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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. GENOMIC APPROACHES FOR CROSS-SPECIES EXTRAPOLATION IN TOXICOLOGY

    EPA Science Inventory

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

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

    PubMed

    Sun, Yong-Hua; Zhu, Zuo-Yan

    2014-06-01

    It is widely accepted that the crosstalk between naive nucleus and maternal factors deposited in the egg cytoplasm before zygotic genome activation is crucial for early development. This crosstalk may also exert some influence on later development. It is interesting to clarify the relative roles of the zygotic genome and the cytoplasmic factors in development. Cross-species nuclear transfer (NT) between two distantly related species provides a unique system to study the relative role and crosstalk between egg cytoplasm and zygotic nucleus in development. In this review, we will summarize the recent progress of cross-species NT, with emphasis on the cross-species NT in fish and the influence of cytoplasmic factors on development. Finally, we conclude that the developmental process and its evolution should be interpreted in a systemic way, rather than in a way that solely focuses on the role of the nuclear genome. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  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. 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...

  10. 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...

  11. 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...

  12. Molecular Understanding of Aβ-hIAPP Cross-Seeding Assemblies on Lipid Membranes.

    PubMed

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

    2017-03-15

    Amyloid-β (Aβ) and human islet polypeptide (hIAPP) are the causative agents responsible for Alzheimer's disease (AD) and type II diabetes (T2D), respectively. While numerous studies have reported the cross-seeding behavior of Aβ and hIAPP in solution, little effort has been made to examine the cross-seeding of Aβ and hIAPP in the presence of cell membranes, which is more biologically relevant to the pathological link between AD and T2D. In this work, we computationally study the cross-seeding and adsorption behaviors of Aβ and hIAPP on zwitterionic POPC and anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG) mixed bilayers using all-atom molecular dynamics (MD) simulations, particularly aiming to the effects of the initial orientation of the Aβ-hIAPP assembly and the lipid composition of cell membranes on mutual structural and interaction changes in both Aβ-hIAPP assembly and lipid bilayers at the atomic level. Aβ-hIAPP cross-seeding assembly always preferred to adopt a specific orientation and interface to associate with both lipid bilayers strongly via the N-terminal strands of Aβ. Such membrane-bound orientation explains experimental observation that hybrid Aβ-hIAPP fibrils on cell membranes showed similar morphologies to pure hIAPP fibrils. Moreover, Aβ-hIAPP assembly, regardless of its initial orientations, interacted more strongly with POPC/POPG bilayer than POPC bilayer, indicating that electrostatic interactions are the major forces governing peptide-lipid interactions. Strong electrostatic interactions were also attributed to the formation of Ca(2+) bridges connecting both negatively charged Glu of Aβ and PO4 head groups of lipids, which facilitate the association of Aβ-hIAPP with the POPC/POPG bilayer. It was also found that the strong peptide-lipid binding reduced lipid fluidity. Both facts imply that Aβ-hIAPP assembly may induce cell damage by altering calcium

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

    PubMed Central

    Li, Fang

    2013-01-01

    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: 10 years of research on highly pathogenic human coronaviruses.” PMID:23994189

  14. 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.

  15. 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". Copyright © 2013 Elsevier B.V. All rights reserved.

  16. 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

  17. 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

  18. Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

    PubMed

    Moreno-Gonzalez, I; Edwards Iii, G; Salvadores, N; Shahnawaz, M; Diaz-Espinoza, R; Soto, C

    2017-09-01

    Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (Aβ) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein. Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology by cross-seeding Aβ, providing a molecular explanation for the link between these diseases. Here, we examined how misfolded IAPP affects Aβ aggregation and AD pathology in vitro and in vivo. We observed that addition of IAPP seeds accelerates Aβ aggregation in vitro in a seeding-like manner and the resulting fibrils are composed of both peptides. Transgenic animals expressing both human proteins exhibited exacerbated AD-like pathology compared with AD transgenic mice or AD transgenic animals with type 1 diabetes (T1D). Remarkably, IAPP colocalized with amyloid plaques in brain parenchymal deposits, suggesting that these peptides may directly interact and aggravate the disease. Furthermore, inoculation of pancreatic IAPP aggregates into the brains of AD transgenic mice resulted in more severe AD pathology and significantly greater memory impairments than untreated animals. These data provide a proof-of-concept for a new disease mechanism involving the interaction of misfolded proteins through cross-seeding events which may contribute to accelerate or exacerbate disease pathogenesis. Our findings could shed light on understanding the linkage between T2D and AD, two of the most prevalent protein misfolding disorders.

  19. 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

  20. FIV cross-species transmission: an evolutionary prospective

    PubMed Central

    Troyer, Jennifer L.; VandeWoude, Sue; Pecon-Slattery, Jill; McIntosh, Carl; Franklin, Sam; Antunes, Agostinho; Johnson, Warren; O'Brien, Stephen J.

    2008-01-01

    Feline and primate immunodeficiency viruses (FIVs, SIVs, and HIV) are transmitted via direct contact (e.g. fighting, sexual contact, and mother-offspring transmission). This dynamic likely poses a behavioral barrier to cross-species transmission in the wild. Recently, several host intracellular anti-viral proteins that contribute to species-specificity of primate lentiviruses have been identified revealing adaptive mechanisms that further limit spread of lentiviruses between species. Consistent with these inter-species transmission barriers, phylogenetic evidence supports the prediction that FIV transmission is an exceedingly rare event between free-ranging cat species, though it has occurred occasionally in captive settings. Recently we documented that puma and bobcats in Southern California share an FIV strain, providing an opportunity to evaluate evolution of both viral strains and host intracellular restriction proteins. These studies are facilitated by the availability of the 2X cat genome sequence annotation. In addition, concurrent viral and host genetic analyses have been used to track patterns of migration of the host species and barriers to transmission of the virus within the African lion. These studies illustrate the utility of FIV as a model to discover the variables necessary for establishment and control of lentiviral infections in new species. PMID:18299153

  1. 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.

  2. 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.

  3. 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

  4. Cross-Species Functionality of Pararetroviral Elements Driving Ribosome Shunting

    PubMed Central

    Pooggin, Mikhail M.; Fütterer, Johannes; Hohn, Thomas

    2008-01-01

    Background Cauliflower mosaic virus (CaMV) and Rice tungro bacilliform virus (RTBV) belong to distinct genera of pararetroviruses infecting dicot and monocot plants, respectively. In both viruses, polycistronic translation of pregenomic (pg) RNA is initiated by shunting ribosomes that bypass a large region of the pgRNA leader with several short (s)ORFs and a stable stem-loop structure. The shunt requires translation of a 5′-proximal sORF terminating near the stem. In CaMV, mutations knocking out this sORF nearly abolish shunting and virus viability. Methodology/Principal Findings Here we show that two distant regions of the CaMV leader that form a minimal shunt configuration comprising the sORF, a bottom part of the stem, and a shunt landing sequence can be replaced by heterologous sequences that form a structurally similar configuration in RTBV without any dramatic effect on shunt-mediated translation and CaMV infectivity. The CaMV-RTBV chimeric leader sequence was largely stable over five viral passages in turnip plants: a few alterations that did eventually occur in the virus progenies are indicative of fine tuning of the chimeric sequence during adaptation to a new host. Conclusions/Significance Our findings demonstrate cross-species functionality of pararetroviral cis-elements driving ribosome shunting and evolutionary conservation of the shunt mechanism. We are grateful to Matthias Müller and Sandra Pauli for technical assistance. This work was initiated at Friedrich Miescher Institute (Basel, Switzerland). We thank Prof. Thomas Boller for hosting the group at the Institute of Botany. PMID:18286203

  5. Asparagine and glutamine ladders promote cross-species prion conversion.

    PubMed

    Kurt, Timothy D; Aguilar-Calvo, Patricia; Jiang, Lin; Rodriguez, José A; Alderson, Nazilla; Eisenberg, David S; Sigurdson, Christina J

    2017-09-20

    Prion transmission between species is governed in part by primary sequence similarity between the infectious prion aggregate, PrP(Sc), and the cellular prion protein of the host, PrP(C) A puzzling feature of prion formation is that certain PrP(C) sequences, such as that of bank vole, can be converted by a remarkably broad array of different mammalian prions, whereas others, such as rabbit, show robust resistance to cross-species prion conversion. To examine the structural determinants that confer susceptibility or resistance to prion conversion, we systematically tested over 40 PrP(C) variants of susceptible and resistant PrP(C) sequences in a prion conversion assay. Five key residue positions markedly impacted prion conversion, four of which were in steric zipper segments where side chains from amino acids tightly interdigitate in a dry interface. Strikingly, all 5 residue substitutions modulating prion conversion involved the gain or loss of an asparagine or glutamine residue. For 2 of 4 positions, N and Q residues were not interchangeable, revealing a strict requirement for either an N or Q residue. Bank voles have a high number of N and Q residues and a high N:Q ratio. These findings suggest that a high number of N and Q residues at specific positions may stabilize β-sheets and lower the energy barrier for crossspecies prion transmission, potentially due to hydrogen bond networks from side chain amides forming extended N/Q ladders. These data also suggest that multiple PrP(C) segments containing N/Q residues may act in concert along a replicative interface to promote prion conversion. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  6. Cross-species queries of large gene expression databases

    PubMed Central

    Le, Hai-Son; Oltvai, Zoltán N.; Bar-Joseph, Ziv

    2010-01-01

    Motivation: Expression databases, including the Gene Expression Omnibus and ArrayExpress, have experienced significant growth over the past decade and now hold hundreds of thousands of arrays from multiple species. Since most drugs are initially tested on model organisms, the ability to compare expression experiments across species may help identify pathways that are activated in a similar way in humans and other organisms. However, while several methods exist for finding co-expressed genes in the same species as a query gene, looking at co-expression of homologs or arbitrary genes in other species is challenging. Unlike sequence, which is static, expression is dynamic and changes between tissues, conditions and time. Thus, to carry out cross-species analysis using these databases, we need methods that can match experiments in one species with experiments in another species. Results: To facilitate queries in large databases, we developed a new method for comparing expression experiments from different species. We define a distance metric between the ranking of orthologous genes in the two species. We show how to solve an optimization problem for learning the parameters of this function using a training dataset of known similar expression experiments pairs. The function we learn outperforms previous methods and simpler rank comparison methods that have been used in the past for single species analysis. We used our method to compare millions of array pairs from mouse and human expression experiments. The resulting matches can be used to find functionally related genes, to hypothesize about biological response mechanisms and to highlight conditions and diseases that are activating similar pathways in both species. Availability: Supporting methods, results and a Matlab implementation are available from http://sb.cs.cmu.edu/ExpQ/ Contact: zivbj@cs.cmu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20702396

  7. Crossing species' range borders: interspecies gene exchange mediated by hybridogenesis

    PubMed Central

    Schmeller, Dirk S; Seitz, Alfred; Crivelli, Alain; Veith, Michael

    2005-01-01

    The distribution of species is limited by their ability to adapt to local environments. For adaptation by selection, genetic variability is crucial. As founder effects reduce genetic variability, extension of species' range borders is usually slow due to the reduced probability of successful colonization. However, the range limit might be extended by incorporating locally adapted genes. In western Palaearctic waterfrogs, interspecies hybrids show hemiclonal gametogenesis, are fertile and reproductively mimic one parental species. Genetic analysis, using allozyme loci, shows that they mediate gene exchange between the two parental species. Selection analysis provides evidence for local adaptation of single locus genotypes. This suggests that hybridogenesis presents a process which increases the number of neoform parental genotypes, exposing these to selection, and thereby revealing locally adapted genotypes which are essential for species range expansion. PMID:16048778

  8. 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.

  9. Bacterial curli protein promotes the conversion of PAP248-286 into the amyloid SEVI: cross-seeding of dissimilar amyloid sequences

    PubMed Central

    Hartman, Kevin; Brender, Jeffrey R.; Monde, Kazuaki; Ono, Akira; Evans, Margery L.; Popovych, Nataliya; Chapman, Matthew R.

    2013-01-01

    Fragments of prostatic acid phosphatase (PAP248-286) in human semen dramatically increase HIV infection efficiency by increasing virus adhesion to target cells. PAP248-286 only enhances HIV infection in the form of amyloid aggregates termed SEVI (Semen Enhancer of Viral Infection), however monomeric PAP248-286 aggregates very slowly in isolation. It has therefore been suggested that SEVI fiber formation in vivo may be promoted by exogenous factors. We show here that a bacterially-produced extracellular amyloid (curli or Csg) acts as a catalytic agent for SEVI formation from PAP248-286 at low concentrations in vitro, producing fibers that retain the ability to enhance HIV (Human Immunodeficiency Virus) infection. Kinetic analysis of the cross-seeding effect shows an unusual pattern. Cross-seeding PAP248-286 with curli only moderately affects the nucleation rate while significantly enhancing the growth of fibers from existing nuclei. This pattern is in contrast to most previous observations of cross-seeding, which show cross-seeding partially bypasses the nucleation step but has little effect on fiber elongation. Seeding other amyloidogenic proteins (IAPP (islet amyloid polypeptide) and Aβ1−40) with curli showed varied results. Curli cross-seeding decreased the lag-time of IAPP amyloid formation but strongly inhibited IAPP elongation. Curli cross-seeding exerted a complicated concentration dependent effect on Aβ1−40 fibrillogenesis kinetics. Combined, these results suggest that the interaction of amyloidogenic proteins with preformed fibers of a different type can take a variety of forms and is not limited to epitaxial nucleation between proteins of similar sequence. The ability of curli fibers to interact with proteins of dissimilar sequences suggests cross-seeding may be a more general phenomenon than previously supposed. PMID:23638387

  10. 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

  11. 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

  12. Host phylogeny constrains cross-species emergence and establishment of rabies virus in bats.

    PubMed

    Streicker, Daniel G; Turmelle, Amy S; Vonhof, Maarten J; Kuzmin, Ivan V; McCracken, Gary F; Rupprecht, Charles E

    2010-08-06

    For RNA viruses, rapid viral evolution and the biological similarity of closely related host species have been proposed as key determinants of the occurrence and long-term outcome of cross-species transmission. Using a data set of hundreds of rabies viruses sampled from 23 North American bat species, we present a general framework to quantify per capita rates of cross-species transmission and reconstruct historical patterns of viral establishment in new host species using molecular sequence data. These estimates demonstrate diminishing frequencies of both cross-species transmission and host shifts with increasing phylogenetic distance between bat species. Evolutionary constraints on viral host range indicate that host species barriers may trump the intrinsic mutability of RNA viruses in determining the fate of emerging host-virus interactions.

  13. CROPPER: a metagene creator resource for cross-platform and cross-species compendium studies

    PubMed Central

    Paananen, Jussi; Storvik, Markus; Wong, Garry

    2006-01-01

    Background Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. Results We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. Conclusion CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies. PMID:16995941

  14. 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

  15. 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. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24829449

  17. 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-...

  18. 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-...

  19. Identification of Simple Sequence Repeat Biomarkers through Cross-Species Comparison in a Tag Cloud Representation

    PubMed Central

    2014-01-01

    Simple sequence repeats (SSRs) are not only applied as genetic markers in evolutionary studies but they also play an important role in gene regulatory activities. Efficient identification of conserved and exclusive SSRs through cross-species comparison is helpful for understanding the evolutionary mechanisms and associations between specific gene groups and SSR motifs. In this paper, we developed an online cross-species comparative system and integrated it with a tag cloud visualization technique for identifying potential SSR biomarkers within fourteen frequently used model species. Ultraconserved or exclusive SSRs among cross-species orthologous genes could be effectively retrieved and displayed through a friendly interface design. Four different types of testing cases were applied to demonstrate and verify the retrieved SSR biomarker candidates. Through statistical analysis and enhanced tag cloud representation on defined functional related genes and cross-species clusters, the proposed system can correctly represent the patterns, loci, colors, and sizes of identified SSRs in accordance with gene functions, pattern qualities, and conserved characteristics among species. PMID:24800246

  20. 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

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

    PubMed Central

    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

    2016-01-01

    ABSTRACT 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

  2. 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

  3. "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.

  4. Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis.

    PubMed

    Park, Eun Sung; Kim, Sun Jin; Kim, Seung Wook; Yoon, Se-Lyun; Leem, Sun-Hee; Kim, Sang-Bae; Kim, Soo Mi; Park, Yun-Yong; Cheong, Jae-Ho; Woo, Hyun Goo; Mills, Gordon B; Fidler, Isaiah J; Lee, Ju-Seog

    2011-10-18

    Although the importance of the cellular microenvironment (soil) during invasion and metastasis of cancer cells (seed) has been well-recognized, technical challenges have limited the ability to assess the influence of the microenvironment on cancer cells at the molecular level. Here, we show that an experimental strategy, competitive cross-species hybridization of microarray experiments, can characterize the influence of different microenvironments on cancer cells by independently extracting gene expression data of cancer and host cells when human cancer cells were xenografted into different organ sites of immunocompromised mice. Surprisingly, the analysis of gene expression data showed that the brain microenvironment induces complete reprogramming of metastasized cancer cells, resulting in a gain of neuronal cell characteristics and mimicking neurogenesis during development. We also show that epigenetic changes coincide with transcriptional reprogramming in cancer cells. These observations provide proof of principle for competitive cross-species hybridization of microarray experiments to characterize the effect of the microenvironment on tumor cell behavior.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

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

    PubMed Central

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

    2011-01-01

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

  12. 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.

  13. 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

  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. XGSA: A statistical method for cross-species gene set analysis.

    PubMed

    Djordjevic, Djordje; Kusumi, Kenro; Ho, Joshua W K

    2016-09-01

    Gene set analysis is a powerful tool for determining whether an experimentally derived set of genes is statistically significantly enriched for genes in other pre-defined gene sets, such as known pathways, gene ontology terms, or other experimentally derived gene sets. Current gene set analysis methods do not facilitate comparing gene sets across different organisms as they do not explicitly deal with homology mapping between species. There lacks a systematic investigation about the effect of complex gene homology on cross-species gene set analysis. In this study, we show that not accounting for the complex homology structure when comparing gene sets in two species can lead to false positive discoveries, especially when comparing gene sets that have complex gene homology relationships. To overcome this bias, we propose a straightforward statistical approach, called XGSA, that explicitly takes the cross-species homology mapping into consideration when doing gene set analysis. Simulation experiments confirm that XGSA can avoid false positive discoveries, while maintaining good statistical power compared to other ad hoc approaches for cross-species gene set analysis. We further demonstrate the effectiveness of XGSA with two real-life case studies that aim to discover conserved or species-specific molecular pathways involved in social challenge and vertebrate appendage regeneration. The R source code for XGSA is available under a GNU General Public License at http://github.com/VCCRI/XGSA CONTACT: jho@victorchang.edu.au. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed

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

    2011-05-01

    Comparative studies of social responsiveness, an ability that is impaired in autism spectrum disorders, can inform our understanding of both autism and the cognitive architecture of social behavior. Because there is no existing quantitative measure of social responsiveness in chimpanzees, we generated a quantitative, cross-species (human-chimpanzee) social responsiveness measure. We translated the Social Responsiveness Scale (SRS), an instrument that quantifies human social responsiveness, into an analogous instrument for chimpanzees. We then retranslated this "Chimpanzee SRS" into a human "Cross-Species SRS" (XSRS). We evaluated three groups of chimpanzees (n = 29) with the Chimpanzee SRS and typical and human children with autism spectrum disorder (ASD; n = 20) with the XSRS. The Chimpanzee SRS demonstrated strong interrater reliability at the three sites (ranges for individual ICCs: 0.534 to 0.866; mean ICCs: 0.851 to 0.970). As has been observed in human beings, exploratory principal components analysis of Chimpanzee SRS scores supports a single factor underlying chimpanzee social responsiveness. Human subjects' XSRS scores were fully concordant with their SRS scores (r = 0.976, p = .001) and distinguished appropriately between typical and ASD subjects. One chimpanzee known for inappropriate social behavior displayed a significantly higher score than all other chimpanzees at its site, demonstrating the scale's ability to detect impaired social responsiveness in chimpanzees. Our initial cross-species social responsiveness scale proved reliable and discriminated differences in social responsiveness across (in a relative sense) and within (in a more objectively quantifiable manner) human beings and chimpanzees. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2013-01-01

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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Human adenovirus type 12: crossing species barriers to immortalize the viral genome.

    PubMed

    Doerfler, Walter

    2007-01-01

    When viruses cross species barriers, they often change their biological and pathogenetic properties. In the author's laboratory the nonproductive interaction of Syrian hamster cells with human adenovirus type 12 (Ad12) has been studied. Ad12 induces undifferentiated tumors in newborn hamsters (Mesocricetus auratus) at high frequency. Ad12 inefficiently enters hamster (BHK21) cells, and only small amounts of viral DNA reach the nucleus. Viral DNA replication and late transcription are blocked. In Ad12-induced tumor cells, multiple copies of viral DNA are chromosomally integrated. The integrated viral DNA becomes de novo methylated. Cellular DNA methylation and transcription patterns in Ad12-transformed cells and in Ad12-induced tumor cells are altered. These changes may be related to the oncogenic potential of Ad12 in hamsters. In this chapter, concepts and techniques for the study of the Ad12-hamster cell system are summarized.

  10. 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

  11. 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.

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

    PubMed Central

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

    2016-01-01

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

  13. 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.

  14. Rhodopseudomonas palustris Regulons Detected by Cross-Species Analysis of Alphaproteobacterial Genomes

    PubMed Central

    Conlan, Sean; Lawrence, Charles; McCue, Lee Ann

    2005-01-01

    Rhodopseudomonas palustris, an α-proteobacterium, carries out three of the chemical reactions that support life on this planet: the conversion of sunlight to chemical-potential energy; the absorption of carbon dioxide, which it converts to cellular material; and the fixation of atmospheric nitrogen into ammonia. Insight into the transcription-regulatory network that coordinates these processes is fundamental to understanding the biology of this versatile bacterium. With this goal in mind, we predicted regulatory signals genomewide, using a two-step phylogenetic-footprinting and clustering process that we had developed previously. In the first step, 4,963 putative transcription factor binding sites, upstream of 2,044 genes and operons, were identified using cross-species Gibbs sampling. Bayesian motif clustering was then employed to group the cross-species motifs into regulons. We have identified 101 putative regulons in R. palustris, including 8 that are of particular interest: a photosynthetic regulon, a flagellar regulon, an organic hydroperoxide resistance regulon, the LexA regulon, and four regulons related to nitrogen metabolism (FixK2, NnrR, NtrC, and σ54). In some cases, clustering allowed us to assign functions to proteins that previously had been annotated with only putative functions; we have identified RPA0828 as the organic hydroperoxide resistance regulator and RPA1026 as a cell cycle methylase. In addition to predicting regulons, we identified a novel inverted repeat that likely forms a highly conserved stem-loop and that occurs downstream of over 100 genes. PMID:16269786

  15. 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.

  16. Identification, validation and cross-species transferability of novel Lavandula EST-SSRs.

    PubMed

    Adal, Ayelign M; Demissie, Zerihun A; Mahmoud, Soheil S

    2015-04-01

    We identified and characterized EST-SSRs with strong discrimination power against Lavandula angustifolia and Lavandula x intermedia . The markers also showed considerable cross-species transferability rate into six related Lavandula species. Lavenders (Lavandula) are important economical crops grown around the globe for essential oil production. In an attempt to develop genetic markers for these plants, we analyzed over 13,000 unigenes developed from L. angustifolia and L. x intermedia EST databases, and identified 3,459 simple sequence repeats (SSR), which were dominated by trinucleotides (41.2 %) and dinucleotides (31.45 %). Approximately, 19 % of the unigenes contained at least one SSR marker, over 60 % of which were localized in the UTRs. Only 252 EST-SSRs were 18 bp or longer from which 31 loci were validated, and 24 amplified discrete fragments with 85 % polymorphism in L. x intermedia and L. angustifolia. The average number of alleles in L. x intermedia and L. angustifolia were 3.42 and 3.71 per marker with average PIC values of 0.47 and 0.52, respectively. These values suggest a moderate to strong level of informativeness for the markers, with some loci producing unique fingerprints. The cross-species transferability rate of the markers ranges 50-100 % across eight species. The utility of these markers was assessed in eight Lavandula species and 15 L. angustifolia and L. x intermedia cultivars, and the dendrogram deduced from their similarity indexes successfully delineated the species into their respective sections and the cultivars into their respective species. These markers have potential for application in fingerprinting, diversity studies and marker-assisted breeding of Lavandula.

  17. 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

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

    PubMed

    Strickler, Allen G; Jeffery, William R

    2009-03-01

    Changes in gene expression were examined by microarray analysis during development of the eyed surface dwelling (surface fish) and blind cave-dwelling (cavefish) forms of the teleost Astyanax mexicanus De Filippi, 1853. The cross-species microarray used surface and cavefish RNA hybridized to a DNA chip prepared from a closely related species, the zebrafish Danio rerio Hamilton, 1822. We identified a total of 67 differentially expressed probe sets at three days post-fertilization: six upregulated and 61 downregulated in cavefish relative to surface fish. Many of these genes function either in eye development and/or maintenance, or in programmed cell death. The upregulated probe set showing the highest mean fold change was similar to the human ubiquitin specific protease 53 gene. The downregulated probe sets showing some of the highest fold changes corresponded to genes with roles in eye development, including those encoding gamma crystallins, the guanine nucleotide binding proteins Gnat1 and Gant2, a BarH-like homeodomain transcription factor, and rhodopsin. Downregulation of gamma-crystallin and rhodopsin was confirmed by in situ hybridization and immunostaining with specific antibodies. Additional downregulated genes encode molecules that inhibit or activate programmed cell death. The results suggest that cross-species microarray can be used for identifying differentially expressed genes in cavefish, that many of these genes might be involved in eye degeneration via apoptotic processes, and that more genes are downregulated than upregulated in cavefish, consistent with the predominance of morphological losses over gains during regressive evolution. © 2009 ISZS, Blackwell Publishing and IOZ/CAS.

  19. 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.

  20. 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

  1. 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

  2. Batesian mimics influence mimicry ring evolution.

    PubMed Central

    Franks, Daniel W.; Noble, Jason

    2004-01-01

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

  3. 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.

  4. 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.

  5. Castleman disease: the great mimic.

    PubMed

    Bonekamp, David; Horton, Karen M; Hruban, Ralph H; Fishman, Elliot K

    2011-10-01

    Castleman disease is a nonclonal lymphoproliferative disorder and one of the more common causes of nonneoplastic lymphadenopathy. Because of its diverse manifestations and ability to affect any body region, Castleman disease is a great mimic of both benign and malignant abnormalities in the neck, chest, abdomen, and pelvis. Castleman disease most commonly manifests as unicentric disease (unicentric Castleman disease) with a hyperenhancing lymph nodal mass and should be considered in the differential diagnosis of lymphoma, metastatic adenopathy, and infectious and/or inflammatory diseases that result in adenopathy. Castleman disease includes a spectrum of pathologic variants, including the classic hyaline vascular type, the less common plasma cell variant of Castleman disease, and the more recently described multicentric Castleman disease and Castleman disease associated with human herpesvirus 8. Castleman disease has been associated with the human immunodeficiency virus, lymphoma, POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, paraneoplastic pemphigus, and plasma cell dyscrasias. Aggressive forms of Castleman disease with systemic manifestations may occur. Unicentric hyaline vascular Castleman disease is often curable with surgery; however, multicentric Castleman disease may require steroid treatment, chemotherapy, antiviral medication, or the use of antiproliferative regimens because a surgical procedure cannot be curative in this setting. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.316115502/-/DC1. © RSNA, 2011.

  6. 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.

  7. A Method to Detect Differential Gene Expression in Cross-Species Hybridization Experiments at Gene and Probe Level

    PubMed Central

    Chen, Ying; Wu, Rebekah; Felton, James; Rocke, David M.; Chakicherla, Anu

    2010-01-01

    Motivation Whole genome microarrays are increasingly becoming the method of choice to study responses in model organisms to disease, stressors or other stimuli. However, whole genome sequences are available for only some model organisms, and there are still many species whose genome sequences are not yet available. Cross-species studies, where arrays developed for one species are used to study gene expression in a closely related species, have been used to address this gap, with some promising results. Current analytical methods have included filtration of some probes or genes that showed low hybridization activities. But consensus filtration schemes are still not available. Results A novel masking procedure is proposed based on currently available target species sequences to filter out probes and study a cross-species data set using this masking procedure and gene-set analysis. Gene-set analysis evaluates the association of some priori defined gene groups with a phenotype of interest. Two methods, Gene Set Enrichment Analysis (GSEA) and Test of Test Statistics (ToTS) were investigated. The results showed that masking procedure together with ToTS method worked well in our data set. The results from an alternative way to study cross-species hybridization experiments without masking are also presented. We hypothesize that the multi-probes structure of Affymetrix microarrays makes it possible to aggregate the effects of both well-hybridized and poorly-hybridized probes to study a group of genes. The principles of gene-set analysis were applied to the probe-level data instead of gene-level data. The results showed that ToTS can give valuable information and thus can be used as a powerful technique for analyzing cross-species hybridization experiments. Availability Software in the form of R code is available at http://anson.ucdavis.edu/~ychen/cross-species.html Supplementary Data Supplementary data are available at http://anson.ucdavis.edu/~ychen/cross-species.html PMID

  8. 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

  9. 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

  10. 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.

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

    PubMed

    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

    2016-01-04

    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. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. 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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. 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

  16. Characterization of microsatellites in Bambusa arundinacea and cross species amplification in other bamboos.

    PubMed

    Nayak, Sumitra; Rout, Gyana Ranjan

    2005-01-01

    Microsatellites, tandem repeats of short nucleotide (1-6 bp) sequences, are the DNA marker of choice because of their highly polymorphic, ubiquitous distribution within genome, ease of genotyping through polymerase chain reaction (PCR), selectively neutral, co-dominant and multi allelic nature. Six microsatellites, three polymorphic and three monomorphic, have been characterized for the first time in a bamboo species, Bambusa arudinacea belonging to the family Poaceae. The number of alleles per locus ranges form 2 to 13. Allelic diversity ranges from 0.041 to 0.870. Polymorphic information content (PIC) values for two loci were > 0.3, an indicator of polymorphic allele. Cross species amplification has been tested in other 18 bamboo species. Monomorphic simple sequence repeats (SSRs) have been found to be cross amplified in most of the tested species while polymorphic ones in only three to four species. The utility of the SSR loci in genetic diversity study of B. arundinacea and other cross amplified bamboo species have been discussed.

  17. Cross-species 3D virtual reality toolbox for visual and cognitive experiments.

    PubMed

    Doucet, Guillaume; Gulli, Roberto A; Martinez-Trujillo, Julio C

    2016-06-15

    Although simplified visual stimuli, such as dots or gratings presented on homogeneous backgrounds, provide strict control over the stimulus parameters during visual experiments, they fail to approximate visual stimulation in natural conditions. Adoption of virtual reality (VR) in neuroscience research has been proposed to circumvent this problem, by combining strict control of experimental variables and behavioral monitoring within complex and realistic environments. We have created a VR toolbox that maximizes experimental flexibility while minimizing implementation costs. A free VR engine (Unreal 3) has been customized to interface with any control software via text commands, allowing seamless introduction into pre-existing laboratory data acquisition frameworks. Furthermore, control functions are provided for the two most common programming languages used in visual neuroscience: Matlab and Python. The toolbox offers milliseconds time resolution necessary for electrophysiological recordings and is flexible enough to support cross-species usage across a wide range of paradigms. Unlike previously proposed VR solutions whose implementation is complex and time-consuming, our toolbox requires minimal customization or technical expertise to interface with pre-existing data acquisition frameworks as it relies on already familiar programming environments. Moreover, as it is compatible with a variety of display and input devices, identical VR testing paradigms can be used across species, from rodents to humans. This toolbox facilitates the addition of VR capabilities to any laboratory without perturbing pre-existing data acquisition frameworks, or requiring any major hardware changes. Copyright © 2016 Z. All rights reserved.

  18. 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.

  19. 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.

  20. 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.

  1. Leuconostoc mesenteroides and Leuconostoc pseudomesenteroides bacteriophages: Genomics and cross-species host ranges.

    PubMed

    Pujato, Silvina A; Guglielmotti, Daniela M; Martínez-García, Manuel; Quiberoni, Andrea; Mojica, Francisco J M

    2017-09-18

    Unveiling virus-host interactions are relevant for understanding the biology and evolution of microbes globally, but in particular, it has also a paramount impact on the manufacture of fermented dairy products. In this study, we aim at characterizing phages infecting the commonly used heterofermentative Leuconostoc spp. on the basis of host range patterns and genome analysis. Host range of six Leuconostoc phages was investigated using three methods (efficiency of plaquing, spot and turbidity tests) against Ln. mesenteroides and Ln. pseudomesenteroides strains. Complete genome sequencing from four out of the six studied Leuconostoc phages were obtained in this work, while the remaining two have been sequenced previously. According to our results, cross-species host specificity was demonstrated, as all phages tested were capable of infecting both Ln. pseudomesenteroides and Ln. mesenteroides strains, although with different efficiency of plaquing (EOP). Phage adsorption rates and ability of low-EOP host strains to propagate phages by crossing the Leuconostoc species' barrier confirm results. At the genome level, phages CHA, CHB, Ln-7, Ln-8 and Ln-9 revealed high similarity with previously characterized phages infecting mostly Ln. mesenteroides strains, while phage LDG was highly similar to phages infecting Ln. pseudomesenteroides. Additionally, correlation between receptor binding protein (RBP) and host range patterns allowed us to unveil a finer clustering of Leuconostoc phages studied into four groups. This is the first report of overlapped phage host ranges between Leuconostoc species. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  5. 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.

  6. 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.

  7. Role of Multiple Hosts in the Cross-Species Transmission and Emergence of a Pandemic Parvovirus

    PubMed Central

    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.

    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. PMID:22072763

  8. 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.

  9. Cross-Species Transmission in the Speciation of the Currently Known Murinae-Associated Hantaviruses

    PubMed Central

    Lin, Xian-Dan; Wang, Wen; Guo, Wen-Ping; Zhang, Xiao-He; Xing, Jian-Guang; Chen, Sheng-Ze; Li, Ming-Hui; Chen, Yi; Xu, Jianguo; Plyusnin, Alexander

    2012-01-01

    To gain more insight into the phylogeny of Dabieshan virus (DBSV), carried by Niviventer confucianus and other Murinae-associated hantaviruses, genome sequences of novel variants of DBSV were recovered from Niviventer rats trapped in the mountainous areas of Wenzhou, China. Genetic analyses show that all known genetic variants of DBSV, including the ones identified in this study, are distinct from other Murinae-associated hantaviruses. DBSV variants show geographic clustering and high intraspecies diversity. The data suggest that DBSV is a distinct species in the genus Hantavirus. Interestingly, DBSV shows the highest sequence identity to Hantaan virus (HTNV), with a >7% difference in the sequences of the N, GPC, and L proteins, while N. confucianus is more closely related to Rattus norvegicus (the host of Seoul virus [SEOV]) than to Apodemus agrarius (the host of HTNV and Saaremaa virus [SAAV]). Further genetic analyses of all known Murinae-associated hantaviruses (both established and tentative species) show that many of them, including DBSV, may have originated from host switching. The estimation of evolutionary rates and divergence time supports the role of cross-species transmission in the evolution of Murinae-associated hantaviruses. The detection of positive selection suggests that genetic drift may contribute to the speciation of Murinae-associated hantaviruses and that adaptation has a role as well. PMID:22855492

  10. Cross-species assessments of Motor and Exploratory Behavior related to Bipolar Disorder

    PubMed Central

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

    2010-01-01

    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. PMID:20398694

  11. Molecular signatures of longevity: Insights from cross-species comparative studies.

    PubMed

    Ma, Siming; Gladyshev, Vadim N

    2017-10-01

    Much of the current research on longevity focuses on the aging process within a single species. Several molecular players (e.g. IGF1 and MTOR), pharmacological compounds (e.g. rapamycin and metformin), and dietary approaches (e.g. calorie restriction and methionine restriction) have been shown to be important in regulating and modestly extending lifespan in model organisms. On the other hand, natural lifespan varies much more significantly across species. Within mammals alone, maximum lifespan differs more than 100 fold, but the underlying regulatory mechanisms remain poorly understood. Recent comparative studies are beginning to shed light on the molecular signatures associated with exceptional longevity. These include genome sequencing of microbats, naked mole rat, blind mole rat, bowhead whale and African turquoise killifish, and comparative analyses of gene expression, metabolites, lipids and ions across multiple mammalian species. Together, they point towards several putative strategies for lifespan regulation and cancer resistance, as well as the pathways and metabolites associated with longevity variation. In particular, longevity may be achieved by both lineage-specific adaptations and common mechanisms that apply across the species. Comparing the resulting cross-species molecular signatures with the within-species lifespan extension strategies will improve our understanding of mechanisms of longevity control and provide a starting point for novel and effective interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Cross-species microarray hybridization to identify developmentally regulated genes in the filamentous fungus Sordaria macrospora.

    PubMed

    Nowrousian, Minou; Ringelberg, Carol; Dunlap, Jay C; Loros, Jennifer J; Kück, Ulrich

    2005-04-01

    The filamentous fungus Sordaria macrospora forms complex three-dimensional fruiting bodies that protect the developing ascospores and ensure their proper discharge. Several regulatory genes essential for fruiting body development were previously isolated by complementation of the sterile mutants pro1, pro11 and pro22. To establish the genetic relationships between these genes and to identify downstream targets, we have conducted cross-species microarray hybridizations using cDNA arrays derived from the closely related fungus Neurospora crassa and RNA probes prepared from wild-type S. macrospora and the three developmental mutants. Of the 1,420 genes which gave a signal with the probes from all the strains used, 172 (12%) were regulated differently in at least one of the three mutants compared to the wild type, and 17 (1.2%) were regulated differently in all three mutant strains. Microarray data were verified by Northern analysis or quantitative real time PCR. Among the genes that are up- or down-regulated in the mutant strains are genes encoding the pheromone precursors, enzymes involved in melanin biosynthesis and a lectin-like protein. Analysis of gene expression in double mutants revealed a complex network of interaction between the pro gene products.

  13. Cross-species association of quail invariant chain with chicken and mouse MHC II molecules.

    PubMed

    Chen, Fangfang; Wu, Chao; Pan, Ling; Xu, Fazhi; Liu, Xuelan; Yu, Weiyi

    2013-05-01

    There are different degrees of similarity among vertebrate invariant chains (Ii). The aim of this study was to determine the relationship between quail and other vertebrate Ii MHC class II molecules. The two quail Ii isoforms (qIi-1, qIi-2) were cloned by RACE, and qRT-PCR analysis of different organs showed that their expression levels were positively correlated with MHC II gene (B-LB) transcription levels. Confocal microscopy indicated that quail full-length Ii co-localized with MHC II of quail, chicken or mouse in 293FT cells co-transfected with both genes. Immunoprecipitation and western blotting further indicated that these aggregates corresponded to polymers of Ii and MHC class II molecules. This cross-species molecular association of quail Ii with chicken and mouse MHC II suggests that Ii molecules have a high structural and functional similarity and may thereby be used as potential immune carriers across species. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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

  16. 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.

  17. 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.

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

    PubMed

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

    2015-04-01

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

  19. A Method to Detect Differential Gene expression in Cross-Species Hybridization Experiments at Gene and Probe Level

    PubMed Central

    Chen, Ying; Wu, Rebekah; Felton, James; Rocke, David M.; Chakicherla, Anu

    2010-01-01

    Motivation Whole genome microarrays are increasingly becoming the method of choice to study responses in model organisms to disease, stressors or other stimuli. However, whole genome sequences are available for only some model organisms, and there are still many species whose genome sequences are not yet available. Cross-species studies, where arrays developed for one species are used to study gene expression in a closely related species, have been used to address this gap, with some promising results. Current analytical methods have included filtration of some probes or genes that showed low hybridization activities. But consensus filtration schemes are still not available. Results A novel masking procedure is proposed based on currently available target species sequences to filter out probes and study a cross-species data set using this masking procedure and gene-set analysis. Gene-set analysis evaluates the association of some priori defined gene groups with a phenotype of interest. Two methods, Gene Set Enrichment Analysis (GSEA) and Test of Test Statistics (ToTS) were investigated. The results showed that masking procedure together with ToTS method worked well in our data set. The results from an alternative way to study cross-species hybridization experiments without masking are also presented. We hypothesize that the multi-probes structure of Affymetrix microarrays makes it possible to aggregate the effects of both well-hybridized and poorly-hybridized probes to study a group of genes. The principles of gene-set analysis were applied to the probe-level data instead of gene-level data. The results showed that ToTS can give valuable information and thus can be used as a powerful technique for analyzing cross-species hybridization experiments. Availability Software in the form of R code is available at http://anson.ucdavis.edu/~ychen/cross-species.html PMID:20798791

  20. Large-scale cross-species chemogenomic platform proposes a new drug discovery strategy of veterinary drug from herbal medicines.

    PubMed

    Huang, Chao; Yang, Yang; Chen, Xuetong; Wang, Chao; Li, Yan; Zheng, Chunli; Wang, Yonghua

    2017-01-01

    Veterinary Herbal Medicine (VHM) is a comprehensive, current, and informative discipline on the utilization of herbs in veterinary practice. Driven by chemistry but progressively directed by pharmacology and the clinical sciences, drug research has contributed more to address the needs for innovative veterinary medicine for curing animal diseases. However, research into veterinary medicine of vegetal origin in the pharmaceutical industry has reduced, owing to questions such as the short of compatibility of traditional natural-product extract libraries with high-throughput screening. Here, we present a cross-species chemogenomic screening platform to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future veterinary medicines, thereby increasing the number of treatment options. First, based on critically examined pharmacology and text mining, we build a cross-species drug-likeness evaluation approach to screen the lead compounds in veterinary medicines. Second, a specific cross-species target prediction model is developed to infer drug-target connections, with the purpose of understanding how drugs work on the specific targets. Third, we focus on exploring the multiple targets interference effects of veterinary medicines by heterogeneous network convergence and modularization analysis. Finally, we manually integrate a disease pathway to test whether the cross-species chemogenomic platform could uncover the active mechanism of veterinary medicine, which is exemplified by a specific network module. We believe the proposed cross-species chemogenomic platform allows for the systematization of current and traditional knowledge of veterinary medicine and, importantly, for the application of this emerging body of knowledge to the development of new drugs for animal diseases.

  1. Structure of arylamine N-acetyltransferase from Mycobacterium tuberculosis determined by cross-seeding with the homologous protein from M. marinum: triumph over adversity.

    PubMed

    Abuhammad, Areej; Lowe, Edward D; McDonough, Michael A; Shaw Stewart, Patrick D; Kolek, Stefan A; Sim, Edith; Garman, Elspeth F

    2013-08-01

    Arylamine N-acetyltransferase from Mycobacterium tuberculosis (TBNAT) plays an important role in the intracellular survival of the microorganism inside macrophages. Medicinal chemistry efforts to optimize inhibitors of the TBNAT enzyme have been hampered by the lack of a three-dimensional structure of the enzyme. In this paper, the first structure of TBNAT, determined using a lone crystal produced using cross-seeding with the homologous protein from M. marinum, is reported. Despite the similarity between the two enzymes (74% sequence identity), they show distinct physical and biochemical characteristics. The structure elegantly reveals the characteristic features of the protein surface as well as details of the active site of TBNAT relevant to drug-discovery efforts. The crystallographic analysis of the diffraction data presented many challenges, since the crystal was twinned and the habit possessed pseudo-translational symmetry.

  2. Modeling neurodevelopmental cognitive deficits in tasks with cross-species translational validity.

    PubMed

    Cope, Z A; Powell, S B; Young, J W

    2016-01-01

    Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to 'develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures' in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross-species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Anthrax Vaccine Induced Antibodies Provide Cross-Species Prediction of Survival to Aerosol Challenge

    PubMed Central

    Fay, Michael P.; Follmann, Dean A.; Lynn, Freyja; Schiffer, Jarad M.; Stark, Greg; Kohberge, Robert; Quinn, Conrad P.; Nuzum, Edwin O.

    2013-01-01

    Because clinical trials to assess the efficacy of vaccines against anthrax are not ethical or feasible, licensure for new anthrax vaccines will likely involve the Food and Drug Administration’s “Animal Rule,” a set of regulations that allow approval of products based on efficacy data only in animals combined with immunogenicity and safety data in animals and humans. US government sponsored animal studies have shown anthrax vaccine efficacy in a variety of settings. We examined data from 21 of those studies to determine if an immunological bridge based on lethal toxin neutralization activity assay (TNA) can predict survival against an inhalation anthrax challenge within and across species and genera. The 21 studies were classified into 11 different settings, each of which had the same animal species, vaccine type and formulation, vaccination schedule, time of TNA measurement, and challenge time. Logistic regression models determined the contribution of vaccine dilution dose and TNA on prediction of survival. For most settings, logistic models using only TNA explained more than 75% of the survival effect of the models with dose additionally included. Cross species survival predictions using TNA were compared to the actual survival and shown to have good agreement (Cohen’s κ ranged from 0.55 to 0.78). In one study design, cynomolgus macaque data predicted 78.6% survival in rhesus macaques (actual survival 83.0%) and 72.6% in rabbits (actual survival, 64.6%). These data add support for the use of TNA as an immunological bridge between species to extrapolate data in animals to predict anthrax vaccine effectiveness in humans. PMID:22972844

  9. 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. © 2014 Society for Reproduction and Fertility.

  10. 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

  11. 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.

  12. Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish.

    PubMed

    Leclercq, Karine; Afrikanova, Tatiana; Langlois, Melanie; De Prins, An; Buenafe, Olivia E; Rospo, Chiara C; Van Eeckhaut, Ann; de Witte, Peter A M; Crawford, Alexander D; Smolders, Ilse; Esguerra, Camila V; Kaminski, Rafal M

    2015-04-01

    Treatment-resistant seizures affect about a third of patients suffering from epilepsy. To fulfill the need for new medications targeting treatment-resistant seizures, a number of rodent models offer the opportunity to assess a variety of potential treatment approaches. The use of such models, however, has proven to be time-consuming and labor-intensive. In this study, we performed pharmacological characterization of the allylglycine (AG) seizure model, a simple in vivo model for which we demonstrated a high level of treatment resistance. (d,l)-Allylglycine inhibits glutamic acid decarboxylase (GAD) - the key enzyme in γ-aminobutyric acid (GABA) biosynthesis - leading to GABA depletion, seizures, and neuronal damage. We performed a side-by-side comparison of mouse and zebrafish acute AG treatments including biochemical, electrographic, and behavioral assessments. Interestingly, seizure progression rate and GABA depletion kinetics were comparable in both species. Five mechanistically diverse antiepileptic drugs (AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and topiramate) showed only a limited protective effect (mainly mortality delay) at doses close to the TD50 (dose inducing motor impairment in 50% of animals) in mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective activity against AG-induced seizures. Experiments performed in zebrafish larvae revealed behavioral AED activity profiles highly analogous to those obtained in mice. Having demonstrated cross-species similarities and limited efficacy of tested AEDs, we propose the use of AG in zebrafish as a convenient and high-throughput model of treatment-resistant seizures. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.

    PubMed

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

    2014-01-01

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

  14. 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. Published by Elsevier Ltd.

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

    PubMed

    Maduna, Simo N; Rossouw, Charné; Roodt-Wilding, Rouvay; Bester-van der Merwe, Aletta E

    2014-06-10

    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. 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. Cross-species amplification of the 35 microsatellites proved to be a time- and cost

  16. 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

  17. 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

  18. Orbitofrontal Neuroadaptations and Cross-Species Synaptic Biomarkers in Heavy-Drinking Macaques

    PubMed Central

    Uys, Joachim D.; Woodward, John J.; Randall, Patrick K.; Ball, Lauren E.

    2017-01-01

    Cognitive impairments, uncontrolled drinking, and neuropathological cortical changes characterize alcohol use disorder. Dysfunction of the orbitofrontal cortex (OFC), a critical cortical subregion that controls learning, decision-making, and prediction of reward outcomes, contributes to executive cognitive function deficits in alcoholic individuals. Electrophysiological and quantitative synaptomics techniques were used to test the hypothesis that heavy drinking produces neuroadaptations in the macaque OFC. Integrative bioinformatics and reverse genetic approaches were used to identify and validate synaptic proteins with novel links to heavy drinking in BXD mice. In drinking monkeys, evoked firing of OFC pyramidal neurons was reduced, whereas the amplitude and frequency of postsynaptic currents were enhanced compared with controls. Bath application of alcohol reduced evoked firing in neurons from control monkeys, but not drinking monkeys. Profiling of the OFC synaptome identified alcohol-sensitive proteins that control glutamate release (e.g., SV2A, synaptogyrin-1) and postsynaptic signaling (e.g., GluA1, PRRT2) with no changes in synaptic GABAergic proteins. Western blot analysis confirmed the increase in GluA1 expression in drinking monkeys. An exploratory analysis of the OFC synaptome found cross-species genetic links to alcohol intake in discrete proteins (e.g., C2CD2L, DIRAS2) that discriminated between low- and heavy-drinking monkeys. Validation studies revealed that BXD mouse strains with the D allele at the C2cd2l interval drank less alcohol than B allele strains. Thus, by profiling of the OFC synaptome, we identified changes in proteins controlling glutamate release and postsynaptic signaling and discovered several proteins related to heavy drinking that have potential as novel targets for treating alcohol use disorder. SIGNIFICANCE STATEMENT Clinical research identified cognitive deficits in alcoholic individuals as a risk factor for relapse, and alcoholic

  19. 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

  20. Preclinical QT safety assessment: cross-species comparisons and human translation from an industry consortium.

    PubMed

    Holzgrefe, Henry; Ferber, Georg; Champeroux, Pascal; Gill, Michael; Honda, Masaki; Greiter-Wilke, Andrea; Baird, Theodore; Meyer, Olivier; Saulnier, Muriel

    2014-01-01

    In vivo models have been required to demonstrate relative cardiac safety, but model sensitivity has not been systematically investigated. Cross-species and human translation of repolarization delay, assessed as QT/QTc prolongation, has not been compared employing common methodologies across multiple species and sites. Therefore, the accurate translation of repolarization results within and between preclinical species, and to man, remains problematic. Six pharmaceutical companies entered into an informal consortium designed to collect high-resolution telemetered data in multiple species (dog; n=34, cynomolgus; n=37, minipig; n=12, marmoset; n=14, guinea pig; n=5, and man; n=57). All animals received vehicle and varying doses of moxifloxacin (3-100 mg/kg, p.o.) with telemetered ECGs (≥500 Hz) obtained for 20-24h post-dose. Individual probabilistic QT-RR relationships were derived for each subject. The rate-correction efficacies of the individual (QTca) and generic correction formulae (Bazett, Fridericia, and Van de Water) were objectively assessed as the mean squared slopes of the QTc-RR relationships. Normalized moxifloxacin QTca responses (Veh Δ%/μM) were derived for 1h centered on the moxifloxacin Tmax. All QT-RR ranges demonstrated probabilistic uncertainty; slopes varied distinctly by species where dog and human exhibited the lowest QT rate-dependence, which was much steeper in the cynomolgus and guinea pig. Incorporating probabilistic uncertainty, the normalized QTca-moxifloxacin responses were similarly conserved across all species, including man. The current results provide the first unambiguous evidence that all preclinical in vivo repolarization assays, when accurately modeled and evaluated, yield results that are consistent with the conservation of moxifloxacin-induced QT prolongation across all common preclinical species. Furthermore, these outcomes are directly transferable across all species including man. The consortium results indicate that the

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

    PubMed

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

    2016-01-15

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

  2. 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

  3. 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.

  4. 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.

  5. Cross-species transcriptional network analysis reveals conservation and variation in response to metal stress in cyanobacteria

    PubMed Central

    2013-01-01

    Background As one of the most dominant bacterial groups on Earth, cyanobacteria play a pivotal role in the global carbon cycling and the Earth atmosphere composition. Understanding their molecular responses to environmental perturbations has important scientific and environmental values. Since important biological processes or networks are often evolutionarily conserved, the cross-species transcriptional network analysis offers a useful strategy to decipher conserved and species-specific transcriptional mechanisms that cells utilize to deal with various biotic and abiotic disturbances, and it will eventually lead to a better understanding of associated adaptation and regulatory networks. Results In this study, the Weighted Gene Co-expression Network Analysis (WGCNA) approach was used to establish transcriptional networks for four important cyanobacteria species under metal stress, including iron depletion and high copper conditions. Cross-species network comparison led to discovery of several core response modules and genes possibly essential to metal stress, as well as species-specific hub genes for metal stresses in different cyanobacteria species, shedding light on survival strategies of cyanobacteria responding to different environmental perturbations. Conclusions The WGCNA analysis demonstrated that the application of cross-species transcriptional network analysis will lead to novel insights to molecular response to environmental changes which will otherwise not be achieved by analyzing data from a single species. PMID:23421563

  6. 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.

  7. PhosphOrtholog: a web-based tool for cross-species mapping of orthologous protein post-translational modifications.

    PubMed

    Chaudhuri, Rima; Sadrieh, Arash; Hoffman, Nolan J; Parker, Benjamin L; Humphrey, Sean J; Stöckli, Jacqueline; Hill, Adam P; James, David E; Yang, Jean Yee Hwa

    2015-08-19

    Most biological processes are influenced by protein post-translational modifications (PTMs). Identifying novel PTM sites in different organisms, including humans and model organisms, has expedited our understanding of key signal transduction mechanisms. However, with increasing availability of deep, quantitative datasets in diverse species, there is a growing need for tools to facilitate cross-species comparison of PTM data. This is particularly important because functionally important modification sites are more likely to be evolutionarily conserved; yet cross-species comparison of PTMs 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 known orthologous phosphosites, and do not enable the cross-species mapping of newly identified modification sites. Here, we addressed this by developing a web-based software tool, PhosphOrtholog ( www.phosphortholog.com ) that accurately maps protein modification sites between different species. This facilitates the comparison of datasets derived from multiple species, and should be a valuable tool for the proteomics community. Here we describe PhosphOrtholog, a web-based application for mapping known and novel orthologous PTM sites from experimental data obtained from different species. PhosphOrtholog is the only generic and automated tool that enables cross-species comparison of large-scale PTM datasets without relying on existing PTM databases. This is achieved through pairwise sequence alignment of orthologous protein residues. To demonstrate its utility we apply it to two sets of human and rat muscle phosphoproteomes generated following insulin and exercise stimulation, respectively, and one publicly available mouse phosphoproteome following cellular stress revealing high mapping and coverage efficiency. Although coverage statistics are dataset dependent, PhosphOrtholog increased the number of cross-species mapped sites

  8. Benign breast lesions that mimic malignancy.

    PubMed

    Torous, Vanda F; Schnitt, Stuart J; Collins, Laura C

    2017-02-01

    Many benign and reactive lesions of the breast show morphological overlap with malignant lesions. These benign mimics of malignancy often present diagnostic challenges to even the most experienced pathologists. This review focuses on several benign lesions of the breast that mimic malignant entities. For each of these lesions, we describe the key morphological and immunohistochemical features, potential diagnostic pitfalls, and our approach to arriving at the correct diagnosis. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  9. 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…

  10. 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.

  11. 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/

  12. Speciation: frog mimics prefer their own.

    PubMed

    Mallet, James

    2014-11-17

    Ranitomeya poison frogs in the Peruvian Amazon are a rare example of Müllerian mimicry in vertebrates. These frogs also prefer to court same-coloured mimics. This suggests that divergence in mimicry plays a role in reproductive isolation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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/

  14. Hybrid mimics and hybrid vigor in Arabidopsis

    PubMed Central

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

    2015-01-01

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

  15. 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.

  16. 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

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

    PubMed

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

    2014-04-01

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

  18. Design factors that influence PCR amplification success of cross-species primers among 1147 mammalian primer pairs

    PubMed Central

    Housley, Donna JE; Zalewski, Zachary A; Beckett, Stephanie E; Venta, Patrick J

    2006-01-01

    Background Cross-species primers have been used with moderate success to address a variety of questions concerning genome structure, evolution, and gene function. However, the factors affecting their success have never been adequately addressed, particularly with respect to producing a consistent method to achieve high throughput. Using 1,147 mammalian cross-species primer pairs (1089 not previously reported), we tested several factors to determine their influence on the probability that a given target will amplify in a given species under a single amplification condition. These factors included: number of mismatches between the two species (the index species) used to identify conserved regions to which the primers were designed, GC-content of the gene and amplified region, CpG dinucleotides in the primer region, degree of encoded protein conservation, length of the primers, and the degree of evolutionary distance between the target species and the two index species. Results The amplification success rate for the cross-species primers was significantly influenced by the number of mismatches between the two index species (6–8% decrease per mismatch in a primer pair), the GC-content within the amplified region (for the dog, GC ≥ 50%, 56.9% amplified; GC<50%, 74.2% amplified), the degree of protein conservation (R2 = 0.14) and the relatedness of the target species to the index species. For the dog, 598 products of 930 primer pairs (64.3%) (excluding primers in which dog was an index species) were sequenced and shown to be the expected product, with an additional three percent producing the incorrect sequence. When hamster DNA was used with the single amplification condition in a microtiter plate-based format, 510 of 1087 primer pairs (46.9%) produced amplified products. The primer pairs are spaced at an average distance of 2.3 Mb in the human genome and may be used to produce up to several hundred thousand bp of species-specific sequence. Conclusion The most

  19. Design factors that influence PCR amplification success of cross-species primers among 1147 mammalian primer pairs.

    PubMed

    Housley, Donna J E; Zalewski, Zachary A; Beckett, Stephanie E; Venta, Patrick J

    2006-10-09

    Cross-species primers have been used with moderate success to address a variety of questions concerning genome structure, evolution, and gene function. However, the factors affecting their success have never been adequately addressed, particularly with respect to producing a consistent method to achieve high throughput. Using 1,147 mammalian cross-species primer pairs (1089 not previously reported), we tested several factors to determine their influence on the probability that a given target will amplify in a given species under a single amplification condition. These factors included: number of mismatches between the two species (the index species) used to identify conserved regions to which the primers were designed, GC-content of the gene and amplified region, CpG dinucleotides in the primer region, degree of encoded protein conservation, length of the primers, and the degree of evolutionary distance between the target species and the two index species. The amplification success rate for the cross-species primers was significantly influenced by the number of mismatches between the two index species (6-8% decrease per mismatch in a primer pair), the GC-content within the amplified region (for the dog, GC > or = 50%, 56.9% amplified; GC<50%, 74.2% amplified), the degree of protein conservation (R2 = 0.14) and the relatedness of the target species to the index species. For the dog, 598 products of 930 primer pairs (64.3%) (excluding primers in which dog was an index species) were sequenced and shown to be the expected product, with an additional three percent producing the incorrect sequence. When hamster DNA was used with the single amplification condition in a microtiter plate-based format, 510 of 1087 primer pairs (46.9%) produced amplified products. The primer pairs are spaced at an average distance of 2.3 Mb in the human genome and may be used to produce up to several hundred thousand bp of species-specific sequence. The most important factors influencing the

  20. Intrastriatal transplantation of cross-species fetal striatal cells reduces abnormal movements in a primate model of Huntington disease.

    PubMed Central

    Hantraye, P; Riche, D; Maziere, M; Isacson, O

    1992-01-01

    Huntington disease is a neurological movement disorder involving massive neuronal death in the caudate-putamen region of the brain. Neither preventive nor curative therapy exists for this disease. The implantation of cross-species striatal neural precursor cells into the lesioned striatum of nonhuman primates (baboons) reduced the abnormal movements seen in the disease model. These abnormal movements reappeared after immunological rejection of the implanted striatal cells and were not modified by transplantation with nonstriatal cells. These findings encourage further experimentation toward the use of cell sources other than human fetal cells in a potential clinical application to Huntington disease. Images PMID:1533285

  1. 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.

  2. 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...

  3. 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...

  4. 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

  5. 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.

  6. Environmental mimics of chemical warfare agents.

    PubMed

    Claborn, David M

    2004-12-01

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

  7. Malware Mimics for Network Security Assessment

    DTIC Science & Technology

    2011-03-01

    Department of Defense, the use of Red Teams results in the most effective, realistic, and comprehensive training for network administrators. Our thesis...complex malware mimic behaviors. 15. NUMBER OF PAGES 129 14. SUBJECT TERMS Malware, Red Team , Computer Network Defense Training, Network...within the Department of Defense, the use of Red Teams results in the most effective, realistic, and comprehensive training for network administrators

  8. 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.

  9. Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research.

    PubMed

    Köhler, Sebastian; Doelken, Sandra C; Ruef, Barbara J; Bauer, Sebastian; Washington, Nicole; Westerfield, Monte; Gkoutos, George; Schofield, Paul; Smedley, Damian; Lewis, Suzanna E; Robinson, Peter N; Mungall, Christopher J

    2013-01-01

    Phenotype analyses, e.g. investigating metabolic processes, tissue formation, or organism behavior, are an important element of most biological and medical research activities. Biomedical researchers are making increased use of ontological standards and methods to capture the results of such analyses, with one focus being the comparison and analysis of phenotype information between species. We have generated a cross-species phenotype ontology for human, mouse and zebrafish that contains classes from the Human Phenotype Ontology, Mammalian Phenotype Ontology, and generated classes for zebrafish phenotypes. We also provide up-to-date annotation data connecting human genes to phenotype classes from the generated ontology. We have included the data generation pipeline into our continuous integration system ensuring stable and up-to-date releases. This article describes the data generation process and is intended to help interested researchers access both the phenotype annotation data and the associated cross-species phenotype ontology. The resource described here can be used in sophisticated semantic similarity and gene set enrichment analyses for phenotype data across species. The stable releases of this resource can be obtained from http://purl.obolibrary.org/obo/hp/uberpheno/.

  10. Identification of broadly conserved cross-species protective Leishmania antigen and its responding CD4+ T cells.

    PubMed

    Mou, Zhirong; Li, Jintao; Boussoffara, Thouraya; Kishi, Hiroyuki; Hamana, Hiroshi; Ezzati, Peyman; Hu, Chuanmin; Yi, Weijing; Liu, Dong; Khadem, Forough; Okwor, Ifeoma; Jia, Ping; Shitaoka, Kiyomi; Wang, Shufeng; Ndao, Momar; Petersen, Christine; Chen, Jianping; Rafati, Sima; Louzir, Hechmi; Muraguchi, Atsushi; Wilkins, John A; Uzonna, Jude E

    2015-10-21

    There is currently no clinically effective vaccine against leishmaniasis because of poor understanding of the antigens that elicit dominant T cell immunity. Using proteomics and cellular immunology, we identified a dominant naturally processed peptide (PEPCK335-351) derived from Leishmania glycosomal phosphoenolpyruvate carboxykinase (PEPCK). PEPCK was conserved in all pathogenic Leishmania, expressed in glycosomes of promastigotes and amastigotes, and elicited strong CD4(+) T cell responses in infected mice and humans. I-A(b)-PEPCK335-351 tetramer identified protective Leishmania-specific CD4(+) T cells at a clonal level, which comprised ~20% of all Leishmania-reactive CD4(+) T cells at the peak of infection. PEPCK335-351-specific CD4(+) T cells were oligoclonal in their T cell receptor usage, produced polyfunctional cytokines (interleukin-2, interferon-γ, and tumor necrosis factor), and underwent expansion, effector activities, contraction, and stable maintenance after lesion resolution. Vaccination with PEPCK peptide, DNA expressing full-length PEPCK, or rPEPCK induced strong durable cross-species protection in both resistant and susceptible mice. The effectiveness and durability of protection in vaccinated mice support the development of a broadly cross-species protective vaccine against different forms of leishmaniasis by targeting PEPCK. Copyright © 2015, American Association for the Advancement of Science.

  11. 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.

  12. A Computational Pipeline for Cross-Species Analysis of RNA-seq Data Using R and Bioconductor

    PubMed Central

    LoVerso, Peter R.; Cui, Feng

    2015-01-01

    RNA sequencing (RNA-seq) has revolutionized transcriptome analysis through profiling the expression of thousands of genes at the same time. Systematic analysis of orthologous transcripts across species is critical for understanding the evolution of gene expression and uncovering important information in animal models of human diseases. Several computational methods have been published for analyzing gene expression between species, but they often lack crucial details and therefore cannot serve as a practical guide. Here, we present the first step-by-step protocol for cross-species RNA-seq analysis with a concise workflow that is largely based on the free open-source R language and Bioconductor packages. This protocol covers the entire process from short-read mapping, gene expression quantification, differential expression analysis to pathway enrichment. Many useful utilities for data visualization are included. This complete and easy-to-follow protocol provides hands-on guidance for users who are new to cross-species gene expression analysis. PMID:26692761

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Harnessing cross-species alignment to discover SNPs and generate a draft genome sequence of a bighorn sheep (Ovis canadensis).

    PubMed

    Miller, Joshua M; Moore, Stephen S; Stothard, Paul; Liao, Xiaoping; Coltman, David W

    2015-05-20

    Whole genome sequences (WGS) have proliferated as sequencing technology continues to improve and costs decline. While many WGS of model or domestic organisms have been produced, a growing number of non-model species are also being sequenced. In the absence of a reference, construction of a genome sequence necessitates de novo assembly which may be beyond the ability of many labs due to the large volumes of raw sequence data and extensive bioinformatics required. In contrast, the presence of a reference WGS allows for alignment which is more tractable than assembly. Recent work has highlighted that the reference need not come from the same species, potentially enabling a wide array of species WGS to be constructed using cross-species alignment. Here we report on the creation a draft WGS from a single bighorn sheep (Ovis canadensis) using alignment to the closely related domestic sheep (Ovis aries). Two sequencing libraries on SOLiD platforms yielded over 865 million reads, and combined alignment to the domestic sheep reference resulted in a nearly complete sequence (95% coverage of the reference) at an average of 12x read depth (104 SD). From this we discovered over 15 million variants and annotated them relative to the domestic sheep reference. We then conducted an enrichment analysis of those SNPs showing fixed differences between the reference and sequenced individual and found significant differences in a number of gene ontology (GO) terms, including those associated with reproduction, muscle properties, and bone deposition. Our results demonstrate that cross-species alignment enables the creation of novel WGS for non-model organisms. The bighorn sheep WGS will provide a resource for future resequencing studies or comparative genomics.

  3. 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

  4. Engineering hydrogels as extracellular matrix mimics

    PubMed Central

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

    2010-01-01

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

  5. Acute epiploic appendagitis and its mimics.

    PubMed

    Singh, Ajay K; Gervais, Debra A; Hahn, Peter F; Sagar, Pallavi; Mueller, Peter R; Novelline, Robert A

    2005-01-01

    Acute epiploic appendagitis most commonly manifests with acute lower quadrant pain. Its clinical features are similar to those of acute diverticulitis or, less commonly, acute appendicitis. The conditions that may mimic acute epiploic appendagitis at computed tomography (CT) include acute omental infarction, mesenteric panniculitis, fat-containing tumor, and primary and secondary acute inflammatory processes in the large bowel (eg, diverticulitis and appendicitis). Whereas the location of acute epiploic appendagitis is most commonly adjacent to the sigmoid colon, acute omental infarction is typically located in the right lower quadrant and often is mistaken for acute appendicitis. It is important to correctly diagnose acute epiploic appendagitis and acute omental infarction on CT images because these conditions may be mistaken for acute abdomen, and the mistake may lead to unnecessary surgery. The CT features of acute epiploic appendagitis include an oval lesion 1.5-3.5 cm in diameter, with attenuation similar to that of fat and with surrounding inflammatory changes, that abuts the anterior sigmoid colon wall. The CT features of acute omental infarction include a well-circumscribed triangular or oval heterogeneous fatty mass with a whorled pattern of concentric linear fat stranding between the anterior abdominal wall and the transverse or ascending colon. As CT increasingly is used for the evaluation of acute abdomen, radiologists are likely to see acute epiploic appendagitis and its mimics more often. Recognition of these conditions on CT images will allow appropriate management of acute abdominal pain and may help to prevent unnecessary surgery. RSNA, 2005.

  6. Right-sided diverticulitis mimics appendicitis.

    PubMed

    Gilmore, Thomas; Jordan, Charlton; Edelstein, Elisabeth

    2013-01-01

    Right-sided diverticulitis is a rare source of right lower quadrant pain in Western society; however, it is quite common in Asian societies. Right-sided diverticulitis presents very similarly to appendicitis, with right lower quadrant pain, fever, nausea, and laboratory abnormalities, and is often seen in young patients. In this report, we present a case of right-sided diverticulitis. We review right-sided diverticulitis' diagnosis and management. It is important to diagnose right-sided diverticulitis because it is a good mimic of appendicitis and ideally should be diagnosed before a patient has unnecessary surgery. A 26-year-old Asian woman presented for evaluation of right lower quadrant pain and fever. She was initially thought to have appendicitis clinically, but had right-sided diverticulitis diagnosed by computed tomography (CT) scan. She was admitted and received intravenous antibiotics and bowel rest. Her right-sided diverticulitis resolved in 3 days. Severe right lower quadrant pain in young patients of Asian descent can be right-sided diverticulitis. Right-sided diverticulitis is a benign condition managed medically that mimics appendicitis. CT imaging seems to be the best way to avoid unnecessary surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. 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.

  8. DNA mimic proteins: functions, structures, and bioinformatic analysis.

    PubMed

    Wang, Hao-Ching; Ho, Chun-Han; Hsu, Kai-Cheng; Yang, Jinn-Moon; Wang, Andrew H-J

    2014-05-13

    DNA mimic proteins have DNA-like negative surface charge distributions, and they function by occupying the DNA binding sites of DNA binding proteins to prevent these sites from being accessed by DNA. DNA mimic proteins control the activities of a variety of DNA binding proteins and are involved in a wide range of cellular mechanisms such as chromatin assembly, DNA repair, transcription regulation, and gene recombination. However, the sequences and structures of DNA mimic proteins are diverse, making them difficult to predict by bioinformatic search. To date, only a few DNA mimic proteins have been reported. These DNA mimics were not found by searching for functional motifs in their sequences but were revealed only by structural analysis of their charge distribution. This review highlights the biological roles and structures of 16 reported DNA mimic proteins. We also discuss approaches that might be used to discover new DNA mimic proteins.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Syndromes that Mimic an Excess of Mineralocorticoids.

    PubMed

    Sabbadin, Chiara; Armanini, Decio

    2016-09-01

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

  18. 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

  19. Developing Human Radiation Biodosimetry Models: Testing Cross-Species Conversion Approaches Using an Ex Vivo Model System.

    PubMed

    Park, Jin G; Paul, Sunirmal; Briones, Natalia; Zeng, Jia; Gillis, Kristin; Wallstrom, Garrick; LaBaer, Joshua; Amundson, Sally A

    2017-06-01

    In the event of a large-scale radiation exposure, accurate and quick assessment of radiation dose received would be critical for triage and medical treatment of large numbers of potentially exposed individuals. Current methods of biodosimetry, such as the dicentric chromosome assay, are time consuming and require sophisticated equipment and highly trained personnel. Therefore, scalable biodosimetry approaches, including gene expression profiles in peripheral blood cells, are being investigated. Due to the limited availability of appropriate human samples, biodosimetry development has relied heavily on mouse models, which are not directly applicable to human response. Therefore, to explore the feasibility of using non-human primate (NHP) models to build and test a biodosimetry algorithm for use in humans, we irradiated ex vivo peripheral blood samples from both humans and rhesus macaques with doses of 0, 2, 5, 6 and 7 Gy, and compared the gene expression profiles 24 h later using Agilent human microarrays. Among the dose-responsive genes in human and using non-human primate, 52 genes showed highly correlated expression patterns between the species, and were enriched in p53/DNA damage response, apoptosis and cell cycle-related genes. When these interspecies-correlated genes were used to build biodosimetry models with using NHP data, the mean prediction accuracy on non-human primate samples was about 90% within 1 Gy of delivered dose in leave-one-out cross-validation. However, tests on human samples suggested that human gene expression values may need to be adjusted prior to application of the NHP model. A "multi-gene" approach utilizing all gene values for cross-species conversion and applying the converted values on the NHP biodosimetry models, gave a leave-one-out cross-validation prediction accuracy for human samples highly comparable (up to 94%) to that for non-human primates. Overall, this study demonstrates that a robust NHP biodosimetry model can be built

  20. Cross-species amplification of human microsatellite markers using noninvasive samples from white-handed gibbons (Hylobates lar).

    PubMed

    Chambers, Karen E; Reichard, Ulrich H; Möller, Asja; Nowak, Katrin; Vigilant, Linda

    2004-09-01

    Analysis of the population genetic structure and reproductive strategies of various primate species has been facilitated by cross-species amplification (i.e., the use of microsatellite markers developed in one species for analysis of another). In this study we screened 47 human-derived markers to assess their utility in the white-handed gibbon (Hylobates lar). Only eight produced accurate, reliable results, and exhibited levels of polymorphism that were adequate for individual identification. This low success rate was surprising given that human microsatellite markers typically work well in species (such as macaques) that are evolutionarily more distant from humans than are gibbons. In addition, we experienced limited success in using a set of microsatellite markers that have been reported to be useful in the closely-related H. muelleri, and applying our set of microsatellite markers to samples obtained from one H. pileatus individual. Our results emphasize the importance of extensively screening potential markers in representatives of the population of interest.

  1. Annotated genes and nonannotated genomes: cross-species use of Gene Ontology in ecology and evolution research.

    PubMed

    Primmer, C R; Papakostas, S; Leder, E H; Davis, M J; Ragan, M A

    2013-06-01

    Recent advances in molecular technologies have opened up unprecedented opportunities for molecular ecologists to better understand the molecular basis of traits of ecological and evolutionary importance in almost any organism. Nevertheless, reliable and systematic inference of functionally relevant information from these masses of data remains challenging. The aim of this review is to highlight how the Gene Ontology (GO) database can be of use in resolving this challenge. The GO provides a largely species-neutral source of information on the molecular function, biological role and cellular location of tens of thousands of gene products. As it is designed to be species-neutral, the GO is well suited for cross-species use, meaning that, functional annotation derived from model organisms can be transferred to inferred orthologues in newly sequenced species. In other words, the GO can provide gene annotation information for species with nonannotated genomes. In this review, we describe the GO database, how functional information is linked with genes/gene products in model organisms, and how molecular ecologists can utilize this information to annotate their own data. Then, we outline various applications of GO for enhancing the understanding of molecular basis of traits in ecologically relevant species. We also highlight potential pitfalls, provide step-by-step recommendations for conducting a sound study in nonmodel organisms, suggest avenues for future research and outline a strategy for maximizing the benefits of a more ecological and evolutionary genomics-oriented ontology by ensuring its compatibility with the GO. © 2013 John Wiley & Sons Ltd.

  2. Cross-species chromosome painting tracks the independent origin of multiple sex chromosomes in two cofamiliar Erythrinidae fishes.

    PubMed

    Cioffi, Marcelo B; Sánchez, Antonio; Marchal, Juan A; Kosyakova, Nadezda; Liehr, Thomas; Trifonov, Vladimir; Bertollo, Luiz Ac

    2011-06-30

    The Erythrinidae fish family is characterized by a large variation with respect to diploid chromosome numbers and sex-determining systems among its species, including two multiple X1X2Y sex systems in Hoplias malabaricus and Erythrinus erythrinus. At first, the occurrence of a same sex chromosome system within a family suggests that the sex chromosomes are correlated and originated from ancestral XY chromosomes that were either homomorphic or at an early stage of differentiation. To identify the origin and evolution of these X1X2Y sex chromosomes, we performed reciprocal cross-species FISH experiments with two sex-chromosome-specific probes designed from microdissected X1 and Y chromosomes of H. malabaricus and E. erythrinus, respectively. Our results yield valuable information regarding the origin and evolution of these sex chromosome systems. Our data indicate that these sex chromosomes evolved independently in these two closed related Erythrinidae species. Different autosomes were first converted into a poorly differentiated XY sex pair in each species, and additional chromosomal rearrangements produced both X1X2Y sex systems that are currently present. Our data provide new insights into the origin and evolution of sex chromosomes, which increases our knowledge about fish sex chromosome evolution.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Meskauskiene, Rasa; Laule, Oliver; Ivanov, Nikolai V; Martin, Florian; Wyss, Markus; Gruissem, Wilhelm; Zimmermann, Philip

    2013-08-06

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-08-01

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

  7. 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

  8. Cross-Species Withdrawal of MCL1 Facilitates Postpartum Uterine Involution in Both the Mouse and Baboon

    PubMed Central

    Kyathanahalli, Chandrashekara; Marks, Jason; Nye, Kennedy; Lao, Belinda; Albrecht, Eugene D.; Aberdeen, Graham W.; Nathanielsz, Peter W.; Jeyasuria, Pancharatnam

    2013-01-01

    A successful postpartum involution permits the postnatal uterus to rapidly regain its prepregnancy function and size to ultimately facilitate an ensuing blastocyst implantation. This study investigates the molecular mechanisms that govern the initiation of the involution process by examining the signaling events that occur as the uterus transitions from the pregnant to postnatal state. Using mouse and baboon uteri, we found a remarkable cross-species conservation at the signal transduction level as the pregnant uterus initiates and progresses through the involution process. This study originated with the observation of elevated levels of caspase-3 activation in both the laboring mouse and baboon uterus, which we found to be apoptotic in nature as evidenced by the concurrent appearance of cleaved poly(ADP-ribose) polymerase. We previously defined a nonapoptotic and potential tocolytic role for uterine caspase-3 during pregnancy regulated by increased antiapoptotic signaling mediated by myeloid cell leukemia sequence 1 and X-linked inhibitor of apoptosis. In contrast, this study determined that diminished antiapoptotic signaling in the postpartum uterus allowed for both endometrial apoptotic and myometrial autophagic episodes, which we speculate are responsible for the rapid reduction in size of the postpartum uterus. Using our human telomerase immortalized myometrial cell line and the Simian virus-40 immortalized endometrial cell line (12Z), we demonstrated that the withdrawal of antiapoptotic signaling was also an upstream event for both the autophagic and apoptotic processes in the human uterine myocyte and endometrial epithelial cell. PMID:24140717

  9. 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.

  10. 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

  11. 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.

  12. 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

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

    PubMed Central

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

    2016-01-01

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

  14. 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

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

    PubMed

    Andersen, Susan L

    2015-05-01

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

  16. 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.

  17. SRLVs: a genetic continuum of lentiviral species in sheep and goats with cumulative evidence of cross species transmission.

    PubMed

    Leroux, Caroline; Cruz, Juliano Cezar Minardi; Mornex, Jean-François

    2010-01-01

    Lentiviruses from distinct animal species have in common their genomic organization, the induction of slowly progressive diseases over months or years, the large spectrum of induced symptoms and concerned organs, the frequent inapparent infection without any detectable clinical signs, their ability to persist into their hosts despite an often strong and mature immune response. Lentiviruses are also characterized by their genomic plasticity and the rapid evolution of the viral species. SRLVs infecting goats and sheep follow a genomic evolution pattern similar to that observed in HIV or in other lentiviruses. Based on limited number of complete sequences, they have been initially described as two distinct genetic groups evolving independently in sheep or goats, the ovine strains being closely related to each other and distinct from the caprine ones. Over the last 2 decades, the description of many partial or complete sequences of caprine and ovine field isolates from various geographical regions and their phylogenetic studies clearly evidenced the existence of a genetic continuum with viruses that did not simply clustered according to the animal species they were isolated from. Three classifications have been successively proposed and allowed to refine the SRLV phylogeny over time. Phylogenetic reconstructions support the existence of SRLV cross-species transmission in domestic and wild small ruminants.

  18. 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.

  19. 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.

  20. Transient ischaemic attacks: mimics and chameleons

    PubMed Central

    Nadarajan, V; Perry, R J; Johnson, J; Werring, D J

    2014-01-01

    Suspected transient ischaemic attack (TIA) is a common diagnostic challenge for physicians in neurology, stroke, general medicine and primary care. It is essential to identify TIAs promptly because of the very high early risk of ischaemic stroke, requiring urgent investigation and preventive treatment. On the other hand, it is also important to identify TIA ‘mimics’, to avoid unnecessary and expensive investigations, incorrect diagnostic labelling and inappropriate long-term prevention treatment. Although the pathophysiology of ischaemic stroke and TIA is identical, and both require rapid and accurate diagnosis, the differential diagnosis differs for TIA owing to the transience of symptoms. For TIA the diagnostic challenge is greater, and the ‘mimic’ rate higher (and more varied), because there is no definitive diagnostic test. TIA heralds a high risk of early ischaemic stroke, and in many cases the stroke can be prevented if the cause is identified, hence the widespread dissemination of guidelines including rapid assessment and risk tools like the ABCD2 score. However, these guidelines do not emphasise the substantial challenges in making the correct diagnosis in patients with transient neurological symptoms. In this article we will mainly consider the common TIA mimics, but also briefly mention the rather less common situations where TIAs can look like something else (‘chameleons’). PMID:24453269

  1. Infantile pulmonary tuberculosis: the great mimic.

    PubMed

    Varik, Roma Subhash; Shubha, Attibele Mahadevaiah; Lewin, Maria; Alexander, Betty; Kini, Usha; Das, Kanishka

    2012-06-01

    Infantile tuberculosis is common in developing countries and rarely presents as space occupying thoracic lesions mimicking congenital malformations. This case series reviews four such infants with varied presentations and their outcome. Four cases of infantile pulmonary/mediastinal tuberculosis that presented like congenital thoracic lesions are described. Details of demography, symptomatology, contact history, immunization status, provisional diagnosis, tuberculin testing, imaging, histopathology, final diagnosis, management and outcome were retrospectively collated and analyzed. They were 4-6-month males, term-born and immunized. They presented with pneumonia/hyperactive airway disease since 2-12 weeks. One had a suspect and another a close tuberculous contact. The provisional diagnosis after imaging were infected congenital lung cyst, posterior mediastinal cyst and bronchopulmonary malformation. Two were tuberculin positive; none had gastric acid-fast bacilli. One underwent a pulmonary lobectomy for necrotic lung cyst; the second had a biopsy and drainage of a posterior mediastinal cyst that contained caseating material and was densely adherent to the esophagus. Surgical biopsy showed necrotizing granulomatous inflammation in both; one with acid-fast bacilli. Both succumbed to postoperative complications. The other two with tuberculous contacts who were managed with early antituberculous therapy, responded well and recovered uneventfully. Infantile pulmonary/mediastinal tuberculosis may mimic congenital thoracic malformations. A review of contact history, investigations and imaging help to establish the tuberculous etiology, avoids surgical misadventures and prompts early antituberculous therapy to achieve a favorable outcome.

  2. Helical peptoid mimics of magainin-2 amide.

    PubMed

    Patch, James A; Barron, Annelise E

    2003-10-08

    A series of peptoid oligomers were designed as helical, cationic, and facially amphipathic mimics of the magainin-2 amide antibacterial peptide. We used circular dichroism spectroscopy to determine the conformation of these peptoids in aqueous buffer and in the presence of bacterial membrane-mimetic lipid vesicles, composed of a 7:3 mol ratio of POPE:POPG. We found that certain peptoids, which displayed characteristically helical CD in buffer and lipid vesicles, exhibit selective (nonhemolytic) and potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In contrast, peptoids that exhibit weak CD, reminiscent of that of a peptide random coil, were ineffective antibiotics. In a manner similar to the natural magainin peptides, we find a correlation between peptoid lipophilicity and hemolytic propensity. We observe that a minimum length of approximately 12 peptoid residues may be required for antibacterial activity. We also see evidence that a helix length between 24 and 34 A may provide optimal antibacterial efficacy. These results provide the first example of a water-soluble, structured, bioactive peptoid.

  3. Cross-species extrapolation of prediction model for lead transfer from soil to corn grain under stress of exogenous lead.

    PubMed

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

    2014-01-01

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

  4. 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.

  5. Hebephilia as mental disorder? A historical, cross-cultural, sociological, cross-species, non-clinical empirical, and evolutionary review.

    PubMed

    Rind, Bruce; Yuill, Richard

    2012-08-01

    Blanchard et al. (2009) demonstrated that hebephilia is a genuine sexual preference, but then proposed, without argument or evidence, that it should be designated as a mental disorder in the DSM-5. A series of Letters-to-the-Editor criticized this proposal as a non sequitur. Blanchard (2009), in rebuttal, reaffirmed his position, but without adequately addressing some central criticisms. In this article, we examine hebephilia-as-disorder in full detail. Unlike Blanchard et al., we discuss definitions of mental disorder, examine extensive evidence from a broad range of sources, and consider alternative (i.e., non-pathological) explanations for hebephilia. We employed Wakefield's (1992b) harmful dysfunction approach to disorder, which holds that a condition only counts as a disorder when it is a failure of a naturally selected mechanism to function as designed, which is harmful to the individual in the current environment. We also considered a harmful-for-others approach to disorder (Brülde, 2007). Examination of historical, cross-cultural, sociological, cross-species, non-clinical empirical, and evolutionary evidence and perspectives indicated that hebephilic interest is an evolved capacity and hebephilic preference an expectable distributional variant, both of which were adaptively neutral or functional, not dysfunctional, in earlier human environments. Hebephilia's conflict with modern society makes it an evolutionary mismatch, not a genuine disorder. Though it should not be classified as a disorder, it could be entered in the DSM's V-code [corrected] section, used for non-disordered conditions that create significant problems in present-day society.

  6. 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

  7. Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.

    PubMed

    Chaudhuri, Rima; Khoo, Poh Sim; Tonks, Katherine; Junutula, Jagath R; Kolumam, Ganesh; Modrusan, Zora; Samocha-Bonet, Dorit; Meoli, Christopher C; Hocking, Samantha; Fazakerley, Daniel J; Stöckli, Jacqueline; Hoehn, Kyle L; Greenfield, Jerry R; Yang, Jean Yee Hwa; James, David E

    2015-01-01

    Insulin resistance (IR) is one of the earliest predictors of type 2 diabetes. However, diagnosis of IR is limited. High fat fed mouse models provide key insights into IR. We hypothesized that early features of IR are associated with persistent changes in gene expression (GE) and endeavored to (a) develop novel methods for improving signal:noise in analysis of human GE using mouse models; (b) identify a GE motif that accurately diagnoses IR in humans; and (c) identify novel biology associated with IR in humans. We integrated human muscle GE data with longitudinal mouse GE data and developed an unbiased three-level cross-species analysis platform (single gene, gene set, and networks) to generate a gene expression motif (GEM) indicative of IR. A logistic regression classification model validated GEM in three independent human data sets (n=115). This GEM of 93 genes substantially improved diagnosis of IR compared with routine clinical measures across multiple independent data sets. Individuals misclassified by GEM possessed other metabolic features raising the possibility that they represent a separate metabolic subclass. The GEM was enriched in pathways previously implicated in insulin action and revealed novel associations between β-catenin and Jak1 and IR. Functional analyses using small molecule inhibitors showed an important role for these proteins in insulin action. This study shows that systems approaches for identifying molecular signatures provides a powerful way to stratify individuals into discrete metabolic groups. Moreover, we speculate that the β-catenin pathway may represent a novel biomarker for IR in humans that warrant future investigation.

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

    PubMed Central

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

    2014-01-01

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

  9. 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

  10. 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

  11. 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

  12. Investigation of Cross-Species Translatability of Pharmacological MRI in Awake Nonhuman Primate - A Buprenorphine Challenge Study

    PubMed Central

    Seah, Stephanie; Asad, Abu Bakar Ali; Baumgartner, Richard; Feng, Dai; Williams, Donald S.; Manigbas, Elaine; Beaver, John D.; Reese, Torsten; Henry, Brian; Evelhoch, Jeffrey L.; Chin, Chih-Liang

    2014-01-01

    Background Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP). Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. Methodology We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV)-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v.), a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC) values from brain areas with high density of µ-opioid receptors. Principal Findings In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p<0.05, n = 4). This observation is strikingly consistent with µ-opioid receptor distribution depicted by [6-O-[11C]methyl]buprenorphine ([11C]BPN) positron emission tomography imaging study in baboons. Furthermore, our findings are consistent with previous buprenorphine phMRI studies in humans and conscious rats which collectively demonstrate the cross-species

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Right Place, Wrong Species: A 20-Year Review of Rabies Virus Cross Species Transmission among Terrestrial Mammals in the United States

    PubMed Central

    Wallace, Ryan M.; Gilbert, Amy; Slate, Dennis; Chipman, Richard; Singh, Amber; Cassie Wedd; Blanton, Jesse D.

    2014-01-01

    Introduction In the continental US, four terrestrial mammalian species are reservoirs for seven antigenic rabies virus variants. Cross species transmission (CST) occurs when a rabies virus variant causes disease in non-reservoir species. Methods This study analyzed national surveillance data for rabies in terrestrial mammals. The CST rate was defined as: number of rabid non-reservoir animals/number of rabid reservoir animals. CST rates were analyzed for trend. Clusters of high CST rate counties were evaluated using space-time scanning statistics. Results The number of counties reporting a raccoon variant CST rate >1.0 increased from 75 in 1992 to 187 in 2011; counties with skunk variant CST rates >1.0 remained unchanged during the same period. As of 2011, for every rabid raccoon reported within the raccoon variant region, there were 0.73 cases of this variant reported in non-reservoir animals. Skunks were the most common non-reservoir animal reported with the raccoon rabies variant. Domestic animals were the most common non-reservoir animal diagnosed with a skunk rabies virus variant (n = 1,601). Cross species transmission rates increased fastest among domestic animals. Conclusions Cross species transmission of rabies virus variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control. Cross species transmission in raccoon rabies enzootic regions increased dramatically during the study period. Pet owners should vaccinate their dogs and cats to ensure against CST, particularly in regions with active foci of rabies circulation. Clusters of high CST activity represent areas for further study to better understand interspecies disease transmission dynamics. Each CST event has the potential to result in a rabies virus adapted for sustained transmission in a new species; therefore further understanding of the dynamics of CST may help in early detection or prevention of the emergence of new terrestrial

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Characterization of a Composite Material to Mimic Human Cranial Bone

    DTIC Science & Technology

    2015-09-01

    ARL-RP-0552 ● SEP 2015 US Army Research Laboratory Characterization of a Composite Material to Mimic Human Cranial Bone by...presented at: 20th International Conference on Composite Materials; 2015 Jul 19–24; Copenhagen, Denmark. Approved for public release...US Army Research Laboratory Characterization of a Composite Material to Mimic Human Cranial Bone by Thomas A Plaisted Weapons and Materials

  3. 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.

  4. 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

  5. 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.

  6. Cross-species microarray analysis with the OSCAR system suggests an INSR->Pax6->NQO1 neuro-protective pathway in aging and Alzheimer's disease

    PubMed Central

    Lu, Yue; He, Xin; Zhong, Sheng

    2007-01-01

    OSCAR is a web platform for cluster and cross-species analysis of microarray data. It provides a comprehensive but friendly environment to both users and algorithm developers. For users, OSCAR provides cluster tools for both single and multiple species data, together with interactive analysis features. For single species data, OSCAR currently provides Hierarchical Clustering, K-means, partition around medoids (PAM), Self-Organizing Map (SOM), Tight Clustering and a novel algorithm called ‘Consensus Tight-clustering’. The new Consensus Tight-clustering algorithm delivers robust gene clusters and its result is more resistant to false positives than other state-of-the-art algorithms. For cross-species data analysis, OSCAR provides two novel computational tools: ‘coherentCluster’, ‘coherentSubset’ and a novel visualization tool: ‘comparative heatmap’. Applying the coherentCluster algorithm to human and fly aging data, we identified several coherent clusters of genes, which share co-regulation patterns that are highly correlated with the aging process in both of the two species. One coherent cluster suggests insulin receptor (INSR) may regulate Pax6 in both species and across different tissues. Further analysis with human brain expression and pathological data suggests an INSR->Pax6->quinone oxidoreductase (NQO1)->detoxification neuro-protective pathway might be present in aging or diseased brain. For algorithm developers, OSCAR is a plug-and-play platform. With little effort, developers can plug their own algorithms into the OSCAR server without revealing the source codes, which will equip their command line executables with user-friendly interface and interactive analysis capability. In summary, OSCAR initiates an open platform for development and application of clustering and cross-species analysis programs. OSCAR stands for an open system for cluster analysis of microarray data. It is available at: http://biocomp.bioen.uiuc.edu/oscar PMID:17545194

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Further evidence for Clock△19 mice as a model for bipolar disorder mania using cross-species tests of exploration and sensorimotor gating

    PubMed Central

    van Enkhuizen, Jordy; Minassian, Arpi; Young, Jared W.

    2013-01-01

    Bipolar disorder (BD) is a pervasive neuropsychiatric disorder characterized by episodes of mania and depression. The switch between mania and depression may reflect seasonal changes and certainly can be affected by alterations in sleep and circadian control. The circadian locomotor output cycles kaput (CLOCK) protein is a key component of the cellular circadian clock. Mutation of the Clock gene encoding this protein in Clock△19 mutant mice leads to behavioral abnormalities reminiscent of BD mania. To date, however, these mice have not been assessed in behavioral paradigms that have cross-species translational validity. In the present studies of Clock△19 and wildtype (WT) littermate mice, we quantified exploratory behavior and sensorimotor gating, which are abnormal in BD manic patients. We also examined the saccharin preference of these mice and their circadian control in different photoperiods. Clock△19 mice exhibited behavioral alterations that are consistent with BD manic patients tested in comparable tasks, including hyperactivity, increased specific exploration, and reduced sensorimotor gating. Moreover, compared to WT mice, Clock△19 mice exhibited a greater preference for sweetened solutions and greater sensitivity to altered photoperiod. In contrast with BD manic patients however, Clock△19 mice exhibited more circumscribed movements during exploration. Future studies will extend the characterization of these mice in measures with cross-species translational relevance to human testing. PMID:23623885

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

    PubMed

    Ou, Wu; Delisle, Josie; Jacques, Jerome; Shih, Joanna; Price, Graeme; Kuhn, Jens H; Wang, Vivian; Verthelyi, Daniela; Kaplan, Gerardo; Wilson, Carolyn A

    2012-01-25

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

  14. 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.

  15. Exploring the Role of 5-HT1A Receptors in the Regulation of Prepulse Inhibition in Mice: Implications for Cross-Species Comparisons

    PubMed Central

    2012-01-01

    Prepulse inhibition (PPI) is a model of sensorimotor gating, a sensory filtering mechanism which is disrupted in schizophrenia. Here, investigation of the role of the serotonin-1A (5-HT1A) receptor in the regulation of PPI in two mouse strains, C57Bl/6 and Balb/c, was used to address findings in the PPI literature on species and mouse strain differences that question the usefulness of PPI as a cross-species preclinical test. Although the full 5-HT1A receptor agonist, 8-OH-DPAT, induced markedly different strain-specific responses in PPI, other selective 5-HT1A receptor ligands with partial agonist or antagonist activity elicited similar effects across strains. Pretreatment with the serotonin precursor, 5-HTP, to increase serotonergic activity in the brain, unmasked a decrease in PPI caused by 8-OH-DPAT in C57Bl/6 mice. Pretreatment with the serotonin synthesis inhibitor, PCPA, to decrease serotonergic activity in the brain, unmasked an 8-OH-DPAT-induced increase in PPI in this strain. These studies show that the strain-dependent involvement of 5-HT1A receptors in PPI can be modulated by the type of 5-HT1A ligand used, or increasing or decreasing serotonin levels in the brain. These results help to clarify some of the mouse strain and species differences in PPI regulation and strengthen its usefulness as a cross-species measure of sensorimotor gating. PMID:23336054

  16. 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.

  17. 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.

  18. Further evidence for ClockΔ19 mice as a model for bipolar disorder mania using cross-species tests of exploration and sensorimotor gating.

    PubMed

    van Enkhuizen, Jordy; Minassian, Arpi; Young, Jared W

    2013-07-15

    Bipolar disorder (BD) is a pervasive neuropsychiatric disorder characterized by episodes of mania and depression. The switch between mania and depression may reflect seasonal changes and certainly can be affected by alterations in sleep and circadian control. The circadian locomotor output cycles kaput (CLOCK) protein is a key component of the cellular circadian clock. Mutation of the Clock gene encoding this protein in ClockΔ19 mutant mice leads to behavioral abnormalities reminiscent of BD mania. To date, however, these mice have not been assessed in behavioral paradigms that have cross-species translational validity. In the present studies of ClockΔ19 and wildtype (WT) littermate mice, we quantified exploratory behavior and sensorimotor gating, which are abnormal in BD manic patients. We also examined the saccharin preference of these mice and their circadian control in different photoperiods. ClockΔ19 mice exhibited behavioral alterations that are consistent with BD manic patients tested in comparable tasks, including hyperactivity, increased specific exploration, and reduced sensorimotor gating. Moreover, compared to WT mice, ClockΔ19 mice exhibited a greater preference for sweetened solutions and greater sensitivity to altered photoperiod. In contrast with BD manic patients however, ClockΔ19 mice exhibited more circumscribed movements during exploration. Future studies will extend the characterization of these mice in measures with cross-species translational relevance to human testing. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Cross-species transmission potential between wild pigs, livestock, poultry, wildlife, and humans: implications for disease risk management in North America.

    PubMed

    Miller, Ryan S; Sweeney, Steven J; Slootmaker, Chris; Grear, Daniel A; Di Salvo, Paul A; Kiser, Deborah; Shwiff, Stephanie A

    2017-08-10

    Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of viral, and 63% of parasitic pathogens caused clinical disease in other species. Non-porcine livestock in the family Bovidae shared the most pathogens with swine (82%). Only 49% of currently listed OIE domestic swine diseases had published wild pig surveillance studies. The co-occurrence of wild pigs and farms increased annually at a rate of 1.2% with as much as 57% of all farms and 77% of all agricultural animals co-occurring with wild pigs. The increasing co-occurrence of wild pigs with livestock and humans along with the large number of pathogens shared is a growing risk for cross-species transmission.

  20. Cross-species transmission potential between wild pigs, livestock, poultry, wildlife, and humans: Implications for disease risk management in North America

    USGS Publications Warehouse

    Miller, Ryan S.; Sweeney, Steven J; Slootmaker, Chris; Grear, Daniel; DiSalvo, Paul A.; Kiser, Deborah; Shwiff, Stephanie A.

    2017-01-01

    Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of viral, and 63% of parasitic pathogens caused clinical disease in other species. Non-porcine livestock in the family Bovidae shared the most pathogens with swine (82%). Only 49% of currently listed OIE domestic swine diseases had published wild pig surveillance studies. The co-occurrence of wild pigs and farms increased annually at a rate of 1.2% with as much as 57% of all farms and 77% of all agricultural animals co-occurring with wild pigs. The increasing co-occurrence of wild pigs with livestock and humans along with the large number of pathogens shared is a growing risk for cross-species transmission.

  1. 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

  2. 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.

  3. Estimation of MIMIC Model Parameters with Multilevel Data

    ERIC Educational Resources Information Center

    Finch, W. Holmes; French, Brian F.

    2011-01-01

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

  4. 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…

  5. A facile method to synthesize histones with posttranslational modification mimics.

    PubMed

    Wang, Zhiyong U; Wang, Yane-Shih; Pai, Pei-Jing; Russell, William K; Russell, David H; Liu, Wenshe R

    2012-07-03

    Using an evolved pyrrolysyl-tRNA synthetase-tRNA(Pyl) pair, a Se-alkylselenocysteine was genetically incorporated into histone H3 with a high protein expression yield. Quantitative oxidative elimination of Se-alkylselenocysteine followed by Michael addition reactions with various thiol nucleophiles generated biologically active mimics of H3 with posttranslational modifications including lysine methylation, lysine acetylation, and serine phosphorylation.

  6. 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

  7. 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.

  8. 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

  9. 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…

  10. 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

  11. Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.

    PubMed

    Colak, Dilek; Nofal, Asmaa; Albakheet, Albandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; Al-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Inan, Mehmet S; 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

  12. 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.

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

    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. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd.

  14. 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

  15. Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure.

    PubMed

    Pfaender, Stephanie; Walter, Stephanie; Todt, Daniel; Behrendt, Patrick; Doerrbecker, Juliane; Wölk, Benno; Engelmann, Michael; Gravemann, Ute; Seltsam, Axel; Steinmann, Joerg; Burbelo, Peter D; Klawonn, Frank; Feige, Karsten; Pietschmann, Thomas; Cavalleri, Jessika-M V; Steinmann, Eike

    2015-09-01

    The recent discovery of hepatitis C virus (HCV)-related viruses in different animal species has raised new speculations regarding the origin of HCV and the possibility of a zoonotic source responsible for the endemic HCV transmission. As a consequence, these new findings prompt questions regarding the potential for cross-species transmissions of hepaciviruses. The closest relatives to HCV discovered to date are the non-primate hepaciviruses (NPHVs), which have been described to infect horses. To evaluate the risk of a potential zoonotic transmission, we analysed NPHV RNA and antibodies in humans with occupational exposure to horses in comparison with a low-risk group. Both groups were negative for NPHV RNA, even though low seroreactivities against various NPHV antigens could be detected irrespective of the group. In conclusion, we did not observe evidence of NPHV transmission between horses and humans.

  16. Cross-species induction and enhancement of antimicrobial activity produced by epibiotic bacteria from marine algae and invertebrates, after exposure to terrestrial bacteria.

    PubMed

    Mearns-Spragg, A; Bregu, M; Boyd, K G; Burgess, J G

    1998-09-01

    Antibiotic producing marine bacteria isolated from surfaces of the marine alga Fucus vesiculosus and the nudibranch Archidoris pseudoargus were exposed to live cells of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and heat-killed cells of Staph. aureus. Twelve out of the 16 marine strains tested showed enhanced antimicrobial activity towards Staph. aureus, E. coli and Ps. aeruginosa following this exposure. Three out of seven strains tested showed enhanced antimicrobial activity when exposed to Ps. aeruginosa and three out of seven strains showed enhanced antimicrobial activity when exposed to E. coli. These results suggest that production of antimicrobial compounds by marine bacteria can be induced by the presence of terrestrial bacteria. This appears to be the first example of cross-species induction and enhancement of antimicrobial activity in marine bacteria and has important implications for the design of antibiotic screening assays and for an understanding of microbial competition in the environment.

  17. Isolation and characterization of microsatellites in the harlequin ladybird, Harmonia axyridis (Coleoptera, Coccinellidae), and cross-species amplification within the family Coccinellidae.

    PubMed

    Loiseau, Anne; Malausa, Thibaut; Lombaert, Eric; Martin, Jean-François; Estoup, Arnaud

    2009-05-01

    A total of 18 microsatellite DNA loci were isolated and characterized from the harlequin ladybird, Harmonia axyridis (Coleoptera: Coccinellidae). We optimized a multiplex panel consisting of two polymerase chain reactions, allowing the genotyping of all loci. The number of alleles and heterozygosity observed at each locus ranged from 1 to 12 and from 0 to 100%, respectively. After Bonferroni correction for multiple tests, none of the loci deviated significantly from Hardy-Weinberg equilibrium and there was no indication of significant linkage disequilibrium among pairs of loci. Successful cross-species amplification was obtained for only three of the seven tested species of Coccinellidae. © 2009 Blackwell Publishing Ltd. No claim to original US government works.

  18. 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.

  19. 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.

  20. Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure

    PubMed Central

    Pfaender, Stephanie; Walter, Stephanie; Todt, Daniel; Behrendt, Patrick; Doerrbecker, Juliane; Wölk, Benno; Engelmann, Michael; Gravemann, Ute; Seltsam, Axel; Steinmann, Joerg; Burbelo, Peter D.; Klawonn, Frank; Feige, Karsten; Pietschmann, Thomas; Cavalleri, Jessika-M. V.

    2015-01-01

    The recent discovery of hepatitis C virus (HCV)-related viruses in different animal species has raised new speculations regarding the origin of HCV and the possibility of a zoonotic source responsible for the endemic HCV transmission. As a consequence, these new findings prompt questions regarding the potential for cross-species transmissions of hepaciviruses. The closest relatives to HCV discovered to date are the non-primate hepaciviruses (NPHVs), which have been described to infect horses. To evaluate the risk of a potential zoonotic transmission, we analysed NPHV RNA and antibodies in humans with occupational exposure to horses in comparison with a low-risk group. Both groups were negative for NPHV RNA, even though low seroreactivities against various NPHV antigens could be detected irrespective of the group. In conclusion, we did not observe evidence of NPHV transmission between horses and humans. PMID:26041875

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Development and characterization of microsatellite markers from tropical forage Stylosanthes species and analysis of genetic variability and cross-species transferability.

    PubMed

    Chandra, Amaresh; Tiwari, K K; Nagaich, D; Dubey, N; Kumar, S; Roy, A K

    2011-12-01

    A limited number of functional molecular markers has slowed the desired genetic improvement of Stylosanthes species. Hence, in an attempt to develop simple sequence repeat (SSR) markers, genomic libraries from Stylosanthes seabrana B.L. Maass & 't Mannetje (2n=2x=20) using 5' anchored degenerate microsatellite primers were constructed. Of the 76 new microsatellites, 21 functional primer pairs were designed. Because of the small number of primer pairs designed, 428 expressed sequence tag (EST) sequences from seven Stylosanthes species were also examined for SSR detection. Approximately 10% of sequences delivered functional primer pairs, and after redundancy elimination, 57 microsatellite repeats were selected. Tetranucleotides followed by trinucleotides were the major repeated sequences in Stylosanthes ESTs. In total, a robust set of 21 genomic-SSR (gSSR) and 20 EST-SSR (eSSR) markers were developed. These markers were analyzed for intraspecific diversity within 20 S. seabrana accessions and for their cross-species transferability. Mean expected (He) and observed (Ho) heterozygosity values with gSSR markers were 0.64 and 0.372, respectively, whereas with eSSR markers these were 0.297 and 0.214, respectively. Dendrograms having moderate bootstrap value (23%-94%) were able to distinguish all accessions of S. seabrana with gSSR markers, whereas eSSR markers showed 100% similarities between few accessions. The set of 21 gSSRs, from S. seabrana, and 20 eSSRs, from selected Stylosanthes species, with their high cross-species transferability (45% with gSSRs, 86% with eSSRs) will facilitate genetic improvement of Stylosanthes species globally.

  7. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-01

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

  10. 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

  11. The ability of lizards to identify an artificial Batesian mimic.

    PubMed

    Beneš, Josef; Veselý, Petr

    2017-08-01

    Birds are usually considered the main predators shaping the evolution of aposematic signals and mimicry. Nevertheless, some lizards also represent predominately visually oriented predators, so they may also play an important role in the evolution of aposematism. Despite this fact, experimental evidence regarding the responses of lizards to aposematic prey is very poor compared to such evidence in birds. Lizards possess very similar sensory and cognitive abilities to those of birds and their response to aposematic prey may thus be affected by very similar processes. We investigated the reactions of a lizard, the Gran Canaria skink (Chalcides sexlineatus), to an aposematic prey and its artificial Batesian mimic. Further, we attempted to ascertain whether the lizard's food experience has any effect on its ability to recognise an artificial Batesian mimic, by using two groups of predators differing in their prior experience with the prey from which the mimic was fabricated. The red firebug (Pyrrhocoris apterus) was used as an aposematic model, and the Guyana spotted roach (Blaptica dubia) as the palatable prey from which the mimic was fabricated. The appearance of the roach was modified by a paper sticker placed on its back. The skinks showed a strong aversion towards the model firebug. They also avoided attacking the cockroaches with the firebug pattern sticker. This suggests that a visual rather than a chemical signal is responsible for this aversion. The protection provided by the firebug sticker was even effective when the skinks were familiar with unmodified cockroaches (previous food experience). Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. 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

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

    PubMed

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

    2016-05-24

    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.

  14. 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

  15. Polymeric ADAM protein mimics interrogate mammalian sperm-egg binding.

    PubMed

    Lee, Younjoo; Sampson, Nicole S

    2009-03-23

    The sperm proteins ADAM2 and ADAM3, members of the ADAM family of proteins, have been implicated in mammalian sperm-egg binding. However, elucidating their roles is complex because of the interdependence of ADAM protein expression in the testis. Hence, multivalent probes containing the three-amino acid binding sequence of ADAM2, glutamate-cysteine-aspartate (ECD), and ADAM3, glutamine-cysteine-aspartate (QCD), were designed, synthesized, and tested to investigate gamete interactions. In this work, ECD polymer mimics were synthesized by ring-opening metathesis polymerization with a faster initiating ruthenium catalyst than previously used. Polymers containing 100 copies of the ECD peptide mimic were found to be the best inhibitors of fertilization. The multivalent QCD polymers were also tested as inhibitors of fertilization. The structure-activity profile was the same as ECD polymers, but the overall potency was lower. Both ECD and QCD polymers require the presence of beta(1) integrin to inhibit fertilization. Next, triblock ABA and ABC copolymers containing both ECD and QCD ligands were synthesized with 96 monomer spacers as their B blocks. Although these polymers had lower densities of ECD and QCD peptides, their potencies correlated with the potencies of their corresponding homopolymers. In addition, no synergy between ECD and QCD mimics was observed. All the data suggest that QCD and ECD bind to the same complex of proteins that includes beta(1) integrin.

  16. 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

  17. A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours

    PubMed Central

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

    2016-01-01

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

  18. CRADA Final Report: Mucin Mimic and Glycopeptide Synthesis

    SciTech Connect

    Bertozzi, Carolyn R.

    2002-10-22

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

  19. 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

  20. Ceragenins: cholic acid-based mimics of antimicrobial peptides.

    PubMed

    Lai, Xin-Zhong; Feng, Yanshu; Pollard, Jacob; Chin, Judy N; Rybak, Michael J; Bucki, Robert; Epand, Raquel F; Epand, Richard M; Savage, Paul B

    2008-10-01

    The prevalence of drug-resistant bacteria drives the quest for new antimicrobials, including those that are not expected to readily engender resistance. One option is to mimic Nature's most ubiquitous means of controlling bacterial growth, antimicrobial peptides, which have evolved over eons. In general, bacteria remain susceptible to these peptides. Human antimicrobial peptides play a central role in innate immunity, and deficiencies in these peptides have been tied to increased rates of infection. However, clinical use of antimicrobial peptides is hampered by issues of cost and stability. The development of nonpeptide mimics of antimicrobial peptides may provide the best of both worlds: a means of using the same mechanism chosen by Nature to control bacterial growth without the problems associated with peptide therapeutics. The ceragenins were developed to mimic the cationic, facially amphiphilic structures of most antimicrobial peptides. These compounds reproduce the required morphology using a bile-acid scaffolding and appended amine groups. The resulting compounds are actively bactericidal against both gram-positive and gram-negative organisms, including drug-resistant bacteria. This antimicrobial activity originates from selective association of the ceragenins with negatively charged bacterial membrane components. Association has been studied with synthetic models of bacterial membrane components, with bacterial lipopolysaccharide, with vesicles derived from bacterial phospholipids, and with whole cells. Comparisons of the antimicrobial activities of ceragenins and representative antimicrobial peptides suggest that these classes of compounds share a mechanism of action. Rapid membrane depolarization is caused by both classes as well as blebbing of bacterial membranes. Bacteria express the same genes in response to both classes of compounds. On the basis of the antibacterial activities of ceragenins and preliminary in vivo studies, we expect these compounds to

  1. 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…

  2. 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…

  3. 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…

  4. Superparamagnetic nanotraps containing MIP based mimic lipase for biotransformations uses

    NASA Astrophysics Data System (ADS)

    Keçili, Rüstem; Özcan, Ayça Atılır; Ersöz, Arzu; Hür, Deniz; Denizli, Adil; Say, Rıdvan

    2011-05-01

    The nanoparticle comprises a superparamagnetic iron oxide nanoparticle core conjugated with trimethoxylsilyl propylmethacrylate (TMSPM) and methacryloylamido serine (MASE), methacryloylamido histidine (MAH), methacryloylamido glutamic acid (MAGA) monomers, and p-nitrophenyl palmitate ( p-NPP) which is a substrate of lipase as a template molecule, which enables the creation of lipase active region. The resulting hybrid superparamagnetic nanotraps are magnetically separable, highly active, and stable under harsh conditions. In this study, the advantages of high selectivity of molecular imprinting technique have used to get mimic lipase for the synthesis of methyl jasmonate and methyl oleate.

  5. 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

  6. 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.

  7. 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.

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

    PubMed

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

    2010-11-10

    Proteome maps of hepatopancreas (midgut gland) and ovarian tissues of the crustacean, Cancer pagurus (Decapoda; edible crab) have been produced by 2D-PAGE and identification of proteins, following trypsin proteolysis, by electrospray MS/MS and database searching. Owing to the lack of sequence information on proteins and fully sequenced genomes amongst the decapod crustaceans and given the evolutionary distance to the nearest full genome database (Daphnia), it was necessary to adopt a non-conventional identification approach. Thus, a strategy was developed for effective identification of decapod proteins by sequence similarity, homology-based cross-species database searching, using various algorithms and a combination of NCBI Crustacea and Arthropoda databases, together with the Arthropoda PartiGene database (Blaxter, University of Edinburgh). In both hepatopancreas and ovary tissues, the largest group of proteins identified were a variety of enzymes, followed by a smaller number of storage/transport proteins [including vitellogenin (yolk protein), several subunits of hemocyanin, cryptocyanin, ferritin and calreticulin], with fewer structural proteins (actin, tubulin) and heat-shock proteins, in addition to a number of proteins of miscellaneous functions. Such protein identifications allow the development of tools, such as antibodies and RNA/DNA probes, to investigate the functions of the proteins in specific tissues during development. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. 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

  11. 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.

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

    PubMed

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

    2015-01-01

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

  13. 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.

  14. Development of the first polymorphic microsatellite markers for the Roman snail Helix pomatia L., 1758 (Helicidae) and cross-species amplification within the genus Helix.

    PubMed

    Krapal, A M; Popa, O P; Iorgu, E I; Cojocaru, L B; Popa, A F; Popa, L O

    2016-09-19

    The terrestrial snail Helix pomatia (Gastropoda: Stylommatophora: Helicidae) is one of the largest gastropod species in Europe. This species is strictly protected in some European Union countries; however, at the same time, it is also farmed and commercialized for human consumption. Here, we describe 11 microsatellite markers that are very useful in population genetic studies for assessing the status of both wild and farmed populations of this species of community interest. The microsatellites were isolated using 454 pyrosequencing technologies and 11 primer pairs were selected and used for genotyping an H. pomatia population and also checked for cross-species amplification on H. lucorum and H. lutescens specimens. The number of alleles per locus ranged from 3 to 13 and observed heterozygosity was between 0.458 and 0.917. Seven of these loci were polymorphic in H. lucorum, and four in H. lutescens. This set of nuclear markers provides a powerful tool for population genetic studies of this species of community interest, and also for closely related species. The described microsatellite markers should also facilitate the identification of populations of conservation concern.

  15. 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.

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

    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.

  17. Development of novel microsatellite markers for Holothurian scabra (Holothuriidae), Apostichopus japonicas (Stichopodidae) and cross-species testing in other sea cucumbers

    NASA Astrophysics Data System (ADS)

    Shangguan, Jingbo; Li, Zhongbao

    2017-06-01

    Thirty-five new microsatellite loci from the sea cucumbers Holothurian scabra (Jaeger, 1833) and Apostichopus japonicas (Selenka, 1867) were screened and characterized using the method of magnetic bead enrichment. Of the twenty-four polymorphic loci tested, eighteen were consistent with Hardy-Weinberg equilibrium after a modified false discovery rate (B-Y FDR) correction, whereas six showed statistically significant deviations (CHS2 and CHS11: P <0.014790; FCS1, FCS6, FCS8 and FCS14: P <0.015377). Furthermore, four species of plesiomorphous and related sea cucumbers (Holothurian scabra, Holothuria leucospilota, Stichopus horrens and Apostichopus japonicas) were tested for mutual cross-amplification using a total of ninety microsatellite loci. Although transferability and universality of all loci were generally low, the results of the cross-species study showed that the markers can be applied to identify individuals to species according to the presence or absence of specific microsatellite alleles. The microsatellite markers reported here will contribute to the study of genetic diversity, assisted breeding, and population conservation in sea cucumbers, as well as allow for the identification of individuals to closely related species.

  18. 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.

  19. 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.

  20. Models and tissue mimics for brain shift simulations.

    PubMed

    Forte, Antonio E; Galvan, Stefano; Dini, Daniele

    2017-09-06

    Capturing the deformation of human brain during neurosurgical operations is an extremely important task to improve the accuracy or surgical procedure and minimize permanent damage in patients. This study focuses on the development of an accurate numerical model for the prediction of brain shift during surgical procedures and employs a tissue mimic recently developed to capture the complexity of the human tissue. The phantom, made of a composite hydrogel, was designed to reproduce the dynamic mechanical behaviour of the brain tissue in a range of strain rates suitable for surgical procedures. The use of a well-controlled, accessible and MRI compatible alternative to real brain tissue allows us to rule out spurious effects due to patient geometry and tissue properties variability, CSF amount uncertainties, and head orientation. The performance of different constitutive descriptions is evaluated using a brain-skull mimic, which enables 3D deformation measurements by means of MRI scans. Our combined experimental and numerical investigation demonstrates the importance of using accurate constitutive laws when approaching the modelling of this complex organic tissue and supports the proposal of a hybrid poro-hyper-viscoelastic material formulation for the simulation of brain shift.

  1. 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

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

    PubMed Central

    Zollinger, Sue Anne; Suthers, Roderick A.

    2004-01-01

    The diverse vocal performances of oscine songbirds are produced by the independent but coordinated patterns of activity in muscles controlling separate sound generators on the left and right sides of their duplex vocal organ, the syrinx. Species with different song styles use the two sides of their syrinx in different ways to produce their species-typical songs. Understanding how a vocal mimic copies another species' song may provide an insight into whether there are alternative motor mechanisms for generating the model's song and what parts of his song are most difficult to produce. We show here that when a vocal mimic, the northern mockingbird, accurately copies the song of another species it also uses the vocal motor pattern employed by the model species. Deviations from the model's production mechanism result in predictable differences in the mockingbird's song. Species-specific acoustic features of the model seem most difficult to copy, suggesting that they have been exposed to the strongest selective pressure to maximize their performance. PMID:15129958

  3. Amphipathic beta-strand mimics as potential membrane disruptive antibiotics.

    PubMed

    Watson, Jessica L; Gillies, Elizabeth R

    2009-08-21

    In recent years, there have been increasing numbers of bacterial strains emerging that are resistant to the currently available antibiotics. In the search for new antibiotics, attention has been focused on natural antimicrobial peptides that act by selectively disrupting the membranes of bacterial cells, a mechanism that is thought to be nonconducive to the development of resistance. It is desirable to mimic the structures and activities of these peptides while introducing properties such as resistance to proteolytic degradation, which make molecules more ideal for development as drugs. Described here is the design and synthesis of beta-strand mimetic oligomers based on alternating alpha-amino acids and azacyclohexenone units that segregate cationic lysine and hydrophobic valine side chains on opposite faces of the beta-strand. (1)H NMR dilution studies demonstrated that despite the incorporation of alternating d- and l-amino acids in order to obtain facial amphiphilicity, these oligomers are capable of dimerizing to beta-sheet mimics in a manner similar to the oligomers containing all l-amino acids. The ability of the molecules to disrupt phospholipid vesicles mimicking the membranes of both bacterial and mammalian cells was investigated using a fluorescent dye leakage assay. Several of the oligomers were found to exhibit activity and selectivity for the bacterial over mammalian membranes. Overall, these studies demonstrate the promise of this class of molecules for the development of new potential antibiotics and provide information on the structural features that are important for activity.

  4. Biologically active metal-independent superoxide dismutase mimics

    SciTech Connect

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

    1990-03-20

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

  5. 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.

  6. Incidence and outcome of functional stroke mimics admitted to a hyperacute stroke unit.

    PubMed

    Gargalas, Sergios; Weeks, Robert; Khan-Bourne, Najma; Shotbolt, Paul; Simblett, Sara; Ashraf, Leah; Doyle, Claire; Bancroft, Victoria; David, Anthony S

    2017-01-01

    Some patients admitted to acute stroke units are diagnosed as stroke mimics. A minority have a functional neurological disorder ('functional mimics'). To determine the incidence of functional stroke mimics admitted to a hyperacute stroke unit (HASU); to compare their clinical characteristics with medical mimics and stroke cases and obtain information about outcomes. Patients admitted to the King's College Hospital HASU between 2011 and 2012 were analysed. Data were obtained from the Stroke Improvement National Audit Programme (SINAP) database. Expert consensus diagnosis was used to classify functional mimics. Follow-up information was obtained from a retrospective case series in primary care over the year following discharge. 1165 patients were admitted to the HASU; 904 patients with stroke (77.6%), 163 medical mimics (14%) and 98 functional mimics (8.4%). Functional mimics were significantly more likely to be female (63.3%) versus 49.7% medical mimics and 45.5% stroke, and younger (mean age (SD)) 49.1 (18.8) than medical mimic (63.5 years (16.7)) and stroke cases (71 years (15.5)). Weakness and slurred speech were the commonest presentations of functional mimics and diagnostic MRI was used more often. Clinician recorded visual and speech symptoms and neglect were significantly more frequent in patients with stroke than either mimic group. Of the 68 functional mimics on whom follow-up information was obtained, 40 (59%) were referred to another service most often for a psychologically-based intervention. Functional stroke mimics are an important subgroup admitted to acute stroke services and have a distinct demographic and clinical profile. Their outcomes are poorly monitored. Services should be developed to better diagnose and manage these patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    PubMed

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-02-21

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

  10. Piezoelectric materials mimic the function of the cochlear sensory epithelium.

    PubMed

    Inaoka, Takatoshi; Shintaku, Hirofumi; Nakagawa, Takayuki; Kawano, Satoyuki; Ogita, Hideaki; Sakamoto, Tatsunori; Hamanishi, Shinji; Wada, Hiroshi; Ito, Juichi

    2011-11-08

    Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application.

  11. 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.

  12. 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

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

    PubMed Central

    Rota, Jadranka; Wagner, David L.

    2006-01-01

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

  14. 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.

  15. 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.

  16. Biofilm streamer formation in a microfluidic porous media mimic

    NASA Astrophysics Data System (ADS)

    Kumar, Aloke; Valiei, Amin; Mukherjee, Partha; Liu, Yang; Thundat, Thomas

    2013-03-01

    Biofilm formation in porous media is of significant importance in many environmental and industrial processes such as bioremediation, oil recovery, and wastewater treatment. Among different biological and environmental factors, hydrodynamics is considered an important determinant of the dynamics of biofilm formation. In the present study, we fabricated a microfluidic porous media mimic and investigated how fluid flow influences the formation of filamentous structures, known as streamers, between porous media structures. Streamers are viscoelastic materials composed of extracellular polymeric substances (EPS) and bacterial cells, and these filamentous structures are typically tethered at either one of both ends to surfaces. We studied evolution of streamers in different flow rates and identified a tangible link between hydrodynamic conditions and development of these filamentous structures. Our results show that hydrodynamic conditions not only determine the limit of the streamers formation, but also influence both temporal evolution and spatial organization of biofilm streamers.

  17. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

    PubMed Central

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

    2016-01-01

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

  18. Piezoelectric materials mimic the function of the cochlear sensory epithelium

    PubMed Central

    Inaoka, Takatoshi; Shintaku, Hirofumi; Nakagawa, Takayuki; Kawano, Satoyuki; Ogita, Hideaki; Sakamoto, Tatsunori; Hamanishi, Shinji; Wada, Hiroshi; Ito, Juichi

    2011-01-01

    Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application. PMID:22025702

  19. 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

  20. Acidic polysaccharide mimics via ring-opening metathesis polymerization.

    PubMed

    Wathier, Michel; Stoddart, Stephanie S; Sheehy, Matthew J; Grinstaff, Mark W

    2010-11-17

    An efficient and general synthetic strategy for the preparation of high-molecular-weight hydrophilic polymers bearing both carboxylic acid and hydroxyl pendant groups is described. Specifically, poly(5,6-dihydroxyoxanorbornane carboxylic acid) with molecular weight ranging from ∼100 000 to 5 000 000 g/mol was prepared by ring-opening metathesis polymerization of methyl 5-oxanorbornene-2-carboxylate in the presence of Grubbs catalyst II and subsequently modified to tune the hydrophobic/hydrophilic properties by the introduction of either hydroxyl or carboxylic acid functionalities. These polymers mimic the natural acidic polysaccharide alginate and form hydrogels with polylysine. These polymers belong to a class of carbohydrate-like polymers, which are of interest for investigating the relationships between chemical structure and rheological properties as well as for providing new synthetic polysaccharide substitutes for applications in the biotechnology and pharmaceutical industries.

  1. Hydrogels as extracellular matrix mimics for 3D cell culture.

    PubMed

    Tibbitt, Mark W; Anseth, Kristi S

    2009-07-01

    Methods for culturing mammalian cells ex vivo are increasingly needed to study cell and tissue physiology and to grow replacement tissue for regenerative medicine. Two-dimensional culture has been the paradigm for typical in vitro cell culture; however, it has been demonstrated that cells behave more natively when cultured in three-dimensional environments. Permissive, synthetic hydrogels and promoting, natural hydrogels have become popular as three-dimensional cell culture platforms; yet, both of these systems possess limitations. In this perspective, we discuss the use of both synthetic and natural hydrogels as scaffolds for three-dimensional cell culture as well as synthetic hydrogels that incorporate sophisticated biochemical and mechanical cues as mimics of the native extracellular matrix. Ultimately, advances in synthetic-biologic hydrogel hybrids are needed to provide robust platforms for investigating cell physiology and fabricating tissue outside of the organism. (c) 2009 Wiley Periodicals, Inc.

  2. 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.

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

    PubMed

    Ankley, Gerald T; Gray, L Earl

    2013-04-01

    Many structural and functional aspects of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis are known to be highly conserved, but the significance of this from a toxicological perspective has received comparatively little attention. High-quality data generated through development and validation of Tier 1 tests for the U.S. Environmenal Protection Agency Endocrine Disruptor Screening Program (EDSP) offer a unique opportunity to compare responses of mammals versus fish to chemicals that may affect shared pathways within the HPG axis. The present study focuses on data generated with model chemicals that act (primarily) as estrogen receptor agonists (17α-ethynylestradiol, methoxychlor, bisphenol A), androgen receptor agonists (methyltestosterone, 17β-trenbolone), androgen receptor antagonists (flutamide, vincolozolin, p,p'-DDE), or inhibitors of different steroidogenic enzymes (ketoconazole, fadrozole, fenarimol, prochloraz). All 12 chemicals had been tested in the EDSP fish short-term (21 d) reproduction assay and in one or more of the four in vivo Tier 1 screens with rats (uterotrophic, Hershberger, male and female pubertal assays). There was a high concordance between the fish and rat assays with respect to identifying chemicals that impacted specific endocrine pathways of concern. Although most chemicals were detected as positive in both rat and fish assays, eliminating data from one class of vertebrate or the other would weaken the battery. For example, the effects of competitive inhibitors of steroid hormone synthesis were far more obvious in the fish assay, whereas the activity of androgen receptor antagonists was clearer in mammalian assays. The observations are significant both to the cross-species extrapolation of toxicity of HPG-active substances and the optimization of screening and testing frameworks for endocrine-disrupting chemicals. Copyright © 2013 SETAC.

  4. Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis.

    PubMed

    Ogawa, Saki; Murakami, Tomoaki; Inoshima, Yasuo; Ishiguro, Naotaka

    2015-01-01

    Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

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

    PubMed

    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

    2014-08-26

    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.

  6. Cross-species comparison of conazole fungicide metabolites using rat and rainbow trout (Onchorhynchus mykiss) hepatic microsomes and purified human CYP 3A4.

    PubMed

    Mazur, Christopher S; Kenneke, John F

    2008-02-01

    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 biotransformation processes. Although inherently complex, metabolite identification is critical to risk assessment since the product(s) formed may pose a greater toxicological threat than the parent molecule. This issue is further complicated by differences observed in metabolic transformation pathways among species. Conazoles represent an important class of azole fungicides that are widely used in both pharmaceutical and agricultural applications. The antifungal property of conazoles occurs via complexation with the cytochrome P450 monooxygenases (CYP) responsible for mediating fungal cell wall synthesis. This mode of action has cause for concern regarding the potential adverse impact of conazoles on the broad spectrum of CYP-based processes within mammalian and aquatic species. In this study, in vitro metabolic profiles were determined for thirteen conazole fungicides using rat and rainbow trout (Oncorhynchus mykiss) liver microsomes and purified human CYP 3A4. Results showed that 10 out of the 13 conazoles tested demonstrated identical metabolite profiles among rat and trout microsomes, and these transformations were well conserved via both aromatic and aliphatic hydroxylation and carbonyl reduction processes. Furthermore, nearly all metabolites detected in the rat and trout microsomal assays were detected within the human CYP 3A4 assays. These results indicate a high degree of metabolic conservation among species with an equivalent isozyme activity of human CYP 3A4 being present in both the rat and trout, and provides insight into xenobiotic biotransformations needed for accurate risk assessment.

  7. 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.

  8. 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

  9. Profiling conserved biological pathways in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) to elucidate key transcriptomic alterations regulating cystogenesis: A cross-species meta-analysis approach.

    PubMed

    Chatterjee, Shatakshee; Verma, Srikant Prasad; Pandey, Priyanka

    2017-09-05

    Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen. Intra-species combined analysis was performed after considering removal of batch effect. Significantly enriched GO biological processes and KEGG pathways were computed and their overlap was observed. For the conserved pathways, biological modules and gene regulatory networks were observed. Additionally, Gene Set Enrichment Analysis (GSEA) using Molecular Signature Database (MSigDB) was performed for genes found in conserved pathways. We obtained 28 modules of significantly enriched GO processes and 5 major functional categories from significantly enriched KEGG pathways conserved in human, mice and rats that in turn suggest a global transcriptomic perturbation affecting cyst - formation, growth and progression. Significantly enriched pathways obtained from up-regulated genes such as Genomic instability, Protein localization in ER and Insulin Resistance were found to regulate cyst formation and growth whereas cyst progression due to increased cell adhesion and inflammation was suggested by perturbations in Angiogenesis, TGF-beta, CAMs, and Infection related pathways. Additionally, networks revealed shared genes among pathways e.g. SMAD2 and SMAD7 in Endocytosis and TGF-beta. Our study suggests cyst formation and progression to be an outcome of interplay between a set of several key deregulated pathways. Thus, further translational research is warranted focusing on developing a combinatorial therapeutic

  10. 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.

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

    PubMed

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

    2016-06-21

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

  12. 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.

  13. 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

  14. Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer.

    PubMed

    Silva, Grace O; He, Xiaping; Parker, Joel S; Gatza, Michael L; Carey, Lisa A; Hou, Jack P; Moulder, Stacy L; Marcom, Paul K; Ma, Jian; Rosen, Jeffrey M; Perou, Charles M

    2015-07-01

    A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent CNAs is key to advancing therapeutics because it is likely that these regions contain breast tumor 'drivers' (i.e., cancer causal genes). This study aims to characterize the genomic landscape of breast cancer CNAs and identify potential subtype-specific drivers using a large set of human breast tumors and genetically engineered mouse (GEM) mammary tumors. Using a novel method called SWITCHplus, we identified subtype-specific DNA CNAs occurring at a 15% or greater frequency, which excluded many well-known breast cancer-related drivers such as amplification of ERBB2, and deletions of TP53 and RB1. A comparison of CNAs between mouse and human breast tumors identified regions with shared subtype-specific CNAs. Additional criteria that included gene expression-to-copy number correlation, a DawnRank network analysis, and RNA interference functional studies highlighted candidate driver genes that fulfilled these multiple criteria. Numerous regions of shared CNAs were observed between human breast tumors and GEM mammary tumor models that shared similar gene expression features. Specifically, we identified chromosome 1q21-23 as a Basal-like subtype-enriched region with multiple potential driver genes including PI4KB, SHC1, and NCSTN. This step-wise computational approach based on a cross-species comparison is applicable to any tumor type for which sufficient human and model system DNA copy number data exist, and in this instance, highlights that a single region of amplification may in fact harbor multiple driver genes.

  15. 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

  16. 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

  17. Restless legs syndrome in Wilson's disease: frequency, characteristics, and mimics.

    PubMed

    Trindade, M C; Bittencourt, T; Lorenzi-Filho, G; Alves, R C; de Andrade, D C; Fonoff, E T; Bor-Seng-Shu, E; Machado, A A; Teixeira, M J; Barbosa, E R; Tribl, G G

    2017-02-01

    To determine characteristics, clinical significance, frequency, and mimics of restless legs syndrome (RLS) in a cohort of Wilson's disease (WD, n = 42/f = 18), compared to healthy, matched controls. Structured clinical interviews (patients and caregiving family members), repeated neurological examinations (afternoon and presleep), comprehensive laboratory tests, WD-, RLS-, and sleep-specific rating scales, and video-polysomnography. Thirteen patients with WD (13/42 = 31.0%) clearly fulfilled the five diagnostic criteria of RLS; in eight patients (19.1%), the burden of RLS was clinically significant. The RLS was of moderate severity, equally distributed among sexes, manifested mainly in the evening and before falling asleep, and had developed mostly after clinical manifestation of WD (time elapsed 10.2 ± 14.5 years), still at a young mean age (27.5 ± 11.5 years). The known RLS-associated features were absent (normal iron and kidney parameters) or rare (positive family history, polyneuropathy). Compared to WD patients without RLS, patients with RLS were significantly elder and had suffered longer from WD. WD-specific RLS mimics as well as RLS confounding motor comorbidities (dystonia, tremor, chorea) were frequent and a diagnostic challenge; in difficult cases, the differentiation was reached by clinical observation of the motor behavior in the evening or at nighttime. RLS was frequent in this cohort of WD and might be causally related to WD. RLS should be included in the diagnostic work-up of WD. In complex motor disorders, differential diagnosis of RLS might require evening/nighttime examination and video-polysomnography. In WD patients with a clinically significant RLS, treatment with dopaminergic substances may be considered. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes

    PubMed Central

    Christen, Urs; Edelmann, Kurt H.; McGavern, Dorian B.; Wolfe, Tom; Coon, Bryan; Teague, Meghann K.; Miller, Stephen D.; Oldstone, Michael B.A.; von Herrath, Matthias G.

    2004-01-01

    We document here that infection of prediabetic mice with a virus expressing an H-2Kb–restricted mimic ligand to a self epitope present on β cells accelerates the development of autoimmune diabetes. Immunization with the mimic ligand expanded autoreactive T cell populations, which was followed by their trafficking to the islets, as visualized in situ by tetramer staining. In contrast, the mimic ligand did not generate sufficient autoreactive T cells in naive mice to initiate disease. Diabetes acceleration did not occur in H-2Kb–deficient mice or in mice tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens accelerate a previously established autoimmune process. Sequential heterologous viral infections might therefore act in concert to precipitate clinical autoimmune disease, even if single exposure to a viral mimic does not always cause sufficient tissue destruction. PMID:15520861

  19. Meningioma mimics: five key imaging features to differentiate them from meningiomas.

    PubMed

    Starr, C J; Cha, S

    2017-09-01

    There are a wide variety of intracranial mass lesions, both benign and malignant, which can closely mimic meningioma on imaging. We present five characteristic imaging features that can alert the radiologist to consider other differential diagnoses. Of the five imaging characteristics that were rarely seen in meningiomas, but common and specific for meningioma mimics, absence of dural tail is the most common (83.7%). Homogeneous T2 hyperintensity or T2 hypointensity are seen in nearly half of meningioma mimics and osseous destruction and leptomeningeal extension are present in 40.5% and 21.6% of meningioma mimics, respectively. The distinction between meningioma and its mimics is important because a large portion of the meningioma mimics requires substantially different clinical and surgical management. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

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

    2015-01-01

    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. 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 cultivated safflower and formed a

  5. 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.

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

    2012-01-01

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

  8. Cross-tissue and cross-species analysis of gene expression in skeletal muscle and electric organ of African weakly-electric fish (Teleostei; Mormyridae).

    PubMed

    Lamanna, Francesco; Kirschbaum, Frank; Waurick, Isabelle; Dieterich, Christoph; Tiedemann, Ralph

    2015-09-03

    African weakly-electric fishes of the family Mormyridae are able to produce and perceive weak electric signals (typically less than one volt in amplitude) owing to the presence of a specialized, muscle-derived electric organ (EO) in their tail region. Such electric signals, also known as Electric Organ Discharges (EODs), are used for objects/prey localization, for the identification of conspecifics, and in social and reproductive behaviour. This feature might have promoted the adaptive radiation of this family by acting as an effective pre-zygotic isolation mechanism. Despite the physiological and evolutionary importance of this trait, the investigation of the genetic basis of its function and modification has so far remained limited. In this study, we aim at: i) identifying constitutive differences in terms of gene expression between electric organ and skeletal muscle (SM) in two mormyrid species of the genus Campylomormyrus: C. compressirostris and C. tshokwe, and ii) exploring cross-specific patterns of gene expression within the two tissues among C. compressirostris, C. tshokwe, and the outgroup species Gnathonemus petersii. Twelve paired-end (100 bp) strand-specific RNA-seq Illumina libraries were sequenced, producing circa 330 M quality-filtered short read pairs. The obtained reads were assembled de novo into four reference transcriptomes. In silico cross-tissue DE-analysis allowed us to identify 271 shared differentially expressed genes between EO and SM in C. compressirostris and C.tshokwe. Many of these genes correspond to myogenic factors, ion channels and pumps, and genes involved in several metabolic pathways. Cross-species analysis has revealed that the electric organ transcriptome is more variable in terms of gene expression levels across species than the skeletal muscle transcriptome. The data obtained indicate that: i) the loss of contractile activity and the decoupling of the excitation-contraction processes are reflected by the down

  9. 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

  10. 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

  11. Antimicrobial polymers as synthetic mimics of host-defense peptides.

    PubMed

    Kuroda, Kenichi; Caputo, Gregory A

    2013-01-01

    Antibiotic-resistant bacteria 'superbugs' are an emerging threat to public health due to the decrease in effective antibiotics as well as the slowed pace of development of new antibiotics to replace those that become ineffective. The need for new antimicrobial agents is a well-documented issue relating to world health. Tremendous efforts have been given to developing compounds that not only show high efficacy, but also those that are less susceptible to resistance development in the bacteria. However, the development of newer, stronger antibiotics which can overcome these acquired resistances is still a scientific challenge because a new mode of antimicrobial action is likely required. To that end, amphiphilic, cationic polymers have emerged as a promising candidate for further development as an antimicrobial agent with decreased potential for resistance development. These polymers are designed to mimic naturally occurring host-defense antimicrobial peptides which act on bacterial cell walls or membranes. Antimicrobial-peptide mimetic polymers display antibacterial activity against a broad spectrum of bacteria including drug-resistant strains and are less susceptible to resistance development in bacteria. These polymers also showed selective activity to bacteria over mammalian cells. Antimicrobial polymers provide a new molecular framework for chemical modification and adaptation to tune their biological functions. The peptide-mimetic design of antimicrobial polymers will be versatile, generating a new generation of antibiotics toward implementation of polymers in biomedical applications. Copyright © 2012 Wiley Periodicals, Inc.

  12. 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.

  13. 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.

  14. The Endemic Mimic: Blastomycosis An Illness Often Misdiagnosed

    PubMed Central

    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. PMID:25125734

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

    PubMed

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

    2012-12-10

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

  16. 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

  17. Chimpanzees and Humans Mimic Pupil-Size of Conspecifics

    PubMed Central

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

    2014-01-01

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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Toward an understanding of the retinal chromophore in rhodopsin mimics.

    PubMed

    Huntress, Mark M; Gozem, Samer; Malley, Konstantin R; Jailaubekov, Askat E; Vasileiou, Chrysoula; Vengris, Mikas; Geiger, James H; Borhan, Babak; Schapiro, Igor; Larsen, Delmar S; Olivucci, Massimo

    2013-09-05

    Recently, a rhodopsin protein mimic was constructed by combining mutants of the cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal chromophore. Here, we present a combined computational quantum mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of CRABPII. We employ the QM/MM models to study the absorption (λ(a)max), fluorescence (λ(f)max), and reactivity of a CRABPII triple mutant incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also study the spectroscopy of the same mutant incorporating the unprotonated chromophore and of another double mutant incorporating the neutral unbound retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary fluorescence spectroscopy and ultrafast transient absorption spectroscopy resolved two different evolving excited state populations which were computationally assigned to distinct locally excited and charge-transfer species. This last species is shown to evolve along reaction paths describing a facile isomerization of the biologically relevant 11-cis and 13-cis double bonds. This work represents a first exploratory attempt to model and study these artificial protein systems. It also indicates directions for improving the QM/MM models so that they could be more effectively used to assist the bottom-up design of genetically encodable probes and actuators employing the retinal chromophore.

  5. 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.

  6. Imaging of the Urachus: Anomalies, Complications, and Mimics.

    PubMed

    Parada Villavicencio, Carolina; Adam, Sharon Z; Nikolaidis, Paul; Yaghmai, Vahid; Miller, Frank H

    2016-01-01

    Urachal anomalies are more common than previously thought, with more cases discovered incidentally, because of the increased use of cross-sectional imaging. Although an abnormal persistence of an embryologic communication between the bladder and the umbilicus is often recognized and managed in childhood, it may persist into adulthood, with a greater risk of morbidity. Congenital urachal anomalies that are detected early can benefit from an optimized management including surgical approach with a complete resection of the urachal remnant in cases when spontaneous resolution or medical management has failed. At imaging, the different types of urachal anomalies have a distinct appearance. A patent urachus is recognized as an elongated patent connection between the bladder and the umbilicus. An umbilical-urachal sinus is depicted as a blind focal dilatation at the umbilical end, whereas a vesicourachal diverticulum is a focal outpouching at the vesical end. Urachal cysts are visualized as midline fluid-filled sacs most frequently located near the bladder dome. Complications of urachal anomalies have nonspecific clinical findings and can mimic other abdominal and pelvic processes. Potential complications, such as infection and tumors, should be recognized early to ensure optimal management. Understanding of the embryonic development of the urachus is necessary for the radiologist to diagnose the wide variety of urachal disease. (©)RSNA, 2016.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

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

    PubMed

    Vesvikar, Mehul S; Al-Dahhan, Muthanna

    2005-03-20

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

  14. 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.

  15. 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.

  16. Fibromuscular dysplasia: a rare disease that can mimic vasculitis.

    PubMed

    Capsoni, Franco; Poletto, Giorgio; Giorgetti, Pier Luigi

    2012-12-01

    Fibromuscular dysplasia (FMD) is an uncommon angiopathy that occurs mainly in young to middle-aged female individuals. It is an idiopathic, segmental, non-inflammatory and non-atherosclerotic vascular disease leading to stenosis of small- and medium-sized arteries. Clinical manifestations are determined by the artery involved, most commonly hypertension (renal artery) and stroke (carotid artery). When FMD affects multiple vascular beds, it may mimic a systemic vasculitis. Here, we present the case of a young female patient with FMD. The patient had a clinical history of bilateral internal carotid artery dissection that required surgical repair. Since a systemic vascular disease was suspected, abdominal angiography was done, showing evidence of a "string of beads" appearance involving the distal two-thirds of the right renal artery. This lesion is considered to be pathognomonic of the medial FMD that accounts for 70-95% of all cases of FMD. Two years later, a new magnetic resonance angiography confirmed the "string of beads" appearance of the middle to distal part of the right renal artery, with significant hemodynamic stenosis that was successfully dilated with percutaneous transluminal angioplasty.

  17. A Guideline to Family-Wide Comparative State-of-the-Art Quantitative RT-PCR Analysis Exemplified with a Brassicaceae Cross-Species Seed Germination Case Study[W][OA

    PubMed Central

    Graeber, Kai; Linkies, Ada; Wood, Andrew T.A.; Leubner-Metzger, Gerhard

    2011-01-01

    Comparative biology includes the comparison of transcriptome and quantitative real-time RT-PCR (qRT-PCR) data sets in a range of species to detect evolutionarily conserved and divergent processes. Transcript abundance analysis of target genes by qRT-PCR requires a highly accurate and robust workflow. This includes reference genes with high expression stability (i.e., low intersample transcript abundance variation) for correct target gene normalization. Cross-species qRT-PCR for proper comparative transcript quantification requires reference genes suitable for different species. We addressed this issue using tissue-specific transcriptome data sets of germinating Lepidium sativum seeds to identify new candidate reference genes. We investigated their expression stability in germinating seeds of L. sativum and Arabidopsis thaliana by qRT-PCR, combined with in silico analysis of Arabidopsis and Brassica napus microarray data sets. This revealed that reference gene expression stability is higher for a given developmental process between distinct species than for distinct developmental processes within a given single species. The identified superior cross-species reference genes may be used for family-wide comparative qRT-PCR analysis of Brassicaceae seed germination. Furthermore, using germinating seeds, we exemplify optimization of the qRT-PCR workflow for challenging tissues regarding RNA quality, transcript stability, and tissue abundance. Our work therefore can serve as a guideline for moving beyond Arabidopsis by establishing high-quality cross-species qRT-PCR. PMID:21666000

  18. A web-based data visualization tool for the MIMIC-II database.

    PubMed

    Lee, Joon; Ribey, Evan; Wallace, James R

    2016-02-04

    Although MIMIC-II, a public intensive care database, has been recognized as an invaluable resource for many medical researchers worldwide, becoming a proficient MIMIC-II researcher requires knowledge of SQL programming and an understanding of the MIMIC-II database schema. These are challenging requirements especially for health researchers and clinicians who may have limited computer proficiency. In order to overcome this challenge, our objective was to create an interactive, web-based MIMIC-II data visualization tool that first-time MIMIC-II users can easily use to explore the database. The tool offers two main features: Explore and Compare. The Explore feature enables the user to select a patient cohort within MIMIC-II and visualize the distributions of various administrative, demographic, and clinical variables within the selected cohort. The Compare feature enables the user to select two patient cohorts and visually compare them with respect to a variety of variables. The tool is also helpful to experienced MIMIC-II researchers who can use it to substantially accelerate the cumbersome and time-consuming steps of writing SQL queries and manually visualizing extracted data. Any interested researcher can use the MIMIC-II data visualization tool for free to quickly and conveniently conduct a preliminary investigation on MIMIC-II with a few mouse clicks. Researchers can also use the tool to learn the characteristics of the MIMIC-II patients. Since it is still impossible to conduct multivariable regression inside the tool, future work includes adding analytics capabilities. Also, the next version of the tool will aim to utilize MIMIC-III which contains more data.

  19. 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.

  20. 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.

  1. 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

  2. [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.

  3. 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. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  4. 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…

  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. Geographic variation in mimetic precision among different species of coral snake mimics.

    PubMed

    Akcali, C K; Pfennig, D W

    2017-07-01

    Batesian mimicry is widespread, but whether and why different species of mimics vary geographically in resemblance to their model is unclear. We characterized geographic variation in mimetic precision among four Batesian mimics of coral snakes. Each mimic occurs where its model is abundant (i.e. in 'deep sympatry'), rare (i.e. at the sympatry/allopatry boundary or 'edge sympatry') and absent (i.e. in allopatry). Geographic variation in mimetic precision was qualitatively different among these mimics. In one mimic, the most precise individuals occurred in edge sympatry; in another, they occurred in deep sympatry; in the third, they occurred in allopatry; and in the fourth, precise mimics were not concentrated anywhere throughout their range. Mimicry was less precise in allopatry than in sympatry in only two mimics. We present several nonmutually exclusive hypotheses for these patterns. Generally, examining geographic variation in mimetic precision - within and among different mimics - offers novel insights into the causes and consequences of mimicry. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  7. 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…

  8. 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).

  9. Description of stroke mimics after complete neurovascular assessment.

    PubMed

    Avellaneda-Gómez, C; Rodríguez Campello, A; Giralt Steinhauer, E; Gómez González, A; Serra Martínez, M; de Ceballos Cerrajería, P; Zabalza de Torres, A; Cuadrado-Godia, E; Ois Santiago, A; Jiménez-Conde, J; Roquer, J

    2017-02-04

    A considerable percentage of events initially diagnosed as ischaemic stroke have non-cerebrovascular causes; these are called stroke mimics (SM). Currently available evidence about these events is heterogeneous and comes from studies with small samples. The purpose of our study is to identify conditions that may present as SM, define their epidemiological and clinical characteristics, and determine the percentage of cases of SM treated with intravenous fibrinolysis. Prospective study including all patients admitted to a tertiary university hospital between June 2005 and April 2015 with a diagnosis of acute stroke. We analysed demographic data, cardiovascular risk factors, time from code stroke activation to admission, stroke severity (NIHSS), final destination after discharge, degree of disability (mRS), and treatment. We compared SM and ischaemic strokes. We ruled out patients with intracranial haemorrhage, subarachnoid haemorrhage, or other causes of SM that may be detected on the baseline CT scan. Four hundred four of the 4,570 included patients (8.8%) were found to have SM. Patients with SM were younger (70.3 vs. 74, P<.0001), less likely to exhibit cardiovascular risk factors and atrial fibrillation (13 vs. 34%, P<.0001), scored lower on the NIHSS at baseline (2 vs. 4, P<.0001), and included fewer cases of aphasia (9.4 vs. 19.6%, P<.02) and dysphagia (1.2 vs. 17%, P<.0001) than patients with stroke. SM caused fewer code stroke activations (28 vs. 40%, P<.0001). Patients with SM required shorter hospital stays (4.9 vs. 7.8 days, P<.0001), were less frequently admitted to the stroke unit (47 vs. 60%, P<.0001) and more frequently discharged home (95 vs. 62%, P<.0001), and had better outcomes (mRS scores 0-2; 76 vs. 54%, P<.0001). Intravenous fibrinolysis was administered to 4.7% of these patients. Epileptic seizures were the most frequent cause of SM (26%). In our sample, 8.8% of all diagnoses of ischaemic stroke were SM. These events have different demographic

  10. Stroke mimics under the drip-and-ship paradigm.

    PubMed

    Mehta, Sonal; Vora, Nirav; Edgell, Randall C; Allam, Hesham; Alawi, Aws; Koehne, Jennifer; Kumar, Abhay; Feen, Eliahu; Cruz-Flores, Salvador; Alshekhlee, Amer

    2014-01-01

    Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). The drip-and-ship paradigm and any psychiatric history predict the diagnosis of

  11. 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.

  12. 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.

  13. 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...

  14. 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

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

    PubMed Central

    Pfennig, David W.; Mullen, Sean P.

    2010-01-01

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

  16. 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.

  17. 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).

  18. 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

  19. 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

  20. 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.

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

    PubMed Central

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

    2014-01-01

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

  2. 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.

  3. 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.

  4. Transfection of microRNA Mimics Should Be Used with Caution

    PubMed Central

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

    2015-01-01

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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Genome-wide discovery of single nucleotide polymorphisms (SNPs) and single nucleotide variants (SNVs) in deep-sea mussels: Potential use in population genomics and cross-species application

    NASA Astrophysics Data System (ADS)

    Xu, Ting; Sun, Jin; Lv, Jia; Kayama Watanabe, Hiromi; Li, Tianqi; Zou, Weiwen; Rouse, Greg W.; Wang, Shi; Qian, Pei-Yuan; Bao, Zhenmin; Qiu, Jian-Wen

    2017-03-01

    The present study aimed to generate genome-wide single nucleotide polymorphisms (SNPs) for the deep-sea mussel Bathymodiolus platifrons via a combination of genome survey sequencing and the type IIB endonuclease restriction-site associated DNA (2b-RAD) sequencing, assess the potential use of SNPs in detecting fine-sale population genetic structure and signatures of divergent selection, as well as their cross-species application in other bathymodioline mussels. Genome survey sequencing was conducted for one individual of B. platifrons. De novo assembly resulted in 781,720 sequences with a scaffold N50 of 2.9 kb. Using these sequences as a reference, 9307 genome-wide SNPs were identified by 2b-RAD for 28 B. platifrons individuals collected from a seep and a vent population. Among these SNPs, nine outliers showed significant evidence for divergent selection, and their positions in the genes or scaffolds were identified. The FST estimated based on the putative neutral SNPs was low (0.0126) indicating the two B. platifrons populations having a high genetic connectivity. However, the permutation test detected significant differences (P<0.00001), indicating the two populations having clearly detectable genetic differentiation. The Bayesian clustering analyses and principle component analyses (PCA) performed based on either the putative neutral or outlier SNPs also showed that these two populations were genetically differentiated. In addition, 2b-RAD was also conducted to detect 10,199, 6429, and 3811 single nucleotide variants (SNVs) respectively in the bathymodioline mussels Bathymodiolus japonicus, Bathymodiolus aduloides and Idas sp. with different phylogenetic distances from B. platifrons. Overall, our study has demonstrated the feasibility and effectiveness of combining genome survey sequencing and 2b-RAD to rapidly generate genomic resources for use in fine-scale population genetic studies, and various cross-species applications.

  13. Protein Misfolding Cyclic Amplification Cross-Species Products of Mouse-Adapted Scrapie Strain 139A and Hamster-Adapted Scrapie Strain 263K with Brain and Muscle Tissues of Opposite Animals Generate Infectious Prions.

    PubMed

    Gao, Chen; Han, Jun; Zhang, Jin; Wei, Jing; Zhang, Bao-Yun; Tian, Chan; Zhang, Jie; Shi, Qi; Dong, Xiao-Ping

    2017-07-01

    Transmission of prions between mammalian species is limited by a "species barrier," a biological effect involving an increase in incubation period to decrease the percentage of animals succumbing to disease. In this study, we used protein misfolding cyclic amplification (PMCA) technique, which accelerates the conversion of prion proteins in vitro. Direct interspecies PMCA involving 144 cycles confirmed that both mouse-adapted scrapie strain 139A and hamster-adapted 263K could use brain homogenates of opposite species to form proteinase K (PK)-resistant PrP proteins (PrP(res)). Newly formed interspecies prions could stably propagate themselves in subsequent serial PMCA passages. The two types of PMCA-generated cross-species PrP(res) changed their glycosylation profiles, which was similar to that observed during interspecies infection by the mouse agent 139A in vivo. These profiles were distinct from individual seeded PrP(Sc) and possessed properties of new hosts. Comparative analysis with respect to PK resistance showed no significant diversity between PMCA-PrP(res) and native PrP(Sc) or between brain and muscle PrP(res). However, PrP(res) from the relatively early cycles of serial PMCA showed lower PK resistance than those from later cycles. Inoculation of these PMCA products amplified with homogeneous or heterogeneous brain tissues (cross-species products) induced experimental transmissible spongiform encephalopathies. These results suggested that PMCA can help prion strains to overcome species barrier and to propagate efficiently both in vitro and in vivo.

  14. MicroRNA-146a Mimics Reduce the Peripheral Neuropathy in Type II Diabetic Mice.

    PubMed

    Liu, Xian Shuang; Fan, Baoyan; Szalad, Alexandra; Jia, Longfei; Wang, Lei; Wang, Xinli; Pan, Wanlong; Zhang, Li; Zhang, Ruilan; Hu, Jiani; Zhang, Xiao Ming; Chopp, Michael; Zhang, Zheng Gang

    2017-09-12

    MicroRNA-146a (miR-146a) regulates multiple immune diseases. However, the role of miR-146a in diabetic peripheral neuropathy (DPN) has not been investigated. We found that mice (db/db) with type II diabetes exhibited substantial down-regulation of miR-146a in sciatic nerve tissue. Systemic administration of miR-146a mimics to diabetic mice elevated miR-146a levels in plasma and sciatic nerve tissue and substantially increased motor and sensory nerve conduction velocities by 29% and 11%, respectively, and regional blood flow by 50% in sciatic nerve tissue. Treatment with miR-146a mimics also considerably decreased the response in db/db mice to thermal stimuli thresholds. Histopathological analysis showed that miR-146a mimics markedly augmented the density of FITC-dextran perfused blood vessels and increased the number of intraepidermal nerve fibers (IENF), myelin thickness and axonal diameters of sciatic nerves. In addition, miR-146a treatment reduced and increased M1 and M2 macrophage phenotype markers, respectively. Analysis of miRNA target array revealed that miR-146a mimics greatly suppressed expression of many proinflammatory genes and downstream related cytokines. Collectively, our data indicate that treatment of diabetic mice with miR-146a mimics robustly reduces DPN and that suppression of hyperglycemia-induced proinflammatory genes by miR-146a mimics may underlie its therapeutic effect. © 2017 by the American Diabetes Association.

  15. 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

  16. Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm.

    PubMed

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

    2015-08-01

    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. 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 mm(3), 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. 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. Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  17. 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

  18. 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.

  19. 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

  20. Molecules that mimic apolipoprotein A-I: potential agents for treating atherosclerosis.

    PubMed

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

    2014-03-27

    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.

  1. 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

  2. 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.

  3. A novel nitrogen-dependent gene associates with the lesion mimic trait in wheat

    USDA-ARS?s Scientific Manuscript database

    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...

  4. 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

  5. Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics

    PubMed Central

    Matsui, Masayuki; Prakash, Thazha P; Corey, David R

    2016-01-01

    MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development. PMID:26903376

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

    PubMed

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

    2016-06-01

    In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. 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.

  8. 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.

  9. 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.

  10. The importance of pattern similarity between Müllerian mimics in predator avoidance learning.

    PubMed Central

    Rowe, Candy; Lindström, Leena; Lyytinen, Anne

    2004-01-01

    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. PMID:15101700

  11. Design of Effective Primary MicroRNA Mimics With Different Basal Stem Conformations

    PubMed Central

    van den Berg, Fiona T; Rossi, John J; Arbuthnot, Patrick; Weinberg, Marc S

    2016-01-01

    Primary microRNA (pri-miRNA) mimics are important mediators of effective gene silencing and are well suited for sustained therapeutic applications. Pri-miRNA mimics are processed in the endogenous miRNA biogenesis pathway, where elements of the secondary RNA structure are crucial for efficient miRNA production. Cleavage of the pri-miRNA to a precursor miRNA (pre-miRNA) by Drosha-DGCR8 typically occurs adjacent to a basal stem of ~11 bp. However, a number of pri-miRNA structures are expected to contain slightly shorter or longer basal stems, which may be further disrupted in predicted folding of the expressed pri-miRNA sequence. We investigated the function and processing of natural and exogenous RNA guides from pri-miRNAs with various basal stems (9–13 bp), where a canonical hairpin was predicted to be well or poorly maintained in predicted structures of the expressed sequence. We have shown that RNA guides can be effectively derived from pri-miRNAs with various basal stem conformations, while predicted guide region stability can explain the function of pri-miRNA mimics, in agreement with previously proposed design principles. This study provides insight for the design of effective mimics based on naturally occurring pri-miRNAs and has identified several novel scaffolds suitable for use in gene silencing applications. PMID:26756196

  12. 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.

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

    PubMed

    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.

  14. 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

  15. 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…

  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. 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.

  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. 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

  20. A novel vascular targeting strategy for brain-derived endothelial cells using a TCR mimic antibody

    PubMed Central

    Bhattacharya, Raktima; Xu, Yan; Rahman, Md. Ashequr; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette B.; Weidanz, Jon A.; Bickel, Ulrich

    2010-01-01

    Organ-specific vascular targeting, for example to the blood-brain barrier, requires the identification of unique molecular addresses on a subset of endothelial cells. The present study describes a crucial step towards tapping the exquisite specificity of the peptide/HLA class I system for this goal. We utilized a novel T-cell receptor (TCR) mimic antibody of high affinity and specificity, which is restricted by HLA-A2 and has been generated to recognize a peptide epitope derived from p68 RNA helicase (YLLPAIVHI). The parent protein is highly expressed by brain endothelial cells. Flow cytometry and confocal imaging showed that the antibody binds to HLA-A2 positive human brain derived endothelial cells, both immortalized hCMEC/D3 cells and primary cells. The TCR mimic antibody undergoes internalization into vesicles, where significant colocalization occurs with the early endosomal marker EEA-1, but barely with caveolin-1. To our knowledge internalization of neither MHC class I protein nor TCR mimics by brain endothelial cells has been previously observed. Knockdown of p68 protein expression by siRNA reduced the presentation of YLLPAIVHI-peptide/HLA-A2 complexes on the cell membrane by half as measured by flow cytometry 48h later. We also found that brain endothelial cells isolated from HLA-A2 transgenic mouse strains express the A2 transgene, and brain endothelial cells of one of these strains also present YLLPAIVHI-peptide/HLA-A2, making these mouse strains suitable models for studying TCR mimic antibodies in vivo. In conclusion, these data strongly support the notion that TCR mimic antibodies could be a new class of therapeutic targeting agents in a wide variety of diseases. PMID:20506235

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. [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.

  10. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.

  12. 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

  13. Mesenchymal tumours of the breast and their mimics: a review with approach to diagnosis.

    PubMed

    Cheah, Alison L; Billings, Steven D; Rowe, J Jordi

    2016-08-01

    Mesenchymal tumours of the breast comprise a broad spectrum of entities that frequently pose diagnostic challenges to surgical pathologists. Metaplastic carcinoma and phyllodes tumour are site-specific mimics that account for the majority of tumours in the breast with a sarcomatoid appearance. Although uncommon, mammary tumours with fibroblastic, adipocytic or vascular differentiation may be encountered, spanning the spectrum from benign to malignant. Tumours with histiocytoid morphology are potential traps due to bland cytomorphology and resemblance to reactive processes. This comprehensive review provides a diagnostic approach to specific challenging mesenchymal tumours of the breast and their mimics, with a discussion on the salient morphological, immunohistochemical and molecular features that allow accurate diagnosis and will help the pathologist avoid potential pitfalls. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  14. 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.

  15. Recent advances in design, synthesis and bioactivity of paclitaxel-mimics.

    PubMed

    Wen, Guan; Qu, Xiao-Xia; Wang, Dan; Chen, Xing-Xiu; Tian, Xin-Chuan; Gao, Feng; Zhou, Xian-Li

    2016-04-01

    Taxane-type anticancer drugs, including paclitaxel and its semi-synthetic derivatives docetaxel and cabazitaxel, are widely applied to chemotherapy of malignancy like breast cancer, ovarian cancer, non-small cell lung cancer and prostate cancer. However, their clinical applications are generally limited by scarce natural resources, various side effects and multidrug resistance. Therefore, it is significant to develop paclitaxel-mimics with simplified structure, fewer side effects and improved pharmaceutical properties. Based on our investigation on chemistry of paclitaxel, the current review summarized the most recent advances in the design, synthesis and biological activities of paclitaxel-mimics, which could be appealing to researchers in the field of medicinal chemistry and oncology. Meanwhile, smart design, interesting synthesis and potential bioactivities of these novel compounds may also provide valuable reference for the wider scientific communities. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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.

  17. Sensitive fluorescence on-off probes for the fast detection of a chemical warfare agent mimic.

    PubMed

    Khan, Muhammad Shar Jhahan; Wang, Ya-Wen; Senge, Mathias O; Peng, Yu

    2017-08-07

    Two highly sensitive probes bearing a nucleophilic imine moiety have been utilized for the selective detection of chemical warfare agent (CWA) mimics. Diethyl chlorophosphate (DCP) was used as mimic CWAs. Both iminocoumarin-benzothiazole-based probes not only demonstrated a remarkable fluorescence ON-OFF response and good recognition, but also exhibited fast response times (10s) along with color changes upon addition of DCP. Limits of detection for the two sensors 1 and 2 were calculated as 0.065μM and 0.21μM, respectively, which are much lower than most other reported probes. These two probes not only show high sensitivity and selectivity in solution, but can also be applied for the recognition of DCP in the gas state, with significant color changes easily observed by the naked eye. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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

  19. 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).

  20. 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

  1. Artificial cell mimics as simplified models for the study of cell biology.

    PubMed

    Salehi-Reyhani, Ali; Ces, Oscar; Elani, Yuval

    2017-07-01

    Living cells are hugely complex chemical systems composed of a milieu of distinct chemical species (including DNA, proteins, lipids, and metabolites) interconnected with one another through a vast web of interactions: this complexity renders the study of cell biology in a quantitative and systematic manner a difficult task. There has been an increasing drive towards the utilization of artificial cells as cell mimics to alleviate this, a development that has been aided by recent advances in artificial cell construction. Cell mimics are simplified cell-like structures, composed from the bottom-up with precisely defined and tunable compositions. They allow specific facets of cell biology to be studied in isolation, in a simplified environment where control of variables can be achieved without interference from a living and responsive cell. This mini-review outlines the core principles of this approach and surveys recent key investigations that use cell mimics to