypes other than Grippotyphosa. With 88% of animals exposed to at least one pathogen, our results suggest that coyotes may serve as important reservoirs and sentinels for etiologic agents. PMID:25121408

  16. ConSite: web-based prediction of regulatory elements using cross-species comparison.

    PubMed

    Sandelin, Albin; Wasserman, Wyeth W; Lenhard, Boris

    2004-07-01

    ConSite is a user-friendly, web-based tool for finding cis-regulatory elements in genomic sequences. Predictions are based on the integration of binding site prediction generated with high-quality transcription factor models and cross-species comparison filtering (phylogenetic footprinting). By incorporating evolutionary constraints, selectivity is increased by an order of magnitude as compared to single-sequence analysis. ConSite offers several unique features, including an interactive expert system for retrieving orthologous regulatory sequences. Programming modules and biological databases that form the foundation of the ConSite service are freely available to the research community. ConSite is available at http:/www.phylofoot.org/consite.

  17. Batesian mimics influence mimicry ring evolution.

    PubMed Central

    Franks, Daniel W.; Noble, Jason

    2004-01-01

    Mathematical models of mimicry typically involve artificial prey species with fixed colorations or appearances; this enables a comparison of predation rates to demonstrate the level of protection a mimic might be afforded. Fruitful theoretical results have been produced using this method, but it is also useful to examine the possible evolutionary consequences of mimicry. To that end, we present individual-based evolutionary simulation models where prey colorations are free to evolve. We use the models to examine the effect of Batesian mimics on Müllerian mimics and mimicry rings. Results show that Batesian mimics can potentially incite Müllerian mimicry relationships and encourage mimicry ring convergence. PMID:15058397

  18. Batesian mimics influence mimicry ring evolution.

    PubMed

    Franks, Daniel W; Noble, Jason

    2004-01-22

    Mathematical models of mimicry typically involve artificial prey species with fixed colorations or appearances; this enables a comparison of predation rates to demonstrate the level of protection a mimic might be afforded. Fruitful theoretical results have been produced using this method, but it is also useful to examine the possible evolutionary consequences of mimicry. To that end, we present individual-based evolutionary simulation models where prey colorations are free to evolve. We use the models to examine the effect of Batesian mimics on Müllerian mimics and mimicry rings. Results show that Batesian mimics can potentially incite Müllerian mimicry relationships and encourage mimicry ring convergence.

  19. Once a Batesian mimic, not always a Batesian mimic: mimic reverts back to ancestral phenotype when the model is absent.

    PubMed

    Prudic, Kathleen L; Oliver, Jeffrey C

    2008-05-22

    Batesian mimics gain protection from predation through the evolution of physical similarities to a model species that possesses anti-predator defences. This protection should not be effective in the absence of the model since the predator does not identify the mimic as potentially dangerous and both the model and the mimic are highly conspicuous. Thus, Batesian mimics should probably encounter strong predation pressure outside the geographical range of the model species. There are several documented examples of Batesian mimics occurring in locations without their models, but the evolutionary responses remain largely unidentified. A mimetic species has four alternative evolutionary responses to the loss of model presence. If predation is weak, it could maintain its mimetic signal. If predation is intense, it is widely presumed the mimic will go extinct. However, the mimic could also evolve a new colour pattern to mimic another model species or it could revert back to its ancestral, less conspicuous phenotype. We used molecular phylogenetic approaches to reconstruct and test the evolution of mimicry in the North American admiral butterflies (Limenitis: Nymphalidae). We confirmed that the more cryptic white-banded form is the ancestral phenotype of North American admiral butterflies. However, one species, Limenitis arthemis, evolved the black pipevine swallowtail mimetic form but later reverted to the white-banded more cryptic ancestral form. This character reversion is strongly correlated with the geographical absence of the model species and its host plant, but not the host plant distribution of L. arthemis. Our results support the prediction that a Batesian mimic does not persist in locations without its model, but it does not go extinct either. The mimic can revert back to its ancestral, less conspicuous form and persist.

  20. Evolution of genome organizations of squirrels (Sciuridae) revealed by cross-species chromosome painting.

    PubMed

    Li, Tangliang; O'Brien, Patricia C M; Biltueva, Larisa; Fu, Beiyuan; Wang, Jinhuan; Nie, Wenhui; Ferguson-Smith, Malcolm A; Graphodatsky, Alexander S; Yang, Fengtang

    2004-01-01

    With complete sets of chromosome-specific painting probes derived from flow-sorted chromosomes of human and grey squirrel (Sciurus carolinensis), the whole genome homologies between human and representatives of tree squirrels (Sciurus carolinensis, Callosciurus erythraeus), flying squirrels (Petaurista albiventer) and chipmunks (Tamias sibiricus) have been defined by cross-species chromosome painting. The results show that, unlike the highly rearranged karyotypes of mouse and rat, the karyotypes of squirrels are highly conserved. Two methods have been used to reconstruct the genome phylogeny of squirrels with the laboratory rabbit (Oryctolagus cuniculus) as the out-group: (1) phylogenetic analysis by parsimony using chromosomal characters identified by comparative cytogenetic approaches; (2) mapping the genome rearrangements onto recently published sequence-based molecular trees. Our chromosome painting results, in combination with molecular data, show that flying squirrels are phylogenetically close to New World tree squirrels. Chromosome painting and G-banding comparisons place chipmunks (Tamias sibiricus ), with a derived karyotype, outside the clade comprising tree and flying squirrels. The superorder Glires (orde Rodentia + order Lagomorpha) is firmly supported by two conserved syntenic associations between human chromosomes 1 and 10p homologues, and between 9 and 11 homologues. PMID:15241012

  1. Cross-species transferability of SSR loci developed from transciptome sequencing in lodgepole pine.

    PubMed

    Lesser, Mark R; Parchman, Thomas L; Buerkle, C Alex

    2012-05-01

    With the advent of next generation sequencing technologies, transcriptome level sequence collections are arising as prominent resources for the discovery of gene-based molecular markers. In a previous study more than 15,000 simple sequence repeats (SSRs) in expressed sequence tag (EST) sequences resulting from 454 pyrosequencing of Pinus contorta cDNA were identified. From these we developed PCR primers for approximately 4000 candidate SSRs. Here, we tested 184 of these SSRs for successful amplification across P. contorta and eight other pine species and examined patterns of polymorphism and allelic variability for a subset of these SSRs. Cross-species transferability was high, with high percentages of loci producing PCR products in all species tested. In addition, 50% of the loci we screened across panels of individuals from three of these species were polymorphic and allelically diverse. We examined levels of diversity in a subset of these SSRs by collecting genotypic data across several populations of Pinus ponderosa in northern Wyoming. Our results indicate the utility of mining pyrosequenced EST collections for gene-based SSRs and provide a source of molecular markers that should bolster evolutionary genetic investigations across the genus Pinus. PMID:22171820

  2. Human prion protein sequence elements impede cross-species chronic wasting disease transmission.

    PubMed

    Kurt, Timothy D; Jiang, Lin; Fernández-Borges, Natalia; Bett, Cyrus; Liu, Jun; Yang, Tom; Spraker, Terry R; Castilla, Joaquín; Eisenberg, David; Kong, Qingzhong; Sigurdson, Christina J

    2015-04-01

    Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission. PMID:25705888

  3. Cross-species fertilization: the hamster egg receptor, Juno, binds the human sperm ligand, Izumo1.

    PubMed

    Bianchi, Enrica; Wright, Gavin J

    2015-02-01

    Fertilization is the culminating event in sexual reproduction and requires the recognition and fusion of the haploid sperm and egg to form a new diploid organism. Specificity in these recognition events is one reason why sperm and eggs from different species are not normally compatible. One notable exception is the unusual ability of zona-free eggs from the Syrian golden hamster (Mesocricetus auratus) to recognize and fuse with human sperm, a phenomenon that has been exploited to assess sperm quality in assisted fertility treatments. Following our recent finding that the interaction between the sperm and egg recognition receptors Izumo1 and Juno is essential for fertilization, we now demonstrate concordance between the ability of Izumo1 and Juno from different species to interact, and the ability of their isolated gametes to cross-fertilize each other in vitro. In particular, we show that Juno from the golden hamster can directly interact with human Izumo1. These data suggest that the interaction between Izumo1 and Juno plays an important role in cross-species gamete recognition, and may inform the development of improved prognostic tests that do not require the use of animals to guide the most appropriate fertility treatment for infertile couples.

  4. Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study

    PubMed Central

    Wang, Yingying; Cai, Yunpeng

    2016-01-01

    Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases. PMID:27407070

  5. Measurement of lentiviral vector titre and copy number by cross-species duplex quantitative PCR.

    PubMed

    Christodoulou, I; Patsali, P; Stephanou, C; Antoniou, M; Kleanthous, M; Lederer, C W

    2016-01-01

    Lentiviruses are the vectors of choice for many preclinical studies and clinical applications of gene therapy. Accurate measurement of biological vector titre before treatment is a prerequisite for vector dosing, and the calculation of vector integration sites per cell after treatment is as critical to the characterisation of modified cell products as it is to long-term follow-up and the assessment of risk and therapeutic efficiency in patients. These analyses are typically based on quantitative real-time PCR (qPCR), but as yet compromise accuracy and comparability between laboratories and experimental systems, the former by using separate simplex reactions for the detection of endogene and lentiviral sequences and the latter by designing different PCR assays for analyses in human cells and animal disease models. In this study, we validate in human and murine cells a qPCR system for the single-tube assessment of lentiviral vector copy numbers that is suitable for analyses in at least 33 different mammalian species, including human and other primates, mouse, pig, cat and domestic ruminants. The established assay combines the accuracy of single-tube quantitation by duplex qPCR with the convenience of one-off assay optimisation for cross-species analyses and with the direct comparability of lentiviral transduction efficiencies in different species. PMID:26202078

  6. Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms.

    PubMed

    Claussnitzer, Melina; Dankel, Simon N; Klocke, Bernward; Grallert, Harald; Glunk, Viktoria; Berulava, Tea; Lee, Heekyoung; Oskolkov, Nikolay; Fadista, Joao; Ehlers, Kerstin; Wahl, Simone; Hoffmann, Christoph; Qian, Kun; Rönn, Tina; Riess, Helene; Müller-Nurasyid, Martina; Bretschneider, Nancy; Schroeder, Timm; Skurk, Thomas; Horsthemke, Bernhard; Spieler, Derek; Klingenspor, Martin; Seifert, Martin; Kern, Michael J; Mejhert, Niklas; Dahlman, Ingrid; Hansson, Ola; Hauck, Stefanie M; Blüher, Matthias; Arner, Peter; Groop, Leif; Illig, Thomas; Suhre, Karsten; Hsu, Yi-Hsiang; Mellgren, Gunnar; Hauner, Hans; Laumen, Helmut

    2014-01-16

    Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.

  7. Multidirectional cross-species painting illuminates the history of karyotypic evolution in Perissodactyla.

    PubMed

    Trifonov, Vladimir A; Stanyon, Roscoe; Nesterenko, Anastasia I; Fu, Beiyuan; Perelman, Polina L; O'Brien, Patricia C M; Stone, Gary; Rubtsova, Nadezhda V; Houck, Marlys L; Robinson, Terence J; Ferguson-Smith, Malcolm A; Dobigny, Gauthier; Graphodatsky, Alexander S; Yang, Fengtang

    2008-01-01

    The order Perissodactyla, the group of odd-toed ungulates, includes three extant families: Equidae, Tapiridae, and Rhinocerotidae. The extremely rapid karyotypic diversification in perissodactyls has so far prevented the establishment of genome-wide homology maps between these three families by traditional cytogenetic approaches. Here we report the first genome-wide comparative chromosome maps of African rhinoceroses, four tapir species, four equine species, and humans. These maps were established by multidirectional chromosome painting, with paint probes derived from flow-sorted chromosomes of Equus grevyi, Tapirus indicus, and Ceratotherium simum as well as painting probes from horse and human. The Malayan tapir (Tapirus indicus), Baird's tapir (T. bairdii), mountain tapir (T. pinchaque), lowland tapir (T. terrestris), and onager (E. hemionus onager), were studied by cross-species chromosome painting for the first time. Our results, when integrated with previously published comparative chromosome maps of the other perissodactyl species, have enabled the reconstruction of perissodactyl, ceratomorph, and equid ancestral karyotypes, and the identification of the defining evolutionary chromosomal rearrangements along each lineage. Our results allow a more reliable estimate of the mode and tempo of evolutionary chromosomal rearrangements, revealing a striking switch between the slowly evolving ceratomorphs and extremely rapidly evolving equids.

  8. Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms.

    PubMed

    Claussnitzer, Melina; Dankel, Simon N; Klocke, Bernward; Grallert, Harald; Glunk, Viktoria; Berulava, Tea; Lee, Heekyoung; Oskolkov, Nikolay; Fadista, Joao; Ehlers, Kerstin; Wahl, Simone; Hoffmann, Christoph; Qian, Kun; Rönn, Tina; Riess, Helene; Müller-Nurasyid, Martina; Bretschneider, Nancy; Schroeder, Timm; Skurk, Thomas; Horsthemke, Bernhard; Spieler, Derek; Klingenspor, Martin; Seifert, Martin; Kern, Michael J; Mejhert, Niklas; Dahlman, Ingrid; Hansson, Ola; Hauck, Stefanie M; Blüher, Matthias; Arner, Peter; Groop, Leif; Illig, Thomas; Suhre, Karsten; Hsu, Yi-Hsiang; Mellgren, Gunnar; Hauner, Hans; Laumen, Helmut

    2014-01-16

    Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms. PMID:24439387

  9. Human prion protein sequence elements impede cross-species chronic wasting disease transmission

    PubMed Central

    Kurt, Timothy D.; Jiang, Lin; Fernández-Borges, Natalia; Bett, Cyrus; Liu, Jun; Yang, Tom; Spraker, Terry R.; Castilla, Joaquín; Eisenberg, David; Kong, Qingzhong; Sigurdson, Christina J.

    2015-01-01

    Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165–175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165–175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission. PMID:25705888

  10. Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis.

    PubMed

    Berthier, Celine C; Bethunaickan, Ramalingam; Gonzalez-Rivera, Tania; Nair, Viji; Ramanujam, Meera; Zhang, Weijia; Bottinger, Erwin P; Segerer, Stephan; Lindenmeyer, Maja; Cohen, Clemens D; Davidson, Anne; Kretzler, Matthias

    2012-07-15

    Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these preclinical models. In this study, we used an unbiased transcriptional network approach to define, in molecular terms, similarities and differences among three lupus models and human LN. Genome-wide gene-expression networks were generated using natural language processing and automated promoter analysis and compared across species via suboptimal graph matching. The three murine models and human LN share both common and unique features. The 20 commonly shared network nodes reflect the key pathologic processes of immune cell infiltration/activation, endothelial cell activation/injury, and tissue remodeling/fibrosis, with macrophage/dendritic cell activation as a dominant cross-species shared transcriptional pathway. The unique nodes reflect differences in numbers and types of infiltrating cells and degree of remodeling among the three mouse strains. To define mononuclear phagocyte-derived pathways in human LN, gene sets activated in isolated NZB/W renal mononuclear cells were compared with human LN kidney profiles. A tissue compartment-specific macrophage-activation pattern was seen, with NF-κB1 and PPARγ as major regulatory nodes in the tubulointerstitial and glomerular networks, respectively. Our study defines which pathologic processes in murine models of LN recapitulate the key transcriptional processes active in human LN and suggests that there are functional differences between mononuclear phagocytes infiltrating different renal microenvironments.

  11. Polymorphic microsatellite loci identified through development and cross-species amplification within shorebirds

    USGS Publications Warehouse

    Williams, I.; Guzzetti, B.M.; Gust, J.R.; Sage, G.K.; Gill, R.E.; Tibbitts, T.L.; Sonsthagen, S.A.; Talbot, S.L.

    2012-01-01

    We developed microsatellite loci for demographic assessments of shorebirds, a group with limited markers. First, we isolated five dinucleotide repeat microsatellite loci from the Black Oystercatcher (Haematopodidae: Haematopus bachmani), and three from the Bristle-thighed Curlew (Scolopacidae: Numenius tahitiensis); both species are of conservation concern. All eight loci were polymorphic in their respective target species. Hbaμ loci were characterized by two to three alleles with observed heterozygosity ranging from 0.07 to 0.33, and two to nine alleles were detected for Nut loci with observed heterozygosity ranging from 0.08 to 0.72. No linkage disequilibrium or departures from Hardy–Weinberg equilibrium were observed. The eight loci were also tested for cross-species amplification in 12 other species within Charadriidae and Scolopacidae, and the results demonstrated transferability across several genera. We further tested all 14 species at 12 additional microsatellite markers developed for other shorebirds: Dunlin (Calidris alpina; four loci) and Ruff (Philomachus pugnax; eight loci). Two markers (Hbaμ4 and Ruff6) were polymorphic in 13 species, while two (Calp6 and Ruff9) were monomorphic. The remaining eight markers revealed polymorphism in one to nine species each. Our results provide further evidence that locus Ruff10 is sex-linked, contrary to the initial description. These markers can be used to enhance our understanding of shorebird biology by, for example, helping to determine migratory connectivity among breeding and wintering populations and detecting relatedness among individuals.

  12. Role of multiple hosts in the cross-species transmission and emergence of a pandemic parvovirus.

    PubMed

    Allison, Andrew B; Harbison, Carole E; Pagan, Israel; Stucker, Karla M; Kaelber, Jason T; Brown, Justin D; Ruder, Mark G; Keel, M Kevin; Dubovi, Edward J; Holmes, Edward C; Parrish, Colin R

    2012-01-01

    Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV-2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence.

  13. Cross-Species Extrapolation of Models for Predicting Lead Transfer from Soil to Wheat Grain

    PubMed Central

    Liu, Ke; Lv, Jialong; Dai, Yunchao; Zhang, Hong; Cao, Yingfei

    2016-01-01

    The transfer of Pb from the soil to crops is a serious food hygiene security problem in China because of industrial, agricultural, and historical contamination. In this study, the characteristics of exogenous Pb transfer from 17 Chinese soils to a popular wheat variety (Xiaoyan 22) were investigated. In addition, bioaccumulation prediction models of Pb in grain were obtained based on soil properties. The results of the analysis showed that pH and OC were the most important factors contributing to Pb uptake by wheat grain. Using a cross-species extrapolation approach, the Pb uptake prediction models for cultivar Xiaoyan 22 in different soil Pb levels were satisfactorily applied to six additional non-modeled wheat varieties to develop a prediction model for each variety. Normalization of the bioaccumulation factor (BAF) to specific soil physico-chemistry is essential, because doing so could significantly reduce the intra-species variation of different wheat cultivars in predicted Pb transfer and eliminate the influence of soil properties on ecotoxicity parameters for organisms of interest. Finally, the prediction models were successfully verified against published data (including other wheat varieties and crops) and used to evaluate the ecological risk of Pb for wheat in contaminated agricultural soils. PMID:27518712

  14. CO2 exposure as translational cross-species experimental model for panic

    PubMed Central

    Leibold, N K; van den Hove, D L A; Viechtbauer, W; Buchanan, G F; Goossens, L; Lange, I; Knuts, I; Lesch, K P; Steinbusch, H W M; Schruers, K R J

    2016-01-01

    The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral–emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies. PMID:27598969

  15. Crossing species barrier by PrPSc replication in vitro generates new infectious prions

    PubMed Central

    Castilla, Joaquín; Gonzalez-Romero, Dennisse; Saá, Paula; Morales, Rodrigo; De Castro, Jorge; Soto, Claudio

    2008-01-01

    Summary Prions are unconventional infectious agents composed exclusively by the misfolded prion protein (PrPSc), which transmits the disease by propagating its abnormal conformation to the cellular prion protein (PrPC). A key characteristic of prions is their species barrier, by which prions from one species can only infect a limited number of other species. Here we report the generation of novel infectious prions by inter-species transmission of PrPSc misfolding in vitro. Hamster PrPC misfolded by mixing with mouse PrPSc generated new prions that were infectious to wild type hamsters. Similarly, new mouse prions were generated by crossing the species barrier in the opposite direction. A detailed characterization of the infectious, biochemical and histological properties of the disease produced indicate that the in vitro generated material across the species barrier correspond to new prion strains. Successive rounds of PMCA amplification result in a progressive adaptation of the in vitro produced prions, in a process reminiscent to the strain stabilization process observed upon serial passage in vivo. Our results indicate that PMCA is a valuable tool to investigate cross-species transmission and suggest that species barrier and strain generation are determined by the propagation of PrP misfolding. PMID:18775309

  16. Anxiety genetics – findings from cross-species genome-wide approaches

    PubMed Central

    2013-01-01

    Anxiety disorders are complex diseases, which often occur in combination with major depression, alcohol use disorder, or general medical conditions. Anxiety disorders were the most common mental disorders within the EU states in 2010 with 14% prevalence. Anxiety disorders are triggered by environmental factors in genetically susceptible individuals, and therefore genetic research offers a great route to unravel molecular basis of these diseases. As anxiety is an evolutionarily conserved response, mouse models can be used to carry out genome-wide searches for specific genes in a setting that controls for the environmental factors. In this review, we discuss translational approaches that aim to bridge results from unbiased genome-wide screens using mouse models to anxiety disorders in humans. Several methods, such as quantitative trait locus mapping, gene expression profiling, and proteomics, have been used in various mouse models of anxiety to identify genes that regulate anxiety or play a role in maintaining pathological anxiety. We first discuss briefly the evolutionary background of anxiety, which justifies cross-species approaches. We then describe how several genes have been identified through genome-wide methods in mouse models and subsequently investigated in human anxiety disorder samples as candidate genes. These studies have led to the identification of completely novel biological pathways that regulate anxiety in mice and humans, and that can be further investigated as targets for therapy. PMID:23659354

  17. Cross-Species Extrapolation of Models for Predicting Lead Transfer from Soil to Wheat Grain.

    PubMed

    Liu, Ke; Lv, Jialong; Dai, Yunchao; Zhang, Hong; Cao, Yingfei

    2016-01-01

    The transfer of Pb from the soil to crops is a serious food hygiene security problem in China because of industrial, agricultural, and historical contamination. In this study, the characteristics of exogenous Pb transfer from 17 Chinese soils to a popular wheat variety (Xiaoyan 22) were investigated. In addition, bioaccumulation prediction models of Pb in grain were obtained based on soil properties. The results of the analysis showed that pH and OC were the most important factors contributing to Pb uptake by wheat grain. Using a cross-species extrapolation approach, the Pb uptake prediction models for cultivar Xiaoyan 22 in different soil Pb levels were satisfactorily applied to six additional non-modeled wheat varieties to develop a prediction model for each variety. Normalization of the bioaccumulation factor (BAF) to specific soil physico-chemistry is essential, because doing so could significantly reduce the intra-species variation of different wheat cultivars in predicted Pb transfer and eliminate the influence of soil properties on ecotoxicity parameters for organisms of interest. Finally, the prediction models were successfully verified against published data (including other wheat varieties and crops) and used to evaluate the ecological risk of Pb for wheat in contaminated agricultural soils. PMID:27518712

  18. Development of polymorphic SSR markers in the razor clam (Sinonovacula constricta) and cross-species amplification.

    PubMed

    Dong, Y H; Yao, H H; Sun, C S; Lv, D M; Li, M Q; Lin, Z H

    2016-01-01

    Next-generation sequencing provides large-scale sequencing data with relative ease and at a reasonable cost, making it possible to identify a large amount of SSR markers in a timely and cost-effective manner. On the basis of the transcriptome database of Sinonovacula constricta obtained by Illumina/Solexa pyrosequencing, 60 polymorphic SSR markers were developed and characterized in 30 individuals. The number of alleles per polymorphic locus ranged from 2 to 7 with an average of 3.75 alleles. The observed and expected heterozygosities varied from 0.050 to 1.000 and from 0.050 to 0.836, respectively. Nineteen loci significantly deviated from Hardy-Weinberg equilibrium (P < 0.01) after Bonferroni's correction for multiple tests. In addition, interspecific transferability revealed that 20 polymorphic loci in Solen linearis were first characterized in this study. To the best of our knowledge, this is the highest number of SSRs in S. constricta and the first report of cross-species amplification. These novel polymorphic SSR markers will be particularly useful for conservation genetics, evolutionary studies, genetic trait mapping, and marker assisted selection in the species. PMID:26909924

  19. Aleutian mink disease virus in striped skunks (Mephitis mephitis): evidence for cross-species spillover.

    PubMed

    Nituch, Larissa A; Bowman, Jeff; Wilson, Paul J; Schulte-Hostedde, Albrecht I

    2015-04-01

    Aleutian mink disease virus (AMDV) causes a parvovirus infection, initially characterized in American mink (Neovison vison), that may have harmful effects on wild populations of susceptible animals. In North America, where American mink are native, the origin, host range, and prevalence of AMDV in wild species is not clear. We studied striped skunks (Mephitis mephitis) and raccoons (Procyon lotor) to determine whether species sympatric with mink are potential reservoirs in the transmission of AMDV to wild mink and mink farms. Antibodies to AMDV were detected in 41% of skunk serum samples (143/347) and AMDV nucleic acids were detected in 32% (14/40) of skunk spleen samples by PCR, indicating that AMDV exposure and infection were frequent in skunks. We detected no AMDV antibodies in 144 raccoon blood samples. Phylogenetic analysis revealed a newly identified AMDV haplogroup consisting of isolates from Ontario skunks and a free-ranging domestic mink from Ontario. Our findings of frequent AMDV infection in skunks, close genetic similarity between skunk and mink AMDV isolates, and evidence of AMDV transmission from skunks to mink support the hypothesis that skunks may be acting as alternative hosts and reservoirs of AMDV to wild mink through cross-species virus spillover. PMID:25647590

  20. CO2 exposure as translational cross-species experimental model for panic.

    PubMed

    Leibold, N K; van den Hove, D L A; Viechtbauer, W; Buchanan, G F; Goossens, L; Lange, I; Knuts, I; Lesch, K P; Steinbusch, H W M; Schruers, K R J

    2016-01-01

    The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral-emotional and bodily response to CO2 exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO2 exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO2, demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies. PMID:27598969

  1. Superinfection reconciles host-parasite association and cross-species transmission.

    PubMed

    Haven, James; Park, Andrew William

    2013-12-01

    Parasites are either dedicated to a narrow host range, or capable of exploiting a wide host range. Understanding how host ranges are determined is very important for public health, as well as wildlife, plant, livestock and agricultural diseases. Our current understanding of host-parasite associations hinges on co-evolution, which assumes evolved host preferences (host specialization) of the parasite. Despite the explanatory power of this framework, we have only a vague understanding of why many parasites routinely cross the host species' barrier. Here we introduce a simple model demonstrating how superinfection (in a heterogeneous community) can promote host-parasite association. Strikingly, the model illustrates that strong host-parasite association occurs in the absence of host specialization, while still permitting cross-species transmission. For decades, host specialization has been foundational in explaining the maintenance of distinct parasites/strains in host species. We argue that host specializations may be exaggerated, and can occur as a byproduct (not necessarily the cause) of host-parasite associations. PMID:24161558

  2. Development of polymorphic SSR markers in the razor clam (Sinonovacula constricta) and cross-species amplification.

    PubMed

    Dong, Y H; Yao, H H; Sun, C S; Lv, D M; Li, M Q; Lin, Z H

    2016-01-01

    Next-generation sequencing provides large-scale sequencing data with relative ease and at a reasonable cost, making it possible to identify a large amount of SSR markers in a timely and cost-effective manner. On the basis of the transcriptome database of Sinonovacula constricta obtained by Illumina/Solexa pyrosequencing, 60 polymorphic SSR markers were developed and characterized in 30 individuals. The number of alleles per polymorphic locus ranged from 2 to 7 with an average of 3.75 alleles. The observed and expected heterozygosities varied from 0.050 to 1.000 and from 0.050 to 0.836, respectively. Nineteen loci significantly deviated from Hardy-Weinberg equilibrium (P < 0.01) after Bonferroni's correction for multiple tests. In addition, interspecific transferability revealed that 20 polymorphic loci in Solen linearis were first characterized in this study. To the best of our knowledge, this is the highest number of SSRs in S. constricta and the first report of cross-species amplification. These novel polymorphic SSR markers will be particularly useful for conservation genetics, evolutionary studies, genetic trait mapping, and marker assisted selection in the species.

  3. Aleutian mink disease virus in striped skunks (Mephitis mephitis): evidence for cross-species spillover.

    PubMed

    Nituch, Larissa A; Bowman, Jeff; Wilson, Paul J; Schulte-Hostedde, Albrecht I

    2015-04-01

    Aleutian mink disease virus (AMDV) causes a parvovirus infection, initially characterized in American mink (Neovison vison), that may have harmful effects on wild populations of susceptible animals. In North America, where American mink are native, the origin, host range, and prevalence of AMDV in wild species is not clear. We studied striped skunks (Mephitis mephitis) and raccoons (Procyon lotor) to determine whether species sympatric with mink are potential reservoirs in the transmission of AMDV to wild mink and mink farms. Antibodies to AMDV were detected in 41% of skunk serum samples (143/347) and AMDV nucleic acids were detected in 32% (14/40) of skunk spleen samples by PCR, indicating that AMDV exposure and infection were frequent in skunks. We detected no AMDV antibodies in 144 raccoon blood samples. Phylogenetic analysis revealed a newly identified AMDV haplogroup consisting of isolates from Ontario skunks and a free-ranging domestic mink from Ontario. Our findings of frequent AMDV infection in skunks, close genetic similarity between skunk and mink AMDV isolates, and evidence of AMDV transmission from skunks to mink support the hypothesis that skunks may be acting as alternative hosts and reservoirs of AMDV to wild mink through cross-species virus spillover.

  4. Novel Microsatellite Markers of Meretrix petechialis and Cross-species Amplification in Related Taxa (Bivalvia: Veneroida)

    PubMed Central

    Kang, Jung-Ha; Kim, Byeng-Hak; Park, Jung-Youn; Lee, Jung-Mi; Jeong, Ji-Eun; Lee, Jun-Sang; Ko, Hyun-Sook; Lee, Yong-Seok

    2012-01-01

    The Asian hard clam, Meretrix petechialis, is an economically important bivalve, but its catch and population sizes are decreasing rapidly, owing to many factors, including large-scale reclamation of its natural habitat on the western coast of the Korean peninsula. Attempts to restore the resources and production of this species require genetic structure and diversity information. In this study, we developed 15 microsatellite markers from a partial genomic library enriched in GT repeats. Nine of these markers were polymorphic, with an average allele number of six, and six were monomorphic in 95 tested individuals. No linkage disequilibrium was found between any pair of loci (p > 0.05), and deviations from the Hardy–Weinberg equilibrium (HWE) test showing excess of heterozygotes was observed in only one of nine loci. In addition, no null alleles or genetic differentiation between two tested populations were detected. A cross-species amplification in 12 species of four families resulted in two M. petechialis-specific loci and three possible universal markers. This information will be useful in the future development of high-quality artificial seedlings and sustainable resource management. PMID:23443103

  5. Karyotypic relationships of horses and zebras: results of cross-species chromosome painting.

    PubMed

    Yang, F; Fu, B; O'Brien, P C M; Robinson, T J; Ryder, O A; Ferguson-Smith, M A

    2003-01-01

    Complete sets of chromosome-specific painting probes, derived from flow-sorted chromosomes of human (HSA), Equus caballus (ECA) and Equus burchelli (EBU) were used to delineate conserved chromosomal segments between human and Equus burchelli, and among four equid species, E. przewalskii (EPR), E. caballus, E. burchelli and E. zebra hartmannae (EZH) by cross-species chromosome painting. Genome-wide comparative maps between these species have been established. Twenty-two human autosomal probes revealed 48 conserved segments in E. burchelli. The adjacent segment combinations HSA3/21, 7/16p, 16q/19q, 14/15, 12/22 and 4/8, presumed ancestral syntenies for all eutherian mammals, were also found conserved in E. burchelli. The comparative maps of equids allow for the unequivocal characterization of chromosomal rearrangements that differentiate the karyotypes of these equid species. The karyotypes of E. przewalskii and E. caballus differ by one Robertsonian translocation (ECA5 = EPR23 + EPR24); numerous Robertsonian translocations and tandem fusions and several inversions account for the karyotypic differences between the horses and zebras. Our results shed new light on the karyotypic evolution of Equidae.

  6. Cross-species fertilization: the hamster egg receptor, Juno, binds the human sperm ligand, Izumo1

    PubMed Central

    Bianchi, Enrica; Wright, Gavin J.

    2015-01-01

    Fertilization is the culminating event in sexual reproduction and requires the recognition and fusion of the haploid sperm and egg to form a new diploid organism. Specificity in these recognition events is one reason why sperm and eggs from different species are not normally compatible. One notable exception is the unusual ability of zona-free eggs from the Syrian golden hamster (Mesocricetus auratus) to recognize and fuse with human sperm, a phenomenon that has been exploited to assess sperm quality in assisted fertility treatments. Following our recent finding that the interaction between the sperm and egg recognition receptors Izumo1 and Juno is essential for fertilization, we now demonstrate concordance between the ability of Izumo1 and Juno from different species to interact, and the ability of their isolated gametes to cross-fertilize each other in vitro. In particular, we show that Juno from the golden hamster can directly interact with human Izumo1. These data suggest that the interaction between Izumo1 and Juno plays an important role in cross-species gamete recognition, and may inform the development of improved prognostic tests that do not require the use of animals to guide the most appropriate fertility treatment for infertile couples. PMID:25533103

  7. Cross-Species Comparison of Genes Related to Nutrient Sensing Mechanisms Expressed along the Intestine

    PubMed Central

    van der Wielen, Nikkie; van Avesaat, Mark; de Wit, Nicole J. W.; Vogels, Jack T. W. E.; Troost, Freddy; Masclee, Ad; Koopmans, Sietse-Jan; van der Meulen, Jan; Boekschoten, Mark V.; Müller, Michael; Hendriks, Henk F. J.; Witkamp, Renger F.; Meijerink, Jocelijn

    2014-01-01

    Introduction Intestinal chemosensory receptors and transporters are able to detect food-derived molecules and are involved in the modulation of gut hormone release. Gut hormones play an important role in the regulation of food intake and the control of gastrointestinal functioning. This mechanism is often referred to as “nutrient sensing”. Knowledge of the distribution of chemosensors along the intestinal tract is important to gain insight in nutrient detection and sensing, both pivotal processes for the regulation of food intake. However, most knowledge is derived from rodents, whereas studies in man and pig are limited, and cross-species comparisons are lacking. Aim To characterize and compare intestinal expression patterns of genes related to nutrient sensing in mice, pigs and humans. Methods Mucosal biopsy samples taken at six locations in human intestine (n = 40) were analyzed by qPCR. Intestinal scrapings from 14 locations in pigs (n = 6) and from 10 locations in mice (n = 4) were analyzed by qPCR and microarray, respectively. The gene expression of glucagon, cholecystokinin, peptide YY, glucagon-like peptide-1 receptor, taste receptor T1R3, sodium/glucose cotransporter, peptide transporter-1, GPR120, taste receptor T1R1, GPR119 and GPR93 was investigated. Partial least squares (PLS) modeling was used to compare the intestinal expression pattern between the three species. Results and conclusion The studied genes were found to display specific expression patterns along the intestinal tract. PLS analysis showed a high similarity between human, pig and mouse in the expression of genes related to nutrient sensing in the distal ileum, and between human and pig in the colon. The gene expression pattern was most deviating between the species in the proximal intestine. Our results give new insights in interspecies similarities and provide new leads for translational research and models aiming to modulate food intake processes in man. PMID:25216051

  8. Cross-species transcriptomic approach reveals genes in hamster implantation sites.

    PubMed

    Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

    2014-12-01

    The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS.

  9. Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages.

    PubMed

    Zhuo, Xiaoyu; Feschotte, Cédric

    2015-01-01

    Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13-25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts. PMID

  10. Ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission.

    PubMed

    Borucki, Monica K; Chen-Harris, Haiyin; Lao, Victoria; Vanier, Gilda; Wadford, Debra A; Messenger, Sharon; Allen, Jonathan E

    2013-11-01

    One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change. PMID:24278493

  11. Development, characterization, and cross-species/genera transferability of SSR markers for rubber tree (Hevea brasiliensis).

    PubMed

    Yu, Fei; Wang, Bao-Hua; Feng, Su-Ping; Wang, Jing-Yi; Li, Wei-Guo; Wu, Yao-Ting

    2011-03-01

    Genomic simple sequence repeat (SSR) markers are particularly valuable in studies of genetic diversity, evolution, genetic linkage map construction, quantitative trait loci tagging, and marker-assisted selection because of their multi-allelic nature, reproducibility, co-dominant inheritance, high abundance, and extensive genome coverage. The traditional methods of SSR marker development, such as genomic-SSR hybrid screening and microsatellite enrichment, have the disadvantages of high cost and complex operation. The selectively amplified microsatellite method is less costly and highly efficient as well as being simple and convenient. In this study, 252 sequences with SSRs were cloned from the rubber tree (Hevea brasiliensis) genome from which 258 SSR loci were obtained. The average repeat number was six. There were only 10 (3.9%) mononucleotide, trinucleotide, and pentanucleotide repeats, whereas the remaining 248 (96.1%) were dinucleotide repeats, including 128 (49.6%) GT/CA repeats, 118 (45.7%) GA/CT repeats, and 2 (0.8%) AT/TA repeats. A total of 126 primer pairs (see ESM) were successfully designed of which 36 primer pairs generated polymorphic products from 12 accessions of the cultivated species, 4 related species, and 3 species of the family Euphorbiaceae. In addition, investigations based on four genomic SSRs (GAR4, ACR22, CTR25, and GTR28) by cloning and sequencing provided evidence for cross-species/genera applicability, and homologous sequences were obtained from the rubber tree and Euphorbiaceae. Further analysis about the variation of the flanking regions of the four markers was carried out. PMID:20960206

  12. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt.

    PubMed

    Weljie, Aalim M; Meerlo, Peter; Goel, Namni; Sengupta, Arjun; Kayser, Matthew S; Abel, Ted; Birnbaum, Morris J; Dinges, David F; Sehgal, Amita

    2015-02-24

    Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets (n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction (P < 0.05, false-discovery rate < 0.2). Elevated phospholipids were also noted after sleep restriction in both species, as well as metabolites associated with an oxidizing environment. In addition, polar metabolites reflective of neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.

  13. Cross-Species Extrapolation of Prediction Models for Cadmium Transfer from Soil to Corn Grain

    PubMed Central

    Yang, Hua; Li, Zhaojun; Lu, Lu; Long, Jian; Liang, Yongchao

    2013-01-01

    Cadmium (Cd) is a highly toxic heavy metal for both plants and animals. The presence of Cd in agricultural soils is of great concern regarding its transfer in the soil-plant system. This study investigated the transfer of Cd (exogenous salts) from a wide range of Chinese soils to corn grain (Zhengdan 958). Through multiple stepwise regressions, prediction models were developed, with the combination of Cd bioconcentration factor (BCF) of Zhengdan 958 and soil pH, organic matter (OM) content, and cation exchange capacity (CEC). Moreover, these prediction models from Zhengdan 958 were applied to other non-model corn species through cross-species extrapolation approach. The results showed that the pH of the soil was the most important factor that controlled Cd uptake and lower pH was more favorable for Cd bioaccumulation in corn grain. There was no significant difference among three prediction models in the different Cd levels. When the prediction models were applied to other non-model corn species, the ratio ranges between the predicted BCF values and the measured BCF values were within an interval of 2 folds and close to the solid line of 1∶1 relationship. Furthermore, these prediction models also reduced the measured BCF intra-species variability for all non-model corn species. Therefore, the prediction models established in this study can be applied to other non-model corn species and be useful for predicting the Cd bioconcentration in corn grain and assessing the ecological risk of Cd in different soils. PMID:24324636

  14. Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages.

    PubMed

    Zhuo, Xiaoyu; Feschotte, Cédric

    2015-01-01

    Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13-25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts.

  15. Cross-species transcriptomic approach reveals genes in hamster implantation sites.

    PubMed

    Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

    2014-12-01

    The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. PMID:25252651

  16. Ultra-Deep Sequencing of Intra-host Rabies Virus Populations during Cross-species Transmission

    PubMed Central

    Borucki, Monica K.; Chen-Harris, Haiyin; Lao, Victoria; Vanier, Gilda; Wadford, Debra A.; Messenger, Sharon; Allen, Jonathan E.

    2013-01-01

    One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change. PMID:24278493

  17. Population genetics of Cryptosporidium meleagridis in humans and birds: evidence for cross-species transmission.

    PubMed

    Wang, Yuanfei; Yang, Wenli; Cama, Vitaliano; Wang, Lin; Cabrera, Lilia; Ortega, Ynes; Bern, Caryn; Feng, Yaoyu; Gilman, Robert; Xiao, Lihua

    2014-07-01

    Population genetic studies have been used to understand the transmission of pathogens in humans and animals, especially the role of zoonotic infections and evolution and dispersal of virulent subtypes. In this study, we analysed the genetic diversity and population structure of Cryptosporidium meleagridis, the only known Cryptosporidium species that infects both avian and mammalian hosts and is responsible for approximately 10% of human cryptosporidiosis in some areas. A total of 62 C. meleagridis specimens from children, AIDS patients, and birds in Lima, Peru were characterised by sequence analysis of the ssrRNA gene and five minisatellite, microsatellite and polymorphic markers in chromosome 6, including the 60 kDa glycoprotein (gp60), 47 kDa glycoprotein (CP47), a serine repeat antigen (MSC6-5), retinitis pigmentosa GTPase regulator (RPGR) and thrombospondin protein 8 (TSP8). The multilocus sequence analysis identified concurrent infections with Cryptosporidium hominis in four AIDS patients and three children. Unique subtypes of C. meleagridis ranged from eight at the gp60 locus (gene diversity -Hd=0.651), three at the RPGR (Hd=0.556), three at the MSC6-5 locus (Hd=0.242), two at TSP8 (Hd=0.198), to one at CP47 (monomorphic), much lower than that of C. hominis in the same area. Intragenic linkage disequilibrium was strong and complete at all gene loci. Intergenic linkage disequilibrium was highly significant (P<0.001) for all pairs of polymorphic loci. Two major groups of subtypes were seen, with most subtypes belonging to group 1. Within group 1, there was no clear population segregation, and two of the 14 multilocus subtypes of C. meleagridis were found in both AIDS patients and birds. We believe that these results provide the first evidence of a clonal population structure of C. meleagridis and the likely occurrence of cross-species transmission of C. meleagridis between birds and humans.

  18. Ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission.

    PubMed

    Borucki, Monica K; Chen-Harris, Haiyin; Lao, Victoria; Vanier, Gilda; Wadford, Debra A; Messenger, Sharon; Allen, Jonathan E

    2013-11-01

    One of the hurdles to understanding the role of viral quasispecies in RNA virus cross-species transmission (CST) events is the need to analyze a densely sampled outbreak using deep sequencing in order to measure the amount of mutation occurring on a small time scale. In 2009, the California Department of Public Health reported a dramatic increase (350) in the number of gray foxes infected with a rabies virus variant for which striped skunks serve as a reservoir host in Humboldt County. To better understand the evolution of rabies, deep-sequencing was applied to 40 unpassaged rabies virus samples from the Humboldt outbreak. For each sample, approximately 11 kb of the 12 kb genome was amplified and sequenced using the Illumina platform. Average coverage was 17,448 and this allowed characterization of the rabies virus population present in each sample at unprecedented depths. Phylogenetic analysis of the consensus sequence data demonstrated that samples clustered according to date (1995 vs. 2009) and geographic location (northern vs. southern). A single amino acid change in the G protein distinguished a subset of northern foxes from a haplotype present in both foxes and skunks, suggesting this mutation may have played a role in the observed increased transmission among foxes in this region. Deep-sequencing data indicated that many genetic changes associated with the CST event occurred prior to 2009 since several nonsynonymous mutations that were present in the consensus sequences of skunk and fox rabies samples obtained from 20032010 were present at the sub-consensus level (as rare variants in the viral population) in skunk and fox samples from 1995. These results suggest that analysis of rare variants within a viral population may yield clues to ancestral genomes and identify rare variants that have the potential to be selected for if environment conditions change.

  19. Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages

    PubMed Central

    Zhuo, Xiaoyu; Feschotte, Cédric

    2015-01-01

    Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13–25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts. PMID

  20. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    PubMed Central

    Ashbrook, David G.; Williams, Robert W.; Lu, Lu; Hager, Reinmar

    2015-01-01

    Bipolar disorder (BD) is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS) have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium's bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis. We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1, and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG, and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG, and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG, and TNR influence intercellular signaling in the striatum. PMID:26190982

  1. Speciation: frog mimics prefer their own.

    PubMed

    Mallet, James

    2014-11-17

    Ranitomeya poison frogs in the Peruvian Amazon are a rare example of Müllerian mimicry in vertebrates. These frogs also prefer to court same-coloured mimics. This suggests that divergence in mimicry plays a role in reproductive isolation.

  2. Microsatellite cross-species amplification and utility in southern African elasmobranchs: A valuable resource for fisheries management and conservation

    PubMed Central

    2014-01-01

    Background Similarly to the rest of the world, southern Africa’s diverse chondrichthyan fauna is currently experiencing high fishing pressures from direct and non-direct fisheries to satisfy market demands for shark products such as fins and meat. In this study, the development of microsatellite markers through cross-species amplification of primer sets previously developed for closely related species is reported as an alternative approach to de novo marker development. This included the design of four microsatellite multiplex assays and their cross-species utility in genetic diversity analysis of southern African elasmobranchs. As this study forms part of a larger project on the development of genetic resources for commercially important and endemic southern African species, Mustelus mustelus was used as a candidate species for testing these multiplex assays in down-stream applications. Results Thirty five microsatellite primer sets previously developed for five elasmobranch species were selected from literature for testing cross-species amplification in 16 elasmobranch species occurring in southern Africa. Cross-species amplification success rates ranged from 28.6%-71.4%. From the successfully amplified microsatellites, 22 loci were selected and evaluated for levels of polymorphism, and four multiplex assays comprising of the 22 microsatellites were successfully constructed, optimised and characterised in a panel of 87 Mustelus mustelus individuals. A total of 125 alleles were observed across all loci, with the number of alleles ranging from 3–12 alleles. Cross-species amplification of the four optimised multiplex assays was further tested on 11 commercially important and endemic southern African elasmobranch species. Percentage of polymorphism ranged from 31.8%-95.5% in these species with polymorphic information content decreasing exponentially with evolutionary distance from the source species. Conclusions Cross-species amplification of the 35

  3. A cross-species bi-clustering approach to identifying conserved co-regulated genes

    PubMed Central

    Sun, Jiangwen; Jiang, Zongliang; Tian, Xiuchun; Bi, Jinbo

    2016-01-01

    Motivation: A growing number of studies have explored the process of pre-implantation embryonic development of multiple mammalian species. However, the conservation and variation among different species in their developmental programming are poorly defined due to the lack of effective computational methods for detecting co-regularized genes that are conserved across species. The most sophisticated method to date for identifying conserved co-regulated genes is a two-step approach. This approach first identifies gene clusters for each species by a cluster analysis of gene expression data, and subsequently computes the overlaps of clusters identified from different species to reveal common subgroups. This approach is ineffective to deal with the noise in the expression data introduced by the complicated procedures in quantifying gene expression. Furthermore, due to the sequential nature of the approach, the gene clusters identified in the first step may have little overlap among different species in the second step, thus difficult to detect conserved co-regulated genes. Results: We propose a cross-species bi-clustering approach which first denoises the gene expression data of each species into a data matrix. The rows of the data matrices of different species represent the same set of genes that are characterized by their expression patterns over the developmental stages of each species as columns. A novel bi-clustering method is then developed to cluster genes into subgroups by a joint sparse rank-one factorization of all the data matrices. This method decomposes a data matrix into a product of a column vector and a row vector where the column vector is a consistent indicator across the matrices (species) to identify the same gene cluster and the row vector specifies for each species the developmental stages that the clustered genes co-regulate. Efficient optimization algorithm has been developed with convergence analysis. This approach was first validated on

  4. A cross-modal, cross-species comparison of connectivity measures in the primate brain.

    PubMed

    Reid, Andrew T; Lewis, John; Bezgin, Gleb; Khundrakpam, Budhachandra; Eickhoff, Simon B; McIntosh, Anthony R; Bellec, Pierre; Evans, Alan C

    2016-01-15

    In systems neuroscience, the term "connectivity" has been defined in numerous ways, according to the particular empirical modality from which it is derived. Due to large differences in the phenomena measured by these modalities, the assumptions necessary to make inferences about axonal connections, and the limitations accompanying each, brain connectivity remains an elusive concept. Despite this, only a handful of studies have directly compared connectivity as inferred from multiple modalities, and there remains much ambiguity over what the term is actually referring to as a biological construct. Here, we perform a direct comparison based on the high-resolution and high-contrast Enhanced Nathan Klein Institute (NKI) Rockland Sample neuroimaging data set, and the CoCoMac database of tract tracing studies. We compare four types of commonly-used primate connectivity analyses: tract tracing experiments, compiled in CoCoMac; group-wise correlation of cortical thickness; tractographic networks computed from diffusion-weighted MRI (DWI); and correlational networks obtained from resting-state BOLD (fMRI). We find generally poor correspondence between all four modalities, in terms of correlated edge weights, binarized comparisons of thresholded networks, and clustering patterns. fMRI and DWI had the best agreement, followed by DWI and CoCoMac, while other comparisons showed striking divergence. Networks had the best correspondence for local ipsilateral and homotopic contralateral connections, and the worst correspondence for long-range and heterotopic contralateral connections. k-Means clustering highlighted the lowest cross-modal and cross-species consensus in lateral and medial temporal lobes, anterior cingulate, and the temporoparietal junction. Comparing the NKI results to those of the lower resolution/contrast International Consortium for Brain Imaging (ICBM) dataset, we find that the relative pattern of intermodal relationships is preserved, but the correspondence

  5. A Hot-Segment-Based Approach for the Design of Cross-Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self-Assembly.

    PubMed

    Andreetto, Erika; Malideli, Eleni; Yan, Li-Mei; Kracklauer, Michael; Farbiarz, Karine; Tatarek-Nossol, Marianna; Rammes, Gerhard; Prade, Elke; Neumüller, Tatjana; Caporale, Andrea; Spanopoulou, Anna; Bakou, Maria; Reif, Bernd; Kapurniotu, Aphrodite

    2015-10-26

    The design of inhibitors of protein-protein interactions mediating amyloid self-assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self-assembly. Here we present a hot-segment-linking approach to design a series of mimics of the IAPP cross-amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self- and cross-seeded IAPP self-assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer's disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self-assembly and pathogenic interactions of other proteins as well.

  6. Cross-species sensitivity to a novel androgen receptor agonist of potential environmental concern, spironolactone.

    PubMed

    LaLone, Carlie A; Villeneuve, Daniel L; Cavallin, Jenna E; Kahl, Michael D; Durhan, Elizabeth J; Makynen, Elizabeth A; Jensen, Kathleen M; Stevens, Kyle E; Severson, Megan N; Blanksma, Chad A; Flynn, Kevin M; Hartig, Philip C; Woodard, Jonne S; Berninger, Jason P; Norberg-King, Teresa J; Johnson, Rodney D; Ankley, Gerald T

    2013-11-01

    Spironolactone is a pharmaceutical that in humans is used to treat conditions like hirsutism, various dermatologic afflictions, and female-pattern hair loss through antagonism of the androgen receptor. Although not routinely monitored in the environment, spironolactone has been detected downstream of a pharmaceutical manufacturer, indicating a potential for exposure of aquatic species. Furthermore, spironolactone has been reported to cause masculinization of female western mosquitofish, a response indicative of androgen receptor activation. Predictive methods to identify homologous proteins to the human and western mosquitofish androgen receptor suggest that vertebrates would be more susceptible to adverse effects mediated by chemicals like spironolactone that target the androgen receptor compared with invertebrate species that lack a relevant homolog. In addition, an adverse outcome pathway previously developed for activation of the androgen receptor suggests that androgen mimics can lead to reproductive toxicity in fish. To assess this, 21-d reproduction studies were conducted with 2 fish species, fathead minnow and Japanese medaka, and the invertebrate Daphnia magna. Spironolactone significantly reduced the fecundity of medaka and fathead minnows at 50 μg/L, whereas daphnia reproduction was not affected by concentrations as large as 500 μg/L. Phenotypic masculinization of females of both fish species was observed at 5 μg/L as evidenced by formation of tubercles in fathead minnows and papillary processes in Japanese medaka. Effects in fish occurred at concentrations below those reported in the environment. These results demonstrate how a priori knowledge of an adverse outcome pathway and the conservation of a key molecular target across vertebrates can be utilized to identify potential chemicals of concern in terms of monitoring and highlight potentially sensitive species and endpoints for testing.

  7. MIMIC Methods for Assessing Differential Item Functioning in Polytomous Items

    ERIC Educational Resources Information Center

    Wang, Wen-Chung; Shih, Ching-Lin

    2010-01-01

    Three multiple indicators-multiple causes (MIMIC) methods, namely, the standard MIMIC method (M-ST), the MIMIC method with scale purification (M-SP), and the MIMIC method with a pure anchor (M-PA), were developed to assess differential item functioning (DIF) in polytomous items. In a series of simulations, it appeared that all three methods…

  8. Tough Ceramic Mimics Mother of Pearl

    ScienceCinema

    Ritchie, Robert

    2016-07-12

    Berkeley Lab scientists have mimicked the structure of mother of pearl to create what may well be the toughest ceramic ever produced. http://newscenter.lbl.gov/press-releases/2008/12/05/scientists-create-tough-ceramic-that-mimics-mother-of-pearl/

  9. A chemical system that mimics decoding operations.

    PubMed

    Giansante, Carlo; Ceroni, Paola; Venturi, Margherita; Sakamoto, Junji; Schlüter, A Dieter

    2009-02-23

    The chemical information stored in equilibrium mixtures of molecular species is larger than the sum of information carried by the individual molecules. Protonation equilibria in dilute dichloromethane solution of a shape-persistent macrocycle bearing two 2,2'-bipyridine units and two Coumarin 2 moieties (see figure) can be exploited to mimic decoding operations.

  10. Tough Ceramic Mimics Mother of Pearl

    SciTech Connect

    Ritchie, Robert

    2009-01-01

    Berkeley Lab scientists have mimicked the structure of mother of pearl to create what may well be the toughest ceramic ever produced. http://newscenter.lbl.gov/press-releases/2008/12/05/scientists-create-tough-ceramic-that-mimics-mother-of-pearl/

  11. Hybrid mimics and hybrid vigor in Arabidopsis

    PubMed Central

    Wang, Li; Greaves, Ian K.; Groszmann, Michael; Wu, Li Min; Dennis, Elizabeth S.; Peacock, W. James

    2015-01-01

    F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture. PMID:26283378

  12. Global patterns of apparent copy number variation in birds revealed by cross-species comparative genomic hybridization.

    PubMed

    Skinner, Benjamin M; Al Mutery, Abdullah; Smith, Deborah; Völker, Martin; Hojjat, Nilofour; Raja, Sannaa; Trim, Steven; Houde, Peter; Boecklen, William J; Griffin, Darren K

    2014-04-01

    There is a growing interest in copy number variation (CNV) and the recognition of its importance in phenotype, disease, adaptation and speciation. CNV data is usually ascertained by array-CGH within-species, but similar inter-species comparisons have also been made in primates, mice and domestic mammals. Here, we conducted a broad appraisal of putative cross-species CNVs in birds, 16 species in all, using the standard array-CGH approach. Using a chicken oligonucleotide microarray, we detected 790 apparent CNVs within 135 unique regions and developed a bioinformatic tool 'CNV Analyser' for analysing and visualising cross-species data sets. We successfully addressed four hypotheses as follows: (a) Cross-species CNVs (compared to chicken) are, as suggested from preliminary evidence, smaller and fewer in number than in mammals; this 'dogma' was rejected in the light of the new evidence. (b) CNVs in birds are likely to have a functional effect through an association with genes; a large proportion of detected regions (70 %) were indeed associated with genes (suggesting functional significance), however, not necessarily more so than in mammals. (c) There are more CNVs in birds with more rearranged karyotypes; this hypothesis was rejected. Indeed, Falco species contained fewer than most with relatively standard (chicken-like) karyotypes. (d) There are more CNVs per megabase on micro-chromosomes than macrochromosomes; this hypothesis was accepted. Indeed, in species with rearranged karyotypes characterised by chromosomal fusions, the fused former microchromosomes still 'behaved' as though they were their microchromosomal ancestors. Gene ontology analysis of CNVRs revealed enrichment in immune response and antigen presentation genes and five CNVRs were perfectly correlated with the unique loss of sexual dichromatism in one Galliformes species.

  13. CROSS-SPECIES COMPARISON OF CONAZOLE FUNGICIDE METABOLITES USING RAT AND RAINBOW TROUT (ONCHLORHYNCHUS MYKISS) HEPATIC MICROSOMES AND PURIFIED HUMAN CYP 3A4

    EPA Science Inventory

    Ecological risk assessment frequently relies on cross-species extrapolation to predict acute toxicity from chemical exposures. A major concern for environmental risk characterization is the degree of uncertainty in assessing xenobiotic biotansformation processes. Although inheren...

  14. Environmental mimics of chemical warfare agents.

    PubMed

    Claborn, David M

    2004-12-01

    There are several natural and artificial factors that mimic the effects of chemical warfare agents, thereby causing unwarranted alarm and confusion on the battlefield. Symptoms associated with chemical warfare include paralysis, muscle tremors, heavy salivation, severe burns, blistering, and corrosive skin injuries among others. Similar symptoms can be produced from a variety of environmental sources, artificial and natural. This article reviews several published and unpublished examples of environmental factors that produce syndromes similar to those caused by these agents. Examples of such mimics include pesticides, blistering exudates from insects and plants, various types of bites, and naturally occurring diseases. The potential for confusion caused by these factors is discussed and means of discriminating between warfare agents and naturally occurring events are identified. Recommendations for the use of this information and for needed research are also discussed. PMID:15646185

  15. HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

    PubMed

    Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

    2013-01-01

    Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons.

  16. Cross-species amplification of microsatellite markers in Mycteria leucocephala Pennant 1769: molted feathers as successful DNA source.

    PubMed

    Sharma, Bharat Bhushan; Mustafa, Mohd; Sharma, Tusha; Banerjee, Basu Dev; Urfi, Abdul Jamil

    2014-10-01

    DNA from molted feathers is being increasingly used for genetic studies on birds. However, the DNA obtained from such non-invasive sources is often not of enough quantity and quality for isolation of new microsatellite markers. The present study examined the potential of shed feathers of near threatened Painted Stork as a source of its DNA for cross-species amplification of microsatellites. Thirty-one shed feathers of varying conditions ('good' and 'deteriorated') and sizes ('large', 'intermediate' and 'small') collected in a north Indian population were used to isolate DNA by a standard isopropanol method and 11 microsatellite markers already developed in the Wood Stork were screened for amplification. Nine plucked feathers from two dead Painted Storks were also used to compare the DNA yield and amplification success. The DNA yield of feathers varied significantly in relation to the calamus size and condition. Among molted feathers, 'good' and 'large' samples provided more DNA than 'deteriorated' and 'small' ones, respectively. 'Large' plucked feathers yielded more DNA than 'large' molted feathers. DNA was almost degraded in all the samples and ratio of absorbance at 260/280 nm varied from 1.0 to 1.8, indicating impurity in many samples. Independent of DNA yields, all microsatellites were cross-amplified in all kinds of feathers, with > 80% success in different feather categories. It is concluded that the shed feathers can be successfully used to isolate DNA in the Painted Stork and for cross-species amplification of microsatellites.

  17. Cross-species protection: Schistosoma mansoni Sm-p80 vaccine confers protection against Schistosoma haematobium in hamsters and baboons.

    PubMed

    Karmakar, Souvik; Zhang, Weidong; Ahmad, Gul; Torben, Workineh; Alam, Mayeen U; Le, Loc; Damian, Raymond T; Wolf, Roman F; White, Gary L; Carey, David W; Carter, Darrick; Reed, Steven G; Siddiqui, Afzal A

    2014-03-01

    The ability of the Schistosoma mansoni antigen, Sm-p80, to provide cross-species protection against Schistosoma haematobium challenge was evaluated in hamster and baboon models. Pronounced reduction in worm burden (48%) and in tissue egg load (64%) was observed in hamsters vaccinated with recombinant Sm-p80 admixed with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Similarly, in baboons, the Sm-p80/GLA-SE vaccine produced a 25% reduction in S. haematobium adult worms and decreased the egg load in the urinary bladder by 64%. A 40% and 53% reduction in fecal and urine egg output, respectively, was observed in vaccinated baboons. A balanced pro-inflammatory (Th17 and Th1) and Th2 type of response was generated after vaccination and appears indicative of augmented prophylactic efficacy. These data on cross-species protection coupled with the prophylactic, therapeutic and antifecundity efficacy against the homologous parasite, S. mansoni, reinforces Sm-p80 as a promising vaccine candidate. It is currently being prepared for GMP-compliant manufacture and for further pre-clinical development leading to human clinical trials. These results solidify the expectation that the Sm-p80 vaccine will provide relief for both the intestinal and the urinary schistosomiasis and thus will be greatly beneficial in reducing the overall burden of schistosomiasis.

  18. Meningeal fibroma: a rare meningioma mimic.

    PubMed

    Kakkar, Aanchal; Sharma, Mehar C; Goyal, Nishant; Sarkar, Chitra; Suri, Vaishali; Garg, Ajay; Kale, Shashank S; Suri, Ashish

    2014-08-01

    Meningeal fibromas are rare intracranial tumors that mimic meningiomas radiologically as well as histologically. The authors report 2 cases of meningeal fibroma with detailed clinical, radiological, histopathological, and immunohistochemical features, and discuss the differential diagnosis of this entity. Knowledge of this rare tumor is essential for pathologists to be able distinguish it from more common meningeal tumors, especially in younger patients. This knowledge is also essential for neurosurgeons, as incomplete resection may lead to tumor recurrence, and such patients require close follow-up.

  19. Segmental arterial mediolysis mimics systemic vasculitis

    PubMed Central

    Kalfa, Melike; Kocanaoğulları, Hayriye; Karabulut, Gonca; Emmungil, Hakan; Çınar, Celal; Yılmaz, Zevcet; Gücenmez, Sercan; Kabasakal, Yasemin

    2016-01-01

    Segmental arterial mediolysis (SAM) is a rare, nonarteriosclerotic, noninflammatory vascular disease and mostly affects medium-to-large sized abdominal arteries as well as presents with hemorrhages in the abdominal cavity. We report the case of a patient with SAM of the celiac, right renal, jejunal branch of the superior mesenteric, left gastric, and splenic arteries who was diagnosed by excluding other causes and in whom transcatheter embolization was performed in two different sessions, but he died because of an undefined reason. SAM mimics systemic vasculitis and causes abdominal pain; it should be considered because abdominal hemorrhage or arterial infarction can result in death. PMID:27733945

  20. Development, characterization and cross species amplification of polymorphic microsatellite markers from expressed sequence tags of turmeric (Curcuma longa L.).

    PubMed

    Siju, S; Dhanya, K; Syamkumar, S; Sasikumar, B; Sheeja, T E; Bhat, A I; Parthasarathy, V A

    2010-02-01

    Expressed sequence tags (ESTs) from turmeric (Curcuma longa L.) were used for the screening of type and frequency of Class I (hypervariable) simple sequence repeats (SSRs). A total of 231 microsatellite repeats were detected from 12,593 EST sequences of turmeric after redundancy elimination. The average density of Class I SSRs accounts to one SSR per 17.96 kb of EST. Mononucleotides were the most abundant class of microsatellite repeat in turmeric ESTs followed by trinucleotides. A robust set of 17 polymorphic EST-SSRs were developed and used for evaluating 20 turmeric accessions. The number of alleles detected ranged from 3 to 8 per loci. The developed markers were also evaluated in 13 related species of C. longa confirming high rate (100%) of cross species transferability. The polymorphic microsatellite markers generated from this study could be used for genetic diversity analysis and resolving the taxonomic confusion prevailing in the genus.

  1. BodyMap-Xs: anatomical breakdown of 17 million animal ESTs for cross-species comparison of gene expression.

    PubMed

    Ogasawara, Osamu; Otsuji, Makiko; Watanabe, Kouji; Iizuka, Takayasu; Tamura, Takuro; Hishiki, Teruyoshi; Kawamoto, Shoko; Okubo, Kousaku

    2006-01-01

    BodyMap-Xs (http://bodymap.jp) is a database for cross-species gene expression comparison. It was created by the anatomical breakdown of 17 million animal expressed sequence tag (EST) records in DDBJ using a sorting program tailored for this purpose. In BodyMap-Xs, users are allowed to compare the expression patterns of orthologous and paralogous genes in a coherent manner. This will provide valuable insights for the evolutionary study of gene expression and identification of a responsive motif for a particular expression pattern. In addition, starting from a concise overview of the taxonomical and anatomical breakdown of all animal ESTs, users can navigate to obtain gene expression ranking of a particular tissue in a particular animal. This method may lead to the understanding of the similarities and differences between the homologous tissues across animal species. BodyMap-Xs will be automatically updated in synchronization with the major update in DDBJ, which occurs periodically.

  2. Cross-species transmission of gibbon and orangutan hepatitis B virus to uPA/SCID mice with human hepatocytes.

    PubMed

    Sa-Nguanmoo, Pattaratida; Tanaka, Yasuhito; Ratanakorn, Parntep; Sugiyama, Masaya; Murakami, Shuko; Payungporn, Sunchai; Sommanustweechai, Angkana; Mizokami, Masashi; Poovorawan, Yong

    2011-06-01

    To investigate the potential of cross-species transmission of non-human primate HBV to humans, severe combined immunodeficiency mice transgenic for urokinase-type plasminogen activator, in which the mouse liver has been engrafted with human hepatocytes, were inoculated with non-human primate HBV. HBV-DNA positive serum samples from a gibbon or orangutan were inoculated into 6 chimeric mice. HBV-DNA, hepatitis B surface antigen (HBsAg), and HB core-related antigen in sera and HBV cccDNA in liver were detectable in 2 of 3 mice each from the gibbon and orangutan. Likewise, applying immunofluorescence HBV core protein was only found in human hepatocytes expressing human albumin. The HBV sequences from mouse sera were identical to those from orangutan and gibbon sera determined prior to inoculation. In conclusion, human hepatocytes have been infected with gibbon/orangutan HBV.

  3. Development of 20 microsatellite markers for Solenocera crassicornis and their cross-species application in Solenocera melantho.

    PubMed

    Liu, Shufang; Liu, Hongbo; Lin, Lin; Yuan, Yanjiao; Dai, Fangqun; Zhuang, Zhimeng

    2012-01-01

    Twenty microsatellite markers were isolated and characterized for Solenocera crassicornis from a (GT)13-enriched genomic library. Their polymorphisms were investigated using 44 wild individuals from the South Yellow Sea. Our investigation revealed that all the markers were polymorphic. The number of alleles per locus varied from 6 to 19 with an average of 12.35. The observed and expected heterozygosities ranged from 0.400 to 0.977 and from 0.609 to 0.940, with averages of 0.788 and 0.859, respectively. Four loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni's correction. Cross-species amplification was also conducted in Solenocera melantho collected from the East China Sea. The result showed that 14 loci could be amplified from Solenocera melantho DNAs. These polymorphic markers would be useful for assessment of genetic variation and population structure of S. crassicornis and S. melantho.

  4. Quantitative Cross-Species Extrapolation between Humans and Fish: The Case of the Anti-Depressant Fluoxetine

    PubMed Central

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Cumming, Rob I.; de Polo, Anna; Winter, Matthew J.; Panter, Grace H.; Rand-Weaver, Mariann; Sumpter, John P.

    2014-01-01

    Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 µg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the

  5. Cross-species hybridisation of human and bovine orthologous genes on high density cDNA microarrays

    PubMed Central

    Adjaye, James; Herwig, Ralf; Herrmann, Doris; Wruck, Wasco; BenKahla, Alia; Brink, Thore C; Nowak, Monika; Carnwath, Joseph W; Hultschig, Claus; Niemann, Heiner; Lehrach, Hans

    2004-01-01

    Background Cross-species gene-expression comparison is a powerful tool for the discovery of evolutionarily conserved mechanisms and pathways of expression control. The usefulness of cDNA microarrays in this context is that broad areas of homology are compared and hybridization probes are sufficiently large that small inter-species differences in nucleotide sequence would not affect the analytical results. This comparative genomics approach would allow a common set of genes within a specific developmental, metabolic, or disease-related gene pathway to be evaluated in experimental models of human diseases. The objective of this study was to investigate the feasibility and reproducibility of cross-species analysis employing a human cDNA microarray as probe. Results As a proof of principle, total RNA derived from human and bovine fetal brains was used as a source of labelled targets for hybridisation onto a human cDNA microarray composed of 349 characterised genes. Each gene was spotted 20 times representing 6,980 data points thus enabling highly reproducible spot quantification. Employing high stringency hybridisation and washing conditions, followed by data analysis, revealed slight differences in the expression levels and reproducibility of the signals between the two species. We also assigned each of the genes into three expression level categories- i.e. high, medium and low. The correlation co-efficient of cross hybridisation between the orthologous genes was 0.94. Verification of the array data by semi-quantitative RT-PCR using common primer sequences enabled co-amplification of both human and bovine transcripts. Finally, we were able to assign gene names to previously uncharacterised bovine ESTs. Conclusions Results of our study demonstrate the harnessing and utilisation power of comparative genomics and prove the feasibility of using human microarrays to facilitate the identification of co-expressed orthologous genes in common tissues derived from different

  6. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat.

    PubMed

    Diaz Quiroz, Juan Felipe; Tsai, Eve; Coyle, Matthew; Sehm, Tina; Echeverri, Karen

    2014-06-01

    Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs) that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum) and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b) is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal's functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander's regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries.

  7. Development of Protein Mimics for Intracellular Delivery

    PubMed Central

    deRonde, Brittany M.; Tew, Gregory N.

    2015-01-01

    Designing delivery agents for therapeutics is an ongoing challenge. As treatments and desired cargoes become more complex, the need for improved delivery vehicles becomes critical. Excellent delivery vehicles must ensure the stability of the cargo, maintain the cargo’s solubility, and promote efficient delivery and release. In order to address these issues, many research groups have looked to nature for design inspiration. Proteins, such as HIV-1 TAT and Antennapedia homeodomain protein, are capable of crossing cellular membranes. However, due to the complexities of their structures, they are synthetically challenging to reproduce in the laboratory setting. Being able to incorporate the key features of these proteins that enable cell entry into simpler scaffolds opens up a wide range of opportunities for the development of new delivery reagents with improved performance. This review charts the development of protein mimics based on cell-penetrating peptides and how structure-activity relationships with these molecules and their protein counterparts ultimately led to the use of polymeric scaffolds. These scaffolds deviate from the normal peptide backbone, allowing for simpler, synthetic procedures to make carriers and tune chemical compositions for application specific needs. Successful design of polymeric protein mimics would allow researchers to further understand the key features in proteins and peptides necessary for efficient delivery and to design the next generation of more efficient delivery reagents. PMID:25858701

  8. Engineering hydrogels as extracellular matrix mimics

    PubMed Central

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun

    2010-01-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. PMID:20394538

  9. Recognizing asthma mimics and asthma complications.

    PubMed

    Amundson, Dennis; Seda, Gilbert; Daheshia, Massoud

    2011-10-01

    Asthma is a chronic inflammatory disorder of the airways characterized by airflow obstruction, bronchial hyperreactivity, and underlying inflammation. Two common reasons asthmatics fail standard therapy are incorrect diagnosis and failure to recognize underlying contributing factors. A correct diagnosis of asthma is of great importance to military practitioners since misdiagnosis or uncontrolled asthma affects an individual's operational readiness or determines whether one can receive a medical waiver to enlist in military service. This article presents four cases of patients with dyspnea that have conditions which mimic asthma or complicate asthma management: vocal cord dysfunction misdiagnosed as asthma, respiratory bronchiolitis interstitial lung disease mistaken as asthma, difficult-to-control asthma because of bronchiectasis and allergic bronchopulmonary aspergillosis, and difficult and fatal asthma. Asthma is contrasted to other respiratory disorders, and an outlined approach to asthma diagnosis and management is presented using the Global Initiative for Asthma guidelines.

  10. Renewable polyethylene mimics derived from castor oil.

    PubMed

    Türünç, Oĝuz; Montero de Espinosa, Lucas; Meier, Michael A R

    2011-09-01

    An increasing number of reports on the syntheses of carbohydrate- and plant oil-based polymers has been published in ongoing efforts to produce plastic materials from renewable resources. Although many of these polymers are biodegradable and this is a desirable property for certain applications, in some cases non-degradable polymers are needed for long-term use purposes. Polyolefins are one of the most important classes of materials that have already taken their places in our daily life. On the other hand, their production relies on fossil resources. Therefore, within this contribution, we discuss synthetic routes toward a number of polyethylene mimics derived from fatty acids via thiol-ene and ADMET polymerization reactions in order to establish more sustainable routes toward this important class of polymers. Two different diene monomers were thus prepared from castor oil derived platform chemicals, their polymerization via the two mentioned routes was optimized and compared to each other, and their thermal properties were investigated.

  11. Abdominal Sarcoidosis May Mimic Peritoneal Carcinomatosis

    PubMed Central

    Gorkem, Umit; Gungor, Tayfun; Bas, Yılmaz; Togrul, Cihan

    2015-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It shows a great variety of clinical presentation, organ involvement, and disease progression. Lungs and lymphoid system are the most common sites involved with a frequency of 90% and 30%, respectively. Extrapulmonary involvement of sarcoidosis is reported in 30% of patients and abdomen is the most frequent site. Furthermore, peritoneal involvement is extremely rare in sarcoidosis. The case presented here described peritoneal manifestations of sarcoidosis without involvement of lungs. A 78-year-old woman possessing signs of malignancy on blood test and abdominal magnetic resonance imaging underwent laparatomy with a suspicion of ovarian malignancy. The macroscopic interpretation during surgery was peritoneal carcinomatosis. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal biopsies, total omentectomy, and appendectomy were performed. Final histopathological result revealed the diagnosis of sarcoidosis. Clinicians must keep in mind that peritoneal sarcoidosis can mimic intra-abdominal malignancies. PMID:26558122

  12. Syndromes that Mimic an Excess of Mineralocorticoids.

    PubMed

    Sabbadin, Chiara; Armanini, Decio

    2016-09-01

    Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of renin and aldosterone. It can be due to endogenous or exogenous substances that mimic the effector mechanisms of aldosterone, leading not only to alterations of electrolytes and hypertension, but also to an increased inflammatory reaction in several tissues. Enzymatic defects of adrenal steroidogenesis (deficiency of 17α-hydroxylase and 11β-hydroxylase), mutations of mineralocorticoid receptor (MR) and alterations of expression or saturation of 11-hydroxysteroid dehydrogenase type 2 (apparent mineralocorticoid excess syndrome, Cushing's syndrome, excessive intake of licorice, grapefruits or carbenoxolone) are the main causes of pseudohyperaldosteronism. In these cases treatment with dexamethasone and/or MR-blockers is useful not only to normalize blood pressure and electrolytes, but also to prevent the deleterious effects of prolonged over-activation of MR in epithelial and non-epithelial tissues. Genetic alterations of the sodium channel (Liddle's syndrome) or of the sodium-chloride co-transporter (Gordon's syndrome) cause abnormal sodium and water reabsorption in the distal renal tubules and hypertension. Treatment with amiloride and thiazide diuretics can respectively reverse the clinical picture and the renin aldosterone system. Finally, many other more common situations can lead to an acquired pseudohyperaldosteronism, like the expansion of volume due to exaggerated water and/or sodium intake, and the use of drugs, as contraceptives, corticosteroids, β-adrenergic agonists and FANS. In conclusion, syndromes or situations that mimic aldosterone excess are not rare and an accurate personal and pharmacological history is mandatory for a correct diagnosis and avoiding unnecessary tests and mistreatments. PMID:27251484

  13. Production of podophyllotoxin using cross-species coculture of Linum flavum hairy roots and Podophyllum hexandrum cell suspensions.

    PubMed

    Lin, Han-wei; Kwok, Kian H; Doran, Pauline M

    2003-01-01

    Novel cross-species coculture systems using Linum flavum hairy roots and Podophyllum hexandrum cell suspensions were applied for in vitro production of podophyllotoxin. The hairy roots and suspensions were cocultured in Linsmaier and Skoog medium in dual shake flasks and dual bioreactors. In separate experiments, coniferin feeding was shown to be an effective strategy for increasing the accumulation of podophyllotoxin in P. hexandrum suspensions. Because roots of L. flavum are a natural source of coniferin, hairy roots of this species were used in coculture with P. hexandrum to provide an in situ supply of coniferin. Compared with P. hexandrum suspensions cultured alone in shake flasks or bioreactors, podophyllotoxin concentrations in cocultured P. hexandrum cells were increased by 240% and 72% in dual shake flask and dual bioreactor systems, respectively. The availability and stability of coniferin in the medium are the most likely factors limiting podophyllotoxin synthesis in coculture. Intensification of the coculture process is required to further improve total podophyllotoxin accumulation on a volumetric basis.

  14. Cross-Species Comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei Quorum-Sensing Regulons

    PubMed Central

    Majerczyk, Charlotte D.; Brittnacher, Mitchell J.; Jacobs, Michael A.; Armour, Christopher D.; Radey, Matthew C.; Bunt, Richard; Hayden, Hillary S.; Bydalek, Ryland

    2014-01-01

    Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei (the Bptm group) are close relatives with very different lifestyles: B. pseudomallei is an opportunistic pathogen, B. thailandensis is a nonpathogenic saprophyte, and B. mallei is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of B. pseudomallei, B. thailandensis, and B. mallei serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of B. pseudomallei and B. mallei. PMID:25182491

  15. Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

    PubMed Central

    Hayes, Dave J.; Northoff, Georg

    2011-01-01

    The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed. PMID:22102836

  16. Identification of novel and diverse rotaviruses in rodents and insectivores, and evidence of cross-species transmission into humans.

    PubMed

    Li, Kun; Lin, Xian-Dan; Huang, Kai-Yu; Zhang, Bing; Shi, Mang; Guo, Wen-Ping; Wang, Miao-Ruo; Wang, Wen; Xing, Jian-Guang; Li, Ming-Hui; Hong, Wang-Sheng; Holmes, Edward C; Zhang, Yong-Zhen

    2016-07-01

    Rotaviruses are an important cause of severe diarrheal illness in children globally. We characterized rotaviruses sampled in humans, insectivores (shrews) and rodents from urban and rural regions of Zhejiang province, China. Phylogenetic analyses revealed seven genotypic constellations of human rotaviruses with six different combinations of G and P genotypes - G3P[8] (50.06%), G9P[8] (36.16%), G1P[8] (8.92%), G2P[4] (4.63%), G3P[3] (0.12%), and G3P[9] (0.12%). In rodents and shrews sampled from the same locality we identified a novel genotype constellation (G32-P[46]-I24-R18-C17-M17-A28-N17-T19-E24-H19), a novel P genotype (P[45]), and two different AU-1-like rotaviruses associated with a G3P[3] genotype combination. Of particular note was a novel rotavirus from a human patient that was closely related to viruses sampled from rodents in the same region, indicative of a local species jump. In sum, these data are suggestive of the cross-species transmission of rodent rotaviruses into humans and for reassortment among human and animal rotaviruses. PMID:27115729

  17. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

    PubMed Central

    Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

    2016-01-01

    Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

  18. Cross-species comparison of the Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei quorum-sensing regulons.

    PubMed

    Majerczyk, Charlotte D; Brittnacher, Mitchell J; Jacobs, Michael A; Armour, Christopher D; Radey, Matthew C; Bunt, Richard; Hayden, Hillary S; Bydalek, Ryland; Greenberg, E Peter

    2014-11-01

    Burkholderia pseudomallei, Burkholderia thailandensis, and Burkholderia mallei (the Bptm group) are close relatives with very different lifestyles: B. pseudomallei is an opportunistic pathogen, B. thailandensis is a nonpathogenic saprophyte, and B. mallei is a host-restricted pathogen. The acyl-homoserine lactone quorum-sensing (QS) systems of these three species show a high level of conservation. We used transcriptome sequencing (RNA-seq) to define the quorum-sensing regulon in each species, and we performed a cross-species analysis of the QS-controlled orthologs. Our analysis revealed a core set of QS-regulated genes in all three species, as well as QS-controlled factors shared by only two species or unique to a given species. This global survey of the QS regulons of B. pseudomallei, B. thailandensis, and B. mallei serves as a platform for predicting which QS-controlled processes might be important in different bacterial niches and contribute to the pathogenesis of B. pseudomallei and B. mallei.

  19. Isolation and characterization of 45 Polymorphie microsatellite loci of turbot ( Scophthalmus maximus) and cross-species amplification

    NASA Astrophysics Data System (ADS)

    Hou, Shiying; Ma, Aijun; Wang, Xin'an; Huang, Zhihui; Xue, Baogui; Yang, Zhi; Qu, Jiangbo

    2011-03-01

    Turbot ( Scophthalmus maximus) is a flatfish species commercially important for aquaculture. In this study, we generated a microsatellite-enriched genomic DNA library for Scophthalmus maximus, and then isolated and characterized 45 microsatellite loci by genotyping 30 individuals. The observed number of alleles ranged from 2 to 19 with an average of 6.24, while the effective number of alleles ranged from 1.30 to 11.11 with an average of 3.66. The expected heterozygosities varied from 0.235 to 0.925 4 and Polymorphie information content ranged from 0.2044 to 0.903 3, with an average of 0.622. Twelve loci deviated significantly from Hardy-Weinberg equilibrium, and no significant linkage disequilibrium was observed between any pair of loci after Bonferroni correction. In cross-species amplification, five flatfish species ( Paralichthys lethostigma, Verasper moseri, platichthys stellatus, Hippoglossoides dubius and Cynoglossus semilaevis) showed at least one Polymorphie locus. These Polymorphie microsatellite loci should prove useful for Population analysis of turbot and other related species.

  20. Limitations to estimating bacterial cross-species transmission using genetic and genomic markers: inferences from simulation modeling

    PubMed Central

    Benavides, Julio A; Cross, Paul C; Luikart, Gordon; Creel, Scott

    2014-01-01

    Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced. PMID:25469159

  1. Network Modules of the Cross-Species Genotype-Phenotype Map Reflect the Clinical Severity of Human Diseases.

    PubMed

    Han, Seong Kyu; Kim, Inhae; Hwang, Jihye; Kim, Sanguk

    2015-01-01

    Recent advances in genome sequencing techniques have improved our understanding of the genotype-phenotype relationship between genetic variants and human diseases. However, genetic variations uncovered from patient populations do not provide enough information to understand the mechanisms underlying the progression and clinical severity of human diseases. Moreover, building a high-resolution genotype-phenotype map is difficult due to the diverse genetic backgrounds of the human population. We built a cross-species genotype-phenotype map to explain the clinical severity of human genetic diseases. We developed a data-integrative framework to investigate network modules composed of human diseases mapped with gene essentiality measured from a model organism. Essential and nonessential genes connect diseases of different types which form clusters in the human disease network. In a large patient population study, we found that disease classes enriched with essential genes tended to show a higher mortality rate than disease classes enriched with nonessential genes. Moreover, high disease mortality rates are explained by the multiple comorbid relationships and the high pleiotropy of disease genes found in the essential gene-enriched diseases. Our results reveal that the genotype-phenotype map of a model organism can facilitate the identification of human disease-gene associations and predict human disease progression.

  2. Controlled vocabularies for plant anatomical parts optimized for use in data analysis tools and for cross-species studies

    PubMed Central

    2013-01-01

    Background It is generally accepted that controlled vocabularies are necessary to systematically integrate data from various sources. During the last decade, several plant ontologies have been developed, some of which are community specific or were developed for a particular purpose. In most cases, the practical application of these ontologies has been limited to systematically storing experimental data. Due to technical constraints, complex data structures and term redundancies, it has been difficult to apply them directly into analysis tools. Results Here, we describe a simplified and cross-species compatible set of controlled vocabularies for plant anatomy, focussing mainly on monocotypledonous and dicotyledonous crop and model plants. Their content was designed primarily for their direct use in graphical visualization tools. Specifically, we created annotation vocabularies that can be understood by non-specialists, are minimally redundant, simply structured, have low tree depth, and we tested them practically in the frame of Genevestigator. Conclusions The application of the proposed ontologies enabled the aggregation of data from hundreds of experiments to visualize gene expression across tissue types. It also facilitated the comparison of expression across species. The described controlled vocabularies are maintained by a dedicated curation team and are available upon request. PMID:23958387

  3. Exposure to early adversity: Points of cross-species translation that can lead to improved understanding of depression.

    PubMed

    Andersen, Susan L

    2015-05-01

    The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer-peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep-wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence. PMID:25997766

  4. Identification of novel and diverse rotaviruses in rodents and insectivores, and evidence of cross-species transmission into humans.

    PubMed

    Li, Kun; Lin, Xian-Dan; Huang, Kai-Yu; Zhang, Bing; Shi, Mang; Guo, Wen-Ping; Wang, Miao-Ruo; Wang, Wen; Xing, Jian-Guang; Li, Ming-Hui; Hong, Wang-Sheng; Holmes, Edward C; Zhang, Yong-Zhen

    2016-07-01

    Rotaviruses are an important cause of severe diarrheal illness in children globally. We characterized rotaviruses sampled in humans, insectivores (shrews) and rodents from urban and rural regions of Zhejiang province, China. Phylogenetic analyses revealed seven genotypic constellations of human rotaviruses with six different combinations of G and P genotypes - G3P[8] (50.06%), G9P[8] (36.16%), G1P[8] (8.92%), G2P[4] (4.63%), G3P[3] (0.12%), and G3P[9] (0.12%). In rodents and shrews sampled from the same locality we identified a novel genotype constellation (G32-P[46]-I24-R18-C17-M17-A28-N17-T19-E24-H19), a novel P genotype (P[45]), and two different AU-1-like rotaviruses associated with a G3P[3] genotype combination. Of particular note was a novel rotavirus from a human patient that was closely related to viruses sampled from rodents in the same region, indicative of a local species jump. In sum, these data are suggestive of the cross-species transmission of rodent rotaviruses into humans and for reassortment among human and animal rotaviruses.

  5. Network Modules of the Cross-Species Genotype-Phenotype Map Reflect the Clinical Severity of Human Diseases

    PubMed Central

    Han, Seong Kyu; Kim, Inhae; Hwang, Jihye; Kim, Sanguk

    2015-01-01

    Recent advances in genome sequencing techniques have improved our understanding of the genotype-phenotype relationship between genetic variants and human diseases. However, genetic variations uncovered from patient populations do not provide enough information to understand the mechanisms underlying the progression and clinical severity of human diseases. Moreover, building a high-resolution genotype-phenotype map is difficult due to the diverse genetic backgrounds of the human population. We built a cross-species genotype-phenotype map to explain the clinical severity of human genetic diseases. We developed a data-integrative framework to investigate network modules composed of human diseases mapped with gene essentiality measured from a model organism. Essential and nonessential genes connect diseases of different types which form clusters in the human disease network. In a large patient population study, we found that disease classes enriched with essential genes tended to show a higher mortality rate than disease classes enriched with nonessential genes. Moreover, high disease mortality rates are explained by the multiple comorbid relationships and the high pleiotropy of disease genes found in the essential gene-enriched diseases. Our results reveal that the genotype-phenotype map of a model organism can facilitate the identification of human disease-gene associations and predict human disease progression. PMID:26301634

  6. Novel Polymorphic Microsatellite Markers for Panulirus ornatus and their Cross-species Primer Amplification in Panulirus homarus.

    PubMed

    Delghandi, Madjid; Afzal, Hasifa; Al Hinai, Manal Saif Nasser; Al-Breiki, Rafaida Dhuhai Gharib; Jerry, Dean R; Dao, Hoc Tan

    2016-10-01

    Polymorphic microsatellite loci were isolated for Panulirus ornatus using 454 GS-FLX Titanium pyrosequencing. Fifteen markers containing perfect di-, tri-, tetra-, and penta-nucleotide motifs were consistently co-amplified in five multiplexes in a panel of 91 randomly selected samples. Observed number of alleles varied from 2 to 14 per locus. Observed and expected heterozygosity ranged from 0.090 to 0.79 and 0.08 to 0.87, respectively. Ten loci deviated from Hardy-Weinberg equilibrium after sequential Bonferroni correction. Genetic linkage disequilibrium analysis between all pairs of the loci showed significant departure from the null hypothesis between 11 loci. The microsatellite markers were also amplified successfully in related Panulirus homarus species with adequate level of polymorphism. The successful cross-species primer amplification of the 15 microsatellites indicates the potential of the developed markers to be transferred to other Panulirus species. The 15 novel microsatellite markers reported in this work add to the previously characterized markers by our group, exhibit adequate levels of polymorphism for wide range of future studies investigating population structure, genetic diversity, and evolutionary relationships among Panulirus species. PMID:27565876

  7. SOX10 mutations mimic isolated hearing loss.

    PubMed

    Pingault, V; Faubert, E; Baral, V; Gherbi, S; Loundon, N; Couloigner, V; Denoyelle, F; Noël-Pétroff, N; Ducou Le Pointe, H; Elmaleh-Bergès, M; Bondurand, N; Marlin, S

    2015-10-01

    Ninety genes have been identified to date that are involved in non-syndromic hearing loss, and more than 300 different forms of syndromic hearing impairment have been described. Mutations in SOX10, one of the genes contributing to syndromic hearing loss, induce a large range of phenotypes, including several subtypes of Waardenburg syndrome and Kallmann syndrome with deafness. In addition, rare mutations have been identified in patients with isolated signs of these diseases. We used the recent characterization of temporal bone imaging aspects in patients with SOX10 mutations to identify possible patients with isolated hearing loss due to SOX10 mutation. We selected 21 patients with isolated deafness and temporal bone morphological defects for mutational screening. We identified two SOX10 mutations and found that both resulted in a non-functional protein in vitro. Re-evaluation of the two affected patients showed that both had previously undiagnosed olfactory defects. Diagnosis of anosmia or hyposmia in young children is challenging, and particularly in the absence of magnetic resonance imaging (MRI), SOX10 mutations can mimic non-syndromic hearing impairment. MRI should complete temporal bones computed tomographic scan in the management of congenital deafness as it can detect brain anomalies, cochlear nerve defects, and olfactory bulb malformation in addition to inner ear malformations.

  8. A nanostructured synthetic collagen mimic for hemostasis.

    PubMed

    Kumar, Vivek A; Taylor, Nichole L; Jalan, Abhishek A; Hwang, Lyahn K; Wang, Benjamin K; Hartgerink, Jeffery D

    2014-04-14

    Collagen is a major component of the extracellular matrix and plays a wide variety of important roles in blood clotting, healing, and tissue remodeling. Natural, animal derived, collagen is used in many clinical applications but concerns exist with respect to its role in inflammation, batch-to-batch variability, and possible disease transfection. Therefore, development of synthetic nanomaterials that can mimic the nanostructure and properties of natural collagen has been a heavily pursued goal in biomaterials. Previously, we reported on the design and multihierarchial self-assembly of a 36 amino acid collagen mimetic peptide (KOD) that forms nanofibrous triple helices that entangle to form a hydrogel. In this report, we utilize this nanofiber forming collagen mimetic peptide as a synthetic biomimetic matrix useful in thrombosis. We demonstrate that nanofibrous KOD synthetic collagen matrices adhere platelets, activate them (indicated by soluble P-selectin secretion), and clot plasma and blood similar to animal derived collagen and control surfaces. In addition to the thrombotic potential, THP-1 monocytes incubated with our KOD collagen mimetic showed minimal proinflammatory cytokine (TNF-α or IL-1β) production. Together, the data presented demonstrates the potential of a novel synthetic collagen mimetic as a hemostat.

  9. A nanostructured synthetic collagen mimic for hemostasis.

    PubMed

    Kumar, Vivek A; Taylor, Nichole L; Jalan, Abhishek A; Hwang, Lyahn K; Wang, Benjamin K; Hartgerink, Jeffery D

    2014-04-14

    Collagen is a major component of the extracellular matrix and plays a wide variety of important roles in blood clotting, healing, and tissue remodeling. Natural, animal derived, collagen is used in many clinical applications but concerns exist with respect to its role in inflammation, batch-to-batch variability, and possible disease transfection. Therefore, development of synthetic nanomaterials that can mimic the nanostructure and properties of natural collagen has been a heavily pursued goal in biomaterials. Previously, we reported on the design and multihierarchial self-assembly of a 36 amino acid collagen mimetic peptide (KOD) that forms nanofibrous triple helices that entangle to form a hydrogel. In this report, we utilize this nanofiber forming collagen mimetic peptide as a synthetic biomimetic matrix useful in thrombosis. We demonstrate that nanofibrous KOD synthetic collagen matrices adhere platelets, activate them (indicated by soluble P-selectin secretion), and clot plasma and blood similar to animal derived collagen and control surfaces. In addition to the thrombotic potential, THP-1 monocytes incubated with our KOD collagen mimetic showed minimal proinflammatory cytokine (TNF-α or IL-1β) production. Together, the data presented demonstrates the potential of a novel synthetic collagen mimetic as a hemostat. PMID:24694012

  10. Daughters mimic sterile neutrinos (almost!) perfectly

    SciTech Connect

    Hasenkamp, Jasper

    2014-09-01

    Since only recently, cosmological observations are sensitive to hot dark matter (HDM) admixtures with sub-eV mass, m{sub hdm}{sup eff} < eV, that are not fully-thermalised, Δ N{sub eff} < 1. We argue that their almost automatic interpretation as a sterile neutrino species is neither from theoretical nor practical parsimony principles preferred over HDM formed by decay products (daughters) of an out-of-equilibrium particle decay. While daughters mimic sterile neutrinos in N{sub eff} and m{sub hdm}{sup eff}, there are opportunities to assess this possibility in likelihood analyses. Connecting cosmological parameters and moments of momentum distribution functions, we show that—also in the case of mass-degenerate daughters with indistinguishable main physical effects—the mimicry breaks down when the next moment, the skewness, is considered. Predicted differences of order one in the root-mean-squares of absolute momenta are too small for current sensitivities.

  11. Identification and characterization of microsatellite from Alternaria brassicicola to assess cross-species transferability and utility as a diagnostic marker.

    PubMed

    Singh, Ruchi; Kumar, Sudheer; Kashyap, Prem Lal; Srivastava, Alok Kumar; Mishra, Sanjay; Sharma, Arun Kumar

    2014-11-01

    Alternaria blight caused by Alternaria brassicicola (Schwein.) Wiltshire and A. brassicae (Berk.) Sacc., is one of the most important disease of rapeseed-mustard, characterized by the formation of spots on leaves, stem, and siliquae with premature defoliation and stunting of growth. These two species are very difficult to differentiate based on disease symptoms or spore morphology. Therefore, the aim of present investigation was to identify and characterize transferable microsatellite loci from A. brassicicola to A. brassicae for the development of diagnostic marker. A total of 8,457 microsatellites were identified from transcript sequences of A. brassicicola. The average density of microsatellites was one microsatellite per 1.94 kb of transcript sequence screened. The most frequent repeat was tri-nucleotide (74.03 %), whereas penta-nucleotide (1.14 %) was least frequent. Among amino acids, arginine (13.11 %) showed maximum abundance followed by lysine (10.11 %). A total of 32 alleles were obtained across the 31 microsatellite loci for the ten isolates of A. brassicicola. In cross-species amplifications, 5 of the 31 markers amplified the corresponding microsatellite regions in twenty isolates of A. brassicae and showed monomorphic banding pattern. Microsatellite locus ABS28 was highly specific for A. brassicicola, as no amplification was observed from twenty-nine other closely related taxa. Primer set, ABS28F/ABS28R, amplified a specific amplicon of 380 bp from all A. brassicicola isolates. Standard curves were generated for A. brassicicola isolate using SYBR Green I fluorescent dye for detection of amplification in real-time PCR assay. The lowest detection limit of assay was 0.01 ng. Thus, the primer set can be used as diagnostic marker to discriminate and diagnose A. brassicicola from synchronously occurring fungus, A. brassicae associated with rapeseed and mustard.

  12. Cross-Species Genome Wide Expression Analysis during Pluripotent Cell Determination in Mouse and Rat Preimplantation Embryos

    PubMed Central

    Cinelli, Paolo

    2012-01-01

    The transition between morula and blastocyst stage during preimplantation development represents the first differentiation event of embryogenesis. Morula cells undergo the first cellular specialization and produce two well-defined populations of cells, the trophoblast and the inner cell mass (ICM). Embryonic stem cells (ESCs) with unlimited self-renewal capacity are believed to represent the in vitro counterpart of the ICM. Both mouse and rat ESCs can be derived from the ICM cells, but their in vitro stability differs. In this study we performed a microarray analysis in which we compared the transcriptome of mouse and rat morula, blastocyst, and ICM. This cross-species comparison represents a good model for understanding the differences in derivation and cultivation of ESCs observed in the two species. In order to identify alternative regulation of important molecular mechanisms the investigation of differential gene expression between the two species was extended at the level of signaling pathways, gene families, and single selected genes of interest. Some of the genes differentially expressed between the two species are already known to be important factors in the maintenance of pluripotency in ESCs, like for example Sox2 or Stat3, or play a role in reprogramming somatic cells to pluripotency like c-Myc, Klf4 and p53 and therefore represent interesting candidates to further analyze in vitro in the rat ESCs. This is the first study investigating the gene expression changes during the transition from morula to blastocyst in the rat preimplantation development. Our data show that in the pluripotent pool of cells of the rat and mouse preimplantation embryo substantial differential regulation of genes is present, which might explain the difficulties observed for the derivation and culture of rat ESCs using mouse conditions. PMID:23077551

  13. Cross-species chromosome painting in bats from Madagascar: the contribution of Myzopodidae to revealing ancestral syntenies in Chiroptera.

    PubMed

    Richards, Leigh R; Rambau, Ramugondo V; Lamb, Jennifer M; Taylor, Peter J; Yang, Fengtang; Schoeman, M Corrie; Goodman, Steven M

    2010-09-01

    The chiropteran fauna of Madagascar comprises eight of the 19 recognized families of bats, including the endemic Myzopodidae. While recent systematic studies of Malagasy bats have contributed to our understanding of the morphological and genetic diversity of the island's fauna, little is known about their cytosystematics. Here we investigate karyotypic relationships among four species, representing four families of Chiroptera endemic to the Malagasy region using cross-species chromosome painting with painting probes of Myotis myotis: Myzopodidae (Myzopoda aurita, 2n = 26), Molossidae (Mormopterus jugularis, 2n = 48), Miniopteridae (Miniopterus griveaudi, 2n = 46), and Vespertilionidae (Myotis goudoti, 2n = 44). This study represents the first time a member of the family Myzopodidae has been investigated using chromosome painting. Painting probes of M. myotis were used to delimit 29, 24, 23, and 22 homologous chromosomal segments in the genomes of M. aurita, M. jugularis, M. griveaudi, and M. goudoti, respectively. Comparison of GTG-banded homologous chromosomes/chromosomal segments among the four species revealed the genome of M. aurita has been structured through 14 fusions of chromosomes and chromosomal segments of M. myotis chromosomes leading to a karyotype consisting solely of bi-armed chromosomes. In addition, chromosome painting revealed a novel X-autosome translocation in M. aurita. Comparison of our results with published chromosome maps provided further evidence for karyotypic conservatism within the genera Mormopterus, Miniopterus, and Myotis. Mapping of chromosomal rearrangements onto a molecular consensus phylogeny revealed ancestral syntenies shared between Myzopoda and other bat species of the infraorders Pteropodiformes and Vespertilioniformes. Our study provides further evidence for the involvement of Robertsonian (Rb) translocations and fusions/fissions in chromosomal evolution within Chiroptera.

  14. Co-infection and cross-species transmission of divergent Hepatocystis lineages in a wild African primate community★

    PubMed Central

    Thurber, Mary I.; Ghai, Ria R.; Hyeroba, Hyeroba; Weny, Geoffrey; Tumukunde, Alex; Chapman, Colin A.; Wiseman, Roger W.; Dinis, Jorge; Steeil, James; Greiner, Ellis C.; Friedrich, Thomas C.; O’Connor, David H.; Goldberg, Tony L.

    2013-01-01

    Hemoparasites of the apicomplexan family Plasmodiidae include the etiological agents of malaria, as well as a suite of non-human primate parasites from which the human malaria agents evolved. Despite the significance of these parasites for global health, little information is available about their ecology in multi-host communities. Primates were investigated in Kibale National Park, Uganda, where ecological relationships among host species are well characterized. Blood samples were examined for parasites of the genera Plasmodium and Hepatocystis using microscopy and PCR targeting the parasite mitochondrial cytochrome b gene, followed by Sanger sequencing. To assess co-infection, “deep sequencing” of a variable region within cytochrome b was performed. Out of nine black-and-white colobus (Colobus guereza), one blue guenon (Cercopithecus mitis), five grey-cheeked mangabeys (Lophocebus albigena), 23 olive baboons (Papio anubis), 52 red colobus (Procolobus rufomitratus) and 12 red-tailed guenons (Cercopithecus ascanius), 79 infections (77.5%) were found, all of which were Hepatocystis spp. Sanger sequencing revealed 25 different parasite haplotypes that sorted phylogenetically into six species-specific but morphologically similar lineages. “Deep sequencing” revealed mixed-lineage co-infections in baboons and red colobus (41.7% and 64.7% of individuals, respectively) but not in other host species. One lineage infecting red colobus also infected baboons, but always as the minor variant, suggesting directional cross-species transmission. Hepatocystis parasites in this primate community are a diverse assemblage of cryptic lineages, some of which co-infect hosts and at least one of which can cross primate species barriers. PMID:23603520

  15. Co-infection and cross-species transmission of divergent Hepatocystis lineages in a wild African primate community.

    PubMed

    Thurber, Mary I; Ghai, Ria R; Hyeroba, David; Weny, Geoffrey; Tumukunde, Alex; Chapman, Colin A; Wiseman, Roger W; Dinis, Jorge; Steeil, James; Greiner, Ellis C; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L

    2013-07-01

    Hemoparasites of the apicomplexan family Plasmodiidae include the etiological agents of malaria, as well as a suite of non-human primate parasites from which the human malaria agents evolved. Despite the significance of these parasites for global health, little information is available about their ecology in multi-host communities. Primates were investigated in Kibale National Park, Uganda, where ecological relationships among host species are well characterized. Blood samples were examined for parasites of the genera Plasmodium and Hepatocystis using microscopy and PCR targeting the parasite mitochondrial cytochrome b gene, followed by Sanger sequencing. To assess co-infection, "deep sequencing" of a variable region within cytochrome b was performed. Out of nine black-and-white colobus (Colobus guereza), one blue guenon (Cercopithecus mitis), five grey-cheeked mangabeys (Lophocebus albigena), 23 olive baboons (Papio anubis), 52 red colobus (Procolobus rufomitratus) and 12 red-tailed guenons (Cercopithecus ascanius), 79 infections (77.5%) were found, all of which were Hepatocystis spp. Sanger sequencing revealed 25 different parasite haplotypes that sorted phylogenetically into six species-specific but morphologically similar lineages. "Deep sequencing" revealed mixed-lineage co-infections in baboons and red colobus (41.7% and 64.7% of individuals, respectively) but not in other host species. One lineage infecting red colobus also infected baboons, but always as the minor variant, suggesting directional cross-species transmission. Hepatocystis parasites in this primate community are a diverse assemblage of cryptic lineages, some of which co-infect hosts and at least one of which can cross primate species barriers. PMID:23603520

  16. Cross-Species Extrapolation of Prediction Model for Lead Transfer from Soil to Corn Grain under Stress of Exogenous Lead

    PubMed Central

    Li, Zhaojun; Yang, Hua; Li, Yupeng; Long, Jian; Liang, Yongchao

    2014-01-01

    There has been increasing concern in recent years regarding lead (Pb) transfer in the soil-plant system. In this study the transfer of Pb (exogenous salts) was investigated from a wide range of Chinese soils to corn grain (Zhengdan 958). Prediction models were developed with combination of the Pb bioconcentration factor (BCF) of Zhengdan 958, and soil pH, organic matter (OM) content, and cation exchange capacity (CEC) through multiple stepwise regressions. Moreover, these prediction models from Zhengdan 958 were applied to other non-model corn species through cross-species extrapolation approach. The results showed that the soil pH and OM were the major factors that controlled Pb transfer from soil to corn grain. The lower pH and OM could improve the bioaccumulation of Pb in corn grain. No significant differences were found between two prediction models derived from the different exogenous Pb contents. When the prediction models were applied to other non-model corn species, the ratio ranges between the predicted BCF values and the measured BCF values were within an interval of 2-fold and close to the solid line of 1∶1 relationship. Moreover, the prediction model i.e. Log[BCF] = −0.098 pH-0.150 log[OM] −1.894 at the treatment of high Pb can effectively reduce the measured BCF intra-species variability for all non-model corn species. These suggested that this prediction model derived from the high Pb content was more adaptable to be applied to other non-model corn species to predict the Pb bioconcentration in corn grain and assess the ecological risk of Pb in different agricultural soils. PMID:24416440

  17. Development of microsatellite markers for a hard-shelled mussel, Mytilus coruscus, and cross-species transfer.

    PubMed

    Kang, J H; Kim, Y K; Park, J Y; Noh, E S; Jeong, J E; Lee, Y S; Choi, T J

    2013-09-27

    The Korean mussel Mytilus coruscus, an endemic marine bivalve mollusk, is economically important. Its population is currently decreasing due to overexploitation and invasion of a more competitive species, Mytilus galloprovincialis. In this study, microsatellite markers for M. coruscus were developed using a cost-effective pyrosequencing technique. Among the 33,859 dinucleotide microsatellite sequences identified, 176 loci that contained more than 8 CA, CT, or AT repeats were selected for primer synthesis. Sixty-four (36.4%) primer sets were produced from the 100- to 200-bp polymerase chain reaction products obtained from 2 M. coruscus individuals. Twenty of these were chosen to amplify DNA from 82 M. coruscus individuals, and 18 polymorphic loci and 2 monomorphic loci were selected as microsatellite markers. The number of alleles and the allele richness of the polymorphic loci ranged from 2 to 22 and from 2.0 to 19.7 with means of 10.8 and 10.1, respectively. Null alleles were detected for all but three loci, which resulted in an observed heterozygosity lower than the expected heterozygosity and therefore an excess of homozygotes. In a cross-species transfer analysis of these markers using 7 Mytilidae species, the locus Mc65 was amplified from all species tested and was found to be polymorphic in all of them. Among the species, M. galloprovincialis, Lithophaga curta, and Hormomya mutabilis showed the same transferability of 25%, but the five amplified loci were polymorphic only in M. galloprovincialis and H. mutabilis. These microsatellite markers may be useful for future resource management and artificial production of juveniles for aquaculture.

  18. Cross-species chromosome painting unveils cytogenetic signatures for the Eulipotyphla and evidence for the polyphyly of Insectivora.

    PubMed

    Ye, Jianping; Biltueva, Larisa; Huang, Ling; Nie, Wenhui; Wang, Jinhuan; Jing, Meidong; Su, Weiting; Vorobieva, Nadezhda V; Jiang, Xuelong; Graphodatsky, Alexander S; Yang, Fengtang

    2006-01-01

    Insectivore-like animals are traditionally believed among the first eutherian mammals that have appeared on the earth. The modern insectivores are thus crucial for understanding the systematics and phylogeny of eutherian mammals as a whole. Here cross-species chromosome painting, with probes derived from flow-sorted chromosomes of human, was used to delimit the homologous chromosomal segments in two Soricidae species, the common shrew (Sorex araneus, 2n = 20/21), and Asiatic short-tailed shrew (Blarinella griselda, 2n = 44), and one Erinaceidae species, the shrew-hedgehog (Neotetracus sinensis, 2n = 32), and human. We report herewith the first comparative maps for the Asiatic short-tailed shrew and the shrew-hedgehog, in addition to a refined comparative map for the common shrew. In total, the 22 human autosomal paints detected 40, 51 and 58 evolutionarily conserved segments in the genomes of common shrew, Asiatic short-tailed shrew, and shrew-hedgehog, respectively, demonstrating that the common shrew has retained a conserved genome organization while the Asiatic short-tailed shrew and shrew-hedgehog have relatively rearranged genomes. In addition to confirming the existence of such ancestral human segmental combinations as HSA 3/21, 12/22, 14/15 and 7/16 that are shared by most eutherian mammals, our study reveals a shared human segmental combination, HSA 4/20, that could phylogenetically unite the Eulipotyphlan (i.e., the core insectivores) species. Our results provide cytogenetic evidence for the polyphyly of the order Insectivora and additional data for the eventual reconstruction of the ancestral eutherian karyotype.

  19. Efficient cross-species capture hybridization and next-generation sequencing of mitochondrial genomes from noninvasively sampled museum specimens.

    PubMed

    Mason, Victor C; Li, Gang; Helgen, Kristofer M; Murphy, William J

    2011-10-01

    The ability to uncover the phylogenetic history of recently extinct species and other species known only from archived museum material has rapidly improved due to the reduced cost and increased sequence capacity of next-generation sequencing technologies. One limitation of these approaches is the difficulty of isolating and sequencing large, orthologous DNA regions across multiple divergent species, which is exacerbated for museum specimens, where DNA quality varies greatly between samples and contamination levels are often high. Here we describe the use of cross-species DNA capture hybridization techniques and next-generation sequencing to selectively isolate and sequence partial to full-length mitochondrial DNA genomes from the degraded DNA of museum specimens, using probes generated from the DNA of a single extant species. We demonstrate our approach on specimens from an enigmatic gliding mammal, the Sunda colugo, which is widely distributed throughout Southeast Asia. We isolated DNA from 13 colugo specimens collected 47-170 years ago, and successfully captured and sequenced mitochondrial DNA from every specimen, frequently recovering fragments with 10%-13% sequence divergence from the capture probe sequence. Phylogenetic results reveal deep genetic divergence among colugos, both within and between the islands of Borneo and Java, as well as between the Malay Peninsula and different Sundaic islands. Our method is based on noninvasive sampling of minute amounts of soft tissue material from museum specimens, leaving the original specimen essentially undamaged. This approach represents a paradigm shift away from standard PCR-based approaches for accessing population genetic and phylogenomic information from poorly known and difficult-to-study species.

  20. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat.

    PubMed

    Diaz Quiroz, Juan Felipe; Tsai, Eve; Coyle, Matthew; Sehm, Tina; Echeverri, Karen

    2014-06-01

    Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs) that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum) and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b) is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal's functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander's regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries. PMID:24719025

  1. Expression profiling and cross-species RNA interference (RNAi) of desiccation-induced transcripts in the anhydrobiotic nematode Aphelenchus avenae

    PubMed Central

    2010-01-01

    Background Some organisms can survive extreme desiccation by entering a state of suspended animation known as anhydrobiosis. The free-living mycophagous nematode Aphelenchus avenae can be induced to enter anhydrobiosis by pre-exposure to moderate reductions in relative humidity (RH) prior to extreme desiccation. This preconditioning phase is thought to allow modification of the transcriptome by activation of genes required for desiccation tolerance. Results To identify such genes, a panel of expressed sequence tags (ESTs) enriched for sequences upregulated in A. avenae during preconditioning was created. A subset of 30 genes with significant matches in databases, together with a number of apparently novel sequences, were chosen for further study. Several of the recognisable genes are associated with water stress, encoding, for example, two new hydrophilic proteins related to the late embryogenesis abundant (LEA) protein family. Expression studies confirmed EST panel members to be upregulated by evaporative water loss, and the majority of genes was also induced by osmotic stress and cold, but rather fewer by heat. We attempted to use RNA interference (RNAi) to demonstrate the importance of this gene set for anhydrobiosis, but found A. avenae to be recalcitrant with the techniques used. Instead, therefore, we developed a cross-species RNAi procedure using A. avenae sequences in another anhydrobiotic nematode, Panagrolaimus superbus, which is amenable to gene silencing. Of 20 A. avenae ESTs screened, a significant reduction in survival of desiccation in treated P. superbus populations was observed with two sequences, one of which was novel, while the other encoded a glutathione peroxidase. To confirm a role for glutathione peroxidases in anhydrobiosis, RNAi with cognate sequences from P. superbus was performed and was also shown to reduce desiccation tolerance in this species. Conclusions This study has identified and characterised the expression profiles of members

  2. Distinguishing between cancer driver and passenger gene alteration candidates via cross-species comparison: a pilot study

    PubMed Central

    2010-01-01

    Background We are developing a cross-species comparison strategy to distinguish between cancer driver- and passenger gene alteration candidates, by utilizing the difference in genomic location of orthologous genes between the human and other mammals. As an initial test of this strategy, we conducted a pilot study with human colorectal cancer (CRC) and its mouse model C57BL/6J ApcMin/+, focusing on human 5q22.2 and 18q21.1-q21.2. Methods We first performed bioinformatics analysis on the evolution of 5q22.2 and 18q21.1-q21.2 regions. Then, we performed exon-targeted sequencing, real time quantitative polymerase chain reaction (qPCR), and real time quantitative reverse transcriptase PCR (qRT-PCR) analyses on a number of genes of both regions with both human and mouse colon tumors. Results These two regions (5q22.2 and 18q21.1-q21.2) are frequently deleted in human CRCs and encode genuine colorectal tumor suppressors APC and SMAD4. They also encode genes such as MCC (mutated in colorectal cancer) with their role in CRC etiology unknown. We have discovered that both regions are evolutionarily unstable, resulting in genes that are clustered in each human region being found scattered at several distinct loci in the genome of many other species. For instance, APC and MCC are within 200 kb apart in human 5q22.2 but are 10 Mb apart in the mouse genome. Importantly, our analyses revealed that, while known CRC driver genes APC and SMAD4 were disrupted in both human colorectal tumors and tumors from ApcMin/+ mice, the questionable MCC gene was disrupted in human tumors but appeared to be intact in mouse tumors. Conclusions These results indicate that MCC may not actually play any causative role in early colorectal tumorigenesis. We also hypothesize that its disruption in human CRCs is likely a mere result of its close proximity to APC in the human genome. Expanding this pilot study to the entire genome may identify more questionable genes like MCC, facilitating the discovery of

  3. A novel endogenous betaretrovirus in the common vampire bat (Desmodus rotundus) suggests multiple independent infection and cross-species transmission events.

    PubMed

    Escalera-Zamudio, Marina; Mendoza, M Lisandra Zepeda; Heeger, Felix; Loza-Rubio, Elizabeth; Rojas-Anaya, Edith; Méndez-Ojeda, Maria L; Taboada, Blanca; Mazzoni, Camila J; Arias, Carlos F; Greenwood, Alex D

    2015-05-01

    The Desmodus rotundus endogenous betaretrovirus (DrERV) is fixed in the vampire bat D. rotundus population and in other phyllostomid bats but is not present in all species from this family. DrERV is not phylogenetically related to Old World bat betaretroviruses but to betaretroviruses from rodents and New World primates, suggesting recent cross-species transmission. A recent integration age estimation of the provirus in some taxa indicates that an exogenous counterpart might have been in recent circulation.

  4. A Novel Endogenous Betaretrovirus in the Common Vampire Bat (Desmodus rotundus) Suggests Multiple Independent Infection and Cross-Species Transmission Events

    PubMed Central

    Mendoza, M. Lisandra Zepeda; Heeger, Felix; Loza-Rubio, Elizabeth; Rojas-Anaya, Edith; Méndez-Ojeda, Maria L.; Taboada, Blanca; Mazzoni, Camila J.; Arias, Carlos F.

    2015-01-01

    The Desmodus rotundus endogenous betaretrovirus (DrERV) is fixed in the vampire bat D. rotundus population and in other phyllostomid bats but is not present in all species from this family. DrERV is not phylogenetically related to Old World bat betaretroviruses but to betaretroviruses from rodents and New World primates, suggesting recent cross-species transmission. A recent integration age estimation of the provirus in some taxa indicates that an exogenous counterpart might have been in recent circulation. PMID:25717107

  5. A novel endogenous betaretrovirus in the common vampire bat (Desmodus rotundus) suggests multiple independent infection and cross-species transmission events.

    PubMed

    Escalera-Zamudio, Marina; Mendoza, M Lisandra Zepeda; Heeger, Felix; Loza-Rubio, Elizabeth; Rojas-Anaya, Edith; Méndez-Ojeda, Maria L; Taboada, Blanca; Mazzoni, Camila J; Arias, Carlos F; Greenwood, Alex D

    2015-05-01

    The Desmodus rotundus endogenous betaretrovirus (DrERV) is fixed in the vampire bat D. rotundus population and in other phyllostomid bats but is not present in all species from this family. DrERV is not phylogenetically related to Old World bat betaretroviruses but to betaretroviruses from rodents and New World primates, suggesting recent cross-species transmission. A recent integration age estimation of the provirus in some taxa indicates that an exogenous counterpart might have been in recent circulation. PMID:25717107

  6. Phenotypic plasticity confers multiple fitness benefits to a mimic.

    PubMed

    Cortesi, Fabio; Feeney, William E; Ferrari, Maud C O; Waldie, Peter A; Phillips, Genevieve A C; McClure, Eva C; Sköld, Helen N; Salzburger, Walter; Marshall, N Justin; Cheney, Karen L

    2015-03-30

    Animal communication is often deceptive; however, such dishonesty can become ineffective if it is used too often, is used out of context, or is too easy to detect [1-3]. Mimicry is a common form of deception, and most mimics gain the greatest fitness benefits when they are rare compared to their models [3, 4]. If mimics are encountered too frequently or if their model is absent, avoidance learning of noxious models is disrupted (Batesian mimicry [3]), or receivers become more vigilant and learn to avoid perilous mimics (aggressive mimicry [4]). Mimics can moderate this selective constraint by imperfectly resembling multiple models [5], through polymorphisms [6], or by opportunistically deploying mimetic signals [1, 7]. Here we uncover a novel mechanism to escape the constraints of deceptive signaling: phenotypic plasticity allows mimics to deceive targets using multiple guises. Using a combination of behavioral, cell histological, and molecular methods, we show that a coral reef fish, the dusky dottyback (Pseudochromis fuscus), flexibly adapts its body coloration to mimic differently colored reef fishes and in doing so gains multiple fitness benefits. We find that by matching the color of other reef fish, dottybacks increase their success of predation upon juvenile fish prey and are therefore able to deceive their victims by resembling multiple models. Furthermore, we demonstrate that changing color also increases habitat-associated crypsis that decreases the risk of being detected by predators. Hence, when mimics and models share common selective pressures, flexible imitation of models might inherently confer secondary benefits to mimics. Our results show that phenotypic plasticity can act as a mechanism to ease constraints that are typically associated with deception. VIDEO ABSTRACT. PMID:25802153

  7. Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer

    PubMed Central

    Matho, Michael H.; Schlossman, Andrew; Meng, Xiangzhi; Benhnia, Mohammed Rafii-El-Idrissi; Kaever, Thomas; Buller, Mark; Doronin, Konstantin; Parker, Scott; Peters, Bjoern; Crotty, Shane; Xiang, Yan; Zajonc, Dirk M.

    2015-01-01

    Vaccinia virus A33 is an extracellular enveloped virus (EEV)-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal antibodies (MAbs) by immunizing mice with live VACV, followed by boosting with the soluble A33 homodimeric ectodomain. Five A33 specific MAbs were capable of neutralizing EEV in the presence of complement. All MAbs bind to conformational epitopes on A33 but not to linear peptides. To identify the epitopes, we have adetermined the crystal structures of three representative neutralizing MAbs in complex with A33. We have further determined the binding kinetics for each of the three antibodies to wild-type A33, as well as to engineered A33 that contained single alanine substitutions within the epitopes of the three crystallized antibodies. While the Fab of both MAbs A2C7 and A20G2 binds to a single A33 subunit, the Fab from MAb A27D7 binds to both A33 subunits simultaneously. A27D7 binding is resistant to single alanine substitutions within the A33 epitope. A27D7 also demonstrated high-affinity binding with recombinant A33 protein that mimics other orthopoxvirus strains in the A27D7 epitope, such as ectromelia, monkeypox, and cowpox virus, suggesting that A27D7 is a potent cross-neutralizer. Finally, we confirmed that A27D7 protects mice against a lethal challenge with ectromelia virus. PMID:26325270

  8. Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure

    PubMed Central

    Trewby, Hannah; Ayele, Gizachew; Borzacchiello, Giuseppe; Brandt, Sabine; Campo, M. Saveria; Del Fava, Claudia; Marais, Johan; Leonardi, Leonardo; Vanselow, Barbara; Biek, Roman

    2014-01-01

    Papillomaviruses are a family of slowly evolving DNA viruses and their evolution is commonly linked to that of their host species. However, whilst bovine papillomavirus-1 (BPV-1) primarily causes warts in its natural host, the cow, it can also cause locally aggressive and invasive skin tumours in equids, known as sarcoids, and thus provides a rare contemporary example of cross-species transmission of a papillomavirus. Here, we describe the first phylogenetic analysis of BPV-1 in equine sarcoids to our knowledge, allowing us to explore the evolutionary history of BPV-1 and investigate its cross-species association with equids. A phylogenetic analysis of the BPV-1 transcriptional promoter region (the long control region or LCR) was conducted on 15 bovine and 116 equine samples from four continents. Incorporating previous estimates for evolutionary rates in papillomavirus implied that the genetic diversity in the LCR variants was ancient and predated domestication of both equids and cattle. The phylogeny demonstrated geographical segregation into an ancestral group (African, South American and Australian samples), and a more recently derived, largely European clade. Whilst our data are consistent with BPV-1 originating in cattle, we found evidence of multiple, probably relatively recent, cross-species transmission events into horses. We also demonstrated the high prevalence of one particular sequence variant (variant 20), and suggest this may indicate that this variant shows a fitness advantage in equids. Although strong host specificity remains the norm in papillomaviruses, our results demonstrate that exceptions to this rule exist and can become epidemiologically relevant. PMID:25185436

  9. Cross-species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live-virus vaccines.

    PubMed

    Louz, Derrick; Bergmans, Hans E; Loos, Birgit P; Hoeben, Rob C

    2005-10-01

    All living organisms are continuously exposed to a plethora of viruses. In general, viruses tend to be restricted to the natural host species which they infect. From time to time viruses cross the host-range barrier expanding their host range. However, in very rare cases cross-species transfer is followed by the establishment and persistence of a virus in the new host species, which may result in disease. Recent examples of viruses that have crossed the species barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI), monkeypox virus, and the SARS-associated coronavirus (SARS-CoV). The opportunities for cross-species transfer of mammalian viruses have increased in recent years due to increased contact between humans and animal reservoirs. However, it is difficult to predict when such events will take place since the viral adaptation that is needed to accomplish this is multifactorial and stochastic. Against this background the intensified use of viruses and their genetically modified variants as viral gene transfer vectors for biomedical research, experimental gene therapy and for live-vector vaccines is a cause for concern. This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross-species transfer of viruses in nature, with emphasis on the occurrence of host-range mutants resulting from either cell culture or tropism engineering. The issues are raised with the intention to assist in risk assessments for activities with vector viruses. PMID:15986492

  10. APOBEC3G polymorphism as a selective barrier to cross-species transmission and emergence of pathogenic SIV and AIDS in a primate host.

    PubMed

    Krupp, Annabel; McCarthy, Kevin R; Ooms, Marcel; Letko, Michael; Morgan, Jennifer S; Simon, Viviana; Johnson, Welkin E

    2013-01-01

    Cellular restriction factors, which render cells intrinsically resistant to viruses, potentially impose genetic barriers to cross-species transmission and emergence of viral pathogens in nature. One such factor is APOBEC3G. To overcome APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that targets APOBEC3G for degradation. As with many restriction factor genes, primate APOBEC3G displays strong signatures of positive selection. This is interpreted as evidence that the primate APOBEC3G locus reflects a long-term evolutionary "arms-race" between retroviruses and their primate hosts. Here, we provide direct evidence that APOBEC3G has functioned as a barrier to cross-species transmission, selecting for viral resistance during emergence of the AIDS-causing pathogen SIVmac in captive colonies of Asian macaques in the 1970s. Specifically, we found that rhesus macaques have multiple, functionally distinct APOBEC3G alleles, and that emergence of SIVmac and simian AIDS required adaptation of the virus to evade APOBEC3G-mediated restriction. Our evidence includes the first comparative analysis of APOBEC3G polymorphism and function in both a reservoir and recipient host species (sooty mangabeys and rhesus macaques, respectively), and identification of adaptations unique to Vif proteins of the SIVmac lineage that specifically antagonize rhesus APOBEC3G alleles. By demonstrating that interspecies variation in a known restriction factor selected for viral counter-adaptations in the context of a documented case of cross-species transmission, our results lend strong support to the evolutionary "arms-race" hypothesis. Importantly, our study confirms that APOBEC3G divergence can be a critical determinant of interspecies transmission and emergence of primate lentiviruses, including viruses with the potential to infect and spread in human populations.

  11. Cross-species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live-virus vaccines.

    PubMed

    Louz, Derrick; Bergmans, Hans E; Loos, Birgit P; Hoeben, Rob C

    2005-10-01

    All living organisms are continuously exposed to a plethora of viruses. In general, viruses tend to be restricted to the natural host species which they infect. From time to time viruses cross the host-range barrier expanding their host range. However, in very rare cases cross-species transfer is followed by the establishment and persistence of a virus in the new host species, which may result in disease. Recent examples of viruses that have crossed the species barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI), monkeypox virus, and the SARS-associated coronavirus (SARS-CoV). The opportunities for cross-species transfer of mammalian viruses have increased in recent years due to increased contact between humans and animal reservoirs. However, it is difficult to predict when such events will take place since the viral adaptation that is needed to accomplish this is multifactorial and stochastic. Against this background the intensified use of viruses and their genetically modified variants as viral gene transfer vectors for biomedical research, experimental gene therapy and for live-vector vaccines is a cause for concern. This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross-species transfer of viruses in nature, with emphasis on the occurrence of host-range mutants resulting from either cell culture or tropism engineering. The issues are raised with the intention to assist in risk assessments for activities with vector viruses.

  12. Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

    SciTech Connect

    Rajagopalan, Raghavan

    2006-01-30

    The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling study revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.

  13. Development of nine new microsatellite loci for the American beaver, Castor canadensis (Rodentia: Castoridae), and cross-species amplification in the European beaver, Castor fiber

    USGS Publications Warehouse

    Pelz-Serrano, K.; Munguia-Vega, A.; Piaggio, A.J.; Neubaum, M.; Munclinger, P.; PArtl, A.; van Riper, Charles; Culver, M.

    2009-01-01

    We developed nine new nuclear dinucleotide microsatellite loci for Castor canadensis. All loci were polymorphic, except for one. The number of alleles ranged from two to four and from five to 12 in populations from Arizona and Wisconsin, respectively. Average heterozygosity ranged from 0.13 to 0.86 per locus. Since cross-species amplification in Castor fiber was successful only in four loci, we tested also nine recently published C. canadensis loci in the Eurasian species. Eight of the published loci amplified; however, three were monomorphic. The number of alleles was lower in C. fiber than in C. canadensis at all loci tested. ?? 2009 Blackwell Publishing Ltd.

  14. Isolation and characterization of microsatellite markers for the ornamental discus fish Symphysodon discus and cross-species amplification in other Heroini cichlid species.

    PubMed

    Amado, Manuella Villar; Hrbek, Tomas; Gravena, Waleska; Fantin, Cleiton; DE Assunção, Enedina Nogueira; Astolfi-Filho, Spartaco; Farias, Izeni P

    2008-11-01

    The discus fishes (Symphysodon spp.) are economically important ornamental species. Thirteen microsatellite markers were developed from a CT(12) - and CA(12) -enriched whole genomic DNA library of Symphysodon discus. Allelic variability was tested on 44 individuals of two species (S. discus and S. aequifasciatus). Allelic richness ranged from two to 11 alleles per locus and observed heterozygosities from 0.083 to 0.998. All loci were at Hardy-Weinberg equilibrium, and no pair of loci showed linkage disequilibrium within a species. Cross-species amplification was also successfully performed in the Neotropical cichlids Uaru amphiacanthoides, Hoplarchus psittacus, Hypselecara coryphaenoides, Pterophyllum sp., Mesonauta sp. and Heros sp.

  15. SuperMimic – Fitting peptide mimetics into protein structures

    PubMed Central

    Goede, Andrean; Michalsky, Elke; Schmidt, Ulrike; Preissner, Robert

    2006-01-01

    Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently. PMID:16403211

  16. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers.

    PubMed

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R; Tucker, Kimberly Pause; Bonde, Robert K; McGuire, Peter M; Lanyon, Janet M

    2010-03-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These cross-species microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals.

  17. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers.

    PubMed

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R; Tucker, Kimberly Pause; Bonde, Robert K; McGuire, Peter M; Lanyon, Janet M

    2010-03-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These cross-species microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals. PMID:21565032

  18. Induction of ebolavirus cross-species immunity using retrovirus-like particles bearing the Ebola virus glycoprotein lacking the mucin-like domain

    PubMed Central

    2012-01-01

    Background The genus Ebolavirus includes five distinct viruses. Four of these viruses cause hemorrhagic fever in humans. Currently there are no licensed vaccines for any of them; however, several vaccines are under development. Ebola virus envelope glycoprotein (GP1,2) is highly immunogenic, but antibodies frequently arise against its least conserved mucin-like domain (MLD). We hypothesized that immunization with MLD-deleted GP1,2 (GPΔMLD) would induce cross-species immunity by making more conserved regions accessible to the immune system. Methods To test this hypothesis, mice were immunized with retrovirus-like particles (retroVLPs) bearing Ebola virus GPΔMLD, DNA plasmids (plasmo-retroVLP) that can produce such retroVLPs in vivo, or plasmo-retroVLP followed by retroVLPs. Results Cross-species neutralizing antibody and GP1,2-specific cellular immune responses were successfully induced. Conclusion Our findings suggest that GPΔMLD presented through retroVLPs may provide a strategy for development of a vaccine against multiple ebolaviruses. Similar vaccination strategies may be adopted for other viruses whose envelope proteins contain highly variable regions that may mask more conserved domains from the immune system. PMID:22273269

  19. Cross-Species Extrapolation of Uptake and Disposition of Neutral Organic Chemicals in Fish Using a Multispecies Physiologically-Based Toxicokinetic Model Framework.

    PubMed

    Brinkmann, Markus; Schlechtriem, Christian; Reininghaus, Mathias; Eichbaum, Kathrin; Buchinger, Sebastian; Reifferscheid, Georg; Hollert, Henner; Preuss, Thomas G

    2016-02-16

    The potential to bioconcentrate is generally considered to be an unwanted property of a substance. Consequently, chemical legislation, including the European REACH regulations, requires the chemical industry to provide bioconcentration data for chemicals that are produced or imported at volumes exceeding 100 tons per annum or if there is a concern that a substance is persistent, bioaccumulative, and toxic. For the filling of the existing data gap for chemicals produced or imported at levels that are below this stipulated volume, without the need for additional animal experiments, physiologically-based toxicokinetic (PBTK) models can be used to predict whole-body and tissue concentrations of neutral organic chemicals in fish. PBTK models have been developed for many different fish species with promising results. In this study, we developed PBTK models for zebrafish (Danio rerio) and roach (Rutilus rutilus) and combined them with existing models for rainbow trout (Onchorhynchus mykiss), lake trout (Salvelinus namaycush), and fathead minnow (Pimephales promelas). The resulting multispecies model framework allows for cross-species extrapolation of the bioaccumulative potential of neutral organic compounds. Predictions were compared with experimental data and were accurate for most substances. Our model can be used for probabilistic risk assessment of chemical bioaccumulation, with particular emphasis on cross-species evaluations. PMID:26794144

  20. A Cross-species Comparison of Facial Morphology and Movement in Humans and Chimpanzees Using the Facial Action Coding System (FACS).

    PubMed

    Vick, Sarah-Jane; Waller, Bridget M; Parr, Lisa A; Smith Pasqualini, Marcia C; Bard, Kim A

    2007-03-01

    A comparative perspective has remained central to the study of human facial expressions since Darwin's [(1872/1998). The expression of the emotions in man and animals (3rd ed.). New York: Oxford University Press] insightful observations on the presence and significance of cross-species continuities and species-unique phenomena. However, cross-species comparisons are often difficult to draw due to methodological limitations. We report the application of a common methodology, the Facial Action Coding System (FACS) to examine facial movement across two species of hominoids, namely humans and chimpanzees. FACS [Ekman & Friesen (1978). Facial action coding system. CA: Consulting Psychology Press] has been employed to identify the repertoire of human facial movements. We demonstrate that FACS can be applied to other species, but highlight that any modifications must be based on both underlying anatomy and detailed observational analysis of movements. Here we describe the ChimpFACS and use it to compare the repertoire of facial movement in chimpanzees and humans. While the underlying mimetic musculature shows minimal differences, important differences in facial morphology impact upon the identification and detection of related surface appearance changes across these two species.

  1. Cross-Species Extrapolation of Uptake and Disposition of Neutral Organic Chemicals in Fish Using a Multispecies Physiologically-Based Toxicokinetic Model Framework.

    PubMed

    Brinkmann, Markus; Schlechtriem, Christian; Reininghaus, Mathias; Eichbaum, Kathrin; Buchinger, Sebastian; Reifferscheid, Georg; Hollert, Henner; Preuss, Thomas G

    2016-02-16

    The potential to bioconcentrate is generally considered to be an unwanted property of a substance. Consequently, chemical legislation, including the European REACH regulations, requires the chemical industry to provide bioconcentration data for chemicals that are produced or imported at volumes exceeding 100 tons per annum or if there is a concern that a substance is persistent, bioaccumulative, and toxic. For the filling of the existing data gap for chemicals produced or imported at levels that are below this stipulated volume, without the need for additional animal experiments, physiologically-based toxicokinetic (PBTK) models can be used to predict whole-body and tissue concentrations of neutral organic chemicals in fish. PBTK models have been developed for many different fish species with promising results. In this study, we developed PBTK models for zebrafish (Danio rerio) and roach (Rutilus rutilus) and combined them with existing models for rainbow trout (Onchorhynchus mykiss), lake trout (Salvelinus namaycush), and fathead minnow (Pimephales promelas). The resulting multispecies model framework allows for cross-species extrapolation of the bioaccumulative potential of neutral organic compounds. Predictions were compared with experimental data and were accurate for most substances. Our model can be used for probabilistic risk assessment of chemical bioaccumulation, with particular emphasis on cross-species evaluations.

  2. Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead.

    PubMed

    Lassiter, Meredith Gooding; Owens, Elizabeth Oesterling; Patel, Molini M; Kirrane, Ellen; Madden, Meagan; Richmond-Bryant, Jennifer; Hines, Erin Pias; Davis, J Allen; Vinikoor-Imler, Lisa; Dubois, Jean-Jacques

    2015-04-01

    The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants.

  3. Estimation of MIMIC Model Parameters with Multilevel Data

    ERIC Educational Resources Information Center

    Finch, W. Holmes; French, Brian F.

    2011-01-01

    The purpose of this simulation study was to assess the performance of latent variable models that take into account the complex sampling mechanism that often underlies data used in educational, psychological, and other social science research. Analyses were conducted using the multiple indicator multiple cause (MIMIC) model, which is a flexible…

  4. Design of the MIMIC Network for Preparing Tomorrow's Teachers.

    ERIC Educational Resources Information Center

    Abate, Ronald J.; Jin, Seung

    This paper provides an overview of the variables critical to the success of an Internet site design. The site under development represents one aspect of dissemination for the Modeling Instruction with Modern Information and Communications Technologies: the MIMIC Project, a U.S. Department of Education Capacity Building Grant. The site focuses on…

  5. Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance

    PubMed Central

    2013-01-01

    Background Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. Methods 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. Results Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). Conclusions Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria. PMID:23398958

  6. Development of Microsatellite Markers in the Deep-Sea Cup Coral Desmophyllum dianthus by 454 Sequencing and Cross-Species Amplifications in Scleractinia Order.

    PubMed

    Addamo, Anna M; García-Jiménez, Ricardo; Taviani, Marco; Machordom, Annie

    2015-01-01

    Microsatellite loci were isolated for the first time for the deep-sea coral Desmophyllum dianthus, using 454 GS-FLX Titanium pyrosequencing. We developed conditions for amplifying 24 markers in 10 multiplex reactions. Three to 16 alleles per locus were detected across 25 samples analyzed from Santa Maria di Leuca coral province (Mediterranean Sea). For the 24 polymorphic loci, observed and expected heterozygosities ranged from 0.211 to 0.880 and 0.383 to 0.910, respectively; 3 loci deviated from Hardy-Weinberg equilibrium, after null allele and sequential Holm-Bonferroni corrections. These newly isolated microsatellites are very useful genetic markers that provide data for future conservation strategies. Cross-amplification of these microsatellites, tested in 46 coral species, representing 40 genera, and 10 families of the phylum Cnidaria, produced informative allelic profiles for 1 to 24 loci. The utility of extending analyses to cross-species amplifications is also discussed.

  7. Microsatellite DNA primers for the candy darter, Etheostoma osburni and variegate darter, Etheostoma variatum, and cross-species amplification in other darters (Percidae)

    USGS Publications Warehouse

    Switzer, J.F.; Welsh, S.A.; King, T.L.

    2008-01-01

    In order to investigate a potential hybrid zone between the candy darter, Etheostoma osburni, and variegate darter, Etheostoma variatum, and examine population variation within E. osburni, a suite of primers for 15 polymorphic microsatellite loci were developed. The average number of alleles per locus was 5.5 in E. osburni and 7.6 in E. variatum, and the average observed heterozygosities were 62.5% and 71.4%, respectively. There were no deviations from Hardy-Weinberg equilibrium and no observed linkage disequilibrium after Bonferroni correction. The utility of these primers was also tested in 11 species of darters representing all four genera of darters. Success of cross-species amplification was largely consistent with phylogenetic relationships of darters. ?? 2007 The Authors.

  8. Cross-species, amplifiable microsatellite markers for neoverrucid barnacles from deep-sea hydrothermal vents developed using next-generation sequencing.

    PubMed

    Nakajima, Yuichi; Shinzato, Chuya; Khalturina, Mariia; Watanabe, Hiromi; Inagaki, Fumio; Satoh, Nori; Mitarai, Satoshi

    2014-08-18

    Barnacles of the genus Neoverruca are abundant near deep-sea hydrothermal vents of the northwestern Pacific Ocean, and are useful for understanding processes of population formation and maintenance of deep-sea vent faunas. Using next-generation sequencing, we isolated 12 polymorphic microsatellite loci from Neoverruca sp., collected in the Okinawa Trough. These microsatellite loci revealed 2-19 alleles per locus. The expected and observed heterozygosities ranged from 0.286 to 1.000 and 0.349 to 0.935, respectively. Cross-species amplification showed that 9 of the 12 loci were successfully amplified for Neoverruca brachylepadoformis in the Mariana Trough. A pairwise FST value calculated using nine loci showed significant genetic differentiation between the two species. Consequently, the microsatellite markers we developed will be useful for further population genetic studies to elucidate genetic diversity, differentiation, classification, and evolutionary processes in the genus Neoverruca.

  9. Chromosome evolution in kangaroos (Marsupialia: Macropodidae): cross species chromosome painting between the tammar wallaby and rock wallaby spp. with the 2n = 22 ancestral macropodid karyotype.

    PubMed

    O'Neill, R J; Eldridge, M D; Toder, R; Ferguson-Smith, M A; O'Brien, P C; Graves, J A

    1999-06-01

    Marsupial mammals show extraordinary karyotype stability, with 2n = 14 considered ancestral. However, macropodid marsupials (kangaroos and wallabies) exhibit a considerable variety of karyotypes, with a hypothesised ancestral karyotype of 2n = 22. Speciation and karyotypic diversity in rock wallabies (Petrogale) is exceptional. We used cross species chromosome painting to examine the chromosome evolution between the tammar wallaby (2n = 16) and three 2n = 22 rock wallaby species groups with the putative ancestral karyotype. Hybridization of chromosome paints prepared from flow sorted chromosomes of the tammar wallaby to Petrogale spp., showed that this ancestral karyotype is largely conserved among 2n = 22 rock wallaby species, and confirmed the identity of ancestral chromosomes which fused to produce the bi-armed chromosomes of the 2n = 16 tammar wallaby. These results illustrate the fission-fusion process of karyotype evolution characteristic of the kangaroo group.

  10. A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease

    PubMed Central

    Onken, Michael D.; Winkler, Ashley E.; Kanchi, Krishna-Latha; Chalivendra, Varun; Law, Jonathan H.; Rickert, Charles G.; Kallogjeri, Dorina; Judd, Nancy P.; Dunn, Gavin P.; Piccirillo, Jay F.; Lewis, James S.; Mardis, Elaine R.; Uppaluri, Ravindra

    2014-01-01

    Purpose Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. Experimental Design Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature and we assessed its representation in 4 independent human datasets comprising 324 patients using weighted voting and Gene Set Enrichment Analysis (GSEA). Kaplan-Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A qRT-PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. Results NGS revealed conservation of human driver pathway mutations in mouse OSCC including in Trp53, MAPK, PI3K, NOTCH, JAK/STAT and FAT1–4. Moreover, comparative analysis between The Cancer Genome Atlas (TCGA) and mouse samples defined AKAP9, MED12L and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in 4 independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified OSCC patients with a 93.5% accuracy. Conclusions These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. PMID:24668645

  11. A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal tissue metabolism and cross-species dosimetry.

    PubMed

    Campbell, Jerry L; Andersen, Melvin E; Clewell, Harvey J

    2014-05-01

    A PBPK model for naphthalene in the rat and human that incorporates a hybrid CFD-PBPK description of the upper respiratory tract was developed to support cross-species dosimetry comparisons of naphthalene concentrations and tissue normalized rate of metabolism in the nasal respiratory and olfactory epithelium, lung and liver. In vitro measurements of metabolic rates from microsomal incubations published for rat and monkey (surrogate for human) were scaled to the specific tissue based on the tissue microsomal content and volume of tissue. The model reproduces time courses for naphthalene blood concentrations from intravenous and inhalation exposures in rats and upper respiratory tract extraction data in both naïve rats and rats pre-treated to inhibit nasal metabolism. This naphthalene model was applied to estimate human equivalent inhalation concentrations (HECs) corresponding to several NOAELs or LOAELs for the non-cancer effects of naphthalene in rats. Two approaches for cross-species extrapolation were compared: (1) equivalence based on tissue naphthalene concentration and (2) equivalence based on amount metabolized per minute (normalized to tissue volume). At the NOAEL of 0.1 ppm, the regional gas dosimetry ratio (RGDR) based on naphthalene concentration was 0.18 for the dorsal olfactory region; however, the RGDR rises to 5.4 when based on the normalized amount metabolized due to the lower of expression of CYP isozymes in the nasal epithelium of primates and humans. The resulting HEC is 0.12 ppm (0.63 mg/m(3)) continuous exposure at the rat NOAEL of 0.1 ppm (6 h/day, 5 days/week).

  12. Multi-linear regression analysis, preliminary biotic ligand modeling, and cross species comparison of the effects of water chemistry on chronic lead toxicity in invertebrates.

    PubMed

    Esbaugh, A J; Brix, K V; Mager, E M; De Schamphelaere, K; Grosell, M

    2012-03-01

    The current study examined the chronic toxicity of lead (Pb) to three invertebrate species: the cladoceran Ceriodaphnia dubia, the snail Lymnaea stagnalis and the rotifer Philodina rapida. The test media consisted of natural waters from across North America, varying in pertinent water chemistry parameters including dissolved organic carbon (DOC), calcium, pH and total CO(2). Chronic toxicity was assessed using reproductive endpoints for C. dubia and P. rapida while growth was assessed for L. stagnalis, with chronic toxicity varying markedly according to water chemistry. A multi-linear regression (MLR) approach was used to identify the relative importance of individual water chemistry components in predicting chronic Pb toxicity for each species. DOC was an integral component of MLR models for C. dubia and L. stagnalis, but surprisingly had no predictive impact on chronic Pb toxicity for P. rapida. Furthermore, sodium and total CO(2) were also identified as important factors affecting C. dubia toxicity; no other factors were predictive for L. stagnalis. The Pb toxicity of P. rapida was predicted by calcium and pH. The predictive power of the C. dubia and L. stagnalis MLR models was generally similar to that of the current C. dubia BLM, with R(2) values of 0.55 and 0.82 for the respective MLR models, compared to 0.45 and 0.79 for the respective BLMs. In contrast the BLM poorly predicted P. rapida toxicity (R(2)=0.19), as compared to the MLR (R(2)=0.92). The cross species variability in the effects of water chemistry, especially with respect to rotifers, suggests that cross species modeling of invertebrate chronic Pb toxicity using a C. dubia model may not always be appropriate.

  13. Varroa destructor changes its cuticular hydrocarbons to mimic new hosts

    PubMed Central

    Le Conte, Y.; Huang, Z. Y.; Roux, M.; Zeng, Z. J.; Christidès, J.-P.; Bagnères, A.-G.

    2015-01-01

    Varroa destructor (Vd) is a honeybee ectoparasite. Its original host is the Asian honeybee, Apis cerana, but it has also become a severe, global threat to the European honeybee, Apis mellifera. Previous studies have shown that Varroa can mimic a host's cuticular hydrocarbons (HC), enabling the parasite to escape the hygienic behaviour of the host honeybees. By transferring mites between the two honeybee species, we further demonstrate that Vd is able to mimic the cuticular HC of a novel host species when artificially transferred to this new host. Mites originally from A. cerana are more efficient than mites from A. mellifera in mimicking HC of both A. cerana and A. mellifera. This remarkable adaptability may explain their relatively recent host-shift from A. cerana to A. mellifera. PMID:26041867

  14. Varroa destructor changes its cuticular hydrocarbons to mimic new hosts.

    PubMed

    Le Conte, Y; Huang, Z Y; Roux, M; Zeng, Z J; Christidès, J-P; Bagnères, A-G

    2015-06-01

    Varroa destructor (Vd) is a honeybee ectoparasite. Its original host is the Asian honeybee, Apis cerana, but it has also become a severe, global threat to the European honeybee, Apis mellifera. Previous studies have shown that Varroa can mimic a host's cuticular hydrocarbons (HC), enabling the parasite to escape the hygienic behaviour of the host honeybees. By transferring mites between the two honeybee species, we further demonstrate that Vd is able to mimic the cuticular HC of a novel host species when artificially transferred to this new host. Mites originally from A. cerana are more efficient than mites from A. mellifera in mimicking HC of both A. cerana and A. mellifera. This remarkable adaptability may explain their relatively recent host-shift from A. cerana to A. mellifera.

  15. Biological Functionalization of Carbon Nanotubes Using Cell Surface Mucin Mimics

    NASA Astrophysics Data System (ADS)

    Chen, Xing; Lee, Goo Soo; Zettl, Alex; Bertozzi, Carolyn

    2004-03-01

    Carbon Nanotubes (CNTs) are molecular wires with remarkable structural, electrical, and mechanical properties. Their potential applications in biology include sensing, imaging, and scaffolding for cell growth, but are presently limited by chemical incompatibility of the CNT surface with biological components and their aqueous milieu. Here we describe a biomimetic surface modification of CNTs using glycosylated polymers designed to mimic natural cell surface mucins. The polymers were end-functionalized with lipid tails for self-assembly on the CNT surface through hydrophobic interactions. Mucin mimic-coated CNTs were soluble in water, resisted non-specific protein binding and bound specifically to biomolecules via receptor-ligand interactions. This strategy for biomimetic surface engineering provides a means to bridge nanomaterials and biological systems.

  16. MIMIC-III, a freely accessible critical care database

    PubMed Central

    Johnson, Alistair E.W.; Pollard, Tom J.; Shen, Lu; Lehman, Li-wei H.; Feng, Mengling; Ghassemi, Mohammad; Moody, Benjamin; Szolovits, Peter; Anthony Celi, Leo; Mark, Roger G.

    2016-01-01

    MIMIC-III (‘Medical Information Mart for Intensive Care’) is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care hospital. Data includes vital signs, medications, laboratory measurements, observations and notes charted by care providers, fluid balance, procedure codes, diagnostic codes, imaging reports, hospital length of stay, survival data, and more. The database supports applications including academic and industrial research, quality improvement initiatives, and higher education coursework. PMID:27219127

  17. MIMIC-III, a freely accessible critical care database.

    PubMed

    Johnson, Alistair E W; Pollard, Tom J; Shen, Lu; Lehman, Li-Wei H; Feng, Mengling; Ghassemi, Mohammad; Moody, Benjamin; Szolovits, Peter; Celi, Leo Anthony; Mark, Roger G

    2016-01-01

    MIMIC-III ('Medical Information Mart for Intensive Care') is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care hospital. Data includes vital signs, medications, laboratory measurements, observations and notes charted by care providers, fluid balance, procedure codes, diagnostic codes, imaging reports, hospital length of stay, survival data, and more. The database supports applications including academic and industrial research, quality improvement initiatives, and higher education coursework.

  18. Photoassisted Synthesis of Enantiopure Alkaloid Mimics Possessing Unprecedented Polyheterocyclic Cores

    PubMed Central

    Bhuvan Kumar, N.N.; Mukhina, Olga A.; Kutateladze, Andrei G.

    2013-01-01

    Enantiopure alkaloid mimics are synthesized via high yielding intramolecular cycloadditions of photogenerated azaxylylenes tethered to pyrroles, with further growth of molecular complexity via post-photochemical transformations of primary photoproducts. This expeditious access to structurally unprecedented polyheterocyclic cores is being developed in the context of diversity-oriented synthesis, as the modular design allows for rapid “pre-assembly” of diverse photoprecursors from simple building blocks/diversity inputs. PMID:23789841

  19. Wong-type dermatomyositis: a mimic of many dermatoses.

    PubMed

    Mutasim, Diya F; Egesi, Adaeze; Spicknall, Kerith E

    2016-09-01

    Wong-type dermatomyositis (DM) is a rare variant characterized by keratotic follicular papules that may mimic pityriasis rubra pilaris. Histopathologic examination shows follicular and non-follicular epidermal invaginations filled with keratin. The diagnosis is often delayed. Twenty-four cases of Wong-type DM have been reported thus far in the literature. Herein, we report the clinical and histopathologic findings of three additional cases in order to raise awareness of the disorder. PMID:27161243

  20. Angiomyolipoma with epithelial cysts: mimic of renal cell carcinoma.

    PubMed

    Rosenkrantz, Andrew B; Hecht, Elizabeth M; Taneja, Samir S; Melamed, Jonathan

    2010-01-01

    Angiomyolipoma with epithelial cysts (AMLEC) is a rare variant of angiomyolipoma with minimal fat that contains epithelial-lined cysts and may mimic a cystic renal cell carcinoma. While 17 cases have been described in the pathology literature since this entity was first described in 2006, the radiologic appearance was not demonstrated in any of these cases. We report the CT and MRI appearance of AMLEC found incidentally in a patient with lupus nephritis.

  1. Manganese superoxide dismutase, MnSOD and its mimics

    PubMed Central

    Miriyala, Sumitra; Spasojevic, Ivan; Tovmasyan, Artak; Salvemini, Daniela; Vujaskovic, Zeljko; St. Clair, Daret; Batinic-Haberle, Ines

    2011-01-01

    Increased understanding of the role of mitochondria under physiological and pathological conditions parallels increased exploration of synthetic and natural compounds able to mimic MnSOD – endogenous mitochondrial antioxidant defense essential for the existence of virtually all aerobic organisms from bacteria to humans. This review describes most successful mitochondrially-targeted redox-active compounds, Mn porphyrins and MitoQ10 in detail, and briefly addresses several other compounds that are either catalysts of O2·− dismutation, or its non-catalytic scavengers, and that reportedly attenuate mitochondrial dysfunction. While not a true catalyst (SOD mimic) of O2·− dismutation, MitoQ10 oxidizes O2·− to O2 with a high rate constant. In vivo it is readily reduced to quinol, MitoQH2, which in turn reduces ONOO− to ·NO2, producing semiquinone radical that subsequently dismutes to MitoQ10 and MitoQH2, completing the “catalytic” cycle. In MitoQ10, the redox-active unit was coupled to alkyl chain and monocationic triphenylphosphonium ion in order to reach mitochondria. Mn porphyrin-based SOD mimics, however, were designed so that their multiple cationic charge and alkyl chains determine both their remarkable SOD potency and carry them into mitochondria. Several animal efficacy studies such as skin carcinogenesis and UVB-mediated mtDNA damage, and subcellular distribution studies of Saccharomyces cerevisiae and mouse heart provided unambiguous evidence that Mn porphyrins mimic the site and action of MnSOD, which in turn contributes to their efficacy in numerous in vitro and in vivo models of oxidative stress. Within a class of Mn porphyrins, lipophilic analogues are particularly effective for treating central nervous system injuries where mitochondria play key role. PMID:22198225

  2. Antibacterial Peptidomimetics: Polymeric Synthetic Mimics of Antimicrobial Peptides

    NASA Astrophysics Data System (ADS)

    Lienkamp, Karen; Madkour, Ahmad E.; Tew, Gregory N.

    Polymer-based peptidomimetics, or proteinomimetics, are a relatively young and dynamic field of research. The ability to successfully mimic the biochemical activity of antimicrobial peptides (AMPs) has been demonstrated by several groups. This has been accomplished by careful tuning of the molecule's hydrophobicity and charge density. At the same time, many important questions remain to be answered, including the role of backbone rigidity, details of membrane insertion, and the role of curvature in the self-assemblies between these novel peptidemimetics and phospholipids. As the biological properties of polymeric synthetic mimics of AMPs (SMAMPs) result from the interplay of many parameters, it is not yet possible to predict the exact properties of such molecules from their mere chemical structure. However, as demonstrated here, the effect of certain design features such as charge and hydrophobicity on the properties across a polymer series is understood. Compared to the mechanistic specifics that are known about the interactions of AMPs or small antibacterial molecules with membranes and cells, relatively little is known concerning the interaction of polymeric SMAMPs with membranes. Beyond SMAMPs, numerous opportunities exist and protein transduction domain mimics are an active area of research in the Tew laboratory. These two examples, one quite new and the other studied for almost a decade, demonstrate that it is possible to teach synthetic polymers to behave like peptides, despite their lack of sequence specificity and secondary structure.

  3. Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

    PubMed Central

    Rebouças, Júlio S.; Spasojević, Ivan

    2010-01-01

    Abstract Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia–reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO3·−, peroxyl radical, and less efficiently H2O2. By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and/or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877–918. PMID:20095865

  4. CRADA Final Report: Mucin Mimic and Glycopeptide Synthesis

    SciTech Connect

    Bertozzi, Carolyn R.

    2002-10-22

    Mucus has several constituents but the most important are the mucins, heavily O-glycosylated proteins characterized by long stretches of tandem repeat sequences rich in glycosylated serine and threonine residues, with N- and C-terminal domains that have determined to a large extent by the viscous and viscoelastic properties of mucin glycoproteins. Indeed, these properties are evident in reconstituted purified mucin glycoproteins. Oligomeric mucin can be deconstructed into its monomeric components and then further into the domains that comprise each mucin molecule. There are two major domain types. "Glycodomains" are defined by stretches of the tandemly repeated Thr/Ser-rich segments that bear the characteristic O-linked glycans of the mucin molecule. The goal of this project is to synthesize polymeric materials that mimic mucin glycodomains. In order to mimic the central features of mucin, these materials should have dense clusters of glycans that bear a similar structure to those found in native mucins, and a fairly rigid polymer backbone. Four different polymers bearing ketone groups for the attachment of sugars were synthesized. GalNAc{alpha}-ONH{sub 2} and Sia{alpha}2,6GaINAc{alpha}·ONH{sub 2} both of which could be ligated to the polymer scaffolds were synthesized. Mucin glycodomain mimics were successfully synthesized by ligation of glycans to polymers.

  5. A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

    PubMed

    Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack; Bortell, Rita; Greiner, Dale L; Shultz, Leonard D; Han, Gang; McCormick, Beth A

    2016-01-01

    Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics. PMID:27452236

  6. Extensive survey on the prevalence and genetic diversity of SIVs in primate bushmeat provides insights into risks for potential new cross-species transmissions.

    PubMed

    Aghokeng, Avelin F; Ayouba, Ahidjo; Mpoudi-Ngole, Eitel; Loul, Severin; Liegeois, Florian; Delaporte, Eric; Peeters, Martine

    2010-04-01

    To evaluate the risk of cross-species transmissions of SIVs from non-human primates to humans at the primate/hunter interface, a total of 2586 samples, derived from primate bushmeat representing 11 different primate species, were collected at 6 distinct remote forest sites in southeastern Cameroon and in Yaoundé, the capital city. SIV prevalences were estimated with an updated SIV lineage specific gp41 peptide ELISA covering the major part of the SIV diversity. SIV positive samples were confirmed by PCR and sequence analysis of partial pol fragments. The updated SIV ELISA showed good performance with overall sensitivity and specificity of 96% and 97.5% respectively. The overall SIV seroprevalence was low, 2.93% (76/2586) and ranged between 0.0% and 5.7% at forest sites, and reached up to 10.3% in Yaoundé. SIV infection was documented in 8 of the 11 species with significantly different prevalence rates per species: 9/859 (1.0%) in Cercopithecus nictitans, 9/864 (1.0%) Cercopithecus cephus, 10/60 (16.7%) Miopithecus ogouensis, 14/78 (17.9%) Colobus guereza, 15/37 (40.5%) Cercopithecus neglectus, 10/27 (33.3%) Mandrillus sphinx, 6/12 (50%) Cercocebus torquatus, and 3/6 (50%) Chlorocebus tantalus. No SIV infection was identified in Cercopithecus pogonias (n=293), Lophocebus albigena (n=168) and Cercocebus agilis (n=182). The SIV prevalences also seem to vary within species according to the sampling site, but most importantly, the highest SIV prevalences are observed in the primate species which represent only 8.5% of the overall primate bushmeat. The phylogenetic tree of partial pol sequences illustrates the high genetic diversity of SIVs between and within different primate species. The tree also showed some interesting features within the SIVdeb lineage suggesting phylogeographic clusters. Overall, the risk for additional cross-species transmissions is not equal throughout southern Cameroon and depends on the hunted species and SIV prevalences in each species

  7. Planetary nebulae and their mimics: The MASH-MEN Project

    NASA Astrophysics Data System (ADS)

    Boissay, Rozenn; Parker, Quentin A.; Frew, David J.; Bojicic, Ivan

    2012-08-01

    The total number of true, likely and possible planetary nebulae (PN) now known in the Milky Way is about 3000, approximately twice the number known a decade ago. The new discoveries are a legacy of the recent availability of wide-field, narrowband imaging surveys, primarily in the light of Hα. The two most important are the AAO/UKST SuperCOSMOS Hα survey SHS and the Isaac Newton photometric Hα survey IPHAS, which are responsible for most of the new discoveries. A serious problem with previous PN catalogs is that several different kinds of astrophysical objects are able to mimic PN in some of their observed properties leading to significant contamination. These objects include H~II regions and Strömgren zones around young O/B stars, reflection nebulae, Wolf-Rayet ejecta, supernova remnants, Herbig-Haro objects, young stellar objects, B[e] stars, symbiotic stars and outflows, late-type stars, cataclysmic variables, low redshift emission-line galaxies, and even image/detector flaws. PN catalogs such as the Macquarie/AAO/Strasbourg Hα Planetary Nebula catalog (MASH) have been carefully vetted to remove these mimics using the wealth of new wide-field multi-wavelength data and our 100% follow-up spectroscopy to produce a compilation of new PN discoveries of high purity. During this process significant numbers of PN mimics have been identified. The aim of this project is to compile these MASH rejects into a catalog of Miscellaneous Emission Nebulae (MEN) and to highlight the most unusual and interesting examples. A new global analysis of these MEN objects is underway before publishing the MEN catalog online categorizing objects by type together with their spectra and multi-wavelength images.

  8. Differentiating Childhood Stroke From Mimics in the Emergency Department

    PubMed Central

    Yock-Corrales, Adriana; Churilov, Leonid; Monagle, Paul; Donnan, Geoffrey A.; Babl, Franz E.

    2016-01-01

    Background and Purpose— Clinical identification of stroke in the pediatric emergency department is critical for improving access to hyperacute therapies. We identified key clinical features associated with childhood stroke or transient ischemic attack compared with mimics. Methods— Two hundred and eighty consecutive children presenting to the emergency department with mimics, prospectively recruited over 18 months from 2009 to 2010, were compared with 102 children with stroke or transient ischemic attack, prospectively/retrospectively recruited from 2003 to 2010. Results— Cerebrovascular diagnoses included arterial ischemic stroke (55), hemorrhagic stroke (37), and transient ischemic attack (10). Mimic diagnoses included migraine (84), seizures (46), Bell’s palsy (29), and conversion disorders (18). Being well in the week before presentation (odds ratio [OR] 5.76, 95% confidence interval [CI] 2.25–14.79), face weakness (OR 2.94, 95% CI 1.19–7.28), arm weakness (OR 8.66, 95% CI, 2.50–30.02), and inability to walk (OR 3.38, 95% CI 1.54–7.42) were independently associated with increased odds of stroke diagnosis. Other symptoms were independently associated with decreased odds of stroke diagnosis (OR 0.28, 95% CI 0.10–0.77). Associations were not observed between seizures or loss of consciousness. Factors associated with stroke differed by arterial and hemorrhagic subtypes. Conclusions— Being well in the week before presentation, inability to walk, face and arm weakness are associated with increased odds of stroke. The lack of positive or negative association between stroke and seizures or loss of consciousness is an important difference to adults. Pediatric stroke pathways and bedside tools need to factor in differences between children and adults and between stroke subtypes. PMID:27601378

  9. Diagnosis of Atopic Dermatitis: Mimics, Overlaps, and Complications

    PubMed Central

    Siegfried, Elaine C.; Hebert, Adelaide A.

    2015-01-01

    Atopic dermatitis (AD) is one of the most common skin diseases affecting infants and children. A smaller subset of adults has persistent or new-onset AD. AD is characterized by pruritus, erythema, induration, and scale, but these features are also typical of several other conditions that can mimic, coexist with, or complicate AD. These include inflammatory skin conditions, infections, infestations, malignancies, genetic disorders, immunodeficiency disorders, nutritional disorders, graft-versus-host disease, and drug eruptions. Familiarity of the spectrum of these diseases and their distinguishing features is critical for correct and timely diagnosis and optimal treatment. PMID:26239454

  10. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    ERIC Educational Resources Information Center

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  11. The MIMIC Method with Scale Purification for Detecting Differential Item Functioning

    ERIC Educational Resources Information Center

    Wang, Wen-Chung; Shih, Ching-Lin; Yang, Chih-Chien

    2009-01-01

    This study implements a scale purification procedure onto the standard MIMIC method for differential item functioning (DIF) detection and assesses its performance through a series of simulations. It is found that the MIMIC method with scale purification (denoted as M-SP) outperforms the standard MIMIC method (denoted as M-ST) in controlling…

  12. Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the bla NDM-1 element and clonal spread of progenitor resistant strains.

    PubMed

    Wang, Xuan; Chen, Gongxiang; Wu, Xiaoyan; Wang, Liangping; Cai, Jiachang; Chan, Edward W; Chen, Sheng; Zhang, Rong

    2015-01-01

    This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the bla NDM-1 element, and the rest of 24 CRE strains were all positive for bla KPC-2. The 21 bla NDM-1-borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross-species transmission of bla NDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to bla NDM-1, several CRE strains were also found to harbor the bla KPC-2, bla VIM-1, and bla IMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas. PMID:26136735

  13. Noninvasive individual and species identification of jaguars (Panthera onca), pumas (Puma concolor) and ocelots (Leopardus pardalis) in Belize, Central America using cross-species microsatellites and faecal DNA.

    PubMed

    Wultsch, Claudia; Waits, Lisette P; Kelly, Marcella J

    2014-11-01

    There is a great need to develop efficient, noninvasive genetic sampling methods to study wild populations of multiple, co-occurring, threatened felids. This is especially important for molecular scatology studies occurring in challenging tropical environments where DNA degrades quickly and the quality of faecal samples varies greatly. We optimized 14 polymorphic microsatellite loci for jaguars (Panthera onca), pumas (Puma concolor) and ocelots (Leopardus pardalis) and assessed their utility for cross-species amplification. Additionally, we tested their reliability for species and individual identification using DNA from faeces of wild felids detected by a scat detector dog across Belize in Central America. All microsatellite loci were successfully amplified in the three target species, were polymorphic with average expected heterozygosities of HE = 0.60 ± 0.18 (SD) for jaguars, HE = 0.65 ± 0.21 (SD) for pumas and HE = 0.70 ± 0.13 (SD) for ocelots and had an overall PCR amplification success of 61%. We used this nuclear DNA primer set to successfully identify species and individuals from 49% of 1053 field-collected scat samples. This set of optimized microsatellite multiplexes represents a powerful tool for future efforts to conduct noninvasive studies on multiple, wild Neotropical felids.

  14. Development and cross-species transferability of unigene-derived microsatellite markers in an edible oil woody plant, Camellia oleifera (Theaceae).

    PubMed

    Jia, B G; Lin, Q; Feng, Y Z; Hu, X Y; Tan, X F; Shao, F G; Zhang, L

    2015-01-01

    Camellia oleifera is an important edible oil woody plant in China. Lack of useful molecular markers hinders current genetic research on this tree species. Transcriptome sequencing of developing C. oleifera seeds generated 69,798 unigenes. A total of 6949 putative microsatellites were discovered among 6042 SSR-containing unigenes. Then, 150 simple sequence repeats (SSRs) were evaluated in 20 varieties of C. oleifera. Of these, 52 SSRs revealed polymorphism, with the number of alleles per locus ranging from 2 to 15 and expected heterozygosity values from 0.269 to 0.888. The polymorphic information content varied from 0.32 to 0.897. Cross-species transferability rates in Camellia chekangoleosa and Camellia japonica were 90.4 and 78.8%, respectively. The 52 polymorphic unigene-derived SSR markers serve to enrich existing microsatellite marker resources for C. oleifera and offer potential for applications in genetic diversity evaluation, molecular fingerprinting, and genetic mapping in C. oleifera, C. chekangoleosa, and C. japonica. PMID:26125898

  15. Characterization of highly informative cross-species microsatellite panels for the Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) including five novel primers

    USGS Publications Warehouse

    Hunter, Margaret Kellogg; Broderick, Damien; Ovenden, Jennifer R.; Tucker, Kimberly Pause; Bonde, Robert K.; McGuire, Peter M.; Lanyon, Janet M.

    2010-01-01

    The Australian dugong (Dugong dugon) and Florida manatee (Trichechus manatus latirostris) are threatened species of aquatic mammals in the order Sirenia. Sirenian conservation and management actions would benefit from a more complete understanding of genetic diversity and population structure. Generally, species-specific microsatellite markers are employed in conservation genetic studies; however, robust markers can be difficult and costly to isolate. To increase the number of available markers, dugong and manatee microsatellite primers were evaluated for cross-species amplification. Furthermore, one manatee and four dugong novel primers are reported. After polymerase chain reaction optimization, 23 (92%) manatee primers successfully amplified dugong DNA, of which 11 (48%) were polymorphic. Of the 32 dugong primers tested, 27 (84%) yielded product in the manatee, of which 17 (63%) were polymorphic. Dugong and manatee primers were compared and the most informative markers were selected to create robust and informative marker-panels for each species. These crossspecies microsatellite marker-panels can be employed to assess other sirenian populations and can provide beneficial information for the protection and management of these unique mammals.

  16. Simian foamy virus in non-human primates and cross-species transmission to humans in Gabon: an emerging zoonotic disease in central Africa?

    PubMed

    Mouinga-Ondémé, Augustin; Kazanji, Mirdad

    2013-06-19

    It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy virus (SFV), from primates to humans. To better understand this retroviral "zoonosis" in natural settings, we evaluated the presence of SFV in both captive and wild non-human primates and in humans at high risk, such as hunters and people bitten by a non-human primate, in Gabon, central Africa. A high prevalence of SFV was found in blood samples from non-human primates and in bush meat collected across the country. Mandrills were found to be highly infected with two distinct strains of SFV, depending on their geographical location. Furthermore, samples collected from hunters and non-human primate laboratory workers showed clear, extensive cross-species transmission of SFV. People who had been bitten by mandrills, gorillas and chimpanzees had persistent SFV infection with low genetic drift. Thus, SFV is presumed to be transmitted from non-human primates mainly through severe bites, involving contact between infected saliva and blood. In this review, we summarize and discuss our five-year observations on the prevalence and dissemination of SFV in humans and non-human primates in Gabon.

  17. Identification of Putative Ortholog Gene Blocks Involved in Gestant and Lactating Mammary Gland Development: A Rodent Cross-Species Microarray Transcriptomics Approach

    PubMed Central

    Rodríguez-Cruz, Maricela; Coral-Vázquez, Ramón M.; Hernández-Stengele, Gabriel; Sánchez, Raúl; Salazar, Emmanuel; Sanchez-Muñoz, Fausto; Encarnación-Guevara, Sergio; Ramírez-Salcedo, Jorge

    2013-01-01

    The mammary gland (MG) undergoes functional and metabolic changes during the transition from pregnancy to lactation, possibly by regulation of conserved genes. The objective was to elucidate orthologous genes, chromosome clusters and putative conserved transcriptional modules during MG development. We analyzed expression of 22,000 transcripts using murine microarrays and RNA samples of MG from virgin, pregnant, and lactating rats by cross-species hybridization. We identified 521 transcripts differentially expressed; upregulated in early (78%) and midpregnancy (89%) and early lactation (64%), but downregulated in mid-lactation (61%). Putative orthologous genes were identified. We mapped the altered genes to orthologous chromosomal locations in human and mouse. Eighteen sets of conserved genes associated with key cellular functions were revealed and conserved transcription factor binding site search entailed possible coregulation among all eight block sets of genes. This study demonstrates that the use of heterologous array hybridization for screening of orthologous gene expression from rat revealed sets of conserved genes arranged in chromosomal order implicated in signaling pathways and functional ontology. Results demonstrate the utilization power of comparative genomics and prove the feasibility of using rodent microarrays to identification of putative coexpressed orthologous genes involved in the control of human mammary gland development. PMID:24288657

  18. Transformation of metabolism with age and lifestyle in Antarctic seals: a case study of systems biology approach to cross-species microarray experiment

    PubMed Central

    2010-01-01

    Background The metabolic transformation that changes Weddell seal pups born on land into aquatic animals is not only interesting for the study of general biology, but it also provides a model for the acquired and congenital muscle disorders which are associated with oxygen metabolism in skeletal muscle. However, the analysis of gene expression in seals is hampered by the lack of specific microarrays and the very limited annotation of known Weddell seal (Leptonychotes weddellii) genes. Results Muscle samples from newborn, juvenile, and adult Weddell seals were collected during an Antarctic expedition. Extracted RNA was hybridized on Affymetrix Human Expression chips. Preliminary studies showed a detectable signal from at least 7000 probe sets present in all samples and replicates. Relative expression levels for these genes was used for further analysis of the biological pathways implicated in the metabolism transformation which occurs in the transition from newborn, to juvenile, to adult seals. Cytoskeletal remodeling, WNT signaling, FAK signaling, hypoxia-induced HIF1 activation, and insulin regulation were identified as being among the most important biological pathways involved in transformation. Conclusion In spite of certain losses in specificity and sensitivity, the cross-species application of gene expression microarrays is capable of solving challenging puzzles in biology. A Systems Biology approach based on gene interaction patterns can compensate adequately for the lack of species-specific genomics information. PMID:20920245

  19. Noninvasive individual and species identification of jaguars (Panthera onca), pumas (Puma concolor) and ocelots (Leopardus pardalis) in Belize, Central America using cross-species microsatellites and faecal DNA.

    PubMed

    Wultsch, Claudia; Waits, Lisette P; Kelly, Marcella J

    2014-11-01

    There is a great need to develop efficient, noninvasive genetic sampling methods to study wild populations of multiple, co-occurring, threatened felids. This is especially important for molecular scatology studies occurring in challenging tropical environments where DNA degrades quickly and the quality of faecal samples varies greatly. We optimized 14 polymorphic microsatellite loci for jaguars (Panthera onca), pumas (Puma concolor) and ocelots (Leopardus pardalis) and assessed their utility for cross-species amplification. Additionally, we tested their reliability for species and individual identification using DNA from faeces of wild felids detected by a scat detector dog across Belize in Central America. All microsatellite loci were successfully amplified in the three target species, were polymorphic with average expected heterozygosities of HE = 0.60 ± 0.18 (SD) for jaguars, HE = 0.65 ± 0.21 (SD) for pumas and HE = 0.70 ± 0.13 (SD) for ocelots and had an overall PCR amplification success of 61%. We used this nuclear DNA primer set to successfully identify species and individuals from 49% of 1053 field-collected scat samples. This set of optimized microsatellite multiplexes represents a powerful tool for future efforts to conduct noninvasive studies on multiple, wild Neotropical felids. PMID:24751217

  20. Rapid development of microsatellite markers for the endangered fish Schizothorax biddulphi (Günther) using next generation sequencing and cross-species amplification.

    PubMed

    Luo, Wei; Nie, Zhulan; Zhan, Fanbin; Wei, Jie; Wang, Weimin; Gao, Zexia

    2012-11-14

    Tarim schizothoracin (Schizothorax biddulphi) is an endemic fish species native to the Tarim River system of Xinjiang and has been classified as an extremely endangered freshwater fish species in China. Here, we used a next generation sequencing platform (ion torrent PGM™) to obtain a large number of microsatellites for S. biddulphi, for the first time. A total of 40577 contigs were assembled, which contained 1379 SSRs. In these SSRs, the number of dinucleotide repeats were the most frequent (77.08%) and AC repeats were the most frequently occurring microsatellite, followed by AG, AAT and AT. Fifty loci were randomly selected for primer development; of these, 38 loci were successfully amplified and 29 loci were polymorphic across panels of 30 individuals. The H(o) ranged from 0.15 to 0.83, and H(e) ranged from 0.15 to 0.85, with 3.5 alleles per locus on average. Cross-species utility indicated that 20 of these markers were successfully amplified in a related, also an endangered fish species, S. irregularis. This study suggests that PGM™ sequencing is a rapid and cost-effective tool for developing microsatellite markers for non-model species and the developed microsatellite markers in this study would be useful in Schizothorax genetic analysis.

  1. Efficient identification of proteins from ovaries and hepatopancreas of the unsequenced edible crab, Cancer pagurus, by mass spectrometry and homology-based, cross-species searching.

    PubMed

    Ward, Deborah A; Sefton, Elaine M; Prescott, Mark C; Webster, Simon G; Wainwright, Geoff; Rees, Huw H; Fisher, Michael J

    2010-11-10

    Proteome maps of hepatopancreas (midgut gland) and ovarian tissues of the crustacean, Cancer pagurus (Decapoda; edible crab) have been produced by 2D-PAGE and identification of proteins, following trypsin proteolysis, by electrospray MS/MS and database searching. Owing to the lack of sequence information on proteins and fully sequenced genomes amongst the decapod crustaceans and given the evolutionary distance to the nearest full genome database (Daphnia), it was necessary to adopt a non-conventional identification approach. Thus, a strategy was developed for effective identification of decapod proteins by sequence similarity, homology-based cross-species database searching, using various algorithms and a combination of NCBI Crustacea and Arthropoda databases, together with the Arthropoda PartiGene database (Blaxter, University of Edinburgh). In both hepatopancreas and ovary tissues, the largest group of proteins identified were a variety of enzymes, followed by a smaller number of storage/transport proteins [including vitellogenin (yolk protein), several subunits of hemocyanin, cryptocyanin, ferritin and calreticulin], with fewer structural proteins (actin, tubulin) and heat-shock proteins, in addition to a number of proteins of miscellaneous functions. Such protein identifications allow the development of tools, such as antibodies and RNA/DNA probes, to investigate the functions of the proteins in specific tissues during development. PMID:20656081

  2. Rapid Development of Microsatellite Markers for the Endangered Fish Schizothorax biddulphi (Günther) Using Next Generation Sequencing and Cross-Species Amplification

    PubMed Central

    Luo, Wei; Nie, Zhulan; Zhan, Fanbin; Wei, Jie; Wang, Weimin; Gao, Zexia

    2012-01-01

    Tarim schizothoracin (Schizothorax biddulphi) is an endemic fish species native to the Tarim River system of Xinjiang and has been classified as an extremely endangered freshwater fish species in China. Here, we used a next generation sequencing platform (ion torrent PGM™) to obtain a large number of microsatellites for S. biddulphi, for the first time. A total of 40577 contigs were assembled, which contained 1379 SSRs. In these SSRs, the number of dinucleotide repeats were the most frequent (77.08%) and AC repeats were the most frequently occurring microsatellite, followed by AG, AAT and AT. Fifty loci were randomly selected for primer development; of these, 38 loci were successfully amplified and 29 loci were polymorphic across panels of 30 individuals. The Ho ranged from 0.15 to 0.83, and He ranged from 0.15 to 0.85, with 3.5 alleles per locus on average. Cross-species utility indicated that 20 of these markers were successfully amplified in a related, also an endangered fish species, S. irregularis. This study suggests that PGM™ sequencing is a rapid and cost-effective tool for developing microsatellite markers for non-model species and the developed microsatellite markers in this study would be useful in Schizothorax genetic analysis. PMID:23203104

  3. Cross-species induction of antimicrobial compounds, biosurfactants and quorum-sensing inhibitors in tropical marine epibiotic bacteria by pathogens and biofouling microorganisms.

    PubMed

    Dusane, Devendra H; Matkar, Pratiek; Venugopalan, Valayam P; Kumar, Ameeta Ravi; Zinjarde, Smita S

    2011-03-01

    Enhancement or induction of antimicrobial, biosurfactant, and quorum-sensing inhibition property in marine bacteria due to cross-species and cross-genera interactions was investigated. Four marine epibiotic bacteria (Bacillus sp. S3, B. pumilus S8, B. licheniformis D1, and Serratia marcescens V1) displaying antimicrobial activity against pathogenic or biofouling fungi (Candida albicans CA and Yarrowia lipolytica YL), and bacteria (Pseudomonas aeruginosa PA and Bacillus pumilus BP) were chosen for this study. The marine epibiotic bacteria when co-cultivated with the aforementioned fungi or bacteria showed induction or enhancement in antimicrobial activity, biosurfactant production, and quorum-sensing inhibition. Antifungal activity against Y. lipolytica YL was induced by co-cultivation of the pathogens or biofouling strains with the marine Bacillus sp. S3, B. pumilus S8, or B. licheniformis D1. Antibacterial activity against Ps. aeruginosa PA or B. pumilus BP was enhanced in most of the marine isolates after co-cultivation. Biosurfactant activity was significantly increased when cells of B. pumilus BP were co-cultivated with S. marcescens V1, B. pumilus S8, or B. licheniformis D1. Pigment reduction in the quorum-sensing inhibition indicator strain Chromobacterium violaceum 12472 was evident when the marine strain of Bacillus sp. S3 was grown in the presence of the inducer strain Ps. aeruginosa PA, suggesting quorum-sensing inhibition. The study has important ecological and biotechnological implications in terms of microbial competition in natural environments and enhancement of secondary metabolite production.

  4. Glycosylasparaginase inhibition studies: competitive inhibitors, transition state mimics, noncompetitive inhibitors.

    PubMed

    Risley, J M; Huang, D H; Kaylor, J J; Malik, J J; Xia, Y Q

    2001-01-01

    Glycosylasparaginase catalyzes the hydrolysis of the N-glycosylic bond between asparagine and N-acetylglucosamine in the catabolism of N-linked glycoproteins. Previously only three competitive inhibitors, one noncompetitive inhibitor, and one irreversible inhibitor of glycosylasparaginase activity had been reported. Using human glycosylasparaginase from human amniotic fluid, L-aspartic acid and four of its analogues, where the alpha-amino group was substituted with a chloro, bromo, methyl or hydrogen, were competitive inhibitors having Ki values between 0.6-7.7 mM. These results provide supporting evidence for a proposed intramolecular autoproteolytic activation reaction. A proposed phosphono transition state mimic and a sulfo transition state mimic were competitive inhibitors with Ki values 0.9 mM and 1.4 mM, respectively. These results support a mechanism for the enzyme-catalyzed reaction involving formation of a tetrahedral high-energy intermediate. Three analogues of the natural substrate were noncompetitive inhibitors with Ki values between 0.56-0.75 mM, indicating the presence of a second binding site that may recognize (substituted)acetamido groups.

  5. Biologically active metal-independent superoxide dismutase mimics

    SciTech Connect

    Mitchell, J.B.; Samuni, A.; Krishna, M.C.; DeGraff, W.G.; Ahn, M.S.; Samuni, U.; Russo, A. )

    1990-03-20

    Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H{sub 2}O{sub 2}, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.

  6. Glutathione peroxidase mimics as novel antioxidants from vegetables.

    PubMed

    Terao, Junji; Hiwada, Mio; Taguchi, Keiko; Takahara, Keigo; Mohri, Satoshi

    2005-01-01

    Vegetables are generally recognized as rich sources of dietary antioxidants for inhibiting lipid peroxidation. Here we investigated lipid hydroperoxide (LOOH)-reducing activity of several vegetables to estimate their role on the prevention of lipid peroxidation in food and the digestive tract. By using HPLC analysis, we screened vegetables possessing the ability to convert 13-hydroperoxyoctadecadienoic acid (13-HPODE) to its reduced derivative, 13-hydroxyoctadecadienoic acid (13-HODE). Welsh onion (Allium fistulosum L.) was found to be highly active in the reduction of 13-HPODE among tested vegetables. There was no relationship between 13-HPODE reducing activity and GSH peroxidase (GPX) activity in the tested vegetables. 13-HPODE-reducing activity of welsh onion was enhanced by the addition of sulfhydryl compounds including glutathione (GSH). Neither GPX inhibitor nor heat treatment suppressed 13-HPODE-reducing activity effectively. These results suggest that welsh onion and other vegetables contain GPX mimics responsible for the reduction of LOOH. GPX mimics may be helpful in the attenuation of harmful effect of LOOH from food. PMID:15817993

  7. De novo design of protein mimics of B-DNA.

    PubMed

    Yüksel, Deniz; Bianco, Piero R; Kumar, Krishna

    2016-01-01

    Structural mimicry of DNA is utilized in nature as a strategy to evade molecular defences mounted by host organisms. One such example is the protein Ocr - the first translation product to be expressed as the bacteriophage T7 infects E. coli. The structure of Ocr reveals an intricate and deliberate arrangement of negative charges that endows it with the ability to mimic ∼24 base pair stretches of B-DNA. This uncanny resemblance to DNA enables Ocr to compete in binding the type I restriction modification (R/M) system, and neutralizes the threat of hydrolytic cleavage of viral genomic material. Here, we report the de novo design and biophysical characterization of DNA mimicking peptides, and describe the inhibitory action of the designed helical bundles on a type I R/M enzyme, EcoR124I. This work validates the use of charge patterning as a design principle for creation of protein mimics of DNA, and serves as a starting point for development of therapeutic peptide inhibitors against human pathogens that employ molecular camouflage as part of their invasion stratagem. PMID:26568416

  8. Novel β-amyloid aggregation inhibitors possessing a turn mimic.

    PubMed

    Hamada, Yoshio; Miyamoto, Naoko; Kiso, Yoshiaki

    2015-04-01

    Amyloid β peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of β-secretase, γ-secretase, and Aβ aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aβ antibodies. Recently, we reported potent small-sized β-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel β-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid β peptides contain a turn structure within the molecule. Here, we designed and synthesized novel β-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid β peptides.

  9. Motor mechanisms of a vocal mimic: implications for birdsong production.

    PubMed

    Zollinger, Sue Anne; Suthers, Roderick A

    2004-03-01

    The diverse vocal performances of oscine songbirds are produced by the independent but coordinated patterns of activity in muscles controlling separate sound generators on the left and right sides of their duplex vocal organ, the syrinx. Species with different song styles use the two sides of their syrinx in different ways to produce their species-typical songs. Understanding how a vocal mimic copies another species' song may provide an insight into whether there are alternative motor mechanisms for generating the model's song and what parts of his song are most difficult to produce. We show here that when a vocal mimic, the northern mockingbird, accurately copies the song of another species it also uses the vocal motor pattern employed by the model species. Deviations from the model's production mechanism result in predictable differences in the mockingbird's song. Species-specific acoustic features of the model seem most difficult to copy, suggesting that they have been exposed to the strongest selective pressure to maximize their performance.

  10. Relating Structure and Internalization for ROMP-based Protein Mimics

    PubMed Central

    Backlund, Coralie M.; Takeuchi, Toshihide; Futaki, Shiroh; Tew, Gregory N.

    2016-01-01

    Elucidating the predominant cellular entry mechanism for protein transduction domains (PTDs) and their synthetic mimics (PTDMs) is a complicated problem that continues to be a significant source of debate in the literature. Several guanidinium-rich homopolymer structures initially designed to mimic oligoarginine, as well as an amphiphilic block copolymer, were end-labeled with FITC. This enabled the monitoring of PTDM internalization into HeLa cells by flow cytometry and confocal imaging. Additionally, their unlabeled counterparts showed improved ability to deliver proteins into cells with added hydrophobic content. In conjunction, pre-incubation with the protein is required, suggesting that the polymers are not just simply interacting with the membrane, but require association with the cargo of interest. However, the mechanism of cellular entry is not dependent on structure within this study, as punctate fluorescence was prevalent within the cells treated with fluorescently labeled samples and protein-polymer complexes. This suggests that the predominant mode of internalization for the presented PTDM structures is endosomal uptake and does not appear to be affected by concentration or structure. The PTDMs reported here provide a well-controlled platform to vary molecular composition for structure activity relationship studies to further our understanding of PTDs, their non-covalent association with cargo, and their cellular internalization pathways. PMID:27039278

  11. De novo design of protein mimics of B-DNA.

    PubMed

    Yüksel, Deniz; Bianco, Piero R; Kumar, Krishna

    2016-01-01

    Structural mimicry of DNA is utilized in nature as a strategy to evade molecular defences mounted by host organisms. One such example is the protein Ocr - the first translation product to be expressed as the bacteriophage T7 infects E. coli. The structure of Ocr reveals an intricate and deliberate arrangement of negative charges that endows it with the ability to mimic ∼24 base pair stretches of B-DNA. This uncanny resemblance to DNA enables Ocr to compete in binding the type I restriction modification (R/M) system, and neutralizes the threat of hydrolytic cleavage of viral genomic material. Here, we report the de novo design and biophysical characterization of DNA mimicking peptides, and describe the inhibitory action of the designed helical bundles on a type I R/M enzyme, EcoR124I. This work validates the use of charge patterning as a design principle for creation of protein mimics of DNA, and serves as a starting point for development of therapeutic peptide inhibitors against human pathogens that employ molecular camouflage as part of their invasion stratagem.

  12. Imaging tissue engineered blood vessel mimics with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Bonnema, Garret Thomas

    Optical coherence tomography (OCT) is a technology that enables 2D cross-sectional images of tissue microstructure. This interferometric technique provides resolutions of approximately 10-20 mum with a penetration depth of 1-2 mm in highly scattering tissues. With the use of fiber optics, OCT systems have been developed for intravascular imaging with a demonstrated improvement in both resolution and dynamic range compared to commercial intravascular ultrasound systems. OCT studies of normal, atherosclerotic, and stented arteries indicate the ability of OCT to visualize arterial structures. These results suggest OCT may be a valuable tool for studying luminal structures in tissue engineered constructs. In the present study, new endoscopic OCT systems and analysis techniques were developed to visualize the growth and response of the cellular lining within a tissue engineered blood vessel mimic (BVM). The BVM consists of two primary components. A biocompatible polymeric scaffold is used to form the tubular structure. Human microvessel cells from adipose tissue are sodded on to the inner surface of the scaffold. These constructs are then developed and imaged within a sterile bioreactor. Three specific aims were defined for the present study. First, an OCT longitudinal scanning endoscope was developed. With this endoscope, a study of 16 BVMs was performed comparing images from OCT and corresponding histological sections. The study demonstrated that endoscopic imaging did not visually damage the mimic cellular lining. OCT images showed excellent correlation with corresponding histological sections. Second, a concentric three element endoscope was developed to provide radial cross-sections of the BVM. OCT images using this endoscope monitored lining development on three types of polymeric scaffolds. In the third specific aim, automated algorithms were developed to assess the percent cellular coverage of a stent using volumetric OCT images. The results of the present study

  13. Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol.

    PubMed

    Bubier, Jason A; Wilcox, Troy D; Jay, Jeremy J; Langston, Michael A; Baker, Erich J; Chesler, Elissa J

    2016-01-01

    Identifying the biological substrates of complex neurobehavioral traits such as alcohol dependency pose a tremendous challenge given the diverse model systems and phenotypic assessments used. To address this problem we have developed a platform for integrated analysis of high-throughput or genome-wide functional genomics studies. A wealth of such data exists, but it is often found in disparate, non-computable forms. Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis. Using this system we identified a gene underlying multiple alcohol-related phenotypes in four species. A search of over 60,000 gene sets in GeneWeaver's database revealed alcohol-related experimental results including genes identified in mouse genetic mapping studies, alcohol selected Drosophila lines, Rattus differential expression, and human alcoholic brains. We identified highly connected genes and compared these to genes currently annotated to alcohol-related behaviors and processes. The most highly connected gene not annotated to alcohol was Pafah1b1. Experimental validation using a Pafah1b1 conditional knock-out mouse confirmed that this gene is associated with an increased preference for alcohol and an altered thermoregulatory response to alcohol. Although this gene has not been previously implicated in alcohol-related behaviors, its function in various neural mechanisms makes a role in alcohol-related phenomena plausible. By making diverse cross-species functional genomics data readily computable, we were able to identify and confirm a novel alcohol-related gene that may have implications for alcohol use disorders and other effects of alcohol.

  14. Cross-Species Analysis of Protein Dynamics Associated with Hydride and Proton Transfer in the Catalytic Cycle of the Light-Driven Enzyme Protochlorophyllide Oxidoreductase.

    PubMed

    Hoeven, Robin; Hardman, Samantha J O; Heyes, Derren J; Scrutton, Nigel S

    2016-02-16

    Experimental interrogation of the relationship between protein dynamics and enzyme catalysis is challenging. Light-activated protochlorophyllide oxidoreductase (POR) is an excellent model for investigating this relationship because photoinitiation of the reaction cycle enables coordinated turnover in a "dark-assembled" ternary enzyme-substrate complex. The catalytic cycle involves sequential hydride and proton transfers (from NADPH and an active site tyrosine residue, respectively) to the substrate protochlorophyllide. Studies with a limited cross-species subset of POR enzymes (n = 4) have suggested that protein dynamics associated with hydride and proton transfer are distinct [Heyes, D. J., Levy, C., Sakuma, M., Robertson, D. L., and Scrutton, N. S. (2011) J. Biol. Chem. 286, 11849-11854]. Here, we use steady-state assays and single-turnover laser flash spectroscopy to analyze hydride and proton transfer dynamics in an extended series of POR enzymes taken from many species, including cyanobacteria, algae, embryophytes, and angiosperms. Hydride/proton transfer in all eukaryotic PORs is faster compared to prokaryotic PORs, suggesting active site architecture has been optimized in eukaryotic PORs following endosymbiosis. Visible pump-probe spectroscopy was also used to demonstrate a common photoexcitation mechanism for representative POR enzymes from different branches of the phylogenetic tree. Dynamics associated with hydride transfer are localized to the active site of all POR enzymes and are conserved. However, dynamics associated with proton transfer are variable. Protein dynamics associated with proton transfer are also coupled to solvent dynamics in cyanobacterial PORs, and these networks are likely required to optimize (shorten) the donor-acceptor distance for proton transfer. These extended networks are absent in algal and plant PORs. Our analysis suggests that extended networks of dynamics are disfavored, possibly through natural selection. Implications for

  15. Cross-species amplification and polymorphism of microsatellite loci in Helicoverpa armigera and Helicoverpa zea (Lepidoptera: Noctuidae) in Brazilian cropping systems.

    PubMed

    Leite, N A; Corrêa, A S; Alves-Pereira, A; Campos, J B; Zucchi, M I; Omoto, C

    2016-01-01

    The Old World bollworm Helicoverpa armigera (Hübner) was recently discovered in Brazil. This species is closely related to the New World bollworm H. zea (Boddie), and mating between these species has already been reported under laboratory conditions. Here, we tested the cross-species amplification of 20 microsatellite (SSR) loci in field populations of H. armigera and H. zea collected from Brazilian cropping systems. Seven SSR loci were successfully amplified and polymorphic in both species except for the locus HaC14, which was monomorphic for H. zea. All SSR loci were in linkage equilibrium, and deviations from Hardy- Weinberg equilibrium were only observed for the locus HarSSR1 in the HaRS-2 population, where null alleles were present. A moderate level of polymorphism was detected in H. armigera and H. zea populations with a mean allele number of 4.14, and 2.24, respectively. Interestingly, most of the populations of the recent invader H. armigera showed higher genetic diversity and inbreeding coefficients than H. zea populations. The genetic identity of each species was recovered using a STRUCTURE analysis, where the populations formed two clusters (K = 2) according to their species. STRUCTURE also suggested the occurrence of potential hybrid offspring between H. armigera and H. zea individuals in natural conditions. These SSR loci will be valuable in characterizing population differentiation, invasion routes, adaptation, reproductive behavior, and intra- and interspecific gene flow in H. armigera and H. zea populations in Brazil, the USA, and other areas where these two pests occur. PMID:27173200

  16. New methods to identify conserved microsatellite loci and develop primer sets of high cross-species utility - as demonstrated for birds.

    PubMed

    Dawson, Deborah A; Horsburgh, Gavin J; Küpper, Clemens; Stewart, Ian R K; Ball, Alexander D; Durrant, Kate L; Hansson, Bengt; Bacon, Ida; Bird, Susannah; Klein, Akos; Krupa, Andrew P; Lee, Jin-Won; Martín-Gálvez, David; Simeoni, Michelle; Smith, Gemma; Spurgin, Lewis G; Burke, Terry

    2010-05-01

    We have developed a new approach to create microsatellite primer sets that have high utility across a wide range of species. The success of this method was demonstrated using birds. We selected 35 avian EST microsatellite loci that had a high degree of sequence homology between the zebra finch Taeniopygia guttata and the chicken Gallus gallus and designed primer sets in which the primer bind sites were identical in both species. For 33 conserved primer sets, on average, 100% of loci amplified in each of 17 passerine species and 99% of loci in five non-passerine species. The genotyping of four individuals per species revealed that 24-76% (mean 48%) of loci were polymorphic in the passerines and 18-26% (mean 21%) in the non-passerines. When at least 17 individuals were genotyped per species for four Fringillidae finch species, 71-85% of loci were polymorphic, observed heterozygosity was above 0.50 for most loci and no locus deviated significantly from Hardy-Weinberg proportions. This new set of microsatellite markers is of higher cross-species utility than any set previously designed. The loci described are suitable for a range of applications that require polymorphic avian markers, including paternity and population studies. They will facilitate comparisons of bird genome organization, including genome mapping and studies of recombination, and allow comparisons of genetic variability between species whilst avoiding ascertainment bias. The costs and time to develop new loci can now be avoided for many applications in numerous species. Furthermore, our method can be readily used to develop microsatellite markers of high utility across other taxa. PMID:21565047

  17. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    NASA Astrophysics Data System (ADS)

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-02-01

    Using a series of immunoprecipitation (IP) – tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  18. Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol.

    PubMed

    Bubier, Jason A; Wilcox, Troy D; Jay, Jeremy J; Langston, Michael A; Baker, Erich J; Chesler, Elissa J

    2016-01-01

    Identifying the biological substrates of complex neurobehavioral traits such as alcohol dependency pose a tremendous challenge given the diverse model systems and phenotypic assessments used. To address this problem we have developed a platform for integrated analysis of high-throughput or genome-wide functional genomics studies. A wealth of such data exists, but it is often found in disparate, non-computable forms. Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis. Using this system we identified a gene underlying multiple alcohol-related phenotypes in four species. A search of over 60,000 gene sets in GeneWeaver's database revealed alcohol-related experimental results including genes identified in mouse genetic mapping studies, alcohol selected Drosophila lines, Rattus differential expression, and human alcoholic brains. We identified highly connected genes and compared these to genes currently annotated to alcohol-related behaviors and processes. The most highly connected gene not annotated to alcohol was Pafah1b1. Experimental validation using a Pafah1b1 conditional knock-out mouse confirmed that this gene is associated with an increased preference for alcohol and an altered thermoregulatory response to alcohol. Although this gene has not been previously implicated in alcohol-related behaviors, its function in various neural mechanisms makes a role in alcohol-related phenomena plausible. By making diverse cross-species functional genomics data readily computable, we were able to identify and confirm a novel alcohol-related gene that may have implications for alcohol use disorders and other effects of alcohol. PMID:26834590

  19. Network analysis and cross species comparison of protein-protein interaction networks of human, mouse and rat cytochrome P450 proteins that degrade xenobiotics.

    PubMed

    Karthikeyan, Bagavathy Shanmugam; Akbarsha, Mohammad Abdulkader; Parthasarathy, Subbiah

    2016-06-21

    Cytochrome P450 (CYP) enzymes that degrade xenobiotics play a critical role in the metabolism and biotransformation of drugs and xenobiotics in humans as well as experimental animal models such as mouse and rat. These proteins function as a network collectively as well as independently. Though there are several reports on the organization, regulation and functionality of various CYP enzymes at the molecular level, the understanding of organization and functionality of these proteins at the holistic level remain unclear. The objective of this study is to understand the organization and functionality of xenobiotic degrading CYP enzymes of human, mouse and rat using network theory approaches and to study species differences that exist among them at the holistic level. For our analysis, a protein-protein interaction (PPI) network for CYP enzymes of human, mouse and rat was constructed using the STRING database. Topology, centrality, modularity and robustness analyses were performed for our predicted CYP PPI networks that were then validated by comparison with randomly generated network models. Network centrality analyses of CYP PPI networks reveal the central/hub proteins in the network. Modular analysis of the CYP PPI networks of human, mouse and rat resulted in functional clusters. These clusters were subjected to ontology and pathway enrichment analysis. The analyses show that the cluster of the human CYP PPI network is enriched with pathways principally related to xenobiotic/drug metabolism. Endo-xenobiotic crosstalk dominated in mouse and rat CYP PPI networks, and they were highly enriched with endogenous metabolic and signaling pathways. Thus, cross-species comparisons and analyses of human, mouse and rat CYP PPI networks gave insights about species differences that existed at the holistic level. More investigations from both reductionist and holistic perspectives can help understand CYP metabolism and species extrapolation in a much better way. PMID:27194593

  20. Cross-species conservation of endocrine pathways: a critical analysis of tier 1 fish and rat screening assays with 12 model chemicals.

    PubMed

    Ankley, Gerald T; Gray, L Earl

    2013-04-01

    Many structural and functional aspects of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis are known to be highly conserved, but the significance of this from a toxicological perspective has received comparatively little attention. High-quality data generated through development and validation of Tier 1 tests for the U.S. Environmenal Protection Agency Endocrine Disruptor Screening Program (EDSP) offer a unique opportunity to compare responses of mammals versus fish to chemicals that may affect shared pathways within the HPG axis. The present study focuses on data generated with model chemicals that act (primarily) as estrogen receptor agonists (17α-ethynylestradiol, methoxychlor, bisphenol A), androgen receptor agonists (methyltestosterone, 17β-trenbolone), androgen receptor antagonists (flutamide, vincolozolin, p,p'-DDE), or inhibitors of different steroidogenic enzymes (ketoconazole, fadrozole, fenarimol, prochloraz). All 12 chemicals had been tested in the EDSP fish short-term (21 d) reproduction assay and in one or more of the four in vivo Tier 1 screens with rats (uterotrophic, Hershberger, male and female pubertal assays). There was a high concordance between the fish and rat assays with respect to identifying chemicals that impacted specific endocrine pathways of concern. Although most chemicals were detected as positive in both rat and fish assays, eliminating data from one class of vertebrate or the other would weaken the battery. For example, the effects of competitive inhibitors of steroid hormone synthesis were far more obvious in the fish assay, whereas the activity of androgen receptor antagonists was clearer in mammalian assays. The observations are significant both to the cross-species extrapolation of toxicity of HPG-active substances and the optimization of screening and testing frameworks for endocrine-disrupting chemicals.

  1. Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol

    PubMed Central

    Bubier, Jason A.; Wilcox, Troy D.; Jay, Jeremy J.; Langston, Michael A.; Baker, Erich J.; Chesler, Elissa J.

    2016-01-01

    Identifying the biological substrates of complex neurobehavioral traits such as alcohol dependency pose a tremendous challenge given the diverse model systems and phenotypic assessments used. To address this problem we have developed a platform for integrated analysis of high-throughput or genome-wide functional genomics studies. A wealth of such data exists, but it is often found in disparate, non-computable forms. Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis. Using this system we identified a gene underlying multiple alcohol-related phenotypes in four species. A search of over 60,000 gene sets in GeneWeaver's database revealed alcohol-related experimental results including genes identified in mouse genetic mapping studies, alcohol selected Drosophila lines, Rattus differential expression, and human alcoholic brains. We identified highly connected genes and compared these to genes currently annotated to alcohol-related behaviors and processes. The most highly connected gene not annotated to alcohol was Pafah1b1. Experimental validation using a Pafah1b1 conditional knock-out mouse confirmed that this gene is associated with an increased preference for alcohol and an altered thermoregulatory response to alcohol. Although this gene has not been previously implicated in alcohol-related behaviors, its function in various neural mechanisms makes a role in alcohol-related phenomena plausible. By making diverse cross-species functional genomics data readily computable, we were able to identify and confirm a novel alcohol-related gene that may have implications for alcohol use disorders and other effects of alcohol. PMID:26834590

  2. The International Society for Developmental Psychobiology Sackler Symposium: Early adversity and the maturation of emotion circuits - a cross-species analysis

    PubMed Central

    Callaghan, Bridget L.; Sullivan, Regina M; Howell, Brittany; Tottenham, Nim

    2016-01-01

    Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from 4 different research laboratories, using 3 different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behaviour with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. PMID:25290865

  3. MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD

    PubMed Central

    Nieratschker, V; Massart, R; Gilles, M; Luoni, A; Suderman, M J; Krumm, B; Meier, S; Witt, S H; Nöthen, M M; Suomi, S J; Peus, V; Scharnholz, B; Dukal, H; Hohmeyer, C; Wolf, I A-C; Cirulli, F; Gass, P; Sütterlin, M W; Filsinger, B; Laucht, M; Riva, M A; Rietschel, M; Deuschle, M; Szyf, M

    2014-01-01

    Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD. PMID:25158004

  4. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    NASA Astrophysics Data System (ADS)

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-02-01

    Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  5. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    PubMed Central

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-01-01

    Using a series of immunoprecipitation (IP) – tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. PMID:26839216

  6. The international society for developmental psychobiology Sackler symposium: early adversity and the maturation of emotion circuits--a cross-species analysis.

    PubMed

    Callaghan, Bridget L; Sullivan, Regina M; Howell, Brittany; Tottenham, Nim

    2014-12-01

    Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations.

  7. Cross-Species Analysis of Protein Dynamics Associated with Hydride and Proton Transfer in the Catalytic Cycle of the Light-Driven Enzyme Protochlorophyllide Oxidoreductase.

    PubMed

    Hoeven, Robin; Hardman, Samantha J O; Heyes, Derren J; Scrutton, Nigel S

    2016-02-16

    Experimental interrogation of the relationship between protein dynamics and enzyme catalysis is challenging. Light-activated protochlorophyllide oxidoreductase (POR) is an excellent model for investigating this relationship because photoinitiation of the reaction cycle enables coordinated turnover in a "dark-assembled" ternary enzyme-substrate complex. The catalytic cycle involves sequential hydride and proton transfers (from NADPH and an active site tyrosine residue, respectively) to the substrate protochlorophyllide. Studies with a limited cross-species subset of POR enzymes (n = 4) have suggested that protein dynamics associated with hydride and proton transfer are distinct [Heyes, D. J., Levy, C., Sakuma, M., Robertson, D. L., and Scrutton, N. S. (2011) J. Biol. Chem. 286, 11849-11854]. Here, we use steady-state assays and single-turnover laser flash spectroscopy to analyze hydride and proton transfer dynamics in an extended series of POR enzymes taken from many species, including cyanobacteria, algae, embryophytes, and angiosperms. Hydride/proton transfer in all eukaryotic PORs is faster compared to prokaryotic PORs, suggesting active site architecture has been optimized in eukaryotic PORs following endosymbiosis. Visible pump-probe spectroscopy was also used to demonstrate a common photoexcitation mechanism for representative POR enzymes from different branches of the phylogenetic tree. Dynamics associated with hydride transfer are localized to the active site of all POR enzymes and are conserved. However, dynamics associated with proton transfer are variable. Protein dynamics associated with proton transfer are also coupled to solvent dynamics in cyanobacterial PORs, and these networks are likely required to optimize (shorten) the donor-acceptor distance for proton transfer. These extended networks are absent in algal and plant PORs. Our analysis suggests that extended networks of dynamics are disfavored, possibly through natural selection. Implications for

  8. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

    2016-07-01

    Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks.

  9. Genomic responses in mouse models poorly mimic human inflammatory diseases

    PubMed Central

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  10. Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

    NASA Astrophysics Data System (ADS)

    Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

    2010-03-01

    Atomistic details of beta-amyloid (Aβ ) protein unfolding and lipid interaction kinetics mediated by the neuronal membrane surface are important for developing new therapeutic strategies to prevent and cure Alzheimer's disease. Using all-atom MD simulations, we explored the early unfolding and insertion kinetics of 40 and 42 residue long Aβ in binary lipid mixtures with and without cholesterol that mimic the cholesterol-depleted and cholesterol-enriched lipid nanodomains of neurons. The protein conformational transition kinetics was evaluated from the secondary structure profile versus simulation time plot. The extent of membrane disruption was examined by the calculated order parameters of lipid acyl chains and cholesterol fused rings as well as the density profiles of water and lipid headgroups at defined regions across the lipid bilayer from our simulations. Our results revealed that both the cholesterol content and the length of the protein affect the protein-insertion and membrane stability in our model lipid bilayer systems.

  11. De Novo Designed Synthetic Mimics of Antimicrobial Peptides

    PubMed Central

    Scott, Richard W.; DeGrado, William F.; Tew, Gregory N.

    2008-01-01

    Summary Antimicrobial peptides are small cationic amphiphiles that play an important role in the innate immune system. Given their broad specificity, they appear to be ideal therapeutic agents. As a result, over the last decade, there has been considerable interest in developing them as intravenously administered antibiotics. However, it has proven difficult to accomplish this goal with peptide-based structures. While it has been possible to solve some relatively simple problems such as susceptibility to proteolysis, more severe problems have included the expense of the materials, toxicity, limited efficacy, and limited tissue distribution. As a result, we developed small synthetic oligomers designed to adopt amphiphilic conformations and exhibit potent antimicrobial activity while being non-toxic to host cells. One class of these synthetic mimics of antimicrobial peptides (SMAMPs) is being developed as intravenous antibiotics PMID:18996193

  12. Synthetic Mimics of Antimicrobial Peptides From Triaryl Scaffolds

    PubMed Central

    Thaker, Hitesh D.; Sgolastra, Federica; Clements, Dylan; Scott, Richard W.; Tew, Gregory N.

    2011-01-01

    In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds, which mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular hydrogen bonds, and the overall hydrophobicity by modifications to the central ring and the side chains. This approach allowed us to better understand the influence of these features on the antimicrobial activity and selectivity. We found that the overall hydrophobicity had a more significant impact on antimicrobial and hemolytic activity than the conformational stiffness. A novel compound was discovered with antimicrobial activity similar to the well known antimicrobial peptide, MSI-78, which have MICs of 0.78 μg/mL against S. aureus and 6.25 μg/mL against E. coli. PMID:21388190

  13. Thalidomide mimics uridine binding to an aromatic cage in cereblon.

    PubMed

    Hartmann, Marcus D; Boichenko, Iuliia; Coles, Murray; Zanini, Fabio; Lupas, Andrei N; Hernandez Alvarez, Birte

    2014-12-01

    Thalidomide and its derivatives lenalidomide and pomalidomide are important anticancer agents but can cause severe birth defects via an interaction with the protein cereblon. The ligand-binding domain of cereblon is found, with a high degree of conservation, in both bacteria and eukaryotes. Using a bacterial model system, we reveal the structural determinants of cereblon substrate recognition, based on a series of high-resolution crystal structures. For the first time, we identify a cellular ligand that is universally present: we show that thalidomide and its derivatives mimic and compete for the binding of uridine, and validate these findings in vivo. The nature of the binding pocket, an aromatic cage of three tryptophan residues, further suggests a role in the recognition of cationic ligands. Our results allow for general evaluation of pharmaceuticals for potential cereblon-dependent teratogenicity.

  14. Predator Mimicry: Metalmark Moths Mimic Their Jumping Spider Predators

    PubMed Central

    Rota, Jadranka; Wagner, David L.

    2006-01-01

    Cases of mimicry provide many of the nature's most convincing examples of natural selection. Here we report evidence for a case of predator mimicry in which metalmark moths in the genus Brenthia mimic jumping spiders, one of their predators. In controlled trials, Brenthia had higher survival rates than other similarly sized moths in the presence of jumping spiders and jumping spiders responded to Brenthia with territorial displays, indicating that Brenthia were sometimes mistaken for jumping spiders, and not recognized as prey. Our experimental results and a review of wing patterns of other insects indicate that jumping spider mimicry is more widespread than heretofore appreciated, and that jumping spiders are probably an important selective pressure shaping the evolution of diurnal insects that perch on vegetation. PMID:17183674

  15. Design, Synthesis, and Evaluation of Novel Auxin Mimic Herbicides.

    PubMed

    Do-Thanh, Chi-Linh; Vargas, Jose J; Thomas, Joseph W; Armel, Gregory R; Best, Michael D

    2016-05-11

    Due to the key roles of auxins as master regulators of plant growth, there is considerable interest in the development of compounds with auxin-like properties for growth management and weed control applications. Herein, we describe the design and multistep synthesis of ten compounds bearing combinations of functional groups commonly associated with auxin-type properties. Following synthesis, these compounds were tested against multiple weed species as well as sweet corn. In general, while these structures were not quite as active as commercial auxin mimic herbicides, multiple compounds exhibited broadleaf weed activity with concurrent selectivity in sweet corn (Zea mays L. var. saccharum). In addition, differential results were observed upon subtle changes to structure, providing insights into the structural properties required for activity. PMID:27086840

  16. Nanorod mediated collagen scaffolds as extra cellular matrix mimics.

    PubMed

    Vedhanayagam, Mohan; Mohan, Ranganathan; Nair, Balachandran Unni; Sreeram, Kalarical Janardhanan

    2015-12-01

    Creating collagen scaffolds that mimic extracellular matrices without using toxic exogenous materials remains a big challenge. A new strategy to create scaffolds through end-to-end crosslinking through functionalized nanorods leading to well-designed architecture is presented here. Self-assembled scaffolds with a denaturation temperature of 110 °C, porosity of 70%, pore size of 0.32 μm and Young's modulus of 231 MPa were developed largely driven by imine bonding between 3-mercapto-1-propanal (MPA) functionalized ZnO nanorods and collagen. The mechanical properties obtained were much higher than that of native collagen, collagen-MPA, collagen-3-mercapto-1-propanol (3MPOH) or collagen- 3-MPOH-ZnO, clearly bringing out the relevance of nanorod mediated assembly of fibrous networks. This new strategy has led to scaffolds with mechanical properties much higher than earlier reports and can provide support for cell growth and facilitation of cell attachment. PMID:26586667

  17. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

    PubMed Central

    Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

    2016-01-01

    Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks. PMID:27443913

  18. A Photoisomerizing Rhodopsin Mimic Observed at Atomic Resolution.

    PubMed

    Nosrati, Meisam; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James H

    2016-07-20

    The members of the rhodopsin family of proteins are involved in many essential light-dependent processes in biology. Specific photoisomerization of the protein-bound retinylidene PSB at a specified wavelength range of light is at the heart of all of these systems. Nonetheless, it has been difficult to reproduce in an engineered system. We have developed rhodopsin mimics, using intracellular lipid binding protein family members as scaffolds, to study fundamental aspects of protein/chromophore interactions. Herein we describe a system that specifically isomerizes the retinylidene protonated Schiff base both thermally and photochemically. This isomerization has been characterized at atomic resolution by quantitatively interconverting the isomers in the crystal both thermally and photochemically. This event is accompanied by a large pKa change of the imine similar to the pKa changes observed in bacteriorhodopsin and visual opsins during isomerization. PMID:27310917

  19. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons.

    PubMed

    Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

    2016-01-01

    Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks. PMID:27443913

  20. Cupric yersiniabactin is a virulence-associated superoxide dismutase mimic.

    PubMed

    Chaturvedi, Kaveri S; Hung, Chia S; Giblin, Daryl E; Urushidani, Saki; Austin, Anthony M; Dinauer, Mary C; Henderson, Jeffrey P

    2014-02-21

    Many Gram-negative bacteria interact with extracellular metal ions by expressing one or more siderophore types. Among these, the virulence-associated siderophore yersiniabactin (Ybt) is an avid copper chelator, forming stable cupric (Cu(II)-Ybt) complexes that are detectable in infected patients. Here we show that Ybt-expressing E. coli are protected from intracellular killing within copper-replete phagocytic cells. This survival advantage is highly dependent upon the phagocyte respiratory burst, during which superoxide is generated by the NADPH oxidase complex. Chemical fractionation links this phenotype to a previously unappreciated superoxide dismutase (SOD)-like activity of Cu(II)-Ybt. Unlike previously described synthetic copper-salicylate (Cu(II)-SA) SOD mimics, the salicylate-based natural product Cu(II)-Ybt retains catalytic activity at physiologically plausible protein concentrations. These results reveal a new virulence-associated adaptation based upon spontaneous assembly of a non-protein catalyst. PMID:24283977

  1. Cupric Yersiniabactin Is a Virulence-Associated Superoxide Dismutase Mimic

    PubMed Central

    2013-01-01

    Many Gram-negative bacteria interact with extracellular metal ions by expressing one or more siderophore types. Among these, the virulence-associated siderophore yersiniabactin (Ybt) is an avid copper chelator, forming stable cupric (Cu(II)-Ybt) complexes that are detectable in infected patients. Here we show that Ybt-expressing E. coli are protected from intracellular killing within copper-replete phagocytic cells. This survival advantage is highly dependent upon the phagocyte respiratory burst, during which superoxide is generated by the NADPH oxidase complex. Chemical fractionation links this phenotype to a previously unappreciated superoxide dismutase (SOD)-like activity of Cu(II)-Ybt. Unlike previously described synthetic copper-salicylate (Cu(II)-SA) SOD mimics, the salicylate-based natural product Cu(II)-Ybt retains catalytic activity at physiologically plausible protein concentrations. These results reveal a new virulence-associated adaptation based upon spontaneous assembly of a non-protein catalyst. PMID:24283977

  2. Exogenous T3 mimics long day lengths in Siberian hamsters.

    PubMed

    Freeman, David A; Teubner, Brett J W; Smith, Carlesia D; Prendergast, Brian J

    2007-06-01

    Siberian hamsters (Phodopus sungorus) exhibit seasonal cycles of reproduction driven by changes in day length. Day length is encoded endogenously by the duration of nocturnal melatonin (Mel) secretion from the pineal gland. Short-duration Mel signals stimulate reproduction and long-duration signals inhibit reproduction. The mechanism by which Mel signals are decoded at the level of neural target tissues remains uncharacterized. In Siberian hamsters, exposure to short day lengths or injections of Mel in long days results in a decrease in hypothalamic expression of type 2 iodothyronine deiodinase (Dio2) mRNA. Dio2 catalyzes the conversion of the thyroid hormone thyroxine to triiodothyronine (T3). Thus exposure to short and long day lengths should decrease and increase hypothalamic T3 concentrations, respectively. We tested the hypothesis that exogenous T3 administered to short-day hamsters would mimic exposure to long day lengths with respect to gonadal stimulation. Hamsters gestated and raised in short day lengths that exhibited photoinhibition of the testes were given daily subutaneous injections of T3 or saline vehicle for 4 wk beginning at week 12 of life. The results indicate that exogenous T3 induced gonadal growth in short-day hamsters and delayed spontaneous gonadal development by an interval equal to the number of weeks during which T3 was administered. T3 injections delayed gonadal regression if given coincident with the transfer of hamsters from long to short day lengths. These results suggest that T3 mimics long day exposure in Siberian hamsters and may serve as an intermediate step between the Mel rhythm and the reproductive response.

  3. Essential Metabolites of Mycobacterium tuberculosis and Their Mimics

    PubMed Central

    Lamichhane, Gyanu; Freundlich, Joel S.; Ekins, Sean; Wickramaratne, Niluka; Nolan, Scott T.; Bishai, William R.

    2011-01-01

    An organism requires a range of biomolecules for its growth. By definition, these are essential molecules which constitute the basic metabolic requirements of an organism. A small organic molecule with chemical similarity to that of an essential metabolite may bind to the enzyme that catalyzes its production and inhibit it, likely resulting in the stasis or death of the organism. Here, we report a high-throughput approach for identifying essential metabolites of an organism using genetic and biochemical approaches and then implement computational approaches to identify metabolite mimics. We generated and genotyped 5,126 Mycobacterium tuberculosis mutants and performed a statistical analysis to determine putative essential genes. The essential molecules of M. tuberculosis were classified as products of enzymes that are encoded by genes in this list. Although incomplete, as many enzymes of M. tuberculosis have yet to be identified and characterized, this is the first report of a large number of essential molecules of the organism. We identified essential metabolites of three distinct metabolic pathways in M. tuberculosis and selected molecules with chemical similarity using cheminformatics strategies that illustrate a variety of different pharmacophores. Our approach is aimed at systematic identification of essential molecules and their mimics as a blueprint for development of effective chemical probes of M. tuberculosis metabolism, with the ultimate goal of seeking drugs that can kill this pathogen. As an illustration of this approach, we report that compounds JFD01307SC and l-methionine-S-sulfoximine, which share chemical similarity with an essential molecule of M. tuberculosis, inhibited the growth of this organism at micromolar concentrations. PMID:21285434

  4. The effects of floral mimics and models on each others' fitness

    PubMed Central

    Anderson, Bruce; Johnson, Steven D

    2006-01-01

    Plants that lack floral rewards may nevertheless attract pollinators by mimicking the flowers of rewarding plants. It has been suggested that both mimics and models should suffer reduced fitness when mimics are abundant relative to their models. By manipulating the relative densities of an orchid mimic Disa nivea and its rewarding model Zaluzianskya microsiphon in small experimental patches within a larger population we demonstrated that the mimic does indeed suffer reduced pollination success when locally common relative to its model. Behavioural experiments suggest that this phenomenon results from the tendency of the long-proboscid fly pollinator to avoid visits to neighbouring plants when encountering the mimic. No negative effect of the mimic on the pollination success of the model was detected. We propose that changes in pollinator flight behaviour, rather than pollinator conditioning, are likely to account for negative frequency-dependent reproductive success in deceptive orchids. PMID:16627282

  5. Does the abundance of hoverfly (Syrphidae) mimics depend on the numbers of their hymenopteran models?

    PubMed

    Howarth, Brigitte; Edmunds, Malcolm; Gilbert, Francis

    2004-02-01

    We tested the prediction that, if hoverflies are Batesian mimics, this may extend to behavioral mimicry such that their numerical abundance at each hour of the day (the daily activity pattern) is related to the numbers of their hymenopteran models. After accounting for site, season, microclimatic responses, and general hoverfly abundance at three sites in northwestern England, the residual numbers of mimics were significantly correlated positively with their models nine times of 17. Sixteen of 17 relationships were positive, itself a highly significant nonrandom pattern. Several eristaline flies showed significant relationships with honeybees even though some of them mimic wasps or bumblebees, perhaps reflecting an ancestral resemblance to honeybees. There was no evidence that good and poor mimics differed in their daily activity pattern relationships with models. However, the common mimics showed significant activity pattern relationships with their models, whereas the rarer mimics did not. We conclude that many hoverflies show behavioral mimicry of their hymenopteran models.

  6. All-metal clusters that mimic the chemistry of halogens.

    PubMed

    Zhao, Tianshan; Li, Yawei; Wang, Qian; Jena, Puru

    2013-10-01

    Owing to their s(2)p(5) electronic configuration, halogen atoms are highly electronegative and constitute the anionic components of salts. Whereas clusters that contain no halogen atoms, such as AlH(4), mimic the chemistry of halogens and readily form salts (e.g., Na(+)(AlH(4))(-)), clusters that are solely composed of metal atoms and yet behave in the same manner as a halogen are rare. Because coinage-metal atoms (Cu, Ag, and Au) only have one valence electron in their outermost electronic shell, as in H, we examined the possibility that, on interacting with Al, in particular as AlX(4) (X=Cu, Ag, Au), these metal atoms may exhibit halogen-like properties. By using density functional theory, we show that AlAu(4) not only mimics the chemistry of halogens, but also, with a vertical detachment energy (VDE) of 3.98 eV in its anionic form, is a superhalogen. Similarly, analogous to XHX superhalogens (X=F, Cl, Br), XAuX species with VDEs of 4.65, 4.50, and 4.34 eV in their anionic form, respectively, also form superhalogens. In addition, Au can also form hyperhalogens, a recently discovered species that show electron affinities (EAs) that are even higher than those of their corresponding superhalogen building blocks. For example, the VDEs of M(AlAu(4))(2)(-) (M=Na and K) and anionic (FAuF)Au(FAuF) range from 4.06 to 5.70 eV. Au-based superhalogen anions, such as AlAu(4)(-) and AuF(2)(-), have the additional advantage that they exhibit wider optical absorption ranges than their H-based analogues, AlH(4)(-) and HF(2)(-). Because of the catalytic properties and the biocompatibility of Au, Au-based superhalogens may be multifunctional. However, similar studies that were carried out for Cu and Ag atoms have shown that, unlike AlAu(4), AlX(4) (X=Cu, Ag) clusters are not superhalogens, a property that can be attributed to the large EA of the Au atom.

  7. Sialylation of prion protein controls the rate of prion amplification, the cross-species barrier, the ratio of PrPSc glycoform and prion infectivity.

    PubMed

    Katorcha, Elizaveta; Makarava, Natallia; Savtchenko, Regina; D'Azzo, Alessandra; Baskakov, Ilia V

    2014-09-01

    The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrP(C)) into the disease-associated, transmissible form (PrP(Sc)). Pr(PC) is a sialoglycoprotein that contains two conserved N-glycosylation sites. Among the key parameters that control prion replication identified over the years are amino acid sequence of host PrP(C) and the strain-specific structure of PrPSc. The current work highlights the previously unappreciated role of sialylation of PrP(C) glycans in prion pathogenesis, including its role in controlling prion replication rate, infectivity, cross-species barrier and PrP(Sc) glycoform ratio. The current study demonstrates that undersialylated PrP(C) is selected during prion amplification in Protein Misfolding Cyclic Amplification (PMCAb) at the expense of oversialylated PrP(C). As a result, PMCAb-derived PrP(Sc) was less sialylated than brain-derived PrP(Sc). A decrease in PrPSc sialylation correlated with a drop in infectivity of PMCAb-derived material. Nevertheless, enzymatic de-sialylation of PrP(C) using sialidase was found to increase the rate of PrP(Sc) amplification in PMCAb from 10- to 10,000-fold in a strain-dependent manner. Moreover, de-sialylation of PrP(C) reduced or eliminated a species barrier of for prion amplification in PMCAb. These results suggest that the negative charge of sialic acid controls the energy barrier of homologous and heterologous prion replication. Surprisingly, the sialylation status of PrP(C) was also found to control PrP(Sc) glycoform ratio. A decrease in Pr(PC) sialylation levels resulted in a higher percentage of the diglycosylated glycoform in PrP(Sc). 2D analysis of charge distribution revealed that the sialylation status of brain-derived PrP(C) differed from that of spleen-derived PrP(C). Knocking out lysosomal sialidase Neu1 did not change the sialylation status of brain-derived PrP(C), suggesting that Neu1 is not responsible for desialylation of Pr

  8. Generation and infectivity titration of an infectious stock of avian hepatitis E virus (HEV) in chickens and cross-species infection of turkeys with avian HEV.

    PubMed

    Sun, Z F; Larsen, C T; Huang, F F; Billam, P; Pierson, F W; Toth, T E; Meng, X J

    2004-06-01

    together with the inoculated ones also became infected through direct contact. This is the first demonstration of cross-species infection by avian HEV.

  9. Bioinformatics resource manager v2.3: an integrated software environment for systems biology with microRNA and cross-species analysis tools

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP) miRNA data in an increasing number of model species. The Bioinformatics Resource Manager (BRM) v2.3 is a software environment for data management, mining, integration and functional annotation of HTP biological data. In this study, we report recent updates to BRM for miRNA data analysis and cross-species comparisons across datasets. Results BRM v2.3 has the capability to query predicted miRNA targets from multiple databases, retrieve potential regulatory miRNAs for known genes, integrate experimentally derived miRNA and mRNA datasets, perform ortholog mapping across species, and retrieve annotation and cross-reference identifiers for an expanded number of species. Here we use BRM to show that developmental exposure of zebrafish to 30 uM nicotine from 6–48 hours post fertilization (hpf) results in behavioral hyperactivity in larval zebrafish and alteration of putative miRNA gene targets in whole embryos at developmental stages that encompass early neurogenesis. We show typical workflows for using BRM to integrate experimental zebrafish miRNA and mRNA microarray datasets with example retrievals for zebrafish, including pathway annotation and mapping to human ortholog. Functional analysis of differentially regulated (p<0.05) gene targets in BRM indicates that nicotine exposure disrupts genes involved in neurogenesis, possibly through misregulation of nicotine-sensitive miRNAs. Conclusions BRM provides the ability to mine complex data for identification of candidate miRNAs or pathways that drive phenotypic outcome and, therefore, is a useful hypothesis

  10. Transcript profiling of two alfalfa genotypes with contrasting cell wall composition in stems using a cross-species platform: optimizing analysis by masking biased probes

    PubMed Central

    2010-01-01

    Background The GeneChip® Medicago Genome Array, developed for Medicago truncatula, is a suitable platform for transcript profiling in tetraploid alfalfa [Medicago sativa (L.) subsp. sativa]. However, previous research involving cross-species hybridization (CSH) has shown that sequence variation between two species can bias transcript profiling by decreasing sensitivity (number of expressed genes detected) and the accuracy of measuring fold-differences in gene expression. Results Transcript profiling using the Medicago GeneChip® was conducted with elongating stem (ES) and post-elongation stem (PES) internodes from alfalfa genotypes 252 and 1283 that differ in stem cell wall concentrations of cellulose and lignin. A protocol was developed that masked probes targeting inter-species variable (ISV) regions of alfalfa transcripts. A probe signal intensity threshold was selected that optimized both sensitivity and accuracy. After masking for both ISV regions and previously identified single-feature polymorphisms (SFPs), the number of differentially expressed genes between the two genotypes in both ES and PES internodes was approximately 2-fold greater than the number detected prior to masking. Regulatory genes, including transcription factor and receptor kinase genes that may play a role in development of secondary xylem, were significantly over-represented among genes up-regulated in 252 PES internodes compared to 1283 PES internodes. Several cell wall-related genes were also up-regulated in genotype 252 PES internodes. Real-time quantitative RT-PCR of differentially expressed regulatory and cell wall-related genes demonstrated increased sensitivity and accuracy after masking for both ISV regions and SFPs. Over 1,000 genes that were differentially expressed in ES and PES internodes of genotypes 252 and 1283 were mapped onto putative orthologous loci on M. truncatula chromosomes. Clustering simulation analysis of the differentially expressed genes suggested co

  11. Isolation and characterization of microsatellite markers from the olive fly, Bactrocera oleae, and their cross-species amplification in the Tephritidae family

    PubMed Central

    Augustinos, Antonios A; Stratikopoulos, Elias E; Drosopoulou, Eleni; Kakani, Evdoxia G; Mavragani-Tsipidou, Penelope; Zacharopoulou, Antigone; Mathiopoulos, Kostas D

    2008-01-01

    Background The Tephritidae family of insects includes the most important agricultural pests of fruits and vegetables, belonging mainly to four genera (Bactrocera, Ceratitis, Anastrepha and Rhagoletis). The olive fruit fly, Bactrocera oleae, is the major pest of the olive fruit. Currently, its control is based on chemical insecticides. Environmentally friendlier methods have been attempted in the past (Sterile Insect Technique), albeit with limited success. This was mainly attributed to the lack of knowledge on the insect's behaviour, ecology and genetic structure of natural populations. The development of molecular markers could facilitate the access in the genome and contribute to the solution of the aforementioned problems. We chose to focus on microsatellite markers due to their abundance in the genome, high degree of polymorphism and easiness of isolation. Results Fifty-eight microsatellite-containing clones were isolated from the olive fly, Bactrocera oleae, bearing a total of sixty-two discrete microsatellite motifs. Forty-two primer pairs were designed on the unique sequences flanking the microsatellite motif and thirty-one of them amplified a PCR product of the expected size. The level of polymorphism was evaluated against wild and laboratory flies and the majority of the markers (93.5%) proved highly polymorphic. Thirteen of them presented a unique position on the olive fly polytene chromosomes by in situ hybridization, which can serve as anchors to correlate future genetic and cytological maps of the species, as well as entry points to the genome. Cross-species amplification of these markers to eleven Tephritidae species and sequencing of thirty-one of the amplified products revealed a varying degree of conservation that declines outside the Bactrocera genus. Conclusion Microsatellite markers are very powerful tools for genetic and population analyses, particularly in species deprived of any other means of genetic analysis. The presented set of

  12. Development of Genomic Microsatellite Markers in Carthamus tinctorius L. (Safflower) Using Next Generation Sequencing and Assessment of Their Cross-Species Transferability and Utility for Diversity Analysis

    PubMed Central

    Variath, Murali Tottekkad; Joshi, Gopal; Bali, Sapinder; Agarwal, Manu; Kumar, Amar; Jagannath, Arun; Goel, Shailendra

    2015-01-01

    Background Safflower (Carthamus tinctorius L.), an Asteraceae member, yields high quality edible oil rich in unsaturated fatty acids and is resilient to dry conditions. The crop holds tremendous potential for improvement through concerted molecular breeding programs due to the availability of significant genetic and phenotypic diversity. Genomic resources that could facilitate such breeding programs remain largely underdeveloped in the crop. The present study was initiated to develop a large set of novel microsatellite markers for safflower using next generation sequencing. Principal Findings Low throughput genome sequencing of safflower was performed using Illumina paired end technology providing ~3.5X coverage of the genome. Analysis of sequencing data allowed identification of 23,067 regions harboring perfect microsatellite loci. The safflower genome was found to be rich in dinucleotide repeats followed by tri-, tetra-, penta- and hexa-nucleotides. Primer pairs were designed for 5,716 novel microsatellite sequences with repeat length ≥ 20 bases and optimal flanking regions. A subset of 325 microsatellite loci was tested for amplification, of which 294 loci produced robust amplification. The validated primers were used for assessment of 23 safflower accessions belonging to diverse agro-climatic zones of the world leading to identification of 93 polymorphic primers (31.6%). The numbers of observed alleles at each locus ranged from two to four and mean polymorphism information content was found to be 0.3075. The polymorphic primers were tested for cross-species transferability on nine wild relatives of cultivated safflower. All primers except one showed amplification in at least two wild species while 25 primers amplified across all the nine species. The UPGMA dendrogram clustered C. tinctorius accessions and wild species separately into two major groups. The proposed progenitor species of safflower, C. oxyacantha and C. palaestinus were genetically closer to

  13. The αGal Epitope of the Histo-Blood Group Antigen Family Is a Ligand for Bovine Norovirus Newbury2 Expected to Prevent Cross-Species Transmission

    PubMed Central

    Zakhour, Maha; Ruvoën-Clouet, Nathalie; Charpilienne, Annie; Langpap, Brigitte; Poncet, Didier; Peters, Thomas; Bovin, Nicolai; Le Pendu, Jacques

    2009-01-01

    Among Caliciviridae, the norovirus genus encompasses enteric viruses that infect humans as well as several animal species, causing gastroenteritis. Porcine strains are classified together with human strains within genogroup II, whilst bovine norovirus strains represent genogroup III. Various GI and GII human strains bind to carbohydrates of the histo-blood group family which may be shared among mammalian species. Genetic relatedness of human and animal strains as well as the presence of potentially shared ligands raises the possibility of norovirus cross-species transmission. In the present study, we identified a carbohydrate ligand for the prototype bovine norovirus strain Bo/Newbury2/76/UK (NB2). Attachment of virus-like particles (VLPs) of the NB2 strain to bovine gut tissue sections showed a complete match with the staining by reagents recognizing the Galα1,3 motif. Alpha-galactosidase treatment confirmed involvement of a terminal alpha-linked galactose. Specific binding of VLPs to the αGal epitope (Galα3Galβ4GlcNAcβ-R) was observed. The binding of Galα3GalαOMe to rNB2 VLPs was characterized at atomic resolution employing saturation transfer difference (STD) NMR experiments. Transfection of human cells with an α1,3galactosyltransferase cDNA allowed binding of NB2 VLPs, whilst inversely, attachment to porcine vascular endothelial cells was lost when the cells originated from an α1,3galactosyltransferase KO animal. The αGal epitope is expressed in all mammalian species with the exception of the Hominidaea family due to the inactivation of the α1,3galactosyltransferase gene (GGTA1). Accordingly, the NB2 carbohydrate ligand is absent from human tissues. Although expressed on porcine vascular endothelial cells, we observed that unlike in cows, it is not present on gut epithelial cells, suggesting that neither man nor pig could be infected by the NB2 bovine strain. PMID:19578439

  14. Nematode infection: A rare mimic of acute appendicitis

    PubMed Central

    Hotchen, Andrew; Chin, Kian; Raja, Mahzar

    2014-01-01

    INTRODUCTION Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures. PRESENTATION OF CASE A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved. DISCUSSION Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided. CONCLUSION This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix. PMID:25024022

  15. Mitochondrial Disorders May Mimic Amyotrophic Lateral Sclerosis at Onset.

    PubMed

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-02-01

    Similarities between a mitochondrial disorder (MID) and amyotrophic lateral sclerosis (ALS) fade with disease progression and the development of mitochondrial multiple organ dysfunction syndrome (MIMODS). However, with mild MIMODS, a MID may still be misinterpreted as ALS. We report a 48-year-old male who presented to the Neurological Hospital Rosenhügel, Vienna, Austria, in February 2001 with slowly progressive weakness, wasting and left upper limb fasciculations which spread to the shoulder girdle and lower limbs. Additionally, he developed tetraspasticity and bulbar involvement. He had been diagnosed with ALS a year previously due to electrophysiological investigations indicative of a chronic neurogenic lesion. However, a muscle biopsy revealed morphological features of a MID and a combined complex-II/III defect. Nerve conduction studies were performed over subsequent years until February 2011. This case demonstrates that MIDs may mimic ALS at onset and begin as a mono-organ disorder but develop into a multi-organ disease with long-term progression. A combined complex II/III defect may manifest with bulbar involvement. PMID:26909222

  16. Mimic therapeutic actions against keloid by thermostatted kinetic theory methods

    NASA Astrophysics Data System (ADS)

    Bianca, Carlo; Riposo, Julien

    2015-08-01

    This paper deals with the modeling of a wound-healing disease under a therapeutic action by employing the methods of the thermostatted kinetic theory for active particles. In particular, in order to test therapeutic actions against keloid formation and the possible development of a cancer, an external force field coupled to a Gaussian thermostat is introduced into a mathematical model recently proposed. Specifically the model depicts the competition of the immune system cells with a virus, the mutated fibroblast cells, and the cancer cells. Employing a computational analysis, the effects of three different external forces mimic therapeutic actions are analyzed: A vaccine for the virus, the PUVA therapy for the keloid and a vaccine for the cancer. The results are in agreement with the evidence that the sole action of the immune system is not sufficient to obtain a total depletion of keloid thus requiring the definition of a therapy. Further refinements and developments of the model are also discussed in the paper.

  17. Reproducing Natural Spider Silks’ Copolymer Behavior in Synthetic Silk Mimics

    PubMed Central

    An, Bo; Jenkins, Janelle E.; Sampath, Sujatha; Holland, Gregory P.; Hinman, Mike; Yarger, Jeffery L.; Lewis, Randolph

    2012-01-01

    Dragline silk from orb-weaving spiders is a copolymer of two large proteins, major ampullate spidroin 1 (MaSp1) and 2 (MaSp2). The ratio of these proteins is known to have a large variation across different species of orb-weaving spiders. NMR results from gland material of two different species of spiders, N. clavipes and A. aurantia, indicates that MaSp1 proteins are more easily formed into β-sheet nanostructures, while MaSp2 proteins form random coil and helical structures. To test if this behavior of natural silk proteins could be reproduced by recombinantly produced spider silk mimic protein, recombinant MaSp1/MaSp2 mixed fibers as well as chimeric silk fibers from MaSp1 and MaSp2 sequences in a single protein were produced based on the variable ratio and conserved motifs of MaSp1 and MaSp2 in native silk fiber. Mechanical properties, solid-state NMR, and XRD results of tested synthetic fibers indicate the differing roles of MaSp1 and MaSp2 in the fiber and verify the importance of postspin stretching treatment in helping the fiber to form the proper spatial structure. PMID:23110450

  18. Chimpanzees and humans mimic pupil-size of conspecifics.

    PubMed

    Kret, Mariska E; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2014-01-01

    Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

  19. A MIMIC approach to modeling the underground economy in Taiwan

    NASA Astrophysics Data System (ADS)

    Wang, David Han-Min; Lin, Jer-Yan; Yu, Tiffany Hui-Kuang

    2006-11-01

    The size of underground economy (UE) expansion usually increases the tax gap, impose a burden on the economy, and results in tax distortions. This study uses the MIMIC approach to model the causal variables and indicating variables to estimate the UE in Taiwan. We also focus on testing the data for non-stationarity and perform diagnostic tests. By using annual time-series data for Taiwan from 1961 to 2003, it is found that the estimated size of the UE varies from 11.0% to 13.1% before 1988, and from 10.6% to 11.8% from 1989 onwards. That the size of the UE experienced a substantial downward shift in 1989 indicates that there was a structural break. The UE is significantly and positively affected by such casual variables as the logarithm of real government consumption and currency inflation, but is negatively affected by the tax burden at 5% significant level. Unemployment rate and crime rate are not significantly correlated with the UE in this study.

  20. Reproducing natural spider silks' copolymer behavior in synthetic silk mimics.

    PubMed

    An, Bo; Jenkins, Janelle E; Sampath, Sujatha; Holland, Gregory P; Hinman, Mike; Yarger, Jeffery L; Lewis, Randolph

    2012-12-10

    Dragline silk from orb-weaving spiders is a copolymer of two large proteins, major ampullate spidroin 1 (MaSp1) and 2 (MaSp2). The ratio of these proteins is known to have a large variation across different species of orb-weaving spiders. NMR results from gland material of two different species of spiders, N. clavipes and A. aurantia , indicates that MaSp1 proteins are more easily formed into β-sheet nanostructures, while MaSp2 proteins form random coil and helical structures. To test if this behavior of natural silk proteins could be reproduced by recombinantly produced spider silk mimic protein, recombinant MaSp1/MaSp2 mixed fibers as well as chimeric silk fibers from MaSp1 and MaSp2 sequences in a single protein were produced based on the variable ratio and conserved motifs of MaSp1 and MaSp2 in native silk fiber. Mechanical properties, solid-state NMR, and XRD results of tested synthetic fibers indicate the differing roles of MaSp1 and MaSp2 in the fiber and verify the importance of postspin stretching treatment in helping the fiber to form the proper spatial structure. PMID:23110450

  1. Reproducing Natural Spider Silks' Copolymer Behavior in Synthetic Silk Mimics

    SciTech Connect

    An, Bo; Jenkins, Janelle E; Sampath, Sujatha; Holland, Gregory P; Hinman, Mike; Yarger, Jeffery L; Lewis, Randolph

    2012-10-30

    Dragline silk from orb-weaving spiders is a copolymer of two large proteins, major ampullate spidroin 1 (MaSp1) and 2 (MaSp2). The ratio of these proteins is known to have a large variation across different species of orb-weaving spiders. NMR results from gland material of two different species of spiders, N. clavipes and A. aurantia, indicates that MaSp1 proteins are more easily formed into β-sheet nanostructures, while MaSp2 proteins form random coil and helical structures. To test if this behavior of natural silk proteins could be reproduced by recombinantly produced spider silk mimic protein, recombinant MaSp1/MaSp2 mixed fibers as well as chimeric silk fibers from MaSp1 and MaSp2 sequences in a single protein were produced based on the variable ratio and conserved motifs of MaSp1 and MaSp2 in native silk fiber. Mechanical properties, solid-state NMR, and XRD results of tested synthetic fibers indicate the differing roles of MaSp1 and MaSp2 in the fiber and verify the importance of postspin stretching treatment in helping the fiber to form the proper spatial structure.

  2. Chimpanzees and Humans Mimic Pupil-Size of Conspecifics

    PubMed Central

    Kret, Mariska E.; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2014-01-01

    Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals. PMID:25140998

  3. A Case Report of Neurosarcoidosis Presenting as a Lymphoma Mimic

    PubMed Central

    Cameron, Lauren; Syritsyna, Olga

    2016-01-01

    Objective. To describe a unique presentation of neurosarcoidosis. Background. Central nervous system involvement is rare in sarcoidosis. Sarcoidosis can be severe and can be mistaken for systemic lymphoma. Case Description. A 55-year-old right-handed white male with past medical history of obstructive sleep apnea, Raynaud's disease, and Hashimoto's thyroiditis was noted to have cognitive decline over a duration of few weeks and 20 lb weight loss. His neurologic exam (including cranial nerves) was normal except for five-minute recall. Head CT revealed a lacrimal gland mass, confirmed on brain MRI, which was suspicious for lymphoma on brain PET/MRI. Subsequent whole-body FDG PET/CT scan showed multiple enlarged lymph nodes. Bone marrow biopsy was negative. Serum and CSF ACE levels were within normal limits. Supraclavicular lymph node biopsy before steroids therapy was initiated and revealed multiple noncaseating granulomas, diagnostic of “sarcoidosis.” He was treated with daily prednisone for two months, followed by weekly infliximab. Brain MRI two months after treatment with prednisone showed decrease in size of lacrimal lesion, and brain PET/MRI showed normal brain metabolism pattern after five months. Neurocognitive evaluation three months after diagnosis demonstrated improvements in memory abilities. Discussion. Both clinically and radiographically, neurosarcoidosis can mimic systemic lymphoma. Biopsy in these types of cases is necessary to establish the diagnosis. PMID:27800198

  4. Mitochondrial Disorders May Mimic Amyotrophic Lateral Sclerosis at Onset

    PubMed Central

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-01-01

    Similarities between a mitochondrial disorder (MID) and amyotrophic lateral sclerosis (ALS) fade with disease progression and the development of mitochondrial multiple organ dysfunction syndrome (MIMODS). However, with mild MIMODS, a MID may still be misinterpreted as ALS. We report a 48-year-old male who presented to the Neurological Hospital Rosenhügel, Vienna, Austria, in February 2001 with slowly progressive weakness, wasting and left upper limb fasciculations which spread to the shoulder girdle and lower limbs. Additionally, he developed tetraspasticity and bulbar involvement. He had been diagnosed with ALS a year previously due to electrophysiological investigations indicative of a chronic neurogenic lesion. However, a muscle biopsy revealed morphological features of a MID and a combined complex-II/III defect. Nerve conduction studies were performed over subsequent years until February 2011. This case demonstrates that MIDs may mimic ALS at onset and begin as a mono-organ disorder but develop into a multi-organ disease with long-term progression. A combined complex II/III defect may manifest with bulbar involvement. PMID:26909222

  5. Rapid Skeletal Turnover In A Radiographic Mimic Of Osteopetrosis

    PubMed Central

    Whyte, Michael P.; Madson, Katherine L.; Mumm, Steven; McAlister, William H.; Novack, Deborah V.; Blair, Jo C.; Helliwell, Timothy R.; Stolina, Marina; Abernethy, Laurence J.; Shaw, Nicholas J.

    2015-01-01

    Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis, and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was > 5,000 IU/L (normal < 850). After partial resection, the granuloma re-grew but then regressed and stabilized during three years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, BMD z-scores reached + 9.1 and + 5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of LRP4, LRP5, or TGFβ1 and for defective SOST, OPG, RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his non-consanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown. PMID:24919763

  6. Alpha-carboxy nucleoside phosphonates as universal nucleoside triphosphate mimics.

    PubMed

    Balzarini, Jan; Das, Kalyan; Bernatchez, Jean A; Martinez, Sergio E; Ngure, Marianne; Keane, Sarah; Ford, Alan; Maguire, Nuala; Mullins, Niki; John, Jubi; Kim, Youngju; Dehaen, Wim; Vande Voorde, Johan; Liekens, Sandra; Naesens, Lieve; Götte, Matthias; Maguire, Anita R; Arnold, Eddy

    2015-03-17

    Polymerases have a structurally highly conserved negatively charged amino acid motif that is strictly required for Mg(2+) cation-dependent catalytic incorporation of (d)NTP nucleotides into nucleic acids. Based on these characteristics, a nucleoside monophosphonate scaffold, α-carboxy nucleoside phosphonate (α-CNP), was designed that is recognized by a variety of polymerases. Kinetic, biochemical, and crystallographic studies with HIV-1 reverse transcriptase revealed that α-CNPs mimic the dNTP binding through a carboxylate oxygen, two phosphonate oxygens, and base-pairing with the template. In particular, the carboxyl oxygen of the α-CNP acts as the potential equivalent of the α-phosphate oxygen of dNTPs and two oxygens of the phosphonate group of the α-CNP chelate Mg(2+), mimicking the chelation by the β- and γ-phosphate oxygens of dNTPs. α-CNPs (i) do not require metabolic activation (phosphorylation), (ii) bind directly to the substrate-binding site, (iii) chelate one of the two active site Mg(2+) ions, and (iv) reversibly inhibit the polymerase catalytic activity without being incorporated into nucleic acids. In addition, α-CNPs were also found to selectively interact with regulatory (i.e., allosteric) Mg(2+)-dNTP-binding sites of nucleos(t)ide-metabolizing enzymes susceptible to metabolic regulation. α-CNPs represent an entirely novel and broad technological platform for the development of specific substrate active- or regulatory-site inhibitors with therapeutic potential. PMID:25733891

  7. Flow pattern visualization in a mimic anaerobic digester using CFD.

    PubMed

    Vesvikar, Mehul S; Al-Dahhan, Muthanna

    2005-03-20

    Three-dimensional steady-state computational fluid dynamics (CFD) simulations were performed in mimic anaerobic digesters to visualize their flow pattern and obtain hydrodynamic parameters. The mixing in the digester was provided by sparging gas at three different flow rates. The gas phase was simulated with air and the liquid phase with water. The CFD results were first evaluated using experimental data obtained by computer automated radioactive particle tracking (CARPT). The simulation results in terms of overall flow pattern, location of circulation cells and stagnant regions, trends of liquid velocity profiles, and volume of dead zones agree reasonably well with the experimental data. CFD simulations were also performed on different digester configurations. The effects of changing draft tube size, clearance, and shape of the tank bottoms were calculated to evaluate the effect of digester design on its flow pattern. Changing the draft tube clearance and height had no influence on the flow pattern or dead regions volume. However, increasing the draft tube diameter or incorporating a conical bottom design helped in reducing the volume of the dead zones as compared to a flat-bottom digester. The simulations showed that the gas flow rate sparged by a single point (0.5 cm diameter) sparger does not have an appreciable effect on the flow pattern of the digesters at the range of gas flow rates used. PMID:15685599

  8. Schwannoma in Sellar Region Mimics Invasive Pituitary Macroadenoma

    PubMed Central

    Kong, Xiangyi; Wu, Huanwen; Ma, Wenbin; Li, Yongning; Yang, Yi; Xing, Bing; Wei, Junji; Yao, Yong; Gao, Jun; Lian, Wei; Xu, Zhiqin; Dou, Wanchen; Ren, Zuyuan; Su, Changbao; Wang, Renzhi

    2016-01-01

    Abstract In central nervous system, schwannomas, as ubiquitous tumors, mostly originate from sensory nerves like auditory and trigeminal nerves. However, intrasellar schwannomas are extremely rare. They are often misdiagnosed as pituitary adenomas. We report a rare case of schwannoma in the sellar region—a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological test. We represent a 65-year-old woman who had suffered from headaches, hypothyroidism, and visual disturbance. Her MRI revealed an abnormal sellar region mixed-signal mass lesion with suprasellar, left parasellar, and sellar floor invasiveness. We present detailed analysis of the patient's disease course and review relevant literatures. Written informed consent was obtained from the patient for publication of this article. A copy of the written consent is available for review by the editors of MEDICINE. Because this article does not involve any human or animal trials, there is no need to conduct special ethic review and the ethical approval is not necessary. When surgically treated, her specimen revealed a typical histopathology pattern of schwannoma. The patient's symptoms improved a lot after surgery and he continues to be under observation. Despite its rarity, intrasellar schwannoma should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas. PMID:26945398

  9. An artificial primitive mimic of the Gramicidin-A channel.

    PubMed

    Barboiu, Mihail; Le Duc, Yann; Gilles, Arnaud; Cazade, Pierre-André; Michau, Mathieu; Marie Legrand, Yves; van der Lee, Arie; Coasne, Benoît; Parvizi, Paria; Post, Joshua; Fyles, Thomas

    2014-06-26

    Gramicidin A (gA) is the simplest known natural channel, and important progress in improving conduction activity has previously been obtained with modified natural gAs. However, simple artificial systems mimicking the gA functions are unknown. Here we show that gA can be mimicked using a simple synthetic triazole or 'T-channel' forming compound (TCT), having similar constitutional functions as the natural gAs. As in gA channels, the carbonyl moieties of the TCT, which point toward the T-channel core and surround the transport direction, are solvated by water. The net-dipolar alignment of water molecules along the chiral pore surfaces influences the conduction of protons/ions, envisioned to diffuse along dipolar hydrophilic pathways. Theoretical simulations and experimental assays reveal that the conduction through the T-channel, similar to that in gA, presents proton/water conduction, cation/anion selectivity and large open channel-conductance states. T-channels--associating supramolecular chirality with dipolar water alignment--represent an artificial primitive mimic of gA.

  10. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    PubMed

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for <1% of all patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows

  11. N-Amino-imidazolin-2-one Peptide Mimic Synthesis and Conformational Analysis

    PubMed Central

    2012-01-01

    Base-promoted 5-exo-dig cyclizations of aza-propargylglycinamides provided N-amino-imidazolin-2-one peptide mimics, which exhibited turn geometry in X-ray crystallographic and NMR spectroscopic analyses. Sonogashira coupling prior to cyclization afforded N-amino-imidazolin-2-ones with diverse 4-position aromatic substituents with potential to serve as Phe and Trp mimics. PMID:22892053

  12. Testing Measurement Invariance Using MIMIC: Likelihood Ratio Test with a Critical Value Adjustment

    ERIC Educational Resources Information Center

    Kim, Eun Sook; Yoon, Myeongsun; Lee, Taehun

    2012-01-01

    Multiple-indicators multiple-causes (MIMIC) modeling is often used to test a latent group mean difference while assuming the equivalence of factor loadings and intercepts over groups. However, this study demonstrated that MIMIC was insensitive to the presence of factor loading noninvariance, which implies that factor loading invariance should be…

  13. Biological Mimics: A New Paradigm in the Detection of Toxic Compounds

    ERIC Educational Resources Information Center

    Monty, Chelsea Nicole

    2009-01-01

    The purpose of this thesis is to introduce a new idea: using biological mimics in the detection of toxic compounds. Biological mimics imitate the active site of a given enzyme or have catalytic chemistry similar to enzymes and can be used in place of biological molecules to provide longer stability and simpler operation. In the following text the…

  14. Batesian mimics influence the evolution of conspicuousness in an aposematic salamander.

    PubMed

    Kraemer, A C; Serb, J M; Adams, D C

    2015-05-01

    Conspicuousness, or having high contrast relative to the surrounding background, is a common feature of unpalatable species. Several hypotheses have been proposed to explain the occurrence of conspicuousness, and while most involve the role of conspicuousness as a direct signal of unpalatability to potential predators, one hypothesis suggests that exaggerated conspicuousness may evolve in unpalatable species to reduce predator confusion with palatable species (potential Batesian mimics). This hypothesis of antagonistic coevolution between palatable and unpalatable species hinges on the 'cost of conspicuousness', in which conspicuousness increases the likelihood of predation more in palatable species than in unpalatable species. Under this mimicry scenario, four patterns are expected: (i) mimics will more closely resemble local models than models from other localities, (ii) there will be a positive relationship between mimic and model conspicuousness, (iii) models will be more conspicuous in the presence of mimics, and (iv) when models and mimics differ in conspicuousness, mimics will be less conspicuous than models. We tested these predictions in the salamander mimicry system involving Notophthalmus viridescens (model) and one colour morph of Plethodon cinereus (mimic). All predictions were supported, indicating that selection for Batesian mimicry not only influences the evolution of mimics, but also the evolution of the models they resemble. These findings indicate that mimicry plays a large role in the evolution of model warning signals, particularly influencing the evolution of conspicuousness.

  15. Touch the Page and Mimic Me: Evaluation of a Talking-Pen Learning Tool

    ERIC Educational Resources Information Center

    Odakura, Abigail

    2013-01-01

    The purpose of this paper is to evaluate the talking-pen device called the Mimic Me, an educational technology product of a large English conversation school in Japan, as an educational learning tool. The product will be reviewed in terms of its developmental appropriateness for the target audience based on current research. Although the Mimic Me…

  16. Editor's Highlight: Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS): A Web-Based Tool for Addressing the Challenges of Cross-Species Extrapolation of Chemical Toxicity.

    PubMed

    LaLone, Carlie A; Villeneuve, Daniel L; Lyons, David; Helgen, Henry W; Robinson, Serina L; Swintek, Joseph A; Saari, Travis W; Ankley, Gerald T

    2016-10-01

    Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) application was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target while remaining amenable to variable degrees of protein characterization, in the context of available information about the chemical/protein interaction and the molecular target itself. To accommodate this flexibility in the analysis, 3 levels of evaluation were developed. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of orthologs); the second level evaluates sequence similarity within selected functional domains (eg, ligand-binding domain); and the third level of analysis compares individual amino acid residue positions of importance for protein conformation and/or interaction with the chemical upon binding. Each level of the SeqAPASS analysis provides additional evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analyses can support prioritization of chemicals for further evaluation, selection of appropriate species for testing, extrapolation of empirical toxicity data, and/or assessment of the cross-species relevance of adverse outcome pathways. Three case studies are described herein to demonstrate application of the SeqAPASS tool: the first 2 focused on predictions of pollinator susceptibility to molt-accelerating compounds and neonicotinoid insecticides, and the third on evaluation of cross-species susceptibility to strobilurin fungicides. These analyses

  17. Editor's Highlight: Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS): A Web-Based Tool for Addressing the Challenges of Cross-Species Extrapolation of Chemical Toxicity.

    PubMed

    LaLone, Carlie A; Villeneuve, Daniel L; Lyons, David; Helgen, Henry W; Robinson, Serina L; Swintek, Joseph A; Saari, Travis W; Ankley, Gerald T

    2016-10-01

    Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) application was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target while remaining amenable to variable degrees of protein characterization, in the context of available information about the chemical/protein interaction and the molecular target itself. To accommodate this flexibility in the analysis, 3 levels of evaluation were developed. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of orthologs); the second level evaluates sequence similarity within selected functional domains (eg, ligand-binding domain); and the third level of analysis compares individual amino acid residue positions of importance for protein conformation and/or interaction with the chemical upon binding. Each level of the SeqAPASS analysis provides additional evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analyses can support prioritization of chemicals for further evaluation, selection of appropriate species for testing, extrapolation of empirical toxicity data, and/or assessment of the cross-species relevance of adverse outcome pathways. Three case studies are described herein to demonstrate application of the SeqAPASS tool: the first 2 focused on predictions of pollinator susceptibility to molt-accelerating compounds and neonicotinoid insecticides, and the third on evaluation of cross-species susceptibility to strobilurin fungicides. These analyses

  18. TRANSGENERATIONAL EFFECTS OF A JUVENILE HORMONE MIMIC ON THE ESTUARINE MYSID, MYSIDOPSIS BAHIA (CRUSTACEA: MYSIDACEA)

    EPA Science Inventory

    Fenoxycarb is a juvenile hormone (JH) mimic used to control insect pests by interfering with reproductive and developmental processes mediated by JH. Crustaceans are ideal organisms to monitor environmental effects of these endocrine disruptors, since they are dominant aquatic ar...

  19. Graphene-supported ferric porphyrin as a peroxidase mimic for electrochemical DNA biosensing.

    PubMed

    Wang, Quanbo; Lei, Jianping; Deng, Shengyuan; Zhang, Lei; Ju, Huangxian

    2013-01-30

    A novel peroxidase mimic was designed by loading ferric porphyrin and streptavidin onto graphene, which was used to recognize a biotinylated molecular beacon for specific electrochemical detection of DNA down to attomolar levels.

  20. Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.

    PubMed

    Huang, Yanyan; Liu, Zhen; Liu, Chaoqun; Ju, Enguo; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

    2016-06-01

    In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. PMID:27098681

  1. Mimics without models: causes and consequences of allopatry in Batesian mimicry complexes

    PubMed Central

    Pfennig, David W.; Mullen, Sean P.

    2010-01-01

    Batesian mimicry evolves when a palatable species (the ‘mimic’) co-opts a warning signal from a dangerous species (the ‘model’) and thereby deceives its potential predators. Longstanding theory predicts that this protection from predation should break down where the model is absent. Thus, mimics are expected to only co-occur with their model. Yet, many mimics violate this prediction and occur in areas where their model is absent. Here, we discuss the causes and consequences of such allopatric mimics. We also describe how these ‘rule-bending’ mimics provide critical insights into diverse topics ranging from how Batesian mimicry evolves to its possible role in speciation. PMID:20484238

  2. Preservation of the Structure of Enzymatically-Degraded Bovine Vitreous Using Synthetic Proteoglycan Mimics

    PubMed Central

    Zhang, Qianru; Filas, Benjamen A.; Roth, Robyn; Heuser, John; Ma, Nan; Sharma, Shaili; Panitch, Alyssa; Beebe, David C.; Shui, Ying-Bo

    2014-01-01

    Purpose. Vitreous liquefaction and subsequent posterior vitreous detachment can lead to several sight-threatening diseases, including retinal detachment, macular hole and macular traction syndrome, nuclear cataracts, and possibly, open-angle glaucoma. In this study, we tested the ability of three novel synthetic chondroitin sulfate proteoglycan mimics to preserve the structure and physical properties of enzymatically-degraded bovine vitreous. Methods. Chondroitin sulfate proteoglycan mimics, designed to bind to type II collagen, hyaluronic acid, or both, were applied to trypsin- or collagenase-treated bovine vitreous in situ and in vitro. Rheology and liquefaction tests were performed to determine the physical properties of the vitreous, while Western blots were used to detect the presence and degradation of soluble collagen II (α1). Deep-etch electron microscopy (DEEM) identified the ultrastructure of mimic-treated and untreated enzyme-degraded bovine vitreous. Results. Proteoglycan mimics preserved the physical properties of trypsin-degraded bovine vitreous and protected against vitreous liquefaction. Although the collagen-binding mimic maintained the physical properties of collagenase-treated vitreous, liquefaction still occurred. Western blots indicated that the mimic provided only marginal protective ability against soluble collagen degradation. Deep-etch electron microscopy, however, showed increased density and isotropy of microstructural components in mimic-treated vitreous, supporting the initial result that vitreous structure was preserved. Conclusions. Proteoglycan mimics preserved bovine vitreous physical properties after enzymatic degradation. These compounds may be useful in delaying or preventing the pathological effects of age-related, or enzymatically-induced, degradation of the vitreous body. PMID:25342623

  3. A comparative protease stability study of synthetic macrocyclic peptides that mimic two endocrine hormones.

    PubMed

    Ferrie, John J; Gruskos, Jessica J; Goldwaser, Ari L; Decker, Megan E; Guarracino, Danielle A

    2013-02-15

    Peptide therapeutics have traditionally faced many challenges including low bioavailability, poor proteolytic stability and difficult cellular uptake. Conformationally constraining the backbone of a peptide into a macrocyclic ring often ameliorates these problems and allows for the development of a variety of new drugs. Such peptide-based pharmaceuticals can enhance the multi-faceted functionality of peptide side chains, permitting the peptides to bind cellular targets and receptors necessary to impart their role, while protecting them from degrading cellular influences. In the work described here, we developed three cyclic peptides, VP mimic1, VP mimic2 and OT mimic1, which mimic endocrine hormones vasopressin and oxytocin. Making notable changes to the overall structure and composition of the parent hormones, we synthesized the mimics and tested their durability against treatment with three proteases chosen for their specificity: pepsin, alpha-chymotrypsin, and pronase. Vasopressin and oxytocin contain a disulfide linkage leaving them particularly vulnerable to deactivation from the reducing environment inside the cell. Thus, we increased the complexity of our assays by adding reducing agent glutathione to each mixture. Subsequently, we discovered each of our mimics withstood protease treatment with less degradation and/or a slower rate of degradation as compared to both parent hormones and a linear control peptide. PMID:23312470

  4. Transfection of microRNA Mimics Should Be Used with Caution

    PubMed Central

    Jin, Hyun Yong; Gonzalez-Martin, Alicia; Miletic, Ana V.; Lai, Maoyi; Knight, Sarah; Sabouri-Ghomi, Mohsen; Head, Steven R.; Macauley, Matthew S.; Rickert, Robert C.; Xiao, Changchun

    2015-01-01

    Transient transfection of chemically synthesized microRNA (miRNA) mimics is being used extensively to study the functions and mechanisms of endogenous miRNAs. However, it remains unclear whether transfected miRNAs behave similarly to endogenous miRNAs. Here we show that transient transfection of miRNA mimics into HeLa cells by a commonly used method led to the accumulation of high molecular weight RNA species and a few hundred fold increase in mature miRNA levels. In contrast, expression of the same miRNAs through lentiviral infection or plasmid transfection of HeLa cells, transgenic expression in primary lymphocytes, and endogenous overexpression in lymphoma and leukemia cell lines did not lead to the appearance of high molecular weight RNA species. The increase of mature miRNA levels in these cells was below 10-fold, which was sufficient to suppress target gene expression and to drive lymphoma development in mice. Moreover, transient transfection of miRNA mimics at high concentrations caused non-specific alterations in gene expression, while at low concentrations achieved expression levels comparable to other methods but failed to efficiently suppress target gene expression. Small RNA deep sequencing analysis revealed that the guide strands of miRNA mimics were frequently mutated, while unnatural passenger strands of some miRNA mimics accumulated to high levels. The high molecular weight RNA species were a heterogeneous mixture of several classes of RNA species generated by concatemerization, 5′- and 3′-end tailing of miRNA mimics. We speculate that the supraphysiological levels of mature miRNAs and these artifactual RNA species led to non-specific changes in gene expression. Our results have important implications for the design and interpretation of experiments primarily employing transient transfection of miRNA mimics. PMID:26697058

  5. Transfection of microRNA Mimics Should Be Used with Caution.

    PubMed

    Jin, Hyun Yong; Gonzalez-Martin, Alicia; Miletic, Ana V; Lai, Maoyi; Knight, Sarah; Sabouri-Ghomi, Mohsen; Head, Steven R; Macauley, Matthew S; Rickert, Robert C; Xiao, Changchun

    2015-01-01

    Transient transfection of chemically synthesized microRNA (miRNA) mimics is being used extensively to study the functions and mechanisms of endogenous miRNAs. However, it remains unclear whether transfected miRNAs behave similarly to endogenous miRNAs. Here we show that transient transfection of miRNA mimics into HeLa cells by a commonly used method led to the accumulation of high molecular weight RNA species and a few hundred fold increase in mature miRNA levels. In contrast, expression of the same miRNAs through lentiviral infection or plasmid transfection of HeLa cells, transgenic expression in primary lymphocytes, and endogenous overexpression in lymphoma and leukemia cell lines did not lead to the appearance of high molecular weight RNA species. The increase of mature miRNA levels in these cells was below 10-fold, which was sufficient to suppress target gene expression and to drive lymphoma development in mice. Moreover, transient transfection of miRNA mimics at high concentrations caused non-specific alterations in gene expression, while at low concentrations achieved expression levels comparable to other methods but failed to efficiently suppress target gene expression. Small RNA deep sequencing analysis revealed that the guide strands of miRNA mimics were frequently mutated, while unnatural passenger strands of some miRNA mimics accumulated to high levels. The high molecular weight RNA species were a heterogeneous mixture of several classes of RNA species generated by concatemerization, 5'- and 3'-end tailing of miRNA mimics. We speculate that the supraphysiological levels of mature miRNAs and these artifactual RNA species led to non-specific changes in gene expression. Our results have important implications for the design and interpretation of experiments primarily employing transient transfection of miRNA mimics. PMID:26697058

  6. A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.

    PubMed

    Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L

    2016-04-13

    Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses.

  7. MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring

    NASA Technical Reports Server (NTRS)

    Saeed, M.; Lieu, C.; Raber, G.; Mark, R. G.

    2002-01-01

    Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

  8. A bioconjugate approach toward squalamine mimics: Insight into the mechanism of biological action.

    PubMed

    Chen, Wen-Hua; Shao, Xue-Bin; Moellering, Robert; Wennersten, Christine; Regen, Steven L

    2006-01-01

    A short and efficient synthesis has been devised for a family of squalamine mimics, based on the use of cholic acid, deoxycholic acid, lithocholic acid, putrescine, and spermine as starting materials. Those mimics that contain two facially amphiphilic sterol-spermidine conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria; their corresponding activities against a broad spectrum of Gram-negative bacteria are relatively moderate. Larger mimics, containing four such sterol-spermidine conjugates, exhibit very weak activities. Reversal of the pendent spermidine moiety and a putrescine linkage on the A- and D-rings had little consequence on the antibacterial activity for the most active of the squalamine mimics, which contained two sterol-polyamine units; similar results were obtained with squalamine mimics made from only one sterol unit. Detailed structure-activity measurements, in combination with kinetic studies carried out using liposomes as model membranes, support a mechanism of action involving noncovalent dimers as ion transporting species, most probably via the formation of pores or channels. PMID:17105239

  9. Comparative cytogenetics of giant trahiras Hoplias aimara and H. intermedius (Characiformes, Erythrinidae): chromosomal characteristics of minor and major ribosomal DNA and cross-species repetitive centromeric sequences mapping differ among morphologically identical karyotypes.

    PubMed

    Blanco, D R; Lui, R L; Vicari, M R; Bertollo, L A C; Moreira-Filho, O

    2011-01-01

    Karyotype and cytogenetic characteristics of 2 species of giant trahiras, Hopliasintermedius, São Francisco river basin, and Hopliasaimara, Arinos river (Amazon basin), were examined by conventional (C-banding, Ag-NOR, DAPI/CMA(3) double-staining) and fluorescent in situ hybridization (FISH) with 5S, 18S rDNA probes and cross-species Cot-1 DNA probing. Both species invariably had diploid chromosome number 2n = 50 and identical karyotypes composed of 10 pairs of metacentric and 15 pairs of submetacentric chromosomes. On the other hand, staining with base-specific fluorochromes (CMA(3), DAPI) and FISH mapping of repetitive DNA sequences showed extensive interspecific differences: while the genome of H. aimara had one submetacentric pair bearing CMA(3)-positive (DAPI-negative) sites, that of H. intermedius had 4 such pairs; while FISH with a 5S rDNA probe showed one (likely homologous) signal-bearing pair, that with 18S rDNA displayed one signal-bearing pair in H. intermedius and 2 such pairs in H. aimara. Cross-species FISH probing with Cot-1 DNA prepared from total DNA of both species showed no signals of Cot-1 DNA from H. aimara on chromosomes of H. intermedius but reciprocally (Cot-1 DNA from H. intermedius on chromosomes of H. aimara) displayed signals on at least 4 chromosome pairs. Present findings indicate (i) different composition of repetitive sequences around centromeres, (ii) different NOR phenotypes and (iii) distinct taxonomic status of both giant trahira species. PMID:20924165

  10. A genetic toolkit for tagging intronic MiMIC containing genes.

    PubMed

    Nagarkar-Jaiswal, Sonal; DeLuca, Steven Z; Lee, Pei-Tseng; Lin, Wen-Wen; Pan, Hongling; Zuo, Zhongyuan; Lv, Jiangxing; Spradling, Allan C; Bellen, Hugo J

    2015-01-01

    Previously, we described a large collection of Minos-Mediated Integration Cassettes (MiMICs) that contain two phiC31 recombinase target sites and allow the generation of a new exon that encodes a protein tag when the MiMIC is inserted in a codon intron (Nagarkar-Jaiswal et al., 2015). These modified genes permit numerous applications including assessment of protein expression pattern, identification of protein interaction partners by immunoprecipitation followed by mass spec, and reversible removal of the tagged protein in any tissue. At present, these conversions remain time and labor-intensive as they require embryos to be injected with plasmid DNA containing the exon tag. In this study, we describe a simple and reliable genetic strategy to tag genes/proteins that contain MiMIC insertions using an integrated exon encoding GFP flanked by FRT sequences. We document the efficiency and tag 60 mostly uncharacterized genes.

  11. Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets.

    PubMed

    Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

    2015-04-01

    Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify D-peptide inhibitors of ebolavirus entry. PMID:25287718

  12. Antimicrobial Effects of Novel Triple Antibiotic Paste–Mimic Scaffolds on Actinomyces naeslundii Biofilm

    PubMed Central

    Albuquerque, Maria T.P.; Ryan, Stuart J.; Münchow, Eliseu A.; Kamocka, Maria M.; Gregory, Richard L.; Valera, Marcia C.; Bottino, Marco C.

    2015-01-01

    Introduction Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)–mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Methods Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm3, n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Results Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. Conclusions Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics. PMID:25917945

  13. The evolution of a Müllerian mimic in a spatially distributed community.

    PubMed

    Joron, Mathieu; Iwasa, Yoh

    2005-11-01

    Strong positive density-dependence should lead to a loss of diversity, but warning-colour and Müllerian mimicry systems show extraordinary levels of diversity. Here, we propose an analytical model to explore the dynamics of two forms of a Müllerian mimic in a heterogeneous environment with two alternative model species. Two connected populations of a dimorphic, chemically defended mimic are allowed to evolve and disperse. The proportions of the respective model species vary spatially. We use a nonlinear approximation of Müller's number-dependent equations to model a situation where the mortality for either form of the mimic decreases hyberbolically when its local density increases. A first non-spatial analysis confirms that the positive density-dependence makes coexistence of mimetic forms unstable in a single isolated patch, but shows that mimicry of the rarer model can be stable once established. The two-patch analysis shows that when models have different abundance in different places, local mimetic diversity in the mimic is maintained only if spatial heterogeneity is strong, or, more interestingly, if the mimic is not too strongly distasteful. Therefore, mildly toxic species can become polymorphic in a wider range of ecological settings. Spatial dynamics thus reveal a region of Müllerian polymorphism separating classical Batesian polymorphism and Müllerian monomorphism along the mimic's palatability spectrum. Such polymorphism-palatability relationship in a spatial environment provides a parsimonious hypothesis accounting for the observed Müllerian polymorphism that does not require quasi-Batesian dynamics. While the stability of coexistence depends on all factors, only the migration rate and strength of selection appear to affect the level of diversity at the polymorphic equilibrium. Local adaptation is predicted in most polymorphic cases. These results are in very good accordance with recent empirical findings on the polymorphic butterflies Heliconius

  14. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    PubMed Central

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-01-01

    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  15. An anthraquinone scaffold for putative, two-face Bim BH3 α-helix mimic.

    PubMed

    Zhang, Zhichao; Li, Xiangqian; Song, Ting; Zhao, Yan; Feng, Yingang

    2012-12-13

    Bim BH3 peptide features an α-helix with hotspot residues on multiple faces. Compound 5 (6-bromo-2,3-dihydroxyanthracene-9,10-dione), which adopts a rigid-plan amphipathic conformation, was designed and evaluated as a scaffold to mimic two faces of Bim α-helix. It reproduced the functionalities of both D67 and I65 on two opposing helical sides. Moreover, it maintained the two-faced binding mode during further evolution. A putative BH3 α-helix mimic and nanomolar Bcl-2/Mcl-1 dual inhibitor, 6, was obtained based on the structure of 5.

  16. Self-Sufficient Formaldehyde-to-Methanol Conversion by Organometallic Formaldehyde Dismutase Mimic.

    PubMed

    van der Waals, Dominic; Heim, Leo E; Vallazza, Simona; Gedig, Christian; Deska, Jan; Prechtl, Martin H G

    2016-08-01

    The catalytic networks of methylotrophic organisms, featuring redox enzymes for the activation of one-carbon moieties, can serve as great inspiration in the development of novel homogeneously catalyzed pathways for the interconversion of C1 molecules at ambient conditions. An imidazolium-tagged arene-ruthenium complex was identified as an effective functional mimic of the bacterial formaldehyde dismutase, which provides a new and highly selective route for the conversion of formaldehyde to methanol in absence of any external reducing agents. Moreover, secondary amines are reductively methylated by the organometallic dismutase mimic in a redox self-sufficient manner with formaldehyde acting both as carbon source and reducing agent.

  17. Lower limb cellulitis and its mimics: part II. Conditions that simulate lower limb cellulitis.

    PubMed

    Hirschmann, Jan V; Raugi, Gregory J

    2012-08-01

    Several common conditions can mimic cellulitis, creating a potential for misdiagnosis and incorrect management. The most common disorders mistaken for lower limb cellulitis include venous eczema, lipodermatosclerosis, irritant dermatitis, and lymphedema. The dermatologist is often consulted when a patient has failed to respond to therapy, and a thorough knowledge of the differential diagnosis is essential. This article focuses on entities that can mimic cellulitis, with an emphasis of elements of the history and physical examination that can help to distinguish between lower limb cellulitis and its simulators.

  18. Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics.

    PubMed

    Matsui, Masayuki; Prakash, Thazha P; Corey, David R

    2016-05-01

    MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development.

  19. Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts.

    PubMed

    Hoffman, Robert M

    2015-08-01

    The majority of human solid tumours do not metastasize when grown subcutaneously in immunocompromised mice; this includes patient-derived xenograft (PDX) models. However, orthotopic implantation of intact tumour tissue can lead to metastasis that mimics that seen in patients. These patient-derived orthotopic xenograft (PDOX) models have a long history and might better recapitulate human tumours than PDX models.

  20. Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen

    PubMed Central

    Liao, Xiaoli; Rabideau, Amy E; Pentelute, Bradley L

    2014-01-01

    Antibody mimics have significant scientific and therapeutic utility for the disruption of protein–protein interactions inside cells; however, their delivery to the cell cytosol remains a major challenge. Here we show that protective antigen (PA), a component of anthrax toxin, efficiently transports commonly used antibody mimics to the cytosol of mammalian cells when conjugated to the N-terminal domain of LF (LFN). In contrast, a cell-penetrating peptide (CPP) was not able to deliver any of these antibody mimics into the cell cytosol. The refolding and binding of a transported tandem monobody to Bcr-Abl (its protein target) in chronic myeloid leukemia cells were confirmed by co-immunoprecipitation. We also observed inhibition of Bcr-Abl kinase activity and induction of apoptosis caused by the monobody. In a separate case, we show disruption of key interactions in the MAPK signaling pathway after PA-mediated delivery of an affibody binder that targets hRaf-1. We show for the first time that PA can deliver bioactive antibody mimics to disrupt intracellular protein–protein interactions. This technology adds a useful tool to expand the applications of these modern agents to the intracellular milieu. PMID:25250705

  1. A novel nitrogen-dependent gene associates with the lesion mimic trait in wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lesion mimic (LM) refers to hypersensitive reaction-like (HRL) symptoms that appears on leaf tissue in the absence of plant pathogens. In a wheat line P7001, LM showed up on the leaves under the 0 g nitrogen (N) treatment, but disappeared when sufficient N was supplied, suggesting that LM is N-respo...

  2. Fluorescent discrimination between traces of chemical warfare agents and their mimics.

    PubMed

    Díaz de Greñu, Borja; Moreno, Daniel; Torroba, Tomás; Berg, Alexander; Gunnars, Johan; Nilsson, Tobias; Nyman, Rasmus; Persson, Milton; Pettersson, Johannes; Eklind, Ida; Wästerby, Pär

    2014-03-19

    An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.

  3. Synthesis of oxime-linked mucin mimics containing thetumor-related TN and sialyl TN antigens

    SciTech Connect

    Marcaurelle, Lisa A.; Shin, Youngsook; Goon, Scarlett; Bertozzi,Carolyn R.

    2001-08-21

    The synthesis of oxime-linked mucin mimics was accomplished via the incorporation of multiple ketone residues into a peptide followed by reaction with aminooxy sugars corresponding to the tumor-related T{sub N} and sialyl T{sub N} (ST{sub N}) antigens.

  4. Fluorescent mimics of cholesterol that rapidly bind surfaces of living mammalian cells.

    PubMed

    Hymel, David; Cai, Sutang; Sun, Qi; Henkhaus, Rebecca S; Perera, Chamani; Peterson, Blake R

    2015-10-01

    Mammalian cells acquire cholesterol, a critical membrane constituent, through multiple mechanisms. We synthesized mimics of cholesterol, fluorescent N-alkyl-3β-cholesterylamine-glutamic acids, that are rapidly incorporated into cellular plasma membranes compared with analogous cholesteryl amides, ethers, esters, carbamates, and a sitosterol analogue. This process was inhibited by ezetimibe, indicating a receptor-mediated uptake pathway. PMID:26287483

  5. Biomimetic assembly of the [FeFe] hydrogenase: synthetic mimics in a biological shell.

    PubMed

    Apfel, Ulf-Peter; Weigand, Wolfgang

    2013-11-25

    Combining synthetic chemistry and biology: A new method that allows the incorporation of synthetic [FeFe] hydrogenase mimics into the apo-hydrogenase is highlighted. Azadithiolato-functionalized model complexes showed similar activity to wild-type enzymes when implemented into the protein.

  6. The importance of pattern similarity between Müllerian mimics in predator avoidance learning.

    PubMed

    Rowe, Candy; Lindström, Leena; Lyytinen, Anne

    2004-02-22

    Müllerian mimicry, where unpalatable prey share common warning patterns, has long fascinated evolutionary biologists. It is commonly assumed that Müllerian mimics benefit by sharing the costs of predator education, thus reducing per capita mortality, although there has been no direct test of this assumption. Here, we specifically measure the selection pressure exerted by avian predators on unpalatable prey with different degrees of visual similarity in their warning patterns. Using wild-caught birds foraging on novel patterned prey in the laboratory, we unexpectedly found that pattern similarity did not increase the speed of avoidance learning, and even dissimilar mimics shared the education of naive predators. This was a consistent finding across two different densities of unpalatable prey, although mortalities were lower at the higher density as expected. Interestingly, the mortalities of Müllerian mimics were affected by pattern similarity in the predicted way by the end of our experiment, although the result was not quite significant. This suggests that the benefits to Müllerian mimics may emerge only later in the learning process, and that predator experience of the patterns may affect the degree to which pattern similarity is important. This highlights the need to measure the behaviour of real predators if we are to understand fully the evolution of mimicry systems.

  7. Migraine mimics.

    PubMed

    Evans, Randolph W

    2015-02-01

    The symptoms of migraine are non-specific and can be present in many other primary and secondary headache disorders, which are reviewed. Even experienced headache specialists may be challenged at times when diagnosing what appears to be first or worst, new type, migraine status, and chronic migraine.

  8. Fe-TAML encapsulated inside mesoporous silica nanoparticles as peroxidase mimic: femtomolar protein detection.

    PubMed

    Kumari, Sushma; Dhar, Basab B; Panda, Chakadola; Meena, Abhishek; Sen Gupta, Sayam

    2014-08-27

    Peroxidase, such as horseradish peroxidase (HRP), conjugated to antibodies are routinely used for the detection of proteins via an ELISA type assay in which a critical step is the catalytic signal amplification by the enzyme to generate a detectable signal. Synthesis of functional mimics of peroxidase enzyme that display catalytic activity which far exceeds the native enzyme is extremely important for the precise and accurate determination of very low quantities of proteins (fM and lower) that is necessary for early clinical diagnosis. Despite great advancements, analyzing proteins of very low abundance colorimetrically, a method that is most sought after since it requires no equipment for the analysis, still faces great challenges. Most reported HRP mimics that show catalytic activity greater than native enzyme (∼10-fold) are based on metal/metal-oxide nanoparticles such as Fe3O4. In this paper, we describe a second generation hybrid material developed by us in which approximately 25,000 alkyne tagged biuret modified Fe-tetraamido macrocyclic ligand (Fe-TAML), a very powerful small molecule synthetic HRP mimic, was covalently attached inside a 40 nm mesoporous silica nanoparticle (MSN). Biuret-modified Fe-TAMLs represent one of the best small molecule functional mimics of the enzyme HRP with reaction rates in water close to the native enzyme and operational stability (pH, ionic strength) far exceeding the natural enzyme. The catalytic activity of this hybrid material is around 1000-fold higher than that of natural HRP and 100-fold higher than that of most metal/metal oxide nanoparticle based HRP mimics reported to date. We also show that using antibody conjugates of this hybrid material it is possible to detect and, most importantly, quantify femtomolar quantities of proteins colorimetrically in an ELISA type assay. This represents at least 10-fold higher sensitivity than other colorimetric protein assays that have been reported using metal/metal oxide

  9. Increased prevalence of carbapenem resistant Enterobacteriaceae in hospital setting due to cross-species transmission of the blaNDM-1 element and clonal spread of progenitor resistant strains

    PubMed Central

    Wang, Xuan; Chen, Gongxiang; Wu, Xiaoyan; Wang, Liangping; Cai, Jiachang; Chan, Edward W.; Chen, Sheng; Zhang, Rong

    2015-01-01

    This study investigated the transmission characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains collected from a hospital setting in China, in which consistent emergence of CRE strains were observable during the period of May 2013 to February 2014. Among the 45 CRE isolates tested, 21 (47%) strains were found to harbor the blaNDM-1 element, and the rest of 24 CRE strains were all positive for blaKPC-2. The 21 blaNDM-1—borne strains were found to comprise multiple Enterobacteriaceae species including nine Enterobacter cloacae, three Escherichia coli, three Citrobacter freundii, two Klebsiella pneumoniae, two Klebsiella oxytoca, and two Morganella morganii strains, indicating that cross-species transmission of blaNDM-1 is a common event. Genetic analyses by PFGE and MLST showed that, with the exception of E. coli and E. cloacae, strains belonging to the same species were often genetically unrelated. In addition to blaNDM-1, several CRE strains were also found to harbor the blaKPC-2, blaVIM-1, and blaIMP-4 elements. Conjugations experiments confirmed that the majority of carbapenem resistance determinants were transferable. Taken together, our findings suggest that transmission of mobile resistance elements among members of Enterobacteriaceae and clonal spread of CRE strains may contribute synergistically to a rapid increase in the population of CRE in clinical settings, prompting a need to implement more rigorous infection control measures to arrest such vicious transmission cycle in CRE-prevalent areas. PMID:26136735

  10. "Eye of tiger sign" mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN).

    PubMed

    Yoganathan, Sangeetha; Sudhakar, Sniya Valsa; Thomas, Maya; Dutta, Atanu Kumar; Danda, Sumita

    2016-05-01

    Neurodegeneration with brain iron accumulation (NBIA) refers to an inherited heterogeneous group of disorders pathologically characterized by focal brain iron deposition. Clinical phenotype, imaging findings and genotype are variable among the different types of this disorder. In this case report, we describe the imaging finding of an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN), a subentity of NBIA. Magnetic resonance imaging of brain revealed hypointensity of globi pallidi with medial medullary lamina appearing as a hyperintense streak in T2 weighted images. Mild cerebellar atrophy in T2 weighted images and blooming of substantia nigra and globi pallidi in susceptibility weighted images were also observed. Imaging findings in patients with MPAN mimics the eye of tiger appearance in patients with pantothenate kinase associated neurodegeneration. Classical phenotype and eye of tiger sign mimic in imaging of patients with NBIA should raise the suspect for MPAN. Genetic studies helps in the confirmation of diagnosis of this neurodegenerative disorder. PMID:26602591

  11. Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

    PubMed Central

    Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

    2012-01-01

    Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

  12. How well does cholesteryl hemisuccinate mimic cholesterol in saturated phospholipid bilayers?

    PubMed

    Kulig, Waldemar; Tynkkynen, Joona; Javanainen, Matti; Manna, Moutusi; Rog, Tomasz; Vattulainen, Ilpo; Jungwirth, Pavel

    2014-02-01

    Cholesteryl hemisuccinate is a detergent that is often used to replace cholesterol in crystallization of membrane proteins. Here we employ atomistic molecular dynamics simulations to characterize how well the properties of cholesteryl hemisuccinate actually match those of cholesterol in saturated protein-free lipid membranes. We show that the protonated form of cholesteryl hemisuccinate mimics many of the membrane properties of cholesterol quite well, while the deprotonated form of cholesteryl hemisuccinate is less convincing in this respect. Based on the results, we suggest that cholesteryl hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions (not investigated here) are not playing a crucial role.

  13. A Chromogenic Probe for the Selective Recognition of Sarin and Soman Mimic DFP**

    PubMed Central

    El Sayed, Sameh; Pascual, Lluís; Agostini, Alessandro; Martínez-Máñez, Ramón; Sancenón, Félix; Costero, Ana M; Parra, Margarita; Gil, Salvador

    2014-01-01

    The synthesis, characterization and sensing features of a novel probe 1 for the selective chromogenic recognition of diisopropylfluorophosphate (DFP), a sarin and soman mimic, in 99:1 (v/v) water/acetonitrile and in the gas phase is reported. Colour modulation is based on the combined reaction of phosphorylation of 1 and fluoride-induced hydrolysis of a silyl ether moiety. As fluoride is a specific reaction product of the reaction between DFP and the −OH group, the probe shows a selective colour modulation in the presence of this chemical. Other nerve agent simulants, certain anions, oxidant species and other organophosphorous compounds were unable to induce colour changes in 1. This is one of the very few examples of a selective detection, in solution and in the gas phase, of a sarin and soman simulant versus other reactive derivatives such as the tabun mimic diethylcyanophosphate (DCNP). PMID:25478309

  14. Mesenchymal tumours of the breast and their mimics: a review with approach to diagnosis.

    PubMed

    Cheah, Alison L; Billings, Steven D; Rowe, J Jordi

    2016-08-01

    Mesenchymal tumours of the breast comprise a broad spectrum of entities that frequently pose diagnostic challenges to surgical pathologists. Metaplastic carcinoma and phyllodes tumour are site-specific mimics that account for the majority of tumours in the breast with a sarcomatoid appearance. Although uncommon, mammary tumours with fibroblastic, adipocytic or vascular differentiation may be encountered, spanning the spectrum from benign to malignant. Tumours with histiocytoid morphology are potential traps due to bland cytomorphology and resemblance to reactive processes. This comprehensive review provides a diagnostic approach to specific challenging mesenchymal tumours of the breast and their mimics, with a discussion on the salient morphological, immunohistochemical and molecular features that allow accurate diagnosis and will help the pathologist avoid potential pitfalls. PMID:27318503

  15. Heteroannelated and 7-deoxygenated goniofufurone mimics with antitumour activity: design, synthesis and preliminary SAR studies.

    PubMed

    Popsavin, Velimir; Francuz, Jovana; Srećo Zelenović, Bojana; Benedeković, Goran; Popsavin, Mirjana; Kojić, Vesna; Bogdanović, Gordana

    2013-10-15

    Cytotoxic (+)-goniofufurone mimic such as benzoxepane 2 was preferentially formed after the treatment of 7-O-benzoyl-5-O-benzyl (+)-goniofufurone derivative 6 with titanium(IV) fluoride. However, the corresponding 7-epimer 5 (derivative of 7-epi-goniofufurone) under the similar reaction conditions gave mainly 7-deoxy derivative 7 as a result of an unexpected 1,5-hydride shift. Extension of this methodology to the enantiomer ent-6 provided cytotoxic (-)-goniofufurone mimics ent-2 and ent-7. Synthesized compounds showed diverse growth inhibitory effects against selected tumour cell lines, but were devoid of any significant toxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that are beneficial for their antiproliferative activity, such as presence of an additional oxepane ring, the absolute stereochemistry and the presence of a deoxy function at the C-7 position. PMID:24021462

  16. Representing life in the Earth system with soil microbial functional traits in the MIMICS model

    NASA Astrophysics Data System (ADS)

    Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Taylor, P. G.; Bonan, G. B.

    2015-06-01

    Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes, and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon (C) cycle-climate feedbacks. We used a microbial trait-based soil C model with two physiologically distinct microbial communities, and evaluate how this model represents soil C storage and response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS) model; these functional groups are akin to "gleaner" vs. "opportunist" plankton in the ocean, or r- vs. K-strategists in plant and animal communities. Here we compare MIMICS to a conventional soil C model, DAYCENT (the daily time-step version of the CENTURY model), in cross-site comparisons of nitrogen (N) enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that MIMICS projects much slower rates of soil C accumulation than a conventional soil biogeochemistry in response to increasing C inputs with elevated carbon dioxide (CO2) - a finding that would reduce the size of the land C sink estimated by the Earth system. Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

  17. Design, synthesis and antiproliferative activity of two new heteroannelated (-)-muricatacin mimics.

    PubMed

    Popsavin, Velimir; Srećo, Bojana; Benedeković, Goran; Popsavin, Mirjana; Francuz, Jovana; Kojić, Vesna; Bogdanović, Gordana

    2008-10-01

    Two new (-)-muricatacin mimics bearing a furano-furanone ring and an oxygen isostere in the side chain have been designed and synthesized and their in vitro antiproliferative activity was evaluated against several human tumour cell lines. Both analogues showed an increased activity against HL-60 cells with 17- and 185-fold higher potency than (-)-muricatacin. A straightforward synthesis of (-)-muricatacin is also disclosed. PMID:18790637

  18. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    PubMed Central

    Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

    2016-01-01

    Background: Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. Methods: We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. Results: The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients. Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders. PMID:26996473

  19. Pictorial essay: CT scan of appendicitis and its mimics causing right lower quadrant pain

    PubMed Central

    Sharma, Monika; Agrawal, Anjali

    2008-01-01

    CT scanning is widely used in the diagnostic workup of right lower quadrant pain. While appendicitis remains the most frequent cause, a majority of patients referred for suspected appendicitis turn out to have alternative diagnoses or a normal CT study. The purpose of our pictorial essay is to present an overview of the CT findings of appendicitis and its common mimics and to highlight the features that provide clues to alternative diagnoses.

  20. Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues

    SciTech Connect

    Beletskiy, Evgeny V.; Schmidt, Jacob C.; Wang, Xue B.; Kass, Steven R.

    2012-11-14

    Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations. Small molecule transition state analogs of oxyanion holes are characterized by gas phase IR and photoelectron spectroscopy and their binding constants in acetonitrile. As a result, a new class of hydrogen bond catalysts is proposed (OH donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel-Crafts reaction.

  1. Fluorescent discrimination between traces of chemical warfare agents and their mimics.

    PubMed

    Díaz de Greñu, Borja; Moreno, Daniel; Torroba, Tomás; Berg, Alexander; Gunnars, Johan; Nilsson, Tobias; Nyman, Rasmus; Persson, Milton; Pettersson, Johannes; Eklind, Ida; Wästerby, Pär

    2014-03-19

    An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds. PMID:24597942

  2. Virulent Burkholderia species mimic host actin polymerases to drive actin-based motility

    PubMed Central

    Benanti, Erin L.; Nguyen, Catherine M.; Welch, Matthew D.

    2015-01-01

    Summary Burkholderia pseudomallei and B. mallei are bacterial pathogens that cause melioidosis and glanders, while their close relative B. thailandensis is nonpathogenic. All use the trimeric autotransporter BimA to facilitate actin-based motility, host cell fusion and dissemination. Here, we show that BimA orthologs mimic different host actin-polymerizing proteins. B. thailandensis BimA activates the host Arp2/3 complex. In contrast, B. pseudomallei and B. mallei BimA mimic host Ena/VASP actin polymerases in their ability to nucleate, elongate and bundle filaments by associating with barbed ends, as well as in their use of WH2 motifs and oligomerization for activity. Mechanistic differences among BimA orthologs resulted in distinct actin filament organization and motility parameters, which affected the efficiency of cell fusion during infection. Our results identify bacterial Ena/VASP mimics and reveal that pathogens imitate the full spectrum of host actin-polymerizing pathways, suggesting that mimicry of different polymerization mechanisms influences key parameters of infection. PMID:25860613

  3. Tunable Molecular MoS2 Edge-Site Mimics for Catalytic Hydrogen Production.

    PubMed

    Garrett, Benjamin R; Polen, Shane M; Click, Kevin A; He, Mingfu; Huang, Zhongjie; Hadad, Christopher M; Wu, Yiying

    2016-04-18

    Molybdenum sulfides represent state-of-the-art, non-platinum electrocatalysts for the hydrogen evolution reaction (HER). According to the Sabatier principle, the hydrogen binding strength to the edge active sites should be neither too strong nor too weak. Therefore, it is of interest to develop a molecular motif that mimics the catalytic sites structurally and possesses tunable electronic properties that influence the hydrogen binding strength. Furthermore, molecular mimics will be important for providing mechanistic insight toward the HER with molybdenum sulfide catalysts. In this work, a modular method to tune the catalytic properties of the S-S bond in MoO(S2)2L2 complexes is described. We studied the homogeneous electrocatalytic hydrogen production performance metrics of three catalysts with different bipyridine substitutions. By varying the electron-donating abilities, we present the first demonstration of using the ligand to tune the catalytic properties of the S-S bond in molecular MoS2 edge-site mimics. This work can shed light on the relationship between the structure and electrocatalytic activity of molecular MoS2 catalysts and thus is of broad importance from catalytic hydrogen production to biological enzyme functions. PMID:27022836

  4. Pd-Ir Core-Shell Nanocubes: A Type of Highly Efficient and Versatile Peroxidase Mimic.

    PubMed

    Xia, Xiaohu; Zhang, Jingtuo; Lu, Ning; Kim, Moon J; Ghale, Kushal; Xu, Ye; McKenzie, Erin; Liu, Jiabin; Ye, Haihang

    2015-10-27

    Peroxidase mimics with dimensions on the nanoscale have received great interest as emerging artificial enzymes for biomedicine and environmental protection. While a variety of peroxidase mimics have been actively developed recently, limited progress has been made toward improving their catalytic efficiency. In this study, we report a type of highly efficient peroxidase mimic that was engineered by depositing Ir atoms as ultrathin skins (a few atomic layers) on Pd nanocubes (i.e., Pd-Ir cubes). The Pd-Ir cubes exhibited significantly enhanced efficiency, with catalytic constants more than 20- and 400-fold higher than those of the initial Pd cubes and horseradish peroxidase (HRP), respectively. As a proof-of-concept demonstration, the Pd-Ir cubes were applied to the colorimetric enzyme-linked immunosorbent assay (ELISA) of human prostate surface antigen (PSA) with a detection limit of 0.67 pg/mL, which is ∼110-fold lower than that of the conventional HRP-based ELISA using the same set of antibodies and the same procedure.

  5. Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens.

    PubMed

    McGrann, Graham R D; Steed, Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K M

    2015-06-01

    Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

  6. Virulent Burkholderia species mimic host actin polymerases to drive actin-based motility.

    PubMed

    Benanti, Erin L; Nguyen, Catherine M; Welch, Matthew D

    2015-04-01

    Burkholderia pseudomallei and B. mallei are bacterial pathogens that cause melioidosis and glanders, whereas their close relative B. thailandensis is non-pathogenic. All use the trimeric autotransporter BimA to facilitate actin-based motility, host cell fusion, and dissemination. Here, we show that BimA orthologs mimic different host actin-polymerizing proteins. B. thailandensis BimA activates the host Arp2/3 complex. In contrast, B. pseudomallei and B. mallei BimA mimic host Ena/VASP actin polymerases in their ability to nucleate, elongate, and bundle filaments by associating with barbed ends, as well as in their use of WH2 motifs and oligomerization for activity. Mechanistic differences among BimA orthologs resulted in distinct actin filament organization and motility parameters, which affected the efficiency of cell fusion during infection. Our results identify bacterial Ena/VASP mimics and reveal that pathogens imitate the full spectrum of host actin-polymerizing pathways, suggesting that mimicry of different polymerization mechanisms influences key parameters of infection.

  7. Sensitive electrochemical assaying of DNA methyltransferase activity based on mimic-hybridization chain reaction amplified strategy.

    PubMed

    Zhang, Linqun; Liu, Yuanjian; Li, Ying; Zhao, Yuewu; Wei, Wei; Liu, Songqin

    2016-08-24

    A mimic-hybridization chain reaction (mimic-HCR) amplified strategy was proposed for sensitive electrochemically detection of DNA methylation and methyltransferase (MTase) activity In the presence of methylated DNA, DNA-gold nanoparticles (DNA-AuNPs) were captured on the electrode by sandwich-type assembly. It then triggered mimic-HCR of two hairpin probes to produce many long double-helix chains for numerous hexaammineruthenium (III) chloride ([Ru(NH3)6](3+), RuHex) inserting. As a result, the signal for electrochemically detection of DNA MTase activity could be amplified. If DNA was non-methylated, however, the sandwich-type assembly would not form because the short double-stranded DNAs (dsDNA) on the Au electrode could be cleaved and digested by restriction endonuclease HpaII (HapII) and exonuclease III (Exo III), resulting in the signal decrement. Based on this, an electrochemical approach for detection of M.SssI MTase activity with high sensitivity was developed. The linear range for M.SssI MTase activity was from 0.05 U mL(-1) to 10 U mL(-1), with a detection limit down to 0.03 U mL(-1). Moreover, this detecting strategy held great promise as an easy-to-use and highly sensitive method for other MTase activity and inhibition detection by exchanging the corresponding DNA sequence.

  8. Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays

    PubMed Central

    Mishra, Laxmi N.; Pepenella, Sharon; Rogge, Ryan; Hansen, Jeffrey C.; Hayes, Jeffrey J.

    2016-01-01

    The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome. In contrast, acetylation mimics within the H3 tail had little effect, but were able to synergize with H4 tail acetylation mimics to further increase accessibility. Moreover, replacement of the central nucleosome with a nucleosome free region also resulted in increased local, but not global DNA accessibility. Our results indicate that modification or disruption of only a single target nucleosome results in significant changes in local chromatin architecture and suggest that very localized chromatin modifications imparted by pioneer transcription factors are sufficient to initiate a cascade of events leading to promoter activation. PMID:27708426

  9. MiRNA mimic screen for improved expression of functional neurotensin receptor from HEK293 cells.

    PubMed

    Xiao, Su; Chen, Yu-Chi; Betenbaugh, Michael J; Martin, Scott E; Shiloach, Joseph

    2015-08-01

    Obtaining adequate quantities of functional mammalian membrane proteins has been a bottleneck in their structural and functional studies because the expression of these proteins from mammalian cells is relatively low. To explore the possibility of enhancing expression of these proteins using miRNA, a stable T-REx-293 cell line expressing the neurotensin receptor type 1 (NTSR1), a hard-to-express G protein-coupled receptor (GPCR), was constructed. The cell line was then subjected to human miRNA mimic library screening. In parallel, an HEK293 cell line expressing luciferase was also screened with the same human miRNA mimic library. Five microRNA mimics: hsa-miR-22-5p, hsa-miR-18a-5p, hsa-miR-22-3p, hsa-miR-429, and hsa-miR-2110were identified from both screens. They led to 48% increase in the expression of functional NTSR1 and to 239% increase of luciferase expression. These miRNAs were also effective in enhancing the expression of secretedglypican-3 hFc-fusion protein from HEK293 cells.The results indicate that these molecules may have a wide role in enhancing the production of proteins with biomedical interest.

  10. Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

    PubMed Central

    McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

    2015-01-01

    Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

  11. A Collection of Target Mimics for Comprehensive Analysis of MicroRNA Function in Arabidopsis thaliana

    PubMed Central

    Paz-Ares, Javier; Weigel, Detlef

    2010-01-01

    Many targets of plant microRNAs (miRNAs) are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for ∼20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA–resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants. PMID:20661442

  12. Molecular Dynamics Studies of Proton Transport in Hydrogenase and Hydrogenase Mimics.

    PubMed

    Ginovska, B; Raugei, S; Shaw, W J

    2016-01-01

    There is extensive interest in hydrogenases based on their ability to rapidly and efficiently interconvert H2 with protons and electrons, and their (typically) superior function relative to molecular mimics. Understanding the function of enzymes is one approach to implementing design features to make better catalysts and is an approach we have implemented in our work. In this review, we will discuss our efforts to develop design principles from enzymes, with specific focus on proton transport. We will also present computational studies of the mimics we have investigated with similar methodologies. We will discuss the mechanisms used by small scaffolds on molecular mimics which in many cases are surprisingly similar to those used by nature, while in other cases, computational analysis allowed us to reveal an unexpected role. Computational methods provide one of the best ways, and in some cases, the only way, to gain insight into the mechanistic details of enzymes. In this review, we illustrate the general computational strategy we used to study the proton pathway of [FeFe]-hydrogenase, and the similar strategy to investigate small molecules. We present the main results we obtained and how our computational work stimulated or worked in concert with experimental investigations. We also focus on estimation of errors and convergence of properties in the simulations. These studies demonstrate the powerful results that can be obtained by the close pairing of experimental and theoretical approaches. PMID:27497163

  13. SOD-Mimic Cu(II) Dimeric Complexes Involving Kinetin and Its Derivative: Preparation and Characterization

    PubMed Central

    Novotná, Radka; Trávníček, Zdeněk; Herchel, Radovan

    2012-01-01

    Two SOD-mimic active dimeric Cu(II) chlorido complexes of the compositions [Cu2(μ-HL1)4Cl2]Cl2 (1) and [Cu2(μ-HL2)2(μ-Cl)2(HL2)2Cl2] · 4H2O (2) involving the cosmetologically relevant cytokinin kinetin (N6-furfuryladenine, HL1) and its derivative N6-(5-methylfurfuryl)adenine (HL2) have been synthesized and characterized by elemental analysis, infrared, and electronic spectroscopy, ESI+ mass spectrometry, conductivity and temperature dependence of magnetic susceptibility measurements, and thermogravimetric (TG) and differential thermal (DTA) analyses. The results of these methods, particularly the temperature dependence of magnetic susceptibility, showed the complexes to be dimeric with a strong antiferromagnetic exchange (J = −290 cm−1 for complex 1 and J = −160 cm−1 for 2). The complexes have been identified as auspicious SOD-mimics, as their antiradical activity evaluated by the in vitro SOD-mimic assay resulted in the IC50 values equal to 8.13 μM (1) and 0.71 μM (2). PMID:22966218

  14. SOD-Mimic Cu(II) Dimeric Complexes Involving Kinetin and Its Derivative: Preparation and Characterization.

    PubMed

    Novotná, Radka; Trávníček, Zdeněk; Herchel, Radovan

    2012-01-01

    Two SOD-mimic active dimeric Cu(II) chlorido complexes of the compositions [Cu(2)(μ-HL(1))(4)Cl(2)]Cl(2) (1) and [Cu(2)(μ-HL(2))(2)(μ-Cl)(2)(HL(2))(2)Cl(2)] · 4H(2)O (2) involving the cosmetologically relevant cytokinin kinetin (N6-furfuryladenine, HL(1)) and its derivative N6-(5-methylfurfuryl)adenine (HL(2)) have been synthesized and characterized by elemental analysis, infrared, and electronic spectroscopy, ESI+ mass spectrometry, conductivity and temperature dependence of magnetic susceptibility measurements, and thermogravimetric (TG) and differential thermal (DTA) analyses. The results of these methods, particularly the temperature dependence of magnetic susceptibility, showed the complexes to be dimeric with a strong antiferromagnetic exchange (J = -290 cm(-1) for complex 1 and J = -160 cm(-1) for 2). The complexes have been identified as auspicious SOD-mimics, as their antiradical activity evaluated by the in vitro SOD-mimic assay resulted in the IC(50) values equal to 8.13 μM (1) and 0.71 μM (2). PMID:22966218

  15. miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells

    PubMed Central

    Li, Wenjuan; Cheng, Peng; Nie, Shangdan; Cui, Wen

    2016-01-01

    Japanese encephalitis (JE) is one of the most severe viral infections of the central nervous system. No effective treatment for JE currently exists, because its pathogenesis remains largely unknown. The present study was designed to screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were collected, after being infected with the Japanese encephalitis virus (JEV). Total miRNAs were extracted and analyzed using an miRNA chip. One of the most severely affected miRNAs was selected, and the role of miR-370 in JEV infection was investigated. Cell viability and apoptosis of the host cells were evaluated. JEV replication was detected via analysis of gene E expression. Real-time polymerase chain reaction was used to determine the levels of endogenous miR-370 and expression of innate immunity-related genes. Following JEV infection, 114 miRNAs were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were upregulated and 84 were downregulated. The changes observed in five miRNAs were confirmed by real-time polymerase chain reaction. One of the significantly downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into the cells, following which the levels of endogenous miR-370 were significantly elevated. Concurrently, JEV replication was significantly reduced 24 hours after transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV-induced apoptosis and the inhibition of host cell proliferation. Following JEV infection, interferon-β and nuclear factor-kappa B were upregulated, whereas miR-370 mimic prevented the upregulation of the genes induced by JEV infection. The present study demonstrated that miR-370 expression in host cells is downregulated following JEV infection, which further mediates innate immunity-related gene expression. Taken together, miR-370 mimic might be useful to prevent viral replication and infection-induced host cell injury. PMID:27703358

  16. In vivo preclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model

    NASA Astrophysics Data System (ADS)

    N'Djin, W. A.; Melodelima, D.; Parmentier, H.; Rivoire, M.; Chapelon, J. Y.

    2010-04-01

    The pig is an ideal animal model for preclinical evaluation of HIFU treatments, especially in the liver. However, there is no liver tumor model available for pigs. In this work, we propose to study an in vivo tumor-mimic model as a tool for evaluating if a sonographycally guided HIFU treatment, delivered by a toroidal-shaped device dedicated for the treatment of liver metastases, is correctly located in the liver. One centimeter tumor-mimics were created in liver tissues. These tumor-mimics were detectable on ultrasound imaging and on gross pathology. Two studies were carried out. First, an in vivo study of tolerance at mid-term (30 days, 10 pigs) revealed that tumor-mimics are suitable for studying HIFU treatments at a preclinical stage, since local and biological tolerances were excellent. The dimensions of the tumor-mimics were reproducible (diameter at day 0: 9.7 ± 2.0 mm) and were the same as a function of time (p = 0.64). A second in vivo study was carried out in ten pigs. Tumor mimics were used as targets in liver tissues in order to determine if the HIFU treatment is correctly located in the liver. A procedure of extensive HIFU ablation using multiple HIFU lesions juxtaposed manually was then tested on eight tumor-mimics. In 88% of the cases (seven out of eight), tumor-mimics were treated with negative margins (>=1 mm) in all directions. On average, negative margins measured 10.0 ± 6.7 mm. These tumor-mimics constitute an excellent reference for studying in vivo the accuracy of HIFU therapy in the liver.

  17. In silico mining and characterization of simple sequence repeats from gilthead sea bream (Sparus aurata) expressed sequence tags (EST-SSRs); PCR amplification, polymorphism evaluation and multiplexing and cross-species assays.

    PubMed

    Vogiatzi, Emmanouella; Lagnel, Jacques; Pakaki, Victoria; Louro, Bruno; Canario, Adelino V M; Reinhardt, Richard; Kotoulas, Georgios; Magoulas, Antonios; Tsigenopoulos, Costas S

    2011-06-01

    We screened for simple sequence repeats (SSRs) found in ESTs derived from an EST-database development project ('Marine Genomics Europe' Network of Excellence). Different motifs of di-, tri-, tetra-, penta- and hexanucleotide SSRs were evaluated for variation in length and position in the expressed sequences, relative abundance and distribution in gilthead sea bream (Sparus aurata). We found 899 ESTs that harbor 997 SSRs (4.94%). On average, one SSR was found per 2.95 kb of EST sequence and the dinucleotide SSRs are the most abundant accounting for 47.6% of the total number. EST-SSRs were used as template for primer design. 664 primer pairs could be successfully identified and a subset of 206 pairs of primers was synthesized, PCR-tested and visualized on ethidium bromide stained agarose gels. The main objective was to further assess the potential of EST-SSRs as informative markers and investigate their cross-species amplification in sixteen teleost fish species: seven sparid species and nine other species from different families. Approximately 78% of the primer pairs gave PCR products of expected size in gilthead sea bream, and as expected, the rate of successful amplification of sea bream EST-SSRs was higher in sparids, lower in other perciforms and even lower in species of the Clupeiform and Gadiform orders. We finally determined the polymorphism and the heterozygosity of 63 markers in a wild gilthead sea bream population; fifty-eight loci were found to be polymorphic with the expected heterozygosity and the number of alleles ranging from 0.089 to 0.946 and from 2 to 27, respectively. These tools and markers are expected to enhance the available genetic linkage map in gilthead sea bream, to assist comparative mapping and genome analyses for this species and further with other model fish species and finally to help advance genetic analysis for cultivated and wild populations and accelerate breeding programs.

  18. Cross-species sequence analysis reveals multiple charged residue-rich domains that regulate nuclear/cytoplasmic partitioning and membrane localization of a kinase anchoring protein 12 (SSeCKS/Gravin).

    PubMed

    Streb, Jeffrey W; Miano, Joseph M

    2005-07-29

    A kinase anchoring proteins (AKAPs) assemble and compartmentalize multiprotein signaling complexes at discrete subcellular locales and thus confer specificity to transduction cascades using ubiquitous signaling enzymes, such as protein kinase A. Intrinsic targeting domains in each AKAP determine the subcellular localization of these complexes and, along with protein-protein interaction domains, form the core of AKAP function. As a foundational step toward elucidating the relationship between location and function, we have used cross-species sequence analysis and deletion mapping to facilitate the identification of the targeting determinants of AKAP12 (also known as SSeCKS or Gravin). Three charged residue-rich regions were identified that regulate two aspects of AKAP12 localization, nuclear/cytoplasmic partitioning and perinuclear/cell periphery targeting. Using deletion mapping and green fluorescent protein chimeras, we uncovered a heretofore unrecognized nuclear localization potential. Five nuclear localization signals, including a novel class of this type of signal termed X2-NLS, are found in the central region of AKAP12 and are important for nuclear targeting. However, this nuclear localization is suppressed by the negatively charged C terminus that mediates nuclear exclusion. In this condition, the distribution of AKAP12 is regulated by an N-terminal targeting domain that simultaneously directs perinuclear and peripheral AKAP12 localization. Three basic residue-rich regions in the N-terminal targeting region have similarity to the MARCKS proteins and were found to control AKAP12 localization to ganglioside-rich regions at the cell periphery. Our data suggest that AKAP12 localization is regulated by a hierarchy of targeting domains and that the localization of AKAP12-assembled signaling complexes may be dynamically regulated. PMID:15923193

  19. Plant Gene and Alternatively Spliced Variant Annotator. A plant genome annotation pipeline for rice gene and alternatively spliced variant identification with cross-species expressed sequence tag conservation from seven plant species.

    PubMed

    Chen, Feng-Chi; Wang, Sheng-Shun; Chaw, Shu-Miaw; Huang, Yao-Ting; Chuang, Trees-Juen

    2007-03-01

    The completion of the rice (Oryza sativa) genome draft has brought unprecedented opportunities for genomic studies of the world's most important food crop. Previous rice gene annotations have relied mainly on ab initio methods, which usually yield a high rate of false-positive predictions and give only limited information regarding alternative splicing in rice genes. Comparative approaches based on expressed sequence tags (ESTs) can compensate for the drawbacks of ab initio methods because they can simultaneously identify experimental data-supported genes and alternatively spliced transcripts. Furthermore, cross-species EST information can be used to not only offset the insufficiency of same-species ESTs but also derive evolutionary implications. In this study, we used ESTs from seven plant species, rice, wheat (Triticum aestivum), maize (Zea mays), barley (Hordeum vulgare), sorghum (Sorghum bicolor), soybean (Glycine max), and Arabidopsis (Arabidopsis thaliana), to annotate the rice genome. We developed a plant genome annotation pipeline, Plant Gene and Alternatively Spliced Variant Annotator (PGAA). Using this approach, we identified 852 genes (931 isoforms) not annotated in other widely used databases (i.e. the Institute for Genomic Research, National Center for Biotechnology Information, and Rice Annotation Project) and found 87% of them supported by both rice and nonrice EST evidence. PGAA also identified more than 44,000 alternatively spliced events, of which approximately 20% are not observed in the other three annotations. These novel annotations represent rich opportunities for rice genome research, because the functions of most of our annotated genes are currently unknown. Also, in the PGAA annotation, the isoforms with non-rice-EST-supported exons are significantly enriched in transporter activity but significantly underrepresented in transcription regulator activity. We have also identified potential lineage-specific and conserved isoforms, which are

  20. Representing life in the Earth system with soil microbial functional traits in the MIMICS model

    NASA Astrophysics Data System (ADS)

    Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Taylor, P. G.; Bonan, G. B.

    2015-02-01

    Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon cycle-climate feedbacks. We used a microbial trait-based soil carbon (C) model, with two physiologically distinct microbial communities to improve current estimates of soil C storage and their likely response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS) model, which incorporates oligotrophic and copiotrophic functional groups, akin to "gleaner" vs. "opportunist" plankton in the ocean, or r vs. K strategists in plant and animals communities. Here we compare MIMICS to a conventional soil C model, DAYCENT, in cross-site comparisons of nitrogen (N) enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that current projections from Earth system models likely overestimate the strength of the land C sink in response to increasing C inputs with elevated carbon dioxide (CO2). Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

  1. Efficient nuclear DNA cleavage in human cancer cells by synthetic bleomycin mimics.

    PubMed

    Li, Qian; van der Wijst, Monique G P; Kazemier, Hinke G; Rots, Marianne G; Roelfes, Gerard

    2014-04-18

    Iron complexes of N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics of the Bleomycins (BLMs), which are a family of natural antibiotics used clinically in the treatment of certain cancers. However, most investigations of DNA cleavage activity of these and related metal complexes were carried out in cell-free systems using plasmid DNA as substrate. The present study evaluated nuclear DNA cleavage activity and cell cytotoxicity of BLM and its synthetic mimics based on the ligand N4Py. The N4Py-based reagents induced nuclear DNA cleavage in living cells as efficiently as BLM and Fe(II)-BLM. Treatment of 2 cancer cell lines and 1 noncancerous cell line indicated improved cytotoxicity of N4Py when compared to BLM. Moreover, some level of selectivity was observed for N4Py on cancerous versus noncancerous cells. It was demonstrated that N4Py-based reagents and BLM induce cell death via different mechanistic pathways. BLM was shown to induce cell cycle arrest, ultimately resulting in mitotic catastrophe. In contrast, N4Py-based reagents were shown to induce apoptosis effectively. To the best of our knowledge, the present study is the first demonstration of efficient nuclear DNA cleavage activity of a synthetic BLM mimic within cells. The results presented here show that it is possible to design synthetic bioinorganic model complexes that are at least as active as the parent natural product and thereby are potentially interesting alternatives for BLM to induce antitumor activity.

  2. In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

    SciTech Connect

    Planche, Olivier; Teriitehau, Christophe; Boudabous, Sana; Robinson, Joey Marie; Rao, Pramod; Deschamps, Frederic; Farouil, Geoffroy; Baere, Thierry de

    2013-02-15

    To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularity of the single-antenna ablation zones measured 0.64 {+-} 0.12, with a diameter of 35.7 {+-} 8.7 mm along the axis of the antenna and 32.7 {+-} 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 {+-} 7.7 along the axis of the antenna and 54.8 {+-} 8.5 mm perpendicular to the feeding point; circularity was 0.70 {+-} 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of {<=}4 cm with no heat sink effect from vessels of {<=}6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.

  3. Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance

    SciTech Connect

    Karig, David K; Siuti, Piro; Dar, Roy D.; Retterer, Scott T; Doktycz, Mitchel John; Simpson, Michael L

    2011-01-01

    Cells offer natural examples of highly efficient networks of nanomachines. Accordingly, both intracellular and intercellular communication mechanisms in nature are looked to as a source of inspiration and instruction for engineered nanocommunication. Harnessing biological functionality in this manner requires an interdisciplinary approach that integrates systems biology, synthetic biology, and nanofabrication. Recent years have seen the amassing of a tremendous wealth of data from the sequencing of new organisms and from high throughput expression experiments. At the same time, a deeper fundamental understanding of individual cell function has been developed, as exemplified by the growth of fields such as noise biology, which seeks to characterize the role of noise in gene expression. The availability of well characterized biological components coupled with a deeper understanding of cell function has led to efforts to engineer both living cells and to create bio-like functionality in non-living substrates in the field of synthetic biology. Here, we present a model system that exemplifies the synergism between these realms of research. We propose a synthetic gene network for operation in a nanofabricated cell mimic array that propagates a biomolecular signal over long distances using the phenomenon of stochastic resonance. Our system consists of a bacterial quorum sensing signal molecule, a bistable genetic switch triggered by this signal, and an array of nanofabricated cell mimic wells that contain the genetic system. An optimal level of noise in the system helps to propagate a time-varying AHL signal over long distances through the array of mimics. This noise level is determined both by the system volume and by the parameters of the genetic network. Our proposed genetically driven stochastic resonance system serves as a testbed for exploring the potential harnessing of gene expression noise to aid in the transmission of a time-varying molecular signal.

  4. The synthesis of methylated, phosphorylated, and phosphonated 3'-aminoacyl-tRNA(Sec) mimics.

    PubMed

    Rigger, Lukas; Schmidt, Rachel L; Holman, Kaitlyn M; Simonović, Miljan; Micura, Ronald

    2013-11-18

    The twenty first amino acid, selenocysteine (Sec), is the only amino acid that is synthesized on its cognate transfer RNA (tRNA(Sec)) in all domains of life. The multistep pathway involves O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS), an enzyme that catalyzes the terminal chemical reaction during which the phosphoseryl-tRNA(Sec) intermediate is converted into selenocysteinyl-tRNA(Sec). The SepSecS architecture and the mode of tRNA(Sec) recognition have been recently determined at atomic resolution. The crystal structure provided valuable insights that gave rise to mechanistic proposals that could not be validated because of the lack of appropriate molecular probes. To further improve our understanding of the mechanism of the biosynthesis of selenocysteine in general and the mechanism of SepSecS in particular, stable tRNA(Sec) substrates carrying aminoacyl moieties that mimic particular reaction intermediates are needed. Here, we report on the accurate synthesis of methylated, phosphorylated, and phosphonated serinyl-derived tRNA(Sec) mimics that contain a hydrolysis-resistant ribose 3'-amide linkage instead of the natural ester bond. The procedures introduced allow for efficient site-specific methylation and/or phosphorylation directly on the solid support utilized in the automated RNA synthesis. For the preparation of (S)-2-amino-4-phosphonobutyric acid-oligoribonucleotide conjugates, a separate solid support was generated. Furthermore, we developed a three-strand enzymatic ligation protocol to obtain the corresponding full-length tRNA(Sec) derivatives. Finally, we developed an electrophoretic mobility shift assay (EMSA) for rapid, qualitative characterization of the SepSecS-tRNA interactions. The novel tRNA(Sec) mimics are promising candidates for further elucidation of the biosynthesis of selenocysteine by X-ray crystallography and other biochemical approaches, and could be attractive for similar studies on other tRNA-dependent enzymes.

  5. Mechanisms of translational regulation by a human eIF5-mimic protein

    PubMed Central

    Singh, Chingakham Ranjit; Watanabe, Ryosuke; Zhou, Donghui; Jennings, Martin D.; Fukao, Akira; Lee, Bumjun; Ikeda, Yuka; Chiorini, John A.; Campbell, Susan G.; Ashe, Mark P.; Fujiwara, Toshinobu; Wek, Ronald C.; Pavitt, Graham D.; Asano, Katsura

    2011-01-01

    The translation factor eIF5 is an important partner of eIF2, directly modulating its function in several critical steps. First, eIF5 binds eIF2/GTP/Met-tRNAiMet ternary complex (TC), promoting its recruitment to 40S ribosomal subunits. Secondly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining. Finally, eIF5 GDP dissociation inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B. The C-terminal domain (CTD) of eIF5, a W2-type HEAT domain, mediates its interaction with eIF2. Here, we characterize a related human protein containing MA3- and W2-type HEAT domains, previously termed BZW2 and renamed here as eIF5-mimic protein 1 (5MP1). Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific translation in mammalian systems. We further test whether 5MP1 is a mimic or competitor of the GEF catalytic subunit eIF2Bε or eIF5, using yeast as a model. Our results suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding to the ribosome. Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function. PMID:21745818

  6. How effectively does a clinostat mimic the ultrastructural effects of microgravity on plant cells?

    NASA Technical Reports Server (NTRS)

    Moore, R.

    1990-01-01

    Columella cells of seedlings of Zea mays L. cv. Bear Hybrid grown in the microgravity of orbital flight allocate significantly larger relative-volumes to hyaloplasm and lipid bodies, and significantly smaller relative-volumes to dictyosomes, plastids, and starch than do columella cells of seedlings grown at 1 g. The ultrastructure of columella cells of seedlings grown at 1 g and on a rotating clinostat is not significantly different. However, the ultrastructure of cells exposed to these treatments differs significantly from that of seedlings grown in microgravity. These results indicate that the actions of a rotating clinostat do not mimic the ultrastructural effects of microgravity in columella cells of Z. mays.

  7. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)

    PubMed Central

    2015-01-01

    3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg2+. The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. PMID:25815153

  8. Simulation of the optical performance of refractive elements to mimic the human eye focusing

    NASA Astrophysics Data System (ADS)

    Diaz-Gonzalez, G.; Santiago-Alvarado, Agustín.; Cruz-Félix, Ángel S.

    2015-09-01

    Refractive optics has evolved and incorporated new elements in optical systems every day, such as conventional lenses, tunable lenses, GRIN lenses, diffractive lenses, intraocular lenses, etc. Some of these elements are reported in the literature together with different proposed models of the human eye. In this work, optical properties of some of these lenses will be studied, and simulations of their behavior will be done in order to analyze which one is better for imaging process. Such lenses will be incorporated in an optical system that mimics the human eye behavior. Analysis and obtained results are reported, as well as the proposed optical system. Finally, we present the conclusions of the work.

  9. Spontaneous activation of [FeFe]-hydrogenases by an inorganic [2Fe] active site mimic

    PubMed Central

    Esselborn, Julian; Berggren, Gustav; Noth, Jens; Siebel, Judith; Hemschemeier, Anja; Artero, Vincent; Reijerse, Edward; Fontecave, Marc; Lubitz, Wolfgang; Happe, Thomas

    2013-01-01

    Hydrogenases catalyze the formation of hydrogen. The cofactor (H-cluster) of [FeFe]-hydrogenases consists of a [4Fe-4S]-cluster bridged to a unique [2Fe]-subcluster whose biosynthesis in vivo requires hydrogenase-specific maturases. Here we show that a chemical mimic of the [2Fe]-subcluster can reconstitute apo-hydrogenase to full activity, independent of helper proteins. The assembled H-cluster is virtually indistinguishable from the native cofactor. This procedure will be a powerful tool for developing novel artificial H2-producing catalysts. PMID:23934246

  10. Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

    PubMed Central

    2008-01-01

    Polyguanidinium oxanorbornene (PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents. PMID:18850741

  11. Differential Diagnoses of Restless Legs Syndrome/Willis-Ekbom Disease: Mimics and Comorbidities.

    PubMed

    Chokroverty, Sudhansu

    2015-09-01

    Restless legs syndrome (RLS) mimics cannot always be differentiated from RLS/Willis-Ekbom disease (WED) based on 4 essential criteria; hence, a fifth criterion has recently been established. RLS comorbidities may provide us important clues for understanding the neurobiology of RLS/WED. Iron-dopamine connection, hypoxia pathway activation, and dopamine-opioid interaction are important pathophysiological mechanisms in RLS; this knowledge is derived from our understanding of RLS associations with a variety of medical, neurologic, and other conditions. Clinicians must formulate an RLS differential diagnosis based on history and physical examination, but laboratory tests may sometimes be needed to arrive at a correct diagnosis. PMID:26329435

  12. Creation of a Tumor-Mimic Model Using a Muscle Paste for Radiofrequency Ablation of the Lung

    SciTech Connect

    Kawai, T. Kaminou, T.; Sugiura, K.; Hashimoto, M.; Ohuchi, Y.; Adachi, A.; Fujioka, S.; Ito, H.; Nakamura, K.; Ogawa, T.

    2009-03-15

    The purpose of this study was to develop an easily created tumor-mimic model and evaluate its efficacy for radiofrequency ablation (RFA) of the lung. The bilateral lungs of eight living adult swine were used. A tumor-mimic model was made by percutaneous injection of 1.0 ml muscle paste through the bone biopsy needle into the lung. An RFA probe was then inserted into the tumor mimics immediately after tumor creation. Ablation time, tissue impedance, and temperature were recorded. The tumor mimics and their coagulated regions were evaluated microscopically and macroscopically. The muscle paste was easily injected into the lung parenchyma through the bone biopsy needle and well visualized under fluoroscopy. In 10 of 12 sites the tumor mimics were oval shaped, localized, and homogeneous on gross specimens. Ten tumor mimics were successfully ablated, and four locations were ablated in the normal lung parenchyma as controls. In the tumor and normal lung parenchyma, ablation times were 8.9 {+-} 3.5 and 4.4 {+-} 1.6 min, respectively; tissue impedances at the start of ablation were 100.6 {+-} 16.6 and 145.8 {+-} 26.8 {Omega}, respectively; and temperatures at the end of ablation were 66.0 {+-} 7.9 and 57.5 {+-} 7.6{sup o}C, respectively. The mean size of tumor mimics was 13.9 x 8.2 mm, and their coagulated area was 18.8 x 13.1 mm. In the lung parenchyma, the coagulated area was 15.3 x 12.0 mm. In conclusion, our tumor-mimic model using muscle paste can be easily and safely created and can be ablated using the ablation algorithm in the clinical setting.

  13. Cleaner wrasse mimics inflict higher costs on their models when they are more aggressive towards signal receivers

    PubMed Central

    Cheney, Karen L.

    2012-01-01

    Aggressive mimics are predatory species that resemble a ‘model’ species to gain access to food, mating opportunities or transportation at the expense of a signal receiver. Costs to the model may be variable, depending on the strength of the interaction between mimics and signal receivers. In the Indopacific, the bluestriped fangblenny Plagiotremus rhinorhynchos mimics juvenile cleaner wrasse Labroides dimidiatus. Instead of removing ectoparasites from larger coral reef fish, fangblennies attack fish to feed on scales and body tissue. In this study, juvenile cleaner wrasse suffered significant costs when associated with P. rhinorhynchos mimics in terms of reduced cleaning activity. Furthermore, the costs incurred by the model increased with heightened aggression by mimics towards signal receivers. This was apparently because of behavioural changes in signal receivers, as cleaning stations with mimics that attacked frequently were visited less. Variation in the costs incurred by the model may influence mimicry accuracy and avoidance learning by the signal receiver and thus affect the overall success and maintenance of the mimicry system. PMID:21865244

  14. Limited damage of tissue mimic caused by a collapsing bubble under low-frequency ultrasound exposure.

    PubMed

    Yoshida, Kenji; Obata, Kazuya; Tsukamoto, Akira; Ushida, Takashi; Watanabe, Yoshiaki

    2014-08-01

    In this study, we investigated the bubble induced serious damage to tissue mimic exposed to 27-kHz ultrasound. The initial bubble radius ranged from 80 to 100 μm, which corresponded approximately to the experimentally-evaluated resonant radius of the given ultrasound frequency. The tissue mimic consisted of 10 wt% gelatine gel covered with cultured canine kidney epithelial cells. The collapsing bubble behaviour during the ultrasound exposure with negative peak pressures of several hundred kPa was captured by a high-speed camera system. After ultrasound exposure, a cell viability test was conducted based on microscopic bright-field images and fluorescence images for living and dead cells. In the viability test, cells played a role in indicating the damaged area. The bubble oscillations killed the cells, and on occasion detached layers of cultured cells from the gel. The damaged area was comparable or slightly larger than the initial bubble size, and smaller than the maximum bubble size. We concluded that only a small area in close proximity to the bubble could be damaged even above transient cavitation threshold.

  15. Micro-fabricated shunt to mimic arachnoid granulations for the treatment of communicating hydrocephalus.

    PubMed

    Kralick, Francis; Oh, Jonghyun; Medina, Tim; Noh, Hongseok Moses

    2012-01-01

    Hydrocephalus is the abnormal accumulation of cerebrospinal fluid (CSF) within the confines of the skull that if left untreated results in significant morbidity and mortality. The treatment for hydrocephalus has remained essentially unchanged for over 50 years. It was a technological advance in materials that allowed John Holter, in conjunction with neurosurgeons Spitzer and Nulsen, to devise a valve and shunt system that diverted excess CSF from the ventricular space to the peritoneum. This ventriculo-peritoneal (VP) shunt is far from ideal, with problems associated with under/over shunting, mechanical mismatch, infection, high failure rates, disconnection and erosion. With the advances in the field of micro-fabrication and micro-machines we propose an innovative shunt system that would mimic the function of arachnoid granulations. This micro-fabricated shunting device, or micro-mechanical arachnoid granulation (MAG), consists of a multiplicity of micro-valves each 210 μm in diameter that each adhere to individual micro-needles. This work demonstrates the design and initial test results of the micro-valve with parameters for low cracking pressure, optimal flow rate, and reflux that would mimic the function of the native arachnoid granulations.

  16. Diatom Mimics: Directing the Formation of Biosilica Nanoparticles by Controlled Folding of Lysine-Leucine Peptides

    PubMed Central

    Baio, Joe E.; Zane, Ariel; Jaeger, Vance; Roehrich, Adrienne M.; Lutz, Helmut; Pfaendtner, Jim; Drobny, Gary P.; Weidner, Tobias

    2015-01-01

    Silaffins, long chain polyamines, and other biomolecules found in diatoms are involved in the assembly of a large number of silica nanostructures under mild, ambient conditions. Nanofabrication researchers have sought to mimic the diatom's biosilica production capabilities by engineering proteins to resemble aspects of naturally occurring biomolecules. Such mimics can produce monodisperse biosilica nanospheres, but in vitro production of the variety of intricate biosilica nanostructures that compose the diatom frustule is not yet possible. In this study we demonstrate how LK peptides, composed solely of lysine (K) and leucine (L) amino acids arranged with varying hydrophobic periodicities, initiate the formation of different biosilica nanostructures in vitro. When L and K residues are arranged with a periodicity of 3.5 the α-helical form of the LK peptide produces monodisperse biosilica nanospheres. However, when the LK periodicity is changed to 3.0, corresponding to a 310 helix, the morphology of the nanoparticles changes to elongated rod-like structures. β-strand LK peptides with a periodicity of 2.0 induce wire-like silica morphologies. This study illustrates how the morphology of biosilica can be changed simply by varying the periodicity of polar and nonpolar amino acids. PMID:25285787

  17. Diatom mimics: directing the formation of biosilica nanoparticles by controlled folding of lysine-leucine peptides.

    PubMed

    Baio, Joe E; Zane, Ariel; Jaeger, Vance; Roehrich, Adrienne M; Lutz, Helmut; Pfaendtner, Jim; Drobny, Gary P; Weidner, Tobias

    2014-10-29

    Silaffins, long chain polyamines, and other biomolecules found in diatoms are involved in the assembly of a large number of silica nanostructures under mild, ambient conditions. Nanofabrication researchers have sought to mimic the diatom's biosilica production capabilities by engineering proteins to resemble aspects of naturally occurring biomolecules. Such mimics can produce monodisperse biosilica nanospheres, but in vitro production of the variety of intricate biosilica nanostructures that compose the diatom frustule is not yet possible. In this study we demonstrate how LK peptides, composed solely of lysine (K) and leucine (L) amino acids arranged with varying hydrophobic periodicities, initiate the formation of different biosilica nanostructures in vitro. When L and K residues are arranged with a periodicity of 3.5 the α-helical form of the LK peptide produces monodisperse biosilica nanospheres. However, when the LK periodicity is changed to 3.0, corresponding to a 310 helix, the morphology of the nanoparticles changes to elongated rod-like structures. β-strand LK peptides with a periodicity of 2.0 induce wire-like silica morphologies. This study illustrates how the morphology of biosilica can be changed simply by varying the periodicity of polar and nonpolar amino acids.

  18. BSA-templated MnO2 nanoparticles as both peroxidase and oxidase mimics.

    PubMed

    Liu, Xing; Wang, Qi; Zhao, Huihui; Zhang, Lichun; Su, Yingying; Lv, Yi

    2012-10-01

    Inorganic nanomaterials that mimic enzymes are fascinating as they potentially have improved properties relative to native enzymes, such as greater resistance to extremes of pH and temperature and lower sensitivity to proteases. Although many artificial enzymes have been investigated, searching for highly-efficient and stable catalysts is still of great interest. In this paper, we first demonstrated that bovine serum albumin (BSA)-stabilized MnO(2) nanoparticles (NPs) exhibited highly peroxidase-, oxidase-, and catalase-like activities. The activities of the BSA-MnO(2) NPs were evaluated using the typical horseradish peroxidase (HRP) substrates o-phenylenediamine (OPD) and 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of either hydrogen peroxide or dissolved oxygen. These small-sized BSA-MnO(2) NPs with good dispersion, solubility and biocompatibility exhibited typical Michaelis-Menten kinetics and high affinity for H(2)O(2), OPD and TMB, indicating that BSA-MnO(2) NPs can be used as satisfactory enzyme mimics. Based on these findings, BSA-MnO(2) NPs were used as colorimetric immunoassay tags for the detection of goat anti-human IgG in place of HRP. The colorimetric immunoassay using BSA-MnO(2) NPs has the advantages of being fast, robust, inexpensive, easily prepared and with no HRP and H(2)O(2) being needed. These water-soluble BSA-MnO(2) NPs may have promising potential applications in biotechnology, bioassays, and biomedicine.

  19. MicroRNA-125b-5p mimic inhibits acute liver failure.

    PubMed

    Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep

    2016-01-01

    The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF. PMID:27336362

  20. A Novel Rodent Model That Mimics the Metabolic Sequelae of Obese Craniopharyngioma Patients

    PubMed Central

    Roth, Christian L.; Blevins, James E.; Ralston, Melissa; Elfers, Clinton; Ogimoto, Kayoko; Kaiyala, Karl J.; Morton, Gregory J.

    2013-01-01

    Patients with craniopharyngioma (CP), a tumor located in the pituitary and/or hypothalamus, are susceptible to developing obesity and many metabolic complications. The study aim was to create a rodent model that mimics the complex neuroanatomical and metabolic disturbances commonly seen in obese CP patients. We compared the metabolic phenotype of animals with three distinct types of hypothalamic lesions: 1) destruction of the arcuate nucleus (ARC) induced by monosodium glutamate (MSG), 2) electrolytic lesion of the adjacent ventromedial nucleus (VMN) alone, 3) both the VMN and dorsomedial nucleus (DMN), or a 4) combined medial hypothalamic lesion (CMHL) affecting the VMN, DMN, and the ARC. Only the CMHL model exhibited all key features observed in patients with hypothalamic obesity induced by CP. These features included excessive weight gain due to increased adiposity, increased food intake, and pronounced hyperinsulinemia and hyperleptinemia. Similar to characteristics of patients with CP, CMHL animals exhibited reduced plasma levels of alpha-melanocyte stimulating hormone and reduced ambulatory activity compared with weight-matched controls. Therefore, the CMHL model best mimics the complex metabolic abnormalities observed in obese CP patients compared with lesions to other hypothalamic areas and provides a foundation for future pharmacological approaches to treat obesity in children with hypothalamic damage. PMID:21372758

  1. Intravital Confocal and Two-photon Imaging of Dual-color Cells and Extracellular Matrix Mimics

    PubMed Central

    Bal, Ufuk; Andresen, Volker; Baggett, Brenda; Utzinger, Urs

    2013-01-01

    To optimize imaging of cells in three dimensional culture we studied confocal backscattering, Second Harmonic Generation (SHG) and autofluorescence as source of contrast in extracellular matrix (ECM) mimics and evaluated the attenuation as well as bleaching of endogenous cellular fluorescence signals. All common ECM mimics exhibit contrast observable with confocal reflectance microscopy. SHG imaging on collagen I based hydrogels provides high contrast and good optical penetration depth. Agarose is a useful embedding medium because it allows for large optical penetration and exhibits minimal autofluorescence while still providing good reflectance to detect voids in the embedding medium. We labeled breast cancer cells’ outline with DsRed2 and nucleus with eGFP. DsRed2 can be excited with confocal imaging at 568nm, and with two photon excitation (TPE) in the red and longer NIR. eGFP was excited at 488nm for confocal and in the NIR for TPE. While there is small difference in the bleaching rate for eGFP between confocal and TPE we observed significant difference for DsRed2 where bleaching is strongest during TPE in the red wavelengths and smallest during confocal imaging. After a few hundred microns depth in a collagen I hydrogel, TPE fluorescence becomes twice as strong compared to confocal imaging. PMID:23380006

  2. Comprehending body language and mimics: an ERP and neuroimaging study on Italian actors and viewers.

    PubMed

    Proverbio, Alice Mado; Calbi, Marta; Manfredi, Mirella; Zani, Alberto

    2014-01-01

    In this study, the neural mechanism subserving the ability to understand people's emotional and mental states by observing their body language (facial expression, body posture and mimics) was investigated in healthy volunteers. ERPs were recorded in 30 Italian University students while they evaluated 280 pictures of highly ecological displays of emotional body language that were acted out by 8 male and female Italian actors. Pictures were briefly flashed and preceded by short verbal descriptions (e.g., "What a bore!") that were incongruent half of the time (e.g., a picture of a very attentive and concentrated person shown after the previous example verbal description). ERP data and source reconstruction indicated that the first recognition of incongruent body language occurred 300 ms post-stimulus. swLORETA performed on the N400 identified the strongest generators of this effect in the right rectal gyrus (BA11) of the ventromedial orbitofrontal cortex, the bilateral uncus (limbic system) and the cingulate cortex, the cortical areas devoted to face and body processing (STS, FFA EBA) and the premotor cortex (BA6), which is involved in action understanding. These results indicate that face and body mimics undergo a prioritized processing that is mostly represented in the affective brain and is rapidly compared with verbal information. This process is likely able to regulate social interactions by providing on-line information about the sincerity and trustfulness of others.

  3. Can artificial reefs mimic natural reef communities? The roles of structural features and age.

    PubMed

    Perkol-Finkel, S; Shashar, N; Benayahu, Y

    2006-03-01

    In light of the deteriorating state of coral reefs worldwide, the need to rehabilitate marine environments has greatly increased. Artificial reefs (ARs) have been suggested as a tool for reef conservation and rehabilitation. Although successions of AR communities have been thoroughly studied, current understanding of the interactions between artificial and natural reefs (NRs) is poor and a fundamental question still to be answered is that of whether AR communities can mimic adjacent NR communities. We suggest three alternative hypotheses: Neighboring ARs and NRs will (1) achieve a similar community structure given sufficient time; (2) be similar only if they possess similar structural features; (3) always differ, regardless of age or structural features. We examined these hypotheses by comparing the community structure on a 119-year old shipwreck to a neighboring NR. Fouling organisms, including stony and soft corals, sponges, tunicates, sea anemones and hydrozoans were recorded and measured along belt transects. The ahermatypic stony coral Tubastrea micrantha dominated vertical AR regions while the soft corals Nephthea sp. and Xenia sp. dominated both artificial and natural horizontal surfaces. Our results support the second hypothesis, indicating that even after a century an AR will mimic its adjacent NR communities only if it possesses structural features similar to those of the natural surroundings. However, if the two differ structurally, their communities will remain distinct.

  4. Identification of Peptide Mimics of a Glycan Epitope on the Surface of Parasitic Nematode Larvae.

    PubMed

    Umair, Saleh; Deng, Qing; Roberts, Joanna M; Shaw, Richard J; Sutherland, Ian A; Pernthaner, Anton

    2016-01-01

    Phage display was used to identify peptide mimics of an immunologically protective nematode glycan (CarLA) by screening a constrained C7C peptide library for ligands that bound to an anti-CarLA mAb (PAB1). Characterisation of these peptide mimotopes revealed functional similarities with an epitope that is defined by PAB1. Mimotope vaccinations of mice with three selected individual phage clones facilitated the induction of antibody responses that recognised the purified, native CarLA molecule which was obtained from Trichostrongylus colubriformis. Furthermore, these mimotopes are specifically recognised by antibodies in the saliva of animals that were immune to natural polygeneric nematode challenge. This shows that antibodies to the PAB1 epitope form part of the mucosal polyclonal anti-CarLA antibody response of nematode immune host animals. This demonstrates that the selected peptide mimotopes are of biological relevance. These peptides are the first to mimic the PAB1 epitope of CarLA, a defined larval glycan epitope which is conserved between many nematode species. PMID:27579674

  5. Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy

    PubMed Central

    Zhou, Mengying; Zhang, Xulang; Wen, Xinyu; Wu, Taihua; Wang, Weidong; Yang, Mingzhou; Wang, Jing; Fang, Ming; Lin, Bingcheng; Lin, Hongli

    2016-01-01

    Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a “glomerulus-on-a-chip” (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease. PMID:27558173

  6. Can artificial reefs mimic natural reef communities? The roles of structural features and age.

    PubMed

    Perkol-Finkel, S; Shashar, N; Benayahu, Y

    2006-03-01

    In light of the deteriorating state of coral reefs worldwide, the need to rehabilitate marine environments has greatly increased. Artificial reefs (ARs) have been suggested as a tool for reef conservation and rehabilitation. Although successions of AR communities have been thoroughly studied, current understanding of the interactions between artificial and natural reefs (NRs) is poor and a fundamental question still to be answered is that of whether AR communities can mimic adjacent NR communities. We suggest three alternative hypotheses: Neighboring ARs and NRs will (1) achieve a similar community structure given sufficient time; (2) be similar only if they possess similar structural features; (3) always differ, regardless of age or structural features. We examined these hypotheses by comparing the community structure on a 119-year old shipwreck to a neighboring NR. Fouling organisms, including stony and soft corals, sponges, tunicates, sea anemones and hydrozoans were recorded and measured along belt transects. The ahermatypic stony coral Tubastrea micrantha dominated vertical AR regions while the soft corals Nephthea sp. and Xenia sp. dominated both artificial and natural horizontal surfaces. Our results support the second hypothesis, indicating that even after a century an AR will mimic its adjacent NR communities only if it possesses structural features similar to those of the natural surroundings. However, if the two differ structurally, their communities will remain distinct. PMID:16198411

  7. Mouse models of liver fibrosis mimic human liver fibrosis of different etiologies

    PubMed Central

    Martínez, Allyson K.; Maroni, Luca; Marzioni, Marco; Ahmed, Syed T.; Milad, Mena; Ray, Debolina; Alpini, Gianfranco; Glaser, Shannon S.

    2014-01-01

    The liver has the amazing capacity to repair itself after injury; however, the same processes that are involved in liver regeneration after acute injury can cause serious consequences during chronic liver injury. In an effort to repair damage, activated hepatic stellate cells trigger a cascade of events that lead to deposition and accumulation of extracellular matrix components causing the progressive replacement of the liver parenchyma by scar tissue, thus resulting in fibrosis. Although fibrosis occurs as a result of many chronic liver diseases, the molecular mechanisms involved depend on the underlying etiology. Since studying liver fibrosis in human subjects is complicated by many factors, mouse models of liver fibrosis that mimic the human conditions fill this void. This review summarizes the general mouse models of liver fibrosis and mouse models that mimic specific human disease conditions that result in liver fibrosis. Additionally, recent progress that has been made in understanding the molecular mechanisms involved in the fibrogenic processes of each of the human disease conditions is highlighted. PMID:25396098

  8. Short exposure of albumin to high concentrations of malondialdehyde does not mimic physiological conditions.

    PubMed

    Millanta, Susanna; Furfaro, Anna Lisa; Carlier, Paolo; Tasso, Bruno; Nitti, Mariapaola; Domenicotti, Cinzia; Odetti, Patrizio; Pronzato, Maria Adelaide; Traverso, Nicola

    2013-02-01

    Malondialdehyde (MDA), a major lipid peroxidation product, spontaneously binds to, and modifies proteins. In vivo, proteins are physiologically exposed to micromolar MDA concentrations for long periods. In order to mimic this process in vitro, protein modification is often performed by short exposure to millimolar MDA concentrations, also in order to generate antigenic structures for antibody production. However, in our study, spectrophotometric and fluorimetric characteristics, electrophoretic migration, susceptibility to trypsin digestion and reactivity to antibodies indicated substantial differences between albumin incubated with millimolar MDA concentrations for a short period of time and albumin incubated with micromolar MDA concentrations for a long period of time. Therefore, our study showed that short incubation of albumin with millimolar MDA concentrations does not mimic the consequences of albumin exposure to long incubation with micromolar MDA concentrations. This casts doubts on the real possibility that antibodies, elicited with proteins modified with millimolar MDA concentrations for a short period, could detect all MDA-modified proteins in vivo. Moreover, natural antibodies against albumin, modified with micromolar MDA concentrations, have been detected in the serum of healthy blood donors, which appears to justify the existence of these kinds of modified proteins in vivo.

  9. Chimeric Aptamer-Gelatin Hydrogels as an Extracellular Matrix Mimic for Loading Cells and Growth Factors

    PubMed Central

    Zhang, Xiaolong; Battig, Mark R.; Chen, Niancao; Gaddes, Erin R.; Duncan, Katelyn L.; Wang, Yong

    2016-01-01

    It is important to synthesize materials to recapitulate critical functions of biological systems for a variety of applications such as tissue engineering and regenerative medicine. The purpose of this study was to synthesize a chimeric hydrogel as a promising extracellular matrix (ECM) mimic using gelatin, a nucleic acid aptamer and polyethylene glycol (PEG). This hydrogel had a macroporous structure that was highly permeable for fast molecular transport. Despite its high permeability, it could strongly sequester and sustainably release growth factors with high bioactivity. Notably, growth factors retained in the hydrogel could maintain ~50% bioactivity during a 14-day release test. It also provided cells with effective binding sites, which led to high efficiency of cell loading into the macroporous hydrogel matrix. When cells and growth factors were co-loaded into the chimeric hydrogel, living cells could still be observed by day 14 in a static serum-reduced culture condition. Thus, this chimeric aptamer-gelatin hydrogel constitutes a promising biomolecular ECM mimic for loading cells and growth factors. PMID:26791559

  10. The supramolecular organization of self-assembling chlorosomal bacteriochlorophyll c, d, or e mimics.

    PubMed

    Jochum, Tobias; Reddy, Chilla Malla; Eichhöfer, Andreas; Buth, Gernot; Szmytkowski, Jedrzej; Kalt, Heinz; Moss, David; Balaban, Teodor Silviu

    2008-09-01

    Bacteriochlorophylls (BChls) c, d, and e are the main light-harvesting pigments of green photosynthetic bacteria that self-assemble into nanostructures within the chlorosomes forming the most efficient antennas of photosynthetic organisms. All previous models of the chlorosomal antennae, which are quite controversially discussed because no single crystals could be grown so far from these organelles, involve a strong hydrogen-bonding interaction between the 3(1) hydroxyl group and the 13(1) carbonyl group. We have synthesized different self-assemblies of BChl c mimics having the same functional groups as the natural counterparts, that is, a hydroxyethyl substituent, a carbonyl group and a divalent metal atom ligated by a tetrapyrrole. These artificial BChl mimics have been shown by single crystal x-ray diffraction to form extended stacks that are packed by hydrophobic interactions and in the absence of hydrogen bonding. Time-resolved photoluminescence proves the ordered nature of the self-assembled stacks. FT-IR spectra show that on self-assembly the carbonyl frequency is shifted by approximately 30 cm(-1) to lower wavenumbers. From the FT-IR data we can infer the proximal interactions between the BChls in the chlorosomes consistent with a single crystal x-ray structure that shows a weak electrostatic interaction between carbonyl groups and the central zinc atom.

  11. Polymer Brushes that Mimic Repulsive Properties of the Boundary Lubricant Glycoprotein Lubricin

    NASA Astrophysics Data System (ADS)

    Torres, Jahn; Jay, Gregory; Ni, Qian; Bello, David; Bothun, Geoffrey; Kim, Kyung-Suk

    2011-03-01

    This is a report on the design of tailored functional groups which mimic the repulsive forces at work in the natural-joint boundary lubricant known as lubricin. Lubricin, an amphiphilic polyelectrolyte biomolecule, decreases friction and cellular adhesion by exhibiting surface force fields based on steric hindrance, Debye electrostatic double layer repulsion and hydration repulsive forces. We have identified a physically and chemically stable candidate polymers for anti-fouling coatings that will mimic lubricin's repulsive properties. Synthetic polymer brushes mimicking lubricin have been produced using these polymers grafted onto a glass surfaces. The average adhesive forces for the polymer brushes measured through atomic force microscopy are as low (56.796 +/- 0.796 mN/m), similar to those exhibited by lubricin coated surfaces and on the same order of magnitude as superhydrophobic surfaces. This work was supported by the Coatings/Biofouling Program and the Maritime Sensing Program of the Office of Naval Research as well as the ILIR Program of the Naval Undersea Warfare Center DIVNPT.

  12. Synthesis of Oxylipin Mimics and Their Antifungal Activity against the Citrus Postharvest Pathogens.

    PubMed

    Ma, Jimei; Li, Yupeng; Chen, Hangwei; Zeng, Zhen; Li, Zi-Long; Jiang, Hong

    2016-01-01

    Nine oxylipin mimics were designed and synthesized starting from d-mannose. Their antifungal activity against three citrus postharvest pathogens was evaluated by spore germination assay. The results indicated that all the compounds significantly inhibited the growth of Penicillium digitatum, Penicillium italicum and Aspergillus niger. The compound (3Z,6Z,8S,9R,10R)-octadeca-3,6-diene-8,9,10-triol (3) exhibited excellent inhibitory effect on both Penicillium digitatum (IC50 = 34 ppm) and Penicillium italicum (IC50 = 94 ppm). Their in vivo antifungal activities against citrus postharvest blue mold were tested with fruit inoculated with the pathogen Penicillium italicum. The compound (3R,4S)-methyl 3,4-dihydroxy-5-octyltetrahydrofuran-2-carboxylate (9) demonstrated significant efficacy by reducing the disease severity to 60%. The antifungal mechanism of these oxylipin mimics was postulated in which both inhibition of pathogenic mycelium and stimuli of the host oxylipin-mediated defense response played important roles. PMID:26907241

  13. Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy.

    PubMed

    Zhou, Mengying; Zhang, Xulang; Wen, Xinyu; Wu, Taihua; Wang, Weidong; Yang, Mingzhou; Wang, Jing; Fang, Ming; Lin, Bingcheng; Lin, Hongli

    2016-08-25

    Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.

  14. Identification of Peptide Mimics of a Glycan Epitope on the Surface of Parasitic Nematode Larvae

    PubMed Central

    Roberts, Joanna M.; Shaw, Richard J.; Sutherland, Ian A.; Pernthaner, Anton

    2016-01-01

    Phage display was used to identify peptide mimics of an immunologically protective nematode glycan (CarLA) by screening a constrained C7C peptide library for ligands that bound to an anti-CarLA mAb (PAB1). Characterisation of these peptide mimotopes revealed functional similarities with an epitope that is defined by PAB1. Mimotope vaccinations of mice with three selected individual phage clones facilitated the induction of antibody responses that recognised the purified, native CarLA molecule which was obtained from Trichostrongylus colubriformis. Furthermore, these mimotopes are specifically recognised by antibodies in the saliva of animals that were immune to natural polygeneric nematode challenge. This shows that antibodies to the PAB1 epitope form part of the mucosal polyclonal anti-CarLA antibody response of nematode immune host animals. This demonstrates that the selected peptide mimotopes are of biological relevance. These peptides are the first to mimic the PAB1 epitope of CarLA, a defined larval glycan epitope which is conserved between many nematode species. PMID:27579674

  15. Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

    PubMed

    Miras, A D; le Roux, C W

    2014-03-01

    The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals. PMID:24213310

  16. Intact Rapid Facial Mimicry as well as Generally Reduced Mimic Responses in Stable Schizophrenia Patients

    PubMed Central

    Chechko, Natalya; Pagel, Alena; Otte, Ellen; Koch, Iring; Habel, Ute

    2016-01-01

    Spontaneous emotional expressions (rapid facial mimicry) perform both emotional and social functions. In the current study, we sought to test whether there were deficits in automatic mimic responses to emotional facial expressions in patients (15 of them) with stable schizophrenia compared to 15 controls. In a perception-action interference paradigm (the Simon task; first experiment), and in the context of a dual-task paradigm (second experiment), the task-relevant stimulus feature was the gender of a face, which, however, displayed a smiling or frowning expression (task-irrelevant stimulus feature). We measured the electromyographical activity in the corrugator supercilii and zygomaticus major muscle regions in response to either compatible or incompatible stimuli (i.e., when the required response did or did not correspond to the depicted facial expression). The compatibility effect based on interactions between the implicit processing of a task-irrelevant emotional facial expression and the conscious production of an emotional facial expression did not differ between the groups. In stable patients (in spite of a reduced mimic reaction), we observed an intact capacity to respond spontaneously to facial emotional stimuli. PMID:27303335

  17. Alkaloid defenses of co-mimics in a putative Müllerian mimetic radiation

    PubMed Central

    2014-01-01

    Background Polytypism in aposematic species is unlikely according to theory, but commonly seen in nature. Ranitomeya imitator is a poison frog species exhibiting polytypic mimicry of three congeneric model species (R. fantastica, R. summersi, and two morphs of R. variabilis) across four allopatric populations (a "mimetic radiation"). In order to investigate chemical defenses in this system, a key prediction of Müllerian mimicry, we analyzed the alkaloids of both models and mimics from four allopatric populations. Results In this study we demonstrate distinct differences in alkaloid profiles between co-mimetic species within allopatric populations. We further demonstrate that R. imitator has a greater number of distinct alkaloid types than the model species and more total alkaloids in all but one population. Conclusions Given that R. imitator is the more abundant species in these populations, R. imitator is likely driving the majority of predator-learned avoidance in these complexes. The success of Ranitomeya imitator as a putative advergent mimic may be a direct result of differences in alkaloid sequestration. Furthermore, we propose that automimicry within co-mimetic species is an important avenue of research. PMID:24707851

  18. Synthesis and biological activity of conformationally restricted gypsy moth pheromone mimics.

    PubMed

    Chen, Hao; Gong, Yongmei; Gries, Regine M; Plettner, Erika

    2010-04-15

    The design and synthesis of a series of conformationally constrained mimics of gypsy moth sex pheromone, (+)-disparlure (7R,8S)-2-methyl-7,8-epoxyoctadecane, are described. The core structure of the mimics is derived from 5-(2'-hydroxyethyl)cyclopent-2-en-1-ol. Substituent optimization of the analogs was accomplished through the synthesis of mini-libraries and pure individual compounds, followed by electrophysiological experiments with male gypsy moth antennae. The electroantennogram results show that the analogs elicited weak to no antennal responses themselves. There was a clear structure-activity pattern for odorant activity, with ethyl substituents being best. Further, when puffed simultaneously with the pheromone, some of the compounds gave a significant enhancement of the antennal depolarization, indicating an additive or synergistic effect. A pure pheromone stimulus following a mixed compound/pheromone stimulus was generally not affected, with two exceptions: one compound enhanced and another inhibited a subsequent stimulus. The compounds also prolonged the stimulation of the antenna, which manifested itself in widened electroantennogram peaks. We tested the hypothesis that this prolonged stimulation may be due to the stabilization of a particular conformer of the pheromone-binding protein (PBP). Compounds that caused PBP2 to adopt a similar conformation than in the presence of pheromone also caused peak widening. This was not the case with PBP1.

  19. Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics

    PubMed Central

    Maas, Sybren L.N.; de Vrij, Jeroen; van der Vlist, Els J.; Geragousian, Biaina; van Bloois, Louis; Mastrobattista, Enrico; Schiffelers, Raymond M.; Wauben, Marca H.M.; Broekman, Marike L.D.; Nolte-'t Hoen, Esther N.M.

    2015-01-01

    Nano-sized extracelullar vesicles (EVs) released by various cell types play important roles in a plethora of (patho)physiological processes and are increasingly recognized as biomarkers for disease. In addition, engineered EV and EV-inspired liposomes hold great potential as drug delivery systems. Major technologies developed for high-throughput analysis of individual EV include nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (tRPS) and high-resolution flow cytometry (hFC). Currently, there is a need for comparative studies on the available technologies to improve standardization of vesicle analysis in diagnostic or therapeutic settings. We investigated the possibilities, limitations and comparability of NTA, tRPS and hFC for analysis of tumor cell-derived EVs and synthetic mimics (i.e. differently sized liposomes). NTA and tRPS instrument settings were identified that significantly affected the quantification of these particles. Furthermore, we detailed the differences in absolute quantification of EVs and liposomes using the three technologies. This study increases our understanding of possibilities and pitfalls of NTA, tRPS and hFC, which will benefit standardized and large-scale clinical application of (engineered) EVs and EV-mimics in the future. PMID:25555362

  20. cNMP-AMs mimic and dissect bacterial nucleotidyl cyclase toxin effects.

    PubMed

    Beckert, Ulrike; Grundmann, Manuel; Wolter, Sabine; Schwede, Frank; Rehmann, Holger; Kaever, Volkhard; Kostenis, Evi; Seifert, Roland

    2014-09-01

    In addition to the well-known second messengers cAMP and cGMP, mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. The Pseudomonas aeruginosa toxin ExoY massively increases cGMP and cUMP in cells, whereas the Bordetella pertussis toxin CyaA increases cAMP and, to a lesser extent, cCMP. To mimic and dissect toxin effects, we synthesized cNMP-acetoxymethylesters as prodrugs. cNMP-AMs rapidly and effectively released the corresponding cNMP in cells. The combination of cGMP-AM plus cUMP-AM mimicked cytotoxicity of ExoY. cUMP-AM and cGMP-AM differentially activated gene expression. Certain cCMP and cUMP effects were independent of the known cNMP effectors protein kinases A and G and guanine nucleotide exchange factor Epac. In conclusion, cNMP-AMs are useful tools to mimic and dissect bacterial nucleotidyl cyclase toxin effects. PMID:25108158

  1. MicroRNA-125b-5p mimic inhibits acute liver failure

    PubMed Central

    Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P.; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep

    2016-01-01

    The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF. PMID:27336362

  2. Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

    PubMed

    Miras, A D; le Roux, C W

    2014-03-01

    The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

  3. Smells like aphids: orchid flowers mimic aphid alarm pheromones to attract hoverflies for pollination.

    PubMed

    Stökl, Johannes; Brodmann, Jennifer; Dafni, Amots; Ayasse, Manfred; Hansson, Bill S

    2011-04-22

    Most insects are dependent on chemical communication for activities such as mate finding or host location. Several plants, and especially orchids, mimic insect semiochemicals to attract insects for unrewarded pollination. Here, we present a new case of pheromone mimicry found in the terrestrial orchid Epipactis veratrifolia. Flowers are visited and pollinated by several species of aphidophagous hoverflies, the females of which also often lay eggs in the flowers. The oviposition behaviour of these hoverflies is mainly guided by aphid-derived kairomones. We show that the flowers produce α- and β-pinene, β-myrcene and β-phellandrene, and that these compounds attract and induce oviposition behaviour in female hoverflies. This floral odour profile is remarkably similar to the alarm pheromone released by several aphid species, such as Megoura viciae. We therefore suggest that E. veratrifolia mimics aphid alarm pheromones to attract hoverflies for pollination; this is the first time, to our knowledge, that such a case of mimicry has been demonstrated.

  4. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

    PubMed

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy. PMID:27575372

  5. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells

    PubMed Central

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy. PMID:27575372

  6. Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions

    NASA Astrophysics Data System (ADS)

    Kubilis, Artur; Abdulkarim, Ali; Eissa, Ahmed M.; Cameron, Neil R.

    2016-08-01

    Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction.

  7. Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions

    PubMed Central

    Kubilis, Artur; Abdulkarim, Ali; Eissa, Ahmed M.; Cameron, Neil R.

    2016-01-01

    Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction. PMID:27576579

  8. Design, Synthesis, and Biological Evaluation of Dabigatran Etexilate Mimics, a Novel Class of Thrombin Inhibitors.

    PubMed

    Wang, Shaochi; Dai, Peng; Xu, Yungen; Chen, Qiufang; Zhu, Qihua; Gong, Guoqing

    2015-08-01

    Human α-thrombin is a particularly promising target for anticoagulant therapy, and identification of oral small-molecular inhibitors of thrombin remains a research focus. On the basis of the X-ray crystal structure of human α-thrombin and its inhibitor dabigatran, we designed and synthesized a series of dabigatran etexilate mimics containing a novel tricyclic fused scaffold. The biological evaluations reveal that all of the compounds possess moderate activity of antiplatelet aggregation induced by thrombin in vitro. Moreover, compound I-8, which contains 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP), a cleavable moiety with antiplatelet activity, shows the best anticoagulant effect among the tested compounds in vivo. Those synthesized compounds that have better in vitro activity were subjected to bleeding complication tests, and the results demonstrate that the novel compounds are less likely to have bleeding risk than dabigatran etexilate.

  9. The Structure of Human 15-Lipoxygenase-2 with a Substrate Mimic*

    PubMed Central

    Kobe, Matthew J.; Neau, David B.; Mitchell, Caitlin E.; Bartlett, Sue G.; Newcomer, Marcia E.

    2014-01-01

    Atherosclerosis is associated with chronic inflammation occurring over decades. The enzyme 15-lipoxygenase-2 (15-LOX-2) is highly expressed in large atherosclerotic plaques, and its activity has been linked to the progression of macrophages to the lipid-laden foam cells present in atherosclerotic plaques. We report here the crystal structure of human 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. The loop is flanked by two Ca2+-binding sites that confer Ca2+-dependent membrane binding. A comparison of the human 15-LOX-2 and 5-LOX structures reveals similarities at the active sites, as well striking differences that can be exploited for design of isoform-selective inhibitors. PMID:24497644

  10. Mutations in the GABAA receptor that mimic the allosteric ligand, etomidate

    PubMed Central

    Forman, Stuart A.; Stewart, Deirdre

    2012-01-01

    Etomidate is a hydrophobic molecule, a potent general anesthetic, and the best understood drug in this group. Etomidate’s target molecules are GABAA receptors, its site of action has been identified with photolabeling, and a quantitative allosteric co-agonist model has emerged for etomidate effects on GABAA receptors. We have shown that when methionine residues that are thought to be adjacent to the etomidate site are mutated to tryptophan, that the bulky hydrophobic side-chains alter mutant GABAA receptor function in ways that mimic the effects of etomidate binding to wild-type receptors. Furthermore, these mutations reduce receptor modulation by etomidate. Both of these observations support the hypothesis that these methionine residues form part of the etomidate binding pocket. PMID:22052498

  11. Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials

    PubMed Central

    Love, Melissa S.; Millholland, Melanie G.; Mishra, Satish; Kulkarni, Swapnil; Freeman, Katie B.; Pan, Wenxi; Kavash, Robert W.; Costanzo, Michael J.; Jo, Hyunil; Daly, Thomas M.; Williams, Dewight R.; Kowalska, M. Anna; Bergman, Lawrence W.; Poncz, Mortimer; DeGrado, William F.; Sinnis, Photini; Scott, Richard W.; Greenbaum, Doron C.

    2012-01-01

    SUMMARY Plasmodium falciparum pathogenesis is affected by various cell types in the blood, including platelets, which can kill intraerythrocytic malaria parasites. Platelets could mediate these antimalarial effects through human defense peptides (HDPs), which exert antimicrobial effects by permeabilizing membranes. Therefore, we screened a panel of HDPs and determined that human platelet factor 4 (hPF4) kills malaria parasites inside erythrocytes by selectively lysing the parasite digestive vacuole (DV). PF4 rapidly accumulates only within infected erythrocytes and is required for parasite killing in infected erythrocyte-platelet cocultures. To exploit this antimalarial mechanism, we tested a library of small, nonpeptidic mimics of HDPs (smHDPs) and identified compounds that kill P. falciparum by rapidly lysing the parasite DV while sparing the erythrocyte plasma membrane. Lead smHDPs also reduced parasitemia in a murine malaria model. Thus, identifying host molecules that control parasite growth can further the development of related molecules with therapeutic potential. PMID:23245326

  12. Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions.

    PubMed

    Kubilis, Artur; Abdulkarim, Ali; Eissa, Ahmed M; Cameron, Neil R

    2016-01-01

    Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction. PMID:27576579

  13. Structural mimics of viruses through peptide/DNA co-assembly.

    PubMed

    Ni, Rong; Chau, Ying

    2014-12-31

    A synthetic mimic of viral structure has been constructed by the synergistic co-assembly of a 16-amino acid peptide and plasmid DNA. The rational design of this short peptide, including segments for binding DNA and forming β-sheet, is inspired by viral capsid protein. The resulting nanostructures, which we term nanococoons, appear as ellipsoids of virus-like dimension (65 × 47 nm) and display repeating stripes of ∼4 nm wide. We propose that the co-assembly process involves DNA as a template to assist the organization of peptide strands by electrostatic interaction, while the bilayer β-sheets and their lateral association stabilize the peptide "capsid" and organize the DNA within. The hierarchy affords an extremely stable structure, protecting peptide and DNA against enzymatic digestion. It opens a new and facile avenue to fabricate viral alternatives with diverse functions.

  14. Fully-branched hyperbranched polymers with a diselenide core as glutathione peroxidase mimics.

    PubMed

    Fu, Yu; Chen, Junyi; Xu, Huaping; Van Oosterwijck, Chantal; Zhang, Xi; Dehaen, Wim; Smet, Mario

    2012-05-14

    A novel glutathione peroxidase (GPx) mimic has been prepared by incorporation of a selenium-based catalytic unit into the focal point of a fully-branched hyperbranched polymer. First, an AB(2) monomer consisting of isatin and an electron rich aromatic moiety was polycondensed in the presence of 5-nitroisatin as a core reagent, resulting in a polymer with 100% degree of branching. The latter was coupled to the catalytically active moiety, Br(CH(2))(5) SeSe(CH(2))(5) Br, by nucleophilic substitution of the bromides by the residual amide groups of the incorporated nitroisatin core. The obtained polymer has demonstrated prominent GPx activity as desired, which could be attributed to the hydrophobic, densely branched and core-shell structure of the polymer surrounding the catalytic center. PMID:22434542

  15. Artificial enzyme mimics for catalysis and double natural enzyme co-immobilization.

    PubMed

    Li, Xiaohua; Zhang, Zhujun; Li, Yongbo

    2014-02-01

    This work presents a new chemiluminescent (CL) probe array assay. The new type CL probe array is based on enzyme mimics of Co3O4-SiO2 mesoporous nanocomposite material, which not only have an excellent catalytic effect on the luminol-H2O2 CL reaction in an alkaline medium but also can be used for the immobilization of enzymes. The linear range of the lactose concentration is 3.0 × 10(-7) to 1.0 × 10(-5) g mL(-1) and the detection limit is 6.9 × 10(-8) g mL(-1). β-Galactosidase and glucose oxidase were selected as a model for enzyme assays to demonstrate the applicability of Co3O4-SiO2 mesoporous nanocomposite material in multienzyme immobilization. The novel bifunctional CL probe array has been successfully applied to the determination of lactose in milk. PMID:24293256

  16. Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice.

    PubMed

    Wang, Da-Ting; He, Jiang; Wu, Ming; Li, Si-Ming; Gao, Qian; Zeng, Qing-Ping

    2015-01-01

    Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity.

  17. A Fluorescent Sensor for Dual-Channel Discrimination between Phosgene and a Nerve-Gas Mimic.

    PubMed

    Zhou, Xin; Zeng, Yiying; Liyan, Chen; Wu, Xue; Yoon, Juyoung

    2016-04-01

    The ability to analyze highly toxic chemical warfare agents (CWAs) and related chemicals in a rapid and precise manner is essential in order to alleviate serious threats to humankind and public security caused by unexpected terrorist attacks and industrial accidents. In this investigation, we designed a o-phenylenediamine-pyronin linked dye that is capable of both fluorogenic and colorimetric discrimination between phosgene and the prototypical nerve-agent mimic, diethyl chlorophosphate (DCP) in the solution or gas phase. Moreover, this dye has been used to construct a portable kit that can be employed for real-time monitoring of DCP and phosgene in the field, both in a discriminatory manner, and in a simple and safe way. PMID:26938275

  18. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

    PubMed Central

    Pearson, Brandon L.; Simon, Jeremy M.; McCoy, Eric S.; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J.

    2016-01-01

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders. PMID:27029645

  19. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.

    PubMed

    Pearson, Brandon L; Simon, Jeremy M; McCoy, Eric S; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J

    2016-01-01

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders. PMID:27029645

  20. A prebiotic role for 8-oxoguanosine as a flavin mimic in pyrimidine dimer photorepair.

    PubMed

    Nguyen, Khiem Van; Burrows, Cynthia J

    2011-09-21

    Redox-active enzyme cofactors derived from ribonucleotides have been called "fossils of the RNA world," suggesting that early catalysts employed modified nucleobases to facilitate redox chemistry in primitive metabolism. Here, we show that the common oxidative damage product 8-oxo-7,8-dihydroguanine (OG), when incorporated into a DNA or RNA strand in proximity to a cyclobutane pyrimidine dimer, can mimic the function of a flavin in photorepair. The OG nucleotide acts catalytically in a mechanism consistent with that of photolyase in which the photoexcited state of the purine donates an electron to a pyrimidine dimer to initiate bond cleavage; subsequent back electron transfer regenerates OG. This unusual example of one form of DNA damage, oxidation, functioning to repair another, photodimerization, may provide insight into the origins of prebiotic redox processes. PMID:21877686

  1. Neurosarcoidosis as an MS Mimic: The trials and tribulations of making a diagnosis.

    PubMed

    MacLean, Heather J; Abdoli, Mohammad

    2015-09-01

    The clinical presentation of neurosarcoidosis is varied as multiple levels of the neuraxis may be affected. When central nervous system involvement occurs, making an accurate diagnosis of the condition can be challenging, especially given the current definition for definite neurosarcoidosis requires histologic confirmation of the affected tissue (brain biopsy). This article will review our current knowledge and manifestations of neurosarcoidosis, discuss the current diagnostic approach as well as the challenges associated with a condition requiring histologic confirmation, discuss the current treatment approach, and highlight the challenges of this diagnosis with a few real-life clinical cases. We also highlight the selected differential diagnosis of neurosarcoidosis as well as multiple sclerosis which could mimic each other.

  2. Artificial enzyme mimics for catalysis and double natural enzyme co-immobilization.

    PubMed

    Li, Xiaohua; Zhang, Zhujun; Li, Yongbo

    2014-02-01

    This work presents a new chemiluminescent (CL) probe array assay. The new type CL probe array is based on enzyme mimics of Co3O4-SiO2 mesoporous nanocomposite material, which not only have an excellent catalytic effect on the luminol-H2O2 CL reaction in an alkaline medium but also can be used for the immobilization of enzymes. The linear range of the lactose concentration is 3.0 × 10(-7) to 1.0 × 10(-5) g mL(-1) and the detection limit is 6.9 × 10(-8) g mL(-1). β-Galactosidase and glucose oxidase were selected as a model for enzyme assays to demonstrate the applicability of Co3O4-SiO2 mesoporous nanocomposite material in multienzyme immobilization. The novel bifunctional CL probe array has been successfully applied to the determination of lactose in milk.

  3. Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping

    PubMed Central

    Agostino, Mark; Yuriev, Elizabeth; Ramsland, Paul A.

    2012-01-01

    Modified gangliosides may be overexpressed in certain types of cancer, thus, they are considered a valuable target in cancer immunotherapy. Structural knowledge of their interaction with antibodies is currently limited, due to the large size and high flexibility of these ligands. In this study, we apply our previously developed site mapping technique to investigate the recognition of cancer-related gangliosides by anti-ganglioside antibodies. The results reveal a potential ganglioside-binding motif in the four antibodies studied, suggesting the possibility of structural convergence in the anti-ganglioside immune response. The structural basis of the recognition of ganglioside-mimetic peptides is also investigated using site mapping and compared to ganglioside recognition. The peptides are shown to act as structural mimics of gangliosides by interacting with many of the same binding site residues as the cognate carbohydrate epitopes. These studies provide important clues as to the structural basis of immunological mimicry of carbohydrates. PMID:22536387

  4. Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl.

    PubMed

    Starck, Matthieu; Sisommay, Nathalie; Laporte, Fanny A; Oros, Stéphane; Lebrun, Colette; Delangle, Pascale

    2015-12-01

    Cyclic peptides with two phosphoserines and two glutamic acids were developed to mimic high-affinity binding sites for uranyl found in proteins such as osteopontin, which is believed to be a privileged target of this ion in vivo. These peptides adopt a β-sheet structure that allows the coordination of the latter amino acid side chains in the equatorial plane of the dioxo uranyl cation. Complementary spectroscopic and analytical methods revealed that these cyclic peptides are efficient uranyl chelating peptides with a large contribution from the phosphorylated residues. The conditional affinity constants were measured by following fluorescence tryptophan quenching and are larger than 10(10) at physiological pH. These compounds are therefore promising models for understanding uranyl chelation by proteins, which is relevant to this actinide ion toxicity. PMID:26583259

  5. Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors.

    PubMed

    Chang, Chun Yun; Esber, Guillem R; Marrero-Garcia, Yasmin; Yau, Hau-Jie; Bonci, Antonello; Schoenbaum, Geoffrey

    2016-01-01

    Correlative studies have strongly linked phasic changes in dopamine activity with reward prediction error signaling. But causal evidence that these brief changes in firing actually serve as error signals to drive associative learning is more tenuous. Although there is direct evidence that brief increases can substitute for positive prediction errors, there is no comparable evidence that similarly brief pauses can substitute for negative prediction errors. In the absence of such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide evidence in support of the proposed linkage, showing in a modified Pavlovian over-expectation task that brief pauses in the firing of dopamine neurons in rat ventral tegmental area at the time of reward are sufficient to mimic the effects of endogenous negative prediction errors. These results support the proposal that brief changes in the firing of dopamine neurons serve as full-fledged bidirectional prediction error signals. PMID:26642092

  6. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.

    PubMed

    Pearson, Brandon L; Simon, Jeremy M; McCoy, Eric S; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J

    2016-03-31

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders.

  7. Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors.

    PubMed

    Chang, Chun Yun; Esber, Guillem R; Marrero-Garcia, Yasmin; Yau, Hau-Jie; Bonci, Antonello; Schoenbaum, Geoffrey

    2016-01-01

    Correlative studies have strongly linked phasic changes in dopamine activity with reward prediction error signaling. But causal evidence that these brief changes in firing actually serve as error signals to drive associative learning is more tenuous. Although there is direct evidence that brief increases can substitute for positive prediction errors, there is no comparable evidence that similarly brief pauses can substitute for negative prediction errors. In the absence of such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide evidence in support of the proposed linkage, showing in a modified Pavlovian over-expectation task that brief pauses in the firing of dopamine neurons in rat ventral tegmental area at the time of reward are sufficient to mimic the effects of endogenous negative prediction errors. These results support the proposal that brief changes in the firing of dopamine neurons serve as full-fledged bidirectional prediction error signals.

  8. Metastatic mimics on bone scan: “All that glitters is not metastatic”

    PubMed Central

    Agrawal, Archi; Purandare, Nilendu; Shah, Sneha; Rangarajan, Venkatesh

    2016-01-01

    In this pictorial review, cases where benign diseases caused a diagnostic dilemma on bone scan are illustrated. This review highlights the value of correlative imaging- single-photon emission computed tomography/computed tomography (CT), CT, and magnetic resonance imaging in solving the diagnostic problem by exact localization and characterization of the lesions. All these eventually lead to increased diagnostic confidence, better and more accurate reporting and avoidance of delay in initiation of treatment due to equivocal results. The imaging features of these benign pathologies – which are “mimics of metastatic disease,” are elaborated so that the reader can incorporate them while reporting so as to avoid mis-interpretations. PMID:27385887

  9. Aminoglycosides: Molecular Insights on the Recognition of RNA and Aminoglycoside Mimics

    PubMed Central

    Chittapragada, Maruthi; Roberts, Sarah; Ham, Young Wan

    2009-01-01

    RNA is increasingly recognized for its significant functions in biological systems and has recently become an important molecular target for therapeutics development. Aminoglycosides, a large class of clinically significant antibiotics, exert their biological functions by binding to prokaryotic ribosomal RNA (rRNA) and interfering with protein translation, resulting in bacterial cell death. They are also known to bind to viral mRNAs such as HIV-1 RRE and TAR. Consequently, aminoglycosides are accepted as the single most important model in understanding the principles that govern small molecule-RNA recognition, which is essential for the development of novel antibacterial, antiviral or even anti-oncogenic agents. This review outlines the chemical structures and mechanisms of molecular recognition and antibacterial activity of aminoglycosides and various aminoglycoside mimics that have recently been devised to improve biological efficacy, binding affinity and selectivity, or to circumvent bacterial resistance. PMID:19812740

  10. Design, synthesis, conformational analysis and application of indolizidin-2-one dipeptide mimics.

    PubMed

    Khashper, Arkady; Lubell, William D

    2014-07-28

    Growth in the field of peptide mimicry over the past few decades has resulted in the synthesis of many new compounds and the investigation of novel pharmacological agents. Azabicyclo[X.Y.0]alkanone amino acids are among the attractive classes of constrained mimics, because they can create rigid peptide structures for probing the conformation and roles of natural motifs in recognition events important for biological activity. Herein, we review the last ten years of the synthesis, conformational analysis and activity of analogs of the azabicyclo[4.3.0]alkan-2-one amino acid subclass, so-called indolizidin-2-one amino acids, with particular attention on their employment as inputs for biological applications. PMID:24899358

  11. Synthetic peptides as functional mimics of a viral discontinuous antigenic site.

    PubMed

    Villén, J; Borràs, E; Schaaper, W M; Meloen, R H; Dávila, M; Domingo, E; Giralt, E; Andreu, D

    2001-01-01

    Functional reproduction of discontinuous antigenic site D of foot-and-mouth disease virus (FMDV) has been achieved by means of synthetic peptide constructions that integrate into a single molecule each of the three protein loops that define the antigenic site. The site D mimics are designed on the basis of the X-ray structure of FMDV type C-S8c1 with the aid of molecular dynamics, so that the five residues assumed to be involved in antigenic recognition are located on the same face of the molecule, exposed to solvent and defining a set of native-like distances and angles. The designed site D mimics are disulphide-linked heterodimers that consist of a larger unit containing VP2(71-84), followed by a polyproline module and by VP3(52-62), and a smaller unit corresponding to VP1(188-194). Guinea pig antisera to the peptides recognize the viral particle and compete with site D-specific monoclonal antibodies, while inoculation with a simple (non-covalently bound) admixture of the three VP1-VP3 sequences yields no detectable virus-specific serum conversion. Similar results have been reproduced in two cattle. Antisera to the peptides are also moderately neutralizing of FMDV in cell culture and partially protective of guinea pigs against challenge with the virus. These results demonstrate functional mimicry of the discontinuous site D by the peptides, which are therefore obvious candidates for a multicomponent peptide-based vaccine against FMDV. PMID:11851326

  12. Effects of disc asymmetries on astrometric measurements. Can they mimic planets?

    NASA Astrophysics Data System (ADS)

    Kral, Q.; Schneider, J.; Kennedy, G.; Souami, D.

    2016-07-01

    Astrometry covers a parameter space that cannot be reached by RV or transit methods to detect terrestrial planets on wide orbits. In addition, high accuracy astrometric measurements are necessary to measure the inclination of the planet's orbits. Here we investigate the principles of an artefact of the astrometric approach, namely the displacement of the photo-centre owing to inhomogeneities in a dust disc around the parent star. Indeed, theory and observations show that circumstellar discs can present strong asymmetries. We model the pseudo-astrometric signal caused by these inhomogeneities, asking whether a dust clump in a disc can mimic the astrometric signal of an Earth-like planet. We show that these inhomogeneities cannot be neglected when using astrometry to find terrestrial planets. We provide the parameter space for which these inhomogeneities can affect the astrometric signals but still not be detected by mid-IR observations. We find that a small cross section of dust corresponding to a cometary mass object is enough to mimic the astrometric signal of an Earth-like planet. Astrometric observations of protoplanetary discs to search for planets can also be affected by the presence of inhomogeneities. Some further tests are given to confirm whether an observation is a real astrometric signal from a planet or an impostor. Eventually, we also study the case where the cross-section of dust is high enough to provide a detectable IR-excess and to have a measurable photometric displacement by actual instruments such as Gaia, IRAC, or GRAVITY. We suggest a new method, which consists of using astrometry to quantify asymmetries (clumpiness) in inner debris discs that cannot be otherwise resolved.

  13. Synthetic collagen heterotrimers: structural mimics of wild-type and mutant collagen type I.

    PubMed

    Gauba, Varun; Hartgerink, Jeffrey D

    2008-06-11

    Collagen type I is an AAB heterotrimer assembled from two alpha1 chains and one alpha2 chain. Missense mutations in either of these chains that substitute a glycine residue in the ubiquitous X-Y-Gly repeat with a bulky amino acid leads to osteogenesis imperfecta (OI) of varying severity. These mutations have been studied in the past using collagen-like peptide homotrimers as a model system. However, homotrimers, which by definition will contain glycine mutations in all the three chains, do not accurately mimic the mutations in their native form and result in an exaggerated effect on stability and folding. In this article, we report the design of a novel model system based upon collagen-like heterotrimers that can mimic the glycine mutations present in either the alpha1 or alpha2 chains of type I collagen. This design utilizes an electrostatic recognition motif in three chains that can force the interaction of any three peptides, including AAA (all same), AAB (two same and one different), or ABC (all different) triple helices. Therefore, the component peptides can be designed in such a way that glycine mutations are present in zero, one, two, or all three chains of the triple helix. With this design, we for the first time report collagen mutants containing one or two glycine substitutions with structures relevant to native forms of OI. Furthermore, we demonstrate the difference in thermal stability and refolding half-life times between triple helices that vary only in the frequency of glycine mutations at a particular position. PMID:18481852

  14. A miniature mimic of host defense peptides with systemic antibacterial efficacy

    PubMed Central

    Sarig, Hadar; Livne, Liran; Held-Kuznetsov, Victoria; Zaknoon, Fadia; Ivankin, Andrey; Gidalevitz, David; Mor, Amram

    2010-01-01

    Oligomers of acylated lysines (OAKs) are synthetic mimics of host defense peptides (HDPs) with promising antimicrobial properties. Here we challenged the OAK concept for its ability to generate both systemically efficient and economically viable lead compounds for fighting multidrug-resistant bacteria. We describe the design and characterization of a miniature OAK composed of only 3 lysyls and 2 acyls (designated C12(ω7)K-β12) that preferentially targets gram-positive species by a bacteriostatic mode of action. To gain insight into the mechanism of action, we examined the interaction of OAK with various potential targets, including phospholipid bilayers, using surface plasmon resonance, and Langmuir monolayers, using insertion assays, epifluorescence microscopy, and grazing incidence X-ray diffraction, in a complementary manner. Collectively, the data support the notion that C12(ω7)K-β12 damages the plasma-membrane architecture similarly to HDPs, that is, following a near-classic 2-step interaction including high-affinity electrostatic adhesion and a subsequent shallow insertion that was limited to the phospholipid head group region. Notably, preliminary acute toxicity and efficacy studies performed with mouse models of infection have consolidated the potential of OAK for treating bacterial infections, including systemic treatments of methicillin-resistant Staphylococcus aureus. Such simple yet robust chemicals might be useful for various antibacterial applications while circumventing potential adverse effects associated with cytolytic compounds.—Sarig, H., Livne, L., Held-Kuznetsov, V., Zaknoon, F., Ivankin, A., Gidalevitz, D., Mor, A. A miniature mimic of host defense peptides with systemic antibacterial efficacy. PMID:20124435

  15. Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an additive manner.

    PubMed

    Katchy, Anne; Pinto, Caroline; Jonsson, Philip; Nguyen-Vu, Trang; Pandelova, Marchela; Riu, Anne; Schramm, Karl-Werner; Samarov, Daniel; Gustafsson, Jan-Åke; Bondesson, Maria; Williams, Cecilia

    2014-03-01

    Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer.

  16. Compound mimicry and trading predators by the males of sexually dimorphic Batesian mimics

    PubMed Central

    Nelson, Ximena J; Jackson, Robert R

    2005-01-01

    Sexual dimorphism is pronounced in Myrmarachne, a large genus of ant-like jumping spiders (Salticidae) and one of the major animal groups in which Batesian mimicry of ants has evolved. Although adult females and juveniles of both sexes are distinctly ant-like in appearance, Myrmarachne males have elongated chelicerae that might appear to detract from their resemblance to ants. Experimental findings suggest that the Myrmarachne male's solution is to adopt compound mimicry (i.e. the male's model seems to be not simply an ant worker but a combination of an ant and something carried in the ant's mandibles: an ‘encumbered ant’). By becoming a mimic of a particular subset of worker ants, Myrmarachne males may have retained their Batesian-mimicry defence against ant-averse predators, but at the price of receiving the unwanted attention of predators for which encumbered ants are preferred prey. Two salticid species were used as predators in the experiments. Portia fimbriata is known to choose other salticids as preferred prey and to avoid unencumbered ants and their mimics (Myrmarachne females). In experiments reported here, P. fimbriata avoided encumbered ants and Myrmarachne males. Ants are the preferred prey of Chalcotropis gulosus. In our experiments, C. gulosus chose safer encumbered ants in preference to more dangerous unencumbered ants, chose Myrmarachne males more often than Myrmarachne females and showed no evidence of distinguishing between Myrmarachne males and encumbered ants. The cost of reconciling sexual dimorphism with Batesian mimicry appears to be that Myrmarachne males attract the unwanted attention of specialist predators of their compound model. PMID:16543180

  17. Compound mimicry and trading predators by the males of sexually dimorphic Batesian mimics.

    PubMed

    Nelson, Ximena J; Jackson, Robert R

    2006-02-01

    Sexual dimorphism is pronounced in Myrmarachne, a large genus of ant-like jumping spiders (Salticidae) and one of the major animal groups in which Batesian mimicry of ants has evolved. Although adult females and juveniles of both sexes are distinctly ant-like in appearance, Myrmarachne males have elongated chelicerae that might appear to detract from their resemblance to ants. Experimental findings suggest that the Myrmarachne male's solution is to adopt compound mimicry (i.e. the male's model seems to be not simply an ant worker but a combination of an ant and something carried in the ant's mandibles: an "encumbered ant"). By becoming a mimic of a particular subset of worker ants, Myrmarachne males may have retained their Batesian-mimicry defence against ant-averse predators, but at the price of receiving the unwanted attention of predators for which encumbered ants are preferred prey. Two salticid species were used as predators in the experiments. Portia fimbriata is known to choose other salticids as preferred prey and to avoid unencumbered ants and their mimics (Myrmarachne females). In experiments reported here, P. fimbriata avoided encumbered ants and Myrmarachne males. Ants are the preferred prey of Chalcotropis gulosus. In our experiments, C. gulosus chose safer encumbered ants in preference to more dangerous unencumbered ants, chose Myrmarachne males more often than Myrmarachne females and showed no evidence of distinguishing between Myrmarachne males and encumbered ants. The cost of reconciling sexual dimorphism with Batesian mimicry appears to be that Myrmarachne males attract the unwanted attention of specialist predators of their compound model.

  18. The Enzyme-mimic Activity of Ferric Nano-Core Residing in Ferritin and Its Biosensing Applications

    SciTech Connect

    Tang, Zhiwen; Wu, Hong J.; Zhang, Youyu; Li, Zhaohui; Lin, Yuehe

    2011-11-15

    Ferritins are nano-scale globular protein cages encapsulating a ferric core. They widely exist in animals, plants, and microbes, playing indispensable roles in iron homeostasis. Interestingly, our study clearly demonstrates that ferritin has an enzyme-mimic activity derived from its ferric nano-core, but not the protein cage. Further study revealed that the mimic-enzyme activity of ferritin is more thermally stable and pH-tolerant compared with horseradish peroxidase. Considering the abundance of ferritin in numerous organisms, this finding may indicate a new role of ferritin in antioxidant and detoxification metabolisms. In addition, as a natural protein-caged nanoparticle with an enzyme-mimic activity, ferritin is readily conjugated with biomolecules to construct nano-biosensors, thus holds promising potential for facile and biocompatible labeling for sensitive and robust bioassays in biomedical applications.

  19. Percutaneous CT-Guided Core Needle Biopsy Versus Fine Needle Aspiration in Diagnosing Pneumonia and Mimics of Pneumonia

    SciTech Connect

    Thanos, Loukas; Galani, Panagiota Mylona, Sophia; Pomoni, Maria; Mpatakis, Nikolaos

    2004-08-15

    The purpose of this study was to determine the diagnostic value of percutaneous core needle biopsy (CNB) relative to fine needle aspiration (FNA) in patients with pneumonia and pneumonia mimics. In this prospective study we present our experience with 48 thoracic FNAs and CNBs carried out on 48 patients with pneumonia and pneumonia mimics. Samples were obtained from all patients using both CNB (with an automated 18-G core biopsy needle and a gun) and FNA (with a 22-G needle). A specific diagnosis was made in 10/48 cases (20.83%) by FNA and in 42/48 (87.5%) by CNB. The main complications encountered were pneumothorax (n = 4) and hemoptysis (n = 2), yielding a total complication rate of 12.5%. We concluded that CNB using an automated biopsy gun results in a higher diagnostic accuracy for pneumonia and pneumonia mimic biopsies than FNA. Complications should be considered and proper patient observation should follow the procedure.

  20. Chlamydomonas reinhardtii Secretes Compounds That Mimic Bacterial Signals and Interfere with Quorum Sensing Regulation in Bacteria1

    PubMed Central

    Teplitski, Max; Chen, Hancai; Rajamani, Sathish; Gao, Mengsheng; Merighi, Massimo; Sayre, Richard T.; Robinson, Jayne B.; Rolfe, Barry G.; Bauer, Wolfgang D.

    2004-01-01

    The unicellular soil-freshwater alga Chlamydomonas reinhardtii was found to secrete substances that mimic the activity of the N-acyl-l-homoserine lactone (AHL) signal molecules used by many bacteria for quorum sensing regulation of gene expression. More than a dozen chemically separable but unidentified substances capable of specifically stimulating the LasR or CepR but not the LuxR, AhyR, or CviR AHL bacterial quorum sensing reporter strains were detected in ethyl acetate extracts of C. reinhardtii culture filtrates. Colonies of C. reinhardtii and Chlorella spp. stimulated quorum sensing-dependent luminescence in Vibrio harveyi, indicating that these algae may produce compounds that affect the AI-2 furanosyl borate diester-mediated quorum sensing system of Vibrio spp. Treatment of the soil bacterium Sinorhizobium meliloti with a partially purified LasR mimic from C. reinhardtii affected the accumulation of 16 of the 25 proteins that were altered in response to the bacterium's own AHL signals, providing evidence that the algal mimic affected quorum sensing-regulated functions in this wild-type bacterium. Peptide mass fingerprinting identified 32 proteins affected by the bacterium's AHLs or the purified algal mimic, including GroEL chaperonins, the nitrogen regulatory protein PII, and a GTP-binding protein. The algal mimic was able to cancel the stimulatory effects of bacterial AHLs on the accumulation of seven of these proteins, providing evidence that the secretion of AHL mimics by the alga could be effective in disruption of quorum sensing in naturally encountered bacteria. PMID:14671013

  1. Integrating microbial physiology and physiochemical principles in soils with the MIcrobial-MIneral Carbon Stabilization (MIMICS) model

    NASA Astrophysics Data System (ADS)

    Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Bonan, G. B.

    2014-01-01

    Previous modeling efforts document divergent responses of microbial explicit soil biogeochemistry models when compared to traditional models that implicitly simulate microbial activity, particularly following environmental perturbations. However, microbial models are needed that capture current soil biogeochemical theories emphasizing the relationships between litter quality, functional differences in microbial physiology, and the physical protection of microbial byproducts in forming stable soil organic matter (SOM). To address these limitations we introduce the MIcrobial-MIneral Carbon Stabilization (MIMICS) model. In MIMICS, the turnover of litter and SOM pools are governed by temperature sensitive Michaelis-Menten kinetics and the activity of two physiologically distinct microbial functional types. The production of microbial residues through microbial turnover provides inputs to SOM pools that are considered physically or chemically protected. Soil clay content determines the physical protection of SOM in different soil environments. MIMICS adequately simulates the mean rate of leaf litter decomposition observed at a temperate and boreal forest sites, and captures observed effects of litter quality on decomposition rates. Initial results from MIMICS suggest that soil C storage can be maximized in sandy soils with low-quality litter inputs, whereas high-quality litter inputs may maximize SOM accumulation in finely textured soils that physically stabilize microbial products. Assumptions in MIMICS about the degree to which microbial functional types differ in the production, turnover, and stabilization of microbial residues provides a~mechanism by which microbial communities may influence SOM dynamics in mineral soils. Although further analyses are needed to validate model results, MIMICS allows us to begin exploring theoretical interactions between substrate quality, microbial community abundance, and the formation of stable SOM.

  2. THE USE OF GENE ARRAYS TO MEASURE CHANGES IN GENE EXPRESSION PATTERNS IN FISH EXPOSED TO COMPOUNDS THAT MIMIC ESTROGEN

    EPA Science Inventory

    We have developed estrogen-sensitive gene arrays to measure changes in gene expression in sheepshead minnows and largemouth bass exposed to anthropogenic chemicals that mimic estrogen. The in vivo exposures, which realize the full physiological response in fish, result in changes...

  3. Fluorometric, water-based sensors for the detection of nerve gas G mimics DMMP, DCP and DCNP.

    PubMed

    Wild, Andreas; Winter, Andreas; Hager, Martin D; Schubert, Ulrich S

    2012-01-25

    Water-based Zn(II) bisterpyridine systems were used as fluorometric sensors for the detection of the nerve gas G mimics DMMP, DCP and DCNP. Analyte concentrations in the range of 10(-7) to 10(-6) M are detectable in solution. The utilization of a test stripe additionally allows the detection of organophosphonates from the gas phase.

  4. Mixture Item Response Theory-MIMIC Model: Simultaneous Estimation of Differential Item Functioning for Manifest Groups and Latent Classes

    ERIC Educational Resources Information Center

    Bilir, Mustafa Kuzey

    2009-01-01

    This study uses a new psychometric model (mixture item response theory-MIMIC model) that simultaneously estimates differential item functioning (DIF) across manifest groups and latent classes. Current DIF detection methods investigate DIF from only one side, either across manifest groups (e.g., gender, ethnicity, etc.), or across latent classes…

  5. Investigation Gender/Ethnicity Heterogeneity in Course Management System Use in Higher Education by Utilizing the MIMIC Model

    ERIC Educational Resources Information Center

    Li, Yi

    2012-01-01

    This study focuses on the issue of learning equity in colleges and universities where teaching and learning have come to depend heavily on computer technologies. The study uses the Multiple Indicators Multiple Causes (MIMIC) latent variable model to quantitatively investigate whether there is a gender /ethnicity difference in using computer based…

  6. Artificial synthetic Mn(IV)Ca-oxido complexes mimic the oxygen-evolving complex in photosystem II.

    PubMed

    Chen, Changhui; Zhang, Chunxi; Dong, Hongxing; Zhao, Jingquan

    2015-03-14

    A novel family of heteronuclear Mn(IV)Ca-oxido complexes containing Mn(IV)Ca-oxido cuboidal moieties and reactive water molecules on Ca(2+) have been synthesized and characterized to mimic the oxygen-evolving complex (OEC) of photosystem II (PSII) in nature. PMID:25662151

  7. Bat reproduction declines when conditions mimic climate change projections for western North America.

    PubMed

    Adams, Rick A

    2010-08-01

    Climate change models predict that much of western North America is becoming significantly warmer and drier, resulting in overall reductions in availability of water for ecosystems. Herein, I demonstrate that significant declines in the reproductive success of female insectivorous bats occur in years when annual environmental conditions mimic the long-term predictions of regional climate change models. Using a data set gathered on bat populations from 1996 through 2008 along the Front Range of Colorado, I compare trends in population numbers and reproductive outcomes of six species of vespertilionid bats with data on mean annual high temperature, precipitation, snow pack, and stream discharge rates. I show that levels of precipitation and flow rates of small streams near maternity colonies is fundamentally tied to successful reproduction in female bats, particularly during the lactation phase. Across years that experienced greater than average mean temperatures with less than average precipitation and stream flow, bat populations responded by slight to profound reductions in reproductive output depending on the severity of drought conditions. In particular, reproductive outputs showed profound declines (32-51%) when discharge rates of the largest stream in the field area dropped below 7 m3/s, indicating a threshold response. Such sensitivity to environmental change portends severe impacts to regional bat populations if current scenarios for climate change in western North America are accurate. In addition, bats act as early-warning indicators of large-scale ecological effects resulting from further regional warming and drying trends currently at play in western North America.

  8. Light paired with serotonin mimics the effect of conditioning on phototactic behavior of Hermissenda.

    PubMed Central

    Crow, T; Forrester, J

    1986-01-01

    A conditioning procedure consisting of pairing-specific stimulation of the eyes and gravity-detecting statocysts in Hermissenda results in a long-term modification of normal positive phototactic behavior. The learning is expressed by a significant suppression of the initiation of locomotion in the presence of light. We now report that an analogue of the classical conditioning procedure, consisting of light paired with serotonin (5-HT) applied directly to the exposed circumesophageal nervous system of otherwise intact animals, mimics the effect of conditioning on long-term changes in phototactic behavior. The effect of the conditioning analogue on behavior shows some specificity with 5-HT since light paired with dopamine or octopamine does not significantly affect phototactic behavior. The conditioning analogue exhibits pairing specificity since unpaired light and 5-HT and 5-HT applied in the dark do not produce behavioral suppression. Animals that initially received unpaired light and 5-HT do show behavioral suppression after receiving paired light and 5-HT. These results indicate that light (the conditioned stimulus) paired with the putative transmitter of the unconditioned stimulus pathway (5-HT) is sufficient to produce long-term phototactic suppression. PMID:3464014

  9. A scale‐down mimic for mapping the process performance of centrifugation, depth and sterile filtration

    PubMed Central

    Joseph, Adrian; Kenty, Brian; Mollet, Michael; Hwang, Kenneth; Rose, Steven; Goldrick, Stephen; Bender, Jean; Farid, Suzanne S.

    2016-01-01

    ABSTRACT In the production of biopharmaceuticals disk‐stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot‐scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale‐down approach based upon the use of a shear device and a bench‐top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large‐scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited. Biotechnol. Bioeng. 2016;113: 1934–1941. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:26927621

  10. Generation of a functional liver tissue mimic using adipose stromal vascular fraction cell-derived vasculatures

    PubMed Central

    Nunes, S. S.; Maijub, J. G.; Krishnan, L.; Ramakrishnan, V. M.; Clayton, L. R.; Williams, S. K.; Hoying, J. B.; Boyd, N. L.

    2013-01-01

    One of the major challenges in cell implantation therapies is to promote integration of the microcirculation between the implanted cells and the host. We used adipose-derived stromal vascular fraction (SVF) cells to vascularize a human liver cell (HepG2) implant. We hypothesized that the SVF cells would form a functional microcirculation via vascular assembly and inosculation with the host vasculature. Initially, we assessed the extent and character of neovasculatures formed by freshly isolated and cultured SVF cells and found that freshly isolated cells have a higher vascularization potential. Generation of a 3D implant containing fresh SVF and HepG2 cells formed a tissue in which HepG2 cells were entwined with a network of microvessels. Implanted HepG2 cells sequestered labeled LDL delivered by systemic intravascular injection only in SVF-vascularized implants demonstrating that SVF cell-derived vasculatures can effectively integrate with host vessels and interface with parenchymal cells to form a functional tissue mimic. PMID:23828203

  11. Fabrication of Magnetically Actuated Polymeric Nanorod Arrays to Mimic Biological Cilia

    NASA Astrophysics Data System (ADS)

    Shields, A. R.; Evans, B. A.; Carroll, R. L.; Superfine, R.

    2006-11-01

    We report on successful fabrication of free-standing polymer nanorod arrays capable of actuation via externally applied magnetic fields. Our primary motivation is to mimic the ability of epithelial lung cilia to promote microscale fluid transport. Additionally, nanoscale actuator arrays of this nature have a wide variety of possible applications including microfluidics, sensing, and photonics. To fabricate these structures we utilize porous polycarbonate track-etched membranes as templates for a dispersion of a magnetic nanoparticle ferrofluid in polydimethylsiloxane (PDMS). Crosslinking of the polymer followed by subsequent dissolution of the membrane releases the rod array. With this method we have successfully fabricated rods with diameters down to 200 nanometers and lengths of 10-25 microns. Rods of various sizes have been successfully actuated with permanent magnets as well as an integrated magnetic force microscope that was developed in-house. We have demonstrated that actuation induces local fluid flow and are currently developing increased control over the array's actuation pattern to more closely resemble that of biological cilia.

  12. MD-simulations of Beta-Amyloid Protein Insertion Efficiency and Kinetics into Neuronal Membrane Mimics

    NASA Astrophysics Data System (ADS)

    Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

    2011-03-01

    Early interaction events of beta-amyloid (A β) peptides with the neuronal membranes play a key role in the pathogenesis of Alzheimer's disease. We have used all-atom MD simulations to study the protein insertion efficiency and kinetics of monomeric A β40 and A β42 into phosphatidylcholine lipid bilayers (PC) with and without 40 mole% cholesterol (CHOL) that mimic the cholesterol-enriched and depleted lipid nanodomains of the neuronal plasma membranes. Independent replicates of 200-ns simulations of each protein pre-inserted in the upper lipid layer were generated. In PC bilayers, only 25% of A β40 and 50% of A β42 in the replicates showed complete insertion into the lower lipid layer, whereas the percentages increased to 50% and 100%, respectively, in PC/CHOL bilayers, providing evidence that cholesterol improves the protein insertion efficiency into the bilayers. The rate of protein insertion was proportional to the hydrophobic, transmembrane helix length of the inserted peptide and depended on the cholesterol content. We propose that the lysine snorkeling and C-terminus anchoring of A β to the PC headgroups at the upper and lower lipid/water interfaces represent the dual-transmembrane stabilization mechanisms of A β in the neuronal membrane domains.

  13. Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics.

    PubMed

    deRonde, Brittany M; Birke, Alexander; Tew, Gregory N

    2015-02-01

    Cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) represent a class of molecules that facilitate the intracellular delivery of various cargo. Previous studies indicated that the presence of aromatic functionalities improved CPPM activity. Given that aromatic functionalities play prominent roles in membrane biology and participate in various π interactions, we explored whether these interactions could be optimized for improved CPPM activity. CPPMs were synthesized by ring-opening metathesis polymerization by using monomers that contained aromatic rings substituted with electron-donating and electron-withdrawing groups and covered an electrostatic potential range from -29.69 to +15.57 kcal mol(-1) . These groups altered the quadrupole moments of the aromatic systems and were used to test if such structural modifications changed CPPM activity. CPPMs were added to dye-loaded vesicles and the release of carboxyfluorescein was monitored as a function of polymer concentration. Changes in the effective polymer concentration to release 50% of the dye (effective concentration, EC50 ) were monitored. Results from this assay showed that the strength of the electron-donating and electron-withdrawing groups incorporated in the CPPMs did not alter polymer EC50 values or activity. This suggests that other design parameters may have a stronger impact on CPPM activity. In addition, these results indicate that a wide range of aromatic groups can be incorporated without negatively impacting polymer activity.

  14. Partly transparent young legume pods: Do they mimic caterpillars for defense and simultaneously enable better photosynthesis?

    PubMed

    Lev-Yadun, Simcha

    2015-01-01

    Being partly or fully transparent as a defense from predation is mostly known in various groups of aquatic animals and various terrestrial arthropods. Plants, being photosynthetic and having cell walls made of various polymers, cannot be wholly transparent. In spite of these inherent limitations, some succulent plant species of arid zones have partially transparent "windows" in order to perform photosynthesis in their below-ground leaves, as defense from herbivores as well as for protection from harsh environmental conditions. Similarly, transparent "windows" or even wholly transparent leaves are found in certain thick or thin, above-ground organs irrespective of aridity. The young pods of various wild annual Mediterranean legume species belonging to the genera Lathyrus, Pisum and Vicia are partly transparent and may therefore look like caterpillars when viewed with back illumination. I propose that this character serves 2 functions: (1) being a type of defensive caterpillar mimicry that may reduce their consumption by various herbivores in that very sensitive stage, and (2) simultaneously allowing better photosynthesis in the rapidly growing seeds and pods. Unlike animals that are transparent for either defensive or aggressive crypsis, in the case of young legume pods it allows them to visually mimic caterpillars for defense.

  15. Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics.

    PubMed

    Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna-Magdalena; Mahrhold, Stefan; Perry, Kay; Cheng, Luisa W; Rummel, Andreas; Jin, Rongsheng

    2015-12-01

    Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes for botulism. BoNT assembles with several auxiliary proteins to survive in the gastrointestinal tract and is subsequently transported through the intestinal epithelium into the general circulation. Several hemagglutinin proteins form a multi-protein complex (HA complex) that recognizes host glycans on the intestinal epithelial cell surface to facilitate BoNT absorption. Blocking carbohydrate binding to the HA complex could significantly inhibit the oral toxicity of BoNT. Here, we identify lactulose, a galactose-containing non-digestible sugar commonly used to treat constipation, as a prototype inhibitor against oral BoNT/A intoxication. As revealed by a crystal structure, lactulose binds to the HA complex at the same site where the host galactose-containing carbohydrate receptors bind. In vitro assays using intestinal Caco-2 cells demonstrated that lactulose inhibits HA from compromising the integrity of the epithelial cell monolayers and blocks the internalization of HA. Furthermore, co-administration of lactulose significantly protected mice against BoNT/A oral intoxication in vivo. Taken together, these data encourage the development of carbohydrate receptor mimics as a therapeutic intervention to prevent BoNT oral intoxication.

  16. Identification of Synthetic Host Defense Peptide Mimics That Exert Dual Antimicrobial and Anti-Inflammatory Activities

    PubMed Central

    Som, Abhigyan; Navasa, Nicolás; Percher, Avital; Scott, Richard W.

    2012-01-01

    A group of synthetic antimicrobial oligomers, inspired by naturally occurring antimicrobial peptides, were analyzed for the ability to modulate innate immune responses to Toll-like receptor (TLR) ligands. These synthetic mimics of antimicrobial peptides (SMAMPs) specifically reduced cytokine production in response to Staphylococcus aureus and the S. aureus component lipoteichoic acid (LTA), a TLR2 agonist. Anti-inflammatory SMAMPs prevented the induction of tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-10 in response to S. aureus or LTA, but no other TLR2 ligands. We show that these SMAMPs bind specifically to LTA in vitro and prevent its interaction with TLR2. Importantly, the SMAMP greatly reduced the induction of TNF and IL-6 in vivo in mice acutely infected with S. aureus while simultaneously reducing bacterial loads dramatically (4 log10). Thus, these SMAMPs can eliminate the damage induced by pathogen-associated molecular patterns (PAMPs) while simultaneously eliminating infection in vivo. They are the first known SMAMPs to demonstrate anti-inflammatory and antibacterial activities in vivo. PMID:22956655

  17. Worm Grunting, Fiddling, and Charming—Humans Unknowingly Mimic a Predator to Harvest Bait

    PubMed Central

    Catania, Kenneth C.

    2008-01-01

    Background For generations many families in and around Florida's Apalachicola National Forest have supported themselves by collecting the large endemic earthworms (Diplocardia mississippiensis). This is accomplished by vibrating a wooden stake driven into the soil, a practice called “worm grunting”. In response to the vibrations, worms emerge to the surface where thousands can be gathered in a few hours. Why do these earthworms suddenly exit their burrows in response to vibrations, exposing themselves to predation? Principal Findings Here it is shown that a population of eastern American moles (Scalopus aquaticus) inhabits the area where worms are collected and that earthworms have a pronounced escape response from moles consisting of rapidly exiting their burrows to flee across the soil surface. Recordings of vibrations generated by bait collectors and moles suggest that “worm grunters” unknowingly mimic digging moles. An alternative possibility, that worms interpret vibrations as rain and surface to avoid drowning is not supported. Conclusions Previous investigations have revealed that both wood turtles and herring gulls vibrate the ground to elicit earthworm escapes, indicating that a range of predators may exploit the predator-prey relationship between earthworms and moles. In addition to revealing a novel escape response that may be widespread among soil fauna, the results show that humans have played the role of “rare predators” in exploiting the consequences of a sensory arms race. PMID:18852902

  18. Trait anxiety mimics age-related cardiovascular autonomic modulation in young adults.

    PubMed

    Sanchez-Gonzalez, M A; Guzik, P; May, R W; Koutnik, A P; Hughes, R; Muniz, S; Kabbaj, M; Fincham, F D

    2015-04-01

    Anxiety produces maladaptive cardiovascular changes and accelerates biological aging. We evaluated cardiovascular reactivity in young and middle-aged individuals with varying anxiety scores to test the hypothesis that anxiety mimics cardiovascular aging by influencing cardiovascular autonomic modulation. The State-Trait Anxiety Inventory was used to classify healthy young individuals (20-29 years) into high (YHA, n=22;10 men) and low (YLA, n=21;10 men) anxiety, and to identify middle-aged individuals (50-60 years) with low anxiety (MLA, n=22;11 men). Heart rate, blood pressure (BP) and their variability (HRV and BPV, respectively) and baroreflex function were analyzed from beat-to-beat finger BP and electrocardiogram recordings collected during 5-min baseline, 6-min speech task (ST) and 3-min post ST recovery. Analyses of covariance showed significant differences (P<0.05) at baseline for HRV, BPV and barorelfex, and low-frequency power of systolic BP variability (LFSBP) was lower, whereas baroreflex and high frequency (HF) normalized units were higher in the YLA compared with YHA and MLA groups. Compared with YLA, YHA and MLA displayed attenuated vagal withdraw response (HF) to ST. BP and LFSBP responses to ST in YHA and MLA were higher compared with the YLA group. These findings suggest that anxiety could be linked to cardiovascular aging as it attenuates cardiac reactivity and exaggerates vascular responses to stress.

  19. A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration.

    PubMed

    Joseph, Adrian; Kenty, Brian; Mollet, Michael; Hwang, Kenneth; Rose, Steven; Goldrick, Stephen; Bender, Jean; Farid, Suzanne S; Titchener-Hooker, Nigel

    2016-09-01

    In the production of biopharmaceuticals disk-stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot-scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale-down approach based upon the use of a shear device and a bench-top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large-scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited. Biotechnol. Bioeng. 2016;113: 1934-1941. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:26927621

  20. High Speed Tomographic PIV Measurements of Copepod Sensitivity to a Suction-Feeding Predator Mimic

    NASA Astrophysics Data System (ADS)

    Yen, J.; Murphy, D. W.; Fan, L.; Skipper, A.; Webster, D. R.

    2013-11-01

    Copepods, which sense their fluid environment with long, setae-bearing antennules, often serve as prey to fish. The fluid disturbance created by fish feeding is a combination of a bow wave created by swimming towards the prey with an open mouth and a sudden, high speed flow into the fish's mouth created by suction. The sensitivity and reaction of copepods to the dynamic, high acceleration flow created by a suction feeding fish have not been well explored. In the present study, a suction feeding piscine predator mimic is developed and tested with copepods from a fish-containing (marine) environment (Calanus finmarchicus) and with copepods from a fish-less (alpine lake) environment (Hesperodiaptomus shoshone). Flow fields created by the impulsive siphon are measured with a high-speed tomographic particle image velocimetry (PIV) system. Escape success and kinematics of the two species are compared. Finally, using volumetric flow measurements, the hydrodynamic signal measured along each copepod's antennules at the time point of escape is compared between species.

  1. ELISA-mimic screen for synthetic polymer nanoparticles with high affinity to target proteins.

    PubMed

    Yonamine, Yusuke; Hoshino, Yu; Shea, Kenneth J

    2012-09-10

    Synthetic polymer nanoparticles (NPs) that display high affinity to protein targets have significant potential for medical and biotechnological applications as protein capture agents or functional replacements of antibodies ("plastic antibodies"). In this study, we modified an immunological assay (enzyme-linked immunosorbent assay: ELISA) into a high-throughput screening method to select nanoparticles with high affinity to target proteins. Histone and fibrinogen were chosen as target proteins to demonstrate this concept. The selection process utilized a biotinylated NP library constructed with combinations of functional monomers. The screen identified NPs with distinctive functional group compositions that exhibited high affinity to either histone or fibrinogen. The variation of protein affinity with changes in the nature and amount of functional groups in the NP provided chemical insight into the principle determinants of protein-NP binding. The NP affinity was semiquantified using the ELISA-mimic assay by varying the NP concentrations. The screening results were found to correlate with solution-based assay results. This screening system utilizing a biotinylated NP is a general approach to optimize functional monomer compositions and can be used to rapidly search for synthetic polymers with high (or low) affinity for target biological macromolecules. PMID:22813352

  2. Medical Textiles as Vascular Implants and Their Success to Mimic Natural Arteries.

    PubMed

    Singh, Charanpreet; Wong, Cynthia S; Wang, Xungai

    2015-06-30

    Vascular implants belong to a specialised class of medical textiles. The basic purpose of a vascular implant (graft and stent) is to act as an artificial conduit or substitute for a diseased artery. However, the long-term healing function depends on its ability to mimic the mechanical and biological behaviour of the artery. This requires a thorough understanding of the structure and function of an artery, which can then be translated into a synthetic structure based on the capabilities of the manufacturing method utilised. Common textile manufacturing techniques, such as weaving, knitting, braiding, and electrospinning, are frequently used to design vascular implants for research and commercial purposes for the past decades. However, the ability to match attributes of a vascular substitute to those of a native artery still remains a challenge. The synthetic implants have been found to cause disturbance in biological, biomechanical, and hemodynamic parameters at the implant site, which has been widely attributed to their structural design. In this work, we reviewed the design aspect of textile vascular implants and compared them to the structure of a natural artery as a basis for assessing the level of success as an implant. The outcome of this work is expected to encourage future design strategies for developing improved long lasting vascular implants.

  3. Colorectal cancer mimics: a review of the usual suspects with pathology correlation.

    PubMed

    Ganguly, Akash; Meredith, Sara; Probert, Cairine; Kraecevic, Jasna; Anosike, Chinedum

    2016-09-01

    Colorectal cancer is the third most commonly diagnosed cancer in men and second most commonly diagnosed cancer in women worldwide. Initial diagnosis of colorectal malignancy is generally made on colonoscopy, sigmoidoscopy or digital rectal examination; however, with increased use of CT as primary investigation in patients with lower gastrointestinal symptoms, the diagnosis of colon cancer is often first apparent to a radiologist prior to more invasive tests. CT can demonstrate a discrete soft-tissue mass that narrows the colonic lumen or focal nodular wall thickening/stricture and a variety of pericolonic changes. Pattern of wall thickening has been described as an aid to differential diagnosis; however, significant overlap remains between primary colonic tumor and non-colonic tumors or benign conditions. Imaging is non-specific, and appropriate clinical history, direct inspection, histological analysis, and sometimes discussion at MDT are essential for accurate diagnosis and treatment planning. In this article, we will review the imaging features of some of these benign and malignant mimics of colorectal cancer, with accompanying histology slides where appropriate. PMID:27178338

  4. Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides

    SciTech Connect

    Chongsiriwatana, Nathaniel P.; Patch, James A.; Czyzewski, Ann M.; Dohm, Michelle T.; Ivankin, Andrey; Gidalevitz, David; Zuckermann, Ronald N.; Barron, Annelise E.

    2008-04-02

    Antimicrobial peptides (AMPs) and their mimics are emerging as promising antibiotic agents. We present a library of 'ampetoids' (antimicrobial peptoid oligomers) with helical structures and biomimetic sequences, several members of which have low-micromolar antimicrobial activities, similar to cationic AMPs like pexiganan. Broad-spectrum activity against six clinically relevant BSL2 pathogens is also shown. This comprehensive structure-activity relationship study, including circular dichroism spectroscopy, minimum inhibitory concentration assays, hemolysis and mammalian cell toxicity studies, and specular x-ray reflectivity measurements shows that the in vitro activities of ampetoids are strikingly similar to those of AMPs themselves, suggesting a strong mechanistic analogy. The ampetoids' antibacterial activity, coupled with their low cytotoxicity against mammalian cells, make them a promising class of antimicrobials for biomedical applications. Peptoids are biostable, with a protease-resistant N-substituted glycine backbone, and their sequences are highly tunable, because an extensive diversity of side chains can be incorporated via facile solid-phase synthesis. Our findings add to the growing evidence that nonnatural foldamers will emerge as an important class of therapeutics.

  5. Modification of inflammatory response to implanted biomedical materials in vivo by surface bound superoxide dismutase mimics.

    PubMed

    Udipi, K; Ornberg, R L; Thurmond, K B; Settle, S L; Forster, D; Riley, D

    2000-09-15

    The healing response to implanted biomedical materials involves varying degrees and stages of inflammation and healing which in some cases leads to device failure. In this article, we describe synthetic methods and in vivo results of a novel surface treatment for biomedical materials involving covalent conjugation of a low molecular weight superoxide dismutase mimic (SODm), which imparts anti-inflammatory character to the material. SODm investigated in this study are a new class of anti-inflammatory drugs consisting of a Mn(II) complex of a macrocyclic polyamine ring that catalyze the dismutation of superoxide at rates equivalent to that of native enzyme. The SODms were covalently linked to small disks of ultra-high molecular weight polyethylene, poly(etherurethane urea), and tantalum metal at two concentrations and implanted in a subcutaneous rat implant model for 3, 7, 14, and 28 days. Histological examination of the implant tissue performed at 3 and 28 days revealed striking anti-inflammatory effects on both acute and chronic inflammatory responses. At 3 days, the formation of a neutrophil-rich acute inflammatory infiltrate seen in control implants was inhibited for all three materials treated with SODm. At 28 days, foreign body giant cell formation (number of FBGCs per field) and fibrous capsule formation (mean thickness of implant capsule) were also significantly inhibited over untreated control implants. A mechanism based on our current understanding of superoxide as an inflammatory mediator at implanted biomedical materials is proposed.

  6. A miniature mimic of host defense peptides with systemic antibacterial efficacy

    SciTech Connect

    Sarig, Hadar; Livne, Liran; Held-Kuznetsov, Victoria; Zaknoon, Fadia; Ivankin, Andrey; Gidalevitz, David; Mor, Amram

    2010-08-23

    Oligomers of acylated lysines (OAKs) are synthetic mimics of host defense peptides (HDPs) with promising antimicrobial properties. Here we challenged the OAK concept for its ability to generate both systemically efficient and economically viable lead compounds for fighting multidrug-resistant bacteria. We describe the design and characterization of a miniature OAK composed of only 3 lysyls and 2 acyls (designated C{sub 12({omega}7)}K-{beta}{sub 12}) that preferentially targets gram-positive species by a bacteriostatic mode of action. To gain insight into the mechanism of action, we examined the interaction of OAK with various potential targets, including phospholipid bilayers, using surface plasmon resonance, and Langmuir monolayers, using insertion assays, epifluorescence microscopy, and grazing incidence X-ray diffraction, in a complementary manner. Collectively, the data support the notion that C{sub 12({omega}7)}K-{beta}{sub 12} damages the plasma-membrane architecture similarly to HDPs, that is, following a near-classic 2-step interaction including high-affinity electrostatic adhesion and a subsequent shallow insertion that was limited to the phospholipid head group region. Notably, preliminary acute toxicity and efficacy studies performed with mouse models of infection have consolidated the potential of OAK for treating bacterial infections, including systemic treatments of methicillin-resistant Staphylococcus aureus. Such simple yet robust chemicals might be useful for various antibacterial applications while circumventing potential adverse effects associated with cytolytic compounds.

  7. Schwannoma in Sellar Region Mimics Invasive Pituitary Macroadenoma: Literature Review With One Case Report.

    PubMed

    Kong, Xiangyi; Wu, Huanwen; Ma, Wenbin; Li, Yongning; Yang, Yi; Xing, Bing; Wei, Junji; Yao, Yong; Gao, Jun; Lian, Wei; Xu, Zhiqin; Dou, Wanchen; Ren, Zuyuan; Su, Changbao; Wang, Renzhi

    2016-03-01

    In central nervous system, schwannomas, as ubiquitous tumors, mostly originate from sensory nerves like auditory and trigeminal nerves. However, intrasellar schwannomas are extremely rare. They are often misdiagnosed as pituitary adenomas. We report a rare case of schwannoma in the sellar region--a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological test. We represent a 65-year-old woman who had suffered from headaches, hypothyroidism, and visual disturbance. Her MRI revealed an abnormal sellar region mixed-signal mass lesion with suprasellar, left parasellar, and sellar floor invasiveness. We present detailed analysis of the patient's disease course and review relevant literatures. Written informed consent was obtained from the patient for publication of this article. A copy of the written consent is available for review by the editors of MEDICINE. Because this article does not involve any human or animal trials, there is no need to conduct special ethic review and the ethical approval is not necessary. When surgically treated, her specimen revealed a typical histopathology pattern of schwannoma. The patient's symptoms improved a lot after surgery and he continues to be under observation. Despite its rarity, intrasellar schwannoma should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas. PMID:26945398

  8. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice.

    PubMed

    Tai, Ningwen; Peng, Jian; Liu, Fuqiang; Gulden, Elke; Hu, Youjia; Zhang, Xiaojun; Chen, Li; Wong, F Susan; Wen, Li

    2016-09-19

    Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8(+) T cell-mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8(+) T cells can be regulated by innate immunity and the gut microbiota. PMID:27621416

  9. Mimics: a symbolic conflict/cooperation simulation program, with embedded protocol recording and automatic psychometric assessment.

    PubMed

    Aidman, Eugene V; Shmelyov, Alexander G

    2002-02-01

    This paper describes an interactive software environment designed as a social interaction simulator with embedded comprehensive recording and flexible assessment facilities. Using schematized visual sketches similar to cross-cultural facial universals (Ekman, 1999), Mimics (Shmelyov & Aidman, 1997) employs a computer-game-like scenario that requires the subject to identify with an avatar and navigate it through a playing field inhabited by hosts who display a range of facial expressions. From these expressions (which are highly consequential), the player has to anticipate the hosts' reactions to the avatar (which may vary from friendly to obstructing or aggressive) and choose between negotiating with a host (by altering the avatar's facial expression), attacking it, or searching for an escape route. Comprehensive recording of player moves and interactions has enabled computation of several finegrained indices of interactive behavior, such as aggressive response styles, efficiency, and motivation in conflict/cooperation contexts. Initial validation data and potential applications of the method in the assessment of personality and social behavior are discussed.

  10. Ouabain Mimics Low Temperature Rescue of F508del-CFTR in Cystic Fibrosis Epithelial Cells

    PubMed Central

    Zhang, Donglei; Ciciriello, Fabiana; Anjos, Suzana M.; Carissimo, Annamaria; Liao, Jie; Carlile, Graeme W.; Balghi, Haouaria; Robert, Renaud; Luini, Alberto; Hanrahan, John W.; Thomas, David Y.

    2012-01-01

    Most cases of cystic fibrosis (CF) are caused by the deletion of a single phenylalanine residue at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR). The mutant F508del-CFTR is retained in the endoplasmic reticulum and degraded, but can be induced by low temperature incubation (29°C) to traffic to the plasma membrane where it functions as a chloride channel. Here we show that, cardiac glycosides, at nanomolar concentrations, can partially correct the trafficking of F508del-CFTR in human CF bronchial epithelial cells (CFBE41o-) and in an F508del-CFTR mouse model. Comparison of the transcriptional profiles obtained with polarized CFBE41o-cells after treatment with ouabain and by low temperature has revealed a striking similarity between the two corrector treatments that is not shared with other correctors. In summary, our study shows a novel function of ouabain and its analogs in the regulation of F508del-CFTR trafficking and suggests that compounds that mimic this low temperature correction of trafficking will provide new avenues for the development of therapeutics for CF. PMID:23060796

  11. Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression.

    PubMed

    Michalovicz, Lindsay T; Konat, Gregory W

    2014-03-01

    We have previously shown that peripherally restricted acute phase response (APR) elicited by intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to excitotoxic insult as seen from profoundly exacerbated kainic acid (KA)-induced seizures. In the present study, we found that this hypersusceptibility was protracted for up to 72 h. RT-PCR profiling of hippocampal gene expression revealed rapid upregulation of 23 genes encoding cytokines, chemokines and chemokine receptors generally within 6 h after PIC challenge. The expression of most of these genes decreased by 24 h. However, two chemokine genes, i.e., Ccl19 and Cxcl13 genes, as well as two chemokine receptor genes, Ccr1 and Ccr7, remained upregulated for 72 h suggesting their possible involvement in the induction and sustenance of seizure hypersusceptibility. Also, 12 genes encoding proteins related to glutamatergic and GABAergic neurotransmission featured initial upregulation or downregulation followed by gradual normalization. The upregulation of the Gabrr3 gene remained upregulated at 72 h, congruent with its plausible role in the hypersusceptible phenotype. Moreover, the expression of ten microRNAs (miRs) was rapidly affected by PIC challenge, but their levels generally exhibited oscillating profiles over the time course of seizure hypersusceptibility. These results indicate that protracted seizure susceptibility following peripheral APR is associated with a robust polygenic response in the hippocampus. PMID:24363211

  12. Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties

    PubMed Central

    Ghosh, Kaustabh; Pan, Zhi; Guan, E; Ge, Shouren; Liu, Yajie; Nakamura, Toshio; Ren, Xiang-Dong; Rafailovich, Miriam; Clark, Richard A.F.

    2009-01-01

    To successfully induce tissue repair or regeneration in vivo, bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different but concurrent signaling mechanisms: ligation-induced signaling, which depends on ECM biological stimuli, and traction-induced signaling, which depends on ECM mechanical stimuli. In this report, we provide a fundamental understanding of how alterations in mechanical stimuli alone, produced by varying the viscoelastic properties of our bioengineered construct, modulate phenotypic behavior at the whole-cell level. Using a physiologically-relevant ECM mimic composed of hyaluronan and fibronectin, we found that adult human dermal fibroblasts modify their mechanical response in order to match substrate stiffness. More specifically, the cells on stiffer substrates had higher modulus and a more stretched and organized actin cytoskeleton (and vice versa), which translated into larger traction forces exerted on the substrate. This modulation of cellular mechanics had contrasting effects on migration and proliferation, where cells migrated faster on softer substrates while proliferating preferentially on the stiffer ones. These findings implicate substrate rigidity as a critical design parameter in the development of bioengineered constructs aimed at eliciting maximal cell and tissue function. PMID:17049594

  13. Designing Reliable Cohorts of Cardiac Patients across MIMIC and eICU

    PubMed Central

    Chronaki, Catherine; Shahin, Abdullah; Mark, Roger

    2016-01-01

    The design of the patient cohort is an essential and fundamental part of any clinical patient study. Knowledge of the Electronic Health Records, underlying Database Management System, and the relevant clinical workflows are central to an effective cohort design. However, with technical, semantic, and organizational interoperability limitations, the database queries associated with a patient cohort may need to be reconfigured in every participating site. i2b2 and SHRINE advance the notion of patient cohorts as first class objects to be shared, aggregated, and recruited for research purposes across clinical sites. This paper reports on initial efforts to assess the integration of Medical Information Mart for Intensive Care (MIMIC) and Philips eICU, two large-scale anonymized intensive care unit (ICU) databases, using standard terminologies, i.e. LOINC, ICD9-CM and SNOMED-CT. Focus of this work is lab and microbiology observations and key demographics for patients with a primary cardiovascular ICD9-CM diagnosis. Results and discussion reflecting on reference core terminology standards, offer insights on efforts to combine detailed intensive care data from multiple ICUs worldwide.

  14. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation.

    PubMed

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S; Maclean, Fiona; Oto, Aytekin

    2016-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. Online supplemental material is available for this article.

  15. Fine mapping of the lesion mimic and early senescence 1 (lmes1) in rice (Oryza sativa).

    PubMed

    Li, Zhi; Zhang, Yingxin; Liu, Lin; Liu, Qunen; Bi, Zhenzhen; Yu, Ning; Cheng, Shihua; Cao, Liyong

    2014-07-01

    A novel rice mutant, lesion mimic and early senescence 1 (lmes1), was induced from the rice 93-11 cultivar in a γ-ray field. This mutant exhibited spontaneous disease-like lesions in the absence of pathogen attack at the beginning of the tillering stage. Moreover, at the booting stage, lmes1 mutants exhibited a significantly increased MDA but decreased chlorophyll content, soluble protein content and photosynthetic rate in the leaves, which are indicative of an early senescence phenotype. The lmes1 mutant was significantly more resistant than 93-11 against rice bacterial blight infection, which was consistent with a marked increase in the expression of three resistance-related genes. Here, we employed a map-based cloning approach to finely map the lmes1 gene. In an initial mapping with 94 F2 individuals derived from a cross between the lmes1 mutant and Nipponbare, the lmes1 gene was located in a 10.6-cM region on the telomere of the long arm of chromosome 7 using simple sequence repeat (SSR) markers. To finely map lmes1, we derived two F2 populations with 940 individuals from two crosses between the lmes1 mutant and two japonica rice varieties, Nipponbare and 02428. Finally, the lmes1 gene was mapped to an 88-kb region between two newly developed inDel markers, Zl-3 and Zl-22, which harbored 15 ORFs.

  16. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity

    NASA Astrophysics Data System (ADS)

    Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei; Eisenberg, David; Nowick, James S.

    2012-11-01

    The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

  17. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.

    PubMed

    Brandhorst, Sebastian; Choi, In Young; Wei, Min; Cheng, Chia Wei; Sedrakyan, Sargis; Navarrete, Gerardo; Dubeau, Louis; Yap, Li Peng; Park, Ryan; Vinciguerra, Manlio; Di Biase, Stefano; Mirzaei, Hamed; Mirisola, Mario G; Childress, Patra; Ji, Lingyun; Groshen, Susan; Penna, Fabio; Odetti, Patrizio; Perin, Laura; Conti, Peter S; Ikeno, Yuji; Kennedy, Brian K; Cohen, Pinchas; Morgan, Todd E; Dorff, Tanya B; Longo, Valter D

    2015-07-01

    Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan. PMID:26094889

  18. Partly transparent young legume pods: Do they mimic caterpillars for defense and simultaneously enable better photosynthesis?

    PubMed

    Lev-Yadun, Simcha

    2015-01-01

    Being partly or fully transparent as a defense from predation is mostly known in various groups of aquatic animals and various terrestrial arthropods. Plants, being photosynthetic and having cell walls made of various polymers, cannot be wholly transparent. In spite of these inherent limitations, some succulent plant species of arid zones have partially transparent "windows" in order to perform photosynthesis in their below-ground leaves, as defense from herbivores as well as for protection from harsh environmental conditions. Similarly, transparent "windows" or even wholly transparent leaves are found in certain thick or thin, above-ground organs irrespective of aridity. The young pods of various wild annual Mediterranean legume species belonging to the genera Lathyrus, Pisum and Vicia are partly transparent and may therefore look like caterpillars when viewed with back illumination. I propose that this character serves 2 functions: (1) being a type of defensive caterpillar mimicry that may reduce their consumption by various herbivores in that very sensitive stage, and (2) simultaneously allowing better photosynthesis in the rapidly growing seeds and pods. Unlike animals that are transparent for either defensive or aggressive crypsis, in the case of young legume pods it allows them to visually mimic caterpillars for defense. PMID:26633565

  19. The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag.

    PubMed

    Szabó, Eszter C; Manguinhas, Rita; Fonseca, Rosalina

    2016-01-01

    Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture. PMID:27650071

  20. A mimic study on effects of fluoride on tooth enamel structures

    NASA Astrophysics Data System (ADS)

    Ma, Guobin; Wang, Mu; Liu, Xiang Yang

    2010-03-01

    Tooth enamel is the hardest tissue in human body, and this superior mechanical property is contributed by its unique microstructures, i.e., oriented growth of rod-like apatite crystals into basic structural units called the prisms Fluoride (F^-) has been recognized to have significant effects on the physical and chemical properties of tooth enamel. However, the role of F^- on microstructures of apatite crystals is not well understood yet. Here we report a detailed investigation on the topic. Mimic in vitro growth of tooth enamel structures is performed at the biophysical conditions in simulated body fluids, using belt-like hydroxyapatite crystals as substrates It shows that F^- on the order of 0.1 mM will dramatically change the morphology of the grown crystals from irregular slabs to nano-needles, and the needles are aligned along the substrate with an average misorientation of ˜12 . Branched growth of bundles of nano-needles occurs with further increase of F^-, and finally, growth of highly porous structures as well as microspheres takes place when the F^- concentration exceeds 5 mM. In comparison with real tooth enamel structures, the relationship between enamel microstructures and tooth caries as well as fluorosis is discussed.

  1. Generation of a human anti-idiotypic antibody that mimics the GD2 antigen.

    PubMed

    Saleh, M N; Stapleton, J D; Khazaeli, M B; LoBuglio, A F

    1993-09-15

    In a phase 1 trial, patients with metastatic melanoma received the anti-GD2 murine mAb 14G2a. All patients developed human anti-14G2a antibodies including anti-Id antibodies. Peripheral blood MNCs from one such patient were fused with the murine myeloma cell line Ag8. Four human anti-14G2a secreting hybridomas were generated and the mAb product of one of the hybridomas was characterized. The human mAb 4B5 (hu-IgG, lambda) binds to the variable region of murine 14G2a (anti-Id). The 4B5 binds to the antigen-combining site of 14G2a and inhibits its binding to GD2 expressing Mel-21 cells. Rabbits were immunized with the human anti-Id 4B5. Sera from the immunized rabbits demonstrated anti-4B5 antibodies and anti-Mel-21 and anti-GD2 reactivity. Furthermore, rabbit sera competitively inhibited binding of 14G2a to Mel-21 cells. Rabbits immunized with 4B5 developed a DTH response when challenged with 4B5 antibody and Mel-21 cells. These studies demonstrate that the human anti-Id 4B5 mimics the GD2 antigen and is capable of eliciting both a humoral and cellular anti-GD2 immune response. This antibody could be potentially used as a human anti-Id vaccine in patients with malignant melanoma. PMID:8376782

  2. The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag.

    PubMed

    Szabó, Eszter C; Manguinhas, Rita; Fonseca, Rosalina

    2016-09-21

    Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture.

  3. Flow pattern visualization in a mimic anaerobic digester: experimental and computational studies.

    PubMed

    Vesvikar, M S; Varma, R; Karim, K; Al-Dahhan, M

    2005-01-01

    Advanced non-invasive experiments like computer automated radioactive particle tracking and computed tomography along with computational fluid dynamics (CFD) simulations were performed in mimic anaerobic digesters to visualize their flow pattern and obtain hydrodynamic parameters. The mixing in the digester was provided by sparging gas at three different flow rates. The simulation results in terms of overall flow pattern, location of circulation cells and stagnant regions, trends of liquid velocity profiles, and volume of dead zones agree reasonably well with the experimental data. CFD simulations were also performed on different digester configurations. The effects of changing draft tube size, clearance, and shape of the tank bottoms were calculated to evaluate the effect of digester design on its flow pattern. Changing the draft tube clearance and height had no influence on the flow pattern or dead regions volume. However increasing the draft tube diameter or incorporating a conical bottom design helped in reducing the volume of the dead zones as compared to a flat bottom digester. The simulations showed that the gas flow rate sparged by a single point (0.5 cm diameter) sparger does not have appreciable effect on the flow pattern of the digesters. PMID:16180475

  4. Defining the loop structures in proteins based on composite β-turn mimics.

    PubMed

    Dhar, Jesmita; Chakrabarti, Pinak

    2015-06-01

    Asx- and ω-turns are β-turn mimics, which replace the conventional main-chain hydrogen bonds seen in the latter by those involving the side chains, and both involve three residues. In this paper we analyzed the cases where these turns occur together--side by side, with or without any gap, overlapping and in any order. These composite turns (of length 3-15 residues), occurring at ∼1 per 100 residues, may constitute the full length of many loops, and when the residues in the two component turns overlap or are adjacent to each other, the composite may take well-defined shape. It is thus possible for non-regular regions in protein structure to form local structural motifs, akin to the regular geometrical features exhibited by secondary structures. Composites having the order ω-turns followed by Asx-turns can constitute N-terminal helix capping motif. Ternary composite turns (made up of ω-, Asx- and ST-turns), some with characteristic shape, have also been identified. Delineation of composite turns would help in characterizing loops in protein structures, which often have functional roles. Some sequence patterns seen in composites can be used for their incorporation in protein design.

  5. Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering.

    PubMed

    Won, Jong-Eun; Yun, Ye-Rang; Jang, Jun-Hyeog; Yang, Sung-Hee; Kim, Joong-Hyun; Chrzanowski, Wojciech; Wall, Ivan B; Knowles, Jonathan C; Kim, Hae-Won

    2015-07-01

    Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

  6. Continuous self-assembly of organic-inorganic nanocomposite coatings that mimic nacre

    NASA Astrophysics Data System (ADS)

    Sellinger, Alan; Weiss, Pilar M.; Nguyen, Anh; Lu, Yunfeng; Assink, Roger A.; Gong, Weiliang; Brinker, C. Jeffrey

    1998-07-01

    Nanocomposite materials are widespread in biological systems. Perhaps the most studied is the nacre of abalone shell, an orientated coating composed of alternating layers of aragonite (CaCO3) and a biopolymer. Its laminated structure simultaneously provides strength, hardness and toughness: containing about 1vol.% polymer, nacre is twice as hard and 1,000 times as tough as its constituent phases. Such remarkable properties have inspired chemists and materials scientists to develop synthetic, `biomimetic' nanocomposite assemblies. Nonetheless, the efficient processing of layered organic-inorganic composites remains an elusive goal. Here we report a rapid, efficient self-assembly process for preparing nanolaminated coatings that mimic the structure of nacre. Beginning with a solution of silica, surfactant and organic monomers, we rely on evaporation during dip-coating to induce the formation of micelles and partitioning of the organic constituents into the micellar interiors. Subsequent self-assembly of the silica-surfactant-monomer micellar species into lyotropic mesophases simultaneously organizes the organic and inorganic precursors into the desired nanolaminated form. Polymerization fixes this structure, completing the nanocomposite assembly process. This approach may be generalized both to other composite architectures and to other materials combinations.

  7. The Design of In Vitro Liver Sinusoid Mimics Using Chitosan–Hyaluronic Acid Polyelectrolyte Multilayers

    PubMed Central

    Kim, Yeonhee; Larkin, Adam L.; Davis, Richey M.

    2010-01-01

    Interactions between hepatocytes and liver sinusoidal endothelial cells (LSECs) are essential for the development and maintenance of hepatic phenotypic functions. We report the assembly of three-dimensional liver sinusoidal mimics comprised of primary rat hepatocytes, LSECs, and an intermediate chitosan–hyaluronic acid polyelectrolyte multilayer (PEM). The height of the PEMs ranged from 30 to 55 nm and exhibited a shear modulus of ∼100 kPa. Hepatocyte–PEM cellular constructs exhibited stable urea and albumin production over a 7-day period, and these values were either higher or similar to cells cultured in a collagen sandwich. This is of significance because the thickness of a collagen gel is ∼1000-fold higher than the height of the chitosan–hyaluronic acid PEM. In the hepatocyte–PEM–LSEC liver-mimetic cellular constructs, LSEC phenotype was maintained, and these cultures exhibited stable urea and albumin production. CYP1A1/2 activity measured over a 7-day period was significantly higher in the hepatocyte–PEM–LSEC constructs than in collagen sandwich cultures. A 16-fold increase in CYP1A1/2 activity was observed for hepatocyte–PEM–10,000 LSEC samples, thereby suggesting that interactions between hepatocytes and LSECs are critical in enhancing the detoxification capability in hepatic cultures in vitro. PMID:20491586

  8. An Ultrasensitive, Selective, Multiplexed Superbioelectronic Nose That Mimics the Human Sense of Smell.

    PubMed

    Kwon, Oh Seok; Song, Hyun Seok; Park, Seon Joo; Lee, Seung Hwan; An, Ji Hyun; Park, Jin Wook; Yang, Heehong; Yoon, Hyeonseok; Bae, Joonwon; Park, Tai Hyun; Jang, Jyongsik

    2015-10-14

    Human sensory-mimicking systems, such as electronic brains, tongues, skin, and ears, have been promoted for use in improving social welfare. However, no significant achievements have been made in mimicking the human nose due to the complexity of olfactory sensory neurons. Combinational coding of human olfactory receptors (hORs) is essential for odorant discrimination in mixtures, and the development of hOR-combined multiplexed systems has progressed slowly. Here, we report the first demonstration of an artificial multiplexed superbioelectronic nose (MSB-nose) that mimics the human olfactory sensory system, leading to high-performance odorant discriminatory ability in mixtures. Specifically, portable MSB-noses were constructed using highly uniform graphene micropatterns (GMs) that were conjugated with two different hORs, which were employed as transducers in a liquid-ion gated field-effect transistor (FET). Field-induced signals from the MSB-nose were monitored and provided high sensitivity and selectivity toward target odorants (minimum detectable level: 0.1 fM). More importantly, the potential of the MSB-nose as a tool to encode hOR combinations was demonstrated using principal component analysis.

  9. Medical Textiles as Vascular Implants and Their Success to Mimic Natural Arteries

    PubMed Central

    Singh, Charanpreet; Wong, Cynthia S.; Wang, Xungai

    2015-01-01

    Vascular implants belong to a specialised class of medical textiles. The basic purpose of a vascular implant (graft and stent) is to act as an artificial conduit or substitute for a diseased artery. However, the long-term healing function depends on its ability to mimic the mechanical and biological behaviour of the artery. This requires a thorough understanding of the structure and function of an artery, which can then be translated into a synthetic structure based on the capabilities of the manufacturing method utilised. Common textile manufacturing techniques, such as weaving, knitting, braiding, and electrospinning, are frequently used to design vascular implants for research and commercial purposes for the past decades. However, the ability to match attributes of a vascular substitute to those of a native artery still remains a challenge. The synthetic implants have been found to cause disturbance in biological, biomechanical, and hemodynamic parameters at the implant site, which has been widely attributed to their structural design. In this work, we reviewed the design aspect of textile vascular implants and compared them to the structure of a natural artery as a basis for assessing the level of success as an implant. The outcome of this work is expected to encourage future design strategies for developing improved long lasting vascular implants. PMID:26133386

  10. Functionalized hybrid nanofibers to mimic native ECM for tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Karuppuswamy, Priyadharsini; Venugopal, Jayarama Reddy; Navaneethan, Balchandar; Laiva, Ashang Luwang; Sridhar, Sreepathy; Ramakrishna, Seeram

    2014-12-01

    Nanotechnology being one of the most promising technologies today shows an extremely huge potential in the field of tissue engineering to mimic the porous topography of natural extracellular matrix (ECM). Natural polymers are incorporated into the synthetic polymers to fabricate functionalized hybrid nanofibrous scaffolds, which improve cell and tissue compatibility. The present study identified the biopolymers - aloe vera, silk fibroin and curcumin incorporated into polycaprolactone (PCL) as suitable substrates for tissue engineering. Different combinations of PCL with natural polymers - PCL/aloe vera, PCL/silk fibroin, PCL/aloe vera/silk fibroin, PCL/aloe vera/silk fibroin/curcumin were electrospun into nanofibrous scaffolds. The fabricated two dimensional nanofibrous scaffolds showed high surface area, appropriate mechanical properties, hydrophilicity and porosity, required for the regeneration of diseased tissues. The nanofibrous scaffolds were characterized by Scanning electron microscope (SEM), porometry, Instron tensile tester, VCA optima contact angle measurement and FTIR to analyze the fiber diameter and morphology, porosity and pore size distribution, mechanical strength, wettability, chemical bonds and functional groups, respectively. The average fiber diameter of obtained fibers ranged from 250 nm to 350 nm and the tensile strength of PCL scaffolds at 4.49 MPa increased upto 8.3 MPa for PCL/silk fibroin scaffolds. Hydrophobicity of PCL decreased with the incorporation of natural polymers, especially for PCL/aloe vera scaffolds. The properties of as-spun nanofiber scaffolds showed their potential as promising scaffold materials in tissue engineering applications.

  11. Structure of a TCR-Mimic Antibody with Target Predicts Pharmacogenetics.

    PubMed

    Ataie, Niloufar; Xiang, Jingyi; Cheng, Neal; Brea, Elliott J; Lu, Wenjie; Scheinberg, David A; Liu, Cheng; Ng, Ho Leung

    2016-01-16

    Antibody therapies currently target only extracellular antigens. A strategy to recognize intracellular antigens is to target peptides presented by immune HLA receptors. ESK1 is a human, T-cell receptor (TCR)-mimic antibody that binds with subnanomolar affinity to the RMF peptide from the intracellular Wilms tumor oncoprotein WT1 in complex with HLA-A*02:01. ESK1 is therapeutically effective in mouse models of WT1(+) human cancers. TCR-based therapies have been presumed to be restricted to one HLA subtype. The mechanism for the specificity and high affinity of ESK1 is unknown. We show in a crystal structure that ESK1 Fab binds to RMF/HLA-A*02:01 in a mode different from that of TCRs. From the structure, we predict and then experimentally confirm high-affinity binding with multiple other HLA-A*02 subtypes, broadening the potential patient pool for ESK1 therapy. Using the crystal structure, we also predict potential off-target binding that we experimentally confirm. Our results demonstrate how protein structure information can contribute to personalized immunotherapy. PMID:26688548

  12. [Search of Neurotrophin-mimic Natural Products for Prevention and Treatment of Neurodegenerative Disease].

    PubMed

    Kubo, Miwa

    2015-01-01

    As part of our continuing studies on neurotrophin-mimic active compounds in natural products, we investigated the chemical constituents of the pericarps of Illicium jiadifengpi and the roots of Indonesian ginger Zingiber purpureum, resulting in the isolation of new seco-prezizaane-type sesquiterpenoid 1 and phenylbutenoid dimer 3-4 and two new curcuminoids 5-6. The MeOH extract of I. jiadifengpi was fractionated, leading to the isolation of compound 1. Compound 1 significantly enhanced neurite outgrowth in primary cell cultures of fetal rat cortical neurons. It is noteworthy that compound 1 has potential significantly to promote differentiation of multipotent neural stem cell line (MEB5 cells) into neurons. Additionally, we investigated the MeOH extract of the root of Bangle (Z. purpureum) that exhibited neuritogenesis activity in PC12 cells at 25 μg/mL, resulting in the isolation of neurotrophic phenylbutenoid dimers 3-4 and new compounds 5-6. Compounds 3 and 4 were found not only significantly to induce neurite sprouting of PC12 cells but also to increase the neurite length and number of neurites in primary cultured rat cortical neurons, and also showed protective activity against cell death caused by deprivation of serum. Furthermore, chronic treatment with these compounds enhanced hippocampal neurogenesis in dementia model olfactory bulbectomized (OBX) mice. Compounds 5 and 6 had significant NGF-potentiating effects on PC12 cells whereas compound 5 enhanced prevention of amyloid β (Aβ) 42 aggregation.

  13. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.

    PubMed

    Boutant, Marie; Kulkarni, Sameer S; Joffraud, Magali; Raymond, Frédéric; Métairon, Sylviane; Descombes, Patrick; Cantó, Carles

    2016-03-01

    Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different. PMID:26923584

  14. Partly transparent young legume pods: Do they mimic caterpillars for defense and simultaneously enable better photosynthesis?

    PubMed Central

    Lev-Yadun, Simcha

    2015-01-01

    Being partly or fully transparent as a defense from predation is mostly known in various groups of aquatic animals and various terrestrial arthropods. Plants, being photosynthetic and having cell walls made of various polymers, cannot be wholly transparent. In spite of these inherent limitations, some succulent plant species of arid zones have partially transparent “windows” in order to perform photosynthesis in their below-ground leaves, as defense from herbivores as well as for protection from harsh environmental conditions. Similarly, transparent “windows” or even wholly transparent leaves are found in certain thick or thin, above-ground organs irrespective of aridity. The young pods of various wild annual Mediterranean legume species belonging to the genera Lathyrus, Pisum and Vicia are partly transparent and may therefore look like caterpillars when viewed with back illumination. I propose that this character serves 2 functions: (1) being a type of defensive caterpillar mimicry that may reduce their consumption by various herbivores in that very sensitive stage, and (2) simultaneously allowing better photosynthesis in the rapidly growing seeds and pods. Unlike animals that are transparent for either defensive or aggressive crypsis, in the case of young legume pods it allows them to visually mimic caterpillars for defense. PMID:26633565

  15. Orchid mimics honey bee alarm pheromone in order to attract hornets for pollination.

    PubMed

    Brodmann, Jennifer; Twele, Robert; Francke, Wittko; Yi-bo, Luo; Xi-qiang, Song; Ayasse, Manfred

    2009-08-25

    Approximately one-third of the world's estimated 30,000 orchid species are deceptive and do not reward their pollinators with nectar or pollen. Most of these deceptive orchids imitate the scent of rewarding flowers or potential mates. In this study, we investigated the floral scent involved in pollinator attraction to the rewardless orchid Dendrobium sinense, a species endemic to the Chinese island Hainan that is pollinated by the hornet Vespa bicolor. Via chemical analyses and electrophysiological methods, we demonstrate that the flowers of D. sinense produce (Z)-11-eicosen-1-ol and that the pollinator can smell this compound. This is a major compound in the alarm pheromones of both Asian (Apis cerana) and European (Apis mellifera) honey bees and is also exploited by the European beewolf (Philanthus triangulum) to locate its prey. This is the first time that (Z)-11-eicosen-1-ol has been identified as a floral volatile. In behavioral experiments, we demonstrate that the floral scent of D. sinense and synthetic (Z)-11-eicosen-1-ol are both attractive to hornets. Because hornets frequently capture honey bees to feed to their larvae, we suggest that the flowers of D. sinense mimic the alarm pheromone of honey bees in order to attract prey-hunting hornets for pollination.

  16. Macroscopic Properties of Restacked, Redox-Liquid Exfoliated Graphite and Graphite Mimics Produced in Bulk Quantities

    SciTech Connect

    Srivastava, Vikram K; Quinlan, Ronald; Agapov, Alexander L; Dunlap, John R; Nelson, Kimberly M; Duranty, Edward R; Sokolov, Alexei P; Bhat, Gajanan; Mays, Jimmy

    2014-01-01

    The excellent properties exhibited by monolayer graphene have spurred the development of exfoliation techniques using bulk graphite to produce large quantities of pristine monolayer sheets. Development of simple chemistry to exfoliate and intercalate graphite and graphite mimics in large quantities is required for numerous applications. To determine the macroscopic behavior of restacked, exfoliated bulk materials, a systematic approach is presented using a simple, redox-liquid sonication process along to obtain large quantities of 2D and 3D hexagonally layered graphite, molybdenum disulfi de, and boron nitride, which are subsequently characterized to observe chemical and structural changes. For MoS 2 sonicated with the antioxidant sodium bisulfi te, results from Raman spectroscopy, X-ray diffraction, and electron microscopy indicate the presence of distorted phases from different polymorphs, and apparent nanotube structures in the bulk, restacked powder. Furthermore, using thermograviemtric analysis, the antioxidant enhances the resistance to oxidative degradation of MoS 2 , upon thermal treatment up to 900 C. The addition of the ionic antioxidant decreased dispersion stability in non-polar solvent, suggesting decreased compatibility with non-polar systems. Using simple chemical methods, the ability to generate tailored multidimensional layered materials with unique macroscopic properties is critical for numerous applications, including electrical devices, reinforced polymer composites, lithium ion capacitors, and chemical sensing.

  17. Detection of influenza virus using peroxidase-mimic of gold nanoparticles.

    PubMed

    Ahmed, Syed Rahin; Kim, Jeonghyo; Suzuki, Tetsuro; Lee, Jaebeom; Park, Enoch Y

    2016-10-01

    A modified enzyme-linked immunosorbent assay (ELISA) with nanomaterials is an effective and powerful method to amplify the signal and reduce the cost of detecting and measuring trace biomarkers or proteins. In this study, an ultra-sensitive colorimetric immunoassay was designed, and its ability to detect influenza viruses using positively charged gold nanoparticles ((+)Au NPs) was assessed as a possible role for peroxidase-mimic inorganic enzymes. This method detected influenza virus A (H1N1) with a linear range up to 10 pg mL(-1) and clinically isolated influenza virus A (H3N2) up to 10 plaque forming units (PFU) mL(-1) , where its sensitivity improved to 500-fold higher than that of commercial virus kits. The sensitivity of this proposed method was not declined even though in complex biological media in compared to conventional ELISA. These results revealed that the (+)AuNP-based colorimetric immunoassay could be suitable for lab-on-a-chip device and open new opportunities for clinical protein diagnostics. Biotechnol. Bioeng. 2016;113: 2298-2303. © 2016 Wiley Periodicals, Inc.

  18. A new buildup biofilm model that mimics accumulation of material in flexible endoscope channels.

    PubMed

    da Costa Luciano, Cristiana; Olson, Nancy; DeGagne, Patricia; Franca, Rodrigo; Tipple, Anaclara Ferreira Veiga; Alfa, Michelle

    2016-08-01

    The objective of this study was to develop a new build up biofilm (BBF) model that was based on repeated exposure to test soil containing Enterococcus faecalis and Pseudomonas aeruginosa and repeated rounds of fixation to mimic the accumulation of patient material in endoscope channels during reprocessing. The new BBF model is a novel adaptation of the minimum biofilm effective concentration (MBEC) 96-well model where biofilm is formed on plastic pegs. The new MBEC-BBF model was developed over eight days and included four rounds of partial fixation using glutaraldehyde. There was 6.14Log10cfu/cm(2) of E. faecalis and 7.71Log10cfu/cm(2) of P. aeruginosa in the final BBF. Four detergents (two enzymatic and two non-enzymatic) were tested alone or in combination with orthophthalaldehyde, glutaraldehyde or accelerated hydrogen peroxide to determine if BBF could be either removed or the bacteria within the BBF killed. None of the detergents alone could remove the biofilm or reduce the bacterial level in the BBF as determined by viable count and scanning electron microscopy. The combination of detergents and disinfectants tested provided a 3 to 5Log10 reduction in viable bacteria but no combination could provide the expected 6Log10 reduction. Our data indicated that once formed BBF was extremely difficult to eliminate. Future research using the BBF model may help develop new cleaning and disinfection methods that can prevent or eliminate BBF within endoscope channels. PMID:27345713

  19. Can f(T) gravity theories mimic ΛCDM cosmic history

    SciTech Connect

    Setare, M.R.; Mohammadipour, N. E-mail: N.Mohammadipour@uok.ac.ir

    2013-01-01

    Recently the teleparallel Lagrangian density described by the torsion scalar T has been extended to a function of T. The f(T) modified teleparallel gravity has been proposed as the natural gravitational alternative for dark energy to explain the late time acceleration of the universe. In order to reconstruct the function f(T) by demanding a background ΛCDM cosmology we assume that, (i) the background cosmic history provided by the flat ΛCDM (the radiation ere with ω{sub eff} = (1/3), matter and de Sitter eras with ω{sub eff} = 0 and ω{sub eff} = −1, respectively) (ii) the radiation dominate in the radiation era with Ω{sub 0r} = 1 and the matter dominate during the matter phases when Ω{sub 0m} = 1. We find the cosmological dynamical system which can obey the ΛCDM cosmic history. In each era, we find a critical lines that, the radiation dominated and the matter dominated are one points of them in the radiation and matter phases, respectively. Also, we drive the cosmologically viability condition for these models. We investigate the stability condition with respect to the homogeneous scalar perturbations in each era and we obtain the stability conditions for the fixed points in each eras. Finally, we reconstruct the function f(T) which mimics cosmic expansion history.

  20. The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag

    PubMed Central

    Szabó, Eszter C.; Manguinhas, Rita; Fonseca, Rosalina

    2016-01-01

    Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture. PMID:27650071