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Sample records for cross-seeding mimics cross-species

  1. 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.

  2. Myositis Mimics.

    PubMed

    Michelle, E Harlan; Mammen, Andrew L

    2015-10-01

    Patients with autoimmune myositis typically present with muscle weakness, elevated serum levels of muscle enzymes, and abnormal muscle biopsies. However, patients with other acquired myopathies or genetic muscle diseases may have remarkably similar presentations. Making the correct diagnosis of another muscle disease can prevent these patients from being exposed to the risks of immunosuppressive medications, which benefit those with myositis, but not those with other types of muscle disease. Here, we review some of the most common acquired and inherited muscle diseases that can mimic autoimmune myositis, including inclusion body myositis, limb girdle muscular dystrophies, metabolic myopathies, mitochondrial myopathies, and endocrine myopathies. We emphasize aspects of the medical history, physical exam, laboratory evaluation, and muscle biopsy analysis that can help clinicians distinguish myositis mimics from true autoimmune myositis.

  3. Performance analysis of cross-seeding WDM-PON system using transfer matrix method

    NASA Astrophysics Data System (ADS)

    Simatupang, Joni Welman; Pukhrambam, Puspa Devi; Huang, Yen-Ru

    2016-12-01

    In this paper, a model based on the transfer matrix method is adopted to analyze the effects of Rayleigh backscattering and Fresnel multiple reflections on a cross-seeding WDM-PON system. As part of analytical approximation methods, this time-independent model is quite simple but very efficient when it is applied to various WDM-PON transmission systems, including the cross-seeding scheme. The cross seeding scheme is most beneficial for systems with low loop-back ONU gain or low reflection loss at the drop fiber for upstream data in bidirectional transmission. However for downstream data transmission, multiple reflections power could destroy the usefulness of the cross-seeding scheme when the reflectivity is high enough and the RN is positioned near OLT or close to ONU.

  4. Cross- species communication in bacterial world.

    PubMed

    Majumdar, Sarangam; Pal, Sukla

    2017-02-20

    Biofilms are the compact association of micro organisms and the communication processes in these biofilms are always a wonder. Electrical and chemical signaling mechanism are the key to understand the bacterial communication network. Quorum sensing so far has been able to explain the coordinated motion of bacteria through its chemical signaling mechanism. Bacteria residing within biofilm communities are trivial to communicate. But the recent observation in 2017 by Humphries et al. has revealed that the ion channels enabled electrical signaling mechanism can be as powerful as to attract the distant cells i.e., this signaling mechanism are capable of holding a long range behavior. As a result long range cross species communication in the bacterial world have been possible. This substantial outcome has brought this field into a new paradigm to investigate the complex co-existence of biofilm communities and distant cells with a possible scope of application in synthetic biology. In this present article, we briefly describe this new signaling mechanism and how it gives rise to a long range communication ability in bacterial communities.

  5. 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...

  6. 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...

  7. 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...

  8. Cross-Species PTM Mapping from Phosphoproteomic Data.

    PubMed

    Chaudhuri, Rima; Yang, Jean Yee Hwa

    2017-01-01

    Protein post-translational modifications (PTMs) are crucial for signal transduction in cells. In order to understand key cell signaling events, identification of functionally important PTMs, which are more likely to be evolutionarily conserved, is necessary. In recent times, high-throughput mass spectrometry (MS) has made quantitative datasets in diverse species readily available, which has led to a growing need for tools to facilitate cross-species comparison of PTM data. Cross-species comparison of PTM sites is difficult since they often lie in structurally disordered protein domains. Current tools that address this can only map known PTMs between species based on previously annotated orthologous phosphosites and do not enable cross-species mapping of newly identified modification sites. Here, we describe an automated web-based tool, PhosphOrtholog, that accurately maps annotated and novel orthologous PTM sites from high-throughput MS-based experimental data obtained from different species without relying on existing PTM databases. Identification of conserved PTMs across species from large-scale experimental data increases our knowledgebase of evolutionarily conserved and functional PTM sites that influence most biological processes. In this Chapter, we illustrate with examples how to use PhosphOrtholog to map novel PTM sites from cross-species MS-based phosphoproteomics data.

  9. Microsatellites Cross-Species Amplification across Some African Cichlids.

    PubMed

    Bezault, Etienne; Rognon, Xavier; Gharbi, Karim; Baroiller, Jean-Francois; Chevassus, Bernard

    2012-01-01

    The transfer of the genomic resources developed in the Nile tilapia, Oreochromis niloticus, to other Tilapiines sensu lato and African cichlid would provide new possibilities to study this amazing group from genetics, ecology, evolution, aquaculture, and conservation point of view. We tested the cross-species amplification of 32 O. niloticus microsatellite markers in a panel of 15 species from 5 different African cichlid tribes: Oreochromines (Oreochromis, Sarotherodon), Boreotilapiines (Tilapia), Chromidotilapines, Hemichromines, and Haplochromines. Amplification was successfully observed for 29 markers (91%), with a frequency of polymorphic (P(95)) loci per species around 70%. The mean number of alleles per locus and species was 3.2 but varied from 3.7 within Oreochromis species to 1.6 within the nontilapia species. The high level of cross-species amplification and polymorphism of the microsatellite markers tested in this study provides powerful tools for a wide range of molecular genetic studies within tilapia species as well as for other African cichlids.

  10. Receptor recognition and cross-species infections of SARS coronavirus.

    PubMed

    Li, Fang

    2013-10-01

    Receptor recognition is a major determinant of the host range, cross-species infections, and pathogenesis of the severe acute respiratory syndrome coronavirus (SARS-CoV). A defined receptor-binding domain (RBD) in the SARS-CoV spike protein specifically recognizes its host receptor, angiotensin-converting enzyme 2 (ACE2). This article reviews the latest knowledge about how RBDs from different SARS-CoV strains interact with ACE2 from several animal species. Detailed research on these RBD/ACE2 interactions has established important principles on host receptor adaptations, cross-species infections, and future evolution of SARS-CoV. These principles may apply to other emerging animal viruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses".

  11. Microsatellites Cross-Species Amplification across Some African Cichlids

    PubMed Central

    Bezault, Etienne; Rognon, Xavier; Gharbi, Karim; Baroiller, Jean-Francois; Chevassus, Bernard

    2012-01-01

    The transfer of the genomic resources developed in the Nile tilapia, Oreochromis niloticus, to other Tilapiines sensu lato and African cichlid would provide new possibilities to study this amazing group from genetics, ecology, evolution, aquaculture, and conservation point of view. We tested the cross-species amplification of 32 O. niloticus microsatellite markers in a panel of 15 species from 5 different African cichlid tribes: Oreochromines (Oreochromis, Sarotherodon), Boreotilapiines (Tilapia), Chromidotilapines, Hemichromines, and Haplochromines. Amplification was successfully observed for 29 markers (91%), with a frequency of polymorphic (P95) loci per species around 70%. The mean number of alleles per locus and species was 3.2 but varied from 3.7 within Oreochromis species to 1.6 within the nontilapia species. The high level of cross-species amplification and polymorphism of the microsatellite markers tested in this study provides powerful tools for a wide range of molecular genetic studies within tilapia species as well as for other African cichlids. PMID:22701809

  12. 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

  13. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    PubMed Central

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  14. A Plea for Cross-species Social Neuroscience.

    PubMed

    Keysers, Christian; Gazzola, Valeria

    2017-01-01

    Over the past two decades, the question of how our brain makes us sensitive to the state of conspecifics and how that affects our behaviour has undergone a profound change. Twenty years ago what would now be called social neuroscience was focused on the visual processing of facial expressions and body movements in temporal lobe structures of primates (Puce and Perrett 2003). With the discovery of mirror neurons, this changed rapidly towards the modern field of social neuroscience, in which high-level vision is but one of many focuses of interest. In this essay, we will argue that for the further progress of the field, the integration of animal neuroscience and human neuroscience is paramount. We will do so, by focusing on the field of embodied social cognition. We will first show how the combination of animal and human neuroscience was critical in how the discovery of mirror neurons placed the motor system on the map of social cognition. We will then argue why an integrated cross-species approach will be pivotal to our understanding of the neural basis of emotional empathy and its link to prosocial behaviour.

  15. CJD mimics and chameleons.

    PubMed

    Mead, Simon; Rudge, Peter

    2017-04-01

    Rapidly progressive dementia mimicking Creutzfeldt-Jakob disease (CJD) is a relatively rare presentation but a rewarding one to become familiar with, as the potential diagnoses range from the universally fatal to the completely reversible. Patients require urgent decisions about assessment and investigation and have quickly evolving needs for treatments and support, through symptom management and end-of-life care in most cases. We have based this pragmatic review on the experiences of a specialist prion referral centre in the UK, which, unsurprisingly, is strongly biased towards seeing patients with CJD. Cases eventually proven not to have prion disease might be described as 'CJD-mimics'; being referred from UK neurologists, these are the most challenging cases. CJD in its classical presentation is very rarely mimicked; however, it is highly heterogeneous, and atypical forms can mimic virtually all common neurodegenerative syndromes. Warning features of a mimic include generalised seizures, hyponatraemia, fever, a facial movement disorder, a normal neurological examination and a modestly rapid presentation. Contrast-enhancing lesions or MRI signal hyperintensity outside the striatum, thalamus or cortex and a cerebrospinal fluid pleocytosis are key investigation pointers to a CJD mimic.

  16. 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

  17. Parasomnias and their mimics.

    PubMed

    Malhotra, Raman K; Avidan, Alon Y

    2012-11-01

    Parasomnias are classified into nonrapid eye movement and rapid eye movement sleep parasomnias. It is important for the clinician to consider other parasomnia mimics that present to the sleep disorders clinic. These conditions can be differentiated by taking a detailed sleep history and conducting nocturnal polysomnograms to evaluate for potential comorbidities and better characterize the disorder. Mainstays of treatment include treating any underlying primary sleep disorders that induce sleep fragmentation and could trigger the parasomnia, as well as implementing safety precautions to protect patients and their household. Pharmacologic treatment of many parasomnias is also available if needed and clinically indicated.

  18. 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

  19. Simultaneously reconstructing viral cross-species transmission history and identifying the underlying constraints

    PubMed Central

    Faria, Nuno Rodrigues; Suchard, Marc A.; Rambaut, Andrew; Streicker, Daniel G.; Lemey, Philippe

    2013-01-01

    The factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens, despite being central for the development of predictive models and assessing the efficacy of prevention strategies. Here, we describe a flexible Bayesian statistical framework to reconstruct virus transmission between different host species based on viral gene sequences, while simultaneously testing and estimating the contribution of several potential predictors of cross-species transmission. Specifically, we use a generalized linear model extension of phylogenetic diffusion to perform Bayesian model averaging over candidate predictors. By further extending this model with branch partitioning, we allow for distinct host transition processes on external and internal branches, thus discriminating between recent cross-species transmissions, many of which are likely to result in dead-end infections, and host shifts that reflect successful onwards transmission in the new host species. Our approach corroborates genetic distance between hosts as a key determinant of both host shifts and cross-species transmissions of rabies virus in North American bats. Furthermore, our results indicate that geographical range overlap is a modest predictor for cross-species transmission, but not for host shifts. Although our evolutionary framework focused on the multi-host reservoir dynamics of bat rabies virus, it is applicable to other pathogens and to other discrete state transition processes. PMID:23382420

  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. Ecological dynamics of influenza A viruses: cross-species transmission and global migration

    PubMed Central

    Ren, Hongguang; Jin, Yuan; Hu, Mingda; Zhou, Jing; Song, Ting; Huang, Zhisong; Li, Beiping; Li, Kaiwu; Zhou, Wei; Dai, Hongmei; Shi, Weifeng; Yue, Junjie; Liang, Long

    2016-01-01

    A comprehensive study of cross-species transmission and inter-regional migration would provide insights into the global ecology of influenza A viruses (IAVs). To this end, we assembled 17,241 non-redundant IAV whole-genome sequences with complete epidemiological information. We hierarchically divided the movements of IAVs into the cross-species transmission in each region and the inter-regional migration driven by each host species. We then systematically identified the potential cross-species transmission and inter-regional migration events. Cross-species transmission networks were obtained for each gene segment of the IAVs. Waterfowl, domestic birds and swine showed higher degrees of connection than did other species in all of the transmission networks. East Asia and Southeast Asia were hot regions for avian-mammal transmissions. Swine and migratory birds were the dominant species for global virus delivery. The importance of swine was reemphasized because it has not only provided an environment for adaptive evolution during the avian-human transmission of IAVs (as incubators) but also served as a key species for the global dissemination of the viruses (as carriers). Therefore, monitoring the global live trade of swine and survey of migratory birds along flyways would be beneficial for the prevention and control of IAVs. PMID:27827462

  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. Cross-species gene-family fluctuations reveal the dynamics of horizontal transfers.

    PubMed

    Grilli, Jacopo; Romano, Mariacristina; Bassetti, Federico; Cosentino Lagomarsino, Marco

    2014-06-01

    Prokaryotes vary their protein repertoire mainly through horizontal transfer and gene loss. To elucidate the links between these processes and the cross-species gene-family statistics, we perform a large-scale data analysis of the cross-species variability of gene-family abundance (the number of members of the family found on a given genome). We find that abundance fluctuations are related to the rate of horizontal transfers. This is rationalized by a minimal theoretical model, which predicts this link. The families that are not captured by the model show abundance profiles that are markedly peaked around a mean value, possibly because of specific abundance selection. Based on these results, we define an abundance variability index that captures a family's evolutionary behavior (and thus some of its relevant functional properties) purely based on its cross-species abundance fluctuations. Analysis and model, combined, show a quantitative link between cross-species family abundance statistics and horizontal transfer dynamics, which can be used to analyze genome 'flux'. Groups of families with different values of the abundance variability index correspond to genome sub-parts having different plasticity in terms of the level of horizontal exchange allowed by natural selection.

  4. Feline immunodeficiency virus cross-species transmission: Implications for emergence of new lentiviral infections

    USGS Publications Warehouse

    Lee, Justin; Malmberg, Jennifer L.; Wood, Britta A.; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark W.; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin E.; Serieys, Laurel E.K.; Riley, Seth P D; Crooks, Kevin R.; VandeWoude, Sue

    2016-01-01

    Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of HIV emergence following human exposures to SIV, understanding processes that promote successful cross-species lentiviral transmissions is highly relevant. We have previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats (Lynx rufus) and mountain lions (Puma concolor) in a small number of animals in California and Florida. In this study we investigate host-specific selection pressures, within-host viral fitness, and inter- vs. intra-species transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analysis of proviral and viral RNA levels demonstrates that PLVA fitness is severely restricted in mountain lions compared to bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but did not detect selection among twenty PLVA isolates from bobcats. These findings support that PLVA is a bobcat-adapted virus, which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals intraspecific PLVA transmission has occurred among panthers (Puma concolor coryi) in Florida following initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to emergence of HIV from nonhuman primates.IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which outcome will occur are complex, and the risk of new virus emergence is therefore difficult to predict. Here

  5. Feline Immunodeficiency Virus Cross-Species Transmission: Implications for Emergence of New Lentiviral Infections.

    PubMed

    Lee, Justin; Malmberg, Jennifer L; Wood, Britta A; Hladky, Sahaja; Troyer, Ryan; Roelke, Melody; Cunningham, Mark; McBride, Roy; Vickers, Winston; Boyce, Walter; Boydston, Erin; Serieys, Laurel; Riley, Seth; Crooks, Kevin; VandeWoude, Sue

    2017-03-01

    Owing to a complex history of host-parasite coevolution, lentiviruses exhibit a high degree of species specificity. Given the well-documented viral archeology of human immunodeficiency virus (HIV) emergence following human exposures to simian immunodeficiency virus (SIV), an understanding of processes that promote successful cross-species lentiviral transmissions is highly relevant. We previously reported natural cross-species transmission of a subtype of feline immunodeficiency virus, puma lentivirus A (PLVA), between bobcats (Lynx rufus) and mountain lions (Puma concolor) for a small number of animals in California and Florida. In this study, we investigate host-specific selection pressures, within-host viral fitness, and inter- versus intraspecies transmission patterns among a larger collection of PLV isolates from free-ranging bobcats and mountain lions. Analyses of proviral and viral RNA levels demonstrate that PLVA fitness is severely restricted in mountain lions compared to that in bobcats. We document evidence of diversifying selection in three of six PLVA genomes from mountain lions, but we did not detect selection among 20 PLVA isolates from bobcats. These findings support the hypothesis that PLVA is a bobcat-adapted virus which is less fit in mountain lions and under intense selection pressure in the novel host. Ancestral reconstruction of transmission events reveals that intraspecific PLVA transmission has occurred among panthers (Puma concolor coryi) in Florida following the initial cross-species infection from bobcats. In contrast, interspecific transmission from bobcats to mountain lions predominates in California. These findings document outcomes of cross-species lentiviral transmission events among felids that compare to the emergence of HIV from nonhuman primates.IMPORTANCE Cross-species transmission episodes can be singular, dead-end events or can result in viral replication and spread in the new species. The factors that determine which outcome

  6. "Controlled, cross-species dataset for exploring biases in genome annotation and modification profiles".

    PubMed

    McAfee, Alison; Michaud, Sarah; Foster, Leonard J

    2015-12-01

    Since the sequencing of the honey bee genome, proteomics by mass spectrometry has become increasingly popular for biological analyses of this insect; but we have observed that the number of honey bee protein identifications is consistently low compared to other organisms [1]. In this dataset, we use nanoelectrospray ionization-coupled liquid chromatography-tandem mass spectrometry (nLC-MS/MS) to systematically investigate the root cause of low honey bee proteome coverage. To this end, we present here data from three key experiments: a controlled, cross-species analyses of samples from Apis mellifera, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Mus musculus and Homo sapiens; a proteomic analysis of an individual honey bee whose genome was also sequenced; and a cross-tissue honey bee proteome comparison. The cross-species dataset was interrogated to determine relative proteome coverages between species, and the other two datasets were used to search for polymorphic sequences and to compare protein cleavage profiles, respectively.

  7. 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.

  8. Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.

    PubMed

    Hodgin, Jeffrey B; Nair, Viji; Zhang, Hongyu; Randolph, Ann; Harris, Raymond C; Nelson, Robert G; Weil, E Jennifer; Cavalcoli, James D; Patel, Jignesh M; Brosius, Frank C; Kretzler, Matthias

    2013-01-01

    Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human-mouse cross-species glomerular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS(-/-) db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications, such as elements of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and vascular endothelial growth factor receptor (VEGFR) signaling pathways. In addition, novel pathways not previously associated with DN and cross-species gene nodes and pathways unique to each of the human-mouse networks were discovered. The human-mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.

  9. 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

  10. 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

  11. 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.

  12. Approaching the Functional Annotation of Fungal Virulence Factors Using Cross-Species Genetic Interaction Profiling

    PubMed Central

    Brown, Jessica C. S.; Madhani, Hiten D.

    2012-01-01

    In many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen Cryptococcus neoformans. This approach involves expression of C. neoformans genes of interest in each member of the Saccharomyces cerevisiae gene deletion library, quantification of their impact on growth, and calculation of the cross-species genetic interaction profiles. To develop functional predictions, we computed and analyzed the correlations of these profiles with existing genetic interaction profiles of S. cerevisiae deletion mutants. For C. neoformans LIV7, which has no S. cerevisiae ortholog, this profiling approach predicted an unanticipated role in the Golgi apparatus. Validation studies in C. neoformans demonstrated that Liv7 is a functional Golgi factor where it promotes the suppression of the exposure of a specific immunostimulatory molecule, mannose, on the cell surface, thereby inhibiting phagocytosis. The genetic interaction profile of another pathogenicity gene that lacks an S. cerevisiae ortholog, LIV6, strongly predicted a role in endosome function. This prediction was also supported by studies of the corresponding C. neoformans null mutant. Our results demonstrate the utility of quantitative cross-species genetic interaction profiling for the functional annotation of fungal pathogenicity proteins of unknown function including, surprisingly, those that are not conserved in sequence across fungi. PMID:23300468

  13. Approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling.

    PubMed

    Brown, Jessica C S; Madhani, Hiten D

    2012-01-01

    In many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen Cryptococcus neoformans. This approach involves expression of C. neoformans genes of interest in each member of the Saccharomyces cerevisiae gene deletion library, quantification of their impact on growth, and calculation of the cross-species genetic interaction profiles. To develop functional predictions, we computed and analyzed the correlations of these profiles with existing genetic interaction profiles of S. cerevisiae deletion mutants. For C. neoformans LIV7, which has no S. cerevisiae ortholog, this profiling approach predicted an unanticipated role in the Golgi apparatus. Validation studies in C. neoformans demonstrated that Liv7 is a functional Golgi factor where it promotes the suppression of the exposure of a specific immunostimulatory molecule, mannose, on the cell surface, thereby inhibiting phagocytosis. The genetic interaction profile of another pathogenicity gene that lacks an S. cerevisiae ortholog, LIV6, strongly predicted a role in endosome function. This prediction was also supported by studies of the corresponding C. neoformans null mutant. Our results demonstrate the utility of quantitative cross-species genetic interaction profiling for the functional annotation of fungal pathogenicity proteins of unknown function including, surprisingly, those that are not conserved in sequence across fungi.

  14. Experimental Cross-Species Infection of Common Marmosets by Titi Monkey Adenovirus

    PubMed Central

    Chen, Eunice C.; Liu, Maria; Brasky, Kathleen M.; Lanford, Robert E.; Kelly, Kristi R.; Bales, Karen L.; Schnurr, David P.; Canfield, Don R.; Patterson, Jean L.; Chiu, Charles Y.

    2013-01-01

    Adenoviruses are DNA viruses that infect a number of vertebrate hosts and are associated with both sporadic and epidemic disease in humans. We previously identified a novel adenovirus, titi monkey adenovirus (TMAdV), as the cause of a fulminant pneumonia outbreak in a colony of titi monkeys (Callicebus cupreus) at a national primate center in 2009. Serological evidence of infection by TMAdV was also found in a human researcher at the facility and household family member, raising concerns for potential cross-species transmission of the virus. Here we present experimental evidence of cross-species TMAdV infection in common marmosets (Callithrix jacchus). Nasal inoculation of a cell cultured-adapted TMAdV strain into three marmosets produced an acute, mild respiratory illness characterized by low-grade fever, reduced activity, anorexia, and sneezing. An increase in virus-specific neutralization antibody titers accompanied the development of clinical signs. Although serially collected nasal swabs were positive for TMAdV for at least 8 days, all 3 infected marmosets spontaneously recovered by day 12 post-inoculation, and persistence of the virus in tissues could not be established. Thus, the pathogenesis of experimental inoculation of TMAdV in common marmosets resembled the mild, self-limiting respiratory infection typically seen in immunocompetent human hosts rather than the rapidly progressive, fatal pneumonia observed in 19 of 23 titi monkeys during the prior 2009 outbreak. These findings further establish the potential for adenovirus cross-species transmission and provide the basis for development of a monkey model useful for assessing the zoonotic potential of adenoviruses. PMID:23894316

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

    PubMed Central

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

    2014-01-01

    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

  16. 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.

  17. A cross-species socio-emotional behaviour development revealed by a multivariate analysis.

    PubMed

    Koshiba, Mamiko; Senoo, Aya; Mimura, Koki; Shirakawa, Yuka; Karino, Genta; Obara, Saya; Ozawa, Shinpei; Sekihara, Hitomi; Fukushima, Yuta; Ueda, Toyotoshi; Kishino, Hirohisa; Tanaka, Toshihisa; Ishibashi, Hidetoshi; Yamanouchi, Hideo; Yui, Kunio; Nakamura, Shun

    2013-01-01

    Recent progress in affective neuroscience and social neurobiology has been propelled by neuro-imaging technology and epigenetic approach in neurobiology of animal behaviour. However, quantitative measurements of socio-emotional development remains lacking, though sensory-motor development has been extensively studied in terms of digitised imaging analysis. Here, we developed a method for socio-emotional behaviour measurement that is based on the video recordings under well-defined social context using animal models with variously social sensory interaction during development. The behaviour features digitized from the video recordings were visualised in a multivariate statistic space using principal component analysis. The clustering of the behaviour parameters suggested the existence of species- and stage-specific as well as cross-species behaviour modules. These modules were used to characterise the behaviour of children with or without autism spectrum disorders (ASDs). We found that socio-emotional behaviour is highly dependent on social context and the cross-species behaviour modules may predict neurobiological basis of ASDs.

  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. Restrictions to cross species transmission of lentiviral infection gleaned from studies of FIV

    PubMed Central

    Troyer, Jennifer; Poss, Mary

    2009-01-01

    More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIV-infected nonhuman primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIVs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: 1. Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; 2. Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; 3. Cellular machinery in the new

  20. Restrictions to cross-species transmission of lentiviral infection gleaned from studies of FIV.

    PubMed

    VandeWoude, Sue; Troyer, Jennifer; Poss, Mary

    2010-03-15

    More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in Southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIV-infected non-human primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIVs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: (1) Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; (2) Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; (3) Cellular machinery in the

  1. 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.

  2. Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma

    PubMed Central

    Mito, Jeffrey K.; Riedel, Richard F.; Dodd, Leslie; Lahat, Guy; Lazar, Alexander J.; Dodd, Rebecca D.; Stangenberg, Lars; Eward, William C.; Hornicek, Francis J.; Yoon, Sam S.; Brigman, Brian E.; Jacks, Tyler; Lev, Dina; Mukherjee, Sayan; Kirsch, David G.

    2009-01-01

    Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-KrasG12D; Trp53Flox/Flox mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we identify expression of the RAS target FOXM1 in human MFH. Expression of Foxm1 is elevated in mouse sarcomas that metastasize to the lung and tissue microarray analysis of human MFH correlates overexpression of FOXM1 with metastasis. These results suggest that genomic alterations present in human MFH are conserved in the LSL-KrasG12D; p53Flox/Flox mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model. PMID:19956606

  3. 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

  4. 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.

  5. 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

  6. Cross-species infection of hepatitis E virus in a zoo-like location, including birds.

    PubMed

    Zhang, W; Shen, Q; Mou, J; Yang, Z B; Yuan, C L; Cui, L; Zhu, J G; Hua, X G; Xu, C M; Hu, J

    2008-08-01

    Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animals are considered to be reservoirs. Thirty-eight faecal samples, obtained from 22 species of animals including birds in a wildlife first-aid centre in Eastern China, were tested for HEV RNA. Our survey revealed that in total 28.9% (95% confidence interval 14.5-43.4) of the faecal samples from various mammals and birds were HEV RNA positive. Sequence and phylogenetic analyses of the 11 isolates demonstrated that all sequences clustered in genotype 4 with 96-100% identity to each other. In addition, serum samples from seven animal handlers have shown that five (71.4%) were seropositive. The findings imply that cross-species infection of HEV had probably occurred in this zoo-like location, and moreover, birds can be infected naturally with mammalian HEV.

  7. 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

  8. Cross-species transferability of microsatellite markers in the genus Lippia.

    PubMed

    Santos, C P; Rocha, D S; Bajay, M M; Santos, F R C; Campos, J B; Pinheiro, J B; Zucchi, M I; Silva-Mann, R; Arrigoni-Blank, M F; Blank, A F

    2014-11-27

    The cross-species transferability of 20 microsatellite markers was tested in the genus Lippia. Eleven markers were polymorphic after screening 19 accessions of Lippia sidoides and Lippia gracilis maintained in the Active Germplasm Bank (AGB) from Universidade Federal de Sergipe. Additionally, 40 accessions of Lippia spp were collected in Sergipe to increase the germplasm bank. A total of 23, 22, and 36 alleles were identified, with an average of 2.3, 2.2, and 3.27 alleles per locus, respectively, for each group. The markers that were used were efficient tools to access genetic diversity in the germplasm bank and will be useful for further research aiming at the conservation and management of these important aromatic species.

  9. 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

  10. Bone tumor mimics: avoiding misdiagnosis.

    PubMed

    Gould, C Frank; Ly, Justin Q; Lattin, Grant E; Beall, Douglas P; Sutcliffe, Joseph B

    2007-01-01

    Whether discovered incidentally or as part of a focused diagnostic evaluation, the finding of a benign osseous lesion that has radiologic features resembling a bone tumor is not uncommon. Some of the more common benign and nonneoplastic entities that can sometimes be confused with tumors are the following: cortical desmoid, Brodie abscess, synovial herniation pit, pseudocyst, enostosis, intraosseous ganglion cyst, fibrous dysplasia, stress fracture, avulsion fracture (healing stage), bone infarct, myositis ossificans, brown tumor, and subchondral cyst. Accurate diagnosis and management of these lesions require a basic understanding of their epidemiology, clinical presentations, anatomic distributions, imaging features, differential considerations, and therapeutic options. This in-depth review of 13 potential bone tumor mimics will assist the radiologist in correctly identifying these benign lesions and in avoiding misdiagnosis and related morbidity. This review will also aid the radiologist in making appropriate recommendations to the referring physician for management or further imaging.

  11. Evolutionary factors affecting the cross-species utility of newly developed microsatellite markers in seabirds.

    PubMed

    Moodley, Yoshan; Masello, Juan F; Cole, Theresa L; Calderon, Luciano; Munimanda, Gopi K; Thali, Marco R; Alderman, Rachael; Cuthbert, Richard J; Marin, Manuel; Massaro, Melanie; Navarro, Joan; Phillips, Richard A; Ryan, Peter G; Suazo, Cristián G; Cherel, Yves; Weimerskirch, Henri; Quillfeldt, Petra

    2015-09-01

    Microsatellite loci are ideal for testing hypotheses relating to genetic segregation at fine spatio-temporal scales. They are also conserved among closely related species, making them potentially useful for clarifying interspecific relationships between recently diverged taxa. However, mutations at primer binding sites may lead to increased nonamplification, or disruptions that may result in decreased polymorphism in nontarget species. Furthermore, high mutation rates and constraints on allele size may also with evolutionary time, promote an increase in convergently evolved allele size classes, biasing measures of interspecific genetic differentiation. Here, we used next-generation sequencing to develop microsatellite markers from a shotgun genome sequence of the sub-Antarctic seabird, the thin-billed prion (Pachyptila belcheri), that we tested for cross-species amplification in other Pachyptila and related sub-Antarctic species. We found that heterozygosity decreased and the proportion of nonamplifying loci increased with phylogenetic distance from the target species. Surprisingly, we found that species trees estimated from interspecific FST provided better approximations of mtDNA relationships among the studied species than those estimated using DC , even though FST was more affected by null alleles. We observed a significantly nonlinear second order polynomial relationship between microsatellite and mtDNA distances. We propose that the loss of linearity with increasing mtDNA distance stems from an increasing proportion of homoplastic allele size classes that are identical in state, but not identical by descent. Therefore, despite high cross-species amplification success and high polymorphism among the closely related Pachyptila species, we caution against the use of microsatellites in phylogenetic inference among distantly related taxa.

  12. Alternative splicing in teleost fish genomes: same-species and cross-species analysis and comparisons.

    PubMed

    Lu, Jianguo; Peatman, Eric; Wang, Wenqi; Yang, Qing; Abernathy, Jason; Wang, Shaolin; Kucuktas, Huseyin; Liu, Zhanjiang

    2010-06-01

    Alternative splicing (AS) is a mechanism by which the coding diversity of the genome can be greatly increased. Rates of AS are known to vary according to the complexity of eukaryotic species potentially explaining the tremendous phenotypic diversity among species with similar numbers of coding genes. Little is known, however, about the nature or rate of AS in teleost fish. Here, we report the characteristics of AS in teleost fish and classification and frequency of five canonical AS types. We conducted both same-species and cross-species analysis utilizing the Genome Mapping and Alignment Program (GMAP) and an AS pipeline (ASpipe) to study AS in four genome-enabled species (Danio rerio, Oryzias latipes, Gasterosteus aculeatus, and Takifugu rubripes) and one species lacking a complete genome sequence, Ictalurus punctatus. AS frequency was lowest in the highly duplicated genome of zebrafish (17% of mapped genes). The compact genome of the pufferfish showed the highest occurrence of AS (approximately 43% of mapped genes). An inverse correlation between AS frequency and genome size was consistent across all analyzed species. Cross-species comparisons utilizing zebrafish as the reference genome allowed the identification of additional putative AS genes not revealed by zebrafish transcripts. Approximately, 50% of AS genes identified by same-species comparisons were shared among two or more species. A searchable website, the Teleost Alternative Splicing Database, was created to allow easy identification and visualization of AS transcripts in the studied teleost genomes. Our results and associated database should further our understanding of alternative splicing as an important functional and evolutionary mechanism in the genomes of teleost fish.

  13. Ketamine Suppresses the Ventral Striatal Response to Reward Anticipation: A Cross-Species Translational Neuroimaging Study

    PubMed Central

    Francois, Jennifer; Grimm, Oliver; Schwarz, Adam J; Schweiger, Janina; Haller, Leila; Risterucci, Celine; Böhringer, Andreas; Zang, Zhenxiang; Tost, Heike; Gilmour, Gary; Meyer-Lindenberg, Andreas

    2016-01-01

    Convergent evidence implicates regional neural responses to reward anticipation in the pathogenesis of several psychiatric disorders, such as schizophrenia, where blunted ventral striatal responses to positive reward are observed in patients and at-risk populations. In vivo oxygen amperometry measurements in the ventral striatum in awake, behaving rats reveal reward-related tissue oxygen changes that closely parallel blood oxygen level dependent (BOLD) signal changes observed in human functional magnetic resonance imaging (fMRI), suggesting that a cross-species approach targeting this mechanism might be feasible in psychopharmacology. The present study explored modulatory effects of acute, subanaesthetic doses of ketamine—a pharmacological model widely used in psychopharmacological research, both preclinically and clinically—on ventral striatum activity during performance of a reward anticipation task in both species, using fMRI in humans and in vivo oxygen amperometry in rats. In a region-of-interest analysis conducted following a cross-over placebo and ketamine study in human subjects, an attenuated ventral striatal response during reward anticipation was observed following ketamine relative to placebo during performance of a monetary incentive delay task. In rats, a comparable attenuation of ventral striatal signal was found after ketamine challenge, relative to vehicle, in response to a conditioned stimulus that predicted delivery of reward. This study provides the first data in both species demonstrating an attenuating effect of acute ketamine on reward-related ventral striatal (O2) and fMRI signals. These findings may help elucidate a deeper mechanistic understanding of the potential role of ketamine as a model for psychosis, show that cross-species pharmacological experiments targeting reward signaling are feasible, and suggest this phenotype as a promising translational biomarker for the development of novel compounds, assessment of disease status, and

  14. Cross-Species Gene Expression Analysis of Species Specific Differences in the Preclinical Assessment of Pharmaceutical Compounds

    PubMed Central

    Okyere, John; Oppon, Ekow; Dzidzienyo, Daniel; Sharma, Lav; Ball, Graham

    2014-01-01

    Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferator-activator receptor (PPAR) α response in rat and human. PMID:24823806

  15. 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.

  16. An RF Performance Sensitivity and Process Yield Model for MIMIC CAD applications. MIMIC Program. Phase 3

    DTIC Science & Technology

    1991-09-16

    AD-A242 266 --III ! I I I 1111 i~tll An RF Performance Sensitivity and Process Yield Model for MIMIC CAD Applications MIMIC Program, Phase 3 Final...DAAL01-89-K-0906-4 September 16, 1991 An RF Performance Sensitivity and Process Yield Model for MIMIC CAD Applications MIMIC Program, Phase 3 Final...Yield Model MIMIC Phase 3 for MIMIC CAD Applications Contract No. DAALO1-89-K-0906-4 6. AUTHOR(S) R.J. Trew, D.E. Stoneking, P.Gilmore, C.T. Kelley

  17. Which polyesters can mimic polyethylene?

    PubMed

    Stempfle, Florian; Ortmann, Patrick; Mecking, Stefan

    2013-01-11

    Self-metathesis of erucic acid by [(PCy(3))(η-C-C(3)H(4)N(2)Mes(2))Cl(2)Ru = CHPh] (Grubbs second- generation catalyst) followed by catalytic hydrogenation and purification via the ester yields 1,26-hexacosanedioate (>99% purity). Polyesterification with 1,26-hexacosanediol, generated from the diester, affords polyester-26,26, which features a T(m) of 114 °C (T(c) = 92 °C, ΔH(m) = 160 J g(-1)). Ultralong-chain model polyesters-38,23 (T(m) = 109 °C) and -44,23 (T(m) = 111 °C), generated via multistep procedures including acyclic diene metathesis polymerization, underline that melting points of such aliphatic polyesters do not gradually increase with methylene sequence chain length. Available data suggest that to mimic linear polyethylenes thermal properties, even longer sequences, amounting to at least four times a fatty acid chain, fully incorporated in a linear fashion are required.

  18. Ion Channel Function and Cross-Species Determinants in Viral Assembly of Nonprimate Hepacivirus p7

    PubMed Central

    Walter, Stephanie; Bollenbach, Alexander; Doerrbecker, Juliane; Pfaender, Stephanie; Brown, Richard J. P.; Vieyres, Gabrielle; Scott, Claire; Foster, Richard; Kumar, Abhinav; Zitzmann, Nicole; Griffin, Stephen; Penin, François; Pietschmann, Thomas

    2016-01-01

    ABSTRACT Nonprimate hepacivirus (NPHV), the closest homolog of hepatitis C virus (HCV) described to date, has recently been discovered in horses. Even though the two viruses share a similar genomic organization, conservation of the encoded hepaciviral proteins remains undetermined. The HCV p7 protein is localized within endoplasmic reticulum (ER) membranes and is important for the production of infectious particles. In this study, we analyzed the structural and functional features of NPHV p7 in addition to its role during virus assembly. Three-dimensional homology models for NPHV p7 using various nuclear magnetic resonance spectroscopy (NMR) structures were generated, highlighting the conserved residues important for ion channel function. By applying a liposome permeability assay, we observed that NPHV p7 exhibited liposome permeability features similar to those of HCV p7, indicative of similar ion channel activity. Next, we characterized the viral protein using a p7-based trans-complementation approach. A similar subcellular localization pattern at the ER membrane was observed, although production of infectious particles was likely hindered by genetic incompatibilities with HCV proteins. To further characterize these cross-species constraints, chimeric viruses were constructed by substituting different regions of HCV p7 with NPHV p7. The N terminus and transmembrane domains were nonexchangeable and therefore constitute a cross-species barrier in hepaciviral assembly. In contrast, the basic loop and the C terminus of NPHV p7 were readily exchangeable, allowing production of infectious trans-complemented viral particles. In conclusion, comparison of NPHV and HCV p7 revealed structural and functional homology of these proteins, including liposome permeability, and broadly acting determinants that modulate hepaciviral virion assembly and contribute to the host-species barrier were identified. IMPORTANCE The recent discovery of new relatives of hepatitis C virus (HCV

  19. Molecular Epidemiology of Cross-Species Giardia duodenalis Transmission in Western Uganda

    PubMed Central

    Johnston, Amanda R.; Gillespie, Thomas R.; Rwego, Innocent B.; Tranby McLachlan, Traci L.; Kent, Angela D.; Goldberg, Tony L.

    2010-01-01

    Background Giardia duodenalis is prevalent in tropical settings where diverse opportunities exist for transmission between people and animals. We conducted a cross-sectional study of G. duodenalis in people, livestock, and wild primates near Kibale National Park, Uganda, where human-livestock-wildlife interaction is high due to habitat disturbance. Our goal was to infer the cross-species transmission potential of G. duodenalis using molecular methods and to investigate clinical consequences of infection. Methodology/Principal Findings Real-time PCR on DNA extracted from fecal samples revealed a combined prevalence of G. duodenalis in people from three villages of 44/108 (40.7%), with prevalence reaching 67.5% in one village. Prevalence rates in livestock and primates were 12.4% and 11.1%, respectively. Age was associated with G. duodenalis infection in people (higher prevalence in individuals ≤15 years) and livestock (higher prevalence in subadult versus adult animals), but other potential risk factors in people (gender, contact with domestic animals, working in fields, working in forests, source of drinking water, and medication use) were not. G. duodenalis infection was not associated with gastrointestinal symptoms in people, nor was clinical disease noted in livestock or primates. Sequence analysis of four G. duodenalis genes identified assemblage AII in humans, assemblage BIV in humans and endangered red colobus monkeys, and assemblage E in livestock and red colobus, representing the first documentation of assemblage E in a non-human primate. In addition, genetic relationships within the BIV assemblage revealed sub-clades of identical G. duodenalis sequences from humans and red colobus. Conclusions/Significance Our finding of G. duodenalis in people and primates (assemblage BIV) and livestock and primates (assemblage E) underscores that cross-species transmission of multiple G. duodenalis assemblages may occur in locations such as western Uganda where people

  20. 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.

  1. 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.

  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

    2016-01-26

    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. 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.

  4. 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.

  5. 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.

  6. Cross species selection scans identify components of C4 photosynthesis in the grasses.

    PubMed

    Huang, Pu; Studer, Anthony J; Schnable, James C; Kellogg, Elizabeth A; Brutnell, Thomas P

    2017-01-01

    C4 photosynthesis is perhaps one of the best examples of convergent adaptive evolution with over 25 independent origins in the grasses (Poaceae) alone. The availability of high quality grass genome sequences presents new opportunities to explore the mechanisms underlying this complex trait using evolutionary biology-based approaches. In this study, we performed genome-wide cross-species selection scans in C4 lineages to facilitate discovery of C4 genes. The study was enabled by the well conserved collinearity of grass genomes and the recently sequenced genome of a C3 panicoid grass, Dichanthelium oligosanthes This method, in contrast to previous studies, does not rely on any a priori knowledge of the genes that contribute to biochemical or anatomical innovations associated with C4 photosynthesis. We identified a list of 88 candidate genes that include both known and potentially novel components of the C4 pathway. This set includes the carbon shuttle enzymes pyruvate, phosphate dikinase, phosphoenolpyruvate carboxylase and NADP malic enzyme as well as several predicted transporter proteins that likely play an essential role in promoting the flux of metabolites between the bundle sheath and mesophyll cells. Importantly, this approach demonstrates the application of fundamental molecular evolution principles to dissect the genetic basis of a complex photosynthetic adaptation in plants. Furthermore, we demonstrate how the output of the selection scans can be combined with expression data to provide additional power to prioritize candidate gene lists and suggest novel opportunities for pathway engineering.

  7. Cross-Species Functional Genomic Analysis Identifies Resistance Genes of the Histone Deacetylase Inhibitor Valproic Acid

    PubMed Central

    Forthun, Rakel Brendsdal; SenGupta, Tanima; Skjeldam, Hanne Kim; Lindvall, Jessica Margareta; McCormack, Emmet; Gjertsen, Bjørn Tore; Nilsen, Hilde

    2012-01-01

    The mechanisms of successful epigenetic reprogramming in cancer are not well characterized as they involve coordinated removal of repressive marks and deposition of activating marks by a large number of histone and DNA modification enzymes. Here, we have used a cross-species functional genomic approach to identify conserved genetic interactions to improve therapeutic effect of the histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in more than 20% of patients with advanced acute myeloid leukemia (AML). Using a bidirectional synthetic lethality screen revealing genes that increased or decreased VPA sensitivity in C. elegans, we identified novel conserved sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which demonstrates a functional relationship between protein acetylation and lysine-specific methylation. The synthetic lethal screen identified resistance programs that compensated for the HDACi-induced global hyper-acetylation, and confirmed MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs represent promising novel targets for refinement of combinatorial epigenetic anti-cancer therapy. PMID:23155442

  8. 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

  9. Cross-species assessments of motor and exploratory behavior related to bipolar disorder.

    PubMed

    Henry, Brook L; Minassian, Arpi; Young, Jared W; Paulus, Martin P; Geyer, Mark A; Perry, William

    2010-07-01

    Alterations in exploratory behavior are a fundamental feature of bipolar mania, typically characterized as motor hyperactivity and increased goal-directed behavior in response to environmental cues. In contrast, abnormal exploration associated with schizophrenia and depression can manifest as prominent withdrawal, limited motor activity, and inattention to the environment. While motor abnormalities are cited frequently as clinical manifestations of these disorders, relatively few empirical studies have quantified human exploratory behavior. This article reviews the literature characterizing motor and exploratory behavior associated with bipolar disorder and genetic and pharmacological animal models of the illness. Despite sophisticated assessment of exploratory behavior in rodents, objective quantification of human motor activity has been limited primarily to actigraphy studies with poor cross-species translational value. Furthermore, symptoms that reflect the cardinal features of bipolar disorder have proven difficult to establish in putative animal models of this illness. Recently, however, novel tools such as the human behavioral pattern monitor provide multivariate translational measures of motor and exploratory activity, enabling improved understanding of the neurobiology underlying psychiatric disorders.

  10. Cross-species Transcriptomic Comparison of In Vitro and In Vivo Mammalian Neural Cells

    PubMed Central

    LoVerso, Peter R.; Wachter, Christopher M.; Cui, Feng

    2015-01-01

    The mammalian brain is characterized by distinct classes of cells that differ in morphology, structure, signaling, and function. Dysregulation of gene expression in these cell populations leads to various neurological disorders. Neural cells often need to be acutely purified from animal brains for research, which requires complicated procedure and specific expertise. Primary culture of these cells in vitro is a viable alternative, but the differences in gene expression of cells grown in vitro and in vivo remain unclear. Here, we cultured three major neural cell classes of rat brain (ie, neurons, astrocytes, and oligodendrocyte precursor cells [OPCs]) obtained from commercial sources. We measured transcript abundance of these cell types by RNA sequencing (RNA-seq) and compared with their counterparts acutely purified from mouse brains. Cross-species RNA-seq data analysis revealed hundreds of genes that are differentially expressed between the cultured and acutely purified cells. Astrocytes have more such genes compared to neurons and OPCs, indicating that signaling pathways are greatly perturbed in cultured astrocytes. This dataset provides a powerful resource to demonstrate the similarities and differences of biological processes in mammalian neural cells grown in vitro and in vivo at the molecular level. PMID:26640375

  11. Novel and highly informative Capsicum SSR markers and their cross-species transferability.

    PubMed

    Buso, G S C; Reis, A M M; Amaral, Z P S; Ferreira, M E

    2016-09-23

    This study was undertaken primarily to develop new simple sequence repeat (SSR) markers for Capsicum. As part of this project aimed at broadening the use of molecular tools in Capsicum breeding, two genomic libraries enriched for AG/TC repeat sequences were constructed for Capsicum annuum. A total of 475 DNA clones were sequenced from both libraries and 144 SSR markers were tested on cultivated and wild species of Capsicum. Forty-five SSR markers were randomly selected to genotype a panel of 48 accessions of the Capsicum germplasm bank. The number of alleles per locus ranged from 2 to 11, with an average of 6 alleles. The polymorphism information content was on average 0.60, ranging from 0.20 to 0.83. The cross-species transferability to seven cultivated and wild Capsicum species was tested with a set of 91 SSR markers. We found that a high proportion of the loci produced amplicons in all species tested. C. frutescens had the highest number of transferable markers, whereas the wild species had the lowest. Our results indicate that the new markers can be readily used in genetic analyses of Capsicum.

  12. 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

  13. 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.

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

    USGS Publications Warehouse

    Williams, I.; Guzzetti, B.M.; Gust, Judy 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Identifying candidate oocyte reprogramming factors using cross-species global transcriptional analysis.

    PubMed

    Awe, Jason P; Byrne, James A

    2013-04-01

    There is mounting evidence to suggest that the epigenetic reprogramming capacity of the oocyte is superior to that of the current factor-based reprogramming approaches and that some factor-reprogrammed induced pluripotent stem cells (iPSCs) retain a degree of epigenetic memory that can influence differentiation capacity and may be linked to the observed expression of immunogenicity genes in iPSC derivatives. One hypothesis for this differential reprogramming capacity is the "chromatin loosening/enhanced reprogramming" concept, as previously described by John Gurdon and Ian Wilmut, as well as others, which postulates that the oocyte possesses factors that loosen the somatic cell chromatin structure, providing the epigenetic and transcriptional regulatory factors more ready access to repressed genes and thereby significantly increasing epigenetic reprogramming. However, to empirically test this hypothesis a list of candidate oocyte reprogramming factors (CORFs) must be ascertained that are significantly expressed in metaphase II oocytes. Previous studies have focused on intraspecies or cross-species transcriptional analysis of up to two different species of oocytes. In this study, we have identified eight CORFs (ARID2, ASF1A, ASF1B, DPPA3, ING3, MSL3, H1FOO, and KDM6B) based on unbiased global transcriptional analysis of oocytes from three different species (human, rhesus monkey, and mouse) that both demonstrate significant (p<0.05, FC>3) expression in oocytes of all three species and have well-established roles in loosening/opening up chromatin structure. We also identified an additional 15 CORFs that fit within our proposed "chromatin opening/fate transformative" (COFT) model. These CORFs may be able to augment Shinya Yamanaka's previously identified reprogramming factors (OCT4, SOX2, KLF4, and cMYC) and potentially facilitate the removal of epigenetic memory in iPSCs and/or reduce the expression of immunogenicity genes in iPSC derivatives, and may have

  1. 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.

  2. Cross-species genomics matches driver mutations and cell compartments to model ependymoma.

    PubMed

    Johnson, Robert A; Wright, Karen D; Poppleton, Helen; Mohankumar, Kumarasamypet M; Finkelstein, David; Pounds, Stanley B; Rand, Vikki; Leary, Sarah E S; White, Elsie; Eden, Christopher; Hogg, Twala; Northcott, Paul; Mack, Stephen; Neale, Geoffrey; Wang, Yong-Dong; Coyle, Beth; Atkinson, Jennifer; DeWire, Mariko; Kranenburg, Tanya A; Gillespie, Yancey; Allen, Jeffrey C; Merchant, Thomas; Boop, Fredrick A; Sanford, Robert A; Gajjar, Amar; Ellison, David W; Taylor, Michael D; Grundy, Richard G; Gilbertson, Richard J

    2010-07-29

    Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumour that arises throughout the central nervous system (CNS). Subgroup-specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumours to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus (that encodes Cdkn2a and b). The transcriptome of human supratentorial ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf(-/-) NSCs. Notably, activation of Ephb2 signalling in these, but not other, NSCs generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human supratentorial tumour. Further, comparative analysis of matched mouse and human tumours revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup-specific driver mutations with cellular compartments to model and interrogate cancer subgroups.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Wildlife-livestock interactions and risk areas for cross-species spread of bovine tuberculosis.

    PubMed

    Meunier, Natascha V; Sebulime, Peregrine; White, Richard G; Kock, Richard

    2017-01-23

    The transmission of diseases between livestock and wildlife can be a hindrance to effective disease control. Maintenance hosts and contact rates should be explored to further understand the transmission dynamics at the wildlife-livestock interface. Bovine tuberculosis (BTB) has been shown to have wildlife maintenance hosts and has been confirmed as present in the African buffalo (Syncerus caffer) in the Queen Elizabeth National Park (QENP) in Uganda since the 1960s. The first aim of this study was to explore the spatio-temporal spread of cattle illegally grazing within the QENP recorded by the Uganda Wildlife Authority (UWA) rangers in a wildlife crime database. Secondly, we aimed to quantify wildlife-livestock interactions and cattle movements, on the border of QENP, using a longitudinal questionnaire completed by 30 livestock owners. From this database, 426 cattle sightings were recorded within QENP in 8 years. Thirteen (3.1%) of these came within a 300 m-4 week space-time window of a buffalo herd, using the recorded GPS data. Livestock owners reported an average of 1.04 (95% CI 0.97-1.11) sightings of Uganda kob, waterbuck, buffalo or warthog per day over a 3-month period, with a rate of 0.22 (95% CI 0.20-0.25) sightings of buffalo per farmer per day. Reports placed 85.3% of the ungulate sightings and 88.0% of the buffalo sightings as further than 50 m away. Ungulate sightings were more likely to be closer to cattle at the homestead (OR 2.0, 95% CI 1.1-3.6) compared with the grazing area. Each cattle herd mixed with an average of five other cattle herds at both the communal grazing and watering points on a daily basis. Although wildlife and cattle regularly shared grazing and watering areas, they seldom came into contact close enough for aerosol transmission. Between species infection transmission is therefore likely to be by indirect or non-respiratory routes, which is suspected to be an infrequent mechanism of transmission of BTB. Occasional cross-species

  9. Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families

    PubMed Central

    Geoghegan, Jemma L.

    2017-01-01

    The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections. However, it is unclear whether some virus families have a greater propensity to jump host species than others. If related viruses have an evolutionary history of co-divergence with their hosts there should be evidence of topological similarities between the virus and host phylogenetic trees, whereas host jumping generates incongruent tree topologies. By analyzing co-phylogenetic processes in 19 virus families and their eukaryotic hosts we provide a quantitative and comparative estimate of the relative frequency of virus-host co-divergence versus cross-species transmission among virus families. Notably, our analysis reveals that cross-species transmission is a near universal feature of the viruses analyzed here, with virus-host co-divergence occurring less frequently and always on a subset of viruses. Despite the overall high topological incongruence among virus and host phylogenies, the Hepadnaviridae, Polyomaviridae, Poxviridae, Papillomaviridae and Adenoviridae, all of which possess double-stranded DNA genomes, exhibited more frequent co-divergence than the other virus families studied here. At the other extreme, the virus and host trees for all the RNA viruses studied here, particularly the Rhabdoviridae and the Picornaviridae, displayed high levels of topological incongruence, indicative of frequent host switching. Overall, we show that cross-species transmission plays a major role in virus evolution, with all the virus families studied here having the potential to jump host species, and that increased sampling will likely reveal more instances of host jumping. PMID:28178344

  10. Short Communication Microsatellite loci in the tetraploid spined loach, Cobitis biwae, and cross-species amplification in four related species.

    PubMed

    Jablonska, O; Marín, A; Kowalewska, K; Fujimoto, T; Arai, K

    2016-09-23

    Fifteen microsatellite loci were identified in the tetraploid spined loach, Cobitis biwae (Teleostei: Cobitidae). Among these, 14 were polymorphic (5-31 alleles) and showed moderate to high cross-species amplification transferability in four related species, Cobitis matsubarai, Cobitis taenia, Misgurnus anguillicaudatus, and Misgurnus fossilis. The loci, described herein, will be useful for population genetics, phylogeny, parentage analysis, and detection of hybridization among Cobitis species.

  11. In search for significant cognitive features in Klinefelter syndrome through cross-species comparison of a supernumerary X chromosome.

    PubMed

    Bruining, H; Swaab, H; de Sonneville, L M J; van Rijn, S; van Engeland, H; Kas, M J H

    2011-08-01

    The behavioral characterization of animals that carry genetic disorder abnormalities in a controlled genetic and environmental background may be used to identify human deficits that are significant to understand underlying neurobiological mechanisms. Here, we studied whether previously reported object recognition impairments in mice with a supernumerary X chromosome relate to specific cognitive deficits in Klinefelter syndrome (47,XXY). We aimed to optimize face validity by studying temporal object recognition in human cognitive assays. Thirty-four boys with Klinefelter syndrome (mean age 12.01) were compared with 90 age-matched normal controls, on a broad range of visual object memory tasks, including tests for pattern and temporal order discrimination. The results indicate that subjects with Klinefelter syndrome have difficulty in the processing of visual object and pattern information. Visual object patterns seem difficult to discriminate especially when temporal information needs to be processed and reproduced. On the basis of cross-species comparison, we propose that impaired temporal processing of object pattern information is an important deficit in Klinefelter syndrome. The current study shows how cross-species behavioral characterization may be used as a starting point to understand the neurobiology of syndromal phenotypic expression. The features of this study may serve as markers for interventions in Klinefelter syndrome. Similar cross-species evaluations of standard mouse behavioral paradigms in different genetic contexts may be powerful tools to optimize genotype-phenotype relationships.

  12. When humans are the exception: cross-species databases at the interface of biological and clinical research.

    PubMed

    Leonelli, Sabina

    2012-04-01

    Cross-species comparison has long been regarded as a stepping-stone for medical research, enabling the discovery and testing of prospective treatments before they undergo clinical trial on humans. Post-genomic medicine has made cross-species comparison crucial in another respect: the 'community databases' developed to collect and disseminate data on model organisms are now often used as a template for the dissemination of data on humans and as a tool for comparing results of medical significance across the human-animal boundary. This paper identifies and discusses four key problems encountered by database curators when integrating human and non-human data within the same database: (1) picking criteria for what counts as reliable evidence, (2) selecting metadata, (3) standardising and describing research materials and (4) choosing nomenclature to classify data. An analysis of these hurdles reveals epistemic disagreement and controversies underlying cross-species comparisons, which in turn highlight important differences in the experimental cultures of biologists and clinicians trying to make sense of these data. By considering database development through the eyes of curators, this study casts new light on the complex conjunctions of biological and clinical practice, model organisms and human subjects, and material and virtual sources of evidence--thus emphasizing the fragmented, localized and inherently translational nature of biomedicine.

  13. 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.

  14. 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…

  15. Detection of Genotype 4 Swine Hepatitis E Virus in Systemic Tissues in Cross-Species Infected Rabbits

    PubMed Central

    Wu, Qiaoxing; An, Junqing; She, Ruiping; Shi, Ruihan; Hao, Wenzhuo; Soomro, MajidHussain; Yuan, Xuerui; Yang, Jinling; Wang, Jingyuan

    2017-01-01

    Increasing evidence demonstrates that hepatitis E virus (HEV) can be transmitted across species. According to previous reports, swine HEV has two genotypes, genotype 3 and 4, and both can infect humans by the fecal-oral route. Thus, it is crucial for the control of HEV zoonotic transmission to evaluate the dynamics of viral shedding and distribution in different tissues during cross-species infection by HEV. In this study, rabbits were infected with genotype 4 swine HEV by the intraperitoneal route. The results showed that HEV RNA not only shed in the feces but also in the saliva of some rabbits during infection with swine HEV. Viremia appeared late after infection, and anti-HEV IgG was not obvious until the appearance of high viremia levels. After the rabbits were euthanized, a histopathological examination showed that the livers developed overt hepatitis accompanied by an elevation of alanine aminotransferase (ALT) and aspartate transaminase (AST). Furthermore, HEV RNA was detected in various tissues, especially in the salivary glands and tonsils. Subsequently, negative-stranded HEV RNA was practiced in tissues with positive HEV RNA, which demonstrated that HEV replicated in the tissues. Next, we harvested additional tissues from the liver, salivary gland, tonsil, spleen, thymus gland, lymph node and intestine, which are known as replication sites of swine HEV. Additionally, we also observed the HEV antigen distributed in the organs above through immunohistochemical staining. These results demonstrate that rabbits could be used as an animal model for researching cross-species infection of genotype 4 HEV. It is also noteworthy that HEV can shed in the saliva and presents the risk of droplet transmission. These new data provide valuable information for understanding cross-species infection by HEV. PMID:28129390

  16. 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/

  17. 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/

  18. Detection of RHDV strains in the Iberian hare (Lepus granatensis): earliest evidence of rabbit lagovirus cross-species infection.

    PubMed

    Lopes, Ana M; Marques, Sara; Silva, Eliane; Magalhães, Maria J; Pinheiro, Ana; Alves, Paulo C; Le Pendu, Jacques; Esteves, Pedro J; Thompson, Gertrude; Abrantes, Joana

    2014-09-24

    Rabbit hemorrhagic disease virus (RHDV) is a highly lethal Lagovirus, family Caliciviridae, that threatens European rabbits (Oryctolagus cuniculus). Although a related virus severely affects hares, cross-species infection was only recently described for new variant RHDV in Cape hares (Lepus capensis mediterraneus). We sequenced two strains from dead Iberian hares (Lepus granatensis) collected in the 1990s in Portugal. Clinical signs were compatible with a Lagovirus infection. Phylogenetic analysis of the complete capsid gene positioned them in the RHDV genogroup that circulated on the Iberian Peninsula at that time. This is the earliest evidence of RHDV affecting a species other than European rabbits.

  19. Hybrid mimics and hybrid vigor in Arabidopsis.

    PubMed

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

    2015-09-01

    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.

  20. 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...

  1. 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

    2013-01-05

    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.

  2. Distribution of baboon endogenous virus among species of African monkeys suggests multiple ancient cross-species transmissions in shared habitats.

    PubMed Central

    van der Kuyl, A C; Dekker, J T; Goudsmit, J

    1995-01-01

    PCR amplification of baboon endogenous virus (BaEV) long terminal repeat, reverse transcriptase gene, and env fragments from 24 different species of African monkeys indicates that BaEV is less widespread than was formerly thought. Instead of being present in every species of African primates, BaEV can be found only in baboons, geladas, and mangabeys (all belonging to the Papionini tribe) and in African green monkey (Cercopithecus aethiops)subspecies. BaEV, which can be activated from baboon and gelada tissues, was most likely introduced in the germ line only recently (less than a few million years ago) and has not been inherited from a common ancestor of all extant African monkeys. Neighbor-joining and maximum-likelihood analyses of the sequences obtained showed that two distinct virus clusters can be distinguished: the first containing baboon, gelada, and African green monkey BaEV sequences and the second consisting of mandrill and mangabey BaEV sequences. This viral evolutionary tree does not follow host phylogeny, indicating the cross-species transmissions and multiple germ line fixations of the virus must have occurred in the past. BaEV sequences are found in monkeys inhabiting savannas (baboons, geladas, and African green monkeys) as well as forests (managabeys and mandrills) and cluster according to the habitats of their hosts, providing evidence for cross-species transmission in shared habitats. PMID:7494300

  3. 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.

  4. Mimics and chameleons in motor neurone disease.

    PubMed

    Turner, Martin R; Talbot, Kevin

    2013-06-01

    The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the 'split hand', head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life.

  5. Mimics and chameleons in motor neurone disease

    PubMed Central

    Turner, Martin R; Talbot, Kevin

    2013-01-01

    The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the ‘split hand’, head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life. PMID:23616620

  6. 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.

  7. 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.

  8. Cross-species transferability of eastern white pine (Pinus strobus) nuclear microsatellite markers to five Mexican white pines.

    PubMed

    Villalobos-Arámbula, A R; Pérez de la Rosa, J A; Arias, A; Rajora, O P

    2014-09-12

    We examined cross-species transferability and usefulness of six nuclear microsatellite markers developed in consubgeneric eastern white pine (Pinus strobus) with regard to ecologically and commercially important Mexican white pine species of conservation genetics concern: Pinus chiapensis (Mart.) Andresen, P. flexilis James, P. strobiformis Engelm., P. ayacahuite Ehrenb. Ex Schltdl, and P. ayacahuite var. veitchii (Roezl) G.R. Shaw. Four to six microsatellite loci were found to be polymorphic in different species, with moderate to high informativeness in a relatively small number of samples (PIC/HE=0.25-0.93). This successful transfer sidesteps the time- and resource-consuming development of species-specific microsatellite markers, and will facilitate population and conservation genetic studies and genetic resource management of the less studied Mexican white pines.

  9. 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

  10. 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.

  11. Segmental arterial mediolysis mimics systemic vasculitis.

    PubMed

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

    2016-09-01

    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.

  12. Clickable glycopeptoids for synthesis of glycopeptide mimic.

    PubMed

    Singhamahapatra, Anadi; Sahoo, Laxminarayan; Loganathan, Duraikkannu

    2013-10-18

    Structurally diverse novel glycopeptoids were synthesized which can be attached to biologically important peptides by click reaction to improve their potential to be used in medicinal chemistry. Triazole-linked αβ-hydrid glycopeptoids were synthesized that mimic the conserved linkage region of N-linked glycoproteins in eukaryotes. The amide bonds were replaced with triazole rings, and αβ-hybrid peptoids were introduced as the backbone modification in peptidomimetics. In addition to their facile synthesis, these modifications have the possibility of introducing otherwise impossible conformations in the peptide backbone.

  13. 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

  14. Do benzodiazepines mimic reverse-turn structures?

    NASA Astrophysics Data System (ADS)

    Hata, Masayuki; Marshall, Garland R.

    2006-05-01

    The role of benzodiazepine derivatives (BZD) as a privileged scaffold that mimics β-turn structures (Ripka et al. (1993) Tetrahedron 49:3593-3608) in peptide/protein recognition was reexamined in detail. Stable BZD ring conformers were determined with MM3, and experimental reverse-turn structures were extracted from the basis set of protein crystal structures previously defined by Ripka et al. Ideal β-turns were also modeled and similarly compared with BZD conformers. Huge numbers of conformers were generated by systematically scanning the torsional degrees of freedom for BZDs, as well as those of ideal β-turns for comparison. Using these structures, conformers of BZDs were fit to experimental structures as suggested by Ripka et al., or modeled classical β-turn conformers, and the root-mean-square deviation (RMSD) values were calculated for each pairwise comparison. Pairs of conformers with the smallest RMSD values for overlap of the four α-β side-chain orientations were selected. All overlaps of BZD conformers with experimental β-turns yielded one or more comparisons where the least RMSD was significantly small, 0.48-0.86 Å, as previously suggested. Utilizing a different methodology, the overall conclusion that benzodiazepines could serve as reverse-turn mimetics of Ripka et al. is justified. The least RMSD values for the overlap of BZDs and modeled classical β-turns were also less than 1 Å. When comparing BZDs with experimental or classical β-turns, the set of experimental β-turns selected by Ripka et al. fit the BZD scaffolds better than modeled classical β-turns; however, all the experimental β-turns did not fit a particular BZD scaffold better. A single BZD ring conformation, and/or chiral orientation, can mimic some, but not all, of the experimental β-turn structures. BZD has two central ring conformations and one chiral center that explains why the four variations of the BZD scaffold can mimic all types of β-turn structure examined. It was

  15. Oxidoreductase mimic activity of natural pyrrhotite

    NASA Astrophysics Data System (ADS)

    Ibáñez de Aldecoa, A. L.; Velasco, F.; Menor-Salván, C.

    2012-09-01

    The theory of the chemo-autotrophic origin of life, also called the "iron-sulfur world hypothesis", proposes that the system FeS/FeS2 present in the primitive Earth crust gave the reductive power necessary to conduct the first protometabolic redox reactions. Some experimental studies demonstrated the redox activity of the FeS/SH2 system, but none of them used natural FeS. Here, we show that the iron sulfide mineral pyrrhotite is able to mimic the redox activity of the enzyme lactate dehydrogenase, which reversibly reduces the pyruvate in lactate, under prebiotic conditions with pyrite formation.

  16. Mining online genomic resources in Anolis carolinensis facilitates rapid and inexpensive development of cross-species microsatellite markers for the Anolis lizard genus.

    PubMed

    Wordley, Claire; Slate, Jon; Stapley, Jessica

    2011-01-01

    Online sequence databases can provide valuable resources for the development of cross-species genetic markers. In particular, mining expressed tag sequences (EST) for microsatellites and developing conserved cross-species microsatellite markers can provide a rapid and relatively inexpensive method to develop new markers for a range of species. Here, we adopt this approach to develop cross-species microsatellite markers in Anolis lizards, which is a model genus in evolutionary biology and ecology. Using EST sequences from Anolis carolinensis, we identified 127 microsatellites that satisfied our criteria, and tested 49 of these in five species of Anolis (carolinensis, distichus, apletophallus, porcatus and sagrei). We identified between 8 and 25 new variable genetic markers for five Anolis species. These markers will be a valuable resource for studies of population genetics, comparative mapping, mating systems, behavioural ecology and adaptive radiations in this diverse lineage.

  17. Cross-species protein sequence and gene structure prediction with fine-tuned Webscipio 2.0 and Scipio

    PubMed Central

    2011-01-01

    Background Obtaining transcripts of homologs of closely related organisms and retrieving the reconstructed exon-intron patterns of the genes is a very important process during the analysis of the evolution of a protein family and the comparative analysis of the exon-intron structure of a certain gene from different species. Due to the ever-increasing speed of genome sequencing, the gap to genome annotation is growing. Thus, tools for the correct prediction and reconstruction of genes in related organisms become more and more important. The tool Scipio, which can also be used via the graphical interface WebScipio, performs significant hit processing of the output of the Blat program to account for sequencing errors, missing sequence, and fragmented genome assemblies. However, Scipio has so far been limited to high sequence similarity and unable to reconstruct short exons. Results Scipio and WebScipio have fundamentally been extended to better reconstruct very short exons and intron splice sites and to be better suited for cross-species gene structure predictions. The Needleman-Wunsch algorithm has been implemented for the search for short parts of the query sequence that were not recognized by Blat. Those regions might either be short exons, divergent sequence at intron splice sites, or very divergent exons. We have shown the benefit and use of new parameters with several protein examples from completely different protein families in searches against species from several kingdoms of the eukaryotes. The performance of the new Scipio version has been tested in comparison with several similar tools. Conclusions With the new version of Scipio very short exons, terminal and internal, of even just one amino acid can correctly be reconstructed. Scipio is also able to correctly predict almost all genes in cross-species searches even if the ancestors of the species separated more than 100 Myr ago and if the protein sequence identity is below 80%. For our test cases Scipio

  18. Preparation of highly efficient manganese catalase mimics.

    PubMed

    Triller, Michael U; Hsieh, Wen-Yuan; Pecoraro, Vincent L; Rompel, Annette; Krebs, Bernt

    2002-10-21

    The series of compounds [Mn(bpia)(mu-OAc)](2)(ClO(4))(2) (1), [Mn(2)(bpia)(2)(muO)(mu-OAc)](ClO(4))(3).CH(3)CN (2), [Mn(bpia)(mu-O)](2)(ClO(4))(2)(PF(6)).2CH(3)CN (3), [Mn(bpia)(Cl)(2)](ClO)(4) (4), and [(Mn(bpia)(Cl))(2)(mu-O)](ClO(4))(2).2CH(3)CN (5) (bpia = bis(picolyl)(N-methylimidazol-2-yl)amine) represents a structural, spectroscopic, and functional model system for manganese catalases. Compounds 3 and 5 have been synthesized from 2 via bulk electrolysis and ligand exchange, respectively. All complexes have been structurally characterized by X-ray crystallography and by UV-vis and EPR spectroscopies. The different bridging ligands including the rare mono-mu-oxo and mono-mu-oxo-mono-mu-carboxylato motifs lead to a variation of the Mn-Mn separation across the four binuclear compounds of 1.50 A (Mn(2)(II,II) = 4.128 A, Mn(2)(III,III) = 3.5326 and 3.2533 A, Mn(2)(III,IV) = 2.624 A). Complexes 1, 2, and 3 are mimics for the Mn(2)(II,II), the Mn(2)(III,III), and the Mn(2)(III,IV) oxidation states of the native enzyme. UV-vis spectra of these compounds show similarities to those of the corresponding oxidation states of manganese catalase from Thermus thermophilus and Lactobacillus plantarum. Compound 2 exhibits a rare example of a Jahn-Teller compression. While complexes 1 and 3 are efficient catalysts for the disproportionation of hydrogen peroxide and contain an N(4)O(2) donor set, 4 and 5 show no catalase activity. These complexes have an N(4)Cl(2) and N(4)OCl donor set, respectively, and serve as mimics for halide inhibited manganese catalases. Cyclovoltammetric data show that the substitution of oxygen donor atoms with chloride causes a shift of redox potentials to more positive values. To our knowledge, complex 1 is the most efficient binuclear functional manganese catalase mimic exhibiting saturation kinetics to date.

  19. Permanent female mimics in a lekking shorebird.

    PubMed

    Jukema, Joop; Piersma, Theunis

    2006-06-22

    Female mimics are known from many species, but permanent, non-conditional, alternative mating strategies are only known from an isopod, a fish, a lizard and a bird. The single bird example refers to lek-breeding ruffs Philomachus pugnax, a shorebird for which two strategies (independent and satellite) have been known for over 50 years. Ruffs also provided the single case of an animal with two, rather than three, permanent alternative mating strategies. Here, we describe a rare female-like morph of ruffs: the 'missing' third alternative mating strategy, which we have called 'faeder'. Faeders are slightly larger than females and in late April have testes 2.5 time the size of testes of normal males. On leks in aviaries and in the wild they appear to combine feminine and masculine behaviours. Faeders may represent the ancestral, care-giving, male strategy, but their relatively large testes suggest that currently they behave as sneakers.

  20. Daughters mimic sterile neutrinos (almost!) perfectly

    NASA Astrophysics Data System (ADS)

    Hasenkamp, Jasper

    2014-09-01

    Since only recently, cosmological observations are sensitive to hot dark matter (HDM) admixtures with sub-eV mass, mhdmeff < eV, that are not fully-thermalised, Δ Neff < 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 Neff and mhdmeff, 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.

  1. 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.

  2. 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.

  3. Bell's palsy syndrome: mimics and chameleons.

    PubMed

    Fuller, Geraint; Morgan, Cathy

    2016-12-01

    In this article we will explore the mimics and chameleons of Bell's palsy and in addition argue that we should use the term 'Bell's palsy syndrome' to help guide clinical reasoning when thinking about patients with facial weakness. The diagnosis of Bell's palsy can usually be made on clinical grounds without the need for further investigations. This is because the diagnosis is not one of exclusion (despite this being commonly how it is described), a lower motor neurone facial weakness where all alternative causes have been eliminated, but rather a positive recognition of a clinical syndrome, with a number of exclusions, which are described below. This perhaps would be more accurately referred to a 'Bell's palsy syndrome'. Treatment with corticosteroids improves outcome; adding an antiviral probably reduces the rates of long-term complications.

  4. Tiny Device Mimics Human Lung Function

    SciTech Connect

    McDonald, Rebecca; Harris, Jennifer; Nath, Pulak

    2016-04-25

    Scientists at Los Alamos National Laboratory are developing a miniature, tissue-engineered artificial lung that mimics the response of the human lung to drugs, toxins and other agents. “We breathe in and out thousands of times every day. And while we have control over what we eat or drink, we don’t always have control over what we breathe in,” said Jennifer Harris of Biosecurity and Public Health at Los Alamos, "and so we’re making this miniature lung to be able to test on actual human cells whether something in the environment, or a drug, is toxic or harmful to us." Nicknamed “PuLMo” for Pulmonary Lung Model (Pulmo is also the Latin word for "lung")the device consists of two major parts, the bronchiolar unit and the alveolar unit—just like the human lung. The units are primarily made from various polymers and are connected by a microfluidic “circuit board” that manages fluid and air flow. “When we build our lung, we not only take into account the aspects of different cell types, the tissues that are involved, we also take into account that a lung is supposed to breathe, so PuLMo actually breathes,” said Pulak Nath of Applied Modern Physics, who leads engineering efforts for the project. The most exciting application of PuLMo is a potentially revolutionary improvement in the reliability of drug-toxicity assessments and the prediction of new pharmaceutical success in humans, according to Harris. The PuLMo may also be designed to mimic lung disease conditions, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, and may be used to study lung air-flow dynamics to better understand the mechanisms of toxins and drug delivery and the effects of smoking, particularly the less-understood effects of e-cigarettes.

  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. Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development

    PubMed Central

    BRETT, ZOË H.; HUMPHREYS, KATHRYN L.; FLEMING, ALISON S.; KRAEMER, GARY W.; DRURY, STACY S.

    2017-01-01

    Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic–pituitary–adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal–infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence. PMID:25997759

  7. Development of novel microsatellite markers for the Northern Goshawk (Accipiter gentilis) and their utility in cross-species amplification

    USGS Publications Warehouse

    Haughey, Christy; Sage, George K.; Degange, Gabriel; Sonsthagen, Sarah A.; Talbot, Sandra

    2016-01-01

    The Northern Goshawk (Accipiter gentilis) is a large forest raptor with a Holarctic distribution and, in some portions of its range, a species of conservation concern. To augment previously reported genetic markers, 13 novel polymorphic microsatellite markers were developed to establish individual identification and familial relationships, to assess levels of genetic diversity, and to identify diagnostic markers. Of the 22 loci tested, 13 were polymorphic, seven were monomorphic, and two failed to amplify. This suite of microsatellite loci yielded a combined probability of parental exclusion of 98%; a single individual sampled from a North American population can be reliably identified using a combination of seven of the 13 polymorphic loci. Cross-species screening in Cooper's Hawks (A. cooperii) and Sharp-shinned Hawks (A. striatus) of the 20 loci that successfully amplified in Northern Goshawks identified 13 loci as polymorphic in each species. Six of these loci (Age1303, Age1308, Age1309, Age1312, and Age1314) appeared to be useful in distinguishing between Accipiter species. These markers will be useful to researchers investigating populations of North American accipiters.

  8. 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.

  9. 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.

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

    PubMed Central

    ANDERSEN, SUSAN L.

    2017-01-01

    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

  11. 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

  12. Cross-species amplification from crop soybean Glycine max provides informative microsatellite markers for the study of inbreeding wild relatives.

    PubMed

    Hempel, K; Peakall, R

    2003-06-01

    The development of microsatellite markers through transfer of primers from related species (cross-species amplification) remains a little-explored alternative to the de novo method in plants. In this study of 100 microsatellite loci from Glycine max, we examined two aspects of primer transfer. First, we tested if source locus properties can predict primer transfer and polymorphism in Glycine cyrtoloba and Glycine clandestina. We transferred 23 primers to G. cyrtoloba and 42 to G. clandestina, with 19 loci polymorphic within G. clandestina. However, we could not predict transfer or polymorphism from the source locus properties. Second, we evaluated the subset of 11 polymorphic loci for study in G. clandestina populations representing two local morphotypes. All loci were informative within populations (population mean He +/- SE = 0.58 +/- 0.04). We directly sequenced 28 alleles at 4 representative loci. The allelic patterns and sequencing results established that 8 of 11 loci were typical microsatellites, confirming the utility of primer transfer as an alternative to de novo development. Additionally, we found that morphotypic differentiation between populations was paralleled by changes in polymorphism level at six loci and size homoplasy at one locus. We interpret these patterns as being a product of selfing in G. clandestina. Our results demonstrate the value of allele sequence knowledge for the most effective use of microsatellites.

  13. Tiny Device Mimics Human Lung Function

    ScienceCinema

    McDonald, Rebecca; Harris, Jennifer; Nath, Pulak

    2016-07-12

    Scientists at Los Alamos National Laboratory are developing a miniature, tissue-engineered artificial lung that mimics the response of the human lung to drugs, toxins and other agents. “We breathe in and out thousands of times every day. And while we have control over what we eat or drink, we don’t always have control over what we breathe in,” said Jennifer Harris of Biosecurity and Public Health at Los Alamos, "and so we’re making this miniature lung to be able to test on actual human cells whether something in the environment, or a drug, is toxic or harmful to us." Nicknamed “PuLMo” for Pulmonary Lung Model (Pulmo is also the Latin word for "lung")the device consists of two major parts, the bronchiolar unit and the alveolar unit—just like the human lung. The units are primarily made from various polymers and are connected by a microfluidic “circuit board” that manages fluid and air flow. “When we build our lung, we not only take into account the aspects of different cell types, the tissues that are involved, we also take into account that a lung is supposed to breathe, so PuLMo actually breathes,” said Pulak Nath of Applied Modern Physics, who leads engineering efforts for the project. The most exciting application of PuLMo is a potentially revolutionary improvement in the reliability of drug-toxicity assessments and the prediction of new pharmaceutical success in humans, according to Harris. The PuLMo may also be designed to mimic lung disease conditions, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, and may be used to study lung air-flow dynamics to better understand the mechanisms of toxins and drug delivery and the effects of smoking, particularly the less-understood effects of e-cigarettes.

  14. Cross-species comparison of orthologous gene expression in human bladder cancer and carcinogen-induced rodent models

    PubMed Central

    Lu, Yan; Liu, Pengyuan; Wen, Weidong; Grubbs, Clinton J; Townsend, Reid R; Malone, James P; Lubet, Ronald A; You, Ming

    2011-01-01

    Genes differentially expressed by tumor cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. This study examined the suitability of rodent models of bladder cancer in B6D2F1 mice and Fischer-344 rats to model clinical bladder cancer specimens in humans. Using a global gene expression approach cross-species analysis showed that 13-34% of total genes in the genome were differentially expressed between tumor and normal tissues in each of five datasets from humans, rats, and mice. About 20% of these differentially expressed genes overlapped among species, corresponding to 2.6 to 4.8% of total genes in the genome. Several genes were consistently dysregulated in bladder tumors in both humans and rodents. Notably, CNN1, MYL9, PDLIM3, ITIH5, MYH11, PCP4 and FM05 were found to commonly down-regulated; while T0P2A, CCNB2, KIF20A and RRM2 were up-regulated. These genes are likely to have conserved functions contributing to bladder carcinogenesis. Gene set enrichment analysis detected a number of molecular pathways commonly activated in both humans and rodent bladder cancer. These pathways affect the cell cycle, HIF-1 and MYC expression, and regulation of apoptosis. We also compared expression changes at mRNA and protein levels in the rat model and identified several genes/proteins exhibiting concordant changes in bladder tumors, including ANXA1, ANXA2, CA2, KRT14, LDHA, LGALS4, SERPINA1, KRT18 and LDHB. In general, rodent models of bladder cancer represent the clinical disease to an extent that will allow successful mining of target genes and permit studies on the molecular mechanisms of bladder carcinogenesis. PMID:21139803

  15. 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.

  16. Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

    PubMed Central

    Kwekel, Joshua C; Forgacs, Agnes L; Burgoon, Lyle D; Williams, Kurt J; Zacharewski, Timothy R

    2009-01-01

    Background Tamoxifen (TAM) is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM) which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level in vivo.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge. Results A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE) in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns. Conclusion Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation. PMID:19400957

  17. Cross-Species Protection Mediated by a Bordetella bronchiseptica Strain Lacking Antigenic Homologs Present in Acellular Pertussis Vaccines▿

    PubMed Central

    Sukumar, Neelima; Sloan, Gina Parise; Conover, Matt S.; Love, Cheraton F.; Mattoo, Seema; Kock, Nancy D.; Deora, Rajendar

    2010-01-01

    The Bordetella species are Gram-negative bacterial pathogens that are characterized by long-term colonization of the mammalian respiratory tract and are causative agents of respiratory diseases in humans and animals. Despite widespread and efficient vaccination, there has been a world-wide resurgence of pertussis, which remains the leading cause of vaccine-preventable death in developed countries. It has been proposed that current acellular vaccines (Pa) composed of only a few bacterial proteins may be less efficacious because of vaccine-induced antigenic shifts and adaptations. To gain insight into the development of a newer generation of vaccines, we constructed a Bordetella bronchiseptica strain (LPaV) that does not express the antigenic homologs included in any of the Pa vaccines currently in use. This strain also lacks adenylate cyclase toxin, an essential virulence factor, and BipA, a surface protein. While LPaV colonized the mouse nose as efficiently as the wild-type strain, it was highly deficient in colonization of the lower respiratory tract and was attenuated in induction of inflammation and injury to the lungs. Strikingly, to our surprise, we found that in an intranasal murine challenge model, LPaV elicited cross-species protection against both B. bronchiseptica and Bordetella pertussis. Our data suggest the presence of immunogenic protective components other than those included in the pertussis vaccine. Combined with the whole-genome sequences of many Bordetella spp. that are available, the results of this study should serve as a platform for strategic development of the next generation of acellular pertussis vaccines. PMID:20176797

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

    PubMed Central

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

    2011-01-01

    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. PMID:21880778

  19. 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.

  20. 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.

  1. Functional interaction of nuclear domain 10 and its components with cytomegalovirus after infections: cross-species host cells versus native cells.

    PubMed

    Cosme, Ruth Cruz; Martínez, Francisco Puerta; Tang, Qiyi

    2011-04-28

    Species-specificity is one of the major characteristics of cytomegaloviruses (CMVs) and is the primary reason for the lack of a mouse model for the direct infection of human CMV (HCMV). It has been determined that CMV cross-species infections are blocked at the post-entry level by intrinsic cellular defense mechanisms, but few details are known. It is important to explore how CMVs interact with the subnuclear structure of the cross-species host cell. In our present study, we discovered that nuclear domain 10 (ND10) of human cells was not disrupted by murine CMV (MCMV) and that the ND10 of mouse cells was not disrupted by HCMV, although the ND10-disrupting protein, immediate-early protein 1 (IE1), also colocalized with ND10 in cross-species infections. In addition, we found that the UL131-repaired HCMV strain AD169 (vDW215-BADrUL131) can infect mouse cells to produce immediate-early (IE) and early (E) proteins but that neither DNA replication nor viral particles were detectable in mouse cells. Unrepaired AD169 can express IE1 only in mouse cells. In both HCMV-infected mouse cells and MCMV-infected human cells, the knocking-down of ND10 components (PML, Daxx, and SP100) resulted in significantly increased viral-protein production. Our observations provide evidence to support our hypothesis that ND10 and ND10 components might be important defensive factors against the CMV cross-species infection.

  2. 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.

  3. 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

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

    2014-12-01

    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.

  4. Surgically Confirmed Intra- and Extratesticular Hematoma Clinically Mimicing Epididymo-Orchitis and Radiologically Mimicing Traumatic Torsion

    PubMed Central

    Akay, Sinan; Kaygisiz, Mustafa; Oztas, Muharrem; Turgut, Mustafa Suphi

    2015-01-01

    Summary Background Scrotal blunt trauma may result in injuries, such as testicular rupture, dislocation, torsion, hematoma, spermatic cord injury or contusion, and epididymal, scrotal, and urethral injuries. Ultrasonography (US) has a crucial role in the evaluation of those kinds of pathologies. Early diagnosis of testicular rupture may lead to the salvaging of the testicle by prompt surgical exploration within 72 h. Case Report A 21-year-old male with right scrotal swelling and pain complaints was admitted to another hospital one month ago. Epididymo-orchitis was diagnosed and the patient was given medical treatment. The patient was admitted to our emergency service with ongoing complaints. The patient stated that the pain and swelling suddenly developed after prolonged marching. On US, a large hematoma was detected between the leaves of the tunica vaginalis, and rupture from the lower pole was diagnosed. On color Doppler US, no vascularity was observed in the heterogeneous testicular parenchyma. Traumatic torsion was primarily suggested. Intraoperatively, an extratesticular hematoma, hematocele, and rupture were confirmed but torsion was not found. Because the hematoma entirely replaced the normal parenchyma, orchiectomy was performed. Conclusions Testicular rupture may occur even after moderate sportive action such as prolonged marching. If any delay occurs in diagnosis and/or operation, the coagulum may replace the entire parenchyma. We think that US and clinical findings may sometimes mislead the physicians and cause misdiagnoses, such as inflammation or torsion. In this paper, we present a complex delayed diagnosed example case of testicular rupture clinically mimicing epididymo-orchitis and radiologically mimicing traumatic testicular torsion. PMID:26600877

  5. 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.

  6. Traumatic aortic injury: CT findings, mimics, and therapeutic options

    PubMed Central

    Lantz, Eric J.; Johnson, C. Michael; Young, Philip M.

    2014-01-01

    Objective Traumatic aortic injury (TAI) is rare, but frequently lethal. However, with prompt diagnosis, patients can undergo life-saving open or endovascular repair. Unfortunately, because these injuries are relatively rare, subtle forms of these injuries may be missed, and normal variants may mimic TAI leading to misdiagnosis. Conclusions We will discuss computed tomography findings of typical injury patterns of traumatic aortic injuries as well as treatment options, diagnostic pitfalls and injury mimics. These are highlighted with clinical case examples. PMID:25009793

  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. Co-mimics have a mutualistic relationship despite unequal defences.

    PubMed

    Rowland, Hannah M; Ihalainen, Eira; Lindström, Leena; Mappes, Johanna; Speed, Michael P

    2007-07-05

    In the first clear mathematical treatment of natural selection, Müller proposed that a shared warning signal (mimicry) would benefit defended prey species by sharing out the per capita mortality incurred during predator education. Although mimicry is a mainstay of adaptationist thinking, there has been repeated debate on whether there is a mutualistic or a parasitic relationship between unequally defended co-mimic species. Here we show that the relationship between unequally defended species is mutualistic. We examined this in a 'novel world' of artificial prey with wild predators (great tit, Parus major). We kept the abundance of a highly defended prey ('model') constant and increased the density of a moderately defended prey ('defended mimic') of either perfect or imperfect mimetic resemblance to the model. Both model and defended mimic showed a net benefit from a density-dependent decrease in their per capita mortality. Even when the effect of dilution through density was controlled for, defended mimics did not induce additional attacks on the model, but we found selection for accurate signal mimicry. In comparison, the addition of fully edible (batesian) mimics did increase additional attacks on the model, but as a result of dilution this resulted in no overall increase in per capita mortality. By ignoring the effects of density, current theories may have overestimated the parasitic costs imposed by less defended mimics on highly defended models.

  9. 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.

  10. 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.

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

    PubMed

    Pelz-Serrano, Karla; Munguia-Vega, Adrian; Piaggio, Antoinette J; Neubaum, Melissa; Munclinger, Pavel; Pártl, Adam; VAN Riper Iii, Charles; Culver, Melanie

    2009-03-01

    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.

  12. 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.

  13. 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.

  14. Molecular Mimics of the Tumour Antigen MUC1

    PubMed Central

    James, Tharappel C.; Bond, Ursula

    2012-01-01

    A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as “self”, and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as ‘proof of principle’ we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1) from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides. PMID:23166757

  15. Genetic differences accounting for evolution and pathogenicity of simian immunodeficiency virus from a sooty mangabey monkey after cross-species transmission to a pig-tailed macaque.

    PubMed Central

    Courgnaud, V; Lauré, F; Fultz, P N; Montagnier, L; Bréchot, C; Sonigo, P

    1992-01-01

    We determined the nucleotide sequences of two related isolates of simian immunodeficiency virus from the sooty mangabey monkey (SIVsmm) that exhibit dramatic differences in virulence. These isolates are separated by one experimental cross-species transmission, from sooty mangabey to pig-tailed macaque. The parental virus (SIVsmm9), nonpathogenic in the original host (sooty mangabeys), causes a chronic AIDS-like disease in macaques. In contrast, the variant virus (SIVsmmPBj14) induces an acute lethal disease in various macaque species and is also pathogenic for sooty mangabeys. The combination of necessary and sufficient mutations that determined the acutely lethal phenotype on the SIVsmm9 genetic background is included within a maximal set of 57 point mutations, plus two insertions located in the long terminal repeat (22 bp spanning an NF-kappa B-like enhancer element) and in the surface envelope glycoprotein (5 amino acids). Comparisons of synonymous and nonsynonymous nucleotide substitutions in the genome of SIVsmm indicated that selective pressures, probably due to the host immune response, favored amino acid changes in the envelope. This immunoevolutionary mechanism could explain the increase in diversity and the apparition of new virulent phenotypes after cross-species transmission. PMID:1727495

  16. 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.

  17. Feline lentivirus evolution in cross-species infection reveals extensive G-to-A mutation and selection on key residues in the viral polymerase.

    PubMed

    Poss, Mary; Ross, Howard A; Painter, Sally L; Holley, David C; Terwee, Julie A; Vandewoude, Sue; Rodrigo, Allen

    2006-03-01

    Factors that restrict a virus from establishing productive infection in a new host species are important to understand because cross-species transmission events are often associated with emergent viral diseases. To determine the evolutionary pressures on viruses in new host species, we evaluated the molecular evolution of a feline immunodeficiency virus derived from a wild cougar, Puma concolor, during infection of domestic cats. Analyses were based on the coding portion of genome sequences recovered at intervals over 37 weeks of infection of six cats inoculated by either intravenous or oral-nasal routes. All cats inoculated intravenously, but only one inoculated orally-nasally, became persistently viremic. There were notable accumulations of lethal errors and predominance of G-to-A alterations throughout the genome, which were marked in the viral polymerase gene, pol. Viral structural (env and gag) and accessory (vif and orfA) genes evolved neutrally or were under purifying selection. However, sites under positive selection were identified in reverse transcriptase that involved residues in the nucleotide binding pocket or those contacting the RNA-DNA duplex. The findings of extensive G-to-A alterations in this cross-species infection are consistent with the recently described editing of host cytidine deaminase on lentivirus genomes. Additionally, we demonstrate that the primary site of hypermutation is the viral pol gene and the dominant selective force acting on this feline immunodeficiency virus as it replicates in a new host species is on key residues of the virus polymerase.

  18. 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.

  19. 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.

  20. Optimal Control In Predation Of Models And Mimics

    NASA Astrophysics Data System (ADS)

    Tsoularis, A.

    2007-09-01

    This paper examines optimal predation by a predator preying upon two types of prey, modes and mimics. Models are unpalatable prey and mimics are palatable prey resembling the models so as to derive some protection from predation. This biological phenomenon is known in Ecology as Batesian mimicry. An optimal control problem in continuous time is formulated with the sole objective to maximize the net energetic benefit to the predator from predation in the presence of evolving prey populations. The constrained optimal control is bang-bang with the scalar control taken as the probability of attacking prey. Conditions for the existence of singular controls are obtained.

  1. Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

    PubMed Central

    Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species

  2. Detection of superficial zone protein in human and animal body fluids by cross-species monoclonal antibodies specific to superficial zone protein.

    PubMed

    Su, J L; Schumacher, B L; Lindley, K M; Soloveychik, V; Burkhart, W; Triantafillou, J A; Kuettner, K; Schmid, T

    2001-06-01

    In this report we describe the purification of human superficial zone protein (SZP), the generation of cross-species monoclonal antibodies (MAbs) and the detection of this protein in human and animal body fluids. Human SZPs, used as immunizing antigens, were purified either from culture media of human cartilage organ cultures or from human synovial fluids. The immunizing antigens were mixed with RIBI adjuvant in one of three forms: nonmodified SZP, superficial zone protein-keyhole limpet hemocyanin conjugate (SZP-KLH), or a mixture of superficial zone protein and hyaluronic acid (SZP-HA). A panel of MAbs including GW4.23, S6.79, S13.52, S13.233, and S17.109 were generated and characterized. Monoclonal antibody (MAb) S6.79, an IgG2b with K(D) 3.14 x 10(-9) M from SZP-KLH immunization, is of particular interest. It reacts strongly to a large molecular weight form of SZP in both enzyme-linked immunosorbent assay (ELISA) and Western blotting. It stains the most superficial layer of articular cartilage in immunohistochemistry, whereas the middle and deep zones of cartilage are not stained. When MAb S6.79 was applied to Western blots of human body fluids, a strong 345-kDa band was detected in samples of synovial fluid and weaker bands of similar size were detected in samples of plasma and serum. MAb S6.79 also showed cross-species immunoreactivity with SZP in samples of synovial fluids harvested from bovine, dog, guinea pig, and rabbit, as demonstrated by Western blotting and antibody absorption experiments. This cross-species MAb will be a useful tool in human and animal model studies for monitoring SZP levels and tissue distribution. It may help define the roles of SZP in normal articular joints and may be of diagnostic or prognostic value for the measurement of SZP in pathological conditions such as osteoarthritis, rheumatoid arthritis, and camptodactyly-arthropathy-coxa vara-pericarditis.

  3. Gene-specific cell labeling using MiMIC transposons

    PubMed Central

    Gnerer, Joshua P.; Venken, Koen J. T.; Dierick, Herman A.

    2015-01-01

    Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. PMID:25712101

  4. Gene-specific cell labeling using MiMIC transposons.

    PubMed

    Gnerer, Joshua P; Venken, Koen J T; Dierick, Herman A

    2015-04-30

    Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family.

  5. Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

    PubMed Central

    Belov, Sergey S; Tarasenko, Yulia V; Silnikov, Vladimir N

    2014-01-01

    Summary An efficient solid-phase-supported peptide synthesis (SPPS) of morpholinoglycine oligonucleotide (MorGly) mimics has been developed. The proposed strategy includes a novel specially designed labile linker group containing the oxalyl residue and the 2-aminomethylmorpholino nucleoside analogues as first subunits. PMID:24991266

  6. 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…

  7. 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…

  8. Cross-Species, Amplifiable Microsatellite Markers for Neoverrucid Barnacles from Deep-Sea Hydrothermal Vents Developed Using Next-Generation Sequencing

    PubMed Central

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

    2014-01-01

    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. PMID:25196437

  9. 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.

  10. Rabbit hepatitis E virus is an opportunistic pathogen in specific-pathogen-free rabbits with the capability of cross-species transmission.

    PubMed

    Liu, Baoyuan; Sun, Yani; Du, Taofeng; Chen, Yiyang; Wang, Xinjie; Huang, Baicheng; Li, Huixia; Nan, Yuchen; Xiao, Shuqi; Zhang, Gaiping; Hiscox, Julian A; Zhou, En-Min; Zhao, Qin

    2017-03-01

    Hepatitis E virus (HEV) has been detected in rabbits, a recently identified natural reservoir. In this study, anti-HEV antibodies and viral RNA were detected in rabbits sourced from a specific-pathogen-free (SPF) rabbit vendor in Shaanxi Province, China. BLAST results of partial HEV ORF2 genes cloned here indicated that two viral strains circulated in the rabbits. Sequence determination of the complete genome (7302bp) of one strain and a partial ORF1 gene (1537bp) of the other strain showed that they shared 90% identity with one another and 78%-94% identity with other known rabbit HEVs. In addition, inoculation with rabbit HEV from SPF rabbits studied here resulted in infection of SPF pigs; this cross-species transmission was evidenced by seroconversion, viremia and faecal virus shedding. These results suggest that to prevent spread of this zoonotic pathogen, rabbits should be tested routinely for HEV RNA in SPF vendor facilities.

  11. 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.

  12. INVESTIGATING THE IMPORTANCE OF ANATOMICAL HOMOLOGY FOR CROSS-SPECIES PHENOTYPE COMPARISONS USING SEMANTIC SIMILARITY. Accepted at Pacific Symposium on Biocomputing, 2016.

    PubMed

    Manda, Prashanti; Mungall, Christopher J; Balhoff, James P; Lapp, Hilmar; Vision, Todd J

    2016-01-01

    There is growing use of ontologies for the measurement of cross-species phenotype similarity. Such similarity measurements contribute to diverse applications, such as identifying genetic models for human diseases, transferring knowledge among model organisms, and studying the genetic basis of evolutionary innovations. Two organismal features, whether genes, anatomical parts, or any other inherited feature, are considered to be homologous when they are evolutionarily derived from a single feature in a common ancestor. A classic example is the homology between the paired fins of fishes and vertebrate limbs. Anatomical ontologies that model the structural relations among parts may fail to include some known anatomical homologies unless they are deliberately added as separate axioms. The consequences of neglecting known homologies for applications that rely on such ontologies has not been well studied. Here, we examine how semantic similarity is affected when external homology knowledge is included. We measure phenotypic similarity between orthologous and non-orthologous gene pairs between humans and either mouse or zebrafish, and compare the inclusion of real with faux homology axioms. Semantic similarity was preferentially increased for orthologs when using real homology axioms, but only in the more divergent of the two species comparisons (human to zebrafish, not human to mouse), and the relative increase was less than 1% to non-orthologs. By contrast, inclusion of both real and faux random homology axioms preferentially increased similarities between genes that were initially more dissimilar in the other comparisons. Biologically meaningful increases in semantic similarity were seen for a select subset of gene pairs. Overall, the effect of including homology axioms on cross-species semantic similarity was modest at the levels of divergence examined here, but our results hint that it may be greater for more distant species comparisons.

  13. Genetic diversity and differentiation in reef-building Millepora species, as revealed by cross-species amplification of fifteen novel microsatellite loci.

    PubMed

    Dubé, Caroline E; Planes, Serge; Zhou, Yuxiang; Berteaux-Lecellier, Véronique; Boissin, Emilie

    2017-01-01

    Quantifying the genetic diversity in natural populations is crucial to address ecological and evolutionary questions. Despite recent advances in whole-genome sequencing, microsatellite markers have remained one of the most powerful tools for a myriad of population genetic approaches. Here, we used the 454 sequencing technique to develop microsatellite loci in the fire coral Millepora platyphylla, an important reef-builder of Indo-Pacific reefs. We tested the cross-species amplification of these loci in five other species of the genus Millepora and analysed its success in correlation with the genetic distances between species using mitochondrial 16S sequences. We succeeded in discovering fifteen microsatellite loci in our target species M. platyphylla, among which twelve were polymorphic with 2-13 alleles and a mean observed heterozygosity of 0.411. Cross-species amplification in the five other Millepora species revealed a high probability of amplification success (71%) and polymorphism (59%) of the loci. Our results show no evidence of decreased heterozygosity with increasing genetic distance. However, only one locus enabled measures of genetic diversity in the Caribbean species M. complanata due to high proportions of null alleles for most of the microsatellites. This result indicates that our novel markers may only be useful for the Indo-Pacific species of Millepora. Measures of genetic diversity revealed significant linkage disequilibrium, moderate levels of observed heterozygosity (0.323-0.496) and heterozygote deficiencies for the Indo-Pacific species. The accessibility to new polymorphic microsatellite markers for hydrozoan Millepora species creates new opportunities for future research on processes driving the complexity of their colonisation success on many Indo-Pacific reefs.

  14. Insights into gene expression changes impacting B-cell transformation: cross-species microarray analysis of bovine leukemia virus tax-responsive genes in ovine B cells.

    PubMed

    Klener, Pavel; Szynal, Maud; Cleuter, Yvette; Merimi, Makram; Duvillier, Hugues; Lallemand, Françoise; Bagnis, Claude; Griebel, Philip; Sotiriou, Christos; Burny, Arsène; Martiat, Philippe; Van den Broeke, Anne

    2006-02-01

    Large-animal models for leukemia have the potential to aid in the understanding of networks that contribute to oncogenesis. Infection of cattle and sheep with bovine leukemia virus (BLV), a complex retrovirus related to human T-cell leukemia virus type 1 (HTLV-1), is associated with the development of B-cell leukemia. Whereas the natural disease in cattle is characterized by a low tumor incidence, experimental infection of sheep leads to overt leukemia in the majority of infected animals, providing a model for studying the pathogenesis associated with BLV and HTLV-1. Tax(BLV), the major oncoprotein, initiates a cascade of events leading toward malignancy, although the basis of transformation is not fully understood. We have taken a cross-species ovine-to-human microarray approach to identify Tax(BLV)-responsive transcriptional changes in two sets of cultured ovine B cells following retroviral vector-mediated delivery of Tax(BLV). Using cDNA-spotted microarrays comprising 10,336 human genes/expressed sequence tags, we identified a cohort of differentially expressed genes, including genes related to apoptosis, DNA transcription, and repair; proto-oncogenes; cell cycle regulators; transcription factors; small Rho GTPases/GTPase-binding proteins; and previously reported Tax(HTLV-1)-responsive genes. Interestingly, genes known to be associated with human neoplasia, especially B-cell malignancies, were extensively represented. Others were novel or unexpected. The results suggest that Tax(BLV) deregulates a broad network of interrelated pathways rather than a single B-lineage-specific regulatory process. Although cross-species approaches do not permit a comprehensive analysis of gene expression patterns, they can provide initial clues for the functional roles of genes that participate in B-cell transformation and pinpoint molecular targets not identified using other methods in animal models.

  15. 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.

  16. Genetic diversity and differentiation in reef-building Millepora species, as revealed by cross-species amplification of fifteen novel microsatellite loci

    PubMed Central

    Planes, Serge; Zhou, Yuxiang; Berteaux-Lecellier, Véronique; Boissin, Emilie

    2017-01-01

    Quantifying the genetic diversity in natural populations is crucial to address ecological and evolutionary questions. Despite recent advances in whole-genome sequencing, microsatellite markers have remained one of the most powerful tools for a myriad of population genetic approaches. Here, we used the 454 sequencing technique to develop microsatellite loci in the fire coral Millepora platyphylla, an important reef-builder of Indo-Pacific reefs. We tested the cross-species amplification of these loci in five other species of the genus Millepora and analysed its success in correlation with the genetic distances between species using mitochondrial 16S sequences. We succeeded in discovering fifteen microsatellite loci in our target species M. platyphylla, among which twelve were polymorphic with 2–13 alleles and a mean observed heterozygosity of 0.411. Cross-species amplification in the five other Millepora species revealed a high probability of amplification success (71%) and polymorphism (59%) of the loci. Our results show no evidence of decreased heterozygosity with increasing genetic distance. However, only one locus enabled measures of genetic diversity in the Caribbean species M. complanata due to high proportions of null alleles for most of the microsatellites. This result indicates that our novel markers may only be useful for the Indo-Pacific species of Millepora. Measures of genetic diversity revealed significant linkage disequilibrium, moderate levels of observed heterozygosity (0.323–0.496) and heterozygote deficiencies for the Indo-Pacific species. The accessibility to new polymorphic microsatellite markers for hydrozoan Millepora species creates new opportunities for future research on processes driving the complexity of their colonisation success on many Indo-Pacific reefs. PMID:28243525

  17. 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

  18. 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

  19. 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

  20. 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

  1. Diversity of the G3 genes of human rotaviruses in isolates from Spain from 2004 to 2006: cross-species transmission and inter-genotype recombination generates alleles.

    PubMed

    Martínez-Laso, Jorge; Román, Angela; Rodriguez, Miriam; Cervera, Isabel; Head, Jacqueline; Rodríguez-Avial, Iciar; Picazo, Juan J

    2009-04-01

    Rotavirus evolves by using multiple genetic mechanisms which are an accumulation of spontaneous point mutations and reassortment events. Other mechanisms, such as cross-species transmission and inter-genotype recombination, may be also involved. One of the most interesting genotypes in the accumulation of these events is the G3 genotype. In this work, six new Spanish G3 sequences belonging to 0-2-year-old patients from Madrid were analysed and compared with 160 others of the same genotype obtained from humans and other host species to establish the evolutionary pathways of the G3 genotype. The following results were obtained: (i) there are four different lineages of the G3 genotype which have evolved in different species; (ii) Spanish G3 rotavirus sequences are most similar to the described sequences that belong to lineage I; (iii) several G3 genotype alleles were reassigned as other G genotypes; and (iv) inter-genotype recombination events in G3 viruses involving G1 and G2 were described. These findings strongly suggest multiple inter-species transmission events between different non-human mammalian species and humans.

  2. Eimeria tenella and E. acervulina: differences in ability to elicit cross-species protection as compared with the turkey coccidium, E. adenoeides.

    PubMed

    Augustine, P C; Danforth, H D

    1995-01-01

    Repeated oral inoculation of turkey poults with large doses (1 x 10(6) oocysts) of the chicken coccidia, Eimeria tenella or E. acervulina, failed to prevent weight loss, poor feed conversion, and intestinal pathology in turkeys challenged with the turkey coccidium, E. adenoeides. Invasion by E. tenella in turkeys was significantly greater than invasion by E. adenoeides in chickens; by 24 hr postinoculation (PI), the numbers of E. tenella and E. adenoeides sporozoites in the ceca had decreased markedly as compared with the numbers that initially invaded, and they did not differ significantly from each other. At 24 hr PI, however, transfer of cecal scrapings from chickens or turkeys inoculated with E. adenoeides produced infection in 53% of the recipient turkeys, but transfer of scrapings from either chickens or turkeys inoculated with E. tenella failed to produce infection in 20 attempts with recipient chickens. Cultured chicken peripheral blood monocytes (PBMs) that were inoculated with E. adenoeides sporozoites contained numerous vesicles that were recognized by the refractile body-specific monoclonal antibody 1209; the number of vesicles was markedly decreased in PBM cultures inoculated with gamma-irradiated E. adenoeides sporozoites. Very few vesicles were detected in the cytoplasm of turkey PBMs that contained E. tenella sporozoites, and none were detected in turkey PBMs containing E. adenoeides sporozoites. The survival of infective sporozoites, along with the secretion of refractile body antigen, may be more critical to the development of cross-species immunity than the number of sporozoites that initially invade the foreign host.

  3. 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.

  4. 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.

  5. 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

  6. The Challenge of Cancer Genomics in Rare Nervous System Neoplasms: Malignant Peripheral Nerve Sheath Tumors as a Paradigm for Cross-Species Comparative Oncogenomics.

    PubMed

    Carroll, Steven L

    2016-03-01

    Comprehensive genomic analyses of common nervous system cancers provide new insights into their pathogenesis, diagnosis, and treatment. Although analogous studies of rare nervous system tumors are needed, there are major barriers to performing such studies. Cross-species comparative oncogenomics, identifying driver mutations in mouse cancer models and validating them in human tumors, is a promising alternative. Although still in its infancy, this approach is being applied to malignant peripheral nerve sheath tumors (MPNSTs), rare Schwann cell-derived malignancies that occur sporadically, after radiotherapy, and in neurofibromatosis type 1. Studies of human neurofibromatosis type 1-associated tumors suggest that NF1 tumor suppressor loss in Schwann cells triggers cell-autonomous and intercellular changes, resulting in development of benign neurofibromas; subsequent neurofibroma-MPNST progression is caused by aberrant growth factor signaling and mutations affecting the p16(INK4A)-cyclin D1-CDK4-Rb and p19(ARF)-Mdm2-p53 cell cycle pathways. Mice with Nf1, Trp53, and/or Cdkn2a mutations that overexpress the Schwann cell mitogen neuregulin-1 or overexpress the epidermal growth factor receptor validate observations in human tumors and, to various degrees, model human tumorigenesis. Genomic analyses of MPNSTs arising in neuregulin-1 and epidermal growth factor receptor-overexpressing mice and forward genetic screens with Sleeping Beauty transposons implicate additional signaling cascades in MPNST pathogenesis. These studies confirm the utility of mouse models for MPNST driver gene discovery and provide new insights into the complexity of MPNST pathogenesis.

  7. 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.

  8. 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

    2015-06-18

    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.

  9. 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.

  10. 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

  11. 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

  12. 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…

  13. 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…

  14. Design of more powerful iron-TAML peroxidase enzyme mimics.

    PubMed

    Ellis, W Chadwick; Tran, Camly T; Denardo, Matthew A; Fischer, Andreas; Ryabov, Alexander D; Collins, Terrence J

    2009-12-23

    Environmentally useful, small molecule mimics of the peroxidase enzymes must exhibit very high reactivity in water near neutral pH. Here we describe the design and structural and kinetic characterization of a second generation of iron(III)-TAML activators with unprecedented peroxidase-mimicking abilities. Iterative design has been used to remove the fluorine that led to the best performers in first-generation iron-TAMLs. The result is a superior catalyst that meets a green chemistry objective by being comprised exclusively of biochemically common elements. The rate constants for bleaching at pH 7, 9, and 11 of the model substrate, Orange II, shows that the new Fe(III)-TAML has the fastest reactivity at pH's closer to neutral of any TAML activator to date. Under appropriate conditions, the new catalyst can decolorize Orange II without loss of activity for at least 10 half-lives, attesting to its exceptional properties as an oxidizing enzyme mimic.

  15. Stump appendicitis: surgical background, CT appearance, and imaging mimics.

    PubMed

    Johnston, Jennifer; Myers, Daniel T; Williams, Todd R

    2015-02-01

    Stump appendicitis, also known as remnant appendicitis, is an uncommon entity with little radiologic literature. It is the result of unintentional incomplete appendectomy with subsequent inflammatory changes in the appendiceal remnant. A retrospective review of the radiology and pathology archives at our institution over an 8-year period yielded six surgically/pathologically confirmed cases. Imaging findings at presentation were evaluated, including appendiceal stump length, appendiceal stump diameter, presence or absence of surrounding stranding in the periappendiceal fat, and presence or absence of complication (perforation or abscess). The CT findings of the six cases had an average surgical specimen appendiceal stump length of 3.5 cm (range 2.0-5 cm) and an average appendiceal diameter of 12.3 mm (range 10-16 mm). All six cases demonstrated the presence of periappendiceal inflammatory fat stranding on the CT scan. Range of imaging presentation is reviewed with pictorial examples as well as examples of potential false-positive cases (mimics) including Crohn's disease, residual surgical drain tract, and epiploic appendagitis. Familiarity with stump appendicitis as well as its imaging mimics may lead to earlier diagnosis and treatment and prevent unnecessary complications.

  16. Single-Walled Carbon Nanotubes: Mimics of Biological Ion Channels

    PubMed Central

    2017-01-01

    Here we report on the ion conductance through individual, small diameter single-walled carbon nanotubes. We find that they are mimics of ion channels found in natural systems. We explore the factors governing the ion selectivity and permeation through single-walled carbon nanotubes by considering an electrostatic mechanism built around a simplified version of the Gouy–Chapman theory. We find that the single-walled carbon nanotubes preferentially transported cations and that the cation permeability is size-dependent. The ionic conductance increases as the absolute hydration enthalpy decreases for monovalent cations with similar solid-state radii, hydrated radii, and bulk mobility. Charge screening experiments using either the addition of cationic or anionic polymers, divalent metal cations, or changes in pH reveal the enormous impact of the negatively charged carboxylates at the entrance of the single-walled carbon nanotubes. These observations were modeled in the low-to-medium concentration range (0.1–2.0 M) by an electrostatic mechanism that mimics the behavior observed in many biological ion channel-forming proteins. Moreover, multi-ion conduction in the high concentration range (>2.0 M) further reinforces the similarity between single-walled carbon nanotubes and protein ion channels. PMID:28103039

  17. Single-Walled Carbon Nanotubes: Mimics of Biological Ion Channels.

    PubMed

    Amiri, Hasti; Shepard, Kenneth L; Nuckolls, Colin; Hernández Sánchez, Raúl

    2017-02-08

    Here we report on the ion conductance through individual, small diameter single-walled carbon nanotubes. We find that they are mimics of ion channels found in natural systems. We explore the factors governing the ion selectivity and permeation through single-walled carbon nanotubes by considering an electrostatic mechanism built around a simplified version of the Gouy-Chapman theory. We find that the single-walled carbon nanotubes preferentially transported cations and that the cation permeability is size-dependent. The ionic conductance increases as the absolute hydration enthalpy decreases for monovalent cations with similar solid-state radii, hydrated radii, and bulk mobility. Charge screening experiments using either the addition of cationic or anionic polymers, divalent metal cations, or changes in pH reveal the enormous impact of the negatively charged carboxylates at the entrance of the single-walled carbon nanotubes. These observations were modeled in the low-to-medium concentration range (0.1-2.0 M) by an electrostatic mechanism that mimics the behavior observed in many biological ion channel-forming proteins. Moreover, multi-ion conduction in the high concentration range (>2.0 M) further reinforces the similarity between single-walled carbon nanotubes and protein ion channels.

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

    PubMed

    Pfennig, David W; Mullen, Sean P

    2010-09-07

    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.

  19. 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

  20. Cross-species transmission of Giardia spp.: inoculation of beavers and muskrats with cysts of human, beaver, mouse, and muskrat origin.

    PubMed Central

    Erlandsen, S L; Sherlock, L A; Januschka, M; Schupp, D G; Schaefer, F W; Jakubowski, W; Bemrick, W J

    1988-01-01

    Giardia cysts isolated from humans, beavers, mice, and muskrats were tested in cross-species transmission experiments for their ability to infect either beavers or muskrats. Giardia cysts, derived from multiple symptomatic human donors and used for inoculation of beavers or muskrats, were shown to be viable by incorporation of fluorogenic dyes, excystation, and their ability to produce infections in the Mongolian gerbil model. Inoculation of beavers with 5 x 10(5) Giardia lamblia cysts resulted in the infection of 75% of the animals (n = 8), as judged by the presence of fecal cysts or intestinal trophozoites at necropsy. The mean prepatent period was 13.1 days. An infective dose experiment, using 5 x 10(1) to 5 x 10(5) viable G. lamblia cysts collected by fluorescence-activated cell sorting, demonstrated that doses of between, less than 50, and less than 500 viable cysts were required to produce infection in beavers. Scanning electron microscopy of beaver small intestine revealed that attachment of G. lamblia trophozoites produced lesions in the microvillous border. Inoculation of muskrats with G. lamblia cysts produced infections when the dose of cysts was equal to or greater than 1.25 x 10(5). The inoculation of beavers with Giardia ondatrae or Giardia muris cysts did not produce any infection; however, the administration to muskrats of Giardia cysts of beaver origin resulted in the infection of 62% of the animals (n = 8), with a prepatent period of 5 days. Our results demonstrated that beavers and muskrats could be infected with Giardia cysts derived from humans, but only by using large numbers of cysts.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:3063208

  1. 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.

  2. 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.

  3. 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

  4. 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

    2016-04-04

    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.

  5. 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

  6. Evaluation of a carbonic anhydrase mimic for industrial carbon capture.

    PubMed

    Floyd, William C; Baker, Sarah E; Valdez, Carlos A; Stolaroff, Joshuah K; Bearinger, Jane P; Satcher, Joe H; Aines, Roger D

    2013-09-03

    Zinc(II) cyclen, a small molecule mimic of the enzyme carbonic anhydrase, was evaluated under rigorous conditions resembling those in an industrial carbon capture process: high pH (>12), nearly saturated salt concentrations (45% K2CO3) and elevated temperatures (100-130 °C). We found that the catalytic activity of zinc cyclen increased with increasing temperature and pH and was retained after exposure to a 45% w/w K2CO3 solution at 130 °C for 6 days. However, high bicarbonate concentrations markedly reduced the activity of the catalyst. Our results establish a benchmark level of stability and provide qualitative insights for the design of improved small-molecule carbon capture catalysts.

  7. 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.

  8. 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

  9. Synthesis of substituted benzimidazolyl curcumin mimics and their anticancer activity.

    PubMed

    Woo, Ho Bum; Eom, Young Woo; Park, Kyu-Sang; Ham, Jungyeob; Ahn, Chan Mug; Lee, Seokjoon

    2012-01-15

    A novel curcumin mimic library (14a-14h and 15a-15h) possessing variously substituted benzimidazole groups was synthesized through the aldol reaction of (E)-4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-one (7) or (E)-4-(3-hydroxy-4-methoxyphenyl)but-3-en-2-one (13) with diversely substituted benzimidazolyl-2-carbaldehyde (12a-12h). The MTT assay of the cancer cells MCF-7, SH-SY5Y, HEP-G2, and H460 showed that compound 14c with IC(50) of 1.0 and 1.9μM has a strong inhibitory effect on the growth of SH-SY5Y and Hep-G2 cells, respectively, and that compound 15h with IC(50) of 1.9μM has a strong inhibitory effect on the growth of MCF-7 cancer cells.

  10. 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.

  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. 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

  13. 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

  14. Essential metabolites of Mycobacterium tuberculosis and their mimics.

    PubMed

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

    2011-02-01

    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.

  15. 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

  16. 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.

  17. 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

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

    PubMed

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

    2013-10-07

    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.

  19. A Molecular Mechanics Analysis of Molecular Recognition by Cyclodextrin Mimics of Alpha-Chymotrypsin

    DTIC Science & Technology

    1989-05-26

    Recognition By Cyclodextrin Mimics of Alpha-Chymotrypsin i by C.A. Venanzi. P.M. Canzius, Z. Zhang, and J.D. Bunce LT IC To Be Published in CLECTE JUN 0 51...Clasification) A Molecular Mechanics Analysis of Molecular Recognition By Cyclodextrin Mimics of Alpha-Chymotrypsin. 12. PERSONAL AUTHOR(S) C.A. Venanzil... CYCLODEXTRIN MIMICS OF 0( -CHYMOTRYPSIN Carol A. Venanzi1 , Preston M. Canzius, Zhifeng Zhang, and Jeffrey D. Bunce Department of Chemical Engineering

  20. Accessing the public MIMIC-II intensive care relational database for clinical research

    PubMed Central

    2013-01-01

    Background The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database is a free, public resource for intensive care research. The database was officially released in 2006, and has attracted a growing number of researchers in academia and industry. We present the two major software tools that facilitate accessing the relational database: the web-based QueryBuilder and a downloadable virtual machine (VM) image. Results QueryBuilder and the MIMIC-II VM have been developed successfully and are freely available to MIMIC-II users. Simple example SQL queries and the resulting data are presented. Clinical studies pertaining to acute kidney injury and prediction of fluid requirements in the intensive care unit are shown as typical examples of research performed with MIMIC-II. In addition, MIMIC-II has also provided data for annual PhysioNet/Computing in Cardiology Challenges, including the 2012 Challenge “Predicting mortality of ICU Patients”. Conclusions QueryBuilder is a web-based tool that provides easy access to MIMIC-II. For more computationally intensive queries, one can locally install a complete copy of MIMIC-II in a VM. Both publicly available tools provide the MIMIC-II research community with convenient querying interfaces and complement the value of the MIMIC-II relational database. PMID:23302652

  1. 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.

  2. Intraneural Ganglion in Superficial Radial Nerve Mimics de Quervain Tenosynovitis

    PubMed Central

    Haller, Justin M.; Potter, Michael Q.; Sinclair, Micah; Hutchinson, Douglas T.

    2014-01-01

    Background Intraneural ganglions in peripheral nerves of the upper extremity are extremely rare and poorly understood. Case Description We report a patient with symptoms consistent with de Quervain tenosynovitis who was found to have an intraneural ganglion in the superficial radial nerve. The ganglion did not communicate with the wrist joint. We removed the intraneural ganglion, and the patient's symptoms resolved. At her 6-month postoperative follow-up, she remained asymptomatic. Literature Review: There is only one case report of intraneural ganglion in the superficial radial nerve. In that case, the patient had symptoms consistent with nerve irritation, including radiating pain and paresthesias. In contrast to that previous report, the patient in the current case had only localized pain, no paresthesias, and a physical exam consistent with de Quervain tenosynovitis. Clinical Relevance This case demonstrates that an intraneural ganglion cyst can mimic the symptoms of de Quervain tenosynovitis without the more usual presentation of painful paresthesias. PMID:25364639

  3. 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.

  4. Approaches to mimic the metallic sheen in beetles

    NASA Astrophysics Data System (ADS)

    Lenau, Torben A.; Aggerbeck, Martin; Nielsen, Steffen

    2009-08-01

    A range of different beetles exhibits brilliant colours and metallic sheen. One of the most spectacular species is the Plusiotis resplendens from Central America with gold metal appearance. The beetle shells are made from chitin and have a number of unique properties that apart from spectacular aesthetic effects include metal sheen from non-metal surfaces combined with electric and thermal insulation. The reflection mechanism has been studied by a number of authors and is well understood. Basically there are 2 different reflection principles. One is the multilayer reflector where alternating layers have high and low refractive index. The other is the Bouligand structure where birefringent chiral nanofibres are organised in spiral structures. The paper describes work done to explore different approaches to mimic these structures using polymer based materials and production methods that are suitable for more complex double curved geometry. One approach is to use alternating layers of 2 different polymers applied by dipping and another is applying cholesteric liquid crystals in paint. However, none of them can yet make the desired metal-looking free-form surfaces.

  5. Biased gene transfer mimics patterns created through shared ancestry

    PubMed Central

    Andam, Cheryl P.; Williams, David; Gogarten, J. Peter

    2010-01-01

    In phylogenetic reconstruction, two types of bacterial tyrosyl-tRNA synthetases (TyrRS) form distinct clades with many bacterial phyla represented in both clades. Very few taxa possess both forms, and maximum likelihood analysis of the distribution of TyrRS types suggests horizontal gene transfer (HGT), rather than an ancient duplication followed by differential gene loss, as the contributor to the evolutionary history of TyrRS in bacteria. However, for each TyrRS type, phylogenetic reconstruction yields phylogenies similar to the ribosomal phylogeny, revealing that frequent gene transfer has not destroyed the expected phylogeny; rather, the expected phylogenetic signal was reinforced or even created by HGT. We show that biased HGT can mimic patterns created through shared ancestry by in silico simulation. Furthermore, in cases where genomic synteny is sufficient to allow comparisons of relative gene positions, both tyrRS types occupy equivalent positions in closely related genomes, rejecting the loss hypothesis. Although the two types of bacterial TyrRS are only distantly related and only rarely coexist in a single genome, they have many features in common with alleles that are swapped between related lineages. We propose to label these functionally similar homologs as homeoalleles. We conclude that the observed phylogenetic pattern reflects both vertical inheritance and biased HGT and that the signal caused by common organismal descent is difficult to distinguish from the signal due to biased gene transfer. PMID:20495090

  6. Biased gene transfer mimics patterns created through shared ancestry.

    PubMed

    Andam, Cheryl P; Williams, David; Gogarten, J Peter

    2010-06-08

    In phylogenetic reconstruction, two types of bacterial tyrosyl-tRNA synthetases (TyrRS) form distinct clades with many bacterial phyla represented in both clades. Very few taxa possess both forms, and maximum likelihood analysis of the distribution of TyrRS types suggests horizontal gene transfer (HGT), rather than an ancient duplication followed by differential gene loss, as the contributor to the evolutionary history of TyrRS in bacteria. However, for each TyrRS type, phylogenetic reconstruction yields phylogenies similar to the ribosomal phylogeny, revealing that frequent gene transfer has not destroyed the expected phylogeny; rather, the expected phylogenetic signal was reinforced or even created by HGT. We show that biased HGT can mimic patterns created through shared ancestry by in silico simulation. Furthermore, in cases where genomic synteny is sufficient to allow comparisons of relative gene positions, both tyrRS types occupy equivalent positions in closely related genomes, rejecting the loss hypothesis. Although the two types of bacterial TyrRS are only distantly related and only rarely coexist in a single genome, they have many features in common with alleles that are swapped between related lineages. We propose to label these functionally similar homologs as homeoalleles. We conclude that the observed phylogenetic pattern reflects both vertical inheritance and biased HGT and that the signal caused by common organismal descent is difficult to distinguish from the signal due to biased gene transfer.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. Berberine inhibits PTP1B activity and mimics insulin action.

    PubMed

    Chen, Chunhua; Zhang, Yuebo; Huang, Cheng

    2010-07-02

    Type 2 diabetes patients show defects in insulin signal transduction that include lack of insulin receptor, decrease in insulin stimulated receptor tyrosine kinase activity and receptor-mediated phosphorylation of insulin receptor substrates (IRSs). A small molecule that could target insulin signaling would be of significant advantage in the treatment of diabetes. Berberine (BBR) has recently been shown to lower blood glucose levels and to improve insulin resistance in db/db mice partly through the activation of AMP-activated protein kinase (AMPK) signaling and induction of phosphorylation of insulin receptor (IR). However, the underlying mechanism remains largely unknown. Here we report that BBR mimics insulin action by increasing glucose uptake ability by 3T3-L1 adipocytes and L6 myocytes in an insulin-independent manner, inhibiting phosphatase activity of protein tyrosine phosphatase 1B (PTP1B), and increasing phosphorylation of IR, IRS1 and Akt in 3T3-L1 adipocytes. In diabetic mice, BBR lowers hyperglycemia and improves impaired glucose tolerance, but does not increase insulin release and synthesis. The results suggest that BBR represents a different class of anti-hyperglycemic agents.

  14. The endemic mimic: blastomycosis an illness often misdiagnosed.

    PubMed

    Bradsher, Robert W

    2014-01-01

    One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region.

  15. 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

  16. UNUSUAL CLINICAL CASES THAT MIMIC ACUTE DISSEMINATED ENCEPHALOMYELITIS.

    PubMed

    Duman, Özgür; Yürekli, Vedat Ali; Gencpinar, Pinar; Karaali, Kamil; Gümüş, Hakan; Okuyaz, Çetin; Hazar, Volkan; Haspolat, Şenay

    2015-09-01

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated monophasic inflammatory demyelinating disorder of the central nervous system which poses a diagnostic challenge. We report on six cases of different etiologies that mimicked the clinical and radiologic findings of ADEM. The cases were collected from four different reference hospitals in Turkey. The same radiologist from the Akdeniz University Faculty of Medicine examined the magnetic resonance images of all patients. Three (50%) patients had antecedent infections. Initial symptoms of the patients were as follows: fever in 50%, altered consciousness in 33.3% and convulsions in 16.7% of patients. Neurologic examination showed long tract signs in 83.3%, ataxia in 50% and altered consciousness in 50% of patients. Cerebrospinal fluid examination revealed lymphocytic pleocytosis only in case 6. Four patients received steroid pulse therapy and one of these initially underwent intravenous immunoglobulin therapy. The patients' definitive diagnoses were as follows: paraspinal neuroblastoma-associated paraneoplastic syndrome; histiocytic sarcoma; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in one patient each, while two patients had hemophagocytic syndrome. The present case series demonstrated difficulties in diagnosing ADEM while revealing extremely rare disorders that mimic ADEM radiologically and clinically.

  17. A Novel Organotypic Model Mimics the Tumor Microenvironment

    PubMed Central

    Nurmenniemi, Sini; Sinikumpu, Teemu; Alahuhta, Ilkka; Salo, Sirpa; Sutinen, Meeri; Santala, Markku; Risteli, Juha; Nyberg, Pia; Salo, Tuula

    2009-01-01

    Carcinoma cell invasion is traditionally studied in three-dimensional organotypic models composed of type I collagen and fibroblasts. However, carcinoma cell behavior is affected by the various cell types and the extracellular matrix (ECM) in the tumor microenvironment. In this study, a novel organotypic model based on human uterine leiomyoma tissue was established and characterized to create a more authentic environment for carcinoma cells. Human tongue squamous cell carcinoma cells (HSC-3) were cultured on top of either collagen or myoma. Organotypic sections were examined by immunohistochemistry and in situ hybridization. The maximal invasion depth of HSC-3 cells was markedly increased in myomas compared with collagen. In myomas, various cell types and ECM components were present, and the HSC-3 cells only expressed ECM molecules in the myoma model. Organotypic media were analyzed by radioimmunoassay, zymography, or Western blotting. During carcinoma cell invasion, matrix metalloprotease-9 production and collagen degradation were enhanced particularly in the myoma model. To evaluate the general applicability of the myoma model, several oral carcinoma, breast carcinoma, and melanoma cell lines were cultured on myomas and found to invade in highly distinct patterns. We conclude that myoma tissue mimics the native tumor microenvironment better than previous organotypic models and possibly enhances epithelial-to-mesenchymal transition. Thus, the myoma model provides a promising tool for analyzing the behavior of carcinoma cells. PMID:19679876

  18. Synthetic human serum albumin Sudlow I binding site mimics.

    PubMed

    Karlsson, Björn C G; Rosengren, Annika M; Näslund, Inga; Andersson, Per Ola; Nicholls, Ian A

    2010-11-25

    Here, we report the design, synthesis, and characterization of molecularly imprinted polymer (MIP) derived mimics of the human serum albumin (HSA) Sudlow I site-the binding site for the anticoagulant warfarin. MIP design was based upon a combination of experimental ((1)H NMR) and computational (molecular dynamics) methods. Two MIPs and corresponding nonimprinted reference polymers were synthesized and characterized (scanning electron microscopy; nitrogen sorption; and Fourier transform infrared spectroscopy). MIP-ligand recognition was examined using radioligand binding studies, where the largest number of selective sites was found in a warfarin-imprinted methacrylic acid-ethylene dimethacrylate copolymer (MAA-MIP). The warfarin selectivity of this MIP was confirmed using radioligand displacement and zonal chromatographic studies. A direct comparison of MIP-warfarin binding characteristics with those of the HSA Sudlow I binding site was made, and similarities in site population (per gram polymer or protein) and affinities were observed. The warfarin selectivity of the MIP suggests its potential for use as a recognition element in a MIP-based warfarin sensor and even as a model to aid in understanding and steering blood-plasma protein-regulated transport processes or even for the development of warfarin sensors.

  19. Young diabetics' compliance in the framework of the MIMIC model.

    PubMed

    Kyngäs, H; Hentinen, M; Koivukangas, P; Ohinmaa, A

    1996-11-01

    The compliance of 346 young diabetics aged 13-17 years with health regimens is analysed in the framework of a MIMIC (multiple indicators, multiple causes) model. The data were compiled by means of a questionnaire on compliance, conditions for compliance, the meaning attached to treatment and the impact of the disease, and the model constructed using the LISREL VII programme, treating compliance as an unobserved variable formulated in terms of observed causes (x-variables) and observed indicators (y-variables). The resulting solutions are entirely satisfactory. The goodness-of-fit index is 0.983, the root mean square residual 0.058 and the chi-squared statistic 43.35 (P < 0.001). The values for the individual parameters in the model are also shown to be reliable and valid. The model shows compliance to be indicated by self-care behaviour, responsibility for treatment, intention to pursue the treatment and collaboration with the physician, and to be greatly determined by motivation, experience of the results of treatment and having the energy and will-power to pursue the treatment and, to a lesser extent, by a sense of normality and fear.

  20. 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

  1. Designed biomaterials to mimic the mechanical properties of muscles.

    PubMed

    Lv, Shanshan; Dudek, Daniel M; Cao, Yi; Balamurali, M M; Gosline, John; Li, Hongbin

    2010-05-06

    The passive elasticity of muscle is largely governed by the I-band part of the giant muscle protein titin, a complex molecular spring composed of a series of individually folded immunoglobulin-like domains as well as largely unstructured unique sequences. These mechanical elements have distinct mechanical properties, and when combined, they provide the desired passive elastic properties of muscle, which are a unique combination of strength, extensibility and resilience. Single-molecule atomic force microscopy (AFM) studies demonstrated that the macroscopic behaviour of titin in intact myofibrils can be reconstituted by combining the mechanical properties of these mechanical elements measured at the single-molecule level. Here we report artificial elastomeric proteins that mimic the molecular architecture of titin through the combination of well-characterized protein domains GB1 and resilin. We show that these artificial elastomeric proteins can be photochemically crosslinked and cast into solid biomaterials. These biomaterials behave as rubber-like materials showing high resilience at low strain and as shock-absorber-like materials at high strain by effectively dissipating energy. These properties are comparable to the passive elastic properties of muscles within the physiological range of sarcomere length and so these materials represent a new muscle-mimetic biomaterial. The mechanical properties of these biomaterials can be fine-tuned by adjusting the composition of the elastomeric proteins, providing the opportunity to develop biomaterials that are mimetic of different types of muscles. We anticipate that these biomaterials will find applications in tissue engineering as scaffold and matrix for artificial muscles.

  2. A novel physiological culture system that mimics luteal angiogenesis.

    PubMed

    Robinson, R S; Hammond, A J; Mann, G E; Hunter, M G

    2008-03-01

    Luteal inadequacy is a major cause of poor embryo development and infertility. Angiogenesis, the formation of new blood vessels, is an essential process underpinning corpus luteum (CL) development and progesterone production. Thus, understanding the factors that regulate angiogenesis during this critical time is essential for the development of novel strategies to alleviate luteal inadequacy and infertility. This study demonstrates the development of a physiologically relevant primary culture system that mimics luteal angiogenesis. This system incorporates all luteal cell types (e.g. endothelial, steroidogenic cells, fibroblasts and pericytes). Using this approach, endothelial cells, identified by the specific marker von Willebrand factor (VWF), start to form clusters on day 2, which then proliferate and develop thread-like structures. After 9 days in culture, these tubule-like structures lengthen, thicken and form highly organized intricate networks resembling a capillary bed. Development of the vasculature was promoted by coating wells with fibronectin, as determined by image analysis (P<0.001). Progesterone production increased with time and was stimulated by LH re-enforcing the physiological relevance of the model in mimicking in vivo luteal function. LH also increased the area stained positively for VWF by twofold (P<0.05). Development of this endothelial cell network was stimulated by fibroblast growth factor 2 and vascular endothelial growth factor A, which increased total area of VWF positive staining on day 9, both independently (three- to fourfold; P<0.01) and in combination (tenfold; P<0.001). In conclusion, the successful development of endothelial cell networks in vitro provides a new opportunity to elucidate the physiological control of the angiogenic process in the developing CL.

  3. 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…

  4. 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.

  5. 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…

  6. [Denervation of mimic muscles during endoscopic lifting of the upper part of face].

    PubMed

    Pinchuk, V D; Tkach, O S

    2013-08-01

    Endoscopic lifting of the upper part of face carry out in 28 patients Chemical or surgical denervation had been done for decreasing of mimic muscles activity. Medical glue with folic acid had been used for tissues fixation. Use of medical glue in conjunction with preliminary chemical denervation of mimic muscles with botulin toxin application decreases surgery duration, prevents complications and increases satisfaction of patients.

  7. A Stochastic Optimal Control Problem For Predation of Models And Mimics

    NASA Astrophysics Data System (ADS)

    Tsoularis, A.

    2007-11-01

    In Ecology, the term mimicry describes a situation in which one type of species, the mimic, shares common external features with another type of species, the model with the sole purpose of confusing potential predators. In Batesian mimicry, named after Henry Walter Bates, the English naturalist, the mimics, which are palatable to predators, send similar signals to model species, which are unpalatable. His theory of mimicry postulates that predators tend to avoid nauseous (in smell or taste) models and the mimics derive some form of protection by resembling the models. This theory carries the assumption that models are more abundant than mimics so that predators can learn to avoid them. In this work a stochastic optimal control problem for optimal predation is presented. The objective is to maximize the predator's net energetic benefit. Mimic consumption is beneficial (positive) whereas model consumption is detrimental (negative).

  8. Mimicry on the edge: why do mimics vary in resemblance to their model in different parts of their geographical range?

    PubMed

    Harper, George R; Pfennig, David W

    2007-08-22

    Batesian mimics-benign species that predators avoid because they resemble a dangerous species-often vary geographically in resemblance to their model. Such geographical variation in mimic-model resemblance may reflect geographical variation in model abundance. Natural selection should favour even poor mimics where their model is common, but only good mimics where their model is rare. We tested these predictions in a snake-mimicry complex where the geographical range of the mimic extends beyond that of its model. Mimics on the edge of their model's range (where the model was rare) resembled the model more closely than did mimics in the centre of their model's range (where the model was common). When free-ranging natural predators on the edge of the model's range were given a choice of attacking replicas of good or poor mimics, they avoided only good mimics. By contrast, those in the centre of the model's range attacked good and poor mimics equally frequently. Generally, although poor mimics may persist in areas where their model is common, only the best mimics should occur in areas where their model is rare. Thus, counter-intuitively, the best mimics may occur on the edge of their model's range.

  9. Shape-based approach for the estimation of individual facial mimics in craniofacial surgery planning

    NASA Astrophysics Data System (ADS)

    Gladilin, Evgeny; Zachow, Stefan; Deuflhard, Peter; Hege, Hans-Christian

    2002-05-01

    Besides the static soft tissue prediction, the estimation of basic facial emotion expressions is another important criterion for the evaluation of craniofacial surgery planning. For a realistic simulation of facial mimics, an adequate biomechanical model of soft tissue including the mimic musculature is needed. In this work, we present an approach for the modeling of arbitrarily shaped muscles and the estimation of basic individual facial mimics, which is based on the geometrical model derived from the individual tomographic data and the general finite element modeling of soft tissue biomechanics.

  10. 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...

  11. Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?

    PubMed Central

    Liberman, Ava L.; Liotta, Eric M.; Caprio, Fan Z.; Ruff, Ilana; Maas, Matthew B.; Bernstein, Richard A.; Khare, Rahul; Bergman, Deborah

    2015-01-01

    Summary An unintended consequence of rapid thrombolysis may be more frequent treatment of stroke mimics, nonvascular conditions that simulate stroke. We explored the relationship between door-to-needle (DTN) times and thrombolysis of stroke mimics at a single academic center by analyzing consecutive quartiles of patients who were treated with IV tissue plasminogen activator for suspected stroke from January 1, 2010 to February 28, 2014. An increase in the proportion of stroke mimic patients (6.7% in each of the 1st and 2nd, 12.9% in the 3rd, and 30% in the last consecutive case quartile; p = 0.03) and a decrease in median DTN time from 89 to 56 minutes (p < 0.01) was found. As more centers reduce DTN times, the rates of stroke mimic treatment should be carefully monitored. PMID:26124982

  12. Scaffolded multiple cyclic peptide libraries for protein mimics by native chemical ligation.

    PubMed

    van de Langemheen, H; van Hoeke, M; Quarles van Ufford, H C; Kruijtzer, J A W; Liskamp, R M J

    2014-07-07

    The accessibility to collections, libraries and arrays of cyclic peptides is increasingly important since cyclic peptides may provide better mimics of the loop-like structures ubiquitously present in and - especially - on the surface of proteins. The next important step is the preparation of libraries of ensembles of scaffolded cyclic peptides, which upon screening may lead to promising protein mimics. Here we describe the synthesis of a tri-cysteine containing scaffold as well as the simultaneous native chemical ligation of three cyclic peptides thereby affording a clean library of multiple cyclic peptides on this scaffold, representing potential mimics of gp120. Members of this collection of protein mimics showed a decent inhibition of the gp120-CD4 interaction.

  13. Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye.

    PubMed

    Barba-Bon, Andrea; Costero, Ana M; Gil, Salvador; Martínez-Máñez, Ramón; Sancenón, Félix

    2014-11-21

    A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared. Probe P4 contains three reactive sites; i.e. (i) a nucleophilic phenol group able to undergo phosphorylation with nerve gases, (ii) a carbonyl group as a reactive site for cyanide; and (iii) a triisopropylsilyl (TIPS) protecting group that is known to react with fluoride. The reaction of P4 with DCNP in acetonitrile resulted in both the phosphorylation of the phenoxy group and the release of cyanide, which was able to react with the carbonyl group of P4 to produce a colour modulation from pink to orange. In contrast, phosphorylation of P4 with DFP in acetonitrile released fluoride that hydrolysed the TIPS group in P4 to yield a colour change from pink to blue. Probe P4 was able to discriminate between DFP and DCNP with remarkable sensitivity; limits of detection of 0.36 and 0.40 ppm for DCNP and DFP, respectively, were calculated. Besides, no interference from other organophosphorous derivatives or with presence of acid was observed. The sensing behaviour of P4 was also retained when incorporated into silica gel plates or onto polyethylene oxide membranes, which allowed the development of simple test strips for the colorimetric detection of DCNP and DFP in the vapour phase. P4 is the first probe capable of colorimetrically differentiating between a Tabun mimic (DCNP) and a Sarin and Soman mimic (DFP).

  14. A near infrared colorimetric and fluorometric probe for organophosphorus nerve agent mimics by intramolecular amidation.

    PubMed

    Hu, Xiao-Xiao; Su, Yue-Ting; Ma, Yun-Wei; Zhan, Xin-Qi; Zheng, Hong; Jiang, Yun-Bao

    2015-10-21

    A near infrared probe for sensitive colorimetric and fluorimetric detection of nerve agent mimics, DCP and DCNP, was reported based on the activation of a carboxylic acid group by the mimics to conduct an intramolecular amidation reaction in the heptamethine chromophore, where its absorption or excitation maximum wavelength could be greatly red-shifted by attenuating the electron-donating ability of the amine group in the bridgehead site of heptamethine cyanine.

  15. Target mimics: an embedded layer of microRNA-involved gene regulatory networks in plants

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) play an essential role in gene regulation in plants. At the same time, the expression of miRNA genes is also tightly controlled. Recently, a novel mechanism called “target mimicry” was discovered, providing another layer for modulating miRNA activities. However, except for the artificial target mimics manipulated for functional studies on certain miRNA genes, only one example, IPS1 (Induced by Phosphate Starvation 1)—miR399 was experimentally confirmed in planta. To date, few analyses for comprehensive identification of natural target mimics have been performed in plants. Thus, limited evidences are available to provide detailed information for interrogating the questionable issue whether target mimicry was widespread in planta, and implicated in certain biological processes. Results In this study, genome-wide computational prediction of endogenous miRNA mimics was performed in Arabidopsis and rice, and dozens of target mimics were identified. In contrast to a recent report, the densities of target mimic sites were found to be much higher within the untranslated regions (UTRs) when compared to those within the coding sequences (CDSs) in both plants. Some novel sequence characteristics were observed for the miRNAs that were potentially regulated by the target mimics. GO (Gene Ontology) term enrichment analysis revealed some functional insights into the predicted mimics. After degradome sequencing data-based identification of miRNA targets, the regulatory networks constituted by target mimics, miRNAs and their downstream targets were constructed, and some intriguing subnetworks were further exploited. Conclusions These results together suggest that target mimicry may be widely implicated in regulating miRNA activities in planta, and we hope this study could expand the current understanding of miRNA-involved regulatory networks. PMID:22613869

  16. Imaging Review of Skeletal Tumors of the Pelvis Malignant Tumors and Tumor Mimics

    PubMed Central

    Girish, Gandikota; Finlay, Karen; Fessell, David; Pai, Deepa; Dong, Qian; Jamadar, David

    2012-01-01

    Malignant lesions of the pelvis are not uncommon and need to be differentiated from benign lesions and tumor mimics. Appearances are sometimes nonspecific leading to consideration of a broad differential diagnosis. Clinical history, anatomic location, and imaging characterization can help narrow the differential diagnosis. The focus of this paper is to demonstrate the imaging features and the role of plain films, computed tomography, and magnetic resonance imaging for detecting and characterizing malignant osseous pelvic lesions and their common mimics. PMID:22593667

  17. Why many Batesian mimics are inaccurate: evidence from hoverfly colour patterns.

    PubMed

    Taylor, Christopher H; Reader, Tom; Gilbert, Francis

    2016-11-16

    Mimicry is considered a classic example of the elaborate adaptations that natural selection can produce, yet often similarity between Batesian (harmless) mimics and their unpalatable models is far from perfect. Variation in mimetic accuracy is a puzzle, as natural selection should favour mimics that are hardest to distinguish from their models. Numerous hypotheses exist to explain the persistence of inaccurate mimics, but most have rarely or never been tested against empirical observations from wild populations. One reason for this is the difficulty in measuring pattern similarity, a key aspect of mimicry. Here, we use a recently developed method, based on the distance transform of binary images, to quantify pattern similarity both within and among species for a group of hoverflies and their hymenopteran models. This allowed us to test three key hypotheses regarding inaccurate mimicry. Firstly, we tested the prediction that selection should be more relaxed in less accurate mimics, but found that levels of phenotypic variation are similar across most hoverfly species. Secondly, we found no evidence that mimics have to compromise between accuracy to multiple model species. However, we did find that darker-coloured hoverflies are less accurate mimics, which could lead to a trade-off between mimicry and thermoregulation in temperate regions. Our results shed light on a classic problem concerning the limitations of natural selection.

  18. 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.

  19. 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

  20. Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS).

    PubMed

    Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M; Ioerger, Thomas R; Burgess, Kevin

    2013-11-28

    Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, "minimalist helical mimics". It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i + 3, i + 7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; (iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain "triads" in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the "side-chain correspondences" (e.g. i, i + 4, i + 7 or i, i

  1. 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.

  2. Rationally designed squaryldiamides - a novel class of sugar-nucleotide mimics?

    PubMed

    Niewiadomski, Sven; Beebeejaun, Zeenat; Denton, Helen; Smith, Terry K; Morris, Richard J; Wagner, Gerd K

    2010-08-07

    Sugar-nucleotides such as GDP-mannose, GDP-fucose and UDP-glucose are important biomolecules with a central role in carbohydrate and glycoconjugate biosynthesis, metabolism and cell signalling. Analogues and mimics of naturally occurring sugar-nucleotides are sought after as chemical tools and inhibitor candidates for sugar-nucleotide-dependent enzymes including glycosyltransferases. Many sugar-nucleotides bind to their target glycosyltransferases via coordination of the diphosphate group to a divalent metal cofactor in the active site. The identification of uncharged, chemically stable surrogates for the diphosphate group, with the ability to coordinate to a divalent metal, is therefore an important design criteria for the development of sugar-nucleotide mimics. Here, we describe the rational design and synthesis of a novel class of sugar-nucleotide mimics based on a squaryldiamide scaffold, an uncharged phosphate isostere. We demonstrate by comprehensive NMR titration experiments that the new sugar-nucleotide mimics coordinate efficiently to Mg(2+), and provide results from biological studies with a therapeutically relevant mannosyltransferase from Trypanosoma brucei. Our findings suggest that squaryldiamides are a promising template for the development of sugar-nucleotide mimics, and illustrate the considerable potential of the squarylamide group as a fragment for inhibitor design.

  3. Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries.

    PubMed

    Mulder, Gwenn E; Quarles van Ufford, H Linda C; van Ameijde, Jeroen; Brouwer, Arwin J; Kruijtzer, John A W; Liskamp, Rob M J

    2013-04-28

    A diversity of protein surface discontinuous epitope mimics is now rapidly and efficiently accessible. Despite the important role of protein-protein interactions involving discontinuous epitopes in a wide range of diseases, mimicry of discontinuous epitopes using peptide-based molecules remains a major challenge. Using copper(I) catalyzed azide-alkyne cycloaddition (CuAAC), we have developed a general and efficient method for the synthesis of collections of discontinuous epitope mimics. Up to three different cyclic peptides, representing discontinuous epitopes in HIV-gp120, were conjugated to a selection of scaffold molecules. Variation of the scaffold molecule, optimization of the ring size of the cyclic peptides and screening of the resulting libraries for successful protein mimics led to an HIV gp120 mimic with an IC50 value of 1.7 μM. The approach described here provides rapid and highly reproducible access to clean, smart libraries of very complex bio-molecular constructs representing protein mimics for use as synthetic vaccines and beyond.

  4. Impedance based detection of chemical warfare agent mimics using ferrocene-lysine modified carbon nanotubes.

    PubMed

    Diakowski, Piotr M; Xiao, Yizhi; Petryk, Michael W P; Kraatz, Heinz-Bernhard

    2010-04-15

    A recognition layer formed by multiwalled carbon nanotubes (MWCNTs) covalently modified with a ferrocene-lysine conjugate deposited on the indium tin oxide (ITO) was investigated as a sensor for chemical warfare agent (CWA) mimics. Electrochemical impedance spectroscopy measurements showed that upon addition of CWA mimic dramatic changes occurred in the electrical properties of the recognition layer. These changes allowed the detection of nerve agent analogues at the micromolar level, and a limited sensitivity was observed toward a sulfur mustard mimic. Experimental parameters were optimized so as to allow the detection of CWAs at single frequency, thereby significantly reducing acquisition time and simplifying data treatment. A proposed method of detection represents a significant step toward the design of an affordable and "fieldable" electrochemical CWA sensor.

  5. New sialyl Lewisx mimic containing an α-substituted β3-amino acid spacer

    PubMed Central

    Pedatella, Silvana; De Nisco, Mauro; Ernst, Beat; Guaragna, Annalisa; Wagner, Beatrice; Woods, Robert J.; Palumbo, Giovanni

    2014-01-01

    A highly convergent and efficient synthesis of a new sialyl Lewisx (sLex) mimic, which was predicted by computational studies to fulfil the spacial requirements for a selectin antagonist, has been developed. With a β2,3-amino acid residue L-galactose (bioisostere of the L-fucose moiety present in the natural sLex) and succinate are linked, leading to a mimic of sLex that contains all the required pharmacophores, namely the 3- and 4-hydroxy group of L-fucose, the 4- and 6-hydroxy group of D-galactose and the carboxylic acid of N-acetylneuraminic acid. The key step of the synthesis involves a tandem reaction consisting of a N-deprotection and a suitable O→N intramolecular acyl migration reaction which is promoted by cerium ammonium nitrate (CAN). Finally, the new sialyl Lewisx mimic was biologically evaluated in a competitive binding assay. PMID:17980866

  6. Avoiding diagnostic pitfalls in mimics of neoplasia: the importance of a comprehensive diagnostic approach

    PubMed Central

    Samsudin, Ely Zarina; Kamarul, Tunku; Mansor, Azura

    2015-01-01

    Any medical diagnosis should take a multimodal approach, especially those involving tumour-like conditions, as entities that mimic neoplasms have overlapping features and may present detrimental outcomes if they are underdiagnosed. These case reports present diagnostic pitfalls resulting from overdependence on a single diagnostic parameter for three musculoskeletal neoplasm mimics: brown tumour (BT) that was mistaken for giant cell tumour (GCT), methicillin-resistant Staphylococcus aureus osteomyelitis mistaken for osteosarcoma and a pseudoaneurysm mistaken for a soft tissue sarcoma. Literature reviews revealed five reports of BT simulating GCT, four reports of osteomyelitis mimicking osteosarcoma and five reports of a pseudoaneurysm imitating a soft tissue sarcoma. Our findings highlight the therapeutic dilemmas that arise with musculoskeletal mimics, as well as the importance of thorough investigation to distinguish mimickers from true neoplasms. PMID:26034328

  7. 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

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

    PubMed Central

    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

    2015-01-01

    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

  9. 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

  10. Carbonic anhydrase mimics for enhanced CO2 absorption in an amine-based capture solvent.

    PubMed

    Kelsey, Rachael A; Miller, David A; Parkin, Sean R; Liu, Kun; Remias, Joe E; Yang, Yue; Lightstone, Felice C; Liu, Kunlei; Lippert, Cameron A; Odom, Susan A

    2016-01-07

    Two new small-molecule enzyme mimics of carbonic anhydrase were prepared and characterized. These complexes contain the salen-like ligand bis(hydroxyphenyl)phenanthroline. This ligand is similar to the salen-type ligands previously incorporated into carbonic anhydrase mimics but contains no hydrolyzable imine groups and therefore serves as a promising ligand scaffold for the synthesis of a more robust CO2 hydration catalyst. These homogeneous catalysts were investigated for CO2 hydration in concentrated primary amine solutions through which a dilute CO2 (14%) fluid stream was flowed and showed exceptional activity for increased CO2 absorption rates.

  11. Molecules that Mimic Apolipoprotein A-I: Potential Agents for Treating Atherosclerosis

    PubMed Central

    Leman, Luke J.; Maryanoff, Bruce E.; Ghadiri, M. Reza

    2013-01-01

    Certain amphipathic α-helical peptides can functionally mimic many of the properties of full-length apolipoproteins, thereby offering an approach to modulate high-density lipoprotein (HDL) for combating atherosclerosis. In this Perspective, we summarize the key findings and advances over the past 25 years in the development of peptides that mimic apolipoproteins, especially apolipoprotein A-I (apoA-I). This assemblage of information provides a reasonably clear picture of the state of the art in the apolipoprotein mimetic field, an appreciation of the potential for such agents in pharmacotherapy, and a sense of the opportunities for optimizing the functional properties of HDL. PMID:24168751

  12. 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...

  13. Stroke mimic: Perfusion magnetic resonance imaging of a patient with ictal paralysis

    PubMed Central

    Sanghvi, D; Goyal, C; Mani, J

    2016-01-01

    We present an uncommon case of clinically diagnosed window period stroke subsequently recognised on diffusion – perfusion MRI as ictal paralysis due to focal inhibitory seizures or negative motor seizures. This case highlights the importance of MRI with perfusion imaging in establishing the diagnosis of stroke mimics and avoiding unnecessary thrombolysis. PMID:27763486

  14. Evaluation of MIMIC-Model Methods for DIF Testing with Comparison to Two-Group Analysis

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Differential item functioning (DIF) occurs when an item on a test or questionnaire has different measurement properties for 1 group of people versus another, irrespective of mean differences on the construct. This study focuses on the use of multiple-indicator multiple-cause (MIMIC) structural equation models for DIF testing, parameterized as item…

  15. Effects of distance from models on the fitness of floral mimics.

    PubMed

    Duffy, K J; Johnson, S D

    2017-02-01

    Rewardless plants can attract pollinators by mimicking floral traits of rewarding heterospecific plants. This should result in the pollination success of floral mimics being dependent on the relative abundance of their models, as pollinator abundance and conditioning on model signals should be higher in the vicinity of the models. However, the attraction of pollinators to signals of the models may be partially innate, such that spatial isolation of mimics from model species may not strongly affect pollination success of mimics. We tested whether pollination rates and fruit set of the rewardless orchid Disa pulchra were influenced by proximity and abundance of its rewarding model species, Watsonia lepida. Pollination success of the orchid increased with proximity to the model species, while fruit set of the orchid increased with local abundance of the model species. Orchids that were experimentally translocated outside the model population experienced reduced pollinaria removal and increased pollinator-mediated self-pollination. These results confirm predictions that the pollination success of floral mimics should be dependent on the proximity and abundance of model taxa, and thus highlight the importance of ecological facilitation among species involved in mimicry systems.

  16. 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.

  17. Inhibition of pyruvate decarboxylase from Z. mobilis by novel analogues of thiamine pyrophosphate: investigating pyrophosphate mimics.

    PubMed

    Erixon, Karl M; Dabalos, Chester L; Leeper, Finian J

    2007-03-07

    Replacement of the thiazolium ring of thiamine pyrophosphate with a triazole gives extremely potent inhibitors of pyruvate decarboxylase from Z. mobilis, with K(I) values down to 20 pM; this system was used to explore pyrophosphate mimics and several effective analogues were discovered.

  18. The guideline of the design and validation of MiRNA mimics.

    PubMed

    Wang, Zhiguo

    2011-01-01

    The miRNA mimic technology (miR-Mimic) is an innovative approach for gene silencing. This approach is to generate nonnatural double-stranded miRNA-like RNA fragments. Such an RNA fragment is designed to have its 5'-end bearing a partially complementary motif to the selected sequence in the 3'UTR unique to the target gene. Once introduced into cells, this RNA fragment, mimicking an endogenous miRNA, can bind specifically to its target gene and produce posttranscriptional repression, more specifically translational inhibition, of the gene. Unlike endogenous miRNAs, miR-Mimics act in a gene-specific fashion. The miR-Mimic approach belongs to the "miRNA-targeting" and "miRNA-gain-of-function" strategy and is primarily used as an exogenous tool to study gene function by targeting mRNA through miRNA-like actions in mammalian cells. The technology was developed by my research group (Department of Medicine, Montreal Heart Institute, University of Montreal) in 2007 (Xiao, et al. J Cell Physiol 212:285-292, 2007; Xiao et al. Nat Cell Biol, in review).

  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. 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.

  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.

  2. Active Immunization Using a Peptide Mimic of a Carbohydrate Tumor Antigen

    DTIC Science & Technology

    2005-03-01

    endothelial cells ( 3 ). The endothelial cells express a ligand known to bind TF-Ag called galectin - 3 ( 3 ). The data showed that the mimic inhibited the...0188), Washlngton, DC 20503 1. AGENCY USE ONLY I 2. REPORT DATE 3 . REPORT TYPE AND DATES COVERED (Leave blank) March 2005 Annual Summary (23 Feb 04 - 22...2 Table of Contents ........................................................................... 3 Introduction

  3. Synthesis of DNA mimics representing HypNA-pPNA hetero-oligomers.

    PubMed

    Efimov, Vladimir A; Chakhmakhcheva, Oksana G

    2005-01-01

    The methods for the synthesis and purification of negatively charged peptide nucleic acid (PNA)-relative deoxyribonucleic acid (DNA) mimics containing alternating residues of phosphono peptide nucleic acid (pPNA) monomers and PNA-like monomers on the base of trans-4-hydroxy-L-proline are described. Examples of the chimeric oligomers hybridization with complementary DNA and ribonucleic acid fragments are demonstrated.

  4. Selection of Peptide Mimics of HIV-1 Epitope Recognized by Neutralizing Antibody VRC01

    PubMed Central

    Chikaev, Anton N.; Bakulina, Anastasiya Yu.; Burdick, Ryan C.; Karpenko, Larisa I.; Pathak, Vinay K.; Ilyichev, Alexander A.

    2015-01-01

    The ability to induce anti-HIV-1 antibodies that can neutralize a broad spectrum of viral isolates from different subtypes seems to be a key requirement for development of an effective HIV-1 vaccine. The epitopes recognized by the most potent broadly neutralizing antibodies that have been characterized are largely discontinuous. Mimetics of such conformational epitopes could be potentially used as components of a synthetic immunogen that can elicit neutralizing antibodies. Here we used phage display technology to identify peptide motifs that mimic the epitope recognized by monoclonal antibody VRC01, which is able to neutralize up to 91% of circulating primary isolates. Three rounds of biopanning were performed against 2 different phage peptide libraries for this purpose. The binding specificity of selected phage clones to monoclonal antibody VRC01 was estimated using dot blot analysis. The putative peptide mimics exposed on the surface of selected phages were analyzed for conformational and linear homology to the surface of HIV-1 gp120 fragment using computational analysis. Corresponding peptides were synthesized and checked for their ability to interfere with neutralization activity of VRC01 in a competitive inhibition assay. One of the most common peptides selected from 12-mer phage library was found to partially mimic a CD4-binding loop fragment, whereas none of the circular C7C-mer peptides was able to mimic any HIV-1 domains. However, peptides identified from both the 12-mer and C7C-mer peptide libraries showed rescue of HIV-1 infectivity in the competitive inhibition assay. The identification of epitope mimics may lead to novel immunogens capable of inducing broadly reactive neutralizing antibodies. PMID:25785734

  5. Prevalence and Mimics of Kleine-Levin Syndrome: A Survey in French-Speaking Switzerland

    PubMed Central

    Habra, Oussama; Heinzer, Raphaël; Haba-Rubio, Jose; Rossetti, Andrea O.

    2016-01-01

    Study Objective: Kleine-Levin syndrome (KLS) is a rare disease of unknown etiology, the diagnosis of which can be challenging. We aimed to estimate KLS prevalence in French-speaking Switzerland, and assess differences with mimicking conditions. Methods: In this cross-sectional study, KLS patients were identified through a population-based approach, including at our hospital and contacting all sleep-certified facilities and neurologists in French-speaking Switzerland. Furthermore, we identified patients referred to our center for suspected KLS that received other diagnoses. Relevant clinical data of these two groups was compared. Results: We identified 7 patients with diagnosed KLS (6 since 2009), leading to a prevalence estimation of 3.19 per million (95% confidence interval: 1.55–6.59). Median age at diagnosis was 17 years (range: 12–19), 71.4% of them were men, and mean diagnosis delay after the first episode was 20.1 ± 10.9 months. We identified 9 mimic patients referred to our center; they differed from KLS patients by their higher age at disease onset (median: 15 [range: 12–16] vs. 19 [range: 16–64] years; p < 0.001), suspected KLS as referral reason (more frequent in mimics, p = 0.003), and the presence of precipitating factors (more frequent in KLS, p = 0.011). Among the mimic patients, 77% (versus 28% in KLS) had a psychiatric diagnosis. Conclusions: This study suggests a relatively higher KLS prevalence than previously reported. As compared to KLS, mimic patients have higher age at symptom onset, are more often initially referred for KLS suspicion, and have a higher prevalence of psychiatric disorders. Citation: Habra O, Heinzer R, Haba-Rubio J, Rossetti AO. Prevalence and mimics of Kleine-Levin syndrome: a survey in French-speaking Switzerland. J Clin Sleep Med 2016;12(8):1083–1087. PMID:27250808

  6. Preclinical Evaluation of the Accuracy of HIFU Treatments Using a Tumor-Mimic Model. Results of Animal Experiments

    NASA Astrophysics Data System (ADS)

    Melodelima, D.; N'Djin, W. A.; Parmentier, H.; Rivoire, M.; Chapelon, J. Y.

    2009-04-01

    Presented in this paper is a tumor-mimic model that allows the evaluation at a preclinical stage of the targeting accuracy of HIFU treatments in the liver. The tumor-mimics were made by injecting a warm mixture of agarose, cellulose, and glycerol that polymerizes immediately in hepatic tissue and forms a 1 cm discrete lesion that is detectable by ultrasound imaging and gross pathology. Three studies were conducted: (i) in vitro experiments were conducted to study acoustical proprieties of the tumor-mimics, (ii) animal experiments were conducted in ten pigs to evaluate the tolerance of the tumor-mimics at mid-term (30 days), (iii) ultrasound-guided HIFU ablation has been performed in ten pigs with tumor-mimics to demonstrate that it is possible to treat a predetermined zone accurately. The attenuation of tumor-mimics was 0.39 dB.cm-1 at 1 MHz, the ultrasound propagation velocity was 1523 m.s-1, and the acoustic impedance was 1.8 MRayls. The pigs tolerated tumor-mimics and treatment well over the experimental period. Tumor-mimics were visible with high contrast on ultrasound images. In addition, it has been demonstrated by using the tumor-mimic as a reference target, that tissue destruction induced by HIFU and observed on gross pathology corresponded to the targeted area on the ultrasound images. The average difference between the predetermined location of the HIFU ablation and the actual coagulated area was 16%. These tumor-mimics are identifiable by ultrasound imaging, they do not modify the geometry of HIFU lesions and thus constitutes a viable mimic of tumors indicated for HIFU therapy.

  7. Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody

    DTIC Science & Technology

    2014-05-01

    endothelial cells using a TCR mimic antibody. J Cell Physiol. 2010;225(3):664-672. 3. Verma B, Jain R, Caseltine S, Rennels A, Bhattacharya R, Markiewski MM...Rawat A, Neethling F, Bickel U, Weidanz JA. TCR Mimic Monoclonal Antibodies Induce Apoptosis of Tumor Cells via Immune Effector- Independent

  8. Photo-induced hydrogen production in a helical peptide incorporating a [FeFe] hydrogenase active site mimic.

    PubMed

    Roy, Anindya; Madden, Christopher; Ghirlanda, Giovanna

    2012-10-11

    There is growing interest in the development of hydrogenase mimics for solar fuel production. Here, we present a bioinspired mimic designed by anchoring a diiron hexacarbonyl cluster to a model helical peptide via an artificial dithiol amino acid. The [FeFe]-peptide complex catalyses photo-induced production of hydrogen in water.

  9. 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

  10. A plant tendril mimic soft actuator with phototunable bending and chiral twisting motion modes.

    PubMed

    Wang, Meng; Lin, Bao-Ping; Yang, Hong

    2016-12-22

    In nature, plant tendrils can produce two fundamental motion modes, bending and chiral twisting (helical curling) distortions, under the stimuli of sunlight, humidity, wetting or other atmospheric conditions. To date, many artificial plant-like mechanical machines have been developed. Although some previously reported materials could realize bending or chiral twisting through tailoring the samples into various ribbons along different orientations, each single ribbon could execute only one deformation mode. The challenging task is how to endow one individual plant tendril mimic material with two different, fully tunable and reversible motion modes (bending and chiral twisting). Here we show a dual-layer, dual-composition polysiloxane-based liquid crystal soft actuator strategy to synthesize a plant tendril mimic material capable of performing two different three-dimensional reversible transformations (bending versus chiral twisting) through modulation of the wavelength band of light stimuli (ultraviolet versus near-infrared). This material has broad application prospects in biomimetic control devices.

  11. A plant tendril mimic soft actuator with phototunable bending and chiral twisting motion modes

    NASA Astrophysics Data System (ADS)

    Wang, Meng; Lin, Bao-Ping; Yang, Hong

    2016-12-01

    In nature, plant tendrils can produce two fundamental motion modes, bending and chiral twisting (helical curling) distortions, under the stimuli of sunlight, humidity, wetting or other atmospheric conditions. To date, many artificial plant-like mechanical machines have been developed. Although some previously reported materials could realize bending or chiral twisting through tailoring the samples into various ribbons along different orientations, each single ribbon could execute only one deformation mode. The challenging task is how to endow one individual plant tendril mimic material with two different, fully tunable and reversible motion modes (bending and chiral twisting). Here we show a dual-layer, dual-composition polysiloxane-based liquid crystal soft actuator strategy to synthesize a plant tendril mimic material capable of performing two different three-dimensional reversible transformations (bending versus chiral twisting) through modulation of the wavelength band of light stimuli (ultraviolet versus near-infrared). This material has broad application prospects in biomimetic control devices.

  12. Adding a Lysine Mimic in the Design of Potent Inhibitors of Histone Lysine Methyltransferases

    SciTech Connect

    Chang, Yanqi; Ganesh, Thota; Horton, John R.; Spannhoff, Astrid; Liu, Jin; Sun, Aiming; Zhang, Xing; Bedford, Mark T.; Shinkai, Yoichi; Snyder, James P.; Cheng, Xiaodong

    2010-07-19

    Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the histone code. One common feature of these activities is the recognition of lysines in methylated and unmethylated states, whether they are substrates, reaction products, or binding partners. We applied the concept of adding a lysine mimic to an established inhibitor (BIX-01294) of histone H3 lysine 9 methyltransferases G9a and G9a-like protein by including a 5-aminopentyloxy moiety, which is inserted into the target lysine-binding channel and becomes methylated by G9a-like protein, albeit slowly. The compound enhances its potency in vitro and reduces cell toxicity in vivo. We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers.

  13. [Clinical Manifestations of Spinal Epidural Hematoma-Stroke Mimic and Pitfalls in Diagnosis].

    PubMed

    Kuriyama, Masaru

    2017-02-01

    Clinical manifestations of spinal epidural hematoma are presented, and the cases mimicking acute ischemic stroke have been reviewed from the literature. Many reports described the cases of spinal epidural hematoma with acute hemiparesis mimicking ischemic stroke in which intravenous thrombolytic treatment with recombinant tissue plasminogen activator was considered. A correct diagnosis of acute ischemic stroke must be made within 4.5 hours from the onset of symptoms, a relatively short window period. A spinal epidural hematoma is a potentially important stroke mimic in a wide variety of conditions that mimic a stroke. The literature review and discussion will emphasize allowing the distinction between these hemiparetic presentation of spinal epidural hematoma and acute ischemic stroke. A spinal epidural hematoma should be considered in the differential diagnosis of patients with acute onset of hemiparesis when associated with neck pain and signs of Horner's syndrome and Brown-Sēquard syndrome.

  14. 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

  15. A Chromogenic Probe for the Selective Recognition of Sarin and Soman Mimic DFP.

    PubMed

    El Sayed, Sameh; Pascual, Lluís; Agostini, Alessandro; Martínez-Máñez, Ramón; Sancenón, Félix; Costero, Ana M; Parra, Margarita; Gil, Salvador

    2014-08-01

    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).

  16. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan

    PubMed Central

    Pearson, Kevin J.; Baur, Joseph A.; Lewis, Kaitlyn N.; Peshkin, Leonid; Price, Nathan L.; Labinskyy, Nazar; Swindell, William R.; Kamara, Davida; Minor, Robin K.; Perez, Evelyn; Jamieson, Hamish A.; Zhang, Yongqing; Dunn, Stephen R.; Sharma, Kumar; Pleshko, Nancy; Woollett, Laura A.; Csiszar, Anna; Ikeno, Yuji; Le Couteur, David; Elliott, Peter J.; Becker, Kevin G.; Navas, Placido; Ingram, Donald K.; Wolf, Norman S.; Ungvari, Zoltan; Sinclair, David A.; de Cabo, Rafael

    2008-01-01

    SUMMARY A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging including reduced albuminuria, decreased inflammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started mid-life. PMID:18599363

  17. 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

  18. Cell-sized liposomes that mimic cell motility and the cell cortex.

    PubMed

    Lemière, Joël; Carvalho, Kevin; Sykes, Cécile

    2015-01-01

    Cells move and change shape by dynamically reorganizing their cytoskeleton next to the plasma membrane. In particular, actin assembly generates forces and stresses that deform the cell membrane. Cell-sized liposomes are designed to mimic this function. The activation of actin polymerization at their membrane is able to push the membrane forward, thus reproducing the mechanism of lamellipodium extension at the cell front. Moreover, the cell cortex, a submicrometer-thick actin shell right beneath the cell membrane can be reproduced; it contributes to cell tension with the action of molecular motors. We will describe experimental methods to prepare liposomes that mimic the inside geometry of a cell, and that reproduce actin-based propulsion of the liposome using an outside geometry. Such systems allow to study how actin-related proteins control and affect actin cortex assembly and can produce forces that drive cell shape changes.

  19. Potential applications of antimicrobial peptides and their mimics in combating caries and pulpal infections.

    PubMed

    Mai, Sui; Mauger, Matthew T; Niu, Li-Na; Barnes, Jonathan B; Kao, Solon; Bergeron, Brian E; Ling, Jun-Qi; Tay, Franklin R

    2017-02-01

    Antimicrobial peptides (AMPs) are short cationic host-defense molecules that provide the early stage of protection against invading microbes. They also have important modulatory roles and act as a bridge between innate and acquired immunity. The types and functions of oral AMPs were reviewed and experimental reports on the use of natural AMPs and their synthetic mimics in caries and pulpal infections were discussed. Natural AMPs in the oral cavity, predominantly defensins, cathelicidins and histatins, possess antimicrobial activities against oral pathogens and biofilms. Incomplete debridement of microorganisms in root canal space may precipitate an exacerbated immune response that results in periradicular bone resorption. Because of their immunomodulatory and wound healing potentials, AMPs stimulate pro-inflammatory cytokine production, recruit host defense cells and regulate immuno-inflammatory responses in the vicinity of the pulp and periapex. Recent rapid advances in the development of synthetic AMP mimics offer exciting opportunities for new therapeutic initiatives in root canal treatment and regenerative endodontics.

  20. Cyclic AMP Mimics the Anti-ageing Effects of Calorie Restriction by Up-Regulating Sirtuin.

    PubMed

    Wang, Zhuoran; Zhang, Lu; Liang, Yaru; Zhang, Chi; Xu, Zhiyu; Zhang, Lang; Fuji, Ryosuke; Mu, Wei; Li, Liyuan; Jiang, Junjun; Ju, Yong; Wang, Zhao

    2015-07-08

    Cyclic adenosine monophosphate (cAMP) plays an important role in many biological processes as a second messenger, and cAMP treatment has been reported to extend the lifespan of wild-type Drosophila melanogaster. Our study showed that exogenous cAMP improved ageing-related phenotypes by increasing the protein level of Sirtuins, which prevented metabolic disorders to mimic the effect of calorie restriction. Experiments in vitro showed that cAMP directly bound to SIRT1 and SIRT3 and consequently increased their activity. These findings suggest that cAMP slows the ageing process and is a good candidate to mimic calorie restriction. Our research provides a promising therapeutic strategy to target metabolic disorder-induced ageing-related diseases.

  1. A plant tendril mimic soft actuator with phototunable bending and chiral twisting motion modes

    PubMed Central

    Wang, Meng; Lin, Bao-Ping; Yang, Hong

    2016-01-01

    In nature, plant tendrils can produce two fundamental motion modes, bending and chiral twisting (helical curling) distortions, under the stimuli of sunlight, humidity, wetting or other atmospheric conditions. To date, many artificial plant-like mechanical machines have been developed. Although some previously reported materials could realize bending or chiral twisting through tailoring the samples into various ribbons along different orientations, each single ribbon could execute only one deformation mode. The challenging task is how to endow one individual plant tendril mimic material with two different, fully tunable and reversible motion modes (bending and chiral twisting). Here we show a dual-layer, dual-composition polysiloxane-based liquid crystal soft actuator strategy to synthesize a plant tendril mimic material capable of performing two different three-dimensional reversible transformations (bending versus chiral twisting) through modulation of the wavelength band of light stimuli (ultraviolet versus near-infrared). This material has broad application prospects in biomimetic control devices. PMID:28004810

  2. Antibacterial TAP-mimic Electrospun Polymer Scaffold – Effects on P. gingivalis-Infected Dentin Biofilm

    PubMed Central

    Albuquerque, Maria Tereza P.; Evans, Joshua D.; Gregory, Richard L.; Valera, Marcia C.; Bottino, Marco C.

    2016-01-01

    Objectives This study sought to investigate, in-vitro, the effects of a recently developed triple antibiotic paste (TAP)-mimic polymer nanofibrous scaffold against Porphyromonas gingivalis (Pg)-infected dentin biofilm. Materials and Methods Dentin specimens (4×4×1mm3) were prepared from human canines. The specimens were sterilized, inoculated with Pg (ATCC 33277), and incubated for one week to allow for biofilm formation. Infected dentin specimens were exposed for 3 days to the following treatments: antibiotic-free polydioxanone scaffold (PDS, control), PDS+25wt.%TAP (25 mg of each antibiotic [metronidazole, ciprofloxacin, and minocycline] per mL of the PDS polymer solution), or a saturated TAP-based solution (50 mg of each antibiotic per mL of saline solution). In order to serve as the negative control, infected dentin specimens were left untreated (bacteria only). To determine the antimicrobial efficacy of the TAP-mimic scaffold, a colony-forming unit (CFU/mL) (n=10/group) measurement was performed. Furthermore, additional specimens (n=2/group) were prepared to qualitatively study biofilm inhibition via scanning electron microscopy (SEM). Statistics were performed and significance was set at the 5% level. Results Both the TAP-mimic scaffold and the positive control (TAP solution) led to complete bacterial elimination, differing statistically (p<0.05) from the negative control group (bacteria only). No statistical differences were observed for CFU/mL data between antibiotic-free scaffolds (2.7 log10 CFU/mL) and the negative control (5.9 log10 CFU/mL). Conclusions The obtained data revealed significant antimicrobial properties of the novel PDS-based TAP-mimic scaffold against an established Pg-infected dentin biofilm. Clinical relevance Collectively, the data suggest that the proposed nanofibrous scaffold might be used as an alternative to the advocated clinical gold standard (i.e., TAP) for intracanal disinfection prior to regenerative endodontics. PMID:26319981

  3. Nonyloxytryptamine Mimics Polysialic Acid and Modulates Neuronal and Glial Functions in Cell Culture

    DTIC Science & Technology

    2014-01-01

    protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5-nonyloxytryptamine mimics Received May 27, 2013; revised manuscript...adhesion molecule (NCAM) and its polysialylated form PSA-NCAM and reduces expression of the microtubuleassociated protein MAP2 in cultured neuroblastoma ...origin and a neuroblastoma cell line as model for easy manipulation (Gotti et al. 1987). Our results show that 5-nonyloxytryptamine binds to a PSA

  4. Evidence that Cerambycid Beetles Mimic Vespid Wasps in Odor as well as Appearance.

    PubMed

    Mitchell, Robert F; Curkovic, Tomislav; Mongold-Diers, Judith A; Neuteboom, Lara; Galbrecht, Hans-Martin; Tröger, Armin; Bergmann, Jan; Francke, Wittko; Hanks, Lawrence M

    2017-01-01

    We present evidence that cerambycid species that are supposed mimics of vespid wasps also mimic their model's odor by producing spiroacetals, common constituents of vespid alarm pheromones. Adults of the North American cerambycids Megacyllene caryae (Gahan) and Megacyllene robiniae (Forster) are conspicuously patterned yellow and black, and are believed to be mimics of aculeate Hymenoptera, such as species of Vespula and Polistes. Adult males of M. caryae produce an aggregation-sex pheromone, but both sexes produce a pungent odor when handled, which has been assumed to be a defensive response. Headspace aerations of agitated females of M. caryae contained 16 compounds with mass spectra characteristic of spiroacetals of eight distinct chemical structures, with the dominant compound being (7E,2E)-7-ethyl-2-methyl-1,6-dioxaspiro[4.5]decane. Headspace samples of agitated males of M. caryae contained five of the same components, with the same dominant compound. Females of M. robiniae produced six different spiroacetals, one of which was not produced by M. caryae, (2E,7E)-2-ethyl-7-methyl-1,6-dioxaspiro[4.5]decane, and five that were shared with M. caryae, including the dominant (2E,8E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane. The latter compound is the sole spiroacetal produced by both males and females of a South American cerambycid species, Callisphyris apicicornis (Fairmaire & Germain), which is also thought to be a wasp mimic. Preliminary work also identified spiroacetals of similar or identical structure released by vespid wasps that co-occur with the Megacyllene species.

  5. Sonography of Abdominal Pain in Children: Appendicitis and Its Common Mimics.

    PubMed

    Sanchez, Thomas Ray; Corwin, Michael T; Davoodian, Andrew; Stein-Wexler, Rebecca

    2016-03-01

    Abdominal pain is very common in the pediatric population (<18 years of age). Sonography is a safe modality that can often differentiate the frequently encountered causes of abdominal pain in children. This pictorial essay will discuss the sonographic findings of acute appendicitis, including the imaging appearance of a perforated appendicitis. It will also present the sonographic features of the relatively common mimics of appendicitis, such as mesenteric adenitis/gastroenteritis, intussusception, Meckel diverticulum, and ovarian torsion.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. A genetic toolkit for tagging intronic MiMIC containing genes

    PubMed Central

    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. DOI: http://dx.doi.org/10.7554/eLife.08469.001 PMID:26102525

  11. Sequence-specific base pair mimics are efficient topoisomerase IB inhibitors.

    PubMed

    Vekhoff, Pierre; Duca, Maria; Guianvarc'h, Dominique; Benhida, Rachid; Arimondo, Paola B

    2012-01-10

    Topoisomerase IB controls DNA topology by cleaving DNA transiently. This property is used by inhibitors, such as camptothecin, that stabilize, by inhibiting the religation step, the cleavage complex, in which the enzyme is covalently attached to the 3'-phosphate of the cleaved DNA strand. These drugs are used in clinics as antitumor agents. Because three-dimensional structural studies have shown that camptothecin derivatives act as base pair mimics and intercalate between two base pairs in the ternary DNA-topoisomerase-inhibitor complex, we hypothesized that base pairs mimics could act like campthotecin and inhibit the religation reaction after the formation of the topoisomerase I-DNA cleavage complex. We show here that three base pair mimics, nucleobases analogues of the aminophenyl-thiazole family, once targeted specifically to a DNA sequence were potent topoisomerase IB inhibitors. The targeting was achieved through covalent linkage to a sequence-specific DNA ligand, a triplex-forming oligonucleotide, and was necessary to position and keep the nucleobase analogue in the cleavage complex. In the absence of triplex formation, only a weak binding to the DNA and topoisomerase I-mediated DNA cleavage was observed. The three compounds were equally active once conjugated, implying that the intercalation of the nucleobase upon triplex formation is the essential feature for the inhibition activity.

  12. Ultrasmall Pt Nanoclusters as Robust Peroxidase Mimics for Colorimetric Detection of Glucose in Human Serum.

    PubMed

    Jin, Lihua; Meng, Zheng; Zhang, Yongqing; Cai, Shijie; Zhang, Zaihua; Li, Cong; Shang, Li; Shen, Yehua

    2017-02-28

    In this work, a new type of ultrasmall Pt nanoclusters (Pt NCs) has been prepared via a facile one-pot approach by using yeast extract as the reductant and stabilizer. Besides their excellent water-solubility, these yeast extract-stabilized Pt NCs also possess attractive peroxidase mimics property. They can efficiently catalyze the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) in the coexistence of hydrogen peroxide (H2O2). Catalytic mechanism analysis suggested that the peroxidase mimics activity of these Pt NCs might originate from their characteristic of accelerating electron transfer between TMB and H2O2, and their enzymatic kinetics followed typical Michaelis-Menten theory. Based on these findings, we developed a new highly sensitive colorimetric method for glucose detection, and the limit of detection was calculated as low as 0.28 μM (S/N = 3). Further application of the present system for glucose detection in human serum has been successfully demonstrated, suggesting its promising utilization as robust peroxidase mimics in the clinical diagnosis, pharmaceutical and environmental chemistry fields.

  13. 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.

  14. The TeleStroke Mimic (TM)‐Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network

    PubMed Central

    Ali, Syed F.; Viswanathan, Anand; Singhal, Aneesh B.; Rost, Natalia S.; Forducey, Pamela G.; Davis, Lawrence W.; Schindler, Joseph; Likosky, William; Schlegel, Sherene; Solenski, Nina; Schwamm, Lee H.

    2014-01-01

    Background Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England–based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver‐operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM‐Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM‐Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision‐support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time‐critical telestroke evaluations. PMID:24958778

  15. 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

  16. Identification of key genes in hepatocellular carcinoma and validation of the candidate gene, cdc25a, using gene set enrichment analysis, meta-analysis and cross-species comparison.

    PubMed

    Lu, Xiaoxu; Sun, Wen; Tang, Yanping; Zhu, Lingqun; Li, Yuan; Ou, Chao; Yang, Chun; Su, Jianjia; Luo, Chengpiao; Hu, Yanling; Cao, Ji

    2016-02-01

    The aim of the present study was to determine key pathways and genes involved in the pathogenesis of hepatocellular carcinoma (HCC) through bioinformatic analyses of HCC microarray data based on cross-species comparison. Microarray data of gene expression in HCC in different species were analyzed using gene set enrichment analysis (GSEA) and meta-analysis. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to determine the mRNA and protein expression levels of cdc25a, one of the identified candidate genes, in human, rat and tree shrew samples. The cell cycle pathway had the largest overlap between the GSEA and meta-analysis. Meta-analyses showed that 25 genes, including cdc25a, in the cell cycle pathway were differentially expressed. Cdc25a mRNA levels in HCC tissues were higher than those in normal liver tissues in humans, rats and tree shrews, and the expression level of cdc25a in HCC tissues was higher than in corresponding paraneoplastic tissues in humans and rats. In human HCC tissues, the cdc25a mRNA level was significantly correlated with clinical stage, portal vein tumor thrombosis and extrahepatic metastasis. Western blotting showed that, cdc25a protein levels were significantly upregulated in HCC tissues in humans, rats and tree shrews. In conclusion, GSEA and meta-analysis can be combined to identify key molecules and pathways involved in HCC. This study demonstrated that the cell cycle pathway and the cdc25a gene may be crucial in the pathogenesis and progression of HCC.

  17. 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

  18. 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.

  19. 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.

  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. Proteolytically Stable Foldamer Mimics of Host-Defense Peptides with Protective Activities in a Murine Model of Bacterial Infection.

    PubMed

    Teyssières, Emilie; Corre, Jean-Philippe; Antunes, Stephanie; Rougeot, Catherine; Dugave, Christophe; Jouvion, Grégory; Claudon, Paul; Mikaty, Guillain; Douat, Céline; Goossens, Pierre L; Guichard, Gilles

    2016-09-22

    The synthesis of bioinspired unnatural backbones leading to foldamers can provide effective peptide mimics with improved properties in a physiological environment. This approach has been applied to the design of structural mimics of membrane active antimicrobial peptides (AMPs) for which activities in vitro have been reported. Yet activities and pharmacokinetic properties in vivo in animal models have remained largely unexplored. Here, we report helical oligourea AMP mimics that are active in vitro against bacterial forms of Bacillus anthracis encountered in vivo, as well as in vivo in inhalational and cutaneous mouse models of B. anthracis infection. The pharmacokinetic profile and the tissue distribution were investigated by β-radio imager whole-body mapping in mice. Low excretion and recovery of the native oligourea in the kidney following intravenous injection is consistent with high stability in vivo. Overall these results provide useful information that support future biomedical development of urea-based foldamer peptide mimics.

  2. Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae

    PubMed Central

    Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

    2017-01-01

    Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition.

  3. 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

  4. 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.

  5. Synthetic mimic of antimicrobial peptide with nonmembrane-disrupting antibacterial properties.

    PubMed

    Gabriel, Gregory J; Madkour, Ahmad E; Dabkowski, Jeffrey M; Nelson, Christopher F; Nüsslein, Klaus; Tew, Gregory N

    2008-11-01

    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.

  6. A rare cause of breast mass that mimics carcinoma: Foreign body reaction to amorphous surgical material.

    PubMed

    Yazici, Burhan; Sever, Ali Riza; Mills, Philippa; Fish, David; Jones, Susan; Jones, Peter

    2007-01-01

    A breast mass caused by foreign body type granulomatous reaction to surgical material is a very rare lesion and may mimic carcinoma. Reported foreign materials have included suture materials, silicone, paraffin, gunpowder and carbon particles used for localization of a nonpalpable breast lesions. To our knowledge, a foreign body reaction to gauze sponge has not been reported previously. A 58-year-old woman who had an enlarging mass that mimicked breast carcinoma, due to foreign body reaction to gauze sponge is presented here, and relevant literature is reviewed.

  7. Metal-organic framework biosensor with high stability and selectivity in a bio-mimic environment.

    PubMed

    Wu, Xiao-Qin; Ma, Jian-Gong; Li, Han; Chen, Di-Ming; Gu, Wen; Yang, Guang-Ming; Cheng, Peng

    2015-06-04

    A water-stable copper metal-organic framework (MOF), {[Cu2(HL)2(μ2-OH)2(H2O)5]·H2O}n (1, H2L = 2,5-dicarboxylic acid-3,4-ethylene dioxythiophene), was applied for the electrochemical detection of ascorbic acid (AA) without further post-modification. A glass carbon electrode covered with 1 was used as a biosensor for the simultaneous detection of AA and L-tryptophan (L-Trp) from both a single-component solution and a bio-mimic environment.

  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. Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody

    DTIC Science & Technology

    2013-05-01

    Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody PRINCIPAL INVESTIGATOR: Ulrich Bickel...of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody 5b. GRANT NUMBER W81XWH-12-1-0184 5c. PROGRAM ELEMENT NUMBER 6...tumors using a brain selective cell line, 231-BR, derived from human breast cancer . Therefore, the experimental model to be used must be immune

  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

    Cheney, Karen L

    2012-02-23

    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.

  14. 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

  15. 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

  16. 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.

  17. Generation 9 polyamidoamine dendrimer encapsulated platinum nanoparticle mimics catalase size, shape, and catalytic activity.

    PubMed

    Wang, Xinyu; Zhang, Yincong; Li, Tianfu; Tian, Wende; Zhang, Qiang; Cheng, Yiyun

    2013-04-30

    Poly(amidoamine) (PAMAM) encapsulated platinum nanoparticles were synthesized and used as catalase mimics. Acetylated generation 9 (Ac-G9) PAMAM dendrimer with a molecular size around 10 nm was used as a template to synthesize platinum nanoparticles. The feeding molar ratio of Pt(4+) and Ac-G9 is 2048, and the synthesized platinum nanoparticle (Ac-G9/Pt NP) has an average size of 3.3 nm. Ac-G9/Pt NP has a similar molecular size and globular shape with catalase (~11 nm). The catalytic activity of Ac-G9/Pt NP on the decomposition of H2O2 is approaching that of catalase at 37 °C. Ac-G9/Pt NP shows differential response to the changes of pH and temperature compared with catalase, which can be explained by different catalytic mechanisms of Ac-G9/Pt NP and catalase. Ac-G9/Pt NP also shows horseradish peroxidase activity and is able to scavenge free radicals such as di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH). Furthermore, Ac-G9/Pt NP shows excellent biocompatibility on different cell lines and can down-regulate H2O2-induced intracellular reactive oxygen species (ROS) in these cells. These results suggest that dendrimers are promising mimics of proteins with different sizes and Ac-G9/Pt NP can be used as an alternative candidate of catalase to decrease oxidation stress in cells.

  18. 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

  19. Asteroid Hyalosis: A Mimic of Vitreous Hemorrhage on Point of Care Ultrasound.

    PubMed

    Stringer, Charles E A; Ahn, Justin S; Kim, Daniel J

    2016-08-30

    Point of care ultrasound in the emergency department (ED) is increasingly being used to diagnose time-sensitive, vision-threatening conditions. We present a case of a 64-year-old female who presented to the ED with a three-day history of worsening left eye floaters. Point of care ocular ultrasound demonstrated a posterior chamber containing many echogenic opacities of varying size without acoustic shadowing. Movement of the eye resulted in significant after-movement of these opacities, giving the classic "washing machine" appearance seen with vitreous hemorrhage (VH). Based on these ultrasound findings, the patient was diagnosed with a VH and was referred to ophthalmology. The consulting ophthalmologist ultimately diagnosed the patient with asteroid hyalosis without VH. Asteroid hyalosis is a benign condition of the vitreous resulting in calcium phosphate and lipid deposits that can mimic more serious VH on point of care ultrasound. Knowledge of this mimic is helpful for communication with specialists and for awareness of the potential for misdiagnosis with ocular ultrasound.

  20. Does Intracerebral Hemorrhage Mimic Benign Dizziness Presentations? A Population Based Study

    PubMed Central

    Kerber, Kevin A.; Burke, James F.; Brown, Devin L.; Meurer, William J.; Smith, Melinda A.; Lisabeth, Lynda D.; Morgenstern, Lewis B.; Zahuranec, Darin B.

    2012-01-01

    Objective A principal reason to order a head computerized tomography (CT) scan for dizziness patients is to exclude stroke. Since CT imaging is substantially limited in assessing for any acute lesions other than hemorrhage, the most important stroke syndrome adequately evaluated by CT is intracerebral hemorrhage (ICH). We used a population-based stroke database to assess the frequency with which ICH might mimic a benign dizziness presentation. Methods The Brain Attack Surveillance in Corpus Christi (BASIC) project was used to identify cases of ICH from January 1, 2000, to December 26, 2007. The hospital records of ICH cases with a National Institutes of Health Stroke Scale (NIHSS) of < 2 were abstracted for more detailed information. Cases were classified as benign dizziness presentations when isolated dizziness and a normal general neurological examination were documented. Results Of 595 ICH cases, only 2.2% (13 of 595) had dizziness as the primary presenting symptom and an NIHSS < 2. No case mimicked a benign dizziness presentation. Only one case had isolated dizziness symptoms but this patient had dysmetria documented on the exam. All other cases had either focal or global neurological symptoms or exam abnormalities. Conclusions This study provides further support for the notion that ICH is highly unlikely to mimic a benign dizziness presentation. Coupled with the limitations of CT to show acute ischemia in the posterior fossa, these results suggest that screening for ICH may not be necessary in benign appearing dizziness presentations, though more research is needed. PMID:21245473

  1. 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

  2. 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

  3. Synthesis of Bi-substrate State Mimics of Dihydropteroate Synthase as Potential Inhibitors and Molecular Probes

    PubMed Central

    Qi, Jianjun; Virga, Kristopher G.; Das, Sourav; Zhao, Ying; Yun, Mi-Kyung; White, Stephen W.; Lee, Richard E.

    2010-01-01

    The increasing emergence of resistant bacteria drives us to design and develop new antimicrobial agents. Pursuant to that goal, a new targeting approach of the dihydropteroate synthase enzyme, which serves as the site of action for the sulfonamide class of antimicrobial agents, is being explored. Using structural information, a new class of transition state mimics has been designed and synthesized that have the capacity to bind to the pterin, phosphate and para-amino binding sites. The design, synthesis and evaluation of these compounds as inhibitors of Bacillus anthracis dihydropteroate synthase is described herein. Outcomes from this work have identified the first trivalent inhibitors of dihydropteroate synthase whose activity displayed slow binding inhibition. The most active compounds in this series contained an oxidized pterin ring. The binding of these inhibitors was modeled into the dihydropteroate synthase active site and demonstrated a good correlation with the observed bioassay data, as well as provided important insight for the future design of higher affinity transition state mimics. PMID:21216602

  4. 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.

  5. 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

    2014-09-05

    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.

  6. Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

    PubMed Central

    Miras, A D; le Roux, C W

    2014-01-01

    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

  7. 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

  8. Low energy photon mimic of the tritium beta decay energy spectrum

    NASA Astrophysics Data System (ADS)

    Malabre-O'Sullivan, Neville

    Tritium is a radioactive hydrogen isotope that is typically produced via neutron interaction with heavy water (D2O), producing tritiated water (DTO). As a result of this, tritium accounts for roughly a third of all occupational exposures at a CANDU type nuclear power plant. This identifies a need to study the biological effects associated with tritium (and low energy electrons in general). However, there are complications regarding the dosimetry of tritium, as well as difficulties in handling and using tritium for the purposes of biophysics experiments. To avoid these difficulties, an experiment has been proposed using photons to mimic the beta decay energy spectrum of tritium. This would allow simulation of the radiation properties of tritium, so that a surrogate photon source can be used for biophysics experiments. Through experimental and computational means, this work has explored the use of characteristic x-rays of various materials to modify the output spectrum of an x-ray source, such that it mimics the tritium beta decay spectrum. Additionally, the resultant primary electron spectrum generated in water from an x-ray source was simulated. The results from this research have indicated that the use of characteristic x-rays is not a viable method for simulating a tritium source. Also, the primary electron spectrum generated in water shows some promise for simulating tritium exposure, however further work must be done to investigate the slowing down electron spectrum. Keywords: Tritium, MCNP, low energy electrons, biophysics, characteristic x-rays.

  9. Compartmentalization Approaches in Soft Matter Science: From Nanoreactor Development to Organelle Mimics.

    PubMed

    Schoonen, Lise; van Hest, Jan C M

    2016-02-10

    Compartmentalization is an essential feature found in living cells to ensure that biological processes occur without being affected by undesired external influences. Over the years many scientists have designed self-assembled soft matter structures that mimic these natural catalytic compartments. The rationale behind this research is threefold. First of all, compartmentalization leads to the creation of a secluded environment for the catalytic species, which solves compatibility issues and which can improve catalyst efficiency and selectivity. Secondly, nano- and micro-compartments are constructed with the aim to obtain microenvironments that more closely mimic the cellular architecture. These biomimetic platforms are used to attain a better understanding of how cellular processes are executed. Thirdly, natural design rules are applied to create biomolecular assemblies with unusual functionality, which for example are used as artificial organelles. Here, recent developments will be discussed regarding these compartmentalized catalytic systems, with a selected number of illustrative examples to demonstrate which strategies have been followed, and to show to what extent the ambitious goals of this field of science have been reached. The focus here is on the field of soft matter science, covering the wide spectrum from polymeric assemblies to protein nanocages.

  10. 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

    2016-02-22

    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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Noncovalent modification of carbon nanotubes with ferrocene-amino acid conjugates for electrochemical sensing of chemical warfare agent mimics.

    PubMed

    Khan, Mohammad A K; Kerman, Kagan; Petryk, Michael; Kraatz, Heinz-Bernhard

    2008-04-01

    The electrochemical detection of chemical warfare agent (CWA) mimics was explored using multiwalled carbon nanotubes (MWCNTs) on indium tin oxide (ITO) surfaces in connection with ferrocene-amino acid conjugates. Various ferrocene-amino acid conjugates were synthesized and utilized as the recognition layer for the detection of CWA mimics. The ferrocene-amino acid conjugates were noncovalently attached to the pretreated MWCNTs on the ITO surface and reacted with CWA mimics, upon which the electrical properties of the MWCNTs and the Fc group were affected significantly. Alternating current voltammetry and capacitance-based detection offered large dynamic ranges for the detection of methylphosphonic acid, diethyl cyanophosphonate, ethylmethylphosphonate, and pinacolyl methylphosphonate in water. Electrochemical measurements showed dramatic changes upon the electrostatic interaction between the CWA mimics and the ferrocene-amino acid conjugates immobilized on MWCNTs on ITO surfaces. Electrochemical sensing in connection with MWCNTs is shown to be a promising analytical tool for the trace-level detection of CWA mimics in aqueous solutions.

  16. Variables That Best Differentiate In-Patient Acute Stroke from Stroke-Mimics with Acute Neurological Deficits

    PubMed Central

    Natteru, P.; Mohebbi, M. R.; George, P.; Wisco, D.; Gebel, J.

    2016-01-01

    Introduction. Strokes and stroke-mimics have been extensively studied in the emergency department setting. Although in-hospital strokes are less studied in comparison to strokes in the emergency department, they are a source of significant direct and indirect costs. Differentiating in-hospital strokes from stroke-mimics is important. Thus, our study aimed to identify variables that can differentiate in-hospital strokes from stroke-mimics. Methods. We present here a retrospective analysis of 93 patients over a one-year period (2009 to 2010), who were evaluated for a concern of in-hospital strokes. Results. About two-thirds (57) of these patients were determined to have a stroke, and the remaining (36) were stroke-mimics. Patients with in-hospital strokes were more likely to be obese (p = 0.03), have been admitted to the cardiology service (p = 0.01), have atrial fibrillation (p = 0.03), have a weak hand or hemiparesis (p = 0.03), and have a prior history of stroke (p = 0.05), whereas, when the consults were called for “altered mental status” but no other deficits (p < 0.0001), it is likely a stroke-mimic. Conclusion. This study demonstrates that in-hospital strokes are a common occurrence, and knowing the variables can aid in their timely diagnosis and treatment. PMID:28050311

  17. 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

  18. Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors

    PubMed Central

    Chang, Chun Yun; Esber, Guillem R; Marrero-Garcia, Yasmin; Yau, Hau-Jie; Bonci, Antonello; Schoenbaum, Geoffrey

    2015-01-01

    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. While 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. Lacking such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide such evidence, 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

  19. 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

    2015-12-07

    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.

  20. A sensitive choline biosensor using Fe3O4 magnetic nanoparticles as peroxidase mimics.

    PubMed

    Zhang, Zhanxia; Wang, Xiaolei; Yang, Xiurong

    2011-12-07

    A sensitive choline biosensor using Fe(3)O(4) magnetic nanoparticles and a choline oxidase modified gold electrode was developed. Fe(3)O(4) magnetic nanoparticles as peroxidase mimics used in the choline biosensor can not only improve the sensitivity of the response signal, but also possess the favorable properties of stability, magnetic separation and easy preparation, etc. When using the reduction currents of square wave voltammetry as the detection signals, the interferences of ascorbic acid and uric acid to the choline biosensor can be reduced effectively. The reduction currents of the square wave voltammetry were increased with the logarithm values of the choline chloride concentration (from 10(-9) to 10(-2) M), the detection limit was estimated to be 0.1 nM (S/N = 3). This choline biosensor also exhibited favorable selectivity and stability in the determination of choline chloride.

  1. A Phosphoenzyme Mimic, Overlapping Catalytic Sites and Reaction Coordinate Motion for Human NAMPT

    SciTech Connect

    Burgos, E.; Ho, M; Almo, S; Schramm, V

    2009-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) is highly evolved to capture nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD+) pool during ADP-ribosylation and transferase reactions. ATP-phosphorylation of an active-site histidine causes catalytic activation, increasing NAM affinity by 160,000. Crystal structures of NAMPT with catalytic site ligands identify the phosphorylation site, establish its role in catalysis, demonstrate unique overlapping ATP and phosphoribosyltransferase sites, and establish reaction coordinate motion. NAMPT structures with beryllium fluoride indicate a covalent H247-BeF3- as the phosphohistidine mimic. Activation of NAMPT by H247-phosphorylation causes stabilization of the enzyme-phosphoribosylpyrophosphate complex, permitting efficient capture of NAM. Reactant and product structures establish reaction coordinate motion for NAMPT to be migration of the ribosyl anomeric carbon from the pyrophosphate leaving group to the nicotinamide-N1 while the 5-phosphoryl group, the pyrophosphate moiety, and the nicotinamide ring remain fixed in the catalytic site.

  2. Structure of Ocr from bacteriophage T7, a protein that mimics B-form DNA.

    PubMed

    Walkinshaw, M D; Taylor, P; Sturrock, S S; Atanasiu, C; Berge, T; Henderson, R M; Edwardson, J M; Dryden, D T F

    2002-01-01

    We have solved, by X-ray crystallography to a resolution of 1.8 A, the structure of a protein capable of mimicking approximately 20 base pairs of B-form DNA. This ocr protein, encoded by gene 0.3 of bacteriophage T7, mimics the size and shape of a bent DNA molecule and the arrangement of negative charges along the phosphate backbone of B-form DNA. We also demonstrate that ocr is an efficient inhibitor in vivo of all known families of the complex type I DNA restriction enzymes. Using atomic force microscopy, we have also observed that type I enzymes induce a bend in DNA of similar magnitude to the bend in the ocr molecule. This first structure of an antirestriction protein demonstrates the construction of structural mimetics of long segments of B-form DNA.

  3. FIESTA: an MR arthrography celebration of shoulder joint anatomy, variants, and their mimics.

    PubMed

    Yu, D; Turmezei, T D; Kerslake, R W

    2013-03-01

    Magnetic resonance (MR) arthrography is currently the gold standard radiological investigation for shoulder joint instability. Not only does this investigation allow for identification of important disease processes, but the reduced slice thickness and increased in-plane resolution allowed by the latest imaging sequences also gives excellent demonstration of shoulder joint internal anatomy. This article describes the technique of MR arthrography of the shoulder practiced at our institution, briefly outlining features of the FIESTA (fast imaging employing steady state acquisition) MR sequence employed, including its advantages and limitations. A pictorial review of shoulder MR arthrography performed with this technique is presented, concentrating on normal shoulder joint internal anatomy and anatomical variants that may mimic pathology.

  4. 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.

  5. Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold.

    PubMed

    Erixon, Karl M; Dabalos, Chester L; Leeper, Finian J

    2008-10-07

    Novel triazole-based pyrophosphate analogues of thiamine pyrophosphate (TPP) have been synthesised and tested for inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis. The thiazolium ring of thiamine was replaced by a triazole in an efficient two-step procedure. Pyrophosphorylation then gave extremely potent triazole inhibitors with K(I) values down to 20 pM, compared to a K(D) value of 0.35 microM for TPP. This triazole scaffold was used for further investigation and six analogues containing mimics of the pyrophosphate group were synthesised and tested for inhibition of PDC. Several effective analogues were found with K(I) values down to around 1 nM.

  6. Preparation of High-Density Fibrillar Collagen Matrices that Mimic Desmoplastic Tumor Stroma

    PubMed Central

    Artym, Vira V.

    2016-01-01

    The stroma of invasive tumors becomes enriched in dense fibrillar collagen as a result of the desmoplastic reaction. This desmoplastic collagen exerts profound effects on tumor and normal cells. In view of these findings, it is important to develop novel in vitro cell systems that mimic this desmoplastic extracellular matrix in order to permit cell studies under in vivo-like conditions. This Unit provides a protocol and troubleshooting guide for the preparation of high density fibrillar collagen (HDFC) matrices that closely model the desmoplastic collagenous matrix of malignant tumors. It then describes the use of this HDFC matrix for in vitro cell studies of invadopodia formation and function in extracellular matrix invasion. In addition, this Unit also provides a detailed protocol for immuno-labeling of invadopodial proteins and detection of HDFC matrix degradation associated with invadopodia to permit invadopodia visualization using fluorescence microscopy. PMID:26930554

  7. A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT

    PubMed Central

    Burgos, Emmanuel S.; Ho, Meng-Chiao; Almo, Steven C.; Schramm, Vern L.

    2009-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) is highly evolved to capture nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD+) pool during ADP-ribosylation and transferase reactions. ATP-phosphorylation of an active-site histidine causes catalytic activation, increasing NAM affinity by 160,000. Crystal structures of NAMPT with catalytic site ligands identify the phosphorylation site, establish its role in catalysis, demonstrate unique overlapping ATP and phosphoribosyltransferase sites, and establish reaction coordinate motion. NAMPT structures with beryllium fluoride indicate a covalent H247-BeF3− as the phosphohistidine mimic. Activation of NAMPT by H247-phosphorylation causes stabilization of the enzyme-phosphoribosylpyrophosphate complex, permitting efficient capture of NAM. Reactant and product structures establish reaction coordinate motion for NAMPT to be migration of the ribosyl anomeric carbon from the pyrophosphate leaving group to the nicotinamide-N1 while the 5-phosphoryl group, the pyrophosphate moiety, and the nicotinamide ring remain fixed in the catalytic site. PMID:19666527

  8. Synthesis of mimics of pramanicin from pyroglutamic acid and their antibacterial activity.

    PubMed

    Tan, Song Wei Benjamin; Chai, Christina L L; Moloney, Mark G; Thompson, Amber L

    2015-03-06

    Epoxypyrrolidinones are available by epoxidation of carboxamide-activated bicyclic lactam substrates derived from pyroglutamate using aqueous hydrogen peroxide and tertiary amine catalysis. In the case of an activating Weinreb carboxamide, further chemoselective elaboration leads to the efficient formation of libraries of epoxyketones. Deprotection may be achieved under acidic conditions to give epoxypyroglutaminols, although the ease of this process can be ameliorated by the presence of internal hydrogen bonding. Bioassay against S. aureus and E. coli indicated that some compounds exhibit antibacterial activity. These libraries may be considered to be structural mimics of the natural products pramanicin and epolactaene. More generally, this outcome suggests that interrogation of bioactive natural products is likely to permit the identification of "privileged" structural scaffolds, providing frameworks suitable for optimization in a short series of chemical steps that may accelerate the discovery of new antibiotic chemotypes. Further optimization of such systems may permit the rapid identification of novel systems suitable for antibacterial drug development.

  9. Illustration of MIMIC-Model DIF Testing with the Schedule for Nonadaptive and Adaptive Personality

    PubMed Central

    Oltmanns, Thomas F.; Turkheimer, Eric

    2010-01-01

    This research provides an example of testing for differential item functioning (DIF) using multiple indicator multiple cause (MIMIC) structural equation models. True/False items on five scales of the Schedule for Nonadaptive and Adaptive Personality (SNAP) were tested for uniform DIF in a sample of Air Force recruits with groups defined by gender and ethnicity. Uniform DIF exists when an item is more easily endorsed for one group than the other, controlling for group mean differences on the variable under study. Results revealed significant DIF for many SNAP items and some effects were quite large. Differentially-functioning items can produce measurement bias and should be either deleted or modeled as if separate items were administered to different groups. Future research should aim to determine whether the DIF observed here holds for other samples. PMID:20442793

  10. Imaging tissue-mimic with light sheet microscopy: A comparative guideline

    PubMed Central

    Andilla, Jordi; Jorand, Raphael; Olarte, Omar E.; Dufour, Alexandre C.; Cazales, Martine; Montagner, Yoann L. E.; Ceolato, Romain; Riviere, Nicolas; Olivo-Marin, Jean-Christophe; Loza-Alvarez, Pablo; Lorenzo, Corinne

    2017-01-01

    Tissue mimics (TMs) on the scale of several hundred microns provide a beneficial cell culture configuration for in vitro engineered tissue and are currently under the spotlight in tissue engineering and regenerative medicine. Due to the cell density and size, TMs are fairly inaccessible to optical observation and imaging within these samples remains challenging. Light Sheet Fluorescence Microscopy (LSFM)- an emerging and attractive technique for 3D optical sectioning of large samples- appears to be a particularly well-suited approach to deal with them. In this work, we compared the effectiveness of different light sheet illumination modalities reported in the literature to improve resolution and/or light exposure for complex 3D samples. In order to provide an acute and fair comparative assessment, we also developed a systematic, computerized benchmarking method. The outcomes of our experiment provide meaningful information for valid comparisons and arises the main differences between the modalities when imaging different types of TMs. PMID:28322312

  11. Unveiling the Reactivity of a Synthetic Mimic of the Oxygen Evolving Complex.

    PubMed

    Raucci, Umberto; Ciofini, Ilaria; Adamo, Carlo; Rega, Nadia

    2016-12-15

    We simulated for the first time the oxygen-oxygen bond formation in a synthetic calcium-tetra manganese complex recently developed by Zhang and co-workers. In spite of promising structural similarities to the native oxygen evolving complex (OEC) in Photosystem II, several uncertainties on the mimic stability in water and on its potential catalytic activity still persist. Here, we characterized at density functional theory level the electronic and structural features of the Sn states of the complex, along with the oxygen-oxygen bond formation reaction, proposing a reasonable model for the hydrate complex. As a main finding, both the synthetic compound and the natural OEC show very close energetic barriers for the oxo-oxyl coupling process, suggesting that key electronic features of the natural OEC reactivity are well reproduced. This result strongly encourages the use of this synthetic complex in combination with other molecular assemblies for the design of successful artificial leaves.

  12. Mimic synaptic behavior with a single floating gate transistor: A MemFlash synapse

    NASA Astrophysics Data System (ADS)

    Ziegler, Martin; Kohlstedt, Hermann

    2013-11-01

    Memristive devices are promising candidates for artificial synapses in neuromorphic circuits. We provide evidence that a single floating gate transistor operating in a memristive mode can be used to mimic synaptic functionality. To ensure the memristive operation mode, the three-terminal device is reduced to a two-terminal device in such a way that the device resistance varied accordingly to the charge flow through the device during source-drain voltage application. Furthermore, based on Hebbian learning, a synaptic analytical expression for the learning rate of this device is derived. The experimental findings are theoretically supported by a capacitive based model. The presented two-terminal MemFlash-synapse can be considered as a potential substitute for any memristive synapses in neuromorphic circuits, cross bar arrays, or reconfigurable logics, and is compatible with state-of-the-art Si-fabrication technology.

  13. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site

    PubMed Central

    Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S.; Wang, Junzhi; Fry, Elizabeth E.; Stuart, David I.; Rao, Zihe

    2017-01-01

    Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention. PMID:28074040

  14. 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.

  15. Imaging tissue-mimic with light sheet microscopy: A comparative guideline

    NASA Astrophysics Data System (ADS)

    Andilla, Jordi; Jorand, Raphael; Olarte, Omar E.; Dufour, Alexandre C.; Cazales, Martine; Montagner, Yoann L. E.; Ceolato, Romain; Riviere, Nicolas; Olivo-Marin, Jean-Christophe; Loza-Alvarez, Pablo; Lorenzo, Corinne

    2017-03-01

    Tissue mimics (TMs) on the scale of several hundred microns provide a beneficial cell culture configuration for in vitro engineered tissue and are currently under the spotlight in tissue engineering and regenerative medicine. Due to the cell density and size, TMs are fairly inaccessible to optical observation and imaging within these samples remains challenging. Light Sheet Fluorescence Microscopy (LSFM)- an emerging and attractive technique for 3D optical sectioning of large samples- appears to be a particularly well-suited approach to deal with them. In this work, we compared the effectiveness of different light sheet illumination modalities reported in the literature to improve resolution and/or light exposure for complex 3D samples. In order to provide an acute and fair comparative assessment, we also developed a systematic, computerized benchmarking method. The outcomes of our experiment provide meaningful information for valid comparisons and arises the main differences between the modalities when imaging different types of TMs.

  16. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.

    PubMed

    Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Wang, Junzhi; Fry, Elizabeth E; Stuart, David I; Rao, Zihe

    2017-01-24

    Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

  17. 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

  18. 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

  19. Regiospecific solid-phase synthesis of branched oligoribonucleotides that mimic intronic lariat RNA intermediates.

    PubMed

    Katolik, Adam; Johnsson, Richard; Montemayor, Eric; Lackey, Jeremy G; Hart, P John; Damha, Masad J

    2014-02-07

    We have developed new solid phase methods for the synthesis of branched RNAs that mimic intronic lariat RNA intermediates. These methods produce branched oligoribonucleotide sequences of arbitrary length, base composition, and regiochemistry at the branchpoint junction. The methods utilize branching monomers that allow for the growth of each branch regioselectively from any of the hydroxyl positions (5′, 3′, or 2′) at the branch-point junction. The integrity and branchpoint connectivity of the synthetic products have been confirmed by HPLC and MS analysis, and cleavage of the 2′,5′ linkage by recombinant debranching enzyme. Nonhydrolyzable branched RNA analogues containing arabinose instead of ribose at the branchpoint junction were shown to inhibit debranching activity and, hence, represent “decoys” for sequestering RNA binding proteins thought to drive amyotrophic lateral sclerosis (ALS).

  20. 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.

  1. 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.

  2. Teacher ratings of child behavior in preschool: A MIMIC investigation of the BESS TRS-P.

    PubMed

    DiStefano, Christine; Ene, Mihaela; Leighton, Elizabeth

    2016-08-01

    The purpose of this study was to conduct further investigations of the latent structure underlying the Behavioral and Emotional Screening System Teacher Rating Scale-Preschool (BESS TRS-P) by examining latent variable differences due to demographic factors of the preschool children being rated. A U.S. representative sample of teacher ratings of more than 1,200 preschoolers was used to examine the latent structure of the BESS TRS-P. A multiple indicator-multiple causes (MIMIC) model used with a bifactor model showed differences on selected latent factor means relative to a child's age and gender, but no relationship with child's race. Use of age and/or gender scoring norms may produce a more accurate estimate of a child's latent score. (PsycINFO Database Record

  3. 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

  4. Regular Alcohol Consumption Mimics Cardiac Preconditioning by Protecting against Ischemia-Reperfusion Injury

    NASA Astrophysics Data System (ADS)

    Miyamae, Masami; Diamond, Ivan; Weiner, Michael W.; Camacho, S. Albert; Figueredo, Vincent M.

    1997-04-01

    Epidemiologic studies indicate that long-term alcohol consumption decreases the incidence of coronary disease and may improve outcome after myocardial infarction. Attenuation of ischemia-reperfusion injury after myocardial infarction improves survival. This study investigates the possibility that alcohol consumption can improve survival after myocardial infarction by reducing ischemia-reperfusion injury. Hearts were isolated from guinea pigs after drinking ethanol for 3-12 weeks and subjected to global ischemia and reperfusion. Hearts from animals drinking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. Adenosine A1 receptor blockade abolished the protection provided by ethanol consumption. These findings indicate that long-term alcohol consumption reduces myocardial ischemia-reperfusion injury and that adenosine A1 receptors are required for this protective effect of ethanol. This cardioprotective effect of long-term alcohol consumption mimics preconditioning and may, in part, account for the beneficial effect of moderate drinking on cardiac health.

  5. 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.

  6. Compound mimicry and trading predators by the males of sexually dimorphic Batesian mimics.

    PubMed

    Nelson, Ximena J; Jackson, Robert R

    2006-02-07

    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.

  7. Arachis hypogaea L. produces mimic and inhibitory quorum sensing like molecules.

    PubMed

    Nievas, F; Vilchez, L; Giordano, W; Bogino, P

    2017-03-29

    A wide variety of plant-associated soil bacteria (rhizobacteria) communicate with each other by quorum sensing (QS). Plants are able to detect and produce mimics and inhibitor molecules of the QS bacterial communicative process. Arachis hypogaea L. (peanut) establishes a nitrogen-fixing symbiosis with rhizobia belonging to the genus Bradyrhizobium. These bacteria use a QS mechanism dependent on the synthesis of N-acyl homoserine lactones (AHLs). Given the relevance that plant-rhizobacteria interactions have at the ecological level, this work addresses the involvement of peanut in taking part in the QS mechanism. By using biosensor bacterial strains capable of detecting AHLs, a series of standard and original bioassays were performed in order to determine both (i) the production of QS-like molecules in vegetal materials and (ii) the expression of the QS mechanism throughout plant-bacteria interaction. Mimic QS-like molecules (mQS) linked to AHLs with long acyl chains (lac-AHL), and inhibitor QS-like molecules (iQS) linked to AHLs with short acyl chains (sac-AHL) were detected in seed and root exudates. The results revealed that synthesis of specific signaling molecules by the plant (such as mQS and iQS) probably modulates the function and composition of the bacterial community established in its rhizosphere. Novel bioassays of QS detection during peanut-Bradyrhizobium interaction showed an intense production of QS signals in the contact zone between root and bacteria. It is demonstrated that root exudates stimulate the root colonization and synthesis of lac-AHL by Bradyrhizobium strains in the plant rhizosphere, which leads to the early stages of the development of beneficial plant-bacteria interactions.

  8. The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport.

    PubMed

    Kohan, Alison B; Vandersall, Abbey E; Yang, Qing; Xu, Min; Jandacek, Ronald J; Tso, Patrick

    2013-02-01

    Despite being banned in the U.S., organochlorine toxins such as DDT are frequently detected in human adipose tissue. The main route of exposure is through the consumption of contaminated foods and subsequent intestinal packaging of DDT into chylomicrons. These chylomicrons, which also contain dietary triacylglycerol (TG), are delivered directly to peripheral tissues without first being metabolized by the liver. The physiological process by which these compounds are delivered from chylomicrons to adipose is not well understood, but is clinically relevant since it bypasses first-pass metabolism. Based on its highly lipophilic nature, it has been assumed that DDT is transferred to peripheral tissues similar to TG; however, this has not been measured. Here, we use the lymph fistula rat to isolate chylomicrons containing both DDT and TG. These chylomicrons are the in vivo DDT delivery vehicle. Using 3T3-L1 adipocytes, we investigated the rate at which DDT transfers from chylomicrons to adipocytes, and mediators of this process. This novel approach closely approximates the in vivo DDT exposure route. We show that: 1) DDT repartitions from chylomicrons to adipocytes, 2) this transport does not require hydrolysis of TG within the chylomicron, and is stimulated by the inhibition of LPL, 3) albumin does not inhibit DDT uptake, 4) DDT dissolved in DMSO does not appropriately mimic in vivo DDT transport; and most importantly, 5) DDT uptake from chylomicrons does not mimic the uptake of TG from the same particles. Understanding these factors is important for designing interventions for human populations exposed to DDT.

  9. Liposomes as chaperone mimics with controllable affinity toward heat-denatured formate dehydrogenase from Candida boidinii.

    PubMed

    Yoshimoto, Makoto; Kozono, Ryohei; Tsubomura, Naoki

    2015-01-20

    Chaperone machinery in living systems can catch denatured enzymes and induce their reactivation. Chaperone mimics are beneficial for applying enzymatic reactions in vitro. In this work, the affinity between liposomes and thermally denatured enzymes was controlled to stabilize the enzyme activity. The model enzyme is formate dehydrogenase from Candida boidinii (CbFDH) which is a homodimer and negatively charged in the phosphate buffer solution (pH 7.2) used. The activity of free CbFDH readily decreased at 58 °C following the first-order kinetics with the half-life t1/2 of 27 min. The turbidity measurements showed that the denatured enzyme molecules formed aggregates. The liposomes composed of zwitterionic phosphatidylcholines (PCs) stabilized the CbFDH activity at 58 °C, as revealed with six different PCs. The PC liposomes were indicated to bind to the aggregate-prone enzyme molecules, allowing reactivation at 25 °C. The cofactor β-reduced nicotinamide adenine dinucleotide (NADH) also stabilized the enzyme activity. The affinity between liposomes and denatured CbFDH could be modulated by incorporating cationic 1,2-dioleoyloxy-3-trimethylammonium propane chloride (DOTAP) in PC membranes. The t1/2 values significantly increased in the presence of liposomes ([lipid] = 1.5 mM) composed of PC and DOTAP at the mole fraction f(D) of 0.1. On the other hand, the DOTAP-rich liposomes (f(D) ≥ 0.7) showed strong affinity toward denatured CbFDH, accelerating its deactivation. The liposomes with low charge density function as chaperone mimics that can efficiently catch the denatured enzymes without interfering with their intramolecular interaction for reactivation.

  10. 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.

  11. New strigolactone mimics: structure-activity relationship and mode of action as germinating stimulants for parasitic weeds.

    PubMed

    Zwanenburg, Binne; Nayak, Sandip K; Charnikhova, Tatsiana V; Bouwmeester, Harro J

    2013-09-15

    Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,β-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds.

  12. 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.

  13. 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

  14. Spinal Epidural Varices, a great Mimic of Intervertebral Disc Prolapse - A Case Series

    PubMed Central

    V, Raghavendra; Haridas, Papanaik; Kumar, Anand; K, Ajith

    2014-01-01

    Introduction: Epidural venous plexus enlargement, presenting with low back pain and radiculopathy, is an uncommon cause of nerve roots impingement. This condition commonly mimics a herniated nucleus pulposus radiologically. The radiological diagnosis is often missed and the diagnosis is made during the surgery. We are hereby presenting 2 such cases of epidural varices mimicking intervertebral disc prolapse with lumbar radiculopathy. Case Report: Case 1: 43 yr old female presented with acute exacerbation of low back ache and significant right L5–S1 radiculopathy without neurological deficit. MRI reported as L5-S1 disc prolapse. Intra-operatively engorged dilated epidural vein seen compressing S1 nerve root. Associated Disc bulge removed and Coagulative ablation of the dilated epidural vein was performed Case 2: 45 year old male manual labourer presented with backache with left sided sciatica since 8 months, increased in severity since past 1month associated with sensory blunting in L5 and S1 dermatomes. Neurologic examination revealed normal muscle power in his lower extremities. Sensations was blunted in L5 and S1 dermatomes. MRI was reported as L5-S1 disc prolapsed compressing left S1 nerve root. Decompression of the L5–S1 intervertebral space was performed through a left –sidelaminotomy. Large, engorged serpentine epidural veins was found in the axilla of S1 nerve root, compressing it. Coagulative ablation of the dilated epidural vein was performed. Retrospectively, features of epidural varices were noted in the preoperative magnetic resonance imaging scans. Both patients had significant improvement in radiculopathy immediate postoperatively, and sensory symptoms resolved over the next 6 weeks in second case. At recent follow up, both patients had significant relief of symptoms and no recurrent radicular symptoms. Conclusion: An abnormal dilated epidural venous plexus that mimics a herniated lumbar disc is a rare entity. This pathology should be always kept

  15. Selenium-containing polymers: promising biomaterials for controlled release and enzyme mimics.

    PubMed

    Xu, Huaping; Cao, Wei; Zhang, Xi

    2013-07-16

    Although researchers have made great progress in the development of responsive polymeric materials for controlled drug release or diagnostics over the last 10 years, therapeutic results still lag behind expectations. The development of special materials that respond to physiological relevant concentrations, typically within the micromolar or nanomolar concentration regime, remains challenging. Therefore, researchers continue to pursue new biomaterials with unique properties and that respond to mild biochemical signals or biomarkers. Selenium is an essential element in human body with potential antioxidant properties. Because of selenium's electronegativity and atomic radius, selenium-containing compounds exhibit unique bond energy (C-Se bond 244 kJ mol⁻¹; Se-Se bond 172 kJ mol⁻¹). These values give the C-Se or Se-Se covalent bonds dynamic character and make them responsive to mild stimuli. Therefore, selenium-containing polymers can disassemble in response to changes under physiological relevant conditions. This property makes them a promising biomaterial for controlled release of drugs or synthetic enzyme mimics. Until recently, few researchers have looked at selenium-containing polymers as novel biomaterials. In this Account, we summarize our recent research on selenium-containing polymers and show their potential application as mild-responsive drug delivery vehicles and artificial enzymes. We begin by reviewing the current state of the art in the synthesis of selenium-containing main chain block copolymers. We highlight the dual redox and gamma-irradiation behaviors of diselenide-containing block copolymers assemblies, discussing the possibility of their use in a combination of chemotherapy and actinotherapy. We also describe the coordination of platinum with monoselenide containing block copolymers. Such structures offer the possibility of fabricating multidrug systems for cooperative chemotherapy. In addition, we summarize the methods for the covalent

  16. 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…

  17. 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.

  18. 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…

  19. Rapid hydrolytic cleavage of the mRNA model compound HPNP by glycine based macrocyclic lanthanide ribonuclease mimics.

    PubMed

    Gunnlaugsson, Thorfinnur; Davies, R Jeremy H; Nieuwenhuyzen, Mark; Stevenson, Clarke S; Viguier, Romain; Mulready, Sinead

    2002-09-21

    The lanthanide ion based macrocyclic complexes 1.Ln mimic the hydrophobic nature of ribonucleases, where the lanthanide ions induce the formation of a hydrophobic cavity for 1, giving rise to a large order of magnitude enhancement in the hydrolytic cleavage of HPNP.

  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. 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

  2. Designed ankyrin repeat proteins: a new approach to mimic complex antigens for diagnostic purposes?

    PubMed

    Hausammann, Stefanie; Vogel, Monique; Kremer Hovinga, Johanna A; Lacroix-Desmazes, Sebastien; Stadler, Beda M; Horn, Michael P

    2013-01-01

    Inhibitory antibodies directed against coagulation factor VIII (FVIII) can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins) mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures.

  3. 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.

  4. 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

  5. Coculture system that mimics in vivo attachment processes in bovine trophoblast cells.

    PubMed

    Sakurai, Toshihiro; Bai, Hanako; Bai, Rulan; Arai, Miki; Iwazawa, Makoto; Zhang, Jinfeng; Konno, Toshihiro; Godkin, James D; Okuda, Kiyoshi; Imakawa, Kazuhiko

    2012-09-01

    The establishment of pregnancy requires bidirectional communication between the developing conceptus and the uterine endometrium. The aim of this study was to establish an in vitro coculture system with bovine trophoblast cells and uterine epithelial cells (EECs) that mimics the in vivo attachment process. We previously reported that expression of interferon tau (IFNT), a major secretory product from the trophectoderm, decreases with changes in chromatin structure when the conceptus successfully attaches to the uterine epithelium. Thus, IFNT is a good marker to assess whether attachment has successfully occurred. In this study, bovine trophoblast CT-1 cells were cultured to generate spheroids, which were then placed on type I collagen-coated plates (monoculture) or bovine EECs (coculture) with or without uterine flushings collected from Day 15 cyclic or Days 15, 17, or 19 pregnant animals. In the coculture but not the monoculture, addition of uterine flushings from Day 15 or 17 pregnant animals resulted in decreased IFNT and CDX2 mRNA expression in CT-1 spheroids, accompanied with changes in histone modifications. In monocultured CT-1 spheroids, integrin subunit ITGA8 and ITGB3 mRNAs were minimally expressed but were induced in cocultured CT-1 spheroids with or without uterine flushings. Expression of CDH2, another marker for bovine conceptus attachment to the uterine epithelium, was also induced in the cocultured CT-1 spheroids. These results suggest that this in vitro coculture system could be used to isolate processes essential for conceptus attachment to uterine EECs.

  6. A de novo designed 2[4Fe-4S] ferredoxin mimic mediates electron transfer.

    PubMed

    Roy, Anindya; Sommer, Dayn Joseph; Schmitz, Robert Arthur; Brown, Chelsea Lynn; Gust, Devens; Astashkin, Andrei; Ghirlanda, Giovanna

    2014-12-10

    [Fe-S] clusters, nature's modular electron transfer units, are often arranged in chains that support long-range electron transfer. Despite considerable interest, the design of biomimetic artificial systems emulating multicluster-binding proteins, with the final goal of integrating them in man-made oxidoreductases, remains elusive. Here, we report a novel bis-[4Fe-4S] cluster binding protein, DSD-Fdm, in which the two clusters are positioned within a distance of 12 Å, compatible with the electronic coupling necessary for efficient electron transfer. The design exploits the structural repeat of coiled coils as well as the symmetry of the starting scaffold, a homodimeric helical protein (DSD). In total, eight hydrophobic residues in the core of DSD were replaced by eight cysteine residues that serve as ligands to the [4Fe-4S] clusters. Incorporation of two [4Fe-4S] clusters proceeds with high yield. The two [4Fe-4S] clusters are located in the hydrophobic core of the helical bundle as characterized by various biophysical techniques. The secondary structure of the apo and holo proteins is conserved; further, the incorporation of clusters results in stabilization of the protein with respect to chemical denaturation. Most importantly, this de novo designed protein can mimic the function of natural ferredoxins: we show here that reduced DSD-Fdm transfers electrons to cytochrome c, thus generating the reduced cyt c stoichiometrically.

  7. Investigating the oxidation of alkenes by non-heme iron enzyme mimics.

    PubMed

    Barry, Sarah M; Mueller-Bunz, Helge; Rutledge, Peter J

    2012-09-28

    Iron is emerging as a key player in the search for efficient and environmentally benign methods for the functionalisation of C-H bonds. Non-heme iron enzymes catalyse a diverse array of oxidative chemistry in nature, and small-molecule complexes designed to mimic the non-heme iron active site have great potential as C-H activation catalysts. Herein we report the synthesis of a series of organic ligands that incorporate key features of the non-heme iron active site. Iron(II) complexes of these ligands have been generated in situ and their ability to promote hydrocarbon oxidation has been investigated. Several of these systems promote the biomimetic dihydroxylation of cyclohexene at low levels, when hydrogen peroxide is used as the oxidant; allylic oxidation products are also observed. An investigation of ligand stability reveals formation of several breakdown products under the conditions of the oxidative turnover reactions. These products arise via oxidative decarboxylation, dehydration and deamination reactions. Taken together these results indicate that competing mechanisms are at play with these systems: biomimetic hydroxylation involving high-valent iron species, and allylic oxidation via Fenton chemistry and Haber-Weiss radical pathways.

  8. 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

  9. 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.

  10. Molecular basis of wing coloration in a Batesian mimic butterfly, Papilio polytes

    PubMed Central

    Nishikawa, Hideki; Iga, Masatoshi; Yamaguchi, Junichi; Saito, Kazuki; Kataoka, Hiroshi; Suzuki, Yutaka; Sugano, Sumio; Fujiwara, Haruhiko

    2013-01-01

    Batesian mimicry protects animals from predators through resemblance with distasteful models in shape, color pattern, or behavior. To elucidate the wing coloration mechanisms involved in the mimicry, we investigated chemical composition and gene expression of the pale yellow and red pigments of a swallowtail butterfly, Papilio polytes, whose females mimic the unpalatable butterfly Pachliopta aristolochiae. Using LC/MS, we showed that the pale yellow wing regions in non-mimetic females consist of kynurenine and N-β-alanyldopamine (NBAD). Moreover, qRT-PCR showed that kynurenine/NBAD biosynthetic genes were upregulated in these regions in non-mimetic females. However, these pigments were absent in mimetic females. RNA-sequencing showed that kynurenine/NBAD synthesis and Toll signaling genes were upregulated in the red spots specific to mimetic female wings. These results demonstrated that drastic changes in gene networks in the red and pale yellow regions can switch wing color patterns between non-mimetic and mimetic females of P. polytes. PMID:24212474

  11. Molecular basis of wing coloration in a Batesian mimic butterfly, Papilio polytes.

    PubMed

    Nishikawa, Hideki; Iga, Masatoshi; Yamaguchi, Junichi; Saito, Kazuki; Kataoka, Hiroshi; Suzuki, Yutaka; Sugano, Sumio; Fujiwara, Haruhiko

    2013-11-11

    Batesian mimicry protects animals from predators through resemblance with distasteful models in shape, color pattern, or behavior. To elucidate the wing coloration mechanisms involved in the mimicry, we investigated chemical composition and gene expression of the pale yellow and red pigments of a swallowtail butterfly, Papilio polytes, whose females mimic the unpalatable butterfly Pachliopta aristolochiae. Using LC/MS, we showed that the pale yellow wing regions in non-mimetic females consist of kynurenine and N-β-alanyldopamine (NBAD). Moreover, qRT-PCR showed that kynurenine/NBAD biosynthetic genes were upregulated in these regions in non-mimetic females. However, these pigments were absent in mimetic females. RNA-sequencing showed that kynurenine/NBAD synthesis and Toll signaling genes were upregulated in the red spots specific to mimetic female wings. These results demonstrated that drastic changes in gene networks in the red and pale yellow regions can switch wing color patterns between non-mimetic and mimetic females of P. polytes.

  12. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan

    PubMed Central

    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.

    2015-01-01

    Summary 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, four 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

  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

    2016-03-08

    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.

  14. Myometrial hyperplasia mimics the clinical presentation of uterine fibroids: a report of 3 cases.

    PubMed

    Newcomb, Patricia M; Cramer, Stewart F; Leppert, Phyllis C

    2013-11-01

    The clinical diagnosis of fibroid uterus is based on physical examination findings and/or ultrasound. However, it is not uncommon for routine pathology examination to report no significant fibroids in such cases. Myometrial hyperplasia (MMH) is a structural variation with irregular zones of hypercellularity and increased nucleus/cell ratio that appears in adolescence, can progress during the childbearing years, and can sometimes cause grossly detectable bulges on pathologic examination. MMH can be inframucosal, intramural (microscopic), or subserosal. Three premenopausal women with a preoperative diagnosis of fibroids on pelvic examination, and/or sonograms, underwent hysterectomies. In all the 3 cases, the Myoma Index (number of fibroids×size of largest fibroid) indicated insignificant fibroids. The pathology simulating fibroids was firm, bulging inframucosal MMH. Firm, bulging MMH can mimic uterine fibroids on ultrasound and physical examination. In hysterectomies for fibroid uterus with a Myoma Index <3.7, it is recommended that pathologists evaluate for MMH as the possible explanation for the findings on physical examination and/or ultrasound.

  15. Design, synthesis, and biological evaluation of conformationally constrained aci-reductone mimics of arachidonic acid.

    PubMed

    Hopper, A T; Witiak, D T; Ziemniak, J

    1998-02-12

    An efficient and convergent synthesis has been developed for the production of 3,4-dihydroxy-5-[4-(2-((2Z)-hexenyl)phenyl)-3-(1Z)-but enyl]-2 (5H)-furanone (12d). This hydrophobic antioxidant is a stable conformationally constrained mimic of arachidonic acid (AA) (1) and its respective aci-reductone analogue (2). Pd(0)-catalyzed cross-coupling of 5-(3-butynyl)-3,4-dihydroxy-2(5H)-furanone (7) with 2-((2Z)-hexenyl)iodobenzene (8d) followed by Lindlar catalyzed hydrogenation produces 12d. Butynyl intermediate 7 is prepared from 2-(benzyloxy)-5-deoxyascorbic acid (15) by iodination (I2, PPh3, Imd), iodo substitution with lithium acetylide ethylenediamine complex (LiAEDA, HMPA, -5 degrees C), and benzyl group cleavage (Ac2O, Pyr, BCl3). The utility of this synthetic method was demonstrated by the synthesis of analogues 10e-k. Biological testing revealed that certain of these antioxidants inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) with comparable efficacy as reported for aspirin and zileuton, respectively. The antioxidant activity of these aci-reductones, measured as a function of their inhibitory effect on CCl4-induced lipid peroxidation of hepatic microsomes, exceeds that produced by alpha-tocopherol. Synthetic routes and initial structure-activity relationships (SAR) for these novel mixed functioning antioxidants are presented.

  16. 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.

  17. Determination of residual manganese in Mn porphyrin-based superoxide dismutase (SOD) and peroxynitrite reductase mimics

    PubMed Central

    Rebouças, Júlio S.; Kos, Ivan; Batinić-Haberle, Ines

    2009-01-01

    The awareness of the beneficial effects of Mn porphyrin-based superoxide dismutase (SOD) mimics and peroxynitrite scavengers on decreasing oxidative stress injuries has increased the use of these compounds as mechanistic probes and potential therapeutics. Simple Mn2+ salts, however, have SOD-like activity in their own right both in vitro and in vivo. Thus, quantification/removal of residual Mn2+ species in Mn-based therapeutics is critical to an unambiguous interpretation of biological data. Herein we report a simple, sensitive, and specific method to determine residual Mn2+ in Mn-porphyrin preparations that combines a hydrometallurgical approach for separation/speciation of metal compounds with a spectrophotometric strategy for Mn determination. The method requires only common chemicals and a spectrophotometer and is based on the extraction of residual Mn2+ by bis(2-ethylhexyl)hydrogenphosphate (D2EHPA) into kerosene, re-extraction into acid, and neutralization followed by UV-vis determination of the Mn2+ levels via a Cd2+-catalyzed metallation of the H2TCPP4− porphyrin indicator. The overall procedure is simple, sensitive, specific, and amenable to adaptation. This quantification method has been routinely used by us for a large variety of water-soluble porphyrins. PMID:19660888

  18. The use of inexact hardware to mimic subgrid-scale variability

    NASA Astrophysics Data System (ADS)

    Düben, Peter D.; Palmer, Tim

    2014-05-01

    We study the use of inexact hardware in numerical weather and climate models. The different setups of inexact hardware promise large savings in power consumption and an increase in computational performance. However, simulations with inexact hardware show numerical errors, such as rounding errors or bit flips. The effect of these errors can be described as an additional forcing term which is added to the governing differential equations. Since hardware errors are hardly correlated in space and time, the forcing term due to inexact hardware has some similarities to a stochastic forcing. Stochastic forcings, however, are used successfully in stochastic parametrisation schemes to mimic subgrid-scale variability within a numerical model and are motivated by physical reasons. We investigate a model of the 1D Burgers equation that is using the stochastic parametrisation scheme of Dolaptchiev et al. based on the MTV stochastic mode reduction strategy. We emulate the use of inexact hardware within the model. The forcing of the stochastic parametrisation scheme is compared to the forcing caused by hardware errors. We show that the forcing of inexact hardware can replace the stochastic forcing of the stochastic parametrisation scheme and lead to a similar quality of solutions, when only small changes are made within the numerical code. We conclude that numerical errors of inexact hardware can be beneficial for physical reasons, at least in idealised setups, while inexact hardware will provide significant savings in computational cost. We will also present results on the use of inexact hardware to setup ensemble simulations.

  19. 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.

  20. Nematophagous fungus Arthrobotrys oligospora mimics olfactory cues of sex and food to lure its nematode prey

    PubMed Central

    Hsueh, Yen-Ping; Gronquist, Matthew R; Schwarz, Erich M; Nath, Ravi David; Lee, Ching-Han; Gharib, Shalha; Schroeder, Frank C; Sternberg, Paul W

    2017-01-01

    To study the molecular basis for predator-prey coevolution, we investigated how Caenorhabditis elegans responds to the predatory fungus Arthrobotrys oligospora. C. elegans and other nematodes were attracted to volatile compounds produced by A. oligospora. Gas-chromatographic mass-spectral analyses of A. oligospora-derived volatile metabolites identified several odors mimicking food cues attractive to nematodes. One compound, methyl 3-methyl-2-butenoate (MMB) additionally triggered strong sex- and stage-specific attraction in several Caenorhabditis species. Furthermore, when MMB is present, it interferes with nematode mating, suggesting that MMB might mimic sex pheromone in Caenorhabditis species. Forward genetic screening suggests that multiple receptors are involved in sensing MMB. Response to fungal odors involves the olfactory neuron AWCs. Single-cell RNA-seq revealed the GPCRs expressed in AWC. We propose that A. oligospora likely evolved the means to use olfactory mimicry to attract its nematode prey through the olfactory neurons in C. elegans and related species. DOI: http://dx.doi.org/10.7554/eLife.20023.001 PMID:28098555

  1. Polymeric enzyme mimics: catalytic activity of ribose-containing polymers for a phosphate substrate.

    PubMed

    Han, Man Jung; Yoo, Kyung Soo; Kim, Young Heui; Chang, Ji Young

    2003-07-07

    The polymers containing ribose rings: poly(5'-acrylamido-5'-deoxy-1',2'-O-isopropylidene-alpha-D-ribose) (11), poly(5'-acrylamido-5'-deoxy-alpha-D-ribose) (12) and poly(5'-acrylamido-5'-deoxy-1'-O-methyl-D-ribose) (13) were prepared as enzyme mimics. Polymers 12 and 13 with free vic-cis-diol groups catalyzed the hydrolysis of phosphodiester (ethyl p-nitrophenyl phosphate and N-methylpyridinium 4-tert-butylcatechol cyclic phosphate) and phosphomonoester substrates with a rate acceleration of 10 approximately equal to 10(3) compared with the uncatalyzed reaction. They also catalyzed the reverse reactions, i.e., the esterification of phosphomonoester to phosphodiester and the phosphorylation of alcohols with phosphate ions. The catalytic activity was attributable to the vic-cis-diols of riboses on polymer chains, which formed hydrogen bonds with two phosphoryl oxygen atoms of phosphates so as to activate the phosphorus atoms to be attacked by nucleophiles. The catalytic activity was negligible for polymer 11 where vic-cis-diol groups were blocked with isopropylidene groups. The catalytic activity was attributable to the vic-cis-diols of riboses on polymer chains, which formed hydrogen bonds with two phosphoryl oxygen atoms of phosphates so as to activate the phosphorus atoms to be attacked by nucleophiles.

  2. 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.

  3. 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.

  4. Design criteria for molecular mimics of fragments of the β-turn. 1. Cα atom analysis

    NASA Astrophysics Data System (ADS)

    Garland, S. L.; Dean, P. M.

    1999-09-01

    Peptides represent an extensive class of biologically active molecules. They may be used as leads in the development of novel therapeutic agents provided the pharmacophoric information present within them can be translated into non-peptide analogs that lack the peptide backbone and are stable to proteolysis. This is the rationale for peptidomimetic drug design. Frequently, the β-turn has been implicated as a conformation important for biological recognition of peptides. Empirical evidence from known peptidomimetics, coupled with a theoretical model of peptide binding and the observation that glycine and proline residues are common within the β-turn, has suggested the design of molecules to mimic placement of between two and four of the side-chains. The moderate number of different β-turn conformations, combined with the combinatoric nature of side-chain selection complicates the procedure. In this paper, cluster analysis has been used to classify the arrangement of C_α atoms about the various fragments of the β-turn. Recombination of the observed patterns provides a general model for the β-turn which may be used as an effective screen for potential peptidomimetic scaffolds in chemical databases.

  5. The tyrosine phosphatase inhibitor orthovanadate mimics NGF-induced neuroprotective signaling in rat hippocampal neurons.

    PubMed

    Gerling, Norbert; Culmsee, Carsten; Klumpp, Susanne; Krieglstein, Josef

    2004-06-01

    Activation of the high affinity neurotrophin receptor tropomyosin-related kinase A (TrkA) by nerve growth factor (NGF) leads to phosphorylation of intracellular tyrosine residues of the receptor with subsequent activation of signaling pathways involved in neuronal survival such as the phosphoinositide-3-kinase (PI3-K)/protein kinase B (PKB/Akt) pathway and the mitogen-activated protein kinase (MAPK) cascade. In the present study, we tested whether inhibition of protein-tyrosine phosphatases (PTP) by orthovanadate could enhance tyrosine phosphorylation of TrkA thereby stimulating NGF-like survival signaling in embryonic hippocampal neurons. We found that the PTP inhibitor orthovanadate (1 microM) enhanced TrkA phosphorylation and protected neurons against staurosporine (STS)-induced apoptosis in a time-and concentration-dependent manner. Inhibition of PTP enhanced TrkA phosphorylation also in the presence of NGF antibodies indicating that NGF binding to TrkA was not required for the effects of orthovanadate. Moreover, orthovanadate enhanced phosphorylation of Akt and the MAPK Erk1/2 suggesting that the signaling pathways involved in the protective effect were similar to those activated by NGF. Accordingly, inhibition of PI3-K by wortmannin and MAPK-kinase (MEK) inhibition by UO126 abolished the neuroprotective effects. In conclusion, the results indicate that orthovanadate mimics the effect of NGF on survival signaling pathways in hippocampal neurons. Thus, PTP inhibition appears to be an appropriate strategy to trigger neuroprotective signaling pathways downstream of neurotrophin receptors.

  6. 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.

  7. 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.

  8. Fabrication of a modular hybrid chip to mimic endothelial-lined microvessels in flow conditions

    NASA Astrophysics Data System (ADS)

    Pitingolo, Gabriele; Vecchione, Raffaele; Falanga, Andrea P.; Guarnieri, Daniela; Netti, Paolo A.

    2017-03-01

    In vitro microvessel models exploiting microfluidic channels have been developed to replicate cardiovascular flow conditions and to more closely mimic the blood vessels by traditionally using plasma or solvent evaporation bonding methods. The drawback of these methods is represented by an irreversible sealing which prevents internal accessibility as well as the reuse of the device. This paper presents a novel, simple, and low cost procedure to fabricate a modular and reusable chip with endotheliazed microvessels in a hybrid configuration based on poly(methyl methacrylate) and polydimethylsiloxane presenting a temporary magnetic bonding. In details, small magnets are embedded in the two poly(methyl methacrylate) substrates each of them carrying a thin polydimethylsiloxane layer which provides enhanced sealing during flow conditions as compared to conventional procedures and makes the microchannels circular as preferred in cell culture. Finally, an endothelial cell layer is formed by culturing brain endothelial bEnd.3 cells inside the proposed microchannels and characterized upon microchannel aperture, demonstrating the preservation of the cell layer.

  9. Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor.

    PubMed Central

    Doudna, J A; Cech, T R; Sullenger, B A

    1995-01-01

    Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identification of an RNA sequence that binds a mouse monoclonal antibody specific for an autoantigenic epitope of human insulin receptor. The RNA ligand binds specifically and with high affinity (apparent Kd congruent to 2 nM) to the anti-insulin receptor antibody and not to other mouse IgGs. The RNA can also act as a decoy, blocking the antibody from binding the insulin receptor. Thus, it probably binds near the combining site on the antibody. Strikingly, the RNA cross-reacts with autoantibodies from patients with extreme insulin resistance. One simple explanation is that the selected RNA may structurally mimic the antigenic epitope on the insulin receptor protein. These results suggest that decoy RNAs may be used in the treatment of autoimmune diseases. Images Fig. 1 Fig. 4 Fig. 5 PMID:7534420

  10. Molecular recognition of oxygen by protein mimics: dynamics on the femtosecond to microsecond time scale.

    PubMed

    Zou, Shouzhong; Baskin, J Spencer; Zewail, Ahmed H

    2002-07-23

    Molecular recognition by biological macromolecules involves many elementary steps, usually convoluted by diffusion processes. Here we report studies of the dynamics, from the femtosecond to the microsecond time scale, of the different elementary processes involved in the bimolecular recognition of a protein mimic, cobalt picket-fence porphyrin, with varying oxygen concentration at controlled temperatures. Electron transfer, bond breakage, and thermal "on" (recombination) and "off" (dissociation) reactions are the different processes involved. The reaction on-rate is 30 to 60 times smaller than that calculated from standard Smoluchowski theory. Introducing a two-step recognition model, with reversibility being part of both steps, removes the discrepancy and provides consistency for the reported thermodynamics, kinetics, and dynamics. The transient intermediates are configurations defined by the contact between oxygen (diatomic) and the picket-fence porphyrin (macromolecule). This intermediate is critical in the description of the potential energy landscape but, as shown here, both enthalpic and entropic contributions to the free energy are important. In the recognition process, the net entropy decrease is -33 cal mol(-1) K(-1); Delta H is -13.4 kcal mol(-1).

  11. 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.

  12. 3-Phosphono-L-alanine as pyrophosphate mimic for DNA synthesis using HIV-1 reverse transcriptase.

    PubMed

    Yang, Shiqiong; Froeyen, Mathy; Lescrinier, Eveline; Marlière, Philippe; Herdewijn, Piet

    2011-01-07

    A series of sulf(on)ate and phosph(on)ate amino acid phosphoramidate analogues of deoxynucleotides were synthesized as potential substrates for HIV-1 reverse transcriptase. Taurine, L-cysteic acid, 3-phosphono-L-alanine, O-sulfonato-L-serine, and O-phospho-L-serine were investigated as leaving groups in an enzyme catalyzed DNA synthesis protocol. Among these analogues, the phosphonate congener performed best and 3-phosphono-L-alanine can be considered as an excellent mimic of the pyrophosphate (PPi) moiety of deoxyadenosine triphosphate, to be used in enzymatic synthesis of nucleic acids. During a single nucleotide incorporation assay the use of 3-phosphono-L-Ala-dAMP as substrate resulted in 95% conversion to a P + 1 strand in 60 min at 50 μM (a concentration 10 times less than found for L-Asp-dAMP) and with improved incorporation kinetics and less stalling. For the sequences investigated, the efficiency of the incorporation is base dependent and decreases in the order (A ≥ T = G > C). In all cases, the incorporation follows Watson-Crick rules.

  13. Do placebo based validation standards mimic real batch products behaviour? Case studies.

    PubMed

    Bouabidi, A; Talbi, M; Bouklouze, A; El Karbane, M; Bourichi, H; El Guezzar, M; Ziemons, E; Hubert, Ph; Rozet, E

    2011-06-01

    Analytical methods validation is a mandatory step to evaluate the ability of developed methods to provide accurate results for their routine application. Validation usually involves validation standards or quality control samples that are prepared in placebo or reconstituted matrix made of a mixture of all the ingredients composing the drug product except the active substance or the analyte under investigation. However, one of the main concerns that can be made with this approach is that it may lack an important source of variability that come from the manufacturing process. The question that remains at the end of the validation step is about the transferability of the quantitative performance from validation standards to real authentic drug product samples. In this work, this topic is investigated through three case studies. Three analytical methods were validated using the commonly spiked placebo validation standards at several concentration levels as well as using samples coming from authentic batch samples (tablets and syrups). The results showed that, depending on the type of response function used as calibration curve, there were various degrees of differences in the results accuracy obtained with the two types of samples. Nonetheless the use of spiked placebo validation standards was showed to mimic relatively well the quantitative behaviour of the analytical methods with authentic batch samples. Adding these authentic batch samples into the validation design may help the analyst to select and confirm the most fit for purpose calibration curve and thus increase the accuracy and reliability of the results generated by the method in routine application.

  14. 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

    2015-07-07

    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.

  15. Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice

    PubMed Central

    Tai, Ningwen; Peng, Jian; Liu, Fuqiang; Hu, Youjia; Zhang, Xiaojun; Chen, Li

    2016-01-01

    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

  16. To die or not to die? Lessons from lesion mimic mutants

    PubMed Central

    Bruggeman, Quentin; Raynaud, Cécile; Benhamed, Moussa; Delarue, Marianne

    2015-01-01

    Programmed cell death (PCD) is a ubiquitous genetically regulated process consisting in an activation of finely controlled signaling pathways that lead to cellular suicide. Although some aspects of PCD control appear evolutionary conserved between plants, animals and fungi, the extent of conservation remains controversial. Over the last decades, identification and characterization of several lesion mimic mutants (LMM) has been a powerful tool in the quest to unravel PCD pathways in plants. Thanks to progress in molecular genetics, mutations causing the phenotype of a large number of LMM and their related suppressors were mapped, and the identification of the mutated genes shed light on major pathways in the onset of plant PCD such as (i) the involvements of chloroplasts and light energy, (ii) the roles of sphingolipids and fatty acids, (iii) a signal perception at the plasma membrane that requires efficient membrane trafficking, (iv) secondary messengers such as ion fluxes and ROS and (v) the control of gene expression as the last integrator of the signaling pathways. PMID:25688254

  17. 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.

  18. Dosimetric evaluation of a Monte Carlo IMRT treatment planning system incorporating the MIMiC

    NASA Astrophysics Data System (ADS)

    Rassiah-Szegedi, P.; Fuss, M.; Sheikh-Bagheri, D.; Szegedi, M.; Stathakis, S.; Lancaster, J.; Papanikolaou, N.; Salter, B.

    2007-12-01

    The high dose per fraction delivered to lung lesions in stereotactic body radiation therapy (SBRT) demands high dose calculation and delivery accuracy. The inhomogeneous density in the thoracic region along with the small fields used typically in intensity-modulated radiation therapy (IMRT) treatments poses a challenge in the accuracy of dose calculation. In this study we dosimetrically evaluated a pre-release version of a Monte Carlo planning system (PEREGRINE 1.6b, NOMOS Corp., Cranberry Township, PA), which incorporates the modeling of serial tomotherapy IMRT treatments with the binary multileaf intensity modulating collimator (MIMiC). The aim of this study is to show the validation process of PEREGRINE 1.6b since it was used as a benchmark to investigate the accuracy of doses calculated by a finite size pencil beam (FSPB) algorithm for lung lesions treated on the SBRT dose regime via serial tomotherapy in our previous study. Doses calculated by PEREGRINE were compared against measurements in homogeneous and inhomogeneous materials carried out on a Varian 600C with a 6 MV photon beam. Phantom studies simulating various sized lesions were also carried out to explain some of the large dose discrepancies seen in the dose calculations with small lesions. Doses calculated by PEREGRINE agreed to within 2% in water and up to 3% for measurements in an inhomogeneous phantom containing lung, bone and unit density tissue.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly.

    PubMed

    Sampath, Srihari C; Marazzi, Ivan; Yap, Kyoko L; Sampath, Srinath C; Krutchinsky, Andrew N; Mecklenbräuker, Ingrid; Viale, Agnes; Rudensky, Eugene; Zhou, Ming-Ming; Chait, Brian T; Tarakhovsky, Alexander

    2007-08-17

    Epigenetic gene silencing in eukaryotes is regulated in part by lysine methylation of the core histone proteins. While histone lysine methylation is known to control gene expression through the recruitment of modification-specific effector proteins, it remains unknown whether nonhistone chromatin proteins are targets for similar modification-recognition systems. Here we show that the histone H3 methyltransferase G9a contains a conserved methylation motif with marked sequence similarity to H3 itself. As with methylation of H3 lysine 9, autocatalytic G9a methylation is necessary and sufficient to mediate in vivo interaction with the epigenetic regulator heterochromatin protein 1 (HP1), and this methyl-dependent interaction can be reversed by adjacent G9a phosphorylation. NMR analysis indicates that the HP1 chromodomain recognizes methyl-G9a through a binding mode similar to that used in recognition of methyl-H3K9, demonstrating that the chromodomain functions as a generalized methyl-lysine binding module. These data reveal histone-like modification cassettes - or "histone mimics" - as a distinct class of nonhistone methylation targets and directly extend the principles of the histone code to the regulation of nonhistone proteins.

  5. Integrating microbial physiology and physio-chemical 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.

    2014-07-01

    A growing body of literature documents the pressing need to develop soil biogeochemistry models that more accurately reflect contemporary understanding of soil processes and better capture soil carbon (C) responses to environmental perturbations. Models that explicitly represent microbial activity offer inroads to improve representations of soil biogeochemical processes, but have yet to consider 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, and evaluate it by comparing site-level soil C projections with observations from a long-term litter decomposition study and soil warming experiment. In MIMICS, the turnover of litter and SOM pools is 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 temperate and boreal forest sites, and captures observed effects of litter quality on decomposition rates. Moreover, MIMICS better captures the response of SOM pools to experimental warming, with rapid SOM losses but declining temperature sensitivity to long-term warming, compared with a more conventional model structure. MIMICS incorporates current microbial theory to explore the mechanisms by which litter C is converted to stable SOM, and to improve predictions of soil C responses to environmental change.

  6. Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.

    PubMed

    Ribeiro, Thales de P; Fonseca, Fernanda L; de Carvalho, Mariana D C; Godinho, Rodrigo M da C; de Almeida, Fernando Pereira; Saint'Pierre, Tatiana D; Rey, Nicolás A; Fernandes, Christiane; Horn, Adolfo; Pereira, Marcos D

    2017-01-15

    Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl2]NO3, [Cu(HPClNOL)(CH3CN)](ClO4)2 and Mn(HPClNOL)(Cl)2}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.

  7. Three-dimensional microfiber devices that mimic physiological environments to probe cell mechanics and signaling.

    PubMed

    Ruder, Warren C; Pratt, Erica D; Bakhru, Sasha; Sitti, Metin; Zappe, Stefan; Cheng, Chao-Min; Antaki, James F; LeDuc, Philip R

    2012-04-24

    Many physiological systems are regulated by cells that alter their behavior in response to changes in their biochemical and mechanical environment. These cells experience this dynamic environment through an endogenous biomaterial matrix that transmits mechanical force and permits chemical exchange with the surrounding tissue. As a result, in vitro systems that mimic three-dimensional, in vivo cellular environments can enable experiments that reveal the nuanced interplay between biomechanics and physiology. Here we report the development of a minimal-profile, three-dimensional (MP3D) experimental microdevice that confines cells to a single focal plane, while allowing the precise application of mechanical displacement to cells and concomitant access to the cell membrane for perfusion with biochemical agonists. The MP3D device--an ordered microfiber scaffold erected on glass--provides a cellular environment that induces physiological cell morphologies. Small manipulations of the scaffold's microfibers allow attached cells to be mechanically probed. Due to the scaffold's minimal height profile, MP3D devices confine cells to a single focal plane, facilitating observation with conventional epifluorescent microscopy. When examining fibroblasts within MP3D devices, we observed robust cellular calcium responses to both a chemical stimulus as well as mechanical displacement of the cell membrane. The observed response differed significantly from previously reported, mechanically-induced calcium responses in the same cell type. Our findings demonstrate a key link between environment, cell morphology, mechanics, and intracellular signal transduction. We anticipate that this device will broadly impact research in fields including biomaterials, tissue engineering, and biophysics.

  8. Sulfinylated azadecalins act as functional mimics of a pollen germination stimulant in Arabidopsis pistils.

    PubMed

    Qin, Yuan; Wysocki, Ronald J; Somogyi, Arpad; Feinstein, Yelena; Franco, Jessica Y; Tsukamoto, Tatsuya; Dunatunga, Damayanthi; Levy, Clara; Smith, Steven; Simpson, Robert; Gang, David; Johnson, Mark A; Palanivelu, Ravishankar

    2011-12-01

    Polarized cell elongation is triggered by small molecule cues during development of diverse organisms. During plant reproduction, pollen interactions with the stigma result in the polar outgrowth of a pollen tube, which delivers sperm cells to the female gametophyte to effect double fertilization. In many plants, pistils stimulate pollen germination. However, in Arabidopsis, the effect of pistils on pollen germination and the pistil factors that stimulate pollen germination remain poorly characterized. Here, we demonstrate that stigma, style, and ovules in Arabidopsis pistils stimulate pollen germination. We isolated an Arabidopsis pistil extract fraction that stimulates Arabidopsis pollen germination, and employed ultra-high resolution electrospray ionization (ESI), Fourier-transform ion cyclotron resonance (FT-ICR) and MS/MS techniques to accurately determine the mass (202.126 Da) of a compound that is specifically present in this pistil extract fraction. Using the molecular formula (C10H19NOS) and tandem mass spectral fragmentation patterns of the m/z (mass to charge ratio) 202.126 ion, we postulated chemical structures, devised protocols, synthesized N-methanesulfinyl 1- and 2-azadecalins that are close structural mimics of the m/z 202.126 ion, and showed that they are sufficient to stimulate Arabidopsis pollen germination in vitro (30 μm stimulated approximately 50% germination) and elicit accession-specific response. Although N-methanesulfinyl 2-azadecalin stimulated pollen germination in three species of Lineage I of Brassicaceae, it did not induce a germination response in Sisymbrium irio (Lineage II of Brassicaceae) and tobacco, indicating that activity of the compound is not random. Our results show that Arabidopsis pistils promote germination by producing azadecalin-like molecules to ensure rapid fertilization by the appropriate pollen.

  9. Earwigs ( Labidura riparia) mimic rotting-flesh odor to deceive vertebrate predators

    NASA Astrophysics Data System (ADS)

    Byers, John A.

    2015-08-01

    Many insects repel predators with caustic chemicals, while insects mimicking odors of wastes/dead insects to fool predators have not been documented. We found that the shore earwig, Labidura riparia (Dermaptera: Labiduridae) when bitten by anole lizards, Anolis carolinenesus, spits a rotting-flesh odor that deceives these insectivores into rejecting prey. Once a lizard attacked and rejected an earwig, the lizard did not attack another earwig during several weeks despite consuming other prey, indicating associative learning after one trial. The fetid odor was found in the head-prothorax containing salivary glands of both male and female earwigs and was comprised of ˜100 ng dimethyl disulfide and ˜600 ng dimethyl trisulfide. Nymphs had <5 ng of either compound. Adults also spit odorous sulfides after prolonged attacks by harvester ants, Pogonomyrmex rugosus, who were only deterred by the earwig's forceps. Sulfides released by the earwig are similar to odors of carrion/feces, which may be innately repulsive to some vertebrate predators. The mean initial discharge percentage (IDP) of sulfides from a cohort of earwigs was 62 %; however, IDPs of individuals were highly variable (3-99 %; mean 57 %). The discharge refill time (DRT) to refill 50 % of the earwig's allomone reservoir was estimated at 13 h. A positive relationship in sulfide amounts with body weight was found only in females in 2009, suggesting metabolic cost tradeoffs were revealed when sulfide content was half that in 2010. This is the first report of insects releasing sulfur-containing compounds that may mimic carrion-fecal odors as a deceptive defense against vertebrate predators.

  10. Estrone 3-sulfate mimics, inhibitors of estrone sulfatase activity: homology model construction and docking studies.

    PubMed

    Howarth, Nicola M; Purohit, Atul; Robinson, James J; Vicker, Nigel; Reed, Michael J; Potter, Barry V L

    2002-12-17

    Steroid sulfatase (STS) is a new target for the endocrine therapy of breast cancer. To ascertain some of the requirements for inhibition of estrone sulfatase activity, a number of novel analogues of estrone 3-O-sulfate possessing sulfate surrogates were synthesized and evaluated as inhibitors of estrone sulfatase (STS) in comparison to a lead inhibitor, estrone-3-O-methylthiophosphonate (E1-3-MTP). Using a selective enzyme digestion, one of the diastereoisomers of this compound, (R(p))-E1-3-MTP, could be prepared and evaluated. From structure-activity studies, we show that chirality at the phosphorus atom, hydrophobicity, basicity, size, and charge all influence the ability of a compound to inhibit estrone sulfatase activity. Of these, hydrophobicity seems to be the most important since simple, active nonsteroidal inhibitors, based on 5,6,7,8-tetrahydronaphth-2-ol (THN), can be prepared, provided that they are lipophilic enough to partition into a nonpolar environment. Also, a negatively charged group is favorable for optimal binding, although it appears that the presence of a potentially cleavable group can compensate for lack of charge in certain cases. A homology model of STS has been constructed from the STS sequence, and molecular docking studies of inhibitors have been performed to broaden the understanding of enzyme/inhibitor interactions. This model clearly shows the positions of the key amino acid residues His136, His290, Lys134, and Lys368 in the putative catalytic region of the formylglycine at position 75, with residues Asp35, Asp36, Asp342, and Gln343 as ligands in the coordination sphere of the magnesium ion. Docking studies using the substrate and estrone-3-sulfate mimics that are active inhibitors indicate they are positioned in the area of proposed catalysis, confirming the predictive power of the model.

  11. Ceropegia sandersonii Mimics Attacked Honeybees to Attract Kleptoparasitic Flies for Pollination.

    PubMed

    Heiduk, Annemarie; Brake, Irina; von Tschirnhaus, Michael; Göhl, Matthias; Jürgens, Andreas; Johnson, Steven D; Meve, Ulrich; Dötterl, Stefan

    2016-10-24

    Four to six percent of plants, distributed over different angiosperm families, entice pollinators by deception [1]. In these systems, chemical mimicry is often used as an efficient way to exploit the olfactory preferences of animals for the purpose of attracting them as pollinators [2,3]. Here, we report a very specific type of chemical mimicry of a food source. Ceropegia sandersonii (Apocynaceae), a deceptive South African plant with pitfall flowers, mimics attacked honeybees. We identified kleptoparasitic Desmometopa flies (Milichiidae) as the main pollinators of C. sandersonii. These flies are well known to feed on honeybees that are eaten by spiders, which we thus predicted as the model chemically mimicked by the plant. Indeed, we found that the floral scent of C. sandersonii is comparable to volatiles released from honeybees when under simulated attack. Moreover, many of these shared compounds elicited physiological responses in antennae of pollinating Desmometopa flies. A mixture of four compounds-geraniol, 2-heptanone, 2-nonanol, and (E)-2-octen-1-yl acetate-was highly attractive to the flies. We conclude that C. sandersonii is specialized on kleptoparasitic fly pollinators by deploying volatiles linked to the flies' food source, i.e., attacked and/or freshly killed honeybees. The blend of compounds emitted by C. sandersonii is unusual among flowering plants and lures kleptoparasitic flies into the trap flowers. This study describes a new example of how a plant can achieve pollination through chemical mimicry of the food sources of adult carnivorous animals.

  12. When homoplasy mimics hybridization: a case study of Cape hakes (Merluccius capensis and M. paradoxus)

    PubMed Central

    von der Heyden, Sophie; Matthee, Conrad A.

    2016-01-01

    In the marine environment, an increasing number of studies have documented introgression and hybridization using genetic markers. Hybridization appears to occur preferentially between sister-species, with the probability of introgression decreasing with an increase in evolutionary divergence. Exceptions to this pattern were reported for the Cape hakes (Merluccius capensis and M. paradoxus), two distantly related Merluciidae species that diverged 3–4.2 million years ago. Yet, it is expected that contemporary hybridization between such divergent species would result in reduced hybrid fitness. We analysed 1,137 hake individuals using nine microsatellite markers and control region mtDNA data to assess the validity of the described hybridization event. To distinguish between interbreeding, ancestral polymorphism and homplasy we sequenced the flanking region of the most divergent microsatellite marker. Simulation and empirical analyses showed that hybrid identification significantly varied with the number of markers, model and approach used. Phylogenetic analyses based on the sequences of the flanking region of Mmerhk-3b, combined with the absence of mito-nuclear discordance, suggest that previously reported hybridization between M. paradoxus and M. capensis cannot be substantiated. Our findings highlight the need to conduct a priori simulation studies to establish the suitability of a particular set of microsatellite loci for detecting multiple hybridization events. In our example, the identification of hybrids was severely influenced by the number of loci and their variability, as well as the different models employed. More importantly, we provide quantifiable evidence showing that homoplasy mimics the effects of heterospecific crossings which can lead to the incorrect identification of hybridization. PMID:27069785

  13. Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics.

    PubMed

    Pinto, Andre; Nosé, Vania; Rojas, Claudia; Fan, Yao-Shan; Gomez-Fernandez, Carmen

    2014-01-01

    Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly

  14. Cirrus cloud mimic surfaces in the laboratory: organic acids, bases and NOx heterogeneous reactions

    NASA Astrophysics Data System (ADS)

    Sodeau, J.; Oriordan, B.

    2003-04-01

    CIRRUS CLOUD MIMIC SURFACES IN THE LABORATORY:ORGANIC ACIDS, BASES AND NOX HETEROGENEOUS REACTIONS. B. ORiordan, J. Sodeau Department of Chemistry and Environment Research Institute, University College Cork, Ireland j.sodeau@ucc.ie /Fax: +353-21-4902680 There are a variety of biogenic and anthropogenic sources for the simple carboxylic acids to be found in the troposphere giving rise to levels as high as 45 ppb in certain urban areas. In this regard it is of note that ants of genus Formica produce some 10Tg of formic acid each year; some ten times that produced by industry. The expected sinks are those generally associated with tropospheric chemistry: the major routes studied, to date, being wet and dry deposition. No studies have been carried out hitherto on the role of water-ice surfaces in the atmospheric chemistry of carboxylic acids and the purpose of this paper is to indicate their potential function in the heterogeneous release of atmospheric species such as HONO. The deposition of formic acid on a water-ice surface was studied using FT-RAIR spectroscopy over a range of temperatures between 100 and 165K. In all cases ionization to the formate (and oxonium) ions was observed. The results were confirmed by TPD (Temperature Programmed Desorption) measurements, which indicated that two distinct surface species adsorb to the ice. Potential reactions between the formic acid/formate ion surface and nitrogen dioxide were subsequently investigated by FT-RAIRS. Co-deposition experiments showed that N2O3 and the NO+ ion (associated with water) were formed as products. A mechanism is proposed to explain these results, which involves direct reaction between the organic acid and nitrogen dioxide. Similar experiments involving acetic acid also indicate ionization on a water-ice surface. The results are put into the context of atmospheric chemistry potentially occuring on cirrus cloud surfaces.

  15. Conformational Melding Permits a Conserved Binding Geometry in TCR Recognition of Foreign and Self Molecular Mimics

    SciTech Connect

    Borbulevych, Oleg Y.; Piepenbrink, Kurt H.; Baker, Brian M.

    2012-03-16

    Molecular mimicry between foreign and self Ags is a mechanism of TCR cross-reactivity and is thought to contribute to the development of autoimmunity. The {alpha}{beta} TCR A6 recognizes the foreign Ag Tax from the human T cell leukemia virus-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found in our study that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics and that in contrast with other recent structures of TCRs with self Ags, A6 engages the HuD Ag with the same traditional binding mode used to engage Tax. Although peptide and MHC conformational changes are needed for recognition of HuD but not Tax and the difference of a single hydroxyl triggers an altered TCR loop conformation, TCR affinity toward HuD is still within the range believed to result in negative selection. Probing further, we found that the HuD-HLA-A2 complex is only weakly stable. Overall, these findings help clarify how molecular mimicry can drive self/nonself cross-reactivity and illustrate how low peptide-MHC stability can permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditional binding mode.

  16. AICAR stimulation metabolome widely mimics electrical contraction in isolated rat epitrochlearis muscle.

    PubMed

    Miyamoto, Licht; Egawa, Tatsuro; Oshima, Rieko; Kurogi, Eriko; Tomida, Yosuke; Tsuchiya, Koichiro; Hayashi, Tatsuya

    2013-12-15

    Physical exercise has potent therapeutic and preventive effects against metabolic disorders. A number of studies have suggested that 5'-AMP-activated protein kinase (AMPK) plays a pivotal role in regulating carbohydrate and lipid metabolism in contracting skeletal muscles, while several genetically manipulated animal models revealed the significance of AMPK-independent pathways. To elucidate significance of AMPK and AMPK-independent signals in contracting skeletal muscles, we conducted a metabolomic analysis that compared the metabolic effects of 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) stimulation with the electrical contraction ex vivo in isolated rat epitrochlearis muscles, in which both α1- and α2-isoforms of AMPK and glucose uptake were equally activated. The metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry detected 184 peaks and successfully annotated 132 small molecules. AICAR stimulation exhibited high similarity to the electrical contraction in overall metabolites. Principal component analysis (PCA) demonstrated that the major principal component characterized common effects whereas the minor principal component distinguished the difference. PCA and a factor analysis suggested a substantial change in redox status as a result of AMPK activation. We also found a decrease in reduced glutathione levels in both AICAR-stimulated and contracting muscles. The muscle contraction-evoked influences related to the metabolism of amino acids, in particular, aspartate, alanine, or lysine, are supposed to be independent of AMPK activation. Our results substantiate the significance of AMPK activation in contracting skeletal muscles and provide novel evidence that AICAR stimulation closely mimics the metabolomic changes in the contracting skeletal muscles.

  17. Erdheim-Chester Disease as a Mimic of IgG4-Related Disease

    PubMed Central

    Gianfreda, Davide; Musetti, Claudio; Nicastro, Maria; Maritati, Federica; Cobelli, Rocco; Corradi, Domenico; Vaglio, Augusto

    2016-01-01

    Abstract Immunoglobulin-G4 (IgG4)-related disease (IgG4RD) is a fibro-inflammatory disorder characterized by tissue-infiltrating IgG4+ plasma cells, and, often, high serum IgG4. Several autoimmune, infectious, or proliferative conditions mimic IgG4RD. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by foamy histiocytic infiltration, fibrosis, and chronic inflammation. ECD and IgG4RD manifestations may overlap. A patient presented with huge fibrous retroperitoneal masses causing compression on neighboring structures; the case posed the challenge of the differential diagnosis between IgG4RD and ECD mainly because of a prominent serum and tissue IgG4 response. Retroperitoneal biopsy led to the diagnosis of ECD; the V600E BRAF mutation was found. Treatment with the BRAF inhibitor vemurafenib was started. Treatment failed to induce mass regression and the patient died after 3 months of therapy. Prompted by this case, we examined serum and tissue IgG4 in a series of 15 ECD patients evaluated at our center, and found that approximately one-fourth of the cases have increased IgG4 in the serum and often in the tissue. The differential diagnosis between IgG4RD and ECD can be challenging, as some ECD patients have prominent IgG4 responses. This suggests the possibility of common pathogenic mechanisms between ECD and IgG4RD. PMID:27227923

  18. L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated Cardiomyocytes.

    PubMed

    Himes, Ryan D; Smolin, Nikolai; Kukol, Andreas; Bossuyt, Julie; Bers, Donald M; Robia, Seth L

    2016-11-08

    To determine if mutations introduced into phospholemman (PLM) could increase the level of PLM-Na,K-ATPase (NKA) binding, we performed scanning mutagenesis of the transmembrane domain of PLM and measured Förster resonance energy transfer (FRET) between each mutant and NKA. We observed an increased level of binding to NKA for several PLM mutants compared to that of the wild type (WT), including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca(2+) transient compared to the GFP control. The Ca(2+) transient amplitude was further increased by L30A PLM overexpression. The L30A mutation also delayed Ca(2+) extrusion and increased the duration of cardiomyocyte contraction. This mimics aspects of the effect of cardiac glycosides, which are known to increase contractility through inhibition of NKA. No significant differences between WT and L30A PLM-expressing myocytes were observed after treatment with isoproterenol, suggesting that the superinhibitory effects of L30A are reversible with β-adrenergic stimulation. We also observed a decrease in the extent of PLM tetramerization with L30A compared to WT using FRET, suggesting that L30 is an important residue for mediating PLM-PLM binding. Molecular dynamics simulations revealed that the potential energy of the L30A tetramer is greater than that of the WT, and that the transmembrane α helix is distorted by the mutation. The results identify PLM residue L30 as an important determinant of PLM tetramerization and of functional inhibition of NKA by PLM.

  19. Novel Selective Estrogen Mimics for the Treatment of Tamoxifen-Resistant Breast Cancer

    PubMed Central

    Molloy, Mary Ellen; Perez White, Bethany E.; Gherezghiher, Teshome; Michalsen, Bradley T.; Xiong, Rui; Patel, Hitisha; Zhao, Huiping; Maximov, Philipp Y.; Jordan, V. Craig; Thatcher, Gregory R. J.; Tonetti, Debra A.

    2014-01-01

    Endocrine-resistant breast cancer is a major clinical obstacle. The use of 17β-estradiol (E2) has re-emerged as a potential treatment option following exhaustive use of tamoxifen (TAM) or aromatase inhibitors although side effects have hindered its clinical usage. Protein kinase C alpha (PKCα) expression was shown to be a predictor of disease outcome for patients receiving endocrine therapy and may predict a positive response to an estrogenic treatment. Here, we have investigated the use of novel benzothiophene selective estrogen mimics (SEMs) as an alternative to E2 for the treatment of TAM-resistant breast cancer. Following in vitro characterization of SEMs, a panel of clinically relevant PKCα-expressing, TAM-resistant models were used to investigate the antitumor effects of these compounds. SEM treatment resulted in growth inhibition and apoptosis of TAM-resistant cell lines in vitro. In vivo SEM treatment induced tumor regression of TAM-resistant T47D:A18/PKCα and T47D:A18-TAM1 tumor models. T47D:A18/PKCα tumor regression was accompanied by translocation of ERα to extranuclear sites, possibly defining a mechanism through which these SEMs initiate tumor regression. SEM treatment did not stimulate growth of E2-dependent T47D:A18/neo tumors. Additionally, unlike E2 or TAM, treatment with SEMs did not stimulate uterine weight gain. These findings suggest the further development of SEMs as a feasible therapeutic strategy for the treatment of endocrine-resistant breast cancer without the side effects associated with E2. PMID:25205655

  20. Methylated Cytokinins from the Phytopathogen Rhodococcus fascians Mimic Plant Hormone Activity.

    PubMed

    Radhika, Venkatesan; Ueda, Nanae; Tsuboi, Yuuri; Kojima, Mikiko; Kikuchi, Jun; Kudo, Takuji; Sakakibara, Hitoshi

    2015-10-01

    Cytokinins (CKs), a class of phytohormones that regulate plant growth and development, are also synthesized by some phytopathogens to disrupt the hormonal balance and to facilitate niche establishment in their hosts. Rhodococcus fascians harbors the fasciation (fas) locus, an operon encoding several genes homologous to CK biosynthesis and metabolism. This pathogen causes unique leafy gall symptoms reminiscent of CK overproduction; however, bacterial CKs have not been clearly correlated with the severe symptoms, and no virulence-associated unique CKs or analogs have been identified. Here, we report the identification of monomethylated N(6)-(∆(2)-isopentenyl)adenine and dimethylated N(6)-(∆(2)-isopentenyl)adenine (collectively, methylated cytokinins [MeCKs]) from R. fascians. MeCKs were recognized by a CK receptor and up-regulated type-A ARABIDOPSIS THALIANA RESPONSE REGULATOR genes. Treatment with MeCKs inhibited root growth, a hallmark of CK action, whereas the receptor mutant was insensitive. MeCKs were retained longer in planta than canonical CKs and were poor substrates for a CK oxidase/dehydrogenase, suggesting enhanced biological stability. MeCKs were synthesized by S-adenosyl methionine-dependent methyltransferases (MT1 and MT2) that are present upstream of the fas genes. The best substrate for methylation was isopentenyl diphosphate. MT1 and MT2 catalyzed distinct methylation reactions; only the MT2 product was used by FAS4 to synthesize monomethylated N(6)-(∆(2)-isopentenyl)adenine. The MT1 product was dimethylated by MT2 and used as a substrate by FAS4 to produce dimethylated N(6)-(∆(2)-isopentenyl)adenine. Chemically synthesized MeCKs were comparable in activity. Our results strongly suggest that MeCKs function as CK mimics and play a role in this plant-pathogen interaction.

  1. Methylated Cytokinins from the Phytopathogen Rhodococcus fascians Mimic Plant Hormone Activity1[OPEN

    PubMed Central

    Radhika, Venkatesan; Ueda, Nanae; Tsuboi, Yuuri; Kojima, Mikiko; Kikuchi, Jun; Kudo, Takuji; Sakakibara, Hitoshi

    2015-01-01

    Cytokinins (CKs), a class of phytohormones that regulate plant growth and development, are also synthesized by some phytopathogens to disrupt the hormonal balance and to facilitate niche establishment in their hosts. Rhodococcus fascians harbors the fasciation (fas) locus, an operon encoding several genes homologous to CK biosynthesis and metabolism. This pathogen causes unique leafy gall symptoms reminiscent of CK overproduction; however, bacterial CKs have not been clearly correlated with the severe symptoms, and no virulence-associated unique CKs or analogs have been identified. Here, we report the identification of monomethylated N6-(∆2-isopentenyl)adenine and dimethylated N6-(∆2-isopentenyl)adenine (collectively, methylated cytokinins [MeCKs]) from R. fascians. MeCKs were recognized by a CK receptor and up-regulated type-A ARABIDOPSIS THALIANA RESPONSE REGULATOR genes. Treatment with MeCKs inhibited root growth, a hallmark of CK action, whereas the receptor mutant was insensitive. MeCKs were retained longer in planta than canonical CKs and were poor substrates for a CK oxidase/dehydrogenase, suggesting enhanced biological stability. MeCKs were synthesized by S-adenosyl methionine-dependent methyltransferases (MT1 and MT2) that are present upstream of the fas genes. The best substrate for methylation was isopentenyl diphosphate. MT1 and MT2 catalyzed distinct methylation reactions; only the MT2 product was used by FAS4 to synthesize monomethylated N6-(∆2-isopentenyl)adenine. The MT1 product was dimethylated by MT2 and used as a substrate by FAS4 to produce dimethylated N6-(∆2-isopentenyl)adenine. Chemically synthesized MeCKs were comparable in activity. Our results strongly suggest that MeCKs function as CK mimics and play a role in this plant-pathogen interaction. PMID:26251309

  2. A mimic of sexually-motivated homicide: insect stings and heat exhaustion in a forest.

    PubMed

    Liu, Nancy X; Pollanen, Michael S

    2017-03-25

    We report the case a woman who was found dead in a forest. The body was nude and the position of the body suggested a sexually motivated homicide. We concluded that death was not related to homicide, but was related to the conjunction of environmental factors, including insect stings, and acute psychosis. A medicolegal death investigation with postmortem examination was undertaken to determine cause of death. At the scene, the body was supine with legs spread apart and the knees flexed, exposing the external genitalia. There were multiple apparent bruises on the body and neck. At autopsy, based on macroscopic and microscopic examination, the apparent bruises were found to be hemorrhagic insect bites. No significant injuries were present and no semen was found. Death appeared to be related to heat exhaustion and innumerable insect stings. Investigation of the medical history revealed longstanding schizoaffective disorder with episodic psychotic decompensations. In the past, during an acute psychotic episode the decedent removed her clothing and ran wildly in a forest, until she was rescued in a state of exhaustion and marked agitation, and taken to hospital for treatment. We concluded that the same circumstances had been repeated but with a fatal outcome. This case is an example of a mimic of sexually-motivated homicide and is a reminder to forensic pathologists to avoid tunnel vision. We need to be skeptical of the allure of common sense based on first impressions of the scene and the body. Forensic pathologists must be unafraid to scientifically explore improbable, but true, alternate explanations.

  3. Vibrational signatures of Watson-Crick base pairing in adenine-thymine mimics.

    PubMed

    Nosenko, Yevgeniy; Kunitski, Maksim; Stark, Tina; Göbel, Michael; Tarakeshwar, Pilarisetty; Brutschy, Bernhard

    2013-07-21

    The vibrational fingerprints of hydrogen-bonding associated with the adenine-thymine (A-T) Watson-Crick (WC) base pair have been identified in an infrared study of the A-T mimics 4-aminopyrimidine-1-methylthymine (4APM-1MT) and 4-aminopyrimidine-6-methyl-4-pyrimidinone (4APM-M4PMN) in the gas-phase. The IR vibrational spectra were measured via a double resonance scheme utilizing femtosecond multiphoton ionization. The changes in the molecular structure, anharmonic vibrational parameters, and the assignment of the observed vibrational spectra in the NH/CH stretch region were investigated by carrying out high-level theoretical calculations of the anharmonic spectra. The experimental observations and theoretical calculations indicate that the hydrogen bonds associated with WC base-pairing are relatively stronger than those associated with reverse WC (rWC) base pairing. This is manifested in a more pronounced red-shift of the H-bonded vibrational modes associated with the WC as compared with the rWC base-pairing. An analysis of the factors contributing to the anharmonicity of the vibrational modes associated with H-bonding reveals that the magnitude of the off-diagonal anharmonic coupling of the H-bonded -NH2 stretch and the -NH2 bend is much smaller in WC base-pairing than in the corresponding rWC base-pairing. The chemical and biological implications of these results, especially in the context of using vibrational spectroscopy as a tool for identifying the signatures of nucleotide base vibrations is addressed.

  4. Characterization of a whole smoke in vitro exposure system (Burghart Mimic Smoker-01).

    PubMed

    Scian, Mariano J; Oldham, Michael J; Kane, David B; Edmiston, Jeffery S; McKinney, Willie J

    2009-02-01

    In vitro systems are frequently used to study mechanisms of mainstream cigarette smoke (MS)-induced lung injury. Traditional methods of exposure involve the capture of MS particulate phase with filter pads or bubbling MS through phosphate buffered saline (PBS) or cell culture medium. Although useful for in vitro experiments, these exposure methods may fail to capture potential interactions between the gas and particulate phases. To better understand the effect of MS on the human airway, in vitro whole smoke exposure systems that utilize freshly generated whole smoke are needed. Here we report the characterization of a new in vitro whole smoke exposure system (Burghart Mimic Smoker-01 (MSB-01)). This system uses a smoke distribution manifold to simultaneously deliver MS to each well of a 96-well plate. Intraday and interday variations for particulate matter deposition were less than 5% and 13% respectively. Cytotoxicity measurements using lung epithelial BEAS-2B cells indicate variations in calculated EC(50) (half maximal effective concentration) values of 13% intraday and 20% interday. Smoke particulate losses and changes in particle size distribution were also analyzed. The data indicate that 45-50% of the MS generated at the smoking ports is lost within the system prior to delivery into the exposure chamber; however, no changes in particle size distribution were detected throughout the system. Overall, the MSB-01 reproducibly delivered mainstream cigarette smoke in a dose dependent manner across the multiwell plate. The MSB-01 is a high throughput system capable of exposing cells to both the MS particulate and gas/vapor phases simultaneously.

  5. Space science applications for conducting polymer particles: synthetic mimics for cosmic dust and micrometeorites.

    PubMed

    Fielding, Lee A; Hillier, Jon K; Burchell, Mark J; Armes, Steven P

    2015-12-11

    Over the last decade or so, a range of polypyrrole-based particles have been designed and evaluated for space science applications. This electrically conductive polymer enables such particles to efficiently acquire surface charge, which in turn allows their acceleration up to the hypervelocity regime (>1 km s(-1)) using a Van de Graaff accelerator. Either organic latex (e.g. polystyrene or poly(methyl methacrylate)) or various inorganic materials (such as silica, olivine or pyrrhotite) can be coated with polypyrrole; these core-shell particles are useful mimics for understanding the hypervelocity impact ionisation behaviour of micro-meteorites (a.k.a. cosmic dust). Impacts on metal targets at relatively low hypervelocities (<10 km s(-1)) generate ionic plasma composed mainly of molecular fragments, whereas higher hypervelocities (>10 km s(-1)) generate predominately atomic species, since many more chemical bonds are cleaved if the particles impinge with higher kinetic energy. Such fundamental studies are relevant to the calibration of the cosmic dust analyser (CDA) onboard the Cassini spacecraft, which was designed to determine the chemical composition of Saturn's dust rings. Inspired by volcanism observed for one of the Jupiter's moons (Io), polypyrrole-coated sulfur-rich latexes have also been designed to help space scientists understand ionisation spectra originating from sulfur-rich dust particles. Finally, relatively large (20 μm diameter) polypyrrole-coated polystyrene latexes have proven to be useful for understanding the extent of thermal ablation of organic projectiles when fired at ultralow density aerogel targets at up to 6.1 km s(-1) using a Light Gas Gun. In this case, the sacrificial polypyrrole overlayer simply provides a sensitive spectroscopic signature (rather than a conductive overlayer), and the scientific findings have important implications for the detection of organic dust grains during the Stardust space mission.

  6. Follicular Pancreatitis: A Distinct Form of Chronic Pancreatitis - An Additional Mimic of Pancreatic Neoplasms

    PubMed Central

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-01-01

    Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, kappa and lambda light chains as well as IgG4 and IgG were performed. We found a total of six patients (male:female = 2:1, mean age = 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis while two presented with abdominal pain, fatigue and elevated liver enzymes. On imaging, three patients had a discrete solid mass while 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2 negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions. IgG4/IgG ratio was <40% in all 6 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID:26563969

  7. Revision of the Western Australian pebble-mimic dragon species-group (Tympanocryptis cephalus: Reptilia: Agamidae).

    PubMed

    Doughty, Paul; Kealley, Luke; Shoo, Luke P; Melville, Jane

    2015-11-03

    Recent work on species complexes of the pebble-mimic dragons of the Australian genus Tympanocryptis has greatly clarified evolutionary relationships among taxa and also indicated that species diversity has been severely underestimated. Here we provide a morphological and molecular appraisal of variation in the T. cephalus species-group and find evidence for recognizing five species-level lineages from Western Australia. Four species-level lineages are strongly supported with a combined mitochondrial and nuclear DNA Bayesian analysis (a fifth population from the Gascoyne region lacked tissue samples). Morphologically, we found subtle, yet consistent, differences among the populations in scalation, color and pattern. True T. cephalus Günther is restricted to the coastal Pilbara region and characterized by five dark blotches on the dorsum, keeled ventrals, and other characters. Two other lineages within the Pilbara, from the Hamersley range and Fortescue/northern Pilbara region, differed from T. cephalus senso stricto by possessing a more elongate body and a plain dorsum. Furthermore, the Hamersley lineage differed from the Fortescue lineage by possessing slightly more reddish coloration and feeble keeling on the snout. Although there are few specimens and no tissue samples available for the Gascoyne population, these individuals are larger, have rugose scales on the snout, and possess scattered enlarged tubercles with three large blotches on the dorsum. The name T. cephalus gigas Mitchell is available for this population. The most widespread lineage, and the one best represented in collections and in field guides, occurs throughout central Western Australia. These Goldfield populations are characterized by a protruding snout, narrow rostral, and uniform reddish-brown coloration, often with a dark wash. Based on the genetic and morphological differences, we redescribe T. cephalus, resurrect and elevate T. gigas to a full species and designate a neotype for this taxon

  8. HIV Fusion Peptide Penetrates, Disorders, and Softens T-Cell Membrane Mimics

    PubMed Central

    Tristram-Nagle, Stephanie; Chan, Rob; Kooijman, Edgar; Uppamoochikkal, Pradeep; Qiang, Wei; Weliky, David P.; Nagle, John F.

    2010-01-01

    This work investigates the interaction of N-terminal gp41 fusion peptide (FP) of human immunodeficiency virus type 1 (HIV-1) with model membranes in order to elucidate how FP leads to fusion of HIV and T-cell membranes. FP constructs were (i) wild-type FP23 (23 N-terminal amino acids of gp41), (ii) water-soluble monomeric FP that adds six lysines on the C-terminus of FP23 (FPwsm), and (iii) the C-terminus covalently linked trimeric version (FPtri) of FPwsm. Model membranes were (i) LM3 (a T-cell mimic), (ii) 1,2-dioleoyl-sn-glycero-3-phosphocholine, (iii) 1,2-dioleoyl-sn-glycero-3-phosphocholine/30 mol% cholesterol, (iv) 1,2-dierucoyl-sn-glycero-3-phosphocholine, and (v) 1,2-dierucoyl-sn-glycero-3-phosphocholine/30 mol% cholesterol. Diffuse synchrotron low-angle x-ray scattering from fully hydrated samples, supplemented by volumetric data, showed that FP23 and FPtri penetrate into the hydrocarbon region and cause membranes to thin. Depth of penetration appears to depend upon a complex combination of factors including bilayer thickness, presence of cholesterol, and electrostatics. X-ray data showed an increase in curvature in hexagonal phase 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, which further indicates that FP23 penetrates into the hydrocarbon region rather than residing in the interfacial headgroup region. Low-angle x-ray scattering data also yielded the bending modulus KC, a measure of membrane stiffness, and wide-angle x-ray scattering yielded the Sxray orientational order parameter. Both FP23 and FPtri decreased KC and Sxray considerably, while the weak effect of FPwsm suggests that it did not partition strongly into LM3 model membranes. Our results are consistent with the HIV FP disordering and softening the T-cell membrane, thereby lowering the activation energy for viral membrane fusion. PMID:20655315

  9. Nanomolecular HLA-DR10 antibody mimics: A potent system for molecular targeted therapy and imaging.

    PubMed

    DeNardo, Gerald L; Natarajan, Arutselvan; Hok, Saphon; Mirick, Gary; DeNardo, Sally J; Corzett, Michele; Sysko, Vladimir; Lehmann, Joerg; Beckett, Laurel; Balhorn, Rod

    2008-12-01

    To mimic the molecular specificity and cell selectivity of monoclonal antibody (mAb) binding while decreasing size, nanomolecules (selective high-affinity ligands; SHALs), based on in silico modeling, have been created to bind to human leukocyte antigen-DR (HLA-DR10), a signaling receptor protein upregulated on the malignant B-lymphocytes of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. SHALs were synthesized with a biotin or DOTA chelate (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), using a solid-phase lysine-polyethyleneglycol backbone to link sets of ligands shown previously to bind to HLA-DR10. Using cell-binding and death assays and confocal microscopy, SHAL uptake, residualization, and cytocidal activity were evaluated in HLA-DR10 expressing and nonexpressing live, human lymphoma cell lines. All of the SHALs tested were selective for, and accumulated in, expressing cells. Reflecting binding to HLA-DR10 inside the cells, SHALs having the Ct ligand (3-(2-([3-chloro-5-trifluoromethyl)-2-pyridinyl]oxy)-anilino)-3-oxopropanionic acid) residualized in expressing cells greater than 179 times more than accountable by cell-surface membrane HLA-DR10. Confocal microscopy confirmed the intracellular residualization of these SHALs. Importantly, SHALs with a Ct ligand had direct cytocidal activity, similar in potency to that of Lym-1 mAb and rituximab, selectively for HLA-DR10 expressing lymphoma cells and xenografts. The results show that SHALs containing the Ct ligand residualize intracellularly and have cytocidal effects mediated by HLA-DR10. These SHALs have extraordinary potential as novel molecules for the selective targeting of lymphoma and leukemia for molecular therapy and imaging. Further, these SHALs can be used to transport and residualize cytotoxic agents near critical sites inside these malignant cells.

  10. Child Abuse Mimic: Avulsion Injury in a Child With Penoscrotal Webbing.

    PubMed

    Deutsch, Stephanie Anne; Long, Christopher J; Srinivasan, Arun K; Wood, Joanne N

    2017-04-01

    Sexual abuse of children is prevalent in today's society. In 2012, approximately 686,000 children (9.2 per 1000) in the United States were determined to be victims of substantiated child abuse and neglect, according to national data compiled by child protective service agencies; victimization rates were highest for children younger than 1 year. Nearly 9.3% of maltreated children were victims of sexual abuse, this finding was reported by US Department of Health and Human Services (http://www.acf.hhs.gov/programs/cb/research-data-technology/statistics-research/child-maltreatment). Previous research has shown that as many as 1 in 3 girls and 1 in 7 boys will be sexually abused during childhood (Child Abuse Negl. 2003;27:1205-1222). Although sexual abuse seems to be less common in boys than girls, this may be partly due to underdiagnosis and underreporting of sexual abuse in boys (Arch Dis Child. 2007;92:328-331). Clinicians should therefore consider the possibility of sexual abuse when boys present with genital injuries, because failing to recognize and diagnose sexual abuse can pose an ongoing safety risk to a child. However, an erroneous diagnosis of sexual abuse can have equally hazardous repercussions, including removal of a child from their caregivers or prosecution of an innocent individual. A number of medical conditions can mimic child sexual abuse injuries, including anal fissures, failure of midline fusion, perianal streptococcal dermatitis, and straddle injury (J Pediatr Health Care. 2009;23:283-288 and Acta Paediatr. 2011;100:590-593). The following case involves a 5-week-old male infant who presented to the pediatric emergency department with an avulsion injury to his penis concerning for sexual abuse. He was ultimately diagnosed with a relatively rare anatomic variant of the genitalia and determined to have sustained an accidental injury whose appearance mimicked abuse.

  11. Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold.

    PubMed

    Werkhoven, P R; Elwakiel, M; Meuleman, T J; Quarles van Ufford, H C; Kruijtzer, J A W; Liskamp, R M J

    2016-01-14

    Mimics of discontinuous epitopes of for example bacterial or viral proteins may have considerable potential for the development of synthetic vaccines, especially if conserved epitopes can be mimicked. However, due to the structural complexity and size of discontinuous epitopes molecular construction of these mimics remains challeging. We present here a convergent route for the assembly of discontinuous epitope mimics by successive azide alkyne cycloaddition on an orthogonal alkyne functionalized scaffold. Here the synthesis of mimics of the HIV gp120 discontinuous epitope that interacts with the CD4 receptor is described. The resulting protein mimics are capable of inhibition of the gp120-CD4 interaction. The route is convergent, robust and should be applicable to other discontinuous epitopes.

  12. Structural basis for the interaction of a vascular endothelial growth factor mimic peptide motif and its corresponding receptors.

    PubMed

    Giordano, Ricardo J; Anobom, Cristiane D; Cardó-Vila, Marina; Kalil, Jorge; Valente, Ana P; Pasqualini, Renata; Almeida, Fabio C L; Arap, Wadih

    2005-10-01

    Vascular endothelial growth factor (VEGF) is central to the survival and development of the vascular and nervous systems. We screened phage display libraries and built a peptide-based ligand-receptor map of binding sites within the VEGF family. We then validated a cyclic peptide, CPQPRPLC, as a VEGF-mimic that binds specifically to neuropilin-1 and VEGF receptor-1. Here, we use NMR spectroscopy to understand the structural basis of the interaction between our mimic peptide and the VEGF receptors. We show that: (1) CPQPRPLC has multiple interactive conformations; (2) receptor binding is mediated by the motif Arg-Pro-Leu; and (3) the Pro residue within Arg-Pro-Leu participates in binding to neuropilin-1 but not to VEGF receptor-1, perhaps representing an evolutionary gain-of-function. Therefore, Arg-Pro-Leu is a differential ligand motif to VEGF receptors and a candidate peptidomimetic lead for VEGF pathway modulation.

  13. Tunable Approach for the Stereoselective Synthesis of 1-C-Diethylphosphono(difluoromethyl) Iminosugars as Glycosyl Phosphate Mimics.

    PubMed

    Cocaud, Chloé; Nicolas, Cyril; Poisson, Thomas; Pannecoucke, Xavier; Legault, Claude Y; Martin, Olivier R

    2017-03-03

    An efficient methodology for the stereoselective and tunable addition of LiCF2P(O)(OEt)2 and BrMgCF2P(O)(OEt)2 reagents to N-t-butanesulfinyl glycosylamines is described with details on the stereochemical effects at play in this process. It provides a practical route to various 1-C-diethylphosphono(difluoromethyl) iminosugars as glycosyl phosphate and sugar nucleotide mimics.

  14. A FRET-based ratiometric fluorescent and colorimetric probe for the facile detection of organophosphonate nerve agent mimic DCP.

    PubMed

    Xuan, Weimin; Cao, Yanting; Zhou, Jiahong; Wang, Wei

    2013-11-18

    A FRET ratiometric fluorescent probe enabling a fast and highly sensitive response to OP nerve agent mimic DCP within 1 min and with as low as 0.17 ppm concentration detection limit has been developed. Moreover, the probe exhibits noticeable color changes under UV light and even with the naked eye. It is also demonstrated that it can detect both liquid and gas nerve agents.

  15. A frame-dependent gravitational effective action mimics a cosmological constant, but modifies the black hole horizon

    NASA Astrophysics Data System (ADS)

    Adler, Stephen L.

    2016-06-01

    A frame-dependent effective action motivated by the postulates of three-space general coordinate invariance and Weyl scaling invariance exactly mimics a cosmological constant in Robertson-Walker spacetimes. However, in a static spherically symmetric Schwarzschild-like geometry it modifies the black hole horizon structure within microscopic distances of the nominal horizon, in such a way that g00 never vanishes. This could have important implications for the black hole “information paradox”.

  16. Various clinical conditions can mimic Crimean-Congo hemorrhagic fever in pediatric patients in endemic regions.

    PubMed

    Kara, Soner S; Kara, Duygu; Fettah, Ali

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with high mortality. Many disorders can mimic CCHF. It is important to recognize the condition and to perform differential diagnosis in endemic countries. Twenty-one children aged 18 years or less with a preliminary diagnosis of CCHF were retrospectively evaluated. Real-time PCR and a confirmatory indirect immunofluorescence assay for negative results were performed. The diagnoses determined that 9 patients had (42.9%) CCHF; 7 patients had (33.3%) viral upper respiratory tract infections (URTI); 2 patients had (9.5%) brucellosis; 1 patients had (4.7%) periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome episode; 1 patient had (4.7%) cerebral palsy, diabetes insipidus, acute gastroenteritis, and hypernatremic dehydration; and 1 patient had (4.7%) cellulitis after a tick bite. The mean age of patients with CCHF was greater than that of the other patients (116.1±53.6 vs. 94.1±52.1 months, p=0.02). Seventeen (81%) of the children included had a history of tick bites, 2 (9.5%) had a history of contact with a patient with CCHF, and 2 (9.5%) had no exposure, but were living in an endemic region. Three patients had an underlying disorder: cerebral palsy and diabetes insipidus, epilepsy, or PFAPA. All of the children experienced fever. Other frequent symptoms were malaise, diarrhea, vomiting, and abdominal pain, but none of these differed statistically between the patient groups. CCHF patients had a longer mean duration of symptoms (10.56±1.42 vs. 6.75±3.62 days, p=0.008) and a longer mean length of hospitalization (8.00±2.08 vs. 3.58±1.56 days, p<0.001) than the other patients. At laboratory examination, patients with CCHF had statistically significant lower leukocyte and platelet counts, more prolonged coagulation parameters, and greater AST, ALT, LDH, and CK levels than the other patients. No mortality or complications occurred in the study. Both infectious causes, such as

  17. A NON-CLEAVABLE UmuD VARIANT THAT ACTS AS A UmuD' MIMIC

    SciTech Connect

    Beuning, P J; Simon, S M; Zemla, A; Barsky, D; Walker, G C

    2005-10-26

    UmuD{sub 2} cleaves and removes its N-terminal 24 amino acids to form UmuD'{sub 2}, which activates UmuC for its role in UV-induced mutagenesis in E. coli. Cells with a non-cleavable UmuD exhibit essentially no UV-induced mutagenesis and are hypersensitive to killing by UV light. UmuD has been shown to bind to the beta processivity clamp (''beta'') of the replicative DNA polymerase, pol III. A possible beta-binding motif has been predicted in the same region of UmuD shown to be important for its interaction with beta. We performed alanine-scanning mutagenesis of this motif (14-TFPLF-18) in UmuD and showed that it has a moderate influence on UV-induced mutagenesis but is required for the cold sensitive phenotype caused by elevated levels of wild-type UmuD and UmuC. Surprisingly, the wild-type and the beta-binding motif variant bind to beta with similar K{sub d} values as determined by changes in tryptophan fluorescence. However, this data also implies that the single tryptophan in beta is in strikingly different environments in the presence of the wild-type versus the variant UmuD proteins, suggesting a distinct change in some aspect of the interaction with little change in its strength. Despite the fact that this novel UmuD variant is noncleavable, we find that cells harboring it exhibit phenotypes more consistent with the cleaved form UmuD', such as resistance to killing by UV light and failure to exhibit the cold sensitive phenotype. Cross-linking and chemical modification experiments indicate that the N-terminal arms of the UmuD variant are less likely to be bound to the globular domain than those of the wild-type, which may be the mechanism by which this UmuD variant acts as a UmuD' mimic.

  18. An iron-iron hydrogenase mimic with appended electron reservoir for efficient proton reduction in aqueous media.

    PubMed

    Becker, René; Amirjalayer, Saeed; Li, Ping; Woutersen, Sander; Reek, Joost N H

    2016-01-01

    The transition from a fossil-based economy to a hydrogen-based economy requires cheap and abundant, yet stable and efficient, hydrogen production catalysts. Nature shows the potential of iron-based catalysts such as the iron-iron hydrogenase (H2ase) enzyme, which catalyzes hydrogen evolution at rates similar to platinum with low overpotential. However, existing synthetic H2ase mimics generally suffer from low efficiency and oxygen sensitivity and generally operate in organic solvents. We report on a synthetic H2ase mimic that contains a redox-active phosphole ligand as an electron reservoir, a feature that is also crucial for the working of the natural enzyme. Using a combination of (spectro)electrochemistry and time-resolved infrared spectroscopy, we elucidate the unique redox behavior of the catalyst. We find that the electron reservoir actively partakes in the reduction of protons and that its electron-rich redox states are stabilized through ligand protonation. In dilute sulfuric acid, the catalyst has a turnover frequency of 7.0 × 10(4) s(-1) at an overpotential of 0.66 V. This catalyst is tolerant to the presence of oxygen, thereby paving the way for a new generation of synthetic H2ase mimics that combine the benefits of the enzyme with synthetic versatility and improved stability.

  19. An iron-iron hydrogenase mimic with appended electron reservoir for efficient proton reduction in aqueous media

    PubMed Central

    Becker, René; Amirjalayer, Saeed; Li, Ping; Woutersen, Sander; Reek, Joost N. H.

    2016-01-01

    The transition from a fossil-based economy to a hydrogen-based economy requires cheap and abundant, yet stable and efficient, hydrogen production catalysts. Nature shows the potential of iron-based catalysts such as the iron-iron hydrogenase (H2ase) enzyme, which catalyzes hydrogen evolution at rates similar to platinum with low overpotential. However, existing synthetic H2ase mimics generally suffer from low efficiency and oxygen sensitivity and generally operate in organic solvents. We report on a synthetic H2ase mimic that contains a redox-active phosphole ligand as an electron reservoir, a feature that is also crucial for the working of the natural enzyme. Using a combination of (spectro)electrochemistry and time-resolved infrared spectroscopy, we elucidate the unique redox behavior of the catalyst. We find that the electron reservoir actively partakes in the reduction of protons and that its electron-rich redox states are stabilized through ligand protonation. In dilute sulfuric acid, the catalyst has a turnover frequency of 7.0 × 104 s−1 at an overpotential of 0.66 V. This catalyst is tolerant to the presence of oxygen, thereby paving the way for a new generation of synthetic H2ase mimics that combine the benefits of the enzyme with synthetic versatility and improved stability. PMID:26844297

  20. Synthetic Mimics of Bacterial Lipid A Trigger Optical Transitions in Liquid Crystal Microdroplets at Ultralow Picogram-per-Milliliter Concentrations

    PubMed Central

    2016-01-01

    We report synthetic six-tailed mimics of the bacterial glycolipid Lipid A that trigger changes in the internal ordering of water-dispersed liquid crystal (LC) microdroplets at ultralow (picogram-per-milliliter) concentrations. These molecules represent the first class of synthetic amphiphiles to mimic the ability of Lipid A and bacterial endotoxins to trigger optical responses in LC droplets at these ultralow concentrations. This behavior stands in contrast to all previously reported synthetic surfactants and lipids, which require near-complete monolayer coverage at the LC droplet surface to trigger ordering transitions. Surface-pressure measurements and SAXS experiments reveal these six-tailed synthetic amphiphiles to mimic key aspects of the self-assembly of Lipid A at aqueous interfaces and in solution. These and other results suggest that these amphiphiles trigger orientational transitions at ultralow concentrations through a unique mechanism that is similar to that of Lipid A and involves formation of inverted self-associated nanostructures at topological defects in the LC droplets. PMID:26562069

  1. Multiple selective pressures apply to a coral reef fish mimic: a case of Batesian-aggressive mimicry.

    PubMed

    Cheney, Karen L

    2010-06-22

    Mimics closely resemble unrelated species to avoid predation, capture prey or gain access to hosts or reproductive opportunities. However, the classification of mimicry systems into three established evolutionary mechanisms (protection, reproduction and foraging) can be contentious because multiple benefits may be gained by mimics, causing the evolution of such systems to be driven by more than one selective agent. However, data on such systems are generally speculative or anecdotal. This study provides empirical evidence that dual benefits apply to a coral reef fish mimic in terms of increased access to food (aggressive mimicry) and reduced predation risk (Batesian mimicry). Bicolour fangblennies Plagiotremus laudandus gained access to more reef fish victims, which they attack to feed on fins and scales, when they spent more time associated with their model Meiacanthus atrodorsalis. Furthermore, exact replicas of P. laudandus incurred fewer approaches from potential predators compared with control replicas that varied in resemblance to P. laudandus. Predators with trichromatic visual systems (three distinct spectral sensitivities) could potentially distinguish between replicas based on colour based on theoretical vision models. Therefore, this mimicry system could be best described as Batesian-aggressive mimicry in which mimicry evolution is driven by multiple simultaneous selective pressures.

  2. DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma.

    PubMed

    Amodio, Nicola; Leotta, Marzia; Bellizzi, Dina; Di Martino, Maria Teresa; D'Aquila, Patrizia; Lionetti, Marta; Fabiani, Fernanda; Leone, Emanuela; Gullà, Anna Maria; Passarino, Giuseppe; Caraglia, Michele; Negrini, Massimo; Neri, Antonino; Giordano, Antonio; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2012-10-01

    Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that recently emerged as master regulator of gene expression by targeting protein-coding mRNAs. However, miRNAs involvement in the regulation of the epigenetic machinery and their potential use as therapeutics in MM remain to be investigated. Here, we provide evidence that the expression of de novo DNA methyltransferases (DNMTs) is deregulated in MM cells. Moreover, we show that miR-29b targets DNMT3A and DNMT3B mRNAs and reduces global DNA methylation in MM cells. In vitro transfection of MM cells with synthetic miR-29b mimics significantly impairs cell cycle progression and also potentiates the growth-inhibitory effects induced by the demethylating agent 5-azacitidine. Most importantly, in vivo intratumor or systemic delivery of synthetic miR-29b mimics, in two clinically relevant murine models of human MM, including the SCID-synth-hu system, induces significant anti-tumor effects. All together, our findings demonstrate that aberrant DNMTs expression is efficiently modulated by tumor suppressive synthetic miR-29b mimics, indicating that methyloma modulation is a novel matter of investigation in miRNA-based therapy of MM.

  3. DNA-demethylating and anti-tumor activity of synthetic miR-29b mimics in multiple myeloma

    PubMed Central

    Amodio, Nicola; Leotta, Marzia; Bellizzi, Dina; Di Martino, Maria Teresa; D'Aquila, Patrizia; Lionetti, Marta; Fabiani, Fernanda; Leone, Emanuela; Gullà, Anna Maria; Passarino, Giuseppe; Caraglia, Michele; Negrini, Massimo; Neri, Antonino; Giordano, Antonio; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2012-01-01

    Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that recently emerged as master regulator of gene expression by targeting protein-coding mRNAs. However, miRNAs involvement in the regulation of the epigenetic machinery and their potential use as therapeutics in MM remain to be investigated. Here, we provide evidence that the expression of de novo DNA methyltransferases (DNMTs) is deregulated in MM cells. Moreover, we show that miR-29b targets DNMT3A and DNMT3B mRNAs and reduces global DNA methylation in MM cells. In vitro transfection of MM cells with synthetic miR-29b mimics significantly impairs cell cycle progression and also potentiates the growth-inhibitory effects induced by the demethylating agent 5-azacitidine. Most importantly, in vivo intratumor or systemic delivery of synthetic miR-29b mimics, in two clinically relevant murine models of human MM, including the SCID-synth-hu system, induces significant anti-tumor effects. All together, our findings demonstrate that aberrant DNMTs expression is efficiently modulated by tumor suppressive synthetic miR-29b mimics, indicating that methyloma modulation is a novel matter of investigation in miRNA-based therapy of MM. PMID:23100393

  4. How to Diagnose and Treat IBD Mimics in the Refractory IBD Patient Who Does Not Have IBD.

    PubMed

    Chachu, Karen A; Osterman, Mark T

    2016-05-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract and includes both Crohn's disease and ulcerative colitis. Patients with IBD often present with abdominal pain, diarrhea, and rectal bleeding but may also have a wide variety of other symptoms such as weight loss, fever, nausea, vomiting, and possibly obstruction. Given that the presentation of IBD is not specific, the differential diagnosis is broad and encompasses a wide spectrum of diseases, many of which can mimic and/or even coexist with IBD. It is important for physicians to differentiate symptoms due to refractory IBD from symptoms due to IBD mimics when a patient is not responding to standard IBD treatment. Many of the various IBD mimics include infectious etiologies (viral, bacterial, mycobacterial, fungal, protozoal, and helminthic infections), vascular causes, other immune causes including autoimmune etiologies, drug-induced processes, radiation-induced, and other etiologies such as small intestinal bacterial overgrowth, diverticulitis, and bile acid malabsorption. Thoughtful consideration and evaluation of these potential etiologies through patient history and physical examination, as well as appropriate tests, endoscopic evaluation, and cross-sectional imaging is required to evaluate any patient presenting with symptoms consistent with IBD.

  5. Synthesis of high-mannose oligosaccharide analogues through click chemistry: true functional mimics of their natural counterparts against lectins?

    PubMed

    François-Heude, Marc; Méndez-Ardoy, Alejandro; Cendret, Virginie; Lafite, Pierre; Daniellou, Richard; Ortiz Mellet, Carmen; García Fernández, José M; Moreau, Vincent; Djedaïni-Pilard, Florence

    2015-01-26

    Terminal "high-mannose oligosaccharides" are involved in a broad range of biological and pathological processes, from sperm-egg fusion to influenza and human immunodeficiency virus infections. In spite of many efforts, their synthesis continues to be very challenging and actually represents a major bottleneck in the field. Whereas multivalent presentation of mannopyranosyl motifs onto a variety of scaffolds has proven to be a successful way to interfere in recognition processes involving high-mannose oligosaccharides, such constructs fail at reproducing the subtle differences in affinity towards the variety of protein receptors (lectins) and antibodies susceptible to binding to the natural ligands. Here we report a family of functional high-mannose oligosaccharide mimics that reproduce not only the terminal mannopyranosyl display, but also the core structure and the branching pattern, by replacing some inner mannopyranosyl units with triazole rings. Such molecular design can be implemented by exploiting "click" ligation strategies, resulting in a substantial reduction of synthetic cost. The binding affinities of the new "click" high-mannose oligosaccharide mimics towards two mannose specific lectins, namely the plant lectin concanavalin A (ConA) and the human macrophage mannose receptor (rhMMR), have been studied by enzyme-linked lectin assays and found to follow identical trends to those observed for the natural oligosaccharide counterparts. Calorimetric determinations against ConA, and X-ray structural data support the conclusion that these compounds are not just another family of multivalent mannosides, but real "structural mimics" of the high-mannose oligosaccharides.

  6. Strigolactone analogues and mimics derived from phthalimide, saccharine, p-tolylmalondialdehyde, benzoic and salicylic acid as scaffolds.

    PubMed

    Zwanenburg, Binne; Mwakaboko, Alinanuswe S

    2011-12-15

    A series of new strigolactone (SL) analogues is derived from simple and cheap starting materials. These SL analogues are designed using a working model. The first analogue is a modified Nijmegen-1, the second contains saccharin as substituent (bio-isosteric replacement of a carbonyl in Nijmegen-1 by a sulfonyl group) and the third one is derived from p-tolylmalondialdehyde. These new SL analogues are appreciably to highly active as germination stimulants of seeds of Striga hermonthica and Orobanche cernua. The SL analogue derived from saccharin is the most active one. A serendipitous and most rewarding finding is that the compound obtained by a direct coupling of saccharin with the chlorobutenolide exhibits a high germination activity especially towards O. cernua seeds. Two other SL mimics are obtained from benzoic and salicylic aid by a direct coupling reaction with chlorobutenolide, both of them are very active germinating agents. These SL mimics represent a new type of germination stimulants. A tentative molecular mechanism for the mode of action of these SL mimics has been proposed.

  7. Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domesticated silkworms: enzymatic adaptation of Bombyx mori to mulberry defense.

    PubMed

    Hirayama, Chikara; Konno, Kotaro; Wasano, Naoya; Nakamura, Masatoshi

    2007-12-01

    Mulberry leaves (Morus spp.) exude latex rich in sugar-mimic alkaloids, 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1) and 1-deoxynojirimycin (DNJ), as a defense against herbivorous insects. Sugar-mimic alkaloids are inhibitors of sugar-metabolizing enzymes, and are toxic to the Eri silkworm, Samia ricini, a generalist herbivore, but not at all to the domesticated silkworm, Bombyx mori, a mulberry specialist. To address the phenomena, we fed both larvae diets containing different sugar sources (sucrose, glucose or none) with or without sugar-mimic alkaloids from mulberry latex. In S. ricini, addition of sugar-mimic alkaloids to the sucrose (the major sugar in mulberry leaves) diet reduced both growth and the absorption ratio of sugar, but it reduced neither in B. mori. The midgut soluble sucrase activity of S. ricini was low and inhibited by very low concentrations of sugar-mimic alkaloids (IC(50)=0.9-8.2microM), but that of B. mori was high and not inhibited even by very high concentrations (IC(50)>1000microM) of sugar-mimic alkaloids. In S. ricini, the addition of sugar-mimic alkaloids to the glucose diet still had considerable negative effects on growth, although it did not reduce the absorption ratio of glucose. The hemolymph of S. ricini fed sugar-mimic alkaloids contained sugar-mimic alkaloids. The trehalose concentration in the hemolymph increased significantly in S. ricini fed sugar-mimic alkaloids, but not in B. mori. The trehalase activities of S. ricini were lower and inhibited by lower concentrations of sugar-mimic alkaloids than those of B. mori. These results suggest that sugar-mimic alkaloids in mulberry latex exert toxicity to S. ricini larvae first by inhibiting midgut sucrase and digestion of sucrose, and secondly, after being absorbed into hemolymph, by inhibiting trehalase and utilization of trehalose, the major blood sugar. Further, our results reveal that B. mori larvae evolved enzymatic adaptation to mulberry defense by developing sucrase and

  8. Diverse functions of cationic Mn(III) substituted N-pyridylporphyrins, known as SOD mimics

    PubMed Central

    Batinic-Haberle, Ines; Rajic, Zrinka; Tovmasyan, Artak; Ye, Xiaodong; Leong, Kam W.; Dewhirst, Mark W.; Vujaskovic, Zeljko; Benov, Ludmil; Spasojevic, Ivan

    2011-01-01

    Oxidative stress, a redox imbalance between the endogenous reactive species and antioxidant systems, is common to numerous pathological conditions such as cancer, central nervous system injuries, radiation injury, diabetes etc. Therefore, compounds able to reduce oxidative stress have been actively sought for over 3 decades. Superoxide is the major species involved in oxidative stress either in its own right or through its progeny, such as ONOO−, H2O2, ·OH, CO3·−, and ·NO2. Therefore, the very first compounds developed in the late 1970-ies were the superoxide dismutase (SOD) mimics. Thus far the most potent mimics have been the cationic meso Mn(III) N-substituted pyridylporphyrins and N,N′-disubstituted imidazolylporphyrins (MnPs), some of them with kcat(O2·−) similar to the kcat of SOD enzymes. Most frequently studied are ortho isomers MnTE-2-PyP5+, MnTnHex-2-PyP5+, and MnTDE-2-ImP5+. The ability to disproportionate O2·− parallels their ability to remove the other major oxidizing species, peroxynitrite, ONOO−. The same structural feature that gives rise to the high kcat (O2·−) and kred (ONOO−), allows MnPs to strongly impact the activation of the redox-sensitive transcription factors, HIF-1α, NF-κB, AP-1, and SP-1, and therefore modify the excessive inflammatory and immune responses. Coupling with cellular reductants and other redox-active endogenous proteins seems to be involved in the actions of Mn porphyrins. While hydrophilic analogues, such as MnTE-2-PyP5+ and MnTDE-2-ImP5+ are potent in numerous animal models of diseases, the lipophilic analogues were developed to cross blood brain barrier and target central nervous system and critical cellular compartment, mitochondria. The modification of its structure, aimed to preserve the SOD-like potency and lipophilicity, and diminish the toxicity, has presently been pursued. The pulmonary radioprotection by MnTnHex-2-PyP5+ was the first efficacy study performed successfully with non

  9. Testicular hemorrhage, necrosis, and vasculopathy: likely manifestations of intermittent torsion that clinically mimic a neoplasm.

    PubMed

    Kao, Chia-Sui; Zhang, Chen; Ulbright, Thomas M

    2014-01-01

    parenchyma in all 30 cases. Clinical follow-up in 20 patients (4 to 131 mo, mean 38 mo) showed no evidence of recurrence in the contralateral testis or later development of systemic vasculitis. The histologic findings were compared with those in 11 orchiectomies resected for clinical acute torsion. All clinical acute torsion cases showed both parenchymal and fibrinoid vascular necrosis, and 10 had hemorrhage/hematoma; they lacked vasculitis, interstitial inflammation, and chronic vascular changes. Testicular vasculopathy, characterized by acute and chronic vascular injury, commonly occurs in testes with parenchymal hemorrhage and necrosis that clinically mimic a tumor. It shares the acute features of recent torsion but also has findings indicative of chronic injury. Testicular vasculopathy is most likely a result of chronic intermittent torsion that leads to localized hemorrhage/necrosis and should be distinguished from cases of systemic vasculitis given the significantly different clinical implications.

  10. A minimalist chemical model of matrix metalloproteinases--can small peptides mimic the more rigid metal binding sites of proteins?

    PubMed

    Árus, Dávid; Nagy, Nóra Veronika; Dancs, Ágnes; Jancsó, Attila; Berkecz, Róbert; Gajda, Tamás

    2013-09-01

    In order to mimic the active center of matrix metalloproteinases (MMPs), we synthesized a pentadecapeptide (Ac-KAHEFGHSLGLDHSK-NH2) corresponding to the catalytic zinc(II) binding site of human MMP-13. The multi-domain structural organization of MMPs fundamentally determines their metal binding affinity, catalytic activity and selectivity. Our potentiometric, UV-visible, CD, EPR, NMR, mass spectrometric and kinetic studies are aimed to explore the usefulness of such flexible peptides to mimic the more rigid metal binding sites of proteins, to examine the intrinsic metal binding properties of this naked sequence, as well as to contribute to the development of a minimalist, peptide-based chemical model of MMPs, including the catalytic properties. Since the multiimidazole environment is also characteristic for copper(II), and recently copper(II) containing variants of MMPs have been identified, we also studied the copper(II) complexes of the above peptide. Around pH 6-7 the peptide, similarly to MMPs, offers a {3Nim} coordination binding site for both zinc(II) and copper(II). In the case of copper(II), the formation of amide coordinated species at higher pH abolished the analogy with the copper(II) containing MMP variant. On the other hand, the zinc(II)-peptide system mimics some basic features of the MMP active sites: the main species around pH7 (ZnH2L) possesses a {3Nim,H2O} coordination environment, the deprotonation of the zinc-bound water takes place near the physiological pH, it forms relatively stable ternary complexes with hydroxamic acids, and the species ZnH2L(OH) and ZnH2L(OH)2 have notable hydrolytic activity between pH7 and 9.

  11. Simulation of carbohydrate-protein interactions: Computer-aided design of a second generation GM1 mimic

    NASA Astrophysics Data System (ADS)

    Bernardi, Anna; Galgano, Marta; Belvisi, Laura; Colombo, Giorgio

    2001-02-01

    The oligosaccharide of ganglioside GM1 [Gal β1-3GalNAc β1-4(NeuAc α2-3)Gal β1-4Glc β1-1Cer] is the cellular target of two bacterial enterotoxins: the cholera toxin (CT) and the heat-labile toxin of E.coli (LT). We recently reported that the pseudosaccharide 2[Gal β1-3GalNAc β1-4(NeuAc α2-3)DCCHD] is a high-affinity ligand for CT, and thus a functional mimic of GM1 (Bernardi, A., Checchia, A., Brocca, P., Sonnino, S. and Zuccotto, F., J. Am. Chem. Soc., 121 (1999) 2032-2036). In this paper we describe the design of a second-generation mimic, formally obtained from 2 by inverting the configuration of a single stereocenter, thus transforming a N-acetyl galactosamine into a N-acetyl glucosamin