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Sample records for mimics transcriptional aspects

  1. Transcription and the aspect ratio of DNA

    DEFF Research Database (Denmark)

    Olsen, Kasper Wibeck; Bohr, Jakob

    2013-01-01

    analysis of transcription. It is shown that under certain reasonable assumptions transcription is only possible if the aspect ratio is in the regime corresponding to further twisting. We find this constraint to be in agreement with long-established crystallographic studies of DNA....

  2. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.

    Science.gov (United States)

    Pearson, Brandon L; Simon, Jeremy M; McCoy, Eric S; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J

    2016-03-31

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders.

  3. Aptamers to the sigma factor mimic promoter recognition and inhibit transcription initiation by bacterial RNA polymerase.

    Science.gov (United States)

    Miropolskaya, Nataliya; Kulbachinskiy, Andrey

    2016-01-08

    Promoter recognition by bacterial RNA polymerase (RNAP) is a multi-step process involving multiple protein-DNA interactions and several structural and kinetic intermediates which remain only partially characterized. We used single-stranded DNA aptamers containing specific promoter motifs to probe the interactions of the Thermus aquaticus RNAP σ(A) subunit with the -10 promoter element in the absence of other parts of the promoter complex. The aptamer binding decreased intrinsic fluorescence of the σ subunit, likely as a result of interactions between the -10 element and conserved tryptophan residues of the σ DNA-binding region 2. By monitoring these changes, we demonstrated that DNA binding proceeds through a single rate-limiting step resulting in formation of very stable complexes. Deletion of the N-terminal domain of the σ(A) subunit increased the rate of aptamer binding while replacement of this domain with an unrelated N-terminal region 1.1 from the Escherichia coli σ(70) subunit restored the original kinetics of σ-aptamer interactions. The results demonstrate that the key step in promoter recognition can be modelled in a simple σ-aptamer system and reveal that highly divergent N-terminal domains similarly modulate the DNA-binding properties of the σ subunit. The aptamers efficiently suppressed promoter-dependent transcription initiation by the holoenzyme of RNA polymerase, suggesting that they may be used for development of novel transcription inhibitors.

  4. Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.

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    Anne-Katrin Rohlfing

    Full Text Available The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.

  5. Scleroderma mimics.

    Science.gov (United States)

    Nashel, Jennifer; Steen, Virginia

    2012-02-01

    Scleroderma is a rare systemic autoimmune disease with multiple organ manifestations, including skin fibrosis. The groups of disorders classified as scleroderma mimics share the common thread of skin thickening but are otherwise quite incongruous in terms of underlying disease process and other organ involvement. This article reviews the clinical presentation, etiology, and treatment options available for scleroderma mimics, including morphea, scleredema, diabetic cheiroarthropathy, scleromyxedema, nephrogenic systemic fibrosis, and eosinophilic fasciitis. Through greater understanding of these diseases and the associated extradermal implications, we hope to facilitate recognition of scleroderma and its mimics.

  6. A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

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    Edward Rockenstein

    Full Text Available Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations. Two lines expressing high (Line 13 and low (Line 2 levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the

  7. Transcriptional responses to sucrose mimic the plant-associated life style of the plant growth promoting endophyte Enterobacter sp. 638.

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    Safiyh Taghavi

    Full Text Available Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involved in motility (e.g., flagella biosynthesis and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability.

  8. Transcriptional responses to sucrose mimic the plant-associated life style of the plant growth promoting endophyte Enterobacter sp. 638.

    Science.gov (United States)

    Taghavi, Safiyh; Wu, Xiao; Ouyang, Liming; Zhang, Yian Biao; Stadler, Andrea; McCorkle, Sean; Zhu, Wei; Maslov, Sergei; van der Lelie, Daniel

    2015-01-01

    Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involved in motility (e.g., flagella biosynthesis) and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability.

  9. Downy mildew resistance induced by Trichoderma harzianum T39 in susceptible grapevines partially mimics transcriptional changes of resistant genotypes

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    Perazzolli Michele

    2012-11-01

    Full Text Available Abstract Background Downy mildew, caused by Plasmopara viticola, is one of the most severe diseases of grapevine and is commonly controlled by fungicide treatments. The beneficial microorganism Trichoderma harzianum T39 (T39 can induce resistance to downy mildew, although the molecular events associated with this process have not yet been elucidated in grapevine. A next generation RNA sequencing (RNA-Seq approach was used to study global transcriptional changes associated with resistance induced by T39 in Vitis vinifera Pinot Noir leaves. The long-term aim was to develop strategies to optimize the use of this agent for downy mildew control. Results More than 14.8 million paired-end reads were obtained for each biological replicate of T39-treated and control leaf samples collected before and 24 h after P. viticola inoculation. RNA-Seq analysis resulted in the identification of 7,024 differentially expressed genes, highlighting the complex transcriptional reprogramming of grapevine leaves during resistance induction and in response to pathogen inoculation. Our data show that T39 has a dual effect: it directly modulates genes related to the microbial recognition machinery, and it enhances the expression of defence-related processes after pathogen inoculation. Whereas several genes were commonly affected by P. viticola in control and T39-treated plants, opposing modulation of genes related to responses to stress and protein metabolism was found. T39-induced resistance partially inhibited some disease-related processes and specifically activated defence responses after P. viticola inoculation, causing a significant reduction of downy mildew symptoms. Conclusions The global transcriptional analysis revealed that defence processes known to be implicated in the reaction of resistant genotypes to downy mildew were partially activated by T39-induced resistance in susceptible grapevines. Genes identified in this work are an important source of markers

  10. Evolutionary aspects of plastid proteins involved in transcription: the transcription of a tiny genome is mediated by a complicated machinery.

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    Yagi, Yusuke; Shiina, Takashi

    2012-01-01

    Chloroplasts in land plants have a small genome consisting of only 100 genes encoding partial sets of proteins for photosynthesis, transcription and translation. Although it has been thought that chloroplast transcription is mediated by a basically cyanobacterium-derived system, due to the endosymbiotic origin of plastids, recent studies suggest the existence of a hybrid transcription machinery containing non-bacterial proteins that have been newly acquired during plant evolution. Here, we highlight chloroplast-specific non-bacterial transcription mechanisms by which land plant chloroplasts have gained novel functions.

  11. Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.

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    Lux, Heike; Flammann, Heiko; Hafner, Mathias; Lux, Andreas

    2010-01-13

    The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's -1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

  12. Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.

    Directory of Open Access Journals (Sweden)

    Heike Lux

    Full Text Available The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's -1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

  13. Myeloblastic Cell Lines Mimic Some but Not All Aspects of Human Cytomegalovirus Experimental Latency Defined in Primary CD34+ Cell Populations

    Science.gov (United States)

    Albright, Emily R.

    2013-01-01

    Human cytomegalovirus (HCMV) is a significant human pathogen that achieves lifelong persistence by establishing latent infections in undifferentiated cells of the myeloid lineage, such as CD34+ hematopoietic progenitor cells. When latency is established, viral lytic gene expression is silenced in part by a cellular intrinsic defense consisting of Daxx and histone deacetylases (HDACs) because pp71, the tegument transactivator that travels to the nucleus and inactivates this defense at the start of a lytic infection in differentiated cells, remains in the cytoplasm. Because the current in vitro and ex vivo latency models have physiological and practical limitations, we evaluated two CD34+ myeloblastic cell lines, KG-1 and Kasumi-3, for their ability to establish, maintain, and reactivate HCMV experimental latent infections. Tegument protein pp71 was cytoplasmic, and immediate-early (IE) genes were silenced as in primary CD34+ cells. However, in contrast to what occurs in primary CD34+ cells ex vivo or in NT2 and THP-1 in vitro model systems, viral IE gene expression from the laboratory-adapted AD169 genome was not induced in the presence of HDAC inhibitors in either KG-1 or Kasumi-3 cells. Furthermore, while the clinical strain FIX was able to reactivate from Kasumi-3 cells, AD169 was not, and neither strain reactivated from KG-1 cells. Thus, KG-1 and Kasumi-3 experimental latent infections differ in important parameters from those in primary CD34+ cell populations. Aspects of latency illuminated through the use of these myeloblastoid cell lines should not be considered independently but integrated with results obtained in primary cell systems when paradigms for HCMV latency are proposed. PMID:23824798

  14. Structural and functional aspects of winged-helix domains at the core of transcription initiation complexes.

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    Teichmann, Martin; Dumay-Odelot, Hélène; Fribourg, Sébastien

    2012-01-01

    The winged helix (WH) domain is found in core components of transcription systems in eukaryotes and prokaryotes. It represents a sub-class of the helix-turn-helix motif. The WH domain participates in establishing protein-DNA and protein-protein-interactions. Here, we discuss possible explanations for the enrichment of this motif in transcription systems.

  15. New human papilloma virus E2 transcription factor mimics: a tripyrrole-peptide conjugate with tight and specific DNA-recognition.

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    Diana E Wetzler

    Full Text Available BACKGROUND: Human papillomavirus (HPV is the main causative agent of cervical cancer, particularly high risk strains such us HPV-16, -18 and -31. The viral encoded E2 protein acts as a transcriptional modulator and exerts a key role in viral DNA replication. Thus, E2 constitutes an attractive target for developing antiviral agents. E2 is a homodimeric protein that interacts with the DNA target through an α-helix of each monomer. However, a peptide corresponding to the DNA recognition helix of HPV-16 E2 binds DNA with lower affinity than its full-length DNA binding domain. Therefore, in an attempt to promote the DNA binding of the isolated peptide, we have designed a conjugate compound of the E2 α-helix peptide and a derivative of the antibiotic distamycin, which involves simultaneous minor- and major-groove interactions. METHODOLOGY/PRINCIPAL FINDINGS: An E2 α-helix peptide-distamycin conjugate was designed and synthesized. It was characterized by NMR and CD spectroscopy, and its DNA binding properties were investigated by CD, DNA melting and gel shift experiments. The coupling of E2 peptide with distamycin does not affect its structural properties. The conjugate improves significantly the affinity of the peptide for specific DNA. In addition, stoichiometric amounts of specific DNA increase meaningfully the helical population of the peptide. The conjugate enhances the DNA binding constant 50-fold, maintaining its specificity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that peptide-distamycin conjugates are a promising tool to obtain compounds that bind the E2 target DNA-sequences with remarkable affinity and suggest that a bipartite major/minor groove binding scaffold can be a useful approach for therapeutic treatment of HPV infection.

  16. The role of Ikaros transcriptional factor in normal hematopoiesis and leukemogenesis: biological and clinical aspects

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    V. S. Vshivkoo

    2015-01-01

    Full Text Available Investigation of the pathogenesis and factors effecting recurrence, progression and drug resistance in acute leukemia (AL remains a major challenge for hematology and other related areas. The role of more than 50 genes and proteins in the AL pathogenesis has been shown, including the well-studied tumor suppressor (CDKN2A/CDKN2B, RB1, PTEN, p53, and classical fusion genes (BCR/ABL1, TEL/AML1, E2A/PBX, MLL translocations. In addition, high frequency of aberrations in genes responsible for lymphoid differentiation have been identified such as transcription factors (PAX5, IKZF1 and EBF1, transcriptional regulation of the genes (ETV6, ERG, and signaling pathways of antigen receptors (BTLA, CD200, TOX, BLNK, VPREB1, as well as genes involved in chemoresistance of leukemia cells (NR3C1. In recent studies, Ikaros abnormalities have been reported to be frequently associated with AL. Ikaros is a member of a Kruppel-like family of zinc finger transcription factors that also includes IKZF2 (Helios, IKZF3 (Aiolos, Eos and Pegasus, and encoded by the IKZF1 gene. In hematopoietic cells Ikaros functions as a transcription factor, a key protein controlling T-, B-, NK-, and dendritic cells early differentiation. At the early hematopoiesis stages, it represses the myeloid and erythroid lineages, and stimulates the lymphoid differentiation. Ikaros also normally modulates immune response and plays role of a tumor suppressor in lymphoid malignances. Data from numerous clinical studies confirmed an association between the presence of IKZF1 aberrations and B-cell and, to a lesser extent, T-cell acute lymphoblastic leukemia (ALL development. Besides, loss of Ikaros function was associated with progression of myeloproliferative diseases to acute myeloid leukemia (AML in children. From clinical point of view, particular intragenic IKZF1 deletions and a short (non-functional protein Ikaros isoforms, which may occur as a result of intragenic deletions or aberrant splicing

  17. MIMIC en Robin Hood

    NARCIS (Netherlands)

    R.A. de Mooij (Ruud); A.L. Bovenberg (Lans); F. van der Ploeg (Ploeg)

    1994-01-01

    textabstractVerlaging van het belastingtarief in de eerste schijf, gefinancierd met verhoging van het tarief in de andere schijven, is in het MIMIC-model van het Centraal Planbureau goed voor de werkgelegenheid. Onlangs werd .in E5B betwijfeld of het CPB de gevolgen van zo'n 'Robin Hood'- beleid

  18. MIMIC en Robin Hood

    OpenAIRE

    Mooij, Ruud; Bovenberg, Lans; Ploeg, Ploeg

    1994-01-01

    textabstractVerlaging van het belastingtarief in de eerste schijf, gefinancierd met verhoging van het tarief in de andere schijven, is in het MIMIC-model van het Centraal Planbureau goed voor de werkgelegenheid. Onlangs werd .in E5B betwijfeld of het CPB de gevolgen van zo'n 'Robin Hood'- beleid goed weergeeft. Het is echter de vraag of de niet-kwantificeerbare effecten wel van zo 'n groot belang zijn.

  19. Arabidopsis Ovate Family Proteins, a Novel Transcriptional Repressor Family, Control Multiple Aspects of Plant Growth and Development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shucai [University of British Columbia, Vancouver; Chang, Ying [Northeast Agricultural University; Guo, Jianjun [Harvard University; Zeng, Qingning [University of British Columbia, Vancouver; Ellis, Brian [University of British Columbia, Vancouver; Chen, Jay [ORNL

    2011-01-01

    BACKGROUND: The Arabidopsis genome contains 18 genes that are predicted to encode Ovate Family Proteins (AtOFPs), a protein family characterized by a conserved OVATE domain, an approximately 70-amino acid domain that was originally found in tomato OVATE protein. Among AtOFP family members, AtOFP1 has been shown to suppress cell elongation, in part, by suppressing the expression of AtGA20ox1, AtOFP4 has been shown to regulate secondary cell wall formation by interact with KNOTTED1-LIKE HOMEODOMAIN PROTEIN 7 (KNAT7), and AtOFP5 has been shown to regulate the activity of a BEL1-LIKEHOMEODOMAIN 1(BLH1)-KNAT3 complex during early embryo sac development, but little is known about the function of other AtOFPs. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated here that AtOFP proteins could function as effective transcriptional repressors in the Arabidopsis protoplast transient expression system. The analysis of loss-of-function alleles of AtOFPs suggested AtOFP genes may have overlapping function in regulating plant growth and development, because none of the single mutants identified, including T-DNA insertion mutants in AtOFP1, AtOFP4, AtOFP8, AtOFP10, AtOFP15 and AtOFP16, displayed any apparent morphological defects. Further, Atofp1 Atofp4 and Atofp15 Atofp16 double mutants still did not differ significantly from wild-type. On the other hand, plants overexpressing AtOFP genes displayed a number of abnormal phenotypes, which could be categorized into three distinct classes, suggesting that AtOFP genes may also have diverse functions in regulating plant growth and development. Further analysis suggested that AtOFP1 regulates cotyledon development in a postembryonic manner, and global transcript profiling revealed that it suppress the expression of many other genes. CONCLUSIONS/SIGNIFICANCE: Our results showed that AtOFPs function as transcriptional repressors and they regulate multiple aspects of plant growth and development. These results provided the first overview of a

  20. Antimicrobial activities of squalamine mimics.

    OpenAIRE

    1997-01-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphyl...

  1. Parasomnias and their mimics.

    Science.gov (United States)

    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.

  2. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.

    Science.gov (United States)

    Barger, Jamie L; Kayo, Tsuyoshi; Vann, James M; Arias, Edward B; Wang, Jelai; Hacker, Timothy A; Wang, Ying; Raederstorff, Daniel; Morrow, Jason D; Leeuwenburgh, Christiaan; Allison, David B; Saupe, Kurt W; Cartee, Gregory D; Weindruch, Richard; Prolla, Tomas A

    2008-06-04

    Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg(-1) day(-1)), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

  3. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.

    Directory of Open Access Journals (Sweden)

    Jamie L Barger

    Full Text Available Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months to old age (30-months either a control diet, a low dose of resveratrol (4.9 mg kg(-1 day(-1, or a calorie restricted (CR diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

  4. Antimicrobial activities of squalamine mimics.

    Science.gov (United States)

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

    1997-07-01

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

  5. Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors

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    Chen Yuzhi

    2009-05-01

    Full Text Available Abstract The unique physiology and function of neurons create differences in their cellular physiology, including their regulation of gene expression. We began several years ago exploring the relationships between the NFκB transcription factor, neuronal survival, and glutamate receptor activation in telencephalic neurons. These studies led us to conclude that this population of cells is nearly incapable of activating the NFκB that is nonetheless expressed at reasonable levels. A subset of the κB cis elements are instead bound by members of the Sp1 family in neurons. Also surprising was our discovery that Sp1 itself, typically described as ubiquitous, is severely restricted in expression within forebrain neurons; Sp4 seems to be substituted during neuronal differentiation. These findings and their implications for neuronal differentiation – as well as potential dedifferentiation during degenerative processes – are discussed here.

  6. Identifying Aspects of the Post-Transcriptional Program Governing the Proteome of the Green Alga Micromonas pusilla.

    Science.gov (United States)

    Waltman, Peter H; Guo, Jian; Reistetter, Emily Nahas; Purvine, Samuel; Ansong, Charles K; van Baren, Marijke J; Wong, Chee-Hong; Wei, Chia-Lin; Smith, Richard D; Callister, Stephen J; Stuart, Joshua M; Worden, Alexandra Z

    2016-01-01

    Micromonas is a unicellular motile alga within the Prasinophyceae, a green algal group that is related to land plants. This picoeukaryote (<2 μm diameter) is widespread in the marine environment but is not well understood at the cellular level. Here, we examine shifts in mRNA and protein expression over the course of the day-night cycle using triplicated mid-exponential, nutrient replete cultures of Micromonas pusilla CCMP1545. Samples were collected at key transition points during the diel cycle for evaluation using high-throughput LC-MS proteomics. In conjunction, matched mRNA samples from the same time points were sequenced using pair-ended directional Illumina RNA-Seq to investigate the dynamics and relationship between the mRNA and protein expression programs of M. pusilla. Similar to a prior study of the marine cyanobacterium Prochlorococcus, we found significant divergence in the mRNA and proteomics expression dynamics in response to the light:dark cycle. Additionally, expressional responses of genes and the proteins they encoded could also be variable within the same metabolic pathway, such as we observed in the oxygenic photosynthesis pathway. A regression framework was used to predict protein levels from both mRNA expression and gene-specific sequence-based features. Several features in the genome sequence were found to influence protein abundance including codon usage as well as 3' UTR length and structure. Collectively, our studies provide insights into the regulation of the proteome over a diel cycle as well as the relationships between transcriptional and translational programs in the widespread marine green alga Micromonas.

  7. Identifying Aspects of the Post-Transcriptional Program Governing the Proteome of the Green Alga Micromonas pusilla

    Energy Technology Data Exchange (ETDEWEB)

    Waltman, Peter H.; Guo, Jian; Reistetter, Emily Nahas; Purvine, Samuel; Ansong, Charles K.; van Baren, Marijke J.; Wong, Chee-Hong; Wei, Chia-Lin; Smith, Richard D.; Callister, Stephen J.; Stuart, Joshua M.; Worden, Alexandra Z.; Mills, Ken

    2016-07-19

    Micromonas is a unicellular green alga that belongs to the prasinophytes, a sister lineage to land plants. This picoeukaryotic (<2 μm diameter) alga is widespread in the marine environment but still not understood at the cellular level. Here, we examine the mRNA and protein level changes that take place over the course of the day-night cycle using mid-exponential nutrient replete cultures of Micromonas pusilla CCMP1545 grown and analyzed in biological triplicate. During the experiment, samples were collected at key transition points during the diel for evaluation using high-throughput LC-MS proteomics. We also sequenced matched mRNA samples from the same time points, using pair-ended directional Illumina RNA-Seq to investigate the dynamics and relationship between the mRNA and protein expression programs of M. pusilla. Similar to a prior study of the marine cyanobacterium Prochlorococcus, we found significant divergence in the mRNA and proteomics expression dynamics in response to the light:dark cycle. Additionally, expressional responses of genes and the proteins they encoded could also be variable within the same metabolic pathway, such as the oxygenic photosynthesis pathway. A regression framework was used to predict protein levels using both mRNA expression and gene-specific sequence-based features. Several features in the genome sequence were found to influence protein abundance including the codon usage and the length of the 3’ UTR. Collectively, our studies provide insights into the regulation of the proteome over a diel as relationships between the transcriptional and translational programs in the widespread marine green alga Micromonas.

  8. Identifying Aspects of the Post-Transcriptional Program Governing the Proteome of the Green Alga Micromonas pusilla.

    Directory of Open Access Journals (Sweden)

    Peter H Waltman

    Full Text Available Micromonas is a unicellular motile alga within the Prasinophyceae, a green algal group that is related to land plants. This picoeukaryote (<2 μm diameter is widespread in the marine environment but is not well understood at the cellular level. Here, we examine shifts in mRNA and protein expression over the course of the day-night cycle using triplicated mid-exponential, nutrient replete cultures of Micromonas pusilla CCMP1545. Samples were collected at key transition points during the diel cycle for evaluation using high-throughput LC-MS proteomics. In conjunction, matched mRNA samples from the same time points were sequenced using pair-ended directional Illumina RNA-Seq to investigate the dynamics and relationship between the mRNA and protein expression programs of M. pusilla. Similar to a prior study of the marine cyanobacterium Prochlorococcus, we found significant divergence in the mRNA and proteomics expression dynamics in response to the light:dark cycle. Additionally, expressional responses of genes and the proteins they encoded could also be variable within the same metabolic pathway, such as we observed in the oxygenic photosynthesis pathway. A regression framework was used to predict protein levels from both mRNA expression and gene-specific sequence-based features. Several features in the genome sequence were found to influence protein abundance including codon usage as well as 3' UTR length and structure. Collectively, our studies provide insights into the regulation of the proteome over a diel cycle as well as the relationships between transcriptional and translational programs in the widespread marine green alga Micromonas.

  9. ‘Is that what I Said?’ Interview Transcript Approval by Participants: An Aspect of Ethics in Qualitative Research

    Directory of Open Access Journals (Sweden)

    Irit Mero-Jaffe

    2011-09-01

    Full Text Available This article deals with insights gained from data analysis of feedback comments on transcripts sent to interviewees. It contributes to understanding of research studies that include transcripts, specifically on the contribution of participants' review of transcripts on the quality of those transcripts, and thus on the quality of research. The transfer of the transcripts to the interviewees was intended to validate the transcripts, to preserve research ethics, and to empower the interviewees by allowing them control of what was written. Interviewee responses related to the ratification of content, the authenticity of that which was said during the interview, corrections of language, additional clarifications, power interactions and changes in the balance of power between the interviewer and interviewees, feelings of embarrassment and threat, research ethics, and reflective responses. The experience of sending the transcripts to the interviewees raised research and ethical issues that require added caution and consideration when sending transcripts to interviewees.

  10. Double-stranded Let-7 mimics, potential candidates for cancer gene therapy.

    Science.gov (United States)

    Wang, Qi-zhao; Lv, Ying-hui; Gong, Yu-hua; Li, Zhao-fa; Xu, William; Diao, Yong; Xu, Ruian

    2012-03-01

    MicroRNAs (miRNAs), a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The ability of one single miRNA regulating multiple functionally related mRNAs makes it a new potential candidate for cancer gene therapy. Let-7s miRNAs have been demonstrated as tumor-suppressor genes in various types of cancers, providing one choice of gene therapy by replenishing this miRNA. In the present studies, we demonstrate that the chemically synthesized, double-stranded Let-7 mimics can inhibit the growth and migration and induce the cell cycle arrest of lung cancer cell lines in vitro. Let-7 mimics silence gene expression by binding to the 3' UTR of targeting mRNAs. Mutation of seed sequence significantly depresses the gene silencing activity of Let-7 mimics. Our results also demonstrate that it is possible to increase the activity of Let-7s through mutating the sequence within the 3'end of the antisense strand. Directly, co-transfection Let-7 mimics with active siRNAs impairs the anti-cancer activities of Let-7 mimics. However, a 3-h interval between the introduction of Let-7 mimics and a kind of siRNA avoids the competition and enhances the anti-cancer activities of Let-7 mimics. Taken together, these results have revealed that Let-7s mimics are potential candidates for cancer gene therapy.

  11. Designing mimics of membrane active proteins.

    Science.gov (United States)

    Sgolastra, Federica; Deronde, Brittany M; Sarapas, Joel M; Som, Abhigyan; Tew, Gregory N

    2013-12-17

    As a semipermeable barrier that controls the flux of biomolecules in and out the cell, the plasma membrane is critical in cell function and survival. Many proteins interact with the plasma membrane and modulate its physiology. Within this large landscape of membrane-active molecules, researchers have focused significant attention on two specific classes of peptides, antimicrobial peptides (AMPs) and cell penetrating peptides (CPPs), because of their unique properties. In this Account, we describe our efforts over the last decade to build and understand synthetic mimics of antimicrobial peptides (SMAMPs). These endeavors represent one specific example of a much larger effort to understand how synthetic molecules interact with and manipulate the plasma membrane. Using both defined molecular weight oligomers and easier to produce, but heterogeneous, polymers, we have generated scaffolds with biological potency exceeding that of the natural analogues. One of these compounds has progressed through a phase II clinical trial for pan-staph infections. Modern biophysical assays have highlighted the interplay between the synthetic scaffold and lipid composition: a negative Gaussian curvature is required both for pore formation and for the initiation of endosome creation. Although work remains to better resolve the complexity of this interplay between lipids, other bilayer components, and the scaffolds, significant new insights have been discovered. These results point to the importance of considering the various aspects of permeation and how these are related to "pore formation". More recently, our efforts have expanded toward protein transduction domains, or mimics of cell penetrating peptides. Using a combination of unique molecular scaffolds and guanidinium-rich side chains, we have produced an array of polymers with robust membrane (and delivery) activity. In this new area, researchers are just beginning to understand the fundamental interactions between these new

  12. Carbocyclic Carbohydrate Mimics as Potential Glycosidase Inhibitors

    DEFF Research Database (Denmark)

    Fanefjord, Mette; Lundt, Inge

    It has been proven that aminocyclopentanols having the aminogroup adjacent to a carbon sidechain could be potential anomer-selective glycosidase inhibitors [1]. A successful pathway for synthesising mimics to L-carbohydrates 2, by introducing nitrogen to the C6 position in compound 1, has been...... developed in our group. A similar strategy has been used for synthesising mimics of D-carbohydrates. The α,β-unsaturated lactone 3 was cyclised to compound 4 which was further transformed into 5. The nitrogen functionality in compound 7 is introduced by an Overman rearrangement of 6 and the hydroxyl...

  13. Carbocyclic Carbohydrate Mimics as Potential Glycosidase Inhibitors

    DEFF Research Database (Denmark)

    Fanefjord, Mette; Lundt, Inge

    functionalities was introduced by either epoxidation or dihydroxylation of 7. Finally, reduction of the lactone ring led to the sugar mimics 8. The synthesis of several isomers of 8 will be presented. [1] a) Kleban, M. ; Hilgers, P. ; Greul, J.N. ; Kugler, R.D. ; Li, J. ; Picasso, S. ; Vogel, P. ; Jäger, V. Chem...

  14. A chemical system that mimics decoding operations.

    Science.gov (United States)

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

    2009-02-23

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

  15. Permanent female mimics in a lekking shorebird

    NARCIS (Netherlands)

    Jukema, Joop; Piersma, Theunis

    2006-01-01

    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 satellit

  16. Mimics and chameleons in motor neurone disease.

    Science.gov (United States)

    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.

  17. Engineering hydrogels as extracellular matrix mimics

    OpenAIRE

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

    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....

  18. A Photoisomerizing Rhodopsin Mimic Observed at Atomic Resolution.

    Science.gov (United States)

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

    2016-07-20

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

  19. A Lesion-Mimic Syntaxin Double Mutant in Arabidopsis Reveals Novel Complexity of Pathogen Defense Signaling

    Institute of Scientific and Technical Information of China (English)

    Ziguo Zhang; Hans Thordal-Christensen; Andrea Lenk; Mats X. Andersson; Torben Gjetting; Carsten Pedersen; Mads E. Nielsen; Marl-Anne Newman; Bi-Huei Hou; Shauna C. Somerville

    2008-01-01

    The lesion-mimicArabidopsis mutant, syp121 syp122, constitutively expresses the salicylic acid (SA) signaling pathway and has low penetration resistance to powdery mildew fungi. Genetic analyses of the lesion-mimic phenotype have expanded our understanding of programmed cell death (PCD) in plants. Inactivation of SA signaling genes in syp121 syp 122 only partially rescues the lesion-mimic phenotype, indicating that additional defenses contribute to the PCD. Whole genome transcriptome analysis confirmed that SA-induced transcripts, as well as numerous other known pathogenresponse transcripts, are up-regulated after inactivation of the syntaxin genes. A suppressor mutant analysis of syp121 syp122 revealed that FMO1, ALD1, and PAD4 are important for lesion development. Mutant alleles of EDS1, NDR1, RAR1, and SGT1b also partially rescued the lesion-mimic phenotype, suggesting that mutating syntaxin genes stimulates TIR-NB-LRR and CC-NB-LRR-type resistances. The syntaxin double knockout potentiated a powdery mildewinduced HR-like response. This required functional PAD4 but not functional SA signaling. However, SA signaling potentiated the PAD4-dependent HR-like response. Analyses of quadruple mutants suggest that EDS5 and SID2 confer separate SA-independent signaling functions, and that FMO1 and ALD1 mediate SA-independent signals that are NPRl-dependent.These studies highlight the contribution of multiple pathways to defense and point to the complexity of their interactions.

  20. Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy or transcriptional dysregulation. The multifaceted aspects of a single mutation.

    Directory of Open Access Journals (Sweden)

    Paola eGiunti

    2015-02-01

    Full Text Available Spinocerebellar Ataxia type 6 is an autosomal dominant neurodegenerative disease characterized by late onset, slowly progressive, mostly pure cerebellar ataxia. It is one of three allelic disorders associated to CACNA1A gene, coding for the Alpha1 A subunit of P/Q type calcium channel Cav2.1 expressed in the brain, particularly in the cerebellum. The other two disorders are Episodic Ataxia type 2, and Familial Hemiplegic Migraine type 1. These disorders show distinct phenotypes that often overlap but have different pathogenic mechanisms. Episodic Ataxia type 2 and Familial Hemiplegic Migraine type 1 are due to mutations causing, respectively, a loss and a gain of channel function. Spinocerebellar Ataxia type 6, instead, is associated with short expansions of a polyglutamine stretch located in the cytoplasmic C-terminal tail of the protein. This domain has a relevant role in channel regulation, as well as in transcription regulation of other neuronal genes; thus the SCA6 CAG repeat expansion results in complex pathogenic molecular mechanisms reflecting the complex Cav2.1 C-terminus activity. We will provide a short review for an update on the Spinocerebellar Ataxia type 6 molecular mechanism.

  1. Stereocontrolled Synthesis of Methyl Silanediol Peptide Mimics

    DEFF Research Database (Denmark)

    Nielsen, Lone; Lindsay, Karl; Faber, Jesper;

    2007-01-01

    with methanolic HCl and the resulting amine extended into peptide chains accordingly. The diphenylsilyl moiety is a resilient protecting group for the corresponding silanediol, which can be unmasked via treatment with TfOH, followed by aqueous hydrolysis. The crude silanediol may be isolated and purified as its...... corresponding bis-TMS siloxane via protection with TMSCl, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described....

  2. Can strange stars mimic dark energy stars?

    CERN Document Server

    Deb, Debabrata; Guha, B K; Ray, Saibal

    2016-01-01

    The possibility of strange stars mixed with dark energy to be one of candidates for dark energy stars is the main issue of the present study. Our investigation shows that quark matter is acting as dark energy after certain yet unknown critical condition inside the quark stars. Our proposed model reveals that strange stars mixed with dark energy feature not only a physically acceptable stable model but also mimic characteristics of dark energy stars. The plausible connections are shown through the mass-radius relation as well as the entropy and temperature. We particulary note that two-fluid distribution is the major reason for anisotropic nature of the spherical stellar system.

  3. Oxidoreductase mimic activity of natural pyrrhotite

    Science.gov (United States)

    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.

  4. Meningeal fibroma: a rare meningioma mimic.

    Science.gov (United States)

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

    2014-08-01

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

  5. Do benzodiazepines mimic reverse-turn structures?

    Science.gov (United States)

    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

  6. Investigating the Ustilago maydis/Zea mays pathosystem: transcriptional responses and novel functional aspects of a fungal calcineurin regulatory B subunit.

    Science.gov (United States)

    Donaldson, Michael E; Meng, Shaowu; Gagarinova, Alla; Babu, Mohan; Lambie, Scott C; Swiadek, Alexander A; Saville, Barry J

    2013-01-01

    The sustainable control of basidiomycete biotrophic plant pathogenesis requires an understanding of host responses to infection, as well as the identification and functional analysis of fungal genes involved in disease development. The creation and analysis of a suppressive subtractive hybridization (SSH) cDNA library from Ustilago maydis-infected Zea mays seedlings enabled the identification of fungal and plant genes expressed during disease development, and uncovered new insights into the interactions of this model system. Candidate U. maydis pathogenesis genes were identified by using the current SSH cDNA library analysis, and by knowledge generated from previous cDNA microarray and comparative genomic analyses. These identifications were supported by the independent determination of transcript level changes in different cell-types and during pathogenic development. The basidiomycete specific um01632, the highly in planta expressed um03046 (zig1), and the calcineurin regulatory B subunit (um10226, cnb1), were chosen for deletion experiments. um01632 and zig1 mutants showed no difference in morphology and did not have a statistically significant impact on pathogenesis. cnb1 mutants had a distinct cell division phenotype and reduced virulence in seedling assays. Infections with reciprocal wild-type×Δcnb1 haploid strain crosses revealed that the wild-type allele was unable to fully compensate for the lack of a second cnb1 allele. This haploinsufficiency was undetected in other fungal cnb1 mutational analyses. The reported data improves U. maydis genome annotation and expands on the current understanding of pathogenesis genes in this model basidiomycete.

  7. Activation of Janus kinase/signal transducers and activators of transcription pathway involved in megakaryocyte proliferation induced by vanadium resembles some aspects of essential thrombocythemia.

    Science.gov (United States)

    Gonzalez-Villalva, Adriana; Piñon-Zarate, Gabriela; Falcon-Rodriguez, Carlos; Lopez-Valdez, Nelly; Bizarro-Nevares, Patricia; Rojas-Lemus, Marcela; Rendon-Huerta, Erika; Colin-Barenque, Laura; Fortoul, Teresa I

    2016-05-01

    Vanadium (V) is an air pollutant released into the atmosphere by burning fossil fuels. Also, it has been recently evaluated for their carcinogenic potential to establish permissible limits of exposure at workplaces. We previously reported an increase in the number and size of platelets and their precursor cells and megakaryocytes in bone marrow and spleen. The aim of this study was to identify the involvement of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and thrombopoietin (TPO) receptor, and myeloproliferative leukemia virus oncogene (Mpl), in megakaryocyte proliferation induced by this compound. Mice were exposed twice a week to vanadium pentoxide inhalation (0.02 M) and were killed at 4th, 6th, and 8th week of exposure. Phosphorylated JAK2 (JAK2 ph), STAT3 (STAT3 ph), STAT5, and Mpl were identified in mice spleen megakaryocytes by cytofluorometry and immunohistochemistry. An increase in JAK2 ph and STAT3 ph, but a decrease in Mpl at 8-week exposure was identified in our findings. Taking together, we propose that the morphological findings, JAK/STAT activation, and decreased Mpl receptor induced by V leads to a condition comparable to essential thrombocythemia, so the effect on megakaryocytes caused by different mechanisms is similar. We also suggest that the decrease in Mpl is a negative feedback mechanism after the JAK/STAT activation. Since megakaryocytes are platelet precursors, their alteration affects platelet morphology and function, which might have implications in hemostasis as demonstrated previously, so it is important to continue evaluating the effects of toxics and pollutants on megakaryocytes and platelets.

  8. Right-sided diverticulitis mimics appendicitis.

    Science.gov (United States)

    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.

  9. Engineering hydrogels as extracellular matrix mimics.

    Science.gov (United States)

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

    2010-04-01

    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.

  10. Preparation of highly efficient manganese catalase mimics.

    Science.gov (United States)

    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.

  11. Recognizing asthma mimics and asthma complications.

    Science.gov (United States)

    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. Renewable polyethylene mimics derived from castor oil.

    Science.gov (United States)

    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.

  13. Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays

    Science.gov (United States)

    Mishra, Laxmi N.; Pepenella, Sharon; Rogge, Ryan; Hansen, Jeffrey C.; Hayes, Jeffrey J.

    2016-01-01

    The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome. In contrast, acetylation mimics within the H3 tail had little effect, but were able to synergize with H4 tail acetylation mimics to further increase accessibility. Moreover, replacement of the central nucleosome with a nucleosome free region also resulted in increased local, but not global DNA accessibility. Our results indicate that modification or disruption of only a single target nucleosome results in significant changes in local chromatin architecture and suggest that very localized chromatin modifications imparted by pioneer transcription factors are sufficient to initiate a cascade of events leading to promoter activation. PMID:27708426

  14. Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis

    Directory of Open Access Journals (Sweden)

    Apweiler Eva

    2012-06-01

    Full Text Available Abstract Background Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays. Results In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system. Conclusions The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

  15. Retropharyngeal Calcific Tendonitis Mimics a Retropharyngeal Abscess

    Directory of Open Access Journals (Sweden)

    Natasha Pollak

    2013-01-01

    Full Text Available Retropharyngeal calcific tendonitis (RCT is an uncommon, self-limiting condition that is often omitted in the differential diagnosis of a retropharyngeal fluid collection. This condition mimics a retropharyngeal abscess and should be considered when evaluating a fluid collection in the retropharyngeal space. Although calcific tendonitis at other sites has been well described in the medical literature, it appears that this entity has been underreported in the otolaryngology literature where only a few case reports have been identified. Presumably, the actual incidence is higher than the reported incidence, due to lack of familiarity with this disorder. As an otolaryngologist’s scope of practice includes the managements of retropharyngeal lesions, it is important for the otolaryngologist to recognize the presentation of acute RCT and be familiar with appropriate treatment strategies. Retropharyngeal calcific tendonitis presents with neck pain, limitation of neck range of motion and includes inflammation, calcifications, and a sterile effusion within the longus colli muscle. Treatment is medical with nonsteroidal anti-inflammatory medications. RCT does not require surgical treatment, and an accurate diagnosis can prevent unnecessary attempts at operative drainage. In this study, we discuss two cases of RCT, summarize the salient features in diagnosis, including key radiologic features, discuss treatment options, and review the literature.

  16. Mycosis Fungoides mimic chronic eczema? Observation

    Directory of Open Access Journals (Sweden)

    Jacek Andruszkiewicz

    2013-07-01

    Full Text Available Mycosis fungoides (MF is the most common type of cutaneous T-cell lymphoma [1]. Because of its great variety of clinical features and nonspecific histological findings (especially in early stages has been named the "great imitator "and can induce many wrong diagnosis [2,3]. Mycosis fungoides (MF, is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known [4,5]. Therefore very often Mycosis fungoides is misdiagnosed as chronic eczema [6]. MF can also mimic: vitiligo [6], alopecia-Areata [7], ecchymosis [8].

  17. Small Undifferentiated Pancreatic Adenocarcinoma which Mimics IPMN at Imaging

    Directory of Open Access Journals (Sweden)

    Mirko D’Onofrio

    2009-07-01

    Full Text Available Context To present the case of an unusual presentation at imaging of a very small solid undifferentiated pancreatic adenocarcinoma which mimics a side-branch intraductal papillary mucinous neoplasm. Case report The patient came to our hospital for a revaluation of a cystic pancreatic lesion. Ultrasound (US and contrast-enhanced ultrasound (CEUS examinations were carried out. A small cystic lesion of about 1.5 cm in diameter was seen in the posterior aspect of the pancreatic uncinate process A very small, solid, vascularized nodule was detected at CEUS within the lesion. Consequently, the patient underwent CT and MRI. MRI confirmed the presence of an intralesional nodule and communication with the main pancreatic duct was demonstrated, suggesting the diagnosis of intraductal papillary mucinous neoplasm with solid intralesional tissue. A pylorus preserving pancreaticoduodenectomy was carried out. An undifferentiated adenocarcinoma having a notable peripheral inflammatory reaction and dilated branch duct was finally diagnosed. Conclusion To our knowledge, we present for the first time, the case of a very small solid undifferentiated pancreatic adenocarcinoma of the uncinate process which mimicked a side-branch intraductal papillary mucinous neoplasm at imaging. The cystic appearance may be an epiphenomenon of a solid lesion and this possibility has to be considered when one encounters incidental cystic lesions at imaging.

  18. Nominal aspect

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    1991-01-01

    In a general way the notion 'aspect' can be defined as the way in which a property or relation is represented in some dimension. Two kinds of aspect can be distinguished: verbal and nominal aspect. The study of verbal aspect has a long tradition, but nominal aspect has only been introduced recently......, at least in the sense in which it is used here (Rijkhoff 1989b, 1990a, 1990b). After a brief look at the more familiar verbal aspects, each of the nominal aspects is discussed in some detail. Then the relevance of nominal aspect will be considered in connection with (i) certain 'number markers' (which...... will be analysed as nominal aspect markers below), (ii) noun-incorporation, and (iii) predicate nouns....

  19. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic substituti

  20. A collection of target mimics for comprehensive analysis of microRNA function in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Marco Todesco

    2010-07-01

    Full Text Available Many targets of plant microRNAs (miRNAs are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for approximately 20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA-resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants.

  1. [Intraluminal Aspect of Femoro-femoral Cross-over Bypass Graft Mimics Bladder Stone].

    Science.gov (United States)

    Sonak, I; Wiedemann, A; Heppner, H J

    2016-04-01

    Iatrogenic bladder perforation with delayed diagnosis and treatment in the context of the placement of a vascular prosthesis, e.g. a femoro-femoral cross-over bypass graft, is extremely rare. This is emphasised by the present publication, which is the second published case study worldwide. To identify such a situation is very important because there is a risk of inappropriate treatment if such a bypass complication remains undetected, and the potential complications of an improperly intended "treatment of a bladder stone" may be deleterious or even lethal. Therefore, the involved disciplines should be aware of this possibility in order to initiate relevant diagnostic measures, especially diagnostic cystoscopy, without any delay if symptoms such as voiding disorders or alguria coincide with vascular bypass grafting.

  2. Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an additive manner.

    Science.gov (United States)

    Katchy, Anne; Pinto, Caroline; Jonsson, Philip; Nguyen-Vu, Trang; Pandelova, Marchela; Riu, Anne; Schramm, Karl-Werner; Samarov, Daniel; Gustafsson, Jan-Åke; Bondesson, Maria; Williams, Cecilia

    2014-03-01

    Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer.

  3. A Batesian mimic and its model share color production mechanisms

    Institute of Scientific and Technical Information of China (English)

    David W.KIKUCHI; David W.PFENNIG

    2012-01-01

    Batesian mimics are harmless prey species that resemble dangerous ones (models),and thus receive protection from predators.How such adaptive resemblances evolve is a classical problem in evolutionary biology.Mimicry is typically thought to be difficult to evolve,especially if the model and mimic produce the convergent phenotype through different proximate mechanisms.However,mimicry may evolve more readily if mimic and model share similar pathways for producing the convergent phenotype.In such cases,these pathways can be co-opted in ancestral mimic populations to produce high-fidelity mimicry without the need for major evolutionary innovations.Here,we show that a Batesian mimic,the scarlet kingsnake Lampropettis elapsoides,produces its coloration using the same physiological mechanisms as does its model,the eastern coral snake Micrurus fulvius.Therefore,precise color mimicry may have been able to evolve easily in this system.Generally,we know relatively little about the proximate mechanisms underlying mimicry.

  4. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available 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.

  5. MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.

    Science.gov (United States)

    Magers, Martin J; Udager, Aaron M; Mehra, Rohit

    2015-10-01

    Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics may have important clinical implications. The differential diagnosis for t-RCC includes a variety of common renal neoplasms, particularly those demonstrating clear cell and papillary features; in addition, because of immunophenotypic overlap and/or shared molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of nonepithelial renal tumors may also warrant consideration. Directed ancillary testing is an essential aspect to the workup of t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break-apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may be helpful in diagnostically challenging cases or when molecular confirmation is needed.

  6. Sucrose mimics the light induction of Arabidopsis nitrate reductase gene transcription

    DEFF Research Database (Denmark)

    Cheng, Chi-Lien; Acedo, Gregoria N; Kristensen, Michael

    1992-01-01

    can replace light in eliciting an increase of nitrate reductase mRNA accumulation in dark-adapted green Arabidopsis plants. We show further that sucrose alone is sufficient for the full expression of nitrate reductase genes in etiolated Arabidopsis plants. Finally, using a reporter gene, we show......Nitrate reductase, the first enzyme in nitrate assimilation, is located at the crossroad of two energy-consuming pathways: nitrate assimilation and carbon fixation. Light, which regulates the expression of many higher-plant carbon fixation genes, also regulates nitrate reductase gene expression....... Located in the cytosol, nitrate reductase obtains its reductant not from photosynthesis but from carbohydrate catabolism. This relationship prompted us to investigate the indirect role that light might play, via photosynthesis, in the regulation of nitrate reductase gene expression. We show that sucrose...

  7. SuperMimic – Fitting peptide mimetics into protein structures

    Directory of Open Access Journals (Sweden)

    Schmidt Ulrike

    2006-01-01

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

  8. SuperMimic – Fitting peptide mimetics into protein structures

    Science.gov (United States)

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

    2006-01-01

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

  9. Transcription factories

    Science.gov (United States)

    Rieder, Dietmar; Trajanoski, Zlatko; McNally, James G.

    2012-01-01

    There is considerable evidence that transcription does not occur homogeneously or diffusely throughout the nucleus, but rather at a number of specialized, discrete sites termed transcription factories. The factories are composed of ~4–30 RNA polymerase molecules, and are associated with many other molecules involved in transcriptional activation and mRNA processing. Some data suggest that the polymerase molecules within a factory remain stationary relative to the transcribed DNA, which is thought to be reeled through the factory site. There is also some evidence that transcription factories could help organize chromatin and nuclear structure, contributing to both the formation of chromatin loops and the clustering of active and co-regulated genes. PMID:23109938

  10. Synthesis of aminocyclopentanols: a-D-galacto configured sugar mimics

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Lundt, Inge

    2005-01-01

    Four aminocyclopentanols, as mimics of putative intermediates in hydrolysis of a-D-galactosides, have been synthesized through a number of stereoselective transformations, using the cis-fused cyclopentane-1,4-lactone (1R, 5S, 7R, 8R)-7,8-dihydroxy-2-oxabicyclo[3.3.0]oct-3-one 1 as a chiral building...

  11. Synthesis of aminocyclopentanols: a-D-galacto configured sugar mimics

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Lundt, Inge

    2005-01-01

    Four aminocyclopentanols, as mimics of putative intermediates in hydrolysis of a-D-galactosides, have been synthesized through a number of stereoselective transformations, using the cis-fused cyclopentane-1,4-lactone (1R, 5S, 7R, 8R)-7,8-dihydroxy-2-oxabicyclo[3.3.0]oct-3-one 1 as a chiral buildi...

  12. Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic

    Science.gov (United States)

    Perry, Kay; Hwang, Young; Bushman, Frederic D.; Van Duyne, Gregory D.

    2010-01-01

    Summary Poxviruses encode their own type IB topoisomerases (TopIBs) which release superhelical tension generated by replication and transcription of their genomes. To investigate the reaction catalyzed viral TopIBs, we have determined the structure of a variola virus topoisomerase-DNA complex trapped as a vanadate transition state mimic. The structure reveals how the viral TopIB enzymes are likely to position the DNA duplex for ligation following relaxation of supercoils and identifies the sources of friction observed in single molecule experiments that argue against free rotation. The structure also identifies a conformational change in the leaving group sugar that must occur prior to cleavage and reveals a mechanism for promoting ligation following relaxation of supercoils that involves a novel Asp-minor groove interaction. Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small vs. large enzyme subfamilies. PMID:20152159

  13. A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing.

    Science.gov (United States)

    Romero, David A; Hasan, Ayad H; Lin, Yu-Fei; Kime, Louise; Ruiz-Larrabeiti, Olatz; Urem, Mia; Bucca, Giselda; Mamanova, Lira; Laing, Emma E; van Wezel, Gilles P; Smith, Colin P; Kaberdin, Vladimir R; McDowall, Kenneth J

    2014-09-30

    Streptomyces coelicolor is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post-genomic studies have revealed complex patterns of gene expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in RNA processing and degradation as well as transcription within a nucleotide-resolution map of the transcriptional landscape. This was achieved by combining RNA-sequencing approaches suited to the analysis of GC-rich organisms. Escherichia coli was analysed in parallel to validate the methodology and allow comparison. Previously, sites of RNA processing and degradation had not been mapped on a transcriptome-wide scale for E. coli. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in S. coelicolor and the identification of host-encoded leaderless mRNA and rRNA processing associated with the generation of specialized ribosomes in E. coli. New regulatory small RNAs were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  14. Data on the catalytic mechanism of thiol peroxidase mimics

    Directory of Open Access Journals (Sweden)

    B. Zadehvakili

    2016-09-01

    Full Text Available We have recently reported SAR data describing the pharmacological activity of a series of phenyl alkyl selenides and tellurides which catalyse the oxidation of thiols by hydrogen peroxide (H2O2, “The design of redox active thiol peroxidase mimics: dihydrolipoic acid recognition correlates with cytotoxicity and prooxidant action” B. Zadehvakili, S.M. McNeill, J.P. Fawcett, G.I. Giles (2016 [1]. This thiol peroxidase (TPx activity is potentially useful for a number of therapeutic applications, as it can alter the outcome of oxidative stress related pathologies and modify redox signalling. This article presents data describing the molecular changes that occur to a TPx mimic upon exposure to H2O2, and then the thiol mercaptoethanol, as characterised by UV–vis spectroscopy and HPLC retention time.

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

    Science.gov (United States)

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

    2015-06-01

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

  16. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    OpenAIRE

    Marrakchi, S.; I. Kammoun; S. Kachboura

    2014-01-01

    Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old ...

  17. CRADA Final Report: Mucin Mimic and Glycopeptide Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Molecular mechanical properties of short-sequence peptide enzyme mimics.

    Science.gov (United States)

    Takahashi, Tsukasa; Vo Ngo, Bao C; Xiao, Leyang; Arya, Gaurav; Heller, Michael J

    2016-01-01

    While considerable attempts have been made to recreate the high turnover rates of enzymes using synthetic enzyme mimics, most have failed and only a few have produced minimal reaction rates that can barely be considered catalytic. One particular approach we have focused on is the use of short-sequence peptides that contain key catalytic groups in close proximity. In this study, we designed six different peptides and tested their ability to mimic the catalytic mechanism of the cysteine proteases. Acetylation and deacylation by Ellman's Reagent trapping experiments showed the importance of having phenylalanine groups surrounding the catalytic sites in order to provide greater proximity between the cysteine, histidine, and aspartate amino acid R-groups. We have also carried out all-atom molecular dynamics simulations to determine the distance between these catalytic groups and the overall mechanical flexibility of the peptides. We found strong correlations between the magnitude of fluctuations in the Cys-His distance, which determines the flexibility and interactions between the cysteine thiol and histidine imidazole groups, and the deacylation rate. We found that, in general, shorter Cys-His distance fluctuations led to a higher deacylation rate constant, implying that greater confinement of the two residues will allow a higher frequency of the acetyl exchange between the cysteine thiol and histidine imidazole R-groups. This may be the key to future design of peptide structures with molecular mechanical properties that lead to viable enzyme mimics.

  19. Short tandem target mimic: a long journey to the engineered molecular landmine for selective destruction/blockage of microRNAs in plants and animals.

    Science.gov (United States)

    Tang, Guiliang; Tang, Xiaoqing

    2013-06-20

    MicroRNAs (miRNAs) are a population of highly conserved specific small ribo-regulators that negatively regulate gene expressions in both plants and animals. They play a key role in post-transcriptional gene regulation by destabilizing the target gene transcripts or blocking protein translation from them. Interestingly, these negative regulators are largely compromised by an upstream layer of negative regulators "target mimics" found in plants or "endogenous competing RNAs" revealed recently in animals. These endogenous regulatory mechanisms of "double negatives making a positive" have now been developed into a key strategy in the study of small RNA functions. This review presents some reflections on the long journey to the short tandem target mimic (STTM) for selective destruction/blockage of specific miRNAs in plants and animals, and the potential applications of STTM are discussed.

  20. Towards "bionic" proteins: replacement of continuous sequences from HIF-1α with proteomimetics to create functional p300 binding HIF-1α mimics.

    Science.gov (United States)

    Burslem, George M; Kyle, Hannah F; Breeze, Alexander L; Edwards, Thomas A; Nelson, Adam; Warriner, Stuart L; Wilson, Andrew J

    2016-04-01

    Using the HIF-1α transcription factor as a model, this manuscript illustrates how an extended sequence of α-amino acids in a polypeptide can be replaced with a non-natural topographical mimic of an α-helix comprised from an aromatic oligoamide. The resultant hybrid is capable of reproducing the molecular recognition profile of the p300 binding sequence of HIF-1α from which it is derived.

  1. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Directory of Open Access Journals (Sweden)

    Jia Fang

    2016-01-01

    Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  2. Transcription elongation

    Science.gov (United States)

    Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku; Kashlev, Mikhail

    2014-01-01

    Regulation of transcription elongation via pausing of RNA polymerase has multiple physiological roles. The pausing mechanism depends on the sequence heterogeneity of the DNA being transcribed, as well as on certain interactions of polymerase with specific DNA sequences. In order to describe the mechanism of regulation, we introduce the concept of heterogeneity into the previously proposed alternative models of elongation, power stroke and Brownian ratchet. We also discuss molecular origins and physiological significances of the heterogeneity. PMID:25764114

  3. Regulatory aspects

    Science.gov (United States)

    Stern, Arthur M.

    1986-07-01

    At this time, there is no US legislation that is specifically aimed at regulating the environmental release of genetically engineered organisms or their modified components, either during the research and development stage or during application. There are some statutes, administered by several federal agencies, whose language is broad enough to allow the extension of intended coverage to include certain aspects of biotechnology. The one possible exception is FIFRA, which has already brought about the registration of several natural microbial pesticides but which also has provision for requiring the registration of “strain improved” microbial pesticides. Nevertheless, there may be gaps in coverage even if all pertinent statutes were to be actively applied to the control of environmental release of genetically modified substances. The decision to regulate biotechnology under TSCA was justified, in part, on the basis of its intended role as a gap-filling piece of environmental legislation. The advantage of regulating biotechnology under TSCA is that this statute, unlike others, is concerned with all media of exposure (air, water, soil, sediment, biota) that may pose health and environmental hazards. Experience may show that extending existing legislation to regulate biotechnology is a poor compromise compared to the promulgation of new legislation specifically designed for this purpose. It appears that many other countries are ultimately going to take the latter course to regulate biotechnology.

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

    Science.gov (United States)

    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…

  5. Bicelles and Other Membrane Mimics: Comparison of Structure, Properties, and Dynamics from MD Simulations

    DEFF Research Database (Denmark)

    Vestergaard, Mikkel; Kraft, Johan Frederik; Vosegaard, Thomas

    2015-01-01

    The increased interest in studying membrane proteins has led to the development of new membrane mimics such as bicelles and nanodiscs. However, only limited knowledge is available of how these membrane mimics are affected by embedded proteins and how well they mimic a lipid bilayer. Herein, we pr...

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    Directory of Open Access Journals (Sweden)

    S. Marrakchi

    2014-01-01

    Full Text Available Background. It is important to recognise Wolff-Parkinson-White (WPW syndrome in electrocardiograms (ECG, as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

  8. The NPM-ALK tyrosine kinase mimics TCR signalling pathways, inducing NFAT and AP-1 by RAS-dependent mechanisms.

    Science.gov (United States)

    Turner, Suzanne D; Yeung, Debra; Hadfield, Kathryn; Cook, Simon J; Alexander, Denis R

    2007-04-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) expression is associated with the lymphoid malignancy anaplastic large cell lymphoma (ALCL) and results from a t(2;5) chromosomal translocation. We show that NPM-ALK induces Ras activation and phosphorylation of the ERK MAP Kinase consistent with activation of the Ras-MAP Kinase pathway. Furthermore, we demonstrate that activation of Ras is necessary for inducing transcription via NFAT/AP-1 composite transcriptional binding sites. This activity is dependent on NPM-ALK forming complexes with proteins that bind to autophosphorylated tyrosine residues at positions 156, 567 and 664, associated with binding to IRS-1, Shc and PLCgamma, respectively. Specifically, NPM-ALK activates transcription from the TRE promoter element, an AP-1 binding region, an activity dependent on both Ras and Shc activity. Our results show that NPM-ALK mimics activated T-cell receptor signalling by inducing pathways associated with the activation of NFAT/AP-1 transcription factors that bind to promoter elements found in a broad array of cytokine genes.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik;

    2014-01-01

    Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable...... protein-like structures in water. However, short peptides can be induced to fold into protein-like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine-tune three-dimensional structure. Such constrained cyclic...... peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...

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

    Science.gov (United States)

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

    2010-03-01

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

  13. Spinal dural arteriovenous fistula: Imaging features and its mimics

    Energy Technology Data Exchange (ETDEWEB)

    Jeog, Ying; Ting, David Yen; Hsu, Hui Ling; Huang, Yen Lin; Chen, Chi Jen; Tseng, Ting Chi [Dept. of Radiology, aipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan (China)

    2015-10-15

    Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular malformation, however it is still rare and underdiagnosed. Magnetic resonance imaging findings such as spinal cord edema and dilated and tortuous perimedullary veins play a pivotal role in the confirmation of the diagnosis. However, spinal angiography remains the gold standard in the diagnosis of SDAVF. Classic angiographic findings of SDAVF are early filling of radicular veins, delayed venous return, and an extensive network of dilated perimedullary venous plexus. A series of angiograms of SDAVF at different locations along the spinal column, and mimics of serpentine perimedullary venous plexus on MR images, are demonstrated. Thorough knowledge of SDAVF aids correct diagnosis and prevents irreversible complications.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  16. Biofilm streamer formation in a microfluidic porous media mimic

    Science.gov (United States)

    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. Malakoplakia mimics urinary bladder cancer: A case report

    Directory of Open Access Journals (Sweden)

    Ristić-Petrović Ana

    2013-01-01

    Full Text Available Introduction. Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. Case report. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Conclusion. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications. [Projekat Ministarstva nauke Republike Srbije, br. 175092

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

    Science.gov (United States)

    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.

  19. Ouabain mimics low temperature rescue of F508del-CFTR in cystic fibrosis epithelial cells

    Directory of Open Access Journals (Sweden)

    Donglei eZhang

    2012-10-01

    Full Text Available ABSTRACT Most cases of cystic fibrosis (CF are caused by the deletion of a single phenylalanine residue at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR. The mutant F508del-CFTR is retained in the endoplasmic reticulum and degraded, but can be induced by low temperature incubation (29°C to traffic to the plasma membrane where it functions as a chloride channel. Here we show that, cardiac glycosides, at nanomolar concentrations, can partially correct the trafficking of F508del-CFTR in human CF bronchial epithelial cells (CFBE41o- and in an F508del-CFTR mouse model. Comparison of the transcriptional profiles obtained with polarized CFBE41o- cells after treatment with ouabain and by low temperature has revealed a striking similarity between the two corrector treatments that is not shared with other correctors. In summary, our study shows a novel function of ouabain and its analogues in the regulation of F508del-CFTR trafficking and suggests that compounds that mimic this low temperature correction of trafficking will provide new avenues for the development of therapeutics for CF.

  20. Endoscopic Aspects of Gastric Syphilis

    Directory of Open Access Journals (Sweden)

    Mariana Souza Varella Frazão

    2012-01-01

    Full Text Available Introduction. Considered as a rare event, gastric syphilis (GS is reported as an organic form of involvement. Low incidence of GS emphasizes the importance of histopathological analysis. Objective. We aim to characterize GS endoscopic aspects in an immunocompetent patient. Case Report. A 23-year-old man presented with epigastric pain associated with nausea, anorexia, generalized malaise and 11 kg weight loss that started 1 month prior to his clinical consultation. Physical examination was normal except for mild abdominal tenderness in epigastrium. Endoscopy observed diminished gastric expandability and diffuse mucosal lesions, from cardia to pylorus. Gastric mucosa was thickened, friable, with nodular aspect, and associated with ulcers lesions. Gastric biopsies were performed, and histopathological analysis resulted in dense inflammatory infiltration rich in plasmocytes. Syphilis serologies were positive for VDRL and Treponema pallidum reagents. Immunohistochemical tests were positive for Treponema pallidum and CD138. The patient was treated with penicillin, leading to resolution of his clinical complaints and endoscopic findings. Conclusion. Diagnosis suspicion of GS is important in view of its nonspecific presentation. Patients with gastric symptoms that mimic neoplastic disease should be investigated thoroughly based on the fact that clinical, endoscopic, and histological findings can easily be mistaken for lymphoma or plastic linitis.

  1. Aspects and Polymorphism in AspectJ

    DEFF Research Database (Denmark)

    Lorenz, David Harel; Ernst, Erik

    2003-01-01

    -oriented programming (AOP). In AOP, pieces of crosscutting behavior are extracted from the base code and localized in aspects, losing as a result their polymorphic capabilities while introducing new and unexplored issues. In this paper, we explore what kinds of polymorphism AOP languages should support, using AspectJ...... as the basis for the presentation. The results are not exclusive to AspectJ---aspectual polymorphism may make aspects in any comparable AOSD language more expressive and reusable across programs, while preserving safety....

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

    Science.gov (United States)

    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. Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. A novel route for preparing 5' cap mimics and capped RNAs: phosphate-modified cap analogues obtained via click chemistry.

    Science.gov (United States)

    Walczak, Sylwia; Nowicka, Anna; Kubacka, Dorota; Fac, Kaja; Wanat, Przemyslaw; Mroczek, Seweryn; Kowalska, Joanna; Jemielity, Jacek

    2017-01-01

    The significant biological role of the mRNA 5' cap in translation initiation makes it an interesting subject for chemical modifications aimed at producing useful tools for the selective modulation of intercellular processes and development of novel therapeutic interventions. However, traditional approaches to the chemical synthesis of cap analogues are time-consuming and labour-intensive, which impedes the development of novel compounds and their applications. Here, we explore a different approach for synthesizing 5' cap mimics, making use of click chemistry (CuAAC) to combine two mononucleotide units and yield a novel class of dinucleotide cap analogues containing a triazole ring within the oligophosphate chain. As a result, we synthesized a library of 36 mRNA cap analogues differing in the location of the triazole ring, the polyphosphate chain length, and the type of linkers joining the phosphate and the triazole moieties. After biochemical evaluation, we identified two analogues that, when incorporated into mRNA, produced transcripts translated with efficiency similar to compounds unmodified in the oligophosphate bridge obtained by traditional synthesis. Moreover, we demonstrated that the triazole-modified cap structures can be generated at the RNA 5' end using two alternative capping strategies: either the typical co-transcriptional approach, or a new post-transcriptional approach based on CuAAC. Our findings open new possibilities for developing chemically modified mRNAs for research and therapeutic applications, including RNA-based vaccinations.

  4. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment

    Institute of Scientific and Technical Information of China (English)

    Xianying Wang; Honghai Wu; Gai Xue; Yanning Hou

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.

  5. AspectKE*

    DEFF Research Database (Denmark)

    Yang, Fan; Masuhara, Hidehiko; Aotani, Tomoyuki

    2010-01-01

    Enforcing security policies to distributed systems is difficult, in particular, when a system contains untrusted components. We designed AspectKE*, a distributed AOP language based on a tuple space, to tackle this issue. In AspectKE*, aspects can enforce access control policies that depend......KE*, and demonstrate usefulness of AspectKE* through a security aspect for a distributed chat system....

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

    Science.gov (United States)

    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

  7. Berberine inhibits PTP1B activity and mimics insulin action.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 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.

  10. Approaches to mimic the metallic sheen in beetles

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Mariska E Kret

    Full Text Available 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.

  15. Decorin mimic inhibits vascular smooth muscle proliferation and migration.

    Directory of Open Access Journals (Sweden)

    Rebecca A Scott

    Full Text Available Over the past 10 years, the number of percutaneous coronary intervention procedures performed in the United States increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, complicates this procedure. A wide range of anti-restenotic therapeutics have been developed, although many elicit non-specific effects that compromise vessel healing. Drawing inspiration from biologically-relevant molecules, our lab developed a mimic of the natural proteoglycan decorin, termed DS-SILY, which can mask exposed collagen and thereby effectively decrease platelet activation, thus contributing to suppression of vascular intimal hyperplasia. Here, we characterize the effects of DS-SILY on both proliferative and quiescent human SMCs to evaluate the potential impact of DS-SILY-SMC interaction on restenosis, and further characterize in vivo platelet interactions. DS-SILY decreased proliferative SMC proliferation and pro-inflammatory cytokine secretion in vitro in a concentration dependent manner as compared to untreated controls. The addition of DS-SILY to in vitro SMC cultures decreased SMC migration and protein synthesis by 95% and 37%, respectively. Furthermore, DS-SILY decreased platelet activation, as well as reduced neointimal hyperplasia by 60%, in vivo using Ossabaw swine. These results indicate that DS-SILY demonstrates multiple biological activities that may all synergistically contribute to an improved treatment paradigm for balloon angioplasty.

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

    Directory of Open Access Journals (Sweden)

    Gurcharanjeet Kaur

    2016-01-01

    Full Text Available 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.

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

    KAUST Repository

    Bruggeman, Quentin

    2015-01-30

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

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

    Directory of Open Access Journals (Sweden)

    Quentin eBruggeman

    2015-01-01

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

  19. Medical Textiles as Vascular Implants and Their Success to Mimic Natural Arteries

    Directory of Open Access Journals (Sweden)

    Charanpreet Singh

    2015-06-01

    Full Text Available Vascular implants belong to a specialised class of medical textiles. The basic purpose of a vascular implant (graft and stent is to act as an artificial conduit or substitute for a diseased artery. However, the long-term healing function depends on its ability to mimic the mechanical and biological behaviour of the artery. This requires a thorough understanding of the structure and function of an artery, which can then be translated into a synthetic structure based on the capabilities of the manufacturing method utilised. Common textile manufacturing techniques, such as weaving, knitting, braiding, and electrospinning, are frequently used to design vascular implants for research and commercial purposes for the past decades. However, the ability to match attributes of a vascular substitute to those of a native artery still remains a challenge. The synthetic implants have been found to cause disturbance in biological, biomechanical, and hemodynamic parameters at the implant site, which has been widely attributed to their structural design. In this work, we reviewed the design aspect of textile vascular implants and compared them to the structure of a natural artery as a basis for assessing the level of success as an implant. The outcome of this work is expected to encourage future design strategies for developing improved long lasting vascular implants.

  20. Escherichia coli transcriptional regulatory network

    Directory of Open Access Journals (Sweden)

    Agustino Martinez-Antonio

    2011-06-01

    Full Text Available Escherichia coli is the most well-know bacterial model about the function of its molecular components. In this review are presented several structural and functional aspects of their transcriptional regulatory network constituted by transcription factors and target genes. The network discussed here represent to 1531 genes and 3421 regulatory interactions. This network shows a power-law distribution with a few global regulators and most of genes poorly connected. 176 of genes in the network correspond to transcription factors, which form a sub-network of seven hierarchical layers where global regulators tend to be set in superior layers while local regulators are located in the lower ones. There is a small set of proteins know as nucleoid-associated proteins, which are in a high cellular concentrations and reshape the nucleoid structure to influence the running of global transcriptional programs, to this mode of regulation is named analog regulation. Specific signal effectors assist the activity of most of transcription factors in E. coli. These effectors switch and tune the activity of transcription factors. To this type of regulation, depending of environmental signals is named the digital-precise-regulation. The integration of regulatory programs have place in the promoter region of transcription units where it is common to observe co-regulation among global and local TFs as well as of TFs sensing exogenous and endogenous conditions. The mechanistic logic to understand the harmonious operation of regulatory programs in the network should consider the globalism of TFs, their signal perceived, coregulation, genome position, and cellular concentration. Finally, duplicated TFs and their horizontal transfer influence the evolvability of members of the network. The most duplicated and transferred TFs are located in the network periphery.

  1. Inhibition of duck hepatitis B virus replication by mimic peptides in vitro

    Science.gov (United States)

    JIA, HONGYU; LIU, CHANGHONG; YANG, YING; ZHU, HAIHONG; CHEN, FENG; LIU, JIHONG; ZHOU, LINFU

    2015-01-01

    The aim of the present study was to investigate the inhibitory effect of specific mimic peptides targeting duck hepatitis B virus polymerase (DHBVP) on duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Phage display technology (PDT) was used to screen for mimic peptides specifically targeting DHBVP and the associated coding sequences were determined using DNA sequencing. The selected mimic peptides were then used to treat primary duck hepatocytes infected with DHBV in vitro. Infected hepatocytes expressing the mimic peptides intracellularly were also prepared. The cells were divided into mimic peptide groups (EXP groups), an entecavir-treated group (positive control) and a negative control group. The medium was changed every 48 h. Following a 10-day incubation, the cell supernatants were collected. DHBV-DNA in the cellular nucleus, cytoplasm and culture supernatant was analyzed by quantitative polymerase chain reaction (qPCR). Eight mimic peptides were selected following three PDT screening rounds for investigation in the DHBV-infected primary duck hepatocytes. The qPCR results showed that following direct treatment with mimic peptide 2 or 7, intracellular expression of mimic peptide 2 or 7, or treatment with entecavir, the DHBV-DNA levels in the culture supernatant and cytoplasm of duck hepatocytes were significantly lower than those in the negative control (P<0.05). The cytoplasmic DHBV-DNA content of the cells treated with mimic peptide 7 was lower than that in the other groups (P<0.05). In addition, the DHBV-DNA content of the nuclear fractions following the intracellular expression of mimic peptide 7 was significantly lower than that in the other groups (P<0.05). Mimic peptides specifically targeting DHBVP, administered directly or expressed intracellularly, can significantly inhibit DHBV replication in vitro. PMID:26640539

  2. Bovine Serum Albumin Metal Complexes for Mimic of SOD

    Indian Academy of Sciences (India)

    GUIFANG YAN; YUFENG HE; GANG LI; YUBING XIONG; PENGFEI SONG; RONG-MIN WANG

    2016-11-01

    Superoxide anion radical (O•−₂ ) is a noxious reactive oxygen species (ROS). Transition metal ion complexes have been generally used as antioxidants to eliminate ROS. In this work, a neoteric watersoluble biopolymer metal complex (BSA-M) was prepared by conjugating the soluble biopolymer bovineserum albumin (BSA) with three transition metal ions (M, M=Cu, Co, Mn). The binding mode and ratio of metal ions bound to albumin were investigated. The BSA-M complexes were characterized by UV-Vis, circular dichroism (CD) spectra and polyacrylamide gel electrophoresis (PAGE). BSA served as polymerscaffold and the metal complex functioned as the catalytic active center. The results demonstrated that the structure of BSA remained unchanged when the binding ratio of transition metal ion complex to BSA was 5:1. Furthermore, the scavenging superoxide anion free radical (O•−₂ ) activity of biopolymer-metal complexes were determined by nitroblue tetrazolium light reduction assay method. The antioxidant capacity of BSA-M has markedly increased. The conjugated BSA-M (M=Cu, Mn) showed preeminent scavenging activity for O•−₂ , and the EC₅₀ value of the BSA-Cu was 0.038±0.0013μmol·L⁻¹, which is comparable to EC₅₀ value (0.041±0.001μmol·L⁻¹) of the natural superoxide dismutase (SOD), the analog quantity reached 107%. As a consequence, it can be considered as a bio-functional mimic of enzyme SOD and has a promising application prospect in antioxidant drug field.

  3. Assessing the potential of surrogate EPS to mimic natural biofilm mechanical properties

    Science.gov (United States)

    Thom, Moritz; Schimmels, Stefan

    2017-04-01

    Biofilms growing on benthic sediments may increase the resistance towards erosion considerably by the sticky nature of extracellular polymeric substances (EPS). The EPS is a biopolymer which is secreted by the microorganisms inhabiting the biofilm matrix and may be regarded as natural glue. However, laboratory studies on the biostabilization effect mediated by biofilms are often hampered by the unavailability of "environmental" flumes in which light intensities, water temperature and nutrient content can be controlled. To allow investigations on biostabilization in "traditional" flume settings the use of surrogate materials is studied. Another advantage of using appropriate surrogates is the potential to reduce the experimental time, as compared to cultivating natural biofilms, the surrogates can readily be designed to mimic biofilms at different growth stages. Furthermore, the use of surrogates which are expected to have more homogeneous mechanical properties could facilitate fundamental studies to improve our knowledge on biostabilization. Even though a number of studies have already utilized EPS surrogates it is not clear how to mix them to correctly mimic natural EPS mechanical properties. In this study the adhesiveness (a measure of stickiness) on the surface of several EPS surrogates (e.g. Xanthan Gum, sodium alginate) is measured. These surrogates which are originally used in the food industry as rheology modifiers are mixed by adding water to a powder at a desired concentration (C). The measured surface adhesion of different surrogates at different concentrations ranged from 0.5 to 6.7 N/m2, which is well in line with values found for laboratory cultured biofilms. We found that the surrogate characteristics differed largely especially in regard to a) the response of the adhesiveness to increased concentrations (powder to water) and b) in their rheological characteristics. A seemingly promising surrogate for the use in biostabilization studies is Xanthan Gum

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  6. Selective Mimics of Strigolactone Actions and Their Potential Use for Controlling Damage Caused by Root Parasitic Weeds

    Institute of Scientific and Technical Information of China (English)

    Kosuke Fukui; Shinsaku Ito; Tadao Asami

    2013-01-01

    Strigolactones (SLs) are a novel class of plant hormones and rhizosphere communication signals,although the molecular mechanisms underlying their activities have not yet been fully determined.Nor is their application in agriculture well developed.The importance of plant hormone agonists has been demonstrated in both basic and applied research,and chemicals that mimic strigolactone functions should greatly facilitate strigolactone research.Here,we report our discovery of a new phenoxyfuranone compound,4-Br debranone (4BD),that shows similar activity to that of the major strigolactone (SL) analog GR24 in many aspects of a biological assay on plants.4BD strongly inhibited tiller bud outgrowth in the SL-deficient rice mutant d10 at the same concentration as GR24,with no adverse effects,even during prolonged cultivation.This result was also observed in the Arabidopsis thaliana SL-deficient mutants max1,max3,and max4.However,the application of 4BD to the Arabidopsis SL-insensitive mutant max2 induced no morphological changes in it.The expression of SL biosynthetic genes was also reduced by 4BD treatment,probably via negative feedback regulation.However,in a seed germination assay on Striga hermonthica,a root parasitic plant,4BD showed far less activity than GR24.These results suggest that 4BD is the first plant-specific strigolactone mimic.

  7. Selective mimics of strigolactone actions and their potential use for controlling damage caused by root parasitic weeds.

    Science.gov (United States)

    Fukui, Kosuke; Ito, Shinsaku; Asami, Tadao

    2013-01-01

    Strigolactones (SLs) are a novel class of plant hormones and rhizosphere communication signals, although the molecular mechanisms underlying their activities have not yet been fully determined. Nor is their application in agriculture well developed. The importance of plant hormone agonists has been demonstrated in both basic and applied research, and chemicals that mimic strigolactone functions should greatly facilitate strigolactone research. Here, we report our discovery of a new phenoxyfuranone compound, 4-Br debranone (4BD), that shows similar activity to that of the major strigolactone (SL) analog GR24 in many aspects of a biological assay on plants. 4BD strongly inhibited tiller bud outgrowth in the SL-deficient rice mutant d10 at the same concentration as GR24, with no adverse effects, even during prolonged cultivation. This result was also observed in the Arabidopsis thaliana SL-deficient mutants max1, max3, and max4. However, the application of 4BD to the Arabidopsis SL-insensitive mutant max2 induced no morphological changes in it. The expression of SL biosynthetic genes was also reduced by 4BD treatment, probably via negative feedback regulation. However, in a seed germination assay on Striga hermonthica, a root parasitic plant, 4BD showed far less activity than GR24. These results suggest that 4BD is the first plant-specific strigolactone mimic.

  8. Effect of rice fat mimics on texture and microstructure of low-fat yoghurt

    Institute of Scientific and Technical Information of China (English)

    XU Dan; KONG Baohua; LIU Huaiwei

    2007-01-01

    This paper made a research on a new kind of rice fat mimics, which was obtained from rice powder hydrolyzed by a -amylase. Through the comparison between the yoghurt added with diverse proportions of above mentioned rice fat mimics and the reduced-fat yoghurt without any fat mimics as well as full-fat ones, the effect of the rice fat mimics in different proportions was examined upon the composition, the microstructure, the texture and the sensory evaluation of reduced-fat yoghurt. The results showed that the yoghurts added with rice fat mimics exhibited similar organoleptic attribute, textual characteristics and acceptability compared to those of full-fat controls(P>0.05), but with lower fat content and looser microstructures.

  9. Our evolving knowledge of the transcriptional landscape.

    Science.gov (United States)

    Hume, David A

    2008-01-01

    The development of a genome-scale approach to identification of the 5' ends of capped mRNAs (CAGE) has given new insights into many aspects of mammalian RNApolII transcription control. They include the identification of the minimal initiator motif, the different types of proximal promoter architecture, the promoters of noncoding RNAs, the transcription of retrotransposons, and the extensive impact of alternative promoters on the proteome. CAGE also offers applications as a form of expression profiling that measures promoter use, allowing more precise development of transcriptional network models.

  10. Aspect and Reference time

    NARCIS (Netherlands)

    Borik, O.

    2002-01-01

    This thesis provides a theory of aspect in Russian based on the notion of Reference time. The main claim advocated in this study is that there are two types of aspect, predicational/telicity aspect and perspective or Reference time aspect. It is argued that these two types should be carefully distin

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

    Science.gov (United States)

    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

  12. Structural insights into transcription complexes.

    Science.gov (United States)

    Berger, Imre; Blanco, Alexandre G; Boelens, Rolf; Cavarelli, Jean; Coll, Miquel; Folkers, Gert E; Nie, Yan; Pogenberg, Vivian; Schultz, Patrick; Wilmanns, Matthias; Moras, Dino; Poterszman, Arnaud

    2011-08-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of structural proteomics on our understanding of the molecular basis of gene expression. While most atomic structures were obtained by X-ray crystallography, the impact of solution NMR and cryo-electron microscopy is far from being negligible. Here, we summarize some highlights and illustrate the importance of specific technologies on the structural biology of protein-protein or protein/DNA transcription complexes: structure/function analysis of components the eukaryotic basal and activated transcription machinery with focus on the TFIID and TFIIH multi-subunit complexes as well as transcription regulators such as members of the nuclear hormone receptor families. We also discuss molecular aspects of promoter recognition and epigenetic control of gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Boosting transcription by transcription: enhancer-associated transcripts.

    Science.gov (United States)

    Darrow, Emily M; Chadwick, Brian P

    2013-12-01

    Enhancers are traditionally viewed as DNA sequences located some distance from a promoter that act in cis and in an orientation-independent fashion to increase utilization of specific promoters and thereby regulate gene expression. Much progress has been made over the last decade toward understanding how these distant elements interact with target promoters, but how transcription is enhanced remains an object of active inquiry. Recent reports convey the prevalence and diversity of enhancer transcription and transcripts and support both as key factors with mechanistically distinct, but not mutually exclusive roles in enhancer function. Decoupling the causes and effects of transcription on the local chromatin landscape and understanding the role of enhancer transcripts in the context of long-range interactions are challenges that require additional attention. In this review, we focus on the possible functions of enhancer transcription by highlighting several recent enhancer RNA papers and, within the context of other enhancer studies, speculate on the role of enhancer transcription in regulating differential gene expression.

  14. Optimising AspectJ

    DEFF Research Database (Denmark)

    Avgustinov, Pavel; Christensen, Aske Simon; Hendren, Laurie

    2005-01-01

    AspectJ, an aspect-oriented extension of Java, is becoming increasingly popular. However, not much work has been directed at optimising compilers for AspectJ. Optimising AOP languages provides many new and interesting challenges for compiler writers, and this paper identifies and addresses three...... all of the techniques in this paper in abc, our AspectBench Compiler for AspectJ, and we demonstrate significant speedups with empirical results. Some of our techniques have already been integrated into the production AspectJ compiler, ajc 1.2.1....

  15. An environment-dependent transcriptional network specifies human microglia identity

    NARCIS (Netherlands)

    Gosselin, David; Skola, Dylan; Coufal, Nicole G.; Holtman, Inge R.; Schlachetzki, Johannes C. M.; Sajti, Eniko; Jaeger, Baptiste N.; O'Connor, Carolyn; Fitzpatrick, Conor; Pasillas, Martina P.; Pena, Monique; Adair, Amy; Gonda, David D.; Levy, Michael L.; Ransohoff, Richard M.; Gage, Fred H.; Glass, Christopher K.

    2017-01-01

    Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microg

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

    Science.gov (United States)

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

    2016-11-08

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

  17. Short Tandem Target Mimic: A Long Journey to the Engineered Molecular Landmine for Selective Destruction/Blockage of MicroRNAs in Plants and Animals

    Institute of Scientific and Technical Information of China (English)

    Guiliang Tang; Xiaoqing Tang

    2013-01-01

    MicroRNAs (miRNAs) are a population of highly conserved specific small ribo-regulators that negatively regulate gene expressions in both plants and animals.They play a key role in post-transcriptional gene regulation by destabilizing the target gene transcripts or blocking protein translation from them.Interestingly,these negative regulators are largely compromised by an upstream layer of negative regulators “target mimics” found in plants or “endogenous competing RNAs” revealed recently in animals.These endogenous regulatory mechanisms of “double negatives making a positive” have now been developed into a key strategy in the study of small RNA functions.This review presents some reflections on the long journey to the short tandem target mimic (STTM) for selective destruction/blockage of specific miRNAs in plants and animals,and the potential applications of STTM are discussed.

  18. Understanding Peptide Dendrimer Interactions with Model Cell Membrane Mimics

    DEFF Research Database (Denmark)

    Lind, Tania Kjellerup

    membranes or highly conserved motifs, effectively making resistance due to mutations less likely to develop and spread. For this we studied the conditions to form supported lipid bilayers with basic systems and further established a protocol for producing biomimetic bacterial model membranes via the vesicle...... fusion method, which presents improved means for studying drug-membrane interactions in the future. The interaction mechanism of a family of dendrimers was examined and in particular one dendrimer (BALY) was extensively studied by the combined use of quartz crystal microbalance, atomic force microscopy...... and neutron reection. The application of several complementary surface-sensitive techniques allowed for systematically addressing the interface-related processes and gain insights into different aspects of the interaction. BALY was found to interact via a uidity-dependent mechanism. It inserted into the outer...

  19. Runx transcription factors in neuronal development

    Directory of Open Access Journals (Sweden)

    Shiga Takashi

    2008-08-01

    Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

  20. Deficiency of Prdm13, a dorsomedial hypothalamus-enriched gene, mimics age-associated changes in sleep quality and adiposity.

    Science.gov (United States)

    Satoh, Akiko; Brace, Cynthia S; Rensing, Nick; Imai, Shin-Ichiro

    2015-04-01

    The dorsomedial hypothalamus (DMH) controls a number of essential physiological responses. We have demonstrated that the DMH plays an important role in the regulation of mammalian aging and longevity. To further dissect the molecular basis of the DMH function, we conducted microarray-based gene expression profiling with total RNA from laser-microdissected hypothalamic nuclei and tried to find the genes highly and selectively expressed in the DMH. We found neuropeptide VF precursor (Npvf), PR domain containing 13 (Prdm13), and SK1 family transcriptional corepressor (Skor1) as DMH-enriched genes. Particularly, Prdm13, a member of the Prdm family of transcription regulators, was specifically expressed in the compact region of the DMH (DMC), where Nk2 homeobox 1 (Nkx2-1) is predominantly expressed. The expression of Prdm13 in the hypothalamus increased under diet restriction, whereas it decreased during aging. Prdm13 expression also showed diurnal oscillation and was significantly upregulated in the DMH of long-lived BRASTO mice. The transcriptional activity of the Prdm13 promoter was upregulated by Nkx2-1, and knockdown of Nkx2-1 suppressed Prdm13 expression in primary hypothalamic neurons. Interestingly, DMH-specific Prdm13-knockdown mice showed significantly reduced wake time during the dark period and decreased sleep quality, which was defined by the quantity of electroencephalogram delta activity during NREM sleep. DMH-specific Prdm13-knockdown mice also exhibited progressive increases in body weight and adiposity. Our findings indicate that Prdm13/Nkx2-1-mediated signaling in the DMC declines with advanced age, leading to decreased sleep quality and increased adiposity, which mimic age-associated pathophysiology, and provides a potential link to DMH-mediated aging and longevity control in mammals.

  1. Discovering Early Aspects

    NARCIS (Netherlands)

    Baniassad, E.; Clements, P.; Araujo, J.; Moreira, A.; Rashid, A.; Tekinerdogan, B.

    2006-01-01

    Traditionally, aspect-oriented software development (AOSD) has focused on the software life cycle's implementation phase: aspects are identified and captured mainly in code. But aspects are evident earlier in the life cycle, such as during requirements gathering and architecture development. Identif

  2. Aspects, Dependencies, and Interactions

    NARCIS (Netherlands)

    Chitchyan, R; Fabry, J.; Bergmans, Lodewijk; Südholt, M.; Consel, C.

    2007-01-01

    For Aspect-Oriented Software Development (AOSD) the topic of Aspects, Dependencies and Interactions is of high importance across the whole range of development activities – from requirements engineering through to language design. Aspect interactions must be adequately addressed all across the softw

  3. Transformation optics that mimics the system outside a Schwarzschild black hole

    OpenAIRE

    Chen, Huanyang; Miao, Rong-Xin; Li, Miao

    2009-01-01

    We applied the transformation optics to mimic a black hole of Schwarzschild form. Similar properties of photon sphere were also found numerically for the metamaterial black hole. Several reduced versions of the black hole systems were proposed for easier implementations.

  4. Assembly of a Library of Trisaccharides as Mimics of Sialyl Lewis X via Random Combination Strategy

    Institute of Scientific and Technical Information of China (English)

    Xiang Bao MENG; Hui LI; Qing LI; Tie Ming CHENG; Zhong Jun LI

    2004-01-01

    A small library containing six positional isomers of fucosyl on the modified lactoside backbone as mimics of the Sialyl Lewis X was synthesized via random combinatorial glycosylation,which was charactered by ESI-MS and HPLC.

  5. Transcription in archaea

    Science.gov (United States)

    Kyrpides, N. C.; Ouzounis, C. A.; Woese, C. R. (Principal Investigator)

    1999-01-01

    Using the sequences of all the known transcription-associated proteins from Bacteria and Eucarya (a total of 4,147), we have identified their homologous counterparts in the four complete archaeal genomes. Through extensive sequence comparisons, we establish the presence of 280 predicted transcription factors or transcription-associated proteins in the four archaeal genomes, of which 168 have homologs only in Bacteria, 51 have homologs only in Eucarya, and the remaining 61 have homologs in both phylogenetic domains. Although bacterial and eukaryotic transcription have very few factors in common, each exclusively shares a significantly greater number with the Archaea, especially the Bacteria. This last fact contrasts with the obvious close relationship between the archaeal and eukaryotic transcription mechanisms per se, and in particular, basic transcription initiation. We interpret these results to mean that the archaeal transcription system has retained more ancestral characteristics than have the transcription mechanisms in either of the other two domains.

  6. 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.

    Science.gov (United States)

    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).

  7. Microdialysis of Soil P: A means to mimic root uptake?

    Science.gov (United States)

    Schack-Kirschner, Helmer; Demand, Dominic; Lang, Friederike

    2017-04-01

    Standard procedures to assess P availability in soils are based on batch experiments with various extractants. However, in most soils P nutrition is less limited by bulk stocks but by slow diffusion of phosphate through the soil solution. More comparable to the root's approach is to strip phosphate locally from the solid phase by lowering the soil-solution concentration, which can be achieved by establishing an infinite diffusional sink, such as DGT. An alternative diffusive sampling technique is microdialysis (MD), well established in pharmacokinetics. Briefly, this method uses miniaturized flow-through probes where the perfusate gets in diffusive contact to the external solution by a semipermeable membrane. Important aspects of P supply to roots resemble MD sampling. This is not only the mostly diffusive transport, but also an elongated capillary tube-like geometry of absorption. The diameter of typical commercial MD probes is around 500μm. One additional inherent feature of microdialysis is the possibility to release low-molecular substances from the perfusate by diffusion into the matrix, such as carboxylates. However, microdialysis has yet not been used for P in soils. We tested microdialysis in topsoils of an acid beech forest, of an unfertilized grassland and of a fertilized crop site. Three perfusates have been used: 1 mM KNO3, electrolyte + 0.1 mM citric acid, and electrolyte + 1 mM citric acid. We observed rates of uptake into the probes in a range between 1.5*10-15 and 6.7*10-14 mol s-1cm-1 in case of no citrate addition. Surprisingly, these uptake rates were mostly independent of the bulk stocks. Citrate addition increased P yields only in the higher concentration but not in the forest soil. The order of magnitude of MD uptake rates from the soil samples matched root-length related uptake rates from other studies. The micro-radial citrate release in MD reflects the processes controlling phosphate mobilization in the rhizosphere better than measurements

  8. INFLUENCE OF MIMIC CARDIAC RATE ON HYDRODYNAMICS OF DIFFERENT MECHANICAL PROSTHETIC CARDIAC VALVES IN VITRO

    Institute of Scientific and Technical Information of China (English)

    Yin-ping Chu; Jin-lian Cheng; Ru-kun Chen; Yu-bo Fan; Fang Pu

    2005-01-01

    Objective To assess the influence of mimic cardiac rate on hydrodynamics of different mechanical prosthetic cardiac valves.Methods US-made CarboMedics bileaflet valve, China-made Jiuling bileaflet valve and C-L tilting disc valve were tested via a pulsatile flow simulator in the aortic position. Testing conditions were set at mimic cardiac rates of 55 bpm, 75 bpm, 100bpm with a constant mimic cardiac output of 4 L/min. The mean pressure differences (△P), leakage volumes (LEV) and closing volumes (CLV) across each valve, and effective orifice areas (EOA) were analyzed.Results Within physiological range, △p, LEV, and CLV decreased as mimic cardiac rate increased, with a large extent of variance. EOA increased along with an increase in mimic cardiac rate. It was a different response in terms of cardiac rate alteration for different types of mechanical prosthetic cardiac valves.Conclusion Mimic cardiac rate change affects hydrodynamics of mechanical prosthetic cardiac valves. Within physiological range, the hydrodynamic of prosthetic bileaflet valve is better than that of tilting disc valve.

  9. Dynamics of transcription-translation networks

    Science.gov (United States)

    Hudson, D.; Edwards, R.

    2016-09-01

    A theory for qualitative models of gene regulatory networks has been developed over several decades, generally considering transcription factors to regulate directly the expression of other transcription factors, without any intermediate variables. Here we explore a class of models that explicitly includes both transcription and translation, keeping track of both mRNA and protein concentrations. We mainly deal with transcription regulation functions that are steep sigmoids or step functions, as is often done in protein-only models, though translation is governed by a linear term. We extend many aspects of the protein-only theory to this new context, including properties of fixed points, description of trajectories by mappings between switching points, qualitative analysis via a state-transition diagram, and a result on periodic orbits for negative feedback loops. We find that while singular behaviour in switching domains is largely avoided, non-uniqueness of solutions can still occur in the step-function limit.

  10. Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics.

    Science.gov (United States)

    Shearer, Jason

    2014-08-19

    /amidate nitrogen donor atoms within the NiSOD ligand set produce a catalytically viable species. These metallopeptide-based mimics have also hinted at the detailed mechanism of SOD catalysis by NiSOD. One such aspect is that the axial imidazole likely remains ligated to the Ni center under rapid catalytic conditions (i.e., high superoxide loads). This reduces the degree of structural rearrangement about the nickel center, leading to higher catalytic rates. Metallopeptide-based mimics have also shown that, although an axial ligand to Ni(III) is required for catalysis, the rates are highest when this is a weak interaction, suggesting a reason for the long axial His-Ni(III) bond found in NiSOD. These mimics have also suggested a surprising mechanistic insight: O2(-) reduction via a "H(•)" tunneling event from a R-S(H(+))-Ni(II) moiety to O2(-) is possible. The importance of this mechanism in NiSOD has not been verified.

  11. A developmental transcriptional network for maize defines coexpression modules.

    Science.gov (United States)

    Downs, Gregory S; Bi, Yong-Mei; Colasanti, Joseph; Wu, Wenqing; Chen, Xi; Zhu, Tong; Rothstein, Steven J; Lukens, Lewis N

    2013-04-01

    Here, we present a genome-wide overview of transcriptional circuits in the agriculturally significant crop species maize (Zea mays). We examined transcript abundance data at 50 developmental stages, from embryogenesis to senescence, for 34,876 gene models and classified genes into 24 robust coexpression modules. Modules were strongly associated with tissue types and related biological processes. Sixteen of the 24 modules (67%) have preferential transcript abundance within specific tissues. One-third of modules had an absence of gene expression in specific tissues. Genes within a number of modules also correlated with the developmental age of tissues. Coexpression of genes is likely due to transcriptional control. For a number of modules, key genes involved in transcriptional control have expression profiles that mimic the expression profiles of module genes, although the expression of transcriptional control genes is not unusually representative of module gene expression. Known regulatory motifs are enriched in several modules. Finally, of the 13 network modules with more than 200 genes, three contain genes that are notably clustered (P < 0.05) within the genome. This work, based on a carefully selected set of major tissues representing diverse stages of maize development, demonstrates the remarkable power of transcript-level coexpression networks to identify underlying biological processes and their molecular components.

  12. Different Aspects of Intercultural Nonverbal Communication

    Directory of Open Access Journals (Sweden)

    Kifayat Aghayeva

    2011-07-01

    Full Text Available It is shown the ways how to manage nonverbal intercultural communication effectively and cultural, political and gender aspects of NVC are investigated in the article. Studies of nonverbal communication indicate that nonverbal communication is constantly used, whether or not people speak to each-other. Non-verbal communication can even alternate a verbal message through mimics, gestures and facial expressions, particularly when people do not speak the same language. A culturally-fluent approach to conflict means working over time to understand these and other ways communication varies across cultures, and applying these understandings in order to enhance relationships across differences. These features influences intercultural communication and can be responsible for increase of conflict when it leads to bad communication or misinterpretation or vice versa can be responsible for escaping of them.

  13. Polymeric Nanocomposite that Mimics in vivo ECM Topography in Tissue using Magnetic Field-induced Particle Self-assembly

    Science.gov (United States)

    Kim, Jiyun; Staunton, Jack; Tanner, Kandice

    3D biomaterials that mimic a certain physical or chemical aspect of cellular environment have been used to recreate the diversity of the tissue microenvironment. Especially, physical characteristics of these materials such as topography, dimension and stiffness, have known to have crucial effects on cell fate and cell malignancy. Here, we propose a technique that is able to create diverse topographies in 3D polymeric scaffold for the purpose of mimicking the structural aspect of tissue microenvironment. To achieve this, we exploit the magnetic field-directed assembly of super paramagnetic particles to fabricate chain-distributed architecture such that we can study the effects of extracellular matrix (ECM) topography on cell behavior. First, we chemically cross-link proteins including fibronectin, laminin and bovine albumin serum on the surface of magnetic particles to make the building blocks for artificial topography. Then, we assemble these particles by applying the parallel magnetic field in a surrogate polymeric matrix and solidify the matrix to maintain the assembled topography. Using this simple technique, we patterned diverse topographies in 3D including globular, fibril or interfaced architectures without chafing other material characteristics of the scaffold matrix, such as stiffness and molecular diffusion. We demonstrated that the fibril architecture guilds the dendritic extension of fibroblasts and neuron-like cells, compared to the cells grown in the globular architecture lacking anisotropic guidance cues.

  14. A phosphorylation defective retinoic acid receptor mutant mimics the effects of retinoic acid on EGFR mediated AP-1 expression and cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    Kim Randie

    2002-10-01

    Full Text Available Abstract Background The effects of the vitamin A metabolite retinoic acid (RA are mediated at the transcriptional level by retinoic acid receptors (RAR. These proteins are part of a superfamily of transcription factors which activate target gene expression when bound to their respective ligands. In addition to ligand binding, heterodimerization with transcriptional cofactors and posttranslational modification such as phosphorylation are also critical for transactivation function. Previous studies have shown that phosphorylation of a serine residue at amino acid 77 in the RARα amino terminus was required for basal activation function of the transcription factor. Results We have determined that RA inhibits cyclin H and cdk7 expression thereby decreasing levels of phosphorylated RARα in human cancer cell lines. To determine the effects of decreased RARα phosphorylation in human cancer cells, we stably transfected a phosphorylation defective mutant RARα expression construct into SCC25 cultures. Cells expressing the mutant RARα proliferated more slowly than control clones. This decreased proliferation was associated with increased cyclin dependent kinase inhibitor expression and decreased S phase entry. In the absence of ligand, the RARα mutant inhibited AP-1 activity to an extent similar to that of RA treated control clones. Levels of some AP-1 proteins were inhibited due to decreased EGFR expression upstream in the signaling pathway. Conclusions These results indicate that hypophosphorylated RARα can mimic the anti-AP-1 effects of RA in the absence of ligand.

  15. Structural basis of transcription by bacterial and eukaryotic RNA polymerases.

    Science.gov (United States)

    Sekine, Shun-ichi; Tagami, Shunsuke; Yokoyama, Shigeyuki

    2012-02-01

    DNA-dependent RNA polymerase (RNAP) is responsible for cellular gene transcription. Although crystallographic studies on prokaryotic and eukaryotic RNAPs have elucidated the basic RNAP architectures, the structural details of many essential events during transcription initiation, elongation, and termination are still largely unknown. Recent crystallographic studies on a bacterial RNAP and yeast RNAP II have revealed different RNAP structural states from that of the normal transcribing complex, as well as the basis of transcription factor functions, advancing our understanding of transcription. These studies have highlighted unexpected similarities in many fundamental aspects of transcription mechanisms between the bacterial and eukaryotic transcription machineries. Remarkable differences also exist between the bacterial and eukaryotic transcription systems, suggesting directions for future studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Mimic Phosphorylation of a βC1 Protein Encoded by TYLCCNB Impairs Its Functions as a Viral Suppressor of RNA Silencing and a Symptom Determinant.

    Science.gov (United States)

    Zhong, Xueting; Wang, Zhan Qi; Xiao, Ruyuan; Cao, Linge; Wang, Yaqin; Xie, Yan; Zhou, Xueping

    2017-08-15

    Phosphorylation of the βC1 protein encoded by the betasatellite of tomato yellow leaf curl China virus (TYLCCNB-βC1) by SNF1-related protein kinase 1 (SnRK1) plays a critical role in defense of host plants against geminivirus infection in Nicotiana benthamiana However, how phosphorylation of TYLCCNB-βC1 impacts its pathogenic functions during viral infection remains elusive. In this study, we identified two additional tyrosine residues in TYLCCNB-βC1 that are phosphorylated by SnRK1. The effects of TYLCCNB-βC1 phosphorylation on its functions as a viral suppressor of RNA silencing (VSR) and a symptom determinant were investigated via phosphorylation mimic mutants in N. benthamiana plants. Mutations that mimic phosphorylation of TYLCCNB-βC1 at tyrosine 5 and tyrosine 110 attenuated disease symptoms during viral infection. The phosphorylation mimics weakened the ability of TYLCCNB-βC1 to reverse transcriptional gene silencing and to suppress posttranscriptional gene silencing and abolished its interaction with N. benthamiana ASYMMETRIC LEAVES 1 in N. benthamiana leaves. The mimic phosphorylation of TYLCCNB-βC1 had no impact on its protein stability, subcellular localization, or self-association. Our data establish an inhibitory effect of phosphorylation of TYLCCNB-βC1 on its pathogenic functions as a VSR and a symptom determinant and provide a mechanistic explanation of how SnRK1 functions as a host defense factor.IMPORTANCE Tomato yellow leaf curl China virus (TYLCCNV), which causes a severe yellow leaf curl disease in China, is a monopartite geminivirus associated with the betasatellite (TYLCCNB). TYLCCNB encodes a single pathogenicity protein, βC1 (TYLCCNB-βC1), which functions as both a viral suppressor of RNA silencing (VSR) and a symptom determinant. Here, we show that mimicking phosphorylation of TYLCCNB-βC1 weakens its ability to reverse transcriptional gene silencing, to suppress posttranscriptional gene silencing, and to interact with N

  17. A moderate increase in ambient temperature modulates the Atlantic cod (Gadus morhua spleen transcriptome response to intraperitoneal viral mimic injection

    Directory of Open Access Journals (Sweden)

    Hori Tiago S

    2012-08-01

    Full Text Available Abstract Background Atlantic cod (Gadus morhua reared in sea-cages can experience large variations in temperature, and these have been shown to affect their immune function. We used the new 20K Atlantic cod microarray to investigate how a water temperature change which, simulates that seen in Newfoundland during the spring-summer (i.e. from 10°C to 16°C, 1°C increase every 5 days impacted the cod spleen transcriptome response to the intraperitoneal injection of a viral mimic (polyriboinosinic polyribocytidylic acid, pIC. Results The temperature regime alone did not cause any significant increases in plasma cortisol levels and only minor changes in spleen gene transcription. However, it had a considerable impact on the fish spleen transcriptome response to pIC [290 and 339 significantly differentially expressed genes between 16°C and 10°C at 6 and 24 hours post-injection (HPI, respectively]. Seventeen microarray-identified transcripts were selected for QPCR validation based on immune-relevant functional annotations. Fifteen of these transcripts (i.e. 88%, including DHX58, STAT1, IRF7, ISG15, RSAD2 and IκBα, were shown by QPCR to be significantly induced by pIC. Conclusions The temperature increase appeared to accelerate the spleen immune transcriptome response to pIC. We found 41 and 999 genes differentially expressed between fish injected with PBS vs. pIC at 10°C and sampled at 6HPI and 24HPI, respectively. In contrast, there were 656 and 246 genes differentially expressed between fish injected with PBS vs. pIC at 16°C and sampled at 6HPI and 24HPI, respectively. Our results indicate that the modulation of mRNA expression of genes belonging to the NF-κB and type I interferon signal transduction pathways may play a role in controlling temperature-induced changes in the spleen’s transcript expression response to pIC. Moreover, interferon effector genes such as ISG15 and RSAD2 were differentially expressed between fish injected with

  18. The retinoblastoma protein as a transcriptional repressor

    DEFF Research Database (Denmark)

    Helin, K; Ed, H

    1993-01-01

    The retinoblastoma protein (pRB) is one of the best-studied tumour suppressor gene products. Its loss during the genesis of many human tumours, its inactivation by several DNA tumour virus oncoproteins, and its ability to inhibit cell growth when introduced into dividing cells all suggest that pRB...... negatively regulates some aspect of normal cell growth. The discovery that pRB associates with transcription factors such as E2F has provided the first model for pRB function. In this review, we discuss how pRB may regulate cell growth by repressing transcription of genes essential for cell proliferation....

  19. Transcriptional networks leading to symbiotic nodule organogenesis.

    Science.gov (United States)

    Soyano, Takashi; Hayashi, Makoto

    2014-08-01

    The symbiosis with nitrogen-fixing bacteria leading to root nodules is a relatively recent evolutionary innovation and limited to a distinct order of land plants. It has long been a mystery how plants have invented this complex trait. However, recent advances in molecular genetics of model legumes has elucidated genes involved in the development of root nodules, providing insights into this process. Here we discuss how the de novo assembly of transcriptional networks may account for the predisposition to nodulate. Transcriptional networks and modes of gene regulation from the arbuscular mycorrhizal symbiosis, nitrate responses and aspects of lateral root development have likely all contributed to the emergence and development of root nodules.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 regenerative endodontics. PMID:25917945

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-04-13

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

  4. Single molecule studies of RNA polymerase II transcription in vitro.

    Science.gov (United States)

    Horn, Abigail E; Goodrich, James A; Kugel, Jennifer F

    2014-01-01

    Eukaryotic mRNA transcription by RNA polymerase II (RNAP II) is the first step in gene expression and a key determinant of cellular regulation. Elucidating the mechanism by which RNAP II synthesizes RNA is therefore vital to determining how genes are controlled under diverse biological conditions. Significant advances in understanding RNAP II transcription have been achieved using classical biochemical and structural techniques; however, aspects of the transcription mechanism cannot be assessed using these approaches. The application of single-molecule techniques to study RNAP II transcription has provided new insight only obtainable by studying molecules in this complex system one at a time.

  5. Lexical and Grammatical Aspect

    NARCIS (Netherlands)

    van Hout, Angeliek; Lidz, Jeffrey; Snyder, William; Pater, Joe

    The temporality of a given situation ‘out there in the world’ can be described in many ways. Tense and aspect offer the essential parameters. Lexical aspect characterizes event descriptions; a situation with a sleeping child can be referred to as a state of affairs (be asleep) or as a happening

  6. Mapping Yeast Transcriptional Networks

    OpenAIRE

    Hughes, Timothy R; de Boer, Carl G.

    2013-01-01

    The term “transcriptional network” refers to the mechanism(s) that underlies coordinated expression of genes, typically involving transcription factors (TFs) binding to the promoters of multiple genes, and individual genes controlled by multiple TFs. A multitude of studies in the last two decades have aimed to map and characterize transcriptional networks in the yeast Saccharomyces cerevisiae. We review the methodologies and accomplishments of these studies, as well as challenges we now face....

  7. A Nonnatural Transcriptional Coactivator

    Science.gov (United States)

    Nyanguile, Origene; Uesugi, Motonari; Austin, David J.; Verdine, Gregory L.

    1997-12-01

    In eukaryotes, sequence-specific DNA-binding proteins activate gene expression by recruiting the transcriptional apparatus and chromatin remodeling proteins to the promoter through protein-protein contacts. In many instances, the connection between DNA-binding proteins and the transcriptional apparatus is established through the intermediacy of adapter proteins known as coactivators. Here we describe synthetic molecules with low molecular weight that act as transcriptional coactivators. We demonstrate that a completely nonnatural activation domain in one such molecule is capable of stimulating transcription in vitro and in vivo. The present strategy provides a means of gaining external control over gene activation through intervention using small molecules.

  8. Massively Systematic Transcript End Readout (MASTER): Transcription Start Site Selection, Transcriptional Slippage, and Transcript Yields

    Science.gov (United States)

    Vvedenskaya, Irina O.; Zhang, Yuanchao; Goldman, Seth R.; Valenti, Anna; Visone, Valeria; Taylor, Deanne M.; Ebright, Richard H.; Nickels, Bryce E.

    2015-01-01

    SUMMARY We report the development of a next-generation sequencing-based technology that entails construction of a DNA library comprising up to at least 47 (~16,000) bar-coded sequences, production of RNA transcripts, and analysis of transcript ends and transcript yields ("massively systematic transcript end readout," MASTER). Using MASTER, we define full inventories of transcription start sites ("TSSomes") of Escherichia coli RNA polymerase for initiation at a consensus core promoter in vitro and in vivo, we define the TSS-region DNA-sequence determinants for TSS selection, reiterative initiation ("slippage synthesis"), and transcript yield, and we define effects of DNA topology and NTP concentration. The results reveal that slippage synthesis occurs from the majority of TSS-region DNA sequences and that TSS-region DNA sequences have profound, up to 100-fold, effects on transcript yield. The results further reveal that TSSomes depend on DNA topology, consistent with the proposal that TSS selection involves transcription-bubble expansion ("scrunching") and transcription-bubble contraction ("anti-scrunching"). PMID:26626484

  9. Massively Systematic Transcript End Readout, "MASTER": Transcription Start Site Selection, Transcriptional Slippage, and Transcript Yields.

    Science.gov (United States)

    Vvedenskaya, Irina O; Zhang, Yuanchao; Goldman, Seth R; Valenti, Anna; Visone, Valeria; Taylor, Deanne M; Ebright, Richard H; Nickels, Bryce E

    2015-12-17

    We report the development of a next-generation sequencing-based technology that entails construction of a DNA library comprising up to at least 4(7) (∼ 16,000) barcoded sequences, production of RNA transcripts, and analysis of transcript ends and transcript yields (massively systematic transcript end readout, "MASTER"). Using MASTER, we define full inventories of transcription start sites ("TSSomes") of Escherichia coli RNA polymerase for initiation at a consensus core promoter in vitro and in vivo; we define the TSS-region DNA sequence determinants for TSS selection, reiterative initiation ("slippage synthesis"), and transcript yield; and we define effects of DNA topology and NTP concentration. The results reveal that slippage synthesis occurs from the majority of TSS-region DNA sequences and that TSS-region DNA sequences have profound, up to 100-fold, effects on transcript yield. The results further reveal that TSSomes depend on DNA topology, consistent with the proposal that TSS selection involves transcription-bubble expansion ("scrunching") and transcription-bubble contraction ("anti-scrunching").

  10. Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator.

    Science.gov (United States)

    Corral-Lugo, Andrés; Daddaoua, Abdelali; Ortega, Alvaro; Espinosa-Urgel, Manuel; Krell, Tino

    2016-01-05

    Quorum sensing is a bacterial communication mechanism that controls genes, enabling bacteria to live as communities, such as biofilms. Homoserine lactone (HSL) molecules function as quorum-sensing signals for Gram-negative bacteria. Plants also produce previously unidentified compounds that affect quorum sensing. We identified rosmarinic acid as a plant-derived compound that functioned as an HSL mimic. In vitro assays showed that rosmarinic acid bound to the quorum-sensing regulator RhlR of Pseudomonas aeruginosa PAO1 and competed with the bacterial ligand N-butanoyl-homoserine lactone (C4-HSL). Furthermore, rosmarinic acid stimulated a greater increase in RhlR-mediated transcription in vitro than that of C4-HSL. In P. aeruginosa, rosmarinic acid induced quorum sensing-dependent gene expression and increased biofilm formation and the production of the virulence factors pyocyanin and elastase. Because P. aeruginosa PAO1 infection induces rosmarinic acid secretion from plant roots, our results indicate that rosmarinic acid secretion is a plant defense mechanism to stimulate a premature quorum-sensing response. P. aeruginosa is a ubiquitous pathogen that infects plants and animals; therefore, identification of rosmarinic acid as an inducer of premature quorum-sensing responses may be useful in agriculture and inform human therapeutic strategies.

  11. Estimating the size of non-observed economy in Croatia using the MIMIC approach

    Directory of Open Access Journals (Sweden)

    Vjekoslav Klarić

    2011-03-01

    Full Text Available This paper gives a quick overview of the approaches that have been used in the research of shadow economy, starting with the definitions of the terms “shadow economy” and “non-observed economy”, with the accent on the ISTAT/Eurostat framework. Several methods for estimating the size of the shadow economy and the non-observed economy are then presented. The emphasis is placed on the MIMIC approach, one of the methods used to estimate the size of the nonobserved economy. After a glance at the theory behind it, the MIMIC model is then applied to the Croatian economy. Considering the described characteristics of different methods, a previous estimate of the size of the non-observed economy in Croatia is chosen to provide benchmark values for the MIMIC model. Using those, the estimates of the size of non-observed economy in Croatia during the period 1998-2009 are obtained.

  12. Catalytic hyperbranched polymers as enzyme mimics; exploiting the principles of encapsulation and supramolecular chemistry.

    Science.gov (United States)

    Kirkorian, Katerina; Ellis, Adam; Twyman, Lance J

    2012-09-21

    Nature uses the principles of encapsulation and supramolecular chemistry to bind and orientate substrates within active catalytic sites. Over the years, synthetic chemistry has generated a number of small molecule active site mimics capable of catalysing reactions involving bound substrates. Another approach uses larger molecules that better represent an enzymes globular structure. These molecules mimic an enzymes structure by incorporating binding/catalytic sites within the globular structure of the polymer. As such, the electronic and steric properties around the binding/catalytic site(s) can be controlled and fine-tuned. One class of polymer that is particularly adept at mimicking the globular structure of enzymes are dendritic polymers. This review will concentrate on the use of hyperbranched polymers as synthetic enzyme mimics.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  15. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

    Science.gov (United States)

    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

  16. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks.

    Directory of Open Access Journals (Sweden)

    Tae-Yun Kang

    Full Text Available 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.

  17. Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics

    Institute of Scientific and Technical Information of China (English)

    Robert; Smolic; Martina; Smolic; John; H; Andorfer; Catherine; H; Wu; Robert; M; Smith; George; Y; Wu

    2010-01-01

    AIM: To examine the effect of hepatitis C virus (HCV) structural mimics of regulatory regions of the genome on HCV replication.METHODS: HCV RNA structural mimics were constructed and tested in a HCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFH-1) HCV genotype 2a infection model.All sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral RNA.Huh7.5 cells bearing the BB7 replicon or infected with JFH-1 virus were trans...

  18. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  19. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein codi...

  20. Mechanical Properties of Transcription

    Science.gov (United States)

    Sevier, Stuart A.; Levine, Herbert

    2017-06-01

    The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

  1. Cognitive Aspects of Prejudice

    Science.gov (United States)

    Tajfel, Henri

    1969-01-01

    This paper is a slightly revised version of a contribution to a symposium on the "Biosocial Aspects of Race," held in London, September, 1968; symposium was published in the "Journal of Biosocial Science," Supplement No. 1, July, 1969. (RJ)

  2. Foundational aspects of security

    DEFF Research Database (Denmark)

    Chatzikokolakis, Konstantinos; Mödersheim, Sebastian Alexander; Palamidessi, Catuscia

    2014-01-01

    This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security.......This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security....

  3. Molecular basis of transcription initiation in Archaea.

    Science.gov (United States)

    De Carlo, Sacha; Lin, Shih-Chieh; Taatjes, Dylan J; Hoenger, Andreas

    2010-01-01

    Compared with eukaryotes, the archaeal transcription initiation machinery-commonly known as the Pre-Initiation Complex-is relatively simple. The archaeal PIC consists of the TFIIB ortholog TFB, TBP, and an 11-subunit RNA polymerase (RNAP). The relatively small size of the entire archaeal PIC makes it amenable to structural analysis. Using purified RNAP, TFB, and TBP from the thermophile Pyrococcus furiosus, we assembled the biochemically active PIC at 65ºC. The intact archaeal PIC was isolated by implementing a cross-linking technique followed by size-exclusion chromatography, and the structure of this 440 kDa assembly was determined using electron microscopy and single-particle reconstruction techniques. Combining difference maps with crystal structure docking of various sub-domains, TBP and TFB were localized within the macromolecular PIC. TBP/TFB assemble near the large RpoB subunit and the RpoD/L "foot" domain behind the RNAP central cleft. This location mimics that of yeast TBP and TFIIB in complex with yeast RNAP II. Collectively, these results define the structural organization of the archaeal transcription machinery and suggest a conserved core PIC architecture.

  4. Storage of Electromagnetic Waves in a Metamaterial that Mimics Electromagnetically Induced Transparency

    CERN Document Server

    Nakanishi, Toshihiro; Tamayama, Yasuhiro; Kitano, Masao

    2013-01-01

    We propose a method for dynamically controlling the properties of a metamaterial that mimics electromagnetically induced transparency (EIT) by introducing varactor diodes to manipulate the structural symmetry of the metamaterial. Dynamic modulation of the EIT property enables the storage and retrieval of electromagnetic waves. We confirmed that the electromagnetic waves were stored and released, while maintaining the phase distribution in the propagating direction.

  5. Synthesis of oxime-linked mucin mimics containing thetumor-related TN and sialyl TN antigens

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    1989-05-26

    Clasification ) A Molecular Mechanics Analysis of Molecular Recognition By Cyclodextrin Mimics of Alpha-Chymotrypsin. 12. PERSONAL AUTHOR(S) C.A. Venanzil...Field Parameters The AMBER force field was developed by Kollmann and coworkers tc 28293 treat proteins and nucleic acids , as well as small molecules2 9

  7. Isolation and characterization of rice lesion mimic mutants from a T-DNA tagged population

    Institute of Scientific and Technical Information of China (English)

    LI Shutian; PEI Zhongyou; LUO Lijuan; TIAN Yingchuan; HE Chaozu

    2005-01-01

    A rice ( Oryza sativa L. ssp. japonica cv. Nipponbare) T-DNA tagged population consisting of about 7000 individual lines was generated and screened for rice lesion mimic mutants in the T1 generation. Ten lines were found to develop spontaneous lesions in the absence of pathogen infection and displayed distinct lesion phenotypes. These mutants were tentatively designated as lm1 -lm10 (for lesion mimic), respectively. Lesion formation of lm mutants was developmentally regulated, and all the mutants showed stunted growth and reduced fertility. Genetic analysis demonstrated that all the mutations were recessive, and five partially fertile mutants (lm4-lm8) were derived from different loci. Mimic lesions occurring on the leaves of lm mutants resulted from cell death as revealed by trypan blue staining. Six of them ( lm3 -lm8 ) exhibited enhanced resistance to five bacterial blight isolates, indicating their wide-spectrum resistance to this pathogen. These results imply that some lesion mimic mutations of rice might be involved in disease resistance signaling pathways,and that isolation of these mutated genes may be useful for elucidating molecular mechanisms of plant disease resistance. Among the mutants, only one mutant, lm6, was preliminarily shown to cosegregate with the inserted T-DNA in its T1 generation, making it feasible to isolate the gene responsible for the phenotype of this mutant.

  8. Molecularly-imprinted polymers as synythetic mimics of bioreceptors. 2. Applications in modern biotechnology

    Directory of Open Access Journals (Sweden)

    Sergeyeva T. A.

    2009-12-01

    Full Text Available The review is devoted to the analysis of publications on the synthesis of artificial mimics of biological receptors as well as their application in biotechnology. The special attention is paid to such areas of biotechnology: sensor technology, solid-phase extraction, pseudoimmunoassay, and chromatography.

  9. Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Suning Huang

    2014-01-01

    Full Text Available Previously, we found that the expression of microRNA-146a (miR-146a was downregulated in hepatocellular carcinoma (HCC formalin-fixed paraffin-embedded (FFPE tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

  10. Effect of the search image on the lizard ability to reveal a Batesian mimic

    OpenAIRE

    Beneš, Josef

    2016-01-01

    The effect of the search image on the ability of hand reared skinks (Chalcides sexlineatus) to reveal a "fake" Batesian mimic was tested with respect to their previous experience with palatable experimental prey (Guyana spotted cockroach Blaptica dubia) which served as a motivational prey as well as midsized mealworm beetle larvae (Tenebrio molitor). The red firebug (Pyrrhocoris apterus) was used as an aposematic model.

  11. Identification and Genetic Mapping of a Lesion Mimic Mutant in Rice

    Institute of Scientific and Technical Information of China (English)

    MA Jian-yang; CHEN Sun-lu; ZHANG Jian-hui; DONG Yan-jun; TENG Sheng

    2012-01-01

    A lesion mimic stripe mutant,designated as Ims1 (lesion mimic stripe 1),was obtained from the M2 progeny of a 60Co Y-radiation treated japonica rice variety Jiahua 1.The Ims1 mutant displayed propagation type lesions across the whole growth and developmental stages.Physiology and histochemistry analysis showed that the mutant exhibited a phenotype of white stripe when grown under high temperature (30 ℃),and the lesion mimic caused by programmed cell death under low temperature (20 ℃).The genetic analysis indicated that this lesion-mimic phenotype is controlled by a single locus recessive nuclear gene.Furthermore,by using simple sequence repeat markers and an F2 segregating population derived from two crosses of Ims1 × 93-11 and Ims1 × Pei'ai 64S,the Ims1 gene was mapped between markers Indel1 and MM0112-4 with a physical distance of 400 kb on chromosome 6 in rice.

  12. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Science.gov (United States)

    Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

    2016-01-01

    Background: Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. Methods: We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. Results: The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients. Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders. PMID:26996473

  13. Efficient Nuclear DNA Cleavage in Human Cancer Cells by Synthetic Bleomycin Mimics

    NARCIS (Netherlands)

    Li, Qian; van der Wijst, Monique G. P.; Kazemier, Hinke G.; Rots, Marianne G.; Roelfes, Gerard

    2014-01-01

    Iron complexes of N,N-bis(2-Pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics of the Bleomycins (BLMs), which are a family of natural antibiotics used clinically in the treatment of certain cancers. However, most investigations of DNA cleavage activity o

  14. The role of the hipermobile mimic muscules of midle face on the postrhinoplastic results

    Directory of Open Access Journals (Sweden)

    Hayk D. Yenokyan

    2011-05-01

    Full Text Available In article questions of influence of mimic muscles on the remote results ринопластических operations are considered. Use Botox (botulotoxin type A for improvement of results rhinoplasties.

  15. Recent advances in compartmentalized synthetic architectures as drug carriers, cell mimics and artificial organelles

    DEFF Research Database (Denmark)

    York-Durán, María José; Gallardo, Maria Godoy; Labay, Cédric Pierre

    2017-01-01

    significant research attention and these assemblies are proposed as candidate materials for a range of biomedical applications. In this Review article, the recent successes of multicompartment architectures as carriers for the delivery of therapeutic cargo or the creation of micro- and nanoreactors that mimic...

  16. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury

    Science.gov (United States)

    Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

    2017-01-01

    Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

  17. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury.

    Science.gov (United States)

    Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

    2017-01-01

    Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

  18. Selection of peptide mimics of HIV-1 epitope recognized by neutralizing antibody VRC01.

    Directory of Open Access Journals (Sweden)

    Anton N Chikaev

    Full Text Available 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.

  19. Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells.

    Science.gov (United States)

    Jin, Ding Jun; Mata Martin, Carmen; Sun, Zhe; Cagliero, Cedric; Zhou, Yan Ning

    2017-02-01

    We have learned a great deal about RNA polymerase (RNA Pol), transcription factors, and the transcriptional regulation mechanisms in prokaryotes for specific genes, operons, or transcriptomes. However, we have only begun to understand how the transcription machinery is three-dimensionally (3D) organized into bacterial chromosome territories to orchestrate the transcription process and to maintain harmony with the replication machinery in the cell. Much progress has been made recently in our understanding of the spatial organization of the transcription machinery in fast-growing Escherichia coli cells using state-of-the-art superresolution imaging techniques. Co-imaging of RNA polymerase (RNA Pol) with DNA and transcription elongation factors involved in ribosomal RNA (rRNA) synthesis, and ribosome biogenesis has revealed similarities between bacteria and eukaryotes in the spatial organization of the transcription machinery for growth genes, most of which are rRNA genes. Evidence supports the notion that RNA Pol molecules are concentrated, forming foci at the clustering of rRNA operons resembling the eukaryotic nucleolus. RNA Pol foci are proposed to be active transcription factories for both rRNA genes expression and ribosome biogenesis to support maximal growth in optimal growing conditions. Thus, in fast-growing bacterial cells, RNA Pol foci mimic eukaryotic Pol I activity, and transcription factories resemble nucleolus-like compartmentation. In addition, the transcription and replication machineries are mostly segregated in space to avoid the conflict between the two major cellular functions in fast-growing cells.

  20. Deciphering modular and dynamic behaviors of transcriptional networks.

    Science.gov (United States)

    Zhan, Ming

    2007-01-01

    The coordinated and dynamic modulation or interaction of genes or proteins acts as an important mechanism used by a cell in functional regulation. Recent studies have shown that many transcriptional networks exhibit a scale-free topology and hierarchical modular architecture. It has also been shown that transcriptional networks or pathways are dynamic and behave only in certain ways and controlled manners in response to disease development, changing cellular conditions, and different environmental factors. Moreover, evolutionarily conserved and divergent transcriptional modules underline fundamental and species-specific molecular mechanisms controlling disease development or cellular phenotypes. Various computational algorithms have been developed to explore transcriptional networks and modules from gene expression data. In silico studies have also been made to mimic the dynamic behavior of regulatory networks, analyzing how disease or cellular phenotypes arise from the connectivity or networks of genes and their products. Here, we review the recent development in computational biology research on deciphering modular and dynamic behaviors of transcriptional networks, highlighting important findings. We also demonstrate how these computational algorithms can be applied in systems biology studies as on disease, stem cells, and drug discovery.

  1. Thermodynamic and kinetic modeling of transcriptional pausing.

    Science.gov (United States)

    Tadigotla, Vasisht R; O Maoiléidigh, Dáibhid; Sengupta, Anirvan M; Epshtein, Vitaly; Ebright, Richard H; Nudler, Evgeny; Ruckenstein, Andrei E

    2006-03-21

    We present a statistical mechanics approach for the prediction of backtracked pauses in bacterial transcription elongation derived from structural models of the transcription elongation complex (EC). Our algorithm is based on the thermodynamic stability of the EC along the DNA template calculated from the sequence-dependent free energy of DNA-DNA, DNA-RNA, and RNA-RNA base pairing associated with (i) the translocational and size fluctuations of the transcription bubble; (ii) changes in the associated DNA-RNA hybrid; and (iii) changes in the cotranscriptional RNA secondary structure upstream of the RNA exit channel. The calculations involve no adjustable parameters except for a cutoff used to discriminate paused from nonpaused complexes. When applied to 100 experimental pauses in transcription elongation by Escherichia coli RNA polymerase on 10 DNA templates, the approach produces statistically significant results. We also present a kinetic model for the rate of recovery of backtracked paused complexes. A crucial ingredient of our model is the incorporation of kinetic barriers to backtracking resulting from steric clashes of EC with the cotranscriptionally generated RNA secondary structure, an aspect not included explicitly in previous attempts at modeling the transcription elongation process.

  2. DNA supercoiling during transcription.

    Science.gov (United States)

    Ma, Jie; Wang, Michelle D

    2016-11-01

    The twin-supercoiled-domain model describes how transcription can drive DNA supercoiling, and how DNA supercoiling, in turn plays an important role in regulating gene transcription. In vivo and in vitro experiments have disclosed many details of the complex interactions in this relationship, and recently new insights have been gained with the help of genome-wide DNA supercoiling mapping techniques and single molecule methods. This review summarizes the general mechanisms of the interplay between DNA supercoiling and transcription, considers the biological implications, and focuses on recent important discoveries and technical advances in this field. We highlight the significant impact of DNA supercoiling in transcription, but also more broadly in all processes operating on DNA.

  3. DNA supercoiling during transcription

    Science.gov (United States)

    Ma, Jie; Wang, Michelle D.

    2017-01-01

    The twin-supercoiled-domain model describes how transcription can drive DNA supercoiling, and how DNA supercoiling, in turn plays an important role in regulating gene transcription. In vivo and in vitro experiments have disclosed many details of the complex interactions in this relationship, and recently new insights have been gained with the help of genome-wide DNA supercoiling mapping techniques and single molecule methods. This review summarizes the general mechanisms of the interplay between DNA supercoiling and transcription, considers the biological implications, and focuses on recent important discoveries and technical advances in this field. We highlight the significant impact of DNA supercoiling in transcription, but also more broadly in all processes operating on DNA.

  4. A multispecies exclusion model inspired by transcriptional interference

    Science.gov (United States)

    Ghosh, Soumendu; Bameta, Tripti; Ghanti, Dipanwita; Chowdhury, Debashish

    2016-12-01

    We introduce exclusion models of two distinguishable species of hard rods with their distinct sites of entry and exit under open boundary conditions. In the first model both species of rods move in the same direction whereas in the other two models they move in the opposite direction. These models are motivated by the biological phenomenon known as transcriptional interference. Therefore, the rules for the kinetics of the models, particularly the rules for the outcome of the encounter of the rods, are also formulated to mimic those observed in transcriptional interference. By a combination of mean-field theory and computer simulation of these models we demonstrate how the flux of one species of rods is completely switched off by the other. Exploring the parameter space of the model we also establish the conditions under which switch-like regulation of two fluxes is possible; from the extensive analysis we discover more than one possible mechanism of this phenomenon.

  5. Organisational aspects of care.

    Science.gov (United States)

    Bloomfield, Jacqueline; Pegram, Anne

    2015-03-04

    Organisational aspects of care, the second essential skills cluster, identifies the need for registered nurses to systematically assess, plan and provide holistic patient care in accordance with individual needs. Safeguarding, supporting and protecting adults and children in vulnerable situations; leading, co-ordinating and managing care; functioning as an effective and confident member of the multidisciplinary team; and managing risk while maintaining a safe environment for patients and colleagues, are vital aspects of this cluster. This article discusses the roles and responsibilities of the newly registered graduate nurse. Throughout their education, nursing students work towards attaining this knowledge and these skills in preparation for their future roles as nurses.

  6. Triazacyclophane (TAC)-scaffolded histidine and aspartic acid residues as mimics of non-heme metalloenzyme active sites

    NARCIS (Netherlands)

    Albada, H.B.; Soulimani, F.; Jacobs, H.J.F.; Versluis, C.; Weckhuysen, B.M.; Liskamp, R.M.J.

    2012-01-01

    We describe the synthesis and coordination behaviour to copper(II) of two close structural triazacyclophane-based mimics of two often encountered aspartic acid and histidine containing metalloenzyme active sites. Coordination of these mimics to copper(I) and their reaction with molecular oxygen lead

  7. Fe-TAML encapsulated inside mesoporous silica nanoparticles as peroxidase mimic: femtomolar protein detection.

    Science.gov (United States)

    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

  8. Macroeconomic aspects of dollarization

    OpenAIRE

    Kolář, Ladislav

    2009-01-01

    The dissertation deals mainly with explanation of the term "de jure dollarization" and confronts the dollarization regime with others. The core of the whole dissertation is to outline the factors which indicate fulfillment of dollarization and the positives or negatives that it brings. It slightly refers to the regional monetary integration in several regions and discovers mutual aspects with the dollarization.

  9. Quantum Chromodynamics: Computational Aspects

    CERN Document Server

    Schaefer, Thomas

    2016-01-01

    We present a brief introduction to QCD, the QCD phase diagram, and non-equilibrium phenomena in QCD. We emphasize aspects of the theory that can be addressed using computational methods, in particular euclidean path integral Monte Carlo, fluid dynamics, kinetic theory, classical field theory and holographic duality.

  10. [Psychosocial aspects of halitosis

    NARCIS (Netherlands)

    Jongh, A. de; Baat, C. de; Horstman, M.

    2012-01-01

    Using a representative sample from the Dutch population, some psychosocial aspects of halitosis were examined. The results of the survey showed that almost 90% of the Dutch population aged 16 years and older were regularly faced with halitosis. Forty percent reported to be exposed to someone with ha

  11. Aspects of Marine Ecology.

    Science.gov (United States)

    Awkerman, Gary L.

    This publication is designed for use in standard science curricula to develop oceanologic manifestations of certain science topics. Included are teacher guides, student activities, and demonstrations to impart ocean science understanding, specifically, aspects of marine ecology, to high school students. The course objectives include the ability of…

  12. Tense, aspect, and modality

    NARCIS (Netherlands)

    Pfau, R.; Steinbach, M.; Woll, B.; Pfau, R.; Steinbach, M.; Woll, B.

    2012-01-01

    Cross-linguistically, the grammatical categories tense, aspect, and modality - when they are overtly expressed - are generally realized by free morphemes (such as adverbials and auxiliaries) or by bound inflectional markers. The discussion in this chapter will make clear that this generalization als

  13. Diagnostic aspects of gonorrhoea

    NARCIS (Netherlands)

    E. Stolz (Ernst)

    1974-01-01

    textabstractIn 1971 an investigation into the epidemiological, clinical, bacteriological and therapeutic aspects of gonorrhoea was started in collaboration with the Bacteriological Laboratory of the University Hospital/Medical Faculty Rotterdam. Jn the framework of this investigation, the data were

  14. Applied and fundamental aspects of BABY BOOM-mediated regeneration

    NARCIS (Netherlands)

    Heidmann, I.A.

    2015-01-01

    Keywords: Somatic embryogenesis, Transcription factor, AINTEGUMENTA-LIKE, BABY BOOM, BBM, Sweet Pepper Transformation Title: Applied and Fundamental Aspects of BBM-mediated Regeneration Author: Iris Heidmann Catergories: Plant regeneration, Plant

  15. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  16. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element

    Science.gov (United States)

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko

    2013-01-01

    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5′-NNCCAC-3′ and 5′-GCGMGN′N′-3′ (M:A or C; N and N′ form Watson–Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences. PMID:23709277

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

    Science.gov (United States)

    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.

  18. Idiopathic Hypertrophic Pyloric Stenosis in an Adult, a Potential Mimic of Gastric Carcinoma

    Directory of Open Access Journals (Sweden)

    Alireza Zarineh

    2010-01-01

    Full Text Available Primary or idiopathic hypertrophy of the pyloric muscle (IHPM is a rare entity with uncertain pathogenesis which both clinically and pathologically mimics gastric cancer. We present a rare late-occurring case of IHPM in a 71-year-old Caucasian man with no apparent predisposing factor. Imaging studies demonstrated gastric distension with air fluid levels and no evidence of extrinsic compression. At upper endoscopy, massive gastric distension and no evidence of any ulcer or other mucosal defects were observed. Microscopically, marked hypertrophy of muscularis mucosa with smooth muscle cells arranged in whorls and fascicles was present which gradually transitioned to normal areas. The muscle fibers stained with smooth muscle actin and trichrome stain highlighted fibrosis between the muscle fibers. Although uncommon, IHPM can clinically and histologically mimic other proliferations in the gastric wall, such as gastrointestinal stromal tumor or a spindle cell neoplasm. The recent advances in understanding the pathogenesis of IHPM are discussed.

  19. How well does cholesteryl hemisuccinate mimic cholesterol in saturated phospholipid bilayers?

    DEFF Research Database (Denmark)

    Kulig, W.; Tynkkynen, J.; Javanainen, M.

    2014-01-01

    Cholesteryl hemisuccinate is a detergent that is often used to replace cholesterol in crystallization of membrane proteins. Here we employ atomistic molecular dynamics simulations to characterize how well the properties of cholesteryl hemisuccinate actually match those of cholesterol in saturated...... protein-free lipid membranes. We show that the protonated form of cholesteryl hemisuccinate mimics many of the membrane properties of cholesterol quite well, while the deprotonated form of cholesteryl hemisuccinate is less convincing in this respect. Based on the results, we suggest that cholesteryl...... hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions (not investigated here) are not playing a crucial role....

  20. Recognition of extended linear and cyclised polyketide mimics by a Type II acyl carrier protein

    OpenAIRE

    Dong, Xu; Bailey, Christopher; Williams, Christopher; Crosby, John; Simpson, Tom; Willis, Chris; Crump, Matthew

    2016-01-01

    Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP’s capacity to sequ...

  1. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    DEFF Research Database (Denmark)

    Rehfeld, A; Dissing, S; Skakkebæk, N E

    2016-01-01

    Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic...... competitively inhibited progesterone-induced Ca(2+) signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility....

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

    Science.gov (United States)

    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 address a wide range of biological questions. It will also place the field in the context of emerging trends, discuss the associated limitations, and outline future directions of the field. Impact statement Recent years have seen an increasing drive to construct cell mimics and use them as simplified experimental models to replicate and understand biological phenomena in a well-defined and controlled system. By summarizing the advances in this burgeoning field, and using case studies as a basis for discussion on the limitations and future directions of this approach, it is hoped that this minireview will spur others in the experimental biology community to use artificial cells as simplified models with which to probe biological systems.

  3. Molecularly imprinted polymers as synthetic mimics of bioreceptors. 1. General principles of molecular imprinting

    Directory of Open Access Journals (Sweden)

    Sergeyeva T. A.

    2009-08-01

    Full Text Available The review is devoted to analysis of the publications in the area of synthesis of artificial mimics of biological receptors using the method of molecular imprinting. General principles of molecular imprinting as well as main types of polymers being used in molecular imprinting are described. The special attention is paid to the polymers-biomimics synthesized using the method of non-covalent molecular imprinting.

  4. Biomolecular Programming of Discrete Nanomaterials for Sensors, Templates and Mimics of Natural Nanoscale Assemblies

    Science.gov (United States)

    2016-10-17

    AFRL-AFOSR-VA-TR-2016-0343 BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS, TEMPLATES AND MIMICS OF NATURAL NANOSCALE ASSEMBLIES...Performance 3. DATES COVERED (From - To) 01 Jun 2011 to 31 May 2016 4. TITLE AND SUBTITLE BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS...responsive elements for assembly of complex morphology switchable nanomaterials , and have combined this with an effort in nature-inspired materials

  5. An electronic nose for the detection of Sarin, Soman and Tabun mimics and interfering agents

    OpenAIRE

    2014-01-01

    An electronic nose system (E-nose) with metal oxide semiconductor sensors (MOS) has been designed to discriminate and quantify different chemical warfare agents (CWA) mimics. The E-nose consists of an array of commercial MOS for different gases, two sensors for temperature sensing, a sample handling system, a data acquisition system and a laptop with the data acquisition system control. With this device, discrimination studies have been carried out to detect specific CWA simulants...

  6. Contact hypersensitivity to mercury in amalgam restorations may mimic oral lichen planus.

    Science.gov (United States)

    Camisa, C; Taylor, J S; Bernat, J R; Helm, T N

    1999-03-01

    Oral lichenoid lesions caused by hypersensitivity to mercury in amalgam fillings may mimic oral lichen planus on clinical and histologic examination. A positive patch test reaction to more than one mercurial allergen increases confidence in the diagnosis and justifies the removal and replacement of all amalgam fillings with those made of other materials. A complete remission may be expected about 3 months after the last amalgam filling is removed.

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Representing life in the Earth system with soil microbial functional traits in the MIMICS model

    Science.gov (United States)

    Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Taylor, P. G.; Bonan, G. B.

    2015-06-01

    Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes, and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon (C) cycle-climate feedbacks. We used a microbial trait-based soil C model with two physiologically distinct microbial communities, and evaluate how this model represents soil C storage and response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS) model; these functional groups are akin to "gleaner" vs. "opportunist" plankton in the ocean, or r- vs. K-strategists in plant and animal communities. Here we compare MIMICS to a conventional soil C model, DAYCENT (the daily time-step version of the CENTURY model), in cross-site comparisons of nitrogen (N) enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that MIMICS projects much slower rates of soil C accumulation than a conventional soil biogeochemistry in response to increasing C inputs with elevated carbon dioxide (CO2) - a finding that would reduce the size of the land C sink estimated by the Earth system. Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

  9. Molecularly imprinted polymers as synthetic mimics of bioreceptors. 1. General principles of molecular imprinting

    OpenAIRE

    Sergeyeva T. A.

    2009-01-01

    The review is devoted to analysis of the publications in the area of synthesis of artificial mimics of biological receptors using the method of molecular imprinting. General principles of molecular imprinting as well as main types of polymers being used in molecular imprinting are described. The special attention is paid to the polymers-biomimics synthesized using the method of non-covalent molecular imprinting.

  10. Some tropical viral diseases that can mimic swine flu in pediatrics

    OpenAIRE

    Wiwanitkit, Viroj

    2009-01-01

    Abstract Swine flu is an important emerging infection that is presently pandemic around the world. The pediatric population is an important group that can be infected with swine flu. Generally, common presentations of swine flu include fever and respiratory presentations. However, there are several infections that can have similar presentations to swine flu. In this specific article, the author will briefly discuss on some tropical viral diseases that can mimic swine flu in pediatrics. ...

  11. Some tropical viral diseases that can mimic swine flu in pediatrics

    Directory of Open Access Journals (Sweden)

    Viroj WIWANITKIT

    2009-11-01

    Full Text Available Swine flu is an important emerging infection that is presently pandemic around the world. The pediatric population is an important group that can be infected with swine flu. Generally, common presentations of swine flu include fever and respiratory presentations. However, there are several infections that can have similar presentations to swine flu. In this specific article, the author will briefly discuss on some tropical viral diseases that can mimic swine flu in pediatrics.

  12. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Institute of Scientific and Technical Information of China (English)

    Jia Fang; Ming-Sheng Liu; Yu-Zhou Guan; Hua Du; Ben-Hong Li; Bo Cui; Qing-Yun Ding

    2016-01-01

    Background:Amyotrophic lateral sclerosis (ALS) and some mimic disorders,such as distal-type cervical spondylotic amyotrophy (CSA),Hirayama disease (HD),and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy.This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders.Methods:We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients,95 patients with distal-type CSA,88 HD patients,43 SBMA patients,and 150 normal controls.Results:The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls.The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls.The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P =0.004).The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA.The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P =0.862).An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (>4.5) were observed exclusively in the ALS patients.Conclusions:The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders,and may aid in distinguishing between ALS and mimic disorders.

  13. Enhancing yeast transcription analysis through integration of heterogeneous data

    DEFF Research Database (Denmark)

    Grotkjær, Thomas; Nielsen, Jens

    2004-01-01

    DNA microarray technology enables the simultaneous measurement of the transcript level of thousands of genes. Primary analysis can be done with basic statistical tools and cluster analysis, but effective and in depth analysis of the vast amount of transcription data requires integration with data...... of Saccharomyces cerevisiae whole genome transcription data. A special focus is on the quantitative aspects of normalisation and mathematical modelling approaches, since they are expected to play an increasing role in future DNA microarray analysis studies. Data analysis is exemplified with cluster analysis...

  14. Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein.

    Science.gov (United States)

    Dong, Xu; Bailey, Christopher D; Williams, Christopher; Crosby, John; Simpson, Thomas J; Willis, Christine L; Crump, Matthew P

    2016-03-01

    Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP's capacity to sequester a non-polar versus a phenolic aromatic ring (that more closely mimics a polyketide intermediate) as well as investigations with extended polyketide chain surrogates. The binding of these mimics has been assessed using high-resolution solution NMR studies and high-resolution structure determination. These results reveal that surprisingly a PKS ACP is able to bind and sequester a bulky non-polar substrate containing an aromatic ring in a fatty acid type binding mode, but the introduction of even a small degree of polarity favours a markedly different association at a surface site that is distinct from that employed by fatty acid ACPs.

  15. Settlement pattern of Posidonia oceanica epibionts along a gradient of ocean acidification: an approach with mimics

    Directory of Open Access Journals (Sweden)

    L. DONNARUMMA

    2014-02-01

    Full Text Available Effects of ocean acidification (OA on the colonization/settlement pattern of the epibiont community of the leaves and rhizomesof the Mediterranean seagrass,Posidoniaoceanica, have been studied at volcanic CO2vents off Ischia (Italy, using “mimics”as artificial substrates. The experiments were conducted in shallowPosidoniastands (2-3 m depth, in three stations on the northand three on the south sides of the study area, distributed along a pH gradient. At each station, 4 rhizome mimics and 6 artificialleaves were collected every three months (Sept 2009-Sept 2010. The epibionts on both leaf and rhizome mimics showed clearchanges along the pH gradient; coralline algae and calcareous invertebrates (bryozoans, serpulid polychaetes and barnacles weredominant at control stations but progressively disappeared at the most acidified stations. In these extremely low pH sites theassemblage was dominated by filamentous algae and non calcareous taxa such as hydroids and tunicates. Settlement pattern onthe artificial leaves and rhizome mimics over time showed a consistent distribution pattern along the pH gradient and highlightedthe peak of recruitment of the various organisms in different periods according to their life history.Posidoniamimics at theacidified station showed a poor and very simplified assemblage where calcifying epibionts seemed less competitive for space. Thisprofound difference in epiphyte communities in low pH conditions suggests cascading effects on the food web of the meadow and,consequently, on the functioning of the system

  16. Settlement pattern of Posidonia oceanica epibionts along a gradient of ocean acidification: an approach with mimics

    Directory of Open Access Journals (Sweden)

    L. DONNARUMMA

    2014-09-01

    Full Text Available Effects of ocean acidification (OA on the colonization/settlement pattern of the epibiont community of the leaves and rhizomesof the Mediterranean seagrass,Posidoniaoceanica, have been studied at volcanic CO2vents off Ischia (Italy, using “mimics”as artificial substrates. The experiments were conducted in shallowPosidoniastands (2-3 m depth, in three stations on the northand three on the south sides of the study area, distributed along a pH gradient. At each station, 4 rhizome mimics and 6 artificialleaves were collected every three months (Sept 2009-Sept 2010. The epibionts on both leaf and rhizome mimics showed clearchanges along the pH gradient; coralline algae and calcareous invertebrates (bryozoans, serpulid polychaetes and barnacles weredominant at control stations but progressively disappeared at the most acidified stations. In these extremely low pH sites theassemblage was dominated by filamentous algae and non calcareous taxa such as hydroids and tunicates. Settlement pattern onthe artificial leaves and rhizome mimics over time showed a consistent distribution pattern along the pH gradient and highlightedthe peak of recruitment of the various organisms in different periods according to their life history.Posidoniamimics at theacidified station showed a poor and very simplified assemblage where calcifying epibionts seemed less competitive for space. Thisprofound difference in epiphyte communities in low pH conditions suggests cascading effects on the food web of the meadow and,consequently, on the functioning of the system

  17. Pd-Ir Core-Shell Nanocubes: A Type of Highly Efficient and Versatile Peroxidase Mimic.

    Science.gov (United States)

    Xia, Xiaohu; Zhang, Jingtuo; Lu, Ning; Kim, Moon J; Ghale, Kushal; Xu, Ye; McKenzie, Erin; Liu, Jiabin; Ye, Haihang

    2015-10-27

    Peroxidase mimics with dimensions on the nanoscale have received great interest as emerging artificial enzymes for biomedicine and environmental protection. While a variety of peroxidase mimics have been actively developed recently, limited progress has been made toward improving their catalytic efficiency. In this study, we report a type of highly efficient peroxidase mimic that was engineered by depositing Ir atoms as ultrathin skins (a few atomic layers) on Pd nanocubes (i.e., Pd-Ir cubes). The Pd-Ir cubes exhibited significantly enhanced efficiency, with catalytic constants more than 20- and 400-fold higher than those of the initial Pd cubes and horseradish peroxidase (HRP), respectively. As a proof-of-concept demonstration, the Pd-Ir cubes were applied to the colorimetric enzyme-linked immunosorbent assay (ELISA) of human prostate surface antigen (PSA) with a detection limit of 0.67 pg/mL, which is ∼110-fold lower than that of the conventional HRP-based ELISA using the same set of antibodies and the same procedure.

  18. Tunable Molecular MoS2 Edge-Site Mimics for Catalytic Hydrogen Production.

    Science.gov (United States)

    Garrett, Benjamin R; Polen, Shane M; Click, Kevin A; He, Mingfu; Huang, Zhongjie; Hadad, Christopher M; Wu, Yiying

    2016-04-18

    Molybdenum sulfides represent state-of-the-art, non-platinum electrocatalysts for the hydrogen evolution reaction (HER). According to the Sabatier principle, the hydrogen binding strength to the edge active sites should be neither too strong nor too weak. Therefore, it is of interest to develop a molecular motif that mimics the catalytic sites structurally and possesses tunable electronic properties that influence the hydrogen binding strength. Furthermore, molecular mimics will be important for providing mechanistic insight toward the HER with molybdenum sulfide catalysts. In this work, a modular method to tune the catalytic properties of the S-S bond in MoO(S2)2L2 complexes is described. We studied the homogeneous electrocatalytic hydrogen production performance metrics of three catalysts with different bipyridine substitutions. By varying the electron-donating abilities, we present the first demonstration of using the ligand to tune the catalytic properties of the S-S bond in molecular MoS2 edge-site mimics. This work can shed light on the relationship between the structure and electrocatalytic activity of molecular MoS2 catalysts and thus is of broad importance from catalytic hydrogen production to biological enzyme functions.

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

    Science.gov (United States)

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

    2016-01-01

    Objectives This study sought to investigate, in-vitro, the effects of a recently developed triple antibiotic paste (TAP)-mimic polymer nanofibrous scaffold against Porphyromonas gingivalis (Pg)-infected dentin biofilm. Materials and Methods Dentin specimens (4×4×1mm3) were prepared from human canines. The specimens were sterilized, inoculated with Pg (ATCC 33277), and incubated for one week to allow for biofilm formation. Infected dentin specimens were exposed for 3 days to the following treatments: antibiotic-free polydioxanone scaffold (PDS, control), PDS+25wt.%TAP (25 mg of each antibiotic [metronidazole, ciprofloxacin, and minocycline] per mL of the PDS polymer solution), or a saturated TAP-based solution (50 mg of each antibiotic per mL of saline solution). In order to serve as the negative control, infected dentin specimens were left untreated (bacteria only). To determine the antimicrobial efficacy of the TAP-mimic scaffold, a colony-forming unit (CFU/mL) (n=10/group) measurement was performed. Furthermore, additional specimens (n=2/group) were prepared to qualitatively study biofilm inhibition via scanning electron microscopy (SEM). Statistics were performed and significance was set at the 5% level. Results Both the TAP-mimic scaffold and the positive control (TAP solution) led to complete bacterial elimination, differing statistically (pregenerative endodontics. PMID:26319981

  20. MiRNA mimic screen for improved expression of functional neurotensin receptor from HEK293 cells.

    Science.gov (United States)

    Xiao, Su; Chen, Yu-Chi; Betenbaugh, Michael J; Martin, Scott E; Shiloach, Joseph

    2015-08-01

    Obtaining adequate quantities of functional mammalian membrane proteins has been a bottleneck in their structural and functional studies because the expression of these proteins from mammalian cells is relatively low. To explore the possibility of enhancing expression of these proteins using miRNA, a stable T-REx-293 cell line expressing the neurotensin receptor type 1 (NTSR1), a hard-to-express G protein-coupled receptor (GPCR), was constructed. The cell line was then subjected to human miRNA mimic library screening. In parallel, an HEK293 cell line expressing luciferase was also screened with the same human miRNA mimic library. Five microRNA mimics: hsa-miR-22-5p, hsa-miR-18a-5p, hsa-miR-22-3p, hsa-miR-429, and hsa-miR-2110were identified from both screens. They led to 48% increase in the expression of functional NTSR1 and to 239% increase of luciferase expression. These miRNAs were also effective in enhancing the expression of secretedglypican-3 hFc-fusion protein from HEK293 cells.The results indicate that these molecules may have a wide role in enhancing the production of proteins with biomedical interest.

  1. Gibberellic and kaurenoic hybrid strigolactone mimics for seed germination of parasitic weeds.

    Science.gov (United States)

    Pereira, Rondinelle G; Cala, Antonio; Fernández-Aparicio, Mónica; Molinillo, José Mg; Boaventura, Maria Ad; Macías, Francisco A

    2017-06-23

    Parasitic weeds are widespread and cause significant losses in important crops. Their germination requires the detection of crop-derived molecules such as strigolactones. Strigolactone mimics are germination-inducing molecules with the potential to apply a suicidal germination strategy for seed bank control of parasitic weeds. The D-ring, which is instrumental in the germination process of seeds of parasitic weeds, was attached to gibberellin (GA3 ) and kaurenoic acid as the scaffold. It was shown that indeed strigolactone mimics prepared from GA3 and kaurenoic acid are active as stimulants when a D-ring is present; some of the mimics are as active as GR24. The starting molecules were plant hormones that had previous growth-regulating activity in other organisms and the products showed enhanced activity towards parasitic weeds. The information generated may contribute to a better understanding of the germination biochemistry of the weed species used. Further research is required in this area but it is clear that the results are promising. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. Virulent Burkholderia species mimic host actin polymerases to drive actin-based motility

    Science.gov (United States)

    Benanti, Erin L.; Nguyen, Catherine M.; Welch, Matthew D.

    2015-01-01

    Summary Burkholderia pseudomallei and B. mallei are bacterial pathogens that cause melioidosis and glanders, while their close relative B. thailandensis is nonpathogenic. All use the trimeric autotransporter BimA to facilitate actin-based motility, host cell fusion and dissemination. Here, we show that BimA orthologs mimic different host actin-polymerizing proteins. B. thailandensis BimA activates the host Arp2/3 complex. In contrast, B. pseudomallei and B. mallei BimA mimic host Ena/VASP actin polymerases in their ability to nucleate, elongate and bundle filaments by associating with barbed ends, as well as in their use of WH2 motifs and oligomerization for activity. Mechanistic differences among BimA orthologs resulted in distinct actin filament organization and motility parameters, which affected the efficiency of cell fusion during infection. Our results identify bacterial Ena/VASP mimics and reveal that pathogens imitate the full spectrum of host actin-polymerizing pathways, suggesting that mimicry of different polymerization mechanisms influences key parameters of infection. PMID:25860613

  3. A search for symbiotic behaviour amongst OH/IR colour mimics

    CERN Document Server

    Seaquist, E R

    1994-01-01

    Recent maser surveys have shown that many potential OH/IR stars have no OH masers in their circumstellar envelopes, despite the modest requirements which should be implicitly met by IRAS colour-selected candidates. It has been suggested that these OH/IR colour mimics must have a degenerate companion which dissociates OH molecules and disrupts the masing action, ie. that they are related to symbiotic Miras. Coincidentally, there is a paucity of long-period symbiotic Miras and symbiotic OH/IR stars. Phenomonologically, those that are known seem to cluster in the zone where field Miras transform into OH/IR stars. If it could be proven that OH/IR colour mimics contain a degenerate star, that observable evidence of this star is hidden from view by CS dust whilst it slowly accretes from the wind of its Mira companion, then we have an excellent explanation for not only the existence of OH/IR colour mimics, but also for the low observed frequency of symbiotic OH/IR stars and the common occurrence of very slow novae i...

  4. MIMIC: An Innovative Methodology for Determining Mobile Laser Scanning System Point Density

    Directory of Open Access Journals (Sweden)

    Conor Cahalane

    2014-08-01

    Full Text Available Understanding how various Mobile Mapping System (MMS laser hardware configurations and operating parameters exercise different influence on point density is important for assessing system performance, which in turn facilitates system design and MMS benchmarking. Point density also influences data processing, as objects that can be recognised using automated algorithms generally require a minimum point density. Although obtaining the necessary point density impacts on hardware costs, survey time and data storage requirements, a method for accurately and rapidly assessing MMS performance is lacking for generic MMSs. We have developed a method for quantifying point clouds collected by an MMS with respect to known objects at specified distances using 3D surface normals, 2D geometric formulae and line drawing algorithms. These algorithms were combined in a system called the Mobile Mapping Point Density Calculator (MIMIC and were validated using point clouds captured by both a single scanner and a dual scanner MMS. Results from MIMIC were promising: when considering the number of scan profiles striking the target, the average error equated to less than 1 point per scan profile. These tests highlight that MIMIC is capable of accurately calculating point density for both single and dual scanner MMSs.

  5. Smad transcription factors.

    Science.gov (United States)

    Massagué, Joan; Seoane, Joan; Wotton, David

    2005-12-01

    Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.

  6. Behavioural aspects of terrorism.

    Science.gov (United States)

    Leistedt, Samuel J

    2013-05-10

    Behavioural and social sciences are useful in collecting and analysing intelligence data, understanding terrorism, and developing strategies to combat terrorism. This article aims to examine the psychopathological concepts of terrorism and discusses the developing roles for behavioural scientists. A systematic review was conducted of studies investigating behavioural aspects of terrorism. These studies were identified by a systematic search of databases, textbooks, and a supplementary manual search of references. Several fundamental concepts were identified that continue to influence the motives and the majority of the behaviours of those who support or engage in this kind of specific violence. Regardless of the psychological aspects and new roles for psychiatrists, the behavioural sciences will continue to be called upon to assist in developing better methods to gather and analyse intelligence, to understand terrorism, and perhaps to stem the radicalisation process. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. ROBOTIC SURGERY: BIOETHICAL ASPECTS

    Science.gov (United States)

    SIQUEIRA-BATISTA, Rodrigo; SOUZA, Camila Ribeiro; MAIA, Polyana Mendes; SIQUEIRA, Sávio Lana

    2016-01-01

    ABSTRACT Introduction: The use of robots in surgery has been increasingly common today, allowing the emergence of numerous bioethical issues in this area. Objective: To present review of the ethical aspects of robot use in surgery. Method: Search in Pubmed, SciELO and Lilacs crossing the headings "bioethics", "surgery", "ethics", "laparoscopy" and "robotic". Results: Of the citations obtained, were selected 17 articles, which were used for the preparation of the article. It contains brief presentation on robotics, its inclusion in health and bioethical aspects, and the use of robots in surgery. Conclusion: Robotic surgery is a reality today in many hospitals, which makes essential bioethical reflection on the relationship between health professionals, automata and patients. PMID:28076489

  8. Aspects of B physics

    Energy Technology Data Exchange (ETDEWEB)

    Gaillard, M.K.

    1987-10-14

    Various aspects of weak decays are commented on. Probing of the standard model and of phenomena beyond the standard model are discussed, followed by a theoretical view of B mesons and some experimental observations on B mesons. The point is made that any data on B decay would be interesting in that it would provide powerful new constraints in analyses of the standard model and extensions thereof. (LEW)

  9. Electrochemical kinetics theoretical aspects

    CERN Document Server

    Vetter, Klaus J

    1967-01-01

    Electrochemical Kinetics: Theoretical Aspects focuses on the processes, methodologies, reactions, and transformations in electrochemical kinetics. The book first offers information on electrochemical thermodynamics and the theory of overvoltage. Topics include equilibrium potentials, concepts and definitions, electrical double layer and electrocapillarity, and charge-transfer, diffusion, and reaction overvoltage. Crystallization overvoltage, total overvoltage, and resistance polarization are also discussed. The text then examines the methods of determining electrochemical reaction mechanisms

  10. LNG project - contractual aspects

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, Bruno Almeida

    2008-07-01

    This paper intends to provide from the legal point of view an outline of the main challenges of a LNG project in the upstream, regulatory aspects, liquefaction, financing and midstream through a basic checklist; an overview of the contractual complexity of a LNG project; some basic discussion of particular LNG contract clauses; and a comparative analysis between the classic clauses of a Gas Transportation Agreement (GTA) through a gas pipeline and LNG logistic. (author)

  11. Strategic Aspects of Hegemony

    OpenAIRE

    Robert E. Goodin; Güth, Werner; Snidal, Duncan

    2005-01-01

    Hegemony is a central feature of contemporary international politics but it remains seriously under-theorized. We draw on cooperative game theory to represent and analyze different aspects of hegemony. After developing a general conception of hegemony, we analyze the circumstances under which a Hegemon needs assistance from allies, examine when prospective allies have incentives to cooperate with or challenge Hegemon and evaluate the prospects for exploitation by Hegemon. Throughout, we conne...

  12. MARKETING MIX THEORETICAL ASPECTS

    OpenAIRE

    Margarita Išoraitė

    2016-01-01

    Aim of article is to analyze marketing mix theoretical aspects. The article discusses that marketing mix is one of the main objectives of the marketing mix elements for setting objectives and marketing budget measures. The importance of each element depends not only on the company and its activities, but also on the competition and time. All marketing elements are interrelated and should be seen in the whole of their actions. Some items may have greater importance than others; it depends main...

  13. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  14. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  15. The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study

    Directory of Open Access Journals (Sweden)

    Jamshid Jamali

    2017-01-01

    Full Text Available Evaluating measurement equivalence (also known as differential item functioning (DIF is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

  16. Genetic and epigenetic control of RKIP transcription.

    Science.gov (United States)

    Datar, Ila; Tegegne, Hanna; Qin, Kevin; Al-Mulla, Fahd; Bitar, Milad S; Trumbly, Robert J; Yeung, Kam C

    2014-01-01

    Raf kinase inhibitory protein (RKIP) is known to modulate key signaling cascades and regulate normal physiological processes such as cellular proliferation, differentiation, and apoptosis. The expression of RKIP is found to be downregulated in several cancer metastases and the repressed RKIP expression can be reactivated on treatment with chemotherapeutic agents. RKIP is a proven tumor metastasis suppressor gene and investigating the mechanisms of transcriptional regulation of RKIP is therefore of immense clinical importance. In this review, we discuss the basal expression of RKIP in various tissues and the genetic aspects of the RKIP chromosomal locus including the structure of the RKIP promoter as well as gene regulatory elements such as enhancers. We also review the genetic and epigenetic modulation of RKIP transcription through EZH2, a component of the polycomb repressive complex 2 (PRC2) and sequence specific transcription factors (TFs) BACH1 and Snail. Emerging experimental evidence supports a unifying model in which both these TFs repress RKIP transcription in cancers by recruiting the EZH2 containing repressive complex to the proximal RKIP promoter. Finally, we review the known mechanisms employed by different types of chemotherapeutic agents to activate RKIP expression in cancer cells.

  17. Rhythm quantization for transcription

    NARCIS (Netherlands)

    Cemgil, A.T.; Desain, P.W.M.; Kappen, H.J.

    1999-01-01

    Automatic Music Transcription is the extraction of an acceptable notation from performed music. One important task in this problem is rhythm quantization which refers to categorization of note durations. Although quantization of a pure mechanical performance is rather straightforward, the task becom

  18. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any a

  19. Mapping yeast transcriptional networks.

    Science.gov (United States)

    Hughes, Timothy R; de Boer, Carl G

    2013-09-01

    The term "transcriptional network" refers to the mechanism(s) that underlies coordinated expression of genes, typically involving transcription factors (TFs) binding to the promoters of multiple genes, and individual genes controlled by multiple TFs. A multitude of studies in the last two decades have aimed to map and characterize transcriptional networks in the yeast Saccharomyces cerevisiae. We review the methodologies and accomplishments of these studies, as well as challenges we now face. For most yeast TFs, data have been collected on their sequence preferences, in vivo promoter occupancy, and gene expression profiles in deletion mutants. These systematic studies have led to the identification of new regulators of numerous cellular functions and shed light on the overall organization of yeast gene regulation. However, many yeast TFs appear to be inactive under standard laboratory growth conditions, and many of the available data were collected using techniques that have since been improved. Perhaps as a consequence, comprehensive and accurate mapping among TF sequence preferences, promoter binding, and gene expression remains an open challenge. We propose that the time is ripe for renewed systematic efforts toward a complete mapping of yeast transcriptional regulatory mechanisms.

  20. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any

  1. The "fourth dimension" of gene transcription.

    Science.gov (United States)

    O'Malley, Bert W

    2009-05-01

    The three dimensions of space provide our relationship to position on the earth, but the fourth dimension of time has an equally profound influence on our lives. Everything from light and sound to weather and biology operate on the principle of measurable temporal periodicity. Consequently, a wide variety of time clocks affect all aspects of our existence. The annual (and biannual) cycles of activity, metabolism, and mating, the monthly physiological clocks of women and men, and the 24-h diurnal rhythms of humans are prime examples. Should it be surprising to us that the fourth dimension also impinges upon gene expression and that the genome itself is regulated by the fastest running of all biological clocks? Recent evidence substantiates the existence of such a ubiquitin-dependent transcriptional clock that is based upon the activation and destruction of transcriptional coactivators.

  2. AspectJ in action practical aspect-oriented programming

    CERN Document Server

    Laddad, Ramnivas

    2003-01-01

    A guide to aspect-oriented programming and the AspectJ language, this book provides code examples that enable quick implementation of functionality in a system. Thorough introductions to AOP and AspectJ will help developers learn or advance their knowledge of AspectJ. Examples of everyday situations in which AspectJ solutions can be applied, such as logging, policy enforcement, resource pooling, business logic, thread-safety, authentication and authorization, and transaction management are provided. In addition, design patterns and idioms are covered, as is business rule implementation. The latest technologies, such as JEES, JAAS, and log4j, are explained and connected with AspectJ.

  3. Transcription Dynamics in Living Cells.

    Science.gov (United States)

    Lenstra, Tineke L; Rodriguez, Joseph; Chen, Huimin; Larson, Daniel R

    2016-07-01

    The transcription cycle can be roughly divided into three stages: initiation, elongation, and termination. Understanding the molecular events that regulate all these stages requires a dynamic view of the underlying processes. The development of techniques to visualize and quantify transcription in single living cells has been essential in revealing the transcription kinetics. They have revealed that (a) transcription is heterogeneous between cells and (b) transcription can be discontinuous within a cell. In this review, we discuss the progress in our quantitative understanding of transcription dynamics in living cells, focusing on all parts of the transcription cycle. We present the techniques allowing for single-cell transcription measurements, review evidence from different organisms, and discuss how these experiments have broadened our mechanistic understanding of transcription regulation.

  4. Forestry certification social aspects

    CSIR Research Space (South Africa)

    Hamman, J

    2000-01-01

    Full Text Available intimidating to respondents. Related to the question of language is the question of race. South Africa's political history has been characterised by colonialist dispossession and racial exclusivity in political decision-making. The effect of this on rural... and environmental aspects of the audit, the forester seems to be more uncomfortable responding to the social auditor. The skill levels required to gain and maintain the trust of the forest management is very high, and the same racial factors play a role...

  5. Fractal aspects of hadrons

    CERN Document Server

    Deppman, Airton

    2016-01-01

    The non extensive aspects of $p_T$ distributions obtained in high energy collisions are discussed in relation to possible fractal structure in hadrons, in the sense of the thermofractal structure recently introduced. The evidences of self-similarity in both theoretical and experimental works in High Energy and in Hadron Physics are discussed, to show that the idea of fractal structure of hadrons and fireballs have being under discussion for decades. The non extensive self-consistent thermodynamics and the thermofractal structure allow one to connect non extensivity to intermittence and possibly to parton distribution functions in a single theoretical framework.

  6. Knockout reactions: experimental aspects

    Energy Technology Data Exchange (ETDEWEB)

    Cortina Gil, D. [Santiago de Compostela Univ. (Spain)

    2007-07-01

    The availability of radioactive beams has given rise to intense activity in the field of direct reactions. The removal of one(two)-nucleon (referred to as nucleon knockout in this text) from a fast exotic projectile has been extensively investigated. This lecture provides a general overview of the experimental results achieved using this technique. The sensitivity of the method to different experimental aspects is illustrated with a few examples. Special attention is given to the application of nucleon-knockout reactions as a general purpose spectroscopic tool. (author)

  7. Neurological aspects of grief.

    Science.gov (United States)

    Silva, Adriana C; de Oliveira Ribeiro, Natalia P; de Mello Schier, Alexandre R; Arias-Carrión, Oscar; Paes, Flavia; Nardi, Antonio E; Machado, Sergio; Pessoa, Tamires M

    2014-01-01

    Despite grief being a universal experience and the increased scientific attention paid to grief and bereavement in recent years, studies that seek to better understand the role of the neurological aspects of grief are still scarce. We found 5 studies that discussed the relationship between the neurological aspects of grief due to the death of a loved one. All studies showed an activation of common areas, i.e., the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), prefrontal cortex (PFC), insula and amygdala. These findings could indicate that there is a group of areas working together and responding to generate the symptomatology of grief. Because grief is a universal experience, it is essential that the necessary and effective support can be provided to those who experience the loss of someone considered important in their lives, and this requires understanding grief's manifestation, its differential diagnosis in reference to other clinical conditions, mainly psychiatric ones, and adequate forms of intervention and treatment when necessary. Proper understanding and support can help prevent the emergence of more serious health problems.

  8. PRAGMATIC ASPECT OF CITATION

    Directory of Open Access Journals (Sweden)

    Tatiana Sergeevna SIRENKO

    2014-01-01

    Full Text Available The article is devoted to the research of the prag-matic aspect of citation in fictional text from the in-tertextual point of view. The theory of intertextuality was formed in the works of M.Bakhtin and devel-oped by Y. Kristeva after the analysis of the works of post-modern writers. So allusion and citation began to be investigated not from the philology point of view only but from the linguistics as well. The pur-pose of the article is to investigate the pragmatic aspect of citation which includes also the investiga-tion of its pragmatic functions. Different views on the citation classification are also mentioned in the article as it is an actual problem in modern linguis-tics. Novels by British writer J. Fforde are the mate-rial for the investigation article because they pos-sess a big amount of intertextual inclusion in the text in general and citation in particular.

  9. RNA polymerase: the vehicle of transcription.

    Science.gov (United States)

    Borukhov, Sergei; Nudler, Evgeny

    2008-03-01

    RNA polymerase (RNAP) is the principal enzyme of gene expression and regulation for all three divisions of life: Eukaryota, Archaea and Bacteria. Recent progress in the structural and biochemical characterization of RNAP illuminates this enzyme as a flexible, multifunctional molecular machine. During each step of the transcription cycle, RNAP undergoes elaborate conformational changes. As many fundamental and previously mysterious aspects of how RNAP works begin to be understood, this enzyme reveals intriguing similarities to man-made engineered devices. These resemblances can be found in the mechanics of RNAP-DNA complex formation, in RNA chain initiation and in the elongation processes. Here we highlight recent advances in understanding RNAP function and regulation.

  10. Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Karig, David K [ORNL; Siuti, Piro [ORNL; Dar, Roy D. [University of Tennessee, Knoxville (UTK); Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL; Simpson, Michael L [ORNL

    2011-01-01

    Cells offer natural examples of highly efficient networks of nanomachines. Accordingly, both intracellular and intercellular communication mechanisms in nature are looked to as a source of inspiration and instruction for engineered nanocommunication. Harnessing biological functionality in this manner requires an interdisciplinary approach that integrates systems biology, synthetic biology, and nanofabrication. Recent years have seen the amassing of a tremendous wealth of data from the sequencing of new organisms and from high throughput expression experiments. At the same time, a deeper fundamental understanding of individual cell function has been developed, as exemplified by the growth of fields such as noise biology, which seeks to characterize the role of noise in gene expression. The availability of well characterized biological components coupled with a deeper understanding of cell function has led to efforts to engineer both living cells and to create bio-like functionality in non-living substrates in the field of synthetic biology. Here, we present a model system that exemplifies the synergism between these realms of research. We propose a synthetic gene network for operation in a nanofabricated cell mimic array that propagates a biomolecular signal over long distances using the phenomenon of stochastic resonance. Our system consists of a bacterial quorum sensing signal molecule, a bistable genetic switch triggered by this signal, and an array of nanofabricated cell mimic wells that contain the genetic system. An optimal level of noise in the system helps to propagate a time-varying AHL signal over long distances through the array of mimics. This noise level is determined both by the system volume and by the parameters of the genetic network. Our proposed genetically driven stochastic resonance system serves as a testbed for exploring the potential harnessing of gene expression noise to aid in the transmission of a time-varying molecular signal.

  11. Language barriers between physicians and patients are not associated with thrombolysis of stroke mimics.

    Science.gov (United States)

    Rostanski, Sara K; Williams, Olajide; Stillman, Joshua I; Marshall, Randolph S; Willey, Joshua Z

    2016-10-01

    Acute stroke is a time-sensitive condition in which rapid diagnosis must be made in order for thrombolytic treatment to be administered. A certain proportion of patients who receive thrombolysis will be found on further evaluation to have a diagnosis other than stroke, so-called "stroke mimics." Little is known about the role of language discordance in the emergency department diagnosis of acute ischemic stroke. This is a retrospective analysis of all acute ischemic stroke patients who received IV tissue plasminogen activator (tPA) in our emergency department between July 2011 and December 2015. Baseline characteristics, patient language, and final diagnosis were compared between encounters in which the treating neurologist and patient spoke the same language (concordant cases) and encounters in which they did not (discordant cases). A total of 350 patients received IV tPA during the study period. English was the primary language for 52.6%, Spanish for 44.9%, and other languages for 2.6%; 60.3% of cases were classified as language concordant and 39.7% as discordant. We found no significant difference in the proportion of stroke mimics in the language concordant compared to discordant groups (16.6% vs 9.4%, p = 0.06). Similarly, the proportion of stroke mimics did not differ between English- and Spanish-speaking patients (15.8% vs 11.5%, p = 0.27). Language discordance was not associated with acute stroke misdiagnosis among patients treated with IV tPA. Prospective evaluation of communication during acute stroke encounters is needed to gain clarity on the role of language discordance in acute stroke misdiagnosis.

  12. Representing life in the Earth system with soil microbial functional traits in the MIMICS model

    Directory of Open Access Journals (Sweden)

    W. R. Wieder

    2015-02-01

    Full Text Available Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon cycle–climate feedbacks. We used a microbial trait-based soil carbon (C model, with two physiologically distinct microbial communities to improve current estimates of soil C storage and their likely response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS model, which incorporates oligotrophic and copiotrophic functional groups, akin to "gleaner" vs. "opportunist" plankton in the ocean, or r vs. K strategists in plant and animals communities. Here we compare MIMICS to a conventional soil C model, DAYCENT, in cross-site comparisons of nitrogen (N enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that current projections from Earth system models likely overestimate the strength of the land C sink in response to increasing C inputs with elevated carbon dioxide (CO2. Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

  13. Macrocyclic beta-sheet peptides that mimic protein quaternary structure through intermolecular beta-sheet interactions.

    Science.gov (United States)

    Khakshoor, Omid; Demeler, Borries; Nowick, James S

    2007-05-02

    This paper reports the design, synthesis, and characterization of a family of cyclic peptides that mimic protein quaternary structure through beta-sheet interactions. These peptides are 54-membered-ring macrocycles comprising an extended heptapeptide beta-strand, two Hao beta-strand mimics [JACS 2000, 122, 7654] joined by one additional alpha-amino acid, and two delta-linked ornithine beta-turn mimics [JACS 2003, 125, 876]. Peptide 3a, as the representative of these cyclic peptides, contains a heptapeptide sequence (TSFTYTS) adapted from the dimerization interface of protein NuG2 [PDB ID: 1mio]. 1H NMR studies of aqueous solutions of peptide 3a show a partially folded monomer in slow exchange with a strongly folded oligomer. NOE studies clearly show that the peptide self-associates through edge-to-edge beta-sheet dimerization. Pulsed-field gradient (PFG) NMR diffusion coefficient measurements and analytical ultracentrifugation (AUC) studies establish that the oligomer is a tetramer. Collectively, these experiments suggest a model in which cyclic peptide 3a oligomerizes to form a dimer of beta-sheet dimers. In this tetrameric beta-sheet sandwich, the macrocyclic peptide 3a is folded to form a beta-sheet, the beta-sheet is dimerized through edge-to-edge interactions, and this dimer is further dimerized through hydrophobic face-to-face interactions involving the Phe and Tyr groups. Further studies of peptides 3b-3n, which are homologues of peptide 3a with 1-6 variations in the heptapeptide sequence, elucidate the importance of the heptapeptide sequence in the folding and oligomerization of this family of cyclic peptides. Studies of peptides 3b-3g show that aromatic residues across from Hao improve folding of the peptide, while studies of peptides 3h-3n indicate that hydrophobic residues at positions R3 and R5 of the heptapeptide sequence are important in oligomerization.

  14. Design and Analyses of High Aspect Ratio Nozzles for Distributed Propulsion Acoustic Measurements

    Science.gov (United States)

    Dippold, Vance F., III

    2016-01-01

    A series of three convergent round-to-rectangular high-aspect ratio nozzles were designed for acoustics measurements. The nozzles have exit area aspect ratios of 8:1, 12:1, and 16:1. With septa inserts, these nozzles will mimic an array of distributed propulsion system nozzles, as found on hybrid wing-body aircraft concepts. Analyses were performed for the three nozzle designs and showed that the flow through the nozzles was free of separated flow and shocks. The exit flow was mostly uniform with the exception of a pair of vortices at each span-wise end of the nozzle.

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

    Science.gov (United States)

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

    2008-11-01

    Polyguanidinium oxanorbornene ( PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents.

  16. [Often an orthopedic problem can manifest as chest pain. Cervical vertebrae syndrome mimics myocardial infarct].

    Science.gov (United States)

    Fromm, B

    2002-04-25

    Up to 20% of all patients with pectoral symptoms have an underlying orthopedic problem. The most common orthopedic conditions that may mimic chest pain radiating into the left arm include slipped disc, cervicothoracic tension syndrome, blockage of intervertebral or rib joints, and intercostal neuralgia. Less common causes of such pain are arthrosis of the shoulder, spondylocystitis, osteoporotic fractures or tumors of the bone. Management is oriented to the underlying cause, and treatment extends from physiotherapeutic measures (rest, heat treatment) via medication (non-steroidal anti-inflammatory drugs, myotonolytic agents) to operative interventions.

  17. Cholesterol atheroembolism of the colon can mimic the endoscopic features of pseudomembranous colitis.

    Science.gov (United States)

    Lim, Geok-Hoon; Roslani, April Camilla; Pang, Brendan; Bih-Shiou, Charles Tsang

    2008-12-01

    The endoscopic features of cholesterol atheroembolism affecting the colon have not been extensively described in the literature, owing to the rarity of this entity. We report a middle-aged man who presented with hematochezia after recent coronary artery bypass graft surgery. Colonoscopy revealed ulcerative skip lesions with overlying slough resembling pseudomembranes distal to the transverse colon, inconsistent with the initial clinical impression of ischemic colitis. As a consequence of continued bleeding with hemodynamic instability, the patient underwent an extended low anterior resection with end transverse colostomy. Histology revealed cholesterol atheroembolism resulting in patchy ischemic ulceration of the colon. Colonic cholesterol atheroembolism can mimic the endoscopic features of pseudomembranous colitis.

  18. Chondromyxoid fibroma of the rib mimics a chondrosarcoma on 18F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William (Dept. of Nuclear Medicine, Brandon Regional Health Centre, Brandon (Canada)), email: makisw79@yahoo.com; Ciarallo, Anthony; Lisbona, Robert (Dept. of Nuclear Medicine, Royal Victoria Hospital, McGill Univ. Health Centre, Montreal (Canada))

    2011-06-15

    Chondromyxoid fibroma (CMF) is a rare benign bone tumor of chondroid origin that occurs mostly in the metaphyses of long bones. CMF can occasionally mimic a chondrosarcoma on CT, and the literature on the 18F-FDG PET/CT imaging characteristics of CMF tumors is limited. In the presented case, a large histologically proven CMF chest wall mass was initially misinterpreted as a chondrosarcoma. This case highlights a potential pitfall in the PET/CT evaluation of these rare benign bone tumors

  19. Tsukamurella: an unrecognized mimic of atypical mycobacterial keratitis? The first case report.

    Science.gov (United States)

    Tam, Patrick M K; Young, Alvin L; Cheng, Lulu; Congdon, Nathan; Lam, Philip T H

    2010-03-01

    The purpose of this study was to report on Tsukamurella as a mimic of atypical mycobacterial infection. We report a patient who had received repeated corneal grafts with culture-proven Tsukamurella keratitis. A slow-progressing corneal abscess that initially developed adjacent to a corneal stitch responded poorly to empiric antibiotic treatment. A preliminary culture report revealed fast-growing mycobacterial species. Treatment adjustments successfully controlled the disease. A final diagnosis of Tsukamurella was subsequently made on the basis of cultures. Tsukamurella exhibits laboratory similarities to mycobacteria and should be considered in the differential of atypical infection of the ocular surface.

  20. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT)

    Science.gov (United States)

    2015-01-01

    3-Hydroxy-4-pyridinones and 5-hydroxy-4-pyrimidinones were identified as inhibitors of catechol-O-methyltransferase (COMT) in a high-throughput screen. These heterocyclic catechol mimics exhibit potent inhibition of the enzyme and an improved toxicity profile versus the marketed nitrocatechol inhibitors tolcapone and entacapone. Optimization of the series was aided by X-ray cocrystal structures of the novel inhibitors in complex with COMT and cofactors SAM and Mg2+. The crystal structures suggest a mechanism of inhibition for these heterocyclic inhibitors distinct from previously disclosed COMT inhibitors. PMID:25815153

  1. Race-related cognitive test bias in the active study: a mimic model approach.

    Science.gov (United States)

    Aiken Morgan, Adrienne T; Marsiske, Michael; Dzierzewski, Joseph M; Jones, Richard N; Whitfield, Keith E; Johnson, Kathy E; Cresci, Mary K

    2010-10-01

    The present study investigated evidence for race-related test bias in cognitive measures used in the baseline assessment of the ACTIVE clinical trial. Test bias against African Americans has been documented in both cognitive aging and early life span studies. Despite significant mean performance differences, Multiple Indicators Multiple Causes (MIMIC) models suggested most differences were at the construct level. There was little evidence that specific measures put either group at particular advantage or disadvantage and little evidence of cognitive test bias in this sample. Small group differences in education, cognitive status, and health suggest positive selection may have attenuated possible biases.

  2. Non-transcriptional regulatory processes shape transcriptional network dynamics

    OpenAIRE

    Ray, J. Christian J; Tabor, Jeffrey J.; Igoshin, Oleg A.

    2011-01-01

    Information about the extra- or intracellular environment is often captured as biochemical signals propagating through regulatory networks. These signals eventually drive phenotypic changes, typically by altering gene expression programs in the cell. Reconstruction of transcriptional regulatory networks has given a compelling picture of bacterial physiology, but transcriptional network maps alone often fail to describe phenotypes. In many cases, the dynamical performance of transcriptional re...

  3. In Vitro Study of Influence of Mimic Cardiac Rate on Hydrodynamics of the Different Mechanical Cardiac Valve Prostheses

    Institute of Scientific and Technical Information of China (English)

    CHU Yin-ping; CHENG Jin-lian; CHEN Ru-kun; FAN Yu-bo; PU Fang

    2005-01-01

    Objective:To assess the influence of mimic cardiac rate on hydrodynamics of the different mechanical prosthetic cardiac valves. Methods: US-made CarboMedics bileaflet valve and China-made Jiuling bileaflet valve and C-L tilting disc valve have been tested in a pulsatile flow simulator in the aortic position. The testing condition was set at the mimic cardiac rate of 55 beats/min,75 beats/min,100beats/min and a constant mimic cardiac output of 4L/min. The mean pressure differences (△P) ,leakage volumes (LEV) and closing volumes (CLV) across each valve,and the effective orifice areas(EOA) have been analyzed. Results:Within the range of physiology,the △P,LEV and CLV were falling as the increasing of mimic cardiac rate,and the extent of variance was larger. The EOA was increasing with the increase of the mimic cardiac rate. It is a different response as the altering of the cardiac rate for the different type of the mechanical prosthetic cardiac valves.Conclusions:The change of the mimic cardiac rate can affect the hydrodynamics of the mechanical prosthetic cardiac valves. The hydrodynamics of the bileaflet valve prosthesis is better than the tilting disc valve.

  4. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... targeting specific cis-acting elements in genes, and by the significant lack of fixed tertiary structure in their extensive intrinsically disordered regions. Recent research in protein intrinsic disorder (ID) has changed our understanding of transcriptional activation domains from 'negative noodles' to ID...... them to participate in large interactomes, how they use only a few hydrophobic residues, short sequence motifs, prestructured motifs, and coupled folding and binding for their interactions with co-activators, and how their accessibility to post-translational modification affects their interactions...

  5. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  6. SNFing HIV transcription

    Directory of Open Access Journals (Sweden)

    Bukrinsky Michael

    2006-08-01

    Full Text Available Abstract The SWI/SNF chromatin remodeling complex is an essential regulator of transcription of cellular genes. HIV-1 infection induces exit of a core component of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre-integration complex. Several recent papers published in EMBO Journal, Journal of Biological Chemistry, and Retrovirology provide new information regarding possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1 has an inhibitory effect on pre-integration steps of HIV replication, but also contributes to stimulation of Tat-mediated transcription. This stimulation involves displacement of the nucleosome positioned at the HIV promoter.

  7. Analysis of the transcription initiation mechanism of tomato spotted wilt virus

    NARCIS (Netherlands)

    Duijsings, D.M.J.M.

    2001-01-01

    Genome replication and transcription of Tomato spotted wilt virus (TSWV, genus Tospovirus ) follows in most aspects the general rules for negative strand RNA viruses with segmented genomes. One common feature is the occurrence of "cap snatching" during transcription initiation. During this process,

  8. Aspects of Color Superconductivity

    CERN Document Server

    Hong, D K

    2001-01-01

    I discuss some aspects of recent developments in color superconductivity in high density quark matter. I calculate the Cooper pair gap and the critical points at high density, where magnetic gluons are not screened. The ground state of high density QCD with three light flavors is shown to be a color-flavor locking state, which can be mapped into the low-density hadronic phase. The meson mass at the CFL superconductor is also calculated. The CFL color superconductor is bosonized, where the Fermi sea is identified as a $Q$-matter and the gapped quarks as topological excitations, called superqualitons, of mesons. Finally, as an application of color supercoductivity, I discuss the neutrino interactions in the CFL color superconductor.

  9. CUSTOMER LOYALTY THEORETICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    Margarita IŠORAITĖ

    2016-08-01

    Full Text Available Customer loyalty - is a voluntary user solution for a long time to build relationships with the company. Loyalty is the user's desire for a long time to continue their relationship with a particular company, because loyal customers are those who purchase goods/services of the company from time to time. Loyalty can be treated as a customer desire, willingness to be a regular customer for a long time, buying and using the goods of the chosen companies by recommending them to friends and colleagues. Loyalty can be seen as a multi-dimension, covering behavioral and positional components, where positional aspect reflects customers' approach to business, while the behavioral dimension reveals a frequent and regular shopping, purchase quantity, size, range, availability, etc.

  10. Psychiatric aspects of burn

    Directory of Open Access Journals (Sweden)

    Dalal P

    2010-10-01

    Full Text Available Burn injuries and their subsequent treatment cause one of the most excruciating forms of pain imaginable. The psychological aspects of burn injury have been researched in different parts of the world, producing different outcomes. Studies have shown that greater levels of acute pain are associated with negative long-term psychological effects such as acute stress disorder, depression, suicidal ideation, and post-traumatic stress disorder for as long as 2 years after the initial burn injury. The concept of allostatic load is presented as a potential explanation for the relationship between acute pain and subsequent psychological outcomes. A biopsychosocial model is also presented as a means of obtaining better inpatient pain management and helping to mediate this relationship.

  11. Formal aspects of resilience

    Directory of Open Access Journals (Sweden)

    Diana-Maria Drigă

    2015-12-01

    Full Text Available The concept of resilience has represented during the recent years a leading concern both in Romania, within the European Union and worldwide. Specialists in economics, management, finance, legal sciences, political sciences, sociology, psychology, grant a particular interest to this concept. Multidisciplinary research of resilience has materialized throughout the time in multiple conceptualizations and theorizing, but without being a consensus between specialists in terms of content, specificity and scope. Through this paper it is intended to clarify the concept of resilience, achieving an exploration of the evolution of this concept in ecological, social and economic environment. At the same time, the paper presents aspects of feedback mechanisms and proposes a formalization of resilience using the logic and mathematical analysis.

  12. Technological Aspects: High Voltage

    CERN Document Server

    Faircloth, D C

    2013-01-01

    This paper covers the theory and technological aspects of high-voltage design for ion sources. Electric field strengths are critical to understanding high-voltage breakdown. The equations governing electric fields and the techniques to solve them are discussed. The fundamental physics of high-voltage breakdown and electrical discharges are outlined. Different types of electrical discharges are catalogued and their behaviour in environments ranging from air to vacuum are detailed. The importance of surfaces is discussed. The principles of designing electrodes and insulators are introduced. The use of high-voltage platforms and their relation to system design are discussed. The use of commercially available high-voltage technology such as connectors, feedthroughs and cables are considered. Different power supply technologies and their procurement are briefly outlined. High-voltage safety, electric shocks and system design rules are covered.

  13. Aspects of Gond Astronomy

    CERN Document Server

    Vahia, M N

    2013-01-01

    The Gond community is considered to be one of the most ancient tribes of India with a continuing history of several thousand years. They are also known for their largely isolated history which they have retained through the millennia. Several of their intellectual traditions therefore are a record of parallel aspects of human intellectual growth, and still preserve their original flavour and have not been homogenised by the later traditions of India. In view of this, the Gonds provide a special window to the different currents that constitute contemporary India. In the present study, we summarise their mythology, genetics and script. We then investigate their astronomical traditions and try to understand this community through a survey of 15 Gond villages spread over Maharashtra, Andhra Pradesh and Madhya Pradesh. We show that they have a distinctly different view of the sky from the conventional astronomical ideas encountered elsewhere in India, which is both interesting and informative. We briefly comment o...

  14. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    RNA); and ii) translation, in which the mRNA is translated into a protein. This thesis focus on the ¿rst of these steps, transcription, and speci¿cally the initiation of this. Simpli¿ed, initiation is preceded by the binding of several proteins, known as transcription factors (TFs), to DNA. This takes place......The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... control spanning the range from completely muted to cranked up to maximum. The volume, in this case, is the production rate of proteins. This production is the result of a two step procedure: i) transcription, in which a small part of DNA from the genome (a gene) is transcribed into an RNA molecule (an m...

  15. Mobile Learning Aspects and Readiness

    National Research Council Canada - National Science Library

    Hana Mohammed Eltayeb Abdall; Mohammed Osman Ali Hegazi

    2014-01-01

      This paper provide the aspects of mobile learning by presenting the differences techniques and aspects of using mobile devices in education according to the perspective of researches and studies...

  16. ROBOTIC SURGERY: BIOETHICAL ASPECTS.

    Science.gov (United States)

    Siqueira-Batista, Rodrigo; Souza, Camila Ribeiro; Maia, Polyana Mendes; Siqueira, Sávio Lana

    2016-01-01

    The use of robots in surgery has been increasingly common today, allowing the emergence of numerous bioethical issues in this area. To present review of the ethical aspects of robot use in surgery. Search in Pubmed, SciELO and Lilacs crossing the headings "bioethics", "surgery", "ethics", "laparoscopy" and "robotic". Of the citations obtained, were selected 17 articles, which were used for the preparation of the article. It contains brief presentation on robotics, its inclusion in health and bioethical aspects, and the use of robots in surgery. Robotic surgery is a reality today in many hospitals, which makes essential bioethical reflection on the relationship between health professionals, automata and patients. A utilização de robôs em procedimentos cirúrgicos tem sido cada vez mais frequente na atualidade, o que permite a emergência de inúmeras questões bioéticas nesse âmbito. Apresentar revisão sobre os aspectos éticos dos usos de robôs em cirurgia. Realizou-se revisão nas bases de dados Pubmed, SciELO e Lilacs cruzando-se os descritores "bioética", "cirurgia", "ética", "laparoscopia" e "robótica". Do total de citações obtidas, selecionou-se 17 artigos, os quais foram utilizados para a elaboração do artigo. Ele contém breve apresentação sobre a robótica, sua inserção na saúde e os aspectos bioéticos da utilização dos robôs em procedimentos cirúrgicos. A cirurgia robótica é uma realidade, hoje, em muitas unidades hospitalares, o que torna essencial a reflexão bioética sobre as relações entre profissionais da saúde, autômatos e pacientes.

  17. Non-transcriptional regulatory processes shape transcriptional network dynamics.

    Science.gov (United States)

    Ray, J Christian J; Tabor, Jeffrey J; Igoshin, Oleg A

    2011-10-11

    Information about the extra- or intracellular environment is often captured as biochemical signals that propagate through regulatory networks. These signals eventually drive phenotypic changes, typically by altering gene expression programmes in the cell. Reconstruction of transcriptional regulatory networks has given a compelling picture of bacterial physiology, but transcriptional network maps alone often fail to describe phenotypes. Cellular response dynamics are ultimately determined by interactions between transcriptional and non-transcriptional networks, with dramatic implications for physiology and evolution. Here, we provide an overview of non-transcriptional interactions that can affect the performance of natural and synthetic bacterial regulatory networks.

  18. Identification and Characterization of Peptide Mimics of Blood Group A Antigen

    Institute of Scientific and Technical Information of China (English)

    Zhaoming TANG; Lin WANG; Lihua HU; Yirong LI; Tianpen CUI; Juan XIONG; Lifang DOU

    2008-01-01

    In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-met peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFrF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A an- tigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.

  19. Comprehending body language and mimics: an ERP and neuroimaging study on Italian actors and viewers.

    Directory of Open Access Journals (Sweden)

    Alice Mado Proverbio

    Full Text Available In this study, the neural mechanism subserving the ability to understand people's emotional and mental states by observing their body language (facial expression, body posture and mimics was investigated in healthy volunteers. ERPs were recorded in 30 Italian University students while they evaluated 280 pictures of highly ecological displays of emotional body language that were acted out by 8 male and female Italian actors. Pictures were briefly flashed and preceded by short verbal descriptions (e.g., "What a bore!" that were incongruent half of the time (e.g., a picture of a very attentive and concentrated person shown after the previous example verbal description. ERP data and source reconstruction indicated that the first recognition of incongruent body language occurred 300 ms post-stimulus. swLORETA performed on the N400 identified the strongest generators of this effect in the right rectal gyrus (BA11 of the ventromedial orbitofrontal cortex, the bilateral uncus (limbic system and the cingulate cortex, the cortical areas devoted to face and body processing (STS, FFA EBA and the premotor cortex (BA6, which is involved in action understanding. These results indicate that face and body mimics undergo a prioritized processing that is mostly represented in the affective brain and is rapidly compared with verbal information. This process is likely able to regulate social interactions by providing on-line information about the sincerity and trustfulness of others.

  20. cNMP-AMs mimic and dissect bacterial nucleotidyl cyclase toxin effects.

    Science.gov (United States)

    Beckert, Ulrike; Grundmann, Manuel; Wolter, Sabine; Schwede, Frank; Rehmann, Holger; Kaever, Volkhard; Kostenis, Evi; Seifert, Roland

    2014-09-05

    In addition to the well-known second messengers cAMP and cGMP, mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. The Pseudomonas aeruginosa toxin ExoY massively increases cGMP and cUMP in cells, whereas the Bordetella pertussis toxin CyaA increases cAMP and, to a lesser extent, cCMP. To mimic and dissect toxin effects, we synthesized cNMP-acetoxymethylesters as prodrugs. cNMP-AMs rapidly and effectively released the corresponding cNMP in cells. The combination of cGMP-AM plus cUMP-AM mimicked cytotoxicity of ExoY. cUMP-AM and cGMP-AM differentially activated gene expression. Certain cCMP and cUMP effects were independent of the known cNMP effectors protein kinases A and G and guanine nucleotide exchange factor Epac. In conclusion, cNMP-AMs are useful tools to mimic and dissect bacterial nucleotidyl cyclase toxin effects.

  1. BSA-templated MnO2 nanoparticles as both peroxidase and oxidase mimics.

    Science.gov (United States)

    Liu, Xing; Wang, Qi; Zhao, Huihui; Zhang, Lichun; Su, Yingying; Lv, Yi

    2012-10-01

    Inorganic nanomaterials that mimic enzymes are fascinating as they potentially have improved properties relative to native enzymes, such as greater resistance to extremes of pH and temperature and lower sensitivity to proteases. Although many artificial enzymes have been investigated, searching for highly-efficient and stable catalysts is still of great interest. In this paper, we first demonstrated that bovine serum albumin (BSA)-stabilized MnO(2) nanoparticles (NPs) exhibited highly peroxidase-, oxidase-, and catalase-like activities. The activities of the BSA-MnO(2) NPs were evaluated using the typical horseradish peroxidase (HRP) substrates o-phenylenediamine (OPD) and 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of either hydrogen peroxide or dissolved oxygen. These small-sized BSA-MnO(2) NPs with good dispersion, solubility and biocompatibility exhibited typical Michaelis-Menten kinetics and high affinity for H(2)O(2), OPD and TMB, indicating that BSA-MnO(2) NPs can be used as satisfactory enzyme mimics. Based on these findings, BSA-MnO(2) NPs were used as colorimetric immunoassay tags for the detection of goat anti-human IgG in place of HRP. The colorimetric immunoassay using BSA-MnO(2) NPs has the advantages of being fast, robust, inexpensive, easily prepared and with no HRP and H(2)O(2) being needed. These water-soluble BSA-MnO(2) NPs may have promising potential applications in biotechnology, bioassays, and biomedicine.

  2. Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy

    Science.gov (United States)

    Zhou, Mengying; Zhang, Xulang; Wen, Xinyu; Wu, Taihua; Wang, Weidong; Yang, Mingzhou; Wang, Jing; Fang, Ming; Lin, Bingcheng; Lin, Hongli

    2016-01-01

    Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a “glomerulus-on-a-chip” (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease. PMID:27558173

  3. Smells like aphids: orchid flowers mimic aphid alarm pheromones to attract hoverflies for pollination.

    Science.gov (United States)

    Stökl, Johannes; Brodmann, Jennifer; Dafni, Amots; Ayasse, Manfred; Hansson, Bill S

    2011-04-22

    Most insects are dependent on chemical communication for activities such as mate finding or host location. Several plants, and especially orchids, mimic insect semiochemicals to attract insects for unrewarded pollination. Here, we present a new case of pheromone mimicry found in the terrestrial orchid Epipactis veratrifolia. Flowers are visited and pollinated by several species of aphidophagous hoverflies, the females of which also often lay eggs in the flowers. The oviposition behaviour of these hoverflies is mainly guided by aphid-derived kairomones. We show that the flowers produce α- and β-pinene, β-myrcene and β-phellandrene, and that these compounds attract and induce oviposition behaviour in female hoverflies. This floral odour profile is remarkably similar to the alarm pheromone released by several aphid species, such as Megoura viciae. We therefore suggest that E. veratrifolia mimics aphid alarm pheromones to attract hoverflies for pollination; this is the first time, to our knowledge, that such a case of mimicry has been demonstrated.

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

    Science.gov (United States)

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

    2013-04-30

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

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

    Science.gov (United States)

    Schoonen, Lise; van Hest, Jan C M

    2016-02-10

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

  6. Synthesis of Oxylipin Mimics and Their Antifungal Activity against the Citrus Postharvest Pathogens

    Directory of Open Access Journals (Sweden)

    Jimei Ma

    2016-02-01

    Full Text Available Nine oxylipin mimics were designed and synthesized starting from d-mannose. Their antifungal activity against three citrus postharvest pathogens was evaluated by spore germination assay. The results indicated that all the compounds significantly inhibited the growth of Penicillium digitatum, Penicillium italicum and Aspergillus niger. The compound (3Z,6Z,8S,9R,10R-octadeca-3,6-diene-8,9,10-triol (3 exhibited excellent inhibitory effect on both Penicillium digitatum (IC50 = 34 ppm and Penicillium italicum (IC50 = 94 ppm. Their in vivo antifungal activities against citrus postharvest blue mold were tested with fruit inoculated with the pathogen Penicillium italicum. The compound (3R,4S-methyl 3,4-dihydroxy-5-octyltetrahydrofuran-2-carboxylate (9 demonstrated significant efficacy by reducing the disease severity to 60%. The antifungal mechanism of these oxylipin mimics was postulated in which both inhibition of pathogenic mycelium and stimuli of the host oxylipin-mediated defense response played important roles.

  7. Comprehending body language and mimics: an ERP and neuroimaging study on Italian actors and viewers.

    Science.gov (United States)

    Proverbio, Alice Mado; Calbi, Marta; Manfredi, Mirella; Zani, Alberto

    2014-01-01

    In this study, the neural mechanism subserving the ability to understand people's emotional and mental states by observing their body language (facial expression, body posture and mimics) was investigated in healthy volunteers. ERPs were recorded in 30 Italian University students while they evaluated 280 pictures of highly ecological displays of emotional body language that were acted out by 8 male and female Italian actors. Pictures were briefly flashed and preceded by short verbal descriptions (e.g., "What a bore!") that were incongruent half of the time (e.g., a picture of a very attentive and concentrated person shown after the previous example verbal description). ERP data and source reconstruction indicated that the first recognition of incongruent body language occurred 300 ms post-stimulus. swLORETA performed on the N400 identified the strongest generators of this effect in the right rectal gyrus (BA11) of the ventromedial orbitofrontal cortex, the bilateral uncus (limbic system) and the cingulate cortex, the cortical areas devoted to face and body processing (STS, FFA EBA) and the premotor cortex (BA6), which is involved in action understanding. These results indicate that face and body mimics undergo a prioritized processing that is mostly represented in the affective brain and is rapidly compared with verbal information. This process is likely able to regulate social interactions by providing on-line information about the sincerity and trustfulness of others.

  8. Lanolin-derived lipid mixtures mimic closely the lipid composition and organization of vernix caseosa lipids.

    Science.gov (United States)

    Rissmann, Robert; Oudshoorn, Marion H M; Kocks, Elise; Hennink, Wim E; Ponec, Maria; Bouwstra, Joke A

    2008-10-01

    The aim of the present study was to use semi-synthetic lipid mixtures to mimic the complex lipid composition, organization and thermotropic behaviour of vernix caseosa (VC) lipids. As VC shows multiple protecting and barrier supporting properties before and after birth, it is suggested that a VC substitute could be an innovative barrier cream for barrier deficient skin. Lanolin was selected as the source of the branched chain sterol esters and wax esters--the main lipid classes of VC. Different lipid fractions were isolated from lanolin and subsequently mixed with squalene, triglycerides, cholesterol, ceramides and fatty acids to generate semi-synthetic lipid mixtures that mimic the lipid composition of VC, as established by high-performance thin-layer chromatography. Differential scanning calorimetry and Fourier transform infrared spectroscopy investigations revealed that triglycerides play an important role in the (lateral) lipid organization and thermotropic behaviour of the synthetic lipid mixtures. Excellent resemblance of VC lipids was obtained when adding unsaturated triglycerides. Moreover, these lipid mixtures showed similar long range ordering as VC. The optimal lipid mixture was evaluated on tape-stripped hairless mouse skin in vivo. The rate of barrier recovery was increased and comparable to VC lipid treatment.

  9. Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics

    Science.gov (United States)

    Maas, Sybren L.N.; de Vrij, Jeroen; van der Vlist, Els J.; Geragousian, Biaina; van Bloois, Louis; Mastrobattista, Enrico; Schiffelers, Raymond M.; Wauben, Marca H.M.; Broekman, Marike L.D.; Nolte-'t Hoen, Esther N.M.

    2015-01-01

    Nano-sized extracelullar vesicles (EVs) released by various cell types play important roles in a plethora of (patho)physiological processes and are increasingly recognized as biomarkers for disease. In addition, engineered EV and EV-inspired liposomes hold great potential as drug delivery systems. Major technologies developed for high-throughput analysis of individual EV include nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (tRPS) and high-resolution flow cytometry (hFC). Currently, there is a need for comparative studies on the available technologies to improve standardization of vesicle analysis in diagnostic or therapeutic settings. We investigated the possibilities, limitations and comparability of NTA, tRPS and hFC for analysis of tumor cell-derived EVs and synthetic mimics (i.e. differently sized liposomes). NTA and tRPS instrument settings were identified that significantly affected the quantification of these particles. Furthermore, we detailed the differences in absolute quantification of EVs and liposomes using the three technologies. This study increases our understanding of possibilities and pitfalls of NTA, tRPS and hFC, which will benefit standardized and large-scale clinical application of (engineered) EVs and EV-mimics in the future. PMID:25555362

  10. Smells like aphids: orchid flowers mimic aphid alarm pheromones to attract hoverflies for pollination

    Science.gov (United States)

    Stökl, Johannes; Brodmann, Jennifer; Dafni, Amots; Ayasse, Manfred; Hansson, Bill S.

    2011-01-01

    Most insects are dependent on chemical communication for activities such as mate finding or host location. Several plants, and especially orchids, mimic insect semiochemicals to attract insects for unrewarded pollination. Here, we present a new case of pheromone mimicry found in the terrestrial orchid Epipactis veratrifolia. Flowers are visited and pollinated by several species of aphidophagous hoverflies, the females of which also often lay eggs in the flowers. The oviposition behaviour of these hoverflies is mainly guided by aphid-derived kairomones. We show that the flowers produce α- and β-pinene, β-myrcene and β-phellandrene, and that these compounds attract and induce oviposition behaviour in female hoverflies. This floral odour profile is remarkably similar to the alarm pheromone released by several aphid species, such as Megoura viciae. We therefore suggest that E. veratrifolia mimics aphid alarm pheromones to attract hoverflies for pollination; this is the first time, to our knowledge, that such a case of mimicry has been demonstrated. PMID:20943694

  11. Molybdate partly mimics insulin-promoted metabolic effects in Drosophila melanogaster.

    Science.gov (United States)

    Rovenko, Bohdana M; Perkhulyn, Natalia V; Lushchak, Oleh V; Storey, Janet M; Storey, Kenneth B; Lushchak, Volodymyr I

    2014-09-01

    Molybdenum-containing salts have been found to attenuate diabetes complications in mammals by affecting processes normally regulated by insulin and thus were believed to mimic insulin activity. In this study, we used a fruit fly model to test sodium molybdate, Na2MoO4, action in relation to insulin-promoted processes and toxicity. We studied how larval food supplementation with sodium molybdate affected levels of body carbohydrates and lipids in two-day old adult Drosophila melanogaster. Molybdate salt, in the concentrations used (0.025, 0.05, 0.5, 5, and 10mM), showed low toxicity to fly larvae and slightly influenced development and the percentage of pupated animals. Additionally, sodium molybdate decreased the level of hemolymph glucose in males by 30%, and increased the level of hemolymph trehalose in flies of both sexes. These changes were accompanied by an increase in whole body trehalose and glycogen of about 30-90%. Although total lipid levels in flies of both sexes were depleted by 25%, an increased amount of triacylglycerides among total lipids was observed. These effects were not related to changes in food intake. Taken together, the present data let us suggest that sodium molybdate may at least partly mimic insulin-related effects in Drosophila.

  12. Polymer Brushes that Mimic Repulsive Properties of the Boundary Lubricant Glycoprotein Lubricin

    Science.gov (United States)

    Torres, Jahn; Jay, Gregory; Ni, Qian; Bello, David; Bothun, Geoffrey; Kim, Kyung-Suk

    2011-03-01

    This is a report on the design of tailored functional groups which mimic the repulsive forces at work in the natural-joint boundary lubricant known as lubricin. Lubricin, an amphiphilic polyelectrolyte biomolecule, decreases friction and cellular adhesion by exhibiting surface force fields based on steric hindrance, Debye electrostatic double layer repulsion and hydration repulsive forces. We have identified a physically and chemically stable candidate polymers for anti-fouling coatings that will mimic lubricin's repulsive properties. Synthetic polymer brushes mimicking lubricin have been produced using these polymers grafted onto a glass surfaces. The average adhesive forces for the polymer brushes measured through atomic force microscopy are as low (56.796 +/- 0.796 mN/m), similar to those exhibited by lubricin coated surfaces and on the same order of magnitude as superhydrophobic surfaces. This work was supported by the Coatings/Biofouling Program and the Maritime Sensing Program of the Office of Naval Research as well as the ILIR Program of the Naval Undersea Warfare Center DIVNPT.

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

    Science.gov (United States)

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

    2017-07-01

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

  14. MicroRNA-125b-5p mimic inhibits acute liver failure

    Science.gov (United States)

    Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P.; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep

    2016-01-01

    The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF. PMID:27336362

  15. Construction and Expression of a Single Chain Antibody Mimicing Human Ovarian Cancer Antigen CA125

    Institute of Scientific and Technical Information of China (English)

    Aidong Li; Zheng Li; Yinghong Wang; Yongming Zhang; Jie Ma

    2006-01-01

    One concept for immune therapy of cancer involves induction of antigen mimic antibodies to trigger the immune response against tumor cells. Anti-idiotypic antibodies directed against the antigen-binding site of antibodies specific for tumor antigen may functionally and even structurally mimic antigen and induce anti-anti-idiotypic immune response. Monoclonal antibody WJ02 is one of such anti-idiotypic antibodies, which contains internal image of CA125. In order to improve the immunospecificity of mAb WJ02, we constructed a single chain of mAb WJ02 in Vl-linker-Vh orientation. The scFv-WJ02 could be expressed and secreted in the recombinant Pichia pastoris system. The secreted scFv protein with a molecular weight of 30 kD retained the biological activity of mAb WJ02, which was proved by a direct binding assay and inhibition experiment. Our results indicated that the scFv-WJ02 could be used as a possible tool for idiotypic therapy against ovarian cancer, which might enhance the possibility of eliminating nonspecific responses induced by mAb WJ02.

  16. Regioselective deiodination of iodothyronamines, endogenous thyroid hormone derivatives, by deiodinase mimics.

    Science.gov (United States)

    Mondal, Santanu; Mugesh, Govindasamy

    2014-08-25

    Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an important role in the activation and inactivation£ of thyroid hormones. It is known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid hormones, act as substrates for deiodinases. To understand whether decarboxylation alters the rate and/or regioselectivity of deiodination by using synthetic deiodinase mimics, we studied the deiodination of different iodothyronamines. The triiodo derivative 3,3',5-triiodothyronamine (T3 AM) is deiodinated at the inner ring by naphthyl-based deiodinase mimics, which is similar to the deiodination of 3,3',5-triiodothyronine (T3). However, T3 AM undergoes much slower deiodination than T3. Detailed experimental and theoretical investigations suggest that T3 AM forms a weaker halogen bond with selenium donors than T3. Kinetic studies and single-crystal X-ray structures of T3 and T3 AM reveal that intermolecular I⋅⋅⋅I interactions may play an important role in deiodination. The formation of hydrogen- and halogen-bonding assemblies, which leads to the formation of a dimeric species of T3 in solution, facilitates the interactions between the selenium and iodine atoms. In contrast, T3 AM, which does not have I⋅⋅⋅I interactions, undergoes much slower deiodination. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. De novo designed protein transduction domain mimics from simple synthetic polymers.

    Science.gov (United States)

    Tezgel, A Özgül; Telfer, Janice C; Tew, Gregory N

    2011-08-08

    Protein transduction domains (PTDs) that readily transverse cellular membranes are of great interest and are attractive tools for the intracellular delivery of bioactive molecules. Learning to program synthetic polymers and oligomers with the appropriate chemical information to capture adequately the biological activity of proteins is critical to our improved understanding of how these natural molecules work. In addition, the versatility of these synthetic mimics provides the opportunity to discover analogs with superior properties compared with their native sequences. Here we report the first detailed structure-activity relationship of a new PTD family of polymers based on a completely abiotic backbone. The synthetic approach easily allows doubling the density of guanidine functional groups, which increases the transduction efficiency of the sequences. Cellular uptake studies on three different cell lines (HEK 293T, CHO, and Jurkat T cells) confirm that these synthetic analogs are highly efficient novel protein transduction domain mimics (PTDMs), which are more effective than TAT(49-57) and nonaarginine (R9) and also highlight the usefulness of polymer chemistry at the chemistry-biology interface.

  18. Decidualized endometrioma during pregnancy: recognizing an imaging mimic of ovarian malignancy.

    Science.gov (United States)

    Poder, Liina; Coakley, Fergus V; Rabban, Joseph T; Goldstein, Ruth B; Aziz, Seerat; Chen, Lee-may

    2008-01-01

    To present the ultrasound and magnetic resonance imaging findings that may allow for a prospective diagnosis and expectant management of decidualized endometriomas because the rare occurrence of decidualization in the ectopic endometrial stroma of an endometrioma during pregnancy can mimic ovarian cancer at imaging. Smooth lobulated mural nodules with prominent internal vascularity were noted in an apparent right ovarian endometrioma on serial ultrasound studies in a 34-year-old woman at 12, 21, 27, and 30 weeks of gestation. Magnetic resonance imaging demonstrated the nodules to be strikingly similar in intensity and texture to the decidualized endometrium in the uterus on T2-weighted sequences. A provisional diagnosis of decidualized endometrioma allowed for expectant management with immediate postpartum resection and confirmation of the diagnosis. Decidualized endometrioma can mimic ovarian malignancy during pregnancy, but a prospective diagnosis may be possible when solid smoothly lobulated nodules with prominent internal vascularity within an endometrioma are seen from early in pregnancy, and the nodules demonstrate marked similarity in signal intensity and texture with the decidualized endometrium in the uterus at magnetic resonance imaging.

  19. Micro-fabricated shunt to mimic arachnoid granulations for the treatment of communicating hydrocephalus.

    Science.gov (United States)

    Kralick, Francis; Oh, Jonghyun; Medina, Tim; Noh, Hongseok Moses

    2012-01-01

    Hydrocephalus is the abnormal accumulation of cerebrospinal fluid (CSF) within the confines of the skull that if left untreated results in significant morbidity and mortality. The treatment for hydrocephalus has remained essentially unchanged for over 50 years. It was a technological advance in materials that allowed John Holter, in conjunction with neurosurgeons Spitzer and Nulsen, to devise a valve and shunt system that diverted excess CSF from the ventricular space to the peritoneum. This ventriculo-peritoneal (VP) shunt is far from ideal, with problems associated with under/over shunting, mechanical mismatch, infection, high failure rates, disconnection and erosion. With the advances in the field of micro-fabrication and micro-machines we propose an innovative shunt system that would mimic the function of arachnoid granulations. This micro-fabricated shunting device, or micro-mechanical arachnoid granulation (MAG), consists of a multiplicity of micro-valves each 210 μm in diameter that each adhere to individual micro-needles. This work demonstrates the design and initial test results of the micro-valve with parameters for low cracking pressure, optimal flow rate, and reflux that would mimic the function of the native arachnoid granulations.

  20. Synthesis and biological activity of conformationally restricted gypsy moth pheromone mimics.

    Science.gov (United States)

    Chen, Hao; Gong, Yongmei; Gries, Regine M; Plettner, Erika

    2010-04-15

    The design and synthesis of a series of conformationally constrained mimics of gypsy moth sex pheromone, (+)-disparlure (7R,8S)-2-methyl-7,8-epoxyoctadecane, are described. The core structure of the mimics is derived from 5-(2'-hydroxyethyl)cyclopent-2-en-1-ol. Substituent optimization of the analogs was accomplished through the synthesis of mini-libraries and pure individual compounds, followed by electrophysiological experiments with male gypsy moth antennae. The electroantennogram results show that the analogs elicited weak to no antennal responses themselves. There was a clear structure-activity pattern for odorant activity, with ethyl substituents being best. Further, when puffed simultaneously with the pheromone, some of the compounds gave a significant enhancement of the antennal depolarization, indicating an additive or synergistic effect. A pure pheromone stimulus following a mixed compound/pheromone stimulus was generally not affected, with two exceptions: one compound enhanced and another inhibited a subsequent stimulus. The compounds also prolonged the stimulation of the antenna, which manifested itself in widened electroantennogram peaks. We tested the hypothesis that this prolonged stimulation may be due to the stabilization of a particular conformer of the pheromone-binding protein (PBP). Compounds that caused PBP2 to adopt a similar conformation than in the presence of pheromone also caused peak widening. This was not the case with PBP1.

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

    Science.gov (United States)

    Miras, A D; le Roux, C W

    2014-03-01

    The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal-jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A 'medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals.

  2. Short exposure of albumin to high concentrations of malondialdehyde does not mimic physiological conditions.

    Science.gov (United States)

    Millanta, Susanna; Furfaro, Anna Lisa; Carlier, Paolo; Tasso, Bruno; Nitti, Mariapaola; Domenicotti, Cinzia; Odetti, Patrizio; Pronzato, Maria Adelaide; Traverso, Nicola

    2013-02-01

    Malondialdehyde (MDA), a major lipid peroxidation product, spontaneously binds to, and modifies proteins. In vivo, proteins are physiologically exposed to micromolar MDA concentrations for long periods. In order to mimic this process in vitro, protein modification is often performed by short exposure to millimolar MDA concentrations, also in order to generate antigenic structures for antibody production. However, in our study, spectrophotometric and fluorimetric characteristics, electrophoretic migration, susceptibility to trypsin digestion and reactivity to antibodies indicated substantial differences between albumin incubated with millimolar MDA concentrations for a short period of time and albumin incubated with micromolar MDA concentrations for a long period of time. Therefore, our study showed that short incubation of albumin with millimolar MDA concentrations does not mimic the consequences of albumin exposure to long incubation with micromolar MDA concentrations. This casts doubts on the real possibility that antibodies, elicited with proteins modified with millimolar MDA concentrations for a short period, could detect all MDA-modified proteins in vivo. Moreover, natural antibodies against albumin, modified with micromolar MDA concentrations, have been detected in the serum of healthy blood donors, which appears to justify the existence of these kinds of modified proteins in vivo.

  3. Pancreatic and peri-pancreatic lesions mimic pancreatic islet cell tumor in multidetector computed tomography

    Institute of Scientific and Technical Information of China (English)

    XUE Hua-dan; LIU Wei; XIAO Yu; SUN Hao; WANG Xuan; LEI Jing; JIN Zheng-yu

    2011-01-01

    Objective This pictorial review aimed to summarize the most possible differential diagnosis of pancreatic islet cell tumor (PICT).Data sources Data used in this review were mainly from Medline and Pubmed in English. And all clinical images in this review were from Department of Radiology, Peking Union Medical College Hospital, Beijing, China.Study selection Cases of pancreatic cystadenoma, solid pseudo-papillary tumor of the pancreas, pancreatic metastasis, pancreatic adenocarcinoma, para-pancreatic neuroendocrine tumors, Castleman disease, gastrointestinal stromal tumor, splenic artery aneurysm and accessory spleen were selected in this pictorial review for differential diagnosis of PICT.Results Careful analysis of imaging features and correlation with the clinical manifestations may allow a more specific diagnosis. It is also important that the radiologist is familiar with the anatomic variants and disease entities which mimic pancreatic islet cell tumor in order to avoid an improper treatment protocol.Conclusions Many congenital anatomic variants or other pancreatic and peri-pancreatic diseases may mimic MDCT appearance of pancreatic islet cell tumor. Radiological, clinical and pathological characteristics should be considered for the final diagnosis.

  4. Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups.

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    Stefania Piersanti

    Full Text Available Brain gene transfer using viral vectors will likely become a therapeutic option for several disorders. Helper-dependent (HD canine adenovirus type 2 vectors (CAV-2 are well suited for this goal. These vectors are poorly immunogenic, efficiently transduce neurons, are retrogradely transported to afferent structures in the brain and lead to long-term transgene expression. CAV-2 vectors are being exploited to unravel behavior, cognition, neural networks, axonal transport and therapy for orphan diseases. With the goal of better understanding and characterizing HD-CAV-2 for brain therapy, we analyzed the transcriptomic modulation induced by HD-CAV-2 in human differentiated neurospheres derived from midbrain progenitors. This 3D model system mimics several aspects of the dynamic nature of human brain. We found that differentiated neurospheres are readily transduced by HD-CAV-2 and that transduction generates two main transcriptional responses: a DNA damage response and alteration of centromeric and microtubule probes. Future investigations on the biochemistry of processes highlighted by probe modulations will help defining the implication of HD-CAV-2 and CAR receptor binding in enchaining these functional pathways. We suggest here that the modulation of DNA damage genes is related to viral DNA, while the alteration of centromeric and microtubule probes is possibly enchained by the interaction of the HD-CAV-2 fibre with CAR.

  5. HISTORICAL ASPECTS OF PHALLOPLASTY

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    P. S. Kyzlasov

    2017-01-01

    Full Text Available Reconstruction of the penis in transgender operations, amputation of the penis, congenital deformities and anomalies of the penis was and remains today an important issue in plastic surgery of the urogenital region. The only method to restore the penis is phalloplasty. In general, over the past decades, generations of clinicians have different ways and flaps for total fallouretheral reconstruction. Thus was formulated the characteristics of an ideal flap for the formation of neophallos, which should be safe, sensitive, without hair, and with long leg. However, despite the fact that the characteristics of a perfect flap, nowadays there is no “gold standard” in the formation of neophallos, as phalloplasty is a fairly complicated surgery, and the choice of method depends on many factors. The choice of methodology is determined by the plastics surgeon and to each patient is individual, depends on the etiology of the disease and the possibility of choosing the form of the donor’s transplant. This article presents a literature review devoted to the historical aspects of phalloplasty. In the article, in chronological order reflected the evolution of the different forming methods neofallos, phallourethrоplasty, describes their advantages and disadvantages.

  6. Cultural aspects of suicide.

    Science.gov (United States)

    Maharajh, Hari D; Abdool, Petal S

    2005-09-08

    Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.

  7. [Psychosocial aspects of halitosis].

    Science.gov (United States)

    de Jongh, A; de Baat, C; Horstman, M

    2012-09-01

    Using a representative sample from the Dutch population, some psychosocial aspects of halitosis were examined. The results of the survey showed that almost 90% of the Dutch population aged 16 years and older were regularly faced with halitosis. Forty percent reported to be exposed to someone with halitosis at least once a week, men significantly more frequently than women. Although less strongly than body odour, halitosis was reported as being one of the most severe 'let-downs' in social interactions. The greater the social distance between subjects, the less likely is the chance that a person's attention will be drawn to halitosis experienced. When it comes to an unknown person, the chance was no more than 7%, suggesting that it is problematic to draw a person's attention to the presence of halitosis. Considering the potential social consequences of halitosis is it important that dentists and dental hygienists draw patients' attention to the presence of halitosis, when this is the case, thereby encouraging them to seek adequate treatment.

  8. Hydrodynamic aspect of caves

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    Franci Gabrovsek

    2008-01-01

    Full Text Available From a hydrological point of view, active caves are a series of connected conduits which drain water through an aquifer. Water tends to choose the easiest way through the system but different geological and morphological barriers act as flow restrictions. The number and characteristics of restrictions depends on the particular speleogenetic environment, which is a function of geological, geomorphological, climatological and hydrological settings. Such a variety and heterogeneity of underground systems has presented a challenge for human understanding for many centuries. Access to many underground passages, theoretical knowledge and recent methods (modeling, water pressure-resistant dataloggers, precise sensors etc. give us the opportunity to get better insight into the hydrodynamic aspect of caves. In our work we tried to approach underground hydrodynamics from both theoretical and practical points of view. We present some theoretical background of open surface and pressurized flow in underground rivers and present results of some possible scenarios. Moreover, two case studies from the Ljubljanica river basin are presented in more detail: the cave system between Planinsko polje and Ljubljansko barje, and the cave system between Bloško polje and Cerkniško polje. The approach and methodology in each case is somewhat different, as the aims were different at the beginning of exploration. However, they both deal with temporal and spatial hydrodynamics of underground waters. In the case of Bloško polje-Cerkniško polje system we also explain the feedback loop between hydrodynamics and Holocene speleogenesis.

  9. Psychiatric Aspects of Infertility

    Directory of Open Access Journals (Sweden)

    Hacer Sezgin

    2014-06-01

    Full Text Available Infertility can be defined as a crisis with cultural, religious, and class related aspects, which coexists with medical, psychiatric, psychological, and social problems. Relation between psychiatric and psychological factors stem from a mutual interaction of both. Family is an important institution in maintaining human existence and raising individuals in line with society's expectations. Fertility and reproduction are seen as universal functions unique to women with raising children as the expected result of the family institution. Incidence of infertility has increased recently and can become a life crisis for a couple. Even though not being able to have a child affects both sexes emotionally, women feel greater amounts of stress, pressure, anxiety, and depression.Consequences of infertility arise from short and long-term devastating effects on both individual's physical and mental health, and marital system. Many studies focus on infertility related psychological and psychiatric disorders (depression, anxiety, grief, marital conflict, gender differences, relation between the causes of infertility and psychopathology, the effects of psychiatric evaluation and intervention -when necessaryon the course of infertility treatment, pregnancy rates, and childbirth. The most important underlying causes of high levels of stress and anxiety that infertile women experience are the loss of maternity, reproduction, sense of self, and genetic continuity. In this review article is to investigate the relationship between medically unexplained symptoms and psychiatric symptoms. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 165-185

  10. Strategic Aspects of Communication

    Science.gov (United States)

    Hagen, Edward; Hammerstein, Peter; Hess, Nicole

    Rarely do human behavioral scientists and scholars study language, music, and other forms of communication as strategies—a means to some end. Some even deny that communication is the primary function of these phenomena. Here we draw upon selections of our earlier work to briefly define the strategy concept and sketch how decision theory, developed to explain the behavior of rational actors, is applied to evolved agents. Communication can then be interpreted as a strategy that advances the "fitness interests" of such agents. When this perspective is applied to agents with conflicts of interest, deception emerges as an important aspect of communication. We briefly review costly signaling, one solution to the problem of honest communication among agents with conflicts of interest. We also explore the subversion of cooperative signals by parasites and by plants defending themselves against herbivores, and we touch on biases in human gossip. Experiments with artificial embodied and communicating agents confirm that when there are conflicts of interest among agents, deception readily evolves. Finally, we consider signaling among super-organisms and the possible implications for understanding human music and language.

  11. Gastric cancer: basic aspects.

    Science.gov (United States)

    Resende, Carlos; Thiel, Alexandra; Machado, José C; Ristimäki, Ari

    2011-09-01

    Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. In the last years, molecular oncobiology studies brought to light a number of genes that are implicated in gastric carcinogenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variants of the genes IL-10, IL-17, MUC1, MUC6, DNMT3B, SMAD4, and SERPINE1 have been reported to modify the risk of developing GC. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation (GSK3β, CD133, DSC2, P-Cadherin, CDH17, CD168, CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through tumor suppressor gene inactivation mechanisms (TFF1, PDX1, BCL2L10, XRCC, psiTPTE-HERV, HAI-2, GRIK2, and RUNX3). It also addressed the role of the inflammatory mediator cyclooxygenase-2 (COX-2) in the process of gastric carcinogenesis and its importance as a potential molecular target for therapy.

  12. Gestational surrogacy: Psychosocial aspects

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    Nicolás Ruiz-Robledillo

    2016-12-01

    Full Text Available Innovation in assisted reproductive technologies together with increased infertility and new family structures are increasing the use of gestational surrogacy as a means to have children. Before, during and after the process, it is necessary to study the psychosocial characteristics of triad members: the gestational surrogate, intended parents, and offspring. Research has indicated positive adaptation to the process and benefits for all members of the triad. Altruism is the main motivation of surrogates. Notably, psychological well-being has been found to be higher in individuals who have become parents through surrogacy than in those who have used egg donation or have followed a natural process of conception. Moreover, no differences in psychosocial characteristics have been observed in the offspring, compared with children born through natural conception or egg donation. Results highlight the positive aspects of surrogacy. Future research should investigate psychosocial factors that modulate the process, acting as risk and protective factors for well-being of the triad members, and identify the optimal profiles of surrogates for the process to be a success.

  13. INTERPERSONAL COMMUNICATION: PSYCHOLINGUISTIC ASPECT

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    Mitrofanova, I.I.

    2016-09-01

    Full Text Available The article considers language as the organization of the speech of any person in any situation, without which it is impossible to characterize the internal structure of the speech stream. Language is exactly a system of guidelines necessary for the activity in the social world. Communication is primarily nothing but as a way of making one or another correction in the image of the interlocutor’s world. In order for a language to serve as a means of communication, it must have a single or a similar understanding of reality behind it. Conversely, the unity of understanding the reality and the unity of coherence presuppose the possibility of adequate communication. A mandatory component of communication is the communicative act, that is, the act of sharing information between people. The speech, i.e. the natural sound language is an important means of conveying information that defines this aspect of the communication process as verbal communication. The idea of dialogue as the space, in which the exchange of information takes place, is defined as initial. Essentially, it is the dialogue that in this case acts as the backbone principle in dealing with problems of language. It is here that the essence of social and psychological transition to the analysis of communication is most visibly concentrated. An individual essentially "lives" in the world of Another person’s worlds, and studying the words of this person, he or she studies the "world" of Another person. Thus, the dialogue is not merely the interaction (verbal with another person, but, ultimately, the interaction with the world of culture.

  14. Computational Aspects of Equilibria

    Science.gov (United States)

    Yannakakis, Mihalis

    Equilibria play a central role in game theory and economics. They characterize the possible outcomes in the interaction of rational, optimizing agents: In a game between rational players that want to optimize their payoffs, the only solutions in which no player has any incentive to switch his strategy are the Nash equilibria. Price equilibria in markets give the prices that allow the market to clear (demand matches supply) while the traders optimize their preferences (utilities). Fundamental theorems of Nash [34] and Arrow-Debreu [2] established the existence of the respective equilibria (under suitable conditions in the market case). The proofs in both cases use a fixed point theorem (relying ultimately on a compactness argument), and are non-constructive, i.e., do not yield an algorithm for constructing an equilibrium. We would clearly like to compute these predicted outcomes. This has led to extensive research since the 60’s in the game theory and mathematical economics literature, with the development of several methods for computation of equilibria, and more generally fixed points. More recently, equilibria problems have been studied intensively in the computer science community, from the point of view of modern computation theory. While we still do not know definitely whether equilibria can be computed in general efficiently or not, these investigations have led to a better understanding of the computational complexity of equilibria, the various issues involved, and the relationship with other open problems in computation. In this talk we will discuss some of these aspects and our current understanding of the relevant problems. We outline below the main points and explain some of the related issues.

  15. Cultural Aspects of Suicide

    Directory of Open Access Journals (Sweden)

    Hari D. Maharajh

    2005-01-01

    Full Text Available Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.

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

    Directory of Open Access Journals (Sweden)

    P. Natteru

    2016-01-01

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

  17. Review of Breast Cancers That Can Mimic a Cystic Component: Ultrasonographic and Pathologic Correlations

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yun Woo; Kwon, Kui Hyang; Choi, Deuk Lin; Lee, Dong Wha [Dept. of Radiology, (Korea, Republic of); Kim, Kyung Whan [Dept. of Radiology, Soonchunhyang Cheonan Hospital, Cheonan (Korea, Republic of); Yang, Seung Bo [Dept. of Radiology, Soonchunhyang Gumi Hospital, Gumi (Korea, Republic of)

    2011-05-15

    We illustrate the sonographic findings of malignant breast masses that can mimic a cystic component with pathologic correlations. The disease entities presented in this study include infiltrating ductal carcinoma, ductal carcinoma in situ (DCIS), papillary carcinoma, mucinous carcinoma, medullary carcinoma, metaplastic carcinoma, and a malignant phyllodes tumor. Malignant masses with a cystic component are often characterized by well-circumscribed round, oval, or lobular masses, thereby appearing benign on ultrasonography. On pathology, the cystic component of a malignant mass is identified by cystic degeneration, hemorrhage, necrosis, or ductal dilatation. If the mass is well-circumscribed with a cystic component, a biopsy should be considered in the analysis of the solid component within a mass.

  18. Differential Diagnoses of Restless Legs Syndrome/Willis-Ekbom Disease: Mimics and Comorbidities.

    Science.gov (United States)

    Chokroverty, Sudhansu

    2015-09-01

    Restless legs syndrome (RLS) mimics cannot always be differentiated from RLS/Willis-Ekbom disease (WED) based on 4 essential criteria; hence, a fifth criterion has recently been established. RLS comorbidities may provide us important clues for understanding the neurobiology of RLS/WED. Iron-dopamine connection, hypoxia pathway activation, and dopamine-opioid interaction are important pathophysiological mechanisms in RLS; this knowledge is derived from our understanding of RLS associations with a variety of medical, neurologic, and other conditions. Clinicians must formulate an RLS differential diagnosis based on history and physical examination, but laboratory tests may sometimes be needed to arrive at a correct diagnosis. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2013-03-01

    Magnetic resonance (MR) arthrography is currently the gold standard radiological investigation for shoulder joint instability. Not only does this investigation allow for identification of important disease processes, but the reduced slice thickness and increased in-plane resolution allowed by the latest imaging sequences also gives excellent demonstration of shoulder joint internal anatomy. This article describes the technique of MR arthrography of the shoulder practiced at our institution, briefly outlining features of the FIESTA (fast imaging employing steady state acquisition) MR sequence employed, including its advantages and limitations. A pictorial review of shoulder MR arthrography performed with this technique is presented, concentrating on normal shoulder joint internal anatomy and anatomical variants that may mimic pathology. Copyright © 2012 Wiley Periodicals, Inc.

  20. Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions

    Science.gov (United States)

    Kubilis, Artur; Abdulkarim, Ali; Eissa, Ahmed M.; Cameron, Neil R.

    2016-08-01

    Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction.

  1. Structural mimics of viruses through peptide/DNA co-assembly.

    Science.gov (United States)

    Ni, Rong; Chau, Ying

    2014-12-31

    A synthetic mimic of viral structure has been constructed by the synergistic co-assembly of a 16-amino acid peptide and plasmid DNA. The rational design of this short peptide, including segments for binding DNA and forming β-sheet, is inspired by viral capsid protein. The resulting nanostructures, which we term nanococoons, appear as ellipsoids of virus-like dimension (65 × 47 nm) and display repeating stripes of ∼4 nm wide. We propose that the co-assembly process involves DNA as a template to assist the organization of peptide strands by electrostatic interaction, while the bilayer β-sheets and their lateral association stabilize the peptide "capsid" and organize the DNA within. The hierarchy affords an extremely stable structure, protecting peptide and DNA against enzymatic digestion. It opens a new and facile avenue to fabricate viral alternatives with diverse functions.

  2. Parry-Romberg syndrome with hemimasticatory spasm in pregnancy; A dystonia mimic

    Directory of Open Access Journals (Sweden)

    Akhila Kumar Panda

    2014-01-01

    Full Text Available Parry-Romberg syndrome (PRS with hemimasticatory spasm (HMS is quite an uncommon overlapping phenomenon which very often mimics jaw closing dystonia. A previously healthy 35-year-old female, during her 5 th month of pregnancy started developing intermittent unilateral painful spasms of jaw while conversation, clinching of teeth, or eating, which led to frequent tongue bites. The spasms were worsened during pregnancy. She used to do certain manoeuvre like sensory tricks in form of touching involved side of the face to relieve the symptoms. Apart from this, she developed progressive hemifacial and hemitongue atrophy. Other medical and neurological examinations were normal. Laboratory investigations as well as neuroimaging were noncontributory. The spasm responded to carbamazepine but hemifacial atrophy persists. To our best knowledge, onset and worsening of this syndrome in pregnancy has not been described earlier which might be correlated either with some hormonal imbalance or some unknown mechanisms.

  3. Extruded highly proliferative benign mucous neck cells: a peculiar histologic mimic of poorly cohesive gastric carcinoma.

    Science.gov (United States)

    Arnason, Thomas; Lauwers, Gregory Y

    2014-10-01

    Histologic mimics of poorly cohesive gastric carcinoma are uncommon but are important for pathologists to recognize. Here we report 2 cases of a novel histologic pattern mimicking poorly cohesive gastric carcinoma. In both cases, light microscopy revealed sheets of discohesive epithelial cells with prominent mitoses that have high proliferative activity, with a Ki67 proliferation index greater than 70%. One case was diagnosed as poorly cohesive carcinoma at an outside hospital and the other was referred in consultation as atypia of undetermined significance. Reexamination of the hematoxylin-eosin slides revealed morphologic clues that these sheets of discohesive cells represent artifactual extrusion of the highly proliferative neck zone from the surrounding benign mucosa. In contrast to poorly cohesive cancer, this artifact lacks all of the following diagnostic features: nuclear atypia, signet ring cell morphology, and intercellular stroma with infiltrating single cells between glands. Eight and 14 months later, both patients remain cancer free. © The Author(s) 2013.

  4. Effects of disc asymmetries on astrometric measurements - Can they mimic planets?

    CERN Document Server

    Kral, Quentin; Kennedy, Grant; Souami, Damya

    2016-01-01

    Astrometry covers a parameter space that cannot be reached by RV or transit methods to detect terrestrial planets on wide orbits. In addition, high accuracy astrometric measurements are necessary to measure the inclination of the planet's orbits. Here we investigate the principles of an artefact of the astrometric approach. Namely, the displacement of the photo-centre due to inhomogeneities in a dust disc around the parent star. Indeed, theory and observations show that circumstellar discs can present strong asymmetries. We model the pseudo-astrometric signal caused by these inhomogeneities, asking whether a dust clump in a disc can mimic the astrometric signal of an Earth-like planet. We show that these inhomogeneities cannot be neglected when using astrometry to find terrestrial planets. We provide the parameter space for which these inhomogeneities can affect the astrometric signals but still not be detected by mid-IR observations. We find that a small cross section of dust corresponding to a cometary mass...

  5. Systemic lupus erythematosis with antiphospholipid antibody syndrome: A mimic of Buerger′s disease

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    Vasugi Zoya

    2006-01-01

    Full Text Available This case report is about a past smoker who presented with history of recurrent ulcers and digital gangrene with claudication pain of the left foot for the past fifteen years. Clinical examination and angiogram showed disease involving the peripheral vessels of lowervlimb. This patient had been labeled as Buerger′s disease 15 years ago based on clinical and demographic profile of the illness. We felt that the progression of the disease despite the patient having stopped smoking 15 years ago along with the presence of elevated inflammatory markers in the blood with proteinuria was not in keeping with the nature of the disease. Furthur evaluation revealed that the patient had systemic lupus erythematosus with antiphospholipid antibody syndrome. This case highlights the need for a careful search for diseases, which can mimic Buerger′s disease in young smokers who present with peripheral vascular disease and who have an atypical clinical presentation or progression.

  6. Nonlinear mechanics of hybrid polymer networks that mimic the complex mechanical environment of cells

    Science.gov (United States)

    Jaspers, Maarten; Vaessen, Sarah L.; van Schayik, Pim; Voerman, Dion; Rowan, Alan E.; Kouwer, Paul H. J.

    2017-05-01

    The mechanical properties of cells and the extracellular environment they reside in are governed by a complex interplay of biopolymers. These biopolymers, which possess a wide range of stiffnesses, self-assemble into fibrous composite networks such as the cytoskeleton and extracellular matrix. They interact with each other both physically and chemically to create a highly responsive and adaptive mechanical environment that stiffens when stressed or strained. Here we show that hybrid networks of a synthetic mimic of biological networks and either stiff, flexible and semi-flexible components, even very low concentrations of these added components, strongly affect the network stiffness and/or its strain-responsive character. The stiffness (persistence length) of the second network, its concentration and the interaction between the components are all parameters that can be used to tune the mechanics of the hybrids. The equivalence of these hybrids with biological composites is striking.

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

    Science.gov (United States)

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

    2016-01-01

    Correlative studies have strongly linked phasic changes in dopamine activity with reward prediction error signaling. But causal evidence that these brief changes in firing actually serve as error signals to drive associative learning is more tenuous. Although there is direct evidence that brief increases can substitute for positive prediction errors, there is no comparable evidence that similarly brief pauses can substitute for negative prediction errors. In the absence of such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide evidence in support of the proposed linkage, showing in a modified Pavlovian over-expectation task that brief pauses in the firing of dopamine neurons in rat ventral tegmental area at the time of reward are sufficient to mimic the effects of endogenous negative prediction errors. These results support the proposal that brief changes in the firing of dopamine neurons serve as full-fledged bidirectional prediction error signals.

  8. Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions.

    Science.gov (United States)

    Kubilis, Artur; Abdulkarim, Ali; Eissa, Ahmed M; Cameron, Neil R

    2016-08-31

    Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction.

  9. Regulated assembly of transcription factors and control of transcription initiation.

    Science.gov (United States)

    Beckett, D

    2001-11-30

    Proteins that function in regulation of transcription initiation are typically homo or hetero-oligomeric. Results of recent biophysical studies of transcription regulators indicate that the assembly of these proteins is often subject to regulation. This regulation of assembly dictates the frequency of transcription initiation via its influence on the affinity of a transcription regulator for DNA and its affect on target site selection. Factors that modulate transcription factor assembly include binding of small molecules, post-translational modification, DNA binding and interactions with other proteins. Here, the results of recent structural and/or thermodynamic studies of a number of transcription regulators that are subject to regulated assembly are reviewed. The accumulated data indicate that this phenomenon is ubiquitous and that mechanisms utilized in eukaryotes and prokaryotes share common features. Copyright 2001 Academic Press.

  10. A Taylor-Made Design of Phenoxyfuranone-Type Strigolactone Mimic

    Directory of Open Access Journals (Sweden)

    Kosuke Fukui

    2017-06-01

    Full Text Available Strigolactones are a class of plant hormones that inhibit axillary bud outgrowth and are released from plant roots to act as a rhizosphere communication signal. The Orobanchaceae parasitic plant Striga hermonthica perceives strigolactone as its germination signal, indicating host presence. After germination, the Striga plant parasitises the host plant and suppresses host growth by draining photosynthetic products, water and other essential nutrients. Because of this way of life, this parasite threatens crop production in sub-Saharan Africa with infestation in crop fields and crop devastation. Crop protection in such areas is among the most concerning problems to be dealt with as immediately as possible. With respect to crop protection from Striga, many strigolactone agonists have been developed and used in research to reveal Striga biology, and have contributed to development of crop protection methods. However, an effective method has yet to be found. In a previous study, we reported debranones as a group of strigolactone mimics that inhibit axillary buds outgrowth with moderate stimulation activity for Striga germination. Debranones would be accessible because they are simply synthesized from commercially available phenols and bromo butenolide. Taking this advantage of debranones for Striga research, we tried to find the debranones stimulating Striga seed germination. To modulate functional selectivity and to enhance germination inducing activity of debranones, we studied structure–activity relationships. We investigated effects of substituent position and functional group on debranone activity and selectivity as a strigolactone mimic. As a result, we improved stimulation activity of debranones for Striga seed germination by chemical modification, and demonstrated the pharmacophore of debranones for selective modulation of distinct strigolactone responses.

  11. Dynamic processes in biological membrane mimics revealed by quasielastic neutron scattering.

    Science.gov (United States)

    Lautner, Lisa; Pluhackova, Kristyna; Barth, Nicolai K H; Seydel, Tilo; Lohstroh, Wiebke; Böckmann, Rainer A; Unruh, Tobias

    2017-08-01

    Neutron scattering is a powerful tool to study relaxation processes in biological membrane mimics in space and time. Combining different inelastic and quasielastic neutron scattering techniques, a large dynamic range can be covered: from atomic to mesoscopic lengths and from femto- to some hundreds of nanoseconds in time. This allows studies on e.g. the diffusion of lipids, the membrane undulation motions, the dispersion of sound waves in membranes as well as the mutual interactions of membrane constituents such as lipids, proteins, and additives. In particular, neutron scattering provides a quite direct experimental approach to the inter-atomic and inter-molecular potentials on length and time scales which are perfectly accessible by molecular dynamics (MD) simulations. Neutron scattering experiments may thus substantially support the further refinement of biomolecular force fields for MD simulations by supplying structural and dynamical information with high spatial and temporal resolution. In turn, MD simulations support the interpretation of neutron scattering data. The combination of both, neutron scattering experiments and MD simulations, yields an unprecedented insight into the molecular interactions governing the structure and dynamics of biological membranes. This review provides an overview of the molecular dynamics in biological membrane mimics as revealed by neutron scattering. It focuses on the latest findings such as the fundamental molecular mechanism of lateral lipid diffusion as well as the influence of additives and proteins on the short-time dynamics of lipids. Special emphasis is placed on the comparison of recent neutron scattering and MD simulation data with respect to molecular membrane dynamics on the pico- to nanosecond time scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    Science.gov (United States)

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Prototyping and Composing Aspect Languages: using an Aspect Interpreter Framework

    NARCIS (Netherlands)

    Havinga, W.K.; Bergmans, Lodewijk; Aksit, Mehmet

    2008-01-01

    Domain specific aspect languages (DSALs) are becoming more popular because they can be designed to represent recurring concerns in a way that is optimized for a specific domain. However, the design and implementation of even a limited domain-specific aspect language can be a tedious job. To address

  14. abc: The AspectBench Compiler for AspectJ

    DEFF Research Database (Denmark)

    Allan, Chris; Avgustinov, Pavel; Christensen, Aske Simon;

    2005-01-01

    abc is an extensible, optimising compiler for AspectJ. It has been designed as a workbench for experimental research in aspect-oriented programming languages and compilers. We outline a programme of research in these areas, and we review how abc can help in achieving those research goals...

  15. IDENTIFICATION OF ASPECTS USING COLOURED PETRINETS AND ASPECT REALIZATION

    Directory of Open Access Journals (Sweden)

    S.SOWMYADEVI

    2013-04-01

    Full Text Available a major impediment to program comprehension, maintenance and resolvability is the existence of crosscutting concerns scattered across different modules tangled with implementations of other concerns. Presence of crosscutting concerns in software systems can lead to bloated and inefficient software systems that are difficult to evolve, hard to analyse, difficult to reuse and costly to maintain. Aspect-oriented programming is a complementary programming technique to the object-oriented programming. It provides tools for managing so called cross-cutting concerns. The concept of aspect orientation with presentation of a method could modulate crosscutting concerns into the single manageable unit called, aspect. This method will solve many problems such as tangling and scattering of code. But the identification and specification of crosscutting concerns and considering it as aspects is not an easy job. The proposed method defines requirements and concerns in the formal form by Petri Nets and named them as requirement nets and concern nets. Concern nets with dependencies which there are between requirement nets, model the final system. The execution of final modelled software system based on Petri Nets and monitoring its transitions, shows crosscutting concerns which are candidate aspects. In this paper, we propose a formal method based on Petri Nets, for the identification of aspect and finding out the most dominant aspect. Then the aspect realization is done by using programming language with some case study.

  16. Molecular Basis for the Recognition of Structurally Distinct Autoinducer Mimics by the Pseudomonas aeruginosa LasR Quorum-Sensing Signaling Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yaozhong; Nair, Satish K.; (UIUC)

    2010-01-12

    The human pathogen Pseudomonas aeruginosa coordinates the expression of virulence factors using quorum sensing, a signaling cascade triggered by the activation of signal receptors by small-molecule autoinducers. These homoserine lactone autoinducers stabilize their cognate receptors and activate their functions as transcription factors. Because quorum sensing regulates the progression of infection and host immune resistance, significant efforts have been devoted toward the identification of small molecules that disrupt this process. Screening efforts have identified a class of triphenyl compounds that are structurally distinct from the homoserine lactone autoinducer, yet interact specifically and potently with LasR receptor to modulate quorum sensing (Muh et al., 2006a). Here we present the high-resolution crystal structures of the ligand binding domain of LasR in complex with the autoinducer N-3-oxo-dodecanoyl homoserine lactone (1.4 {angstrom} resolution), and with the triphenyl mimics TP-1, TP-3, and TP-4 (to between 1.8 {angstrom} and 2.3 {angstrom} resolution). These crystal structures provide a molecular rationale for understanding how chemically distinct compounds can be accommodated by a highly selective receptor, and provide the framework for the development of novel quorum-sensing regulators, utilizing the triphenyl scaffold.

  17. Development and Characterization of a Novel Anti-idiotypic Monoclonal Antibody to Growth Hormone, Which Can Mimic Physiological Functions of Growth Hormone in Primary Porcine Hepatocytes.

    Science.gov (United States)

    Lan, Hai-Nan; Jiang, Hai-Long; Li, Wei; Wu, Tian-Cheng; Hong, Pan; Li, Yu Meng; Zhang, Hui; Cui, Huan-Zhong; Zheng, Xin

    2015-04-01

    B-32 is one of a panel of monoclonal anti-idiotypic antibodies to growth hormone (GH) that we developed. To characterize and identify its potential role as a novel growth hormone receptor (GHR) agonist, we determined that B-32 behaved as a typical Ab2β based on a series of enzyme-linked immunosorbent assay assays. The results of fluorescence-activated cell sorting, indirect immunofluorescence and competitive receptor binding assays demonstrated that B-32 specifically binds to the GHR expressed on target cells. Next, we examined the resulting signal transduction pathways triggered by this antibody in primary porcine hepatocytes. We found that B-32 can activate the GHR and Janus kinase (2)/signal transducers and activators of transcription (JAK2/STAT5) signalling pathways. The phosphorylation kinetics of JAK2/STAT5 induced by either GH or B-32 were analysed in dose-response and time course experiments. In addition, B32 could also stimulate porcine hepatocytes to secrete insulin-like growth factors-1. Our work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.

  18. Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2.

    Science.gov (United States)

    Bretscher, Peter; Egger, Julian; Shamshiev, Abdijapar; Trötzmüller, Martin; Köfeler, Harald; Carreira, Erick M; Kopf, Manfred; Freigang, Stefan

    2015-05-01

    Exposure of biological membranes to reactive oxygen species creates a complex mixture of distinct oxidized phospholipid (OxPL) species, which contribute to the development of chronic inflammatory diseases and metabolic disorders. While the ability of OxPL to modulate biological processes is increasingly recognized, the nature of the biologically active OxPL species and the molecular mechanisms underlying their signaling remain largely unknown. We have employed a combination of mass spectrometry, synthetic chemistry, and immunobiology approaches to characterize the OxPL generated from the abundant phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and investigated their bioactivities and signaling pathways in vitro and in vivo. Our study defines epoxycyclopentenones as potent anti-inflammatory lipid mediators that mimic the signaling of endogenous, pro-resolving prostanoids by activating the transcription factor nuclear factor E2-related factor 2 (Nrf2). Using a library of OxPL variants, we identified a synthetic OxPL derivative, which alleviated endotoxin-induced lung injury and inhibited development of pro-inflammatory T helper (Th) 1 cells. These findings provide a molecular basis for the negative regulation of inflammation by lipid peroxidation products and propose a novel class of highly bioactive compounds for the treatment of inflammatory diseases.

  19. The Enzyme-mimic Activity of Ferric Nano-Core Residing in Ferritin and Its Biosensing Applications

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhiwen; Wu, Hong J.; Zhang, Youyu; Li, Zhaohui; Lin, Yuehe

    2011-11-15

    Ferritins are nano-scale globular protein cages encapsulating a ferric core. They widely exist in animals, plants, and microbes, playing indispensable roles in iron homeostasis. Interestingly, our study clearly demonstrates that ferritin has an enzyme-mimic activity derived from its ferric nano-core, but not the protein cage. Further study revealed that the mimic-enzyme activity of ferritin is more thermally stable and pH-tolerant compared with horseradish peroxidase. Considering the abundance of ferritin in numerous organisms, this finding may indicate a new role of ferritin in antioxidant and detoxification metabolisms. In addition, as a natural protein-caged nanoparticle with an enzyme-mimic activity, ferritin is readily conjugated with biomolecules to construct nano-biosensors, thus holds promising potential for facile and biocompatible labeling for sensitive and robust bioassays in biomedical applications.

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

    Science.gov (United States)

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

    2013-09-15

    Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,β-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    . Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

  2. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

  3. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...

  4. DNA topology and transcription

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions. PMID:24755522

  5. DNA topology and transcription.

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions.

  6. Heroe, Egregio, para contrabaixo e cravo: aspectos didáticos e interpretativos em uma transcrição de uma cantata do repertório colonial brasileiro Heroe, Egregio for double and harpsichord: interpretive and pedagogical aspects in a transcription of a cantata from the Brazilian colonial repertory

    Directory of Open Access Journals (Sweden)

    Fausto Borém

    2008-12-01

    Full Text Available O ainda restrito acesso a partituras e concertos do vasto repertório musical brasileiro dos séculos XVIII e XIX e sua instrumentação estereotipada (quase sempre obras vocais religiosas com acompanhamento orquestral são obstáculos para sua inclusão nos currículos dos cursos de música no país e sua apreciação por um público mais amplo. Uma alternativa para mudar este quadro é a transcrição de obras desse repertório e adaptação de sua instrumentação para grupos de câmara menores, com exclusão até mesmo da voz na sua instrumentação. Essas transcrições podem proporcionar, de maneira mais eficaz, o contato e a experimentação com as assim-chamadas práticas de performance historicamente informadas (Historically Informed Performance ou HIP, seja a partir da adaptação de referências (auditivas e textuais já consolidadas na interpretação do repertório europeu, seja a partir da análise de elementos históricos, formais e possíveis figuras de retórica. No presente trabalho, estas questões são abordadas no Recitativo e Aria da cantata acadêmica Heroe, egregio, douto, peregrino (anônimo, Salvador, 1759 para soprano, dois violinos e baixo contínuo, transcrita para um instrumento de cordas orquestral solista (violino, viola, violoncelo ou contrabaixo e cravo.The still limited access to scores and concerts of the vast Brazilian music repertoire from the eighteenth and nineteenth centuries and its stereotyped instrumentation (almost always sacred vocal music with orchestral accompaniment are obstacles for the inclusion of this repertory in the country's instrumental music curricula and its appreciation by a wider audience. An alternative for this situation is the transcription of works and change of their instrumentation to fit smaller chamber formations, including those without singing. Moreover, these transcriptions could also allow the contact and experimentation with the so-called Historically Informed Performance

  7. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. The post-transcriptional operon...... model (PTO) is used to describe data from an assortment of methods (e.g. RIP-Chip, CLIP-Chip, miRNA profiling, ribosome profiling) that globally address the functionality of mRNA. Several examples of post-transcriptional operons have been documented in the literature and demonstrate the usefulness...

  8. Promoter-mediated transcriptional dynamics.

    Science.gov (United States)

    Zhang, Jiajun; Zhou, Tianshou

    2014-01-21

    Genes in eukaryotic cells are typically regulated by complex promoters containing multiple binding sites for a variety of transcription factors, but how promoter dynamics affect transcriptional dynamics has remained poorly understood. In this study, we analyze gene models at the transcriptional regulation level, which incorporate the complexity of promoter structure (PS) defined as transcriptional exits (i.e., ON states of the promoter) and the transition pattern (described by a matrix consisting of transition rates among promoter activity states). We show that multiple exits of transcription are the essential origin of generating multimodal distributions of mRNA, but promoters with the same transition pattern can lead to multimodality of different modes, depending on the regulation of transcriptional factors. In turn, for similar mRNA distributions in the models, the mean ON or OFF time distributions may exhibit different characteristics, thus providing the supplemental information on PS. In addition, we demonstrate that the transcriptional noise can be characterized by a nonlinear function of mean ON and OFF times. These results not only reveal essential characteristics of promoter-mediated transcriptional dynamics but also provide signatures useful for inferring PS based on characteristics of transcriptional outputs. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Mastering Transcription: Multiplexed Analysis of Transcription Start Site Sequences.

    Science.gov (United States)

    Hochschild, Ann

    2015-12-17

    In this issue of Molecular Cell, Vvedenskaya et al. (2015) describe a high-throughput sequencing-based methodology for the massively parallel analysis of transcription from a high-complexity barcoded template library both in vitro and in vivo, providing a powerful new tool for the study of transcription.

  10. Tense and Aspect in English

    DEFF Research Database (Denmark)

    Davidsen-Nielsen, Niels

    2013-01-01

    In the 1990's the author cooperated with Carl Bache on a grammar of English. It turned out that the views they had previously arrived at individually on tense and aspect could be combined by operating with a fused system involving four ordered choices resulting in sixteen tense-aspect forms...

  11. Aspects of spirituality concerning illness

    NARCIS (Netherlands)

    van Leeuwen, Rene; Tiesinga, Lucas J.; Jochemasen, Henk; Post, Doeke

    2007-01-01

    The spiritual dimension of illness, health and care may be seen as a unique aspect in addition to the physical, mental and social dimension. This contribution describes experiences of patients, nurses and hospital chaplains in relation to the spiritual aspects of being ill. Qualitative research was

  12. Practical aspects of cervical cancer

    NARCIS (Netherlands)

    Tillaart, Sabrina Ada Hendrika Maria van den

    2013-01-01

    The thesis describes studies on practical aspects of cervical cancer, concering surgical considerations, and aspects of tumour behaviour and tumour spread. The thesis comprises studies on: the comparison of nerve-sparing and non-nerve-sparing radical hysterectomy for cervical cancer; a new surgical

  13. Aspects of spirituality concerning illness

    NARCIS (Netherlands)

    van Leeuwen, Rene; Tiesinga, Lucas J.; Jochemasen, Henk; Post, Doeke

    2007-01-01

    The spiritual dimension of illness, health and care may be seen as a unique aspect in addition to the physical, mental and social dimension. This contribution describes experiences of patients, nurses and hospital chaplains in relation to the spiritual aspects of being ill. Qualitative research was

  14. HDAC inhibitors stimulate viral transcription by multiple mechanisms

    Directory of Open Access Journals (Sweden)

    Milavetz Barry

    2008-03-01

    Full Text Available Abstract Background The effects of histone deacetylase inhibitor (HDACi treatment on SV40 transcription and replication were determined by monitoring the levels of early and late expression, the extent of replication, and the percentage of SV40 minichromosomes capable of transcription and replication following treatment with sodium butyrate (NaBu and trichostatin A (TSA. Results The HDACi treatment was found to maximally stimulate early transcription at early times and late transcription at late times through increased numbers of minichromosomes which carry RNA polymerase II (RNAPII transcription complexes and increased occupancy of the transcribing minichromosomes by RNAPII. HDACi treatment also partially relieved the normal down-regulation of early transcription by T-antigen seen later in infection. The increased recruitment of transcribing minichromosomes at late times was correlated to a corresponding reduction in SV40 replication and the percentage of minichromosomes capable of replication. Conclusion These results suggest that histone deacetylation plays a critical role in the regulation of many aspects of an SV40 lytic infection.

  15. Transcriptional and post-transcriptional profile of human chromosome 21.

    Science.gov (United States)

    Nikolaev, Sergey I; Deutsch, Samuel; Genolet, Raphael; Borel, Christelle; Parand, Leila; Ucla, Catherine; Schütz, Frederic; Duriaux Sail, Genevieve; Dupré, Yann; Jaquier-Gubler, Pascale; Araud, Tanguy; Conne, Beatrice; Descombes, Patrick; Vassalli, Jean-Dominique; Curran, Joseph; Antonarakis, Stylianos E

    2009-08-01

    Recent studies have demonstrated extensive transcriptional activity across the human genome, a substantial fraction of which is not associated with any functional annotation. However, very little is known regarding the post-transcriptional processes that operate within the different classes of RNA molecules. To characterize the post-transcriptional properties of expressed sequences from human chromosome 21 (HSA21), we separated RNA molecules from three cell lines (GM06990, HeLa S3, and SK-N-AS) according to their ribosome content by sucrose gradient fractionation. Polyribosomal-associated RNA and total RNA were subsequently hybridized to genomic tiling arrays. We found that approximately 50% of the transcriptional signals were located outside of annotated exons and were considered as TARs (transcriptionally active regions). Although TARs were observed among polysome-associated RNAs, RT-PCR and RACE experiments revealed that approximately 40% were likely to represent nonspecific cross-hybridization artifacts. Bioinformatics discrimination of TARs according to conservation and sequence complexity allowed us to identify a set of high-confidence TARs. This set of TARs was significantly depleted in the polysomes, suggesting that it was not likely to be involved in translation. Analysis of polysome representation of RefSeq exons showed that at least 15% of RefSeq transcripts undergo significant post-transcriptional regulation in at least two of the three cell lines tested. Among the regulated transcripts, enrichment analysis revealed an over-representation of genes involved in Alzheimer's disease (AD), including APP and the BACE1 protease that cleaves APP to produce the pathogenic beta 42 peptide. We demonstrate that the combination of RNA fractionation and tiling arrays is a powerful method to assess the transcriptional and post-transcriptional properties of genomic regions.

  16. Mechanosensitive mechanisms in transcriptional regulation.

    Science.gov (United States)

    Mammoto, Akiko; Mammoto, Tadanori; Ingber, Donald E

    2012-07-01

    Transcriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine.

  17. Transcriptional networks controlling adipocyte differentiation

    DEFF Research Database (Denmark)

    Siersbæk, R; Mandrup, Susanne

    2011-01-01

    Adipocyte differentiation is regulated by a complex cascade of signals that drive the transcriptional reprogramming of the fibroblastic precursors. Genome-wide analyses of chromatin accessibility and binding of adipogenic transcription factors make it possible to generate "snapshots" of the trans...

  18. Structural basis of transcription activation.

    Science.gov (United States)

    Feng, Yu; Zhang, Yu; Ebright, Richard H

    2016-06-10

    Class II transcription activators function by binding to a DNA site overlapping a core promoter and stimulating isomerization of an initial RNA polymerase (RNAP)-promoter closed complex into a catalytically competent RNAP-promoter open complex. Here, we report a 4.4 angstrom crystal structure of an intact bacterial class II transcription activation complex. The structure comprises Thermus thermophilus transcription activator protein TTHB099 (TAP) [homolog of Escherichia coli catabolite activator protein (CAP)], T. thermophilus RNAP σ(A) holoenzyme, a class II TAP-dependent promoter, and a ribotetranucleotide primer. The structure reveals the interactions between RNAP holoenzyme and DNA responsible for transcription initiation and reveals the interactions between TAP and RNAP holoenzyme responsible for transcription activation. The structure indicates that TAP stimulates isomerization through simple, adhesive, stabilizing protein-protein interactions with RNAP holoenzyme. Copyright © 2016, American Association for the Advancement of Science.

  19. Structural basis of transcription elongation.

    Science.gov (United States)

    Martinez-Rucobo, Fuensanta W; Cramer, Patrick

    2013-01-01

    For transcription elongation, all cellular RNA polymerases form a stable elongation complex (EC) with the DNA template and the RNA transcript. Since the millennium, a wealth of structural information and complementary functional studies provided a detailed three-dimensional picture of the EC and many of its functional states. Here we summarize these studies that elucidated EC structure and maintenance, nucleotide selection and addition, translocation, elongation inhibition, pausing and proofreading, backtracking, arrest and reactivation, processivity, DNA lesion-induced stalling, lesion bypass, and transcriptional mutagenesis. In the future, additional structural and functional studies of elongation factors that control the EC and their possible allosteric modes of action should result in a more complete understanding of the dynamic molecular mechanisms underlying transcription elongation. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Thermodynamic Model of Transcription Elongation

    Science.gov (United States)

    Tadigotla, Vasisht; O'Maoileidigh, Daibhid; Sengupta, Anirvan; Epshtein, Vitaly; Ebright, Richard; Nudler, Evgeny; Ruckenstein, Andrei

    2006-03-01

    We present a statistical mechanics approach to the prediction of backtracked pauses in prokaryotic transcription elongation derived from structural models of the transcription elongation complex (TEC). Our algorithm is based on the thermodynamic stability of TEC along the DNA template calculated from the sequence dependent free-energy of DNA-DNA, DNA-RNA and RNA-RNA base pairing associated with (a) the translocation and size fluctuations of the transcription bubble; (b) the changes in the DNA-RNA hybrid; and (c) the changes in the RNA folding free-energy. The calculations involve no adjustable parameters apart from a cutoff used to discriminate paused from non-paused complexes. When applied to 100 experimental pauses in transcription elongation by E. coli RNA polymerase on ten DNA templates the approach produces highly statistically significant results. Transcription elongation is an inherently kinetic process and a simplified kinetic model with the same predictive power is presented separately.

  1. Synthesis of Pyridinic-Rich N, S Co-doped Carbon Quantum Dots as Effective Enzyme Mimics

    Science.gov (United States)

    Liu, Teng; Cui, Zhi-wei; Zhou, Jun; Wang, Ying; Zou, Zhi-gang

    2017-05-01

    N and S co-doped carbon quantum dots (N, S-CQDs) with high N- and S-doping level were synthesized by microwave solid-phase pyrolysis within 50 s. Owing to the dominant pyridinic N injection into the conjugated framework, both high enzyme mimics catalytic activity and photoluminescence quantum yield are achieved simultaneously.

  2. Enzyme active site mimics based on TriAzaCyclophane (TAC)-scaffolded peptides and amino acid residues

    NARCIS (Netherlands)

    Albada, H.B.

    2009-01-01

    This thesis describes the scope and limitations of the application of TriAzaCyclophane (TAC)-scaffolded peptides or amino acid residues as enzyme active site mimics, as ligands in asymmetric catalysis and as hydrolysis catalysts attached to vancomycin. For the mimicry of functional group enzymes, of

  3. Fluorometric, water-based sensors for the detection of nerve gas G mimics DMMP, DCP and DCNP.

    Science.gov (United States)

    Wild, Andreas; Winter, Andreas; Hager, Martin D; Schubert, Ulrich S

    2012-01-25

    Water-based Zn(II) bisterpyridine systems were used as fluorometric sensors for the detection of the nerve gas G mimics DMMP, DCP and DCNP. Analyte concentrations in the range of 10(-7) to 10(-6) M are detectable in solution. The utilization of a test stripe additionally allows the detection of organophosphonates from the gas phase.

  4. A strategy for depositing different types of cells in three dimensions to mimic tubular structures in tissues.

    Science.gov (United States)

    Yuan, Bo; Jin, Yu; Sun, Yi; Wang, Dong; Sun, Jiashu; Wang, Zhuo; Zhang, Wei; Jiang, Xingyu

    2012-02-14

    The fabrication of tubular structures, with multiple cell types forming different layers of the tube walls, is described using a stress-induced rolling membrane (SIRM). Cell orientation inside the tubes can also be controlled by topographical contact guidance. These layered tubes precisely mimic blood vessels and many other tubular structures, suggesting that they may be of great use in tissue engineering.

  5. The pattern recognition molecule deleted in malignant brain tumors 1 (DMBT1) and synthetic mimics inhibit liposomal nucleic acid delivery

    DEFF Research Database (Denmark)

    Lund Hansen, Pernille; Blaich, Stephanie; End, Caroline;

    2011-01-01

    Liposomal nucleic acid delivery is a preferred option for therapeutic settings. The cellular pattern recognition molecule DMBT1, secreted at high levels in various diseases, and synthetic mimics efficiently inhibit liposomal nucleic acid delivery to human cells. These findings may have relevance...

  6. Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

    DEFF Research Database (Denmark)

    Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

    2010-01-01

    to lower the level of NADH and ATP, respectively. We used a global interaction network, comprising of protein interactions, transcriptional regulation, and metabolic networks, to integrate data from transcription profiles, metabolic fluxes, and the metabolite levels. We identified high-scoring networks...... for the two strains. The results revealed a smaller, but denser network for perturbations of ATP level, compared with that of NADH level. The action of many global transcription factors such as ArcA, Fnr, CRP, and IHF commonly involved both NADH and ATP, whereas others responded to either ATP or NADH....... Overexpressing NADH oxidase invokes response in widespread aspects of metabolism involving the redox cofactors (NADH and NADPH), whereas ATPase has a more focused response to restore ATP level by enhancing proton translocation mechanisms and repressing biosynthesis. Interestingly, NADPH played a key role...

  7. Triggering a false alarm: wounding mimics prey capture in the carnivorous Venus flytrap (Dionaea muscipula).

    Science.gov (United States)

    Pavlovič, Andrej; Jakšová, Jana; Novák, Ondřej

    2017-08-29

    In the carnivorous plant Venus flytrap (Dionaea muscipula), the sequence of events after prey capture resembles the well-known plant defence signalling pathway in response to pathogen or herbivore attack. Here, we used wounding to mimic prey capture to show the similarities and differences between botanical carnivory and plant defence mechanisms. We monitored movement, electrical signalling, jasmonate accumulation and digestive enzyme secretion in local and distal (systemic) traps in response to prey capture, the mechanical stimulation of trigger hairs and wounding. The Venus flytrap cannot discriminate between wounding and mechanical trigger hair stimulation. Both induced the same action potentials, rapid trap closure, hermetic trap sealing, the accumulation of jasmonic acid (JA) and its isoleucine conjugate (JA-Ile), and the secretion of proteases (aspartic and cysteine proteases), phosphatases and type I chitinase. The jasmonate accumulation and enzyme secretion were confined to the local traps, to which the stimulus was applied, which correlates with the propagation of electrical signals and the absence of a systemic response in the Venus flytrap. In contrast to plant defence mechanisms, the absence of a systemic response in carnivorous plant may represent a resource-saving strategy. During prey capture, it could be quite expensive to produce digestive enzymes in the traps on the plant without prey. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  8. Ring-down gravity waves: How far wormhole observables can mimic those of a black hole?

    CERN Document Server

    Nandi, Kamal K; Yanbekov, Almir A; Shayakhmetov, Azat A

    2016-01-01

    It has been argued that the recently detected ring-down gravity waveforms could be indicative only of the presence of light rings in a horizonless object, such as a surgical Schwarzschild wormhole, with the frequencies differing drastically from those of the horizon quasinormal mode frequencies $\\omega _{\\text{QNM}}$. While the possibility of such a horizonless alternative is novel by itself, we show by an appropriate example that the difference in frequencies need not be drastic. We shall consider here an analytic (as opposed to surgical) stable traversable Ellis-Bronnikov wormhole and show that observables such as the $\\omega _{\\text{QNM}}$, strong field Bozza lensing parameters and the accretion disk signatures of the Ellis-Bronnikov wormhole could actually be very close to those of a black hole (say, SgrA$^{\\ast }$ hosted by our galaxy) of the same mass. This situation indicates that the wormhole observables could remarkably mimic those of a black hole unless highly precise measurements distinguishing the...

  9. Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.

    Science.gov (United States)

    Osako, Tomo; Takeuchi, Kengo; Horii, Rie; Iwase, Takuji; Akiyama, Futoshi

    2013-10-01

    Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers. We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC. In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis. © 2013 John Wiley & Sons Ltd.

  10. Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics.

    Science.gov (United States)

    deRonde, Brittany M; Birke, Alexander; Tew, Gregory N

    2015-02-09

    Cell-penetrating peptides (CPPs) and their synthetic mimics (CPPMs) represent a class of molecules that facilitate the intracellular delivery of various cargo. Previous studies indicated that the presence of aromatic functionalities improved CPPM activity. Given that aromatic functionalities play prominent roles in membrane biology and participate in various π interactions, we explored whether these interactions could be optimized for improved CPPM activity. CPPMs were synthesized by ring-opening metathesis polymerization by using monomers that contained aromatic rings substituted with electron-donating and electron-withdrawing groups and covered an electrostatic potential range from -29.69 to +15.57 kcal mol(-1) . These groups altered the quadrupole moments of the aromatic systems and were used to test if such structural modifications changed CPPM activity. CPPMs were added to dye-loaded vesicles and the release of carboxyfluorescein was monitored as a function of polymer concentration. Changes in the effective polymer concentration to release 50% of the dye (effective concentration, EC50 ) were monitored. Results from this assay showed that the strength of the electron-donating and electron-withdrawing groups incorporated in the CPPMs did not alter polymer EC50 values or activity. This suggests that other design parameters may have a stronger impact on CPPM activity. In addition, these results indicate that a wide range of aromatic groups can be incorporated without negatively impacting polymer activity.

  11. Cultivation of Human Microvascular Endothelial Cells on Topographical Substrates to Mimic the Human Corneal Endothelium

    Directory of Open Access Journals (Sweden)

    Jie Shi Chua

    2013-03-01

    Full Text Available Human corneal endothelial cells have a limited ability to replicate in vivo and in vitro. Allograft transplantation becomes necessary when an accident or trauma results in excessive cell loss. The reconstruction of the cornea endothelium using autologous cell sources is a promising alternative option for therapeutic or in vitro drug testing applications. The native corneal endothelium rests on the Descemet’s membrane, which has nanotopographies of fibers and pores. The use of synthetic topographies mimics the native environment, and it is hypothesized that this can direct the behavior and growth of human microvascular endothelial cells (HMVECs to resemble the corneal endothelium. In this study, HMVECs are cultivated on substrates with micron and nano-scaled pillar and well topographies. Closely packed HMVEC monolayers with polygonal cells and well-developed tight junctions were formed on the topographical substrates. Sodium/potassium (Na+/K+ adenine triphosphatase (ATPase expression was enhanced on the microwells substrate, which also promotes microvilli formation, while more hexagonal-like cells are found on the micropillars samples. The data obtained suggests that the use of optimized surface patterning, in particular, the microtopographies, can induce HMVECs to adopt a more corneal endothelium-like morphology with similar barrier and pump functions. The mechanism involved in cell contact guidance by the specific topographical features will be of interest for future studies.

  12. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation1

    Science.gov (United States)

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S.; Maclean, Fiona; Oto, Aytekin

    2017-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. PMID:26587887

  13. [Video Instruction for Synchronous Video Recording of Mimic Movement of Patients with Facial Palsy].

    Science.gov (United States)

    Schaede, Rebecca Anna; Volk, Gerd Fabian; Modersohn, Luise; Barth, Jodi Maron; Denzler, Joachim; Guntinas-Lichius, Orlando

    2017-05-03

    Photografy and video are necessary to record the severity of a facial palsy or to allow offline grading with a grading system. There is no international standard for the video recording urgently needed to allow a standardized comparison of different patient cohorts. A video instruction was developed. The instruction was shown to the patient and presents several mimic movements. At the same time the patient is recorded while repeating the presented movement using commercial hardware. Facial movements were selected in such a way that it was afterwards possible to evaluate the recordings with standard grading systems (House-Brackmann, Sunnybrook, Stennert, Yanagihara) or even with (semi)automatic software. For quality control, the patients evaluated the instruction using a questionnaire. The video instruction takes 11 min and 05 and is divided in 3 parts: 1) Explanation of the procedure; 2) Foreplay and recreating of the facial movements; 3) Repeating of sentences to analyze the communication skills. So far 13 healthy subjects and 10 patients with acute or chronic facial palsy were recorded. All recordings could be assessed by the above mentioned grading systems. The instruction was rated as well explaining and easy to follow by healthy persons and patients. There is now a video instruction available for standardized recording of facial movement. This instruction is recommended for use in clinical routine and in clinical trials. This will allow a standardized comparison of patients within Germany and international patient cohorts. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Can f(T) gravity theories mimic ΛCDM cosmic history

    Energy Technology Data Exchange (ETDEWEB)

    Setare, M.R.; Mohammadipour, N., E-mail: rezakord@ipm.ir, E-mail: N.Mohammadipour@uok.ac.ir [Department of Science, University of Kurdistan, Sanandaj (Iran, Islamic Republic of)

    2013-01-01

    Recently the teleparallel Lagrangian density described by the torsion scalar T has been extended to a function of T. The f(T) modified teleparallel gravity has been proposed as the natural gravitational alternative for dark energy to explain the late time acceleration of the universe. In order to reconstruct the function f(T) by demanding a background ΛCDM cosmology we assume that, (i) the background cosmic history provided by the flat ΛCDM (the radiation ere with ω{sub eff} = (1/3), matter and de Sitter eras with ω{sub eff} = 0 and ω{sub eff} = −1, respectively) (ii) the radiation dominate in the radiation era with Ω{sub 0r} = 1 and the matter dominate during the matter phases when Ω{sub 0m} = 1. We find the cosmological dynamical system which can obey the ΛCDM cosmic history. In each era, we find a critical lines that, the radiation dominated and the matter dominated are one points of them in the radiation and matter phases, respectively. Also, we drive the cosmologically viability condition for these models. We investigate the stability condition with respect to the homogeneous scalar perturbations in each era and we obtain the stability conditions for the fixed points in each eras. Finally, we reconstruct the function f(T) which mimics cosmic expansion history.

  15. [Search of Neurotrophin-mimic Natural Products for Prevention and Treatment of Neurodegenerative Disease].

    Science.gov (United States)

    Kubo, Miwa

    2015-01-01

    As part of our continuing studies on neurotrophin-mimic active compounds in natural products, we investigated the chemical constituents of the pericarps of Illicium jiadifengpi and the roots of Indonesian ginger Zingiber purpureum, resulting in the isolation of new seco-prezizaane-type sesquiterpenoid 1 and phenylbutenoid dimer 3-4 and two new curcuminoids 5-6. The MeOH extract of I. jiadifengpi was fractionated, leading to the isolation of compound 1. Compound 1 significantly enhanced neurite outgrowth in primary cell cultures of fetal rat cortical neurons. It is noteworthy that compound 1 has potential significantly to promote differentiation of multipotent neural stem cell line (MEB5 cells) into neurons. Additionally, we investigated the MeOH extract of the root of Bangle (Z. purpureum) that exhibited neuritogenesis activity in PC12 cells at 25 μg/mL, resulting in the isolation of neurotrophic phenylbutenoid dimers 3-4 and new compounds 5-6. Compounds 3 and 4 were found not only significantly to induce neurite sprouting of PC12 cells but also to increase the neurite length and number of neurites in primary cultured rat cortical neurons, and also showed protective activity against cell death caused by deprivation of serum. Furthermore, chronic treatment with these compounds enhanced hippocampal neurogenesis in dementia model olfactory bulbectomized (OBX) mice. Compounds 5 and 6 had significant NGF-potentiating effects on PC12 cells whereas compound 5 enhanced prevention of amyloid β (Aβ) 42 aggregation.

  16. System of elastic hard spheres which mimics the transport properties of a granular gas.

    Science.gov (United States)

    Santos, Andrés; Astillero, Antonio

    2005-09-01

    The prototype model of a fluidized granular system is a gas of inelastic hard spheres (IHS) with a constant coefficient of normal restitution alpha. Using a kinetic theory description we investigate the two basic ingredients that a model of elastic hard spheres (EHS) must have in order to mimic the most relevant transport properties of the underlying IHS gas. First, the EHS gas is assumed to be subject to the action of an effective drag force with a friction constant equal to half the cooling rate of the IHS gas, the latter being evaluated in the local equilibrium approximation for simplicity. Second, the collision rate of the EHS gas is reduced by a factor (1/2)(1+alpha), relative to that of the IHS gas. Comparison between the respective Navier-Stokes transport coefficients shows that the EHS model reproduces almost perfectly the self-diffusion coefficient and reasonably well the two transport coefficients defining the heat flux, the shear viscosity being reproduced within a deviation less than 14% (for alpha > or = 0.5). Moreover, the EHS model is seen to agree with the fundamental collision integrals of inelastic mixtures and dense gases. The approximate equivalence between IHS and EHS is used to propose kinetic models for inelastic collisions as simple extensions of known kinetic models for elastic collisions.

  17. Inhibiting oral intoxication of botulinum neurotoxin A complex by carbohydrate receptor mimics.

    Science.gov (United States)

    Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna-Magdalena; Mahrhold, Stefan; Perry, Kay; Cheng, Luisa W; Rummel, Andreas; Jin, Rongsheng

    2015-12-01

    Botulinum neurotoxins (BoNTs) cause the disease botulism manifested by flaccid paralysis that could be fatal to humans and animals. Oral ingestion of the toxin with contaminated food is one of the most common routes for botulism. BoNT assembles with several auxiliary proteins to survive in the gastrointestinal tract and is subsequently transported through the intestinal epithelium into the general circulation. Several hemagglutinin proteins form a multi-protein complex (HA complex) that recognizes host glycans on the intestinal epithelial cell surface to facilitate BoNT absorption. Blocking carbohydrate binding to the HA complex could significantly inhibit the oral toxicity of BoNT. Here, we identify lactulose, a galactose-containing non-digestible sugar commonly used to treat constipation, as a prototype inhibitor against oral BoNT/A intoxication. As revealed by a crystal structure, lactulose binds to the HA complex at the same site where the host galactose-containing carbohydrate receptors bind. In vitro assays using intestinal Caco-2 cells demonstrated that lactulose inhibits HA from compromising the integrity of the epithelial cell monolayers and blocks the internalization of HA. Furthermore, co-administration of lactulose significantly protected mice against BoNT/A oral intoxication in vivo. Taken together, these data encourage the development of carbohydrate receptor mimics as a therapeutic intervention to prevent BoNT oral intoxication.

  18. Unofficial Economy Estimation by the MIMIC Model: the Case of Kenya, Namibia, Ghana and Nigeria

    Directory of Open Access Journals (Sweden)

    Dennis Nchor

    2015-01-01

    Full Text Available This study investigates the size and trend of the underground economies in selected African countries. Underground economies are present in all countries, but they are endemic in developing economies. Their presence is not necessarily bad for the economies, in which they prevail. It could however cause huge losses to government revenue and could also constitute serious violation of Labor regulations. The study uses the Multiple Indicators and Multiple Causes model (MIMIC, a variant of Simultaneous Equations Model (SEM. It involves two sets of variables: the observed variables and the indicator variables. The former include size of government, indirect tax rates, total tax rates, business regulation, interest rate on deposits, unemployment rate, quality of public services, and GDP per capita. The indicator variables were Labor participation rate in the official economy, the amount of cash held outside the banking system and growth in GDP per capita. This study found the average level of underground economies in Kenya, Namibia, Ghana and Nigeria as 33.7%, 29.1%, 36% and 47%, respectively. The estimated results show that the causes of shadow economic activities vary among the countries. The data was obtained from the World Bank country indicators and the International Financial Statistics.

  19. The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag.

    Science.gov (United States)

    Szabó, Eszter C; Manguinhas, Rita; Fonseca, Rosalina

    2016-09-21

    Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture.

  20. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation.

    Science.gov (United States)

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S; Maclean, Fiona; Oto, Aytekin

    2016-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. Online supplemental material is available for this article.

  1. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity

    Science.gov (United States)

    Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei; Eisenberg, David; Nowick, James S.

    2012-11-01

    The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

  2. Macroscopic Properties of Restacked, Redox-Liquid Exfoliated Graphite and Graphite Mimics Produced in Bulk Quantities

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Vikram K [ORNL; Quinlan, Ronald [ORNL; Agapov, Alexander L [ORNL; Dunlap, John R [ORNL; Nelson, Kimberly M [ORNL; Duranty, Edward R [ORNL; Sokolov, Alexei P [ORNL; Bhat, Gajanan [ORNL; Mays, Jimmy [ORNL

    2014-01-01

    The excellent properties exhibited by monolayer graphene have spurred the development of exfoliation techniques using bulk graphite to produce large quantities of pristine monolayer sheets. Development of simple chemistry to exfoliate and intercalate graphite and graphite mimics in large quantities is required for numerous applications. To determine the macroscopic behavior of restacked, exfoliated bulk materials, a systematic approach is presented using a simple, redox-liquid sonication process along to obtain large quantities of 2D and 3D hexagonally layered graphite, molybdenum disulfi de, and boron nitride, which are subsequently characterized to observe chemical and structural changes. For MoS 2 sonicated with the antioxidant sodium bisulfi te, results from Raman spectroscopy, X-ray diffraction, and electron microscopy indicate the presence of distorted phases from different polymorphs, and apparent nanotube structures in the bulk, restacked powder. Furthermore, using thermograviemtric analysis, the antioxidant enhances the resistance to oxidative degradation of MoS 2 , upon thermal treatment up to 900 C. The addition of the ionic antioxidant decreased dispersion stability in non-polar solvent, suggesting decreased compatibility with non-polar systems. Using simple chemical methods, the ability to generate tailored multidimensional layered materials with unique macroscopic properties is critical for numerous applications, including electrical devices, reinforced polymer composites, lithium ion capacitors, and chemical sensing.

  3. Functionalized hybrid nanofibers to mimic native ECM for tissue engineering applications

    Science.gov (United States)

    Karuppuswamy, Priyadharsini; Venugopal, Jayarama Reddy; Navaneethan, Balchandar; Laiva, Ashang Luwang; Sridhar, Sreepathy; Ramakrishna, Seeram

    2014-12-01

    Nanotechnology being one of the most promising technologies today shows an extremely huge potential in the field of tissue engineering to mimic the porous topography of natural extracellular matrix (ECM). Natural polymers are incorporated into the synthetic polymers to fabricate functionalized hybrid nanofibrous scaffolds, which improve cell and tissue compatibility. The present study identified the biopolymers - aloe vera, silk fibroin and curcumin incorporated into polycaprolactone (PCL) as suitable substrates for tissue engineering. Different combinations of PCL with natural polymers - PCL/aloe vera, PCL/silk fibroin, PCL/aloe vera/silk fibroin, PCL/aloe vera/silk fibroin/curcumin were electrospun into nanofibrous scaffolds. The fabricated two dimensional nanofibrous scaffolds showed high surface area, appropriate mechanical properties, hydrophilicity and porosity, required for the regeneration of diseased tissues. The nanofibrous scaffolds were characterized by Scanning electron microscope (SEM), porometry, Instron tensile tester, VCA optima contact angle measurement and FTIR to analyze the fiber diameter and morphology, porosity and pore size distribution, mechanical strength, wettability, chemical bonds and functional groups, respectively. The average fiber diameter of obtained fibers ranged from 250 nm to 350 nm and the tensile strength of PCL scaffolds at 4.49 MPa increased upto 8.3 MPa for PCL/silk fibroin scaffolds. Hydrophobicity of PCL decreased with the incorporation of natural polymers, especially for PCL/aloe vera scaffolds. The properties of as-spun nanofiber scaffolds showed their potential as promising scaffold materials in tissue engineering applications.

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

    Energy Technology Data Exchange (ETDEWEB)

    An, Bo; Jenkins, Janelle E; Sampath, Sujatha; Holland, Gregory P; Hinman, Mike; Yarger, Jeffery L; Lewis, Randolph [Wyoming; (Sandia); (Utah SU); (AZU)

    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.

  5. BioMimic fabrication of electrospun nanofibers with high-throughput

    Energy Technology Data Exchange (ETDEWEB)

    He Jihuan [Key Laboratory of Science and Technology of Eco-Textile, Donghua University, Ministry of Education (China); Modern Textile Institute, Donghua University, 1882 Yan' an Xilu Road, Shanghai 200051 (China)], E-mail: jhhe@dhu.edu.cn; Liu Yong; Xu Lan; Yu Jianyong; Sun Gang [Key Laboratory of Science and Technology of Eco-Textile, Donghua University, Ministry of Education (China); Modern Textile Institute, Donghua University, 1882 Yan' an Xilu Road, Shanghai 200051 (China)

    2008-08-15

    Spider-spun fiber is of extraordinary strength and toughness comparable to those of electrospun fiber, the later needs a very high voltage (from several thousands voltage to several ten thousands voltages) applied to water-soluble protein 'soup' that was produced by a spider, furthermore, its mechanical strength dramatically decreases comparable to spider silk. A possible mechanism in spider-spinning process is given, the distinct character in spider-spinning is that its spinneret consists of millions of nano scale tubes, and a bubble can be produced at the apex of each nano-tube. The surface tension of each bubble is extremely small such that it can be spun into nanofibers with an awfully small force, either by the spider's body weight or tension created by the rear legs. We mimic the spider-spinning in electrospinning using an aerated solution, which leads to various small bubbles on surface with very small surface tension, as a result the bubble can be easily electrospun into nanofibers with low applied voltage. This fabrication process possesses features of high productivity, versatility, in addition, the minimum diameter of nanofibers produced by this process can reach as small as 50 nm.

  6. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.

    Science.gov (United States)

    Boutant, Marie; Kulkarni, Sameer S; Joffraud, Magali; Raymond, Frédéric; Métairon, Sylviane; Descombes, Patrick; Cantó, Carles

    2016-03-08

    Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different.

  7. MD-simulations of Beta-Amyloid Protein Insertion Efficiency and Kinetics into Neuronal Membrane Mimics

    Science.gov (United States)

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

    2011-03-01

    Early interaction events of beta-amyloid (A β) peptides with the neuronal membranes play a key role in the pathogenesis of Alzheimer's disease. We have used all-atom MD simulations to study the protein insertion efficiency and kinetics of monomeric A β40 and A β42 into phosphatidylcholine lipid bilayers (PC) with and without 40 mole% cholesterol (CHOL) that mimic the cholesterol-enriched and depleted lipid nanodomains of the neuronal plasma membranes. Independent replicates of 200-ns simulations of each protein pre-inserted in the upper lipid layer were generated. In PC bilayers, only 25% of A β40 and 50% of A β42 in the replicates showed complete insertion into the lower lipid layer, whereas the percentages increased to 50% and 100%, respectively, in PC/CHOL bilayers, providing evidence that cholesterol improves the protein insertion efficiency into the bilayers. The rate of protein insertion was proportional to the hydrophobic, transmembrane helix length of the inserted peptide and depended on the cholesterol content. We propose that the lysine snorkeling and C-terminus anchoring of A β to the PC headgroups at the upper and lower lipid/water interfaces represent the dual-transmembrane stabilization mechanisms of A β in the neuronal membrane domains.

  8. Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties

    Science.gov (United States)

    Ghosh, Kaustabh; Pan, Zhi; Guan, E; Ge, Shouren; Liu, Yajie; Nakamura, Toshio; Ren, Xiang-Dong; Rafailovich, Miriam; Clark, Richard A.F.

    2009-01-01

    To successfully induce tissue repair or regeneration in vivo, bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different but concurrent signaling mechanisms: ligation-induced signaling, which depends on ECM biological stimuli, and traction-induced signaling, which depends on ECM mechanical stimuli. In this report, we provide a fundamental understanding of how alterations in mechanical stimuli alone, produced by varying the viscoelastic properties of our bioengineered construct, modulate phenotypic behavior at the whole-cell level. Using a physiologically-relevant ECM mimic composed of hyaluronan and fibronectin, we found that adult human dermal fibroblasts modify their mechanical response in order to match substrate stiffness. More specifically, the cells on stiffer substrates had higher modulus and a more stretched and organized actin cytoskeleton (and vice versa), which translated into larger traction forces exerted on the substrate. This modulation of cellular mechanics had contrasting effects on migration and proliferation, where cells migrated faster on softer substrates while proliferating preferentially on the stiffer ones. These findings implicate substrate rigidity as a critical design parameter in the development of bioengineered constructs aimed at eliciting maximal cell and tissue function. PMID:17049594

  9. Intratemporal facial nerve neuromas and their mimics: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Han, Moon Hee; Chang, Kee Hyun; Lee, Kyung Hwan; Cha, Sang Hoon; Kim, Chong Sun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Sang Joon [Chungang Gil General Hospital, Seoul (Korea, Republic of)

    1992-05-15

    CT and MR findings of nine cases with intra temporal facial nerve neuromas were described and compared with CT findings of 3 cases with facial nerve palsy and facial nerve canal erosion which may mimic facial nerve neuroma. The tympanic segment of the facial nerve was involved in 8 cases, mastoid segment in 7 cases and labyrinthine segment in 5 cases. The lesions were easily diagnosed with high resolution CT with bone algorithms by showing the expansion of bony structures along the course of the facial nerves. In 4 cases with large vertical segment tumors, extensive destruction of mastoid air cells and external auditory canals posed difficulty in making a diagnosis. Two out of 5 cases with labyrinthine segment involvement were presented as middle cranial fossa masses. MRI with enhancement was performed in 4 cases and was useful in characterizing the lesion as a tumor with its superior sensitivity to enhancement. Three cases of facial neuroma-mimicking lesion including post-inflammatory peri neural thickening, peri neural extension from parotid adenoid cystic carcinoma, and congenita; cholesteatoma showed irregular erosion or mild expansion of the facial nerve canal which may be helpful for differential diagnosis from neuromas.

  10. Phage-displayed peptides that mimic epitopes of hepatitis E virus capsid.

    Science.gov (United States)

    Larralde, Osmany; Petrik, Juraj

    2017-08-01

    Hepatitis E is an emerging zoonotic infection of increasing public health threat for the UK, especially for immunosuppressed individuals. A human recombinant vaccine has been licensed only in China and is not clear whether it protects against hepatitis E virus (HEV) genotype 3, the most prevalent in Europe. The aim of this study was to use phage display technology as a tool to identify peptides that mimic epitopes of HEV capsid (mimotopes). We identified putative linear and conformational mimotopes using sera from Scottish blood donors that have the immunological imprint of past HEV infection. Four mimotopes did not have homology with the primary sequence of HEV ORF2 capsid but competed effectively with a commercial HEV antigen for binding to anti-HEV reference serum. When the reactivity profile of each mimotope was compared with Wantai HEV-IgG ELISA, the most sensitive HEV immunoassay, mimotopes showed 95.2-100% sensitivity while the specificity ranged from 81.5 to 95.8%. PepSurf algorithm was used to map affinity-selected peptides onto the ORF2 crystal structure of HEV genotype 3, which predicted that these four mimototopes are clustered in the P domain of ORF2 capsid, near conformational epitopes of anti-HEV neutralising monoclonal antibodies. These HEV mimotopes may have potential applications in the design of structural vaccines and the development of new diagnostic tests.

  11. Fine-Needle Aspiration Cytology of Parathyroid Carcinoma Mimic Hürthle Cell Thyroid Neoplasm

    Directory of Open Access Journals (Sweden)

    Chutintorn Sriphrapradang

    2014-01-01

    Full Text Available Background. Fine-needle aspiration (FNA can cause misdiagnosis of cytomorphological findings between parathyroid and thyroid lesions. Case Presentation. A 31-year-old man presented with a palpable neck mass on the right thyroid lobe. FNA cytology was reported as intrathyroidal lymphoid hyperplasia. After 5 years, repeated FNA was done on the enlarged nodule with result of Hürthle cell lesion. Prior to right lobectomy, laboratories revealed elevated serum calcium and parathyroid hormone (PTH. Careful history taking revealed chronic knee pain and ossifying fibroma at the maxilla. Ultrasonography showed a 2.8 cm mass inferior to right thyroid lobe. Pathology from en bloc resection was parathyroid carcinoma and immunohistochemical study revealed positivity for PTH. Genetic analysis found somatic mutation of CDC73 gene in exon1 (c.70delG which caused premature stop codon in amino acid 26 (p.Glu24Lysfs2*. The final diagnosis was hyperparathyroidism-jaw tumor syndrome. Conclusions. FNA cytology of parathyroid can mimic thyroid lesion. It is important to consider and correlate the entire information from clinical history, laboratory, imaging, and FNA.

  12. A mimic study on effects of fluoride on tooth enamel structures

    Science.gov (United States)

    Ma, Guobin; Wang, Mu; Liu, Xiang Yang

    2010-03-01

    Tooth enamel is the hardest tissue in human body, and this superior mechanical property is contributed by its unique microstructures, i.e., oriented growth of rod-like apatite crystals into basic structural units called the prisms Fluoride (F^-) has been recognized to have significant effects on the physical and chemical properties of tooth enamel. However, the role of F^- on microstructures of apatite crystals is not well understood yet. Here we report a detailed investigation on the topic. Mimic in vitro growth of tooth enamel structures is performed at the biophysical conditions in simulated body fluids, using belt-like hydroxyapatite crystals as substrates It shows that F^- on the order of 0.1 mM will dramatically change the morphology of the grown crystals from irregular slabs to nano-needles, and the needles are aligned along the substrate with an average misorientation of ˜12 . Branched growth of bundles of nano-needles occurs with further increase of F^-, and finally, growth of highly porous structures as well as microspheres takes place when the F^- concentration exceeds 5 mM. In comparison with real tooth enamel structures, the relationship between enamel microstructures and tooth caries as well as fluorosis is discussed.

  13. Synthetic Random Copolymers as a Molecular Platform To Mimic Host-Defense Antimicrobial Peptides.

    Science.gov (United States)

    Takahashi, Haruko; Caputo, Gregory A; Vemparala, Satyavani; Kuroda, Kenichi

    2017-05-17

    Synthetic polymers have been used as a molecular platform to develop host-defense antimicrobial peptide (AMP) mimetics which are effective in killing drug-resistant bacteria. In this topical review, we will discuss the AMP-mimetic design and chemical optimization strategies as well as the biological and biophysical implications of AMP mimicry by synthetic polymers. Traditionally, synthetic polymers have been used as a chemical means to replicate the chemical functionalities and physicochemical properties of AMPs (e.g., cationic charge, hydrophobicity) to recapitulate their mode of action. However, we propose a new perception that AMP-mimetic polymers are an inherently bioactive platform as whole molecules, which mimic more than the side chain functionalities of AMPs. The tunable nature and chemical simplicity of synthetic random polymers facilitate the development of potent, cost-effective, broad-spectrum antimicrobials. The polymer-based approach offers the potential for many antimicrobial applications to be used directly in solution or attached to surfaces to fight against drug-resistant bacteria.

  14. Tumour-derived microvesicles (TMV) mimic the effect of tumour cells on monocyte subpopulations.

    Science.gov (United States)

    Baj-Krzyworzeka, Monika; Baran, Jaroslaw; Weglarczyk, Kazimierz; Szatanek, Rafal; Szaflarska, Anna; Siedlar, Maciej; Zembala, Marek

    2010-09-01

    Monocytes/macrophages may be affected by tumour cells via cell-to-cell contact, soluble factors and by tumour-derived microvesicles (TMV). Previous observations indicate that TMV interact with monocytes and alter their immunophenotype and activity. This study was designed to determine interactions of TMV with subpopulations (CD14(++)CD16(-) and CD14(+)CD16(++)) of human monocytes. Engulfment of TMV by subsets of monocytes was analysed by flow cytometry. Moreover cytokine release and production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) by CD14(++)CD16(-) and CD14(+)CD16(++) cells after TMV stimulation was determined. It was found that TMV are engulfed more efficiently by CD14(++)CD16(-) than CD14(+)CD16(++) cells. TMV-activated CD14(++)CD16(-) cells produce more ROI and interleukin -10 (IL-10) than CD14(++)CD16(+). CD14(+)CD16(++) cells following TMV stimulation showed an increased release of tumour necrosis factor alpha, IL-12p40 and RNI. TMV significantly modulate biological activity of monocyte subsets with a pattern similar to tumour cells. Therefore, TMV mimic the activating effect of tumour cells on monocytes as assessed by release of cytokines, ROI and RNI.

  15. ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis.

    Science.gov (United States)

    Sarapas, Joel M; Backlund, Coralie M; deRonde, Brittany M; Minter, Lisa M; Tew, Gregory N

    2017-05-17

    Cell-penetrating peptides are an important class of molecules with promising applications in bioactive cargo delivery. A diverse series of guanidinium-containing polymeric cell-penetrating peptide mimics (CPPMs) with varying backbone chemistries was synthesized and assessed for delivery of both GFP and fluorescently tagged siRNA. Specifically, we examined CPPMs based on norbornene, methacrylate, and styrene backbones to determine how backbone structure impacted internalization of these two cargoes. Either charge content or degree of polymerization was held constant at 20, with diguanidinium norbornene molecules being polymerized to both 10 and 20 repeat units. Generally, homopolymer CPPMs delivered low amounts of siRNA into Jurkat T cells, with no apparent backbone dependence; however, by adding a short hydrophobic methyl methacrylate block to the guanidinium-rich methacrylate polymer, siRNA delivery to nearly the entire cell population was achieved. Protein internalization yielded similar results for most of the CPPMs, though the block polymer was unable to deliver proteins. In contrast, the styrene-based CPPM yielded the highest internalization for GFP (≈40 % of cells affected), showing that indeed backbone chemistry impacts protein delivery, specifically through the incorporation of an aromatic group. These results demonstrate that an understanding of how polymer structure affects cargo-dependent internalization is critical to designing new, more effective CPPMs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Cardiac cell culture model as a left ventricle mimic for cardiac tissue generation.

    Science.gov (United States)

    Nguyen, Mai-Dung; Tinney, Joseph P; Yuan, Fangping; Roussel, Thomas J; El-Baz, Ayman; Giridharan, Guruprasad; Keller, Bradley B; Sethu, Palaniappan

    2013-09-17

    A major challenge in cardiac tissue engineering is the delivery of hemodynamic mechanical cues that play a critical role in the early development and maturation of cardiomyocytes. Generation of functional cardiac tissue capable of replacing or augmenting cardiac function therefore requires physiologically relevant environments that can deliver complex mechanical cues for cardiomyocyte functional maturation. The goal of this work is the development and validation of a cardiac cell culture model (CCCM) microenvironment that accurately mimics pressure-volume changes seen in the left ventricle and to use this system to achieve cardiac cell maturation under conditions where mechanical loads such as pressure and stretch are gradually increased from the unloaded state to conditions seen in vivo. The CCCM platform, consisting of a cell culture chamber integrated within a flow loop was created to accomplish culture of 10 day chick embryonic ventricular cardiomyocytes subject to 4 days of stimulation (10 mmHg, ∼13% stretch at a frequency of 2 Hz). Results clearly show that CCCM conditioned cardiomyocytes accelerate cardiomyocyte structural and functional maturation in comparison to static unloaded controls as evidenced by increased proliferation, alignment of actin cytoskeleton, bundle-like sarcomeric α-actinin expression, higher pacing beat rate at lower threshold voltages, and increased shortening. These results confirm the CCCM microenvironment can accelerate immature cardiac cell structural and functional maturation for potential cardiac regenerative applications.

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

    Directory of Open Access Journals (Sweden)

    Stefanie Hausammann

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

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

    Science.gov (United States)

    Brandhorst, Sebastian; Choi, In Young; Wei, Min; Cheng, Chia Wei; Sedrakyan, Sargis; Navarrete, Gerardo; Dubeau, Louis; Yap, Li Peng; Park, Ryan; Vinciguerra, Manlio; Di Biase, Stefano; Mirzaei, Hamed; Mirisola, Mario G.; Childress, Patra; Ji, Lingyun; Groshen, Susan; Penna, Fabio; Odetti, Patrizio; Perin, Laura; Conti, Peter S.; Ikeno, Yuji; Kennedy, Brian K.; Cohen, Pinchas; Morgan, Todd E.; Dorff, Tanya B.; Longo, Valter D.

    2015-01-01

    Summary Prolonged fasting (PF) promotes stress resistance but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, four days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems; an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan. PMID:26094889

  19. Mimics: a symbolic conflict/cooperation simulation program, with embedded protocol recording and automatic psychometric assessment.

    Science.gov (United States)

    Aidman, Eugene V; Shmelyov, Alexander G

    2002-02-01

    This paper describes an interactive software environment designed as a social interaction simulator with embedded comprehensive recording and flexible assessment facilities. Using schematized visual sketches similar to cross-cultural facial universals (Ekman, 1999), Mimics (Shmelyov & Aidman, 1997) employs a computer-game-like scenario that requires the subject to identify with an avatar and navigate it through a playing field inhabited by hosts who display a range of facial expressions. From these expressions (which are highly consequential), the player has to anticipate the hosts' reactions to the avatar (which may vary from friendly to obstructing or aggressive) and choose between negotiating with a host (by altering the avatar's facial expression), attacking it, or searching for an escape route. Comprehensive recording of player moves and interactions has enabled computation of several finegrained indices of interactive behavior, such as aggressive response styles, efficiency, and motivation in conflict/cooperation contexts. Initial validation data and potential applications of the method in the assessment of personality and social behavior are discussed.

  20. Hereditary and inflammatory neuropathies: a review of reported associations, mimics and misdiagnoses.

    Science.gov (United States)

    Rajabally, Yusuf A; Adams, David; Latour, Philippe; Attarian, Shahram

    2016-10-01

    Distinguishing between hereditary and inflammatory neuropathy is usually straightforward on clinical grounds with the help of a family history. There are nevertheless cases where the distinction is less clear. The advent of molecular genetics has in the past several years aided confirmatory diagnosis for an increasing proportion of patients with genetic neuropathy. Various reports have described associations of Charcot-Marie-Tooth disease with a suspected or confirmed inflammatory neuropathy occasionally responding to immunotherapy. Possible predisposition to an inflammatory component was suggested in a subset of patients. Such reports have, however, been relatively few in number, suggesting the rarity of such associations and of such a predisposition if it exists. There have been a number of publications detailing clinical presentations suggestive of inflammatory neuropathy in patients with a known or later proven genetic aetiology, and subsequently felt to be part of the phenotype rather than representing an association. A number of genetically mediated multisystemic diseases with neuropathy have otherwise been reported as mimicking chronic inflammatory demyelinating polyneuropathy (CIDP). The most common example is that of familial amyloid polyneuropathy, of particular concern for the clinician when misdiagnosed as CIDP, in view of the therapeutic implications. We review the literature on reported associations, mimics and misdiagnoses of hereditary and inflammatory neuropathy and attempt to determine a practical approach to the problem in clinical practice using clinical features, electrophysiology, histopathology and targeted early genetic testing. The issue of attempting immunomodulatory therapy is discussed in view of the published literature.

  1. HIF transcription factors, inflammation, and immunity.

    Science.gov (United States)

    Palazon, Asis; Goldrath, Ananda W; Nizet, Victor; Johnson, Randall S

    2014-10-16

    The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors; these play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity.

  2. Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells

    Science.gov (United States)

    Hollenhorst, Peter C.; Ferris, Mary W.; Hull, Megan A.; Chae, Heejoon; Kim, Sun; Graves, Barbara J.

    2011-01-01

    The aberrant expression of an oncogenic ETS transcription factor is implicated in the progression of the majority of prostate cancers, 40% of melanomas, and most cases of gastrointestinal stromal tumor and Ewing's sarcoma. Chromosomal rearrangements in prostate cancer result in overexpression of any one of four ETS transcription factors. How these four oncogenic ETS genes differ from the numerous other ETS genes expressed in normal prostate and contribute to tumor progression is not understood. We report that these oncogenic ETS proteins, but not other ETS factors, enhance prostate cell migration. Genome-wide binding analysis matched this specific biological function to occupancy of a unique set of genomic sites highlighted by the presence of ETS- and AP-1-binding sequences. ETS/AP-1-binding sequences are prototypical RAS-responsive elements, but oncogenic ETS proteins activated a RAS/MAPK transcriptional program in the absence of MAPK activation. Thus, overexpression of oncogenic ETS proteins can replace RAS/MAPK pathway activation in prostate cells. The genomic description of this ETS/AP-1-regulated, RAS-responsive, gene expression program provides a resource for understanding the role of these ETS factors in both an oncogenic setting and the developmental processes where these genes normally function. PMID:22012618

  3. Transcriptional control of fleshy fruit development and ripening.

    Science.gov (United States)

    Karlova, Rumyana; Chapman, Natalie; David, Karine; Angenent, Gerco C; Seymour, Graham B; de Maagd, Ruud A

    2014-08-01

    Fleshy fruits have evolved to be attractive to frugivores in order to enhance seed dispersal, and have become an indispensable part of the human diet. Here we review the recent advances in the understanding of transcriptional regulation of fleshy fruit development and ripening with a focus on tomato. While aspects of fruit development are probably conserved throughout the angiosperms, including the model plant Arabidopsis thaliana, it is shown that the likely orthologues of Arabidopsis genes have distinct functions in fleshy fruits. The model for the study of fleshy fruit development is tomato, because of the availability of single gene mutants and transgenic knock-down lines. In other species, our knowledge is often incomplete or absent. Tomato fruit size and shape are co-determined by transcription factors acting during formation of the ovary. Other transcription factors play a role in fruit chloroplast formation, and upon ripening impact quality aspects such as secondary metabolite content. In tomato, the transcription factors NON-RIPENING (NOR), COLORLESS NON-RIPENING (CNR), and RIPENING INHIBITOR (MADS-RIN) in concert with ethylene signalling regulate ripening, possibly in response to a developmental switch. Additional components include TOMATO AGAMOUS-LIKE1 (TAGL1), APETALA2a (AP2a), and FRUITFULL (FUL1 and FUL2). The links between this highly connected regulatory network and downstream effectors modulating colour, texture, and flavour are still relatively poorly understood. Intertwined with this network is post-transcriptional regulation by fruit-expressed microRNAs targeting several of these transcription factors. This important developmental process is also governed by changes in DNA methylation levels and possibly chromatin remodelling.

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

    Science.gov (United States)

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

    2017-01-15

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

  5. Metabolic and transcriptional response to cofactor perturbations in Escherichia coli.

    Science.gov (United States)

    Holm, Anders K; Blank, Lars M; Oldiges, Marco; Schmid, Andreas; Solem, Christian; Jensen, Peter R; Vemuri, Goutham N

    2010-06-04

    Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli to lower the level of NADH and ATP, respectively. We used a global interaction network, comprising of protein interactions, transcriptional regulation, and metabolic networks, to integrate data from transcription profiles, metabolic fluxes, and the metabolite levels. We identified high-scoring networks for the two strains. The results revealed a smaller, but denser network for perturbations of ATP level, compared with that of NADH level. The action of many global transcription factors such as ArcA, Fnr, CRP, and IHF commonly involved both NADH and ATP, whereas others responded to either ATP or NADH. Overexpressing NADH oxidase invokes response in widespread aspects of metabolism involving the redox cofactors (NADH and NADPH), whereas ATPase has a more focused response to restore ATP level by enhancing proton translocation mechanisms and repressing biosynthesis. Interestingly, NADPH played a key role in restoring redox homeostasis through the concerted activity of isocitrate dehydrogenase and UdhA transhydrogenase. We present a reconciled network of regulation that illustrates the overlapping and distinct aspects of metabolism controlled by NADH and ATP. Our study contributes to the general understanding of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli.

  6. Transcriptional divergence and conservation of human and mouse erythropoiesis.

    Science.gov (United States)

    Pishesha, Novalia; Thiru, Prathapan; Shi, Jiahai; Eng, Jennifer C; Sankaran, Vijay G; Lodish, Harvey F

    2014-03-18

    Mouse models have been used extensively for decades and have been instrumental in improving our understanding of mammalian erythropoiesis. Nonetheless, there are several examples of variation between human and mouse erythropoiesis. We performed a comparative global gene expression study using data from morphologically identical stage-matched sorted populations of human and mouse erythroid precursors from early to late erythroblasts. Induction and repression of major transcriptional regulators of erythropoiesis, as well as major erythroid-important proteins, are largely conserved between the species. In contrast, at a global level we identified a significant extent of divergence between the species, both at comparable stages and in the transitions between stages, especially for the 500 most highly expressed genes during development. This suggests that the response of multiple developmentally regulated genes to key erythroid transcriptional regulators represents an important modification that has occurred in the course of erythroid evolution. In developing a systematic framework to understand and study conservation and divergence between human and mouse erythropoiesis, we show how mouse models can fail to mimic specific human diseases and provide predictions for translating findings from mouse models to potential therapies for human disease.

  7. Transcriptional responses of Arabidopsis thaliana plants to As (V stress

    Directory of Open Access Journals (Sweden)

    Yuan Joshua S

    2008-08-01

    Full Text Available Abstract Background Arsenic is toxic to plants and a common environmental pollutant. There is a strong chemical similarity between arsenate [As (V] and phosphate (Pi. Whole genome oligonucleotide microarrays were employed to investigate the transcriptional responses of Arabidopsis thaliana plants to As (V stress. Results Antioxidant-related genes (i.e. coding for superoxide dismutases and peroxidases play prominent roles in response to arsenate. The microarray experiment revealed induction of chloroplast Cu/Zn superoxide dismutase (SOD (at2g28190, Cu/Zn SOD (at1g08830, as well as an SOD copper chaperone (at1g12520. On the other hand, Fe SODs were strongly repressed in response to As (V stress. Non-parametric rank product statistics were used to detect differentially expressed genes. Arsenate stress resulted in the repression of numerous genes known to be induced by phosphate starvation. These observations were confirmed with qRT-PCR and SOD activity assays. Conclusion Microarray data suggest that As (V induces genes involved in response to oxidative stress and represses transcription of genes induced by phosphate starvation. This study implicates As (V as a phosphate mimic in the cell by repressing genes normally induced when available phosphate is scarce. Most importantly, these data reveal that arsenate stress affects the expression of several genes with little or unknown biological functions, thereby providing new putative gene targets for future research.

  8. Administrative Aspects of Human Experimentation.

    Science.gov (United States)

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  9. Verb aspect, alternations and quantification

    Directory of Open Access Journals (Sweden)

    Svetla Koeva

    2015-11-01

    Full Text Available Verb aspect, alternations and quantification In this paper we are briefly discuss the nature of Bulgarian verb aspect and argue that the verb aspect pairs are different lexical units with different (although related meaning, different argument structure (reflecting categories, explicitness and referential status of arguments and different sets of semantic and syntactic alternations. The verb prefixes resulting in perfective verbs derivation in some cases can be interpreted as lexical quantifiers as well. Thus the Bulgarian verb aspect is related (in different way both with the potential for the generation of alternations and with the prefixal lexical quantification. It is shown that the scope of the lexical quantification by means of verbal prefixes is the quantified verb phrase and the scope remains constant in all derived alternations. The paper concerns the basic issues of these complex problems, while the detailed description of the conditions satisfying particular alternation or particular lexical quantification are subject of a more detailed study.

  10. Laboratory Aspects of Hyperprolactinemia Diagnosis

    OpenAIRE

    Rykova, O.V.

    2015-01-01

    The paper presents the modern laboratory aspects of diagnosing hyperprolactinemia and monitoring the effectiveness of treatment according to the Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline 2011.

  11. 2014 SRP Integration Transcript

    Science.gov (United States)

    Steinberg, Susan

    2014-01-01

    HRP's mission is to reduce the risks to human health and performance during long-duration spaceflight. The HRP Integrated Research Plan (IRP) contains the research plans for the 32 risks that require research to characterize and mitigate. From its inception the "integrate" aspect of the IRP has denoted the integrated nature of risks to human health and performance. Even though each risk in the IRP has its own research plan and is tracked separately, the interrelated nature of health and performance requires that they be addressed in an integrative or holistic fashion so that the connectedness of physiological systems within the human body and the integrated response to spaceflight can be addressed. Common characteristics of the spaceflight environment include altered gravity, atmospheres, and light/dark cycles; space radiation; isolation; noise; and periods of high or low workload. Long-term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive, and anthropometric changes; circadian misalignment; fluid shifts; cardiovascular deconditioning; immune dysregulation; and altered nutritional requirements. Expanding cross-disciplinary integrative approaches that synthesize concepts or data from two or more disciplines would improve the identification and characterization risk factors, and enable the development of countermeasures relevant to multiple risks. Cross-disciplinary approaches might also help to illuminate problem areas that may arise when a countermeasure adversely impacts risks other than those which it was developed to mitigate, or to identify groupings of physiological changes that are likely to occur that may impact the overall risk posture. In 2014 HRP embarked on a pilot study that combined four SRPs (and 12 HRP risks) - Behavioral Health, Sensorimotor, Cardiovascular, and Bone/Muscle - specifically to discuss cross-disciplinary integration. The points outlined below were suggested to seed the

  12. Motivational aspects of sport volunteers

    OpenAIRE

    Mičinec, Adam

    2017-01-01

    Title: The motivational aspects of sport volunteerism. Objectives: The main aim of this bachelor work is to find out motivational aspects of sport volunteers, who have taken part in sport event. Methods: In this thesis was used quality method to get informations - specifically it was a structure interview with associated questions. Results: It was find out that it is appropriate to get those volunteers with inner motivation. These volunteers do not need to be so much motivated by external mot...

  13. The Populus Class III HD ZIP transcription factor POPCORONA affects cell differentiation during secondary growth of woody stems

    Science.gov (United States)

    Juan Du; Eriko Miura; Marcel Robischon; Ciera Martinez; Andrew Groover

    2011-01-01

    The developmental mechanisms regulating cell differentiation and patterning during the secondary growth of woody tissues are poorly understood. Class III HD ZIP transcription factors are evolutionarily ancient and play fundamental roles in various aspects of plant development. Here we investigate the role of a Class III HD ZIP transcription factor, ...

  14. Direct Regulation of tRNA and 5S rRNA Gene Transcription by Polo-like Kinase 1

    NARCIS (Netherlands)

    Fairley, Jennifer A.; Mitchell, Louise E.; Berg, Tracy; Kenneth, Niall S.; von Schubert, Conrad; Sillje, Herman H. W.; Medema, Rene H.; Nigg, Erich A.; White, Robert J.

    2012-01-01

    Polo-like kinase Plk1 controls numerous aspects of cell-cycle progression. We show that it associates with tRNA and 5S rRNA genes and regulates their transcription by RNA polymerase Ill (pol Ill) through direct binding and phosphorylation of transcription factor Brit During interphase, Plk1 promotes

  15. Direct Regulation of tRNA and 5S rRNA Gene Transcription by Polo-like Kinase 1

    NARCIS (Netherlands)

    Fairley, Jennifer A.; Mitchell, Louise E.; Berg, Tracy; Kenneth, Niall S.; von Schubert, Conrad; Sillje, Herman H. W.; Medema, Rene H.; Nigg, Erich A.; White, Robert J.

    2012-01-01

    Polo-like kinase Plk1 controls numerous aspects of cell-cycle progression. We show that it associates with tRNA and 5S rRNA genes and regulates their transcription by RNA polymerase Ill (pol Ill) through direct binding and phosphorylation of transcription factor Brit During interphase, Plk1 promotes

  16. SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63▿

    OpenAIRE

    Bornstein, Chamutal; Brosh, Ran; Molchadsky, Alina; Madar, Shalom; Kogan-Sakin, Ira; Goldstein, Ido; Chakravarti, Deepavali; Flores, Elsa R.; Goldfinger, Naomi; Sarig, Rachel; Rotter, Varda

    2011-01-01

    The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by...

  17. Transcription regulation mechanisms of bacteriophages

    Science.gov (United States)

    Yang, Haiquan; Ma, Yingfang; Wang, Yitian; Yang, Haixia; Shen, Wei; Chen, Xianzhong

    2014-01-01

    Phage diversity significantly contributes to ecology and evolution of new bacterial species through horizontal gene transfer. Therefore, it is essential to understand the mechanisms underlying phage-host interactions. After initial infection, the phage utilizes the transcriptional machinery of the host to direct the expression of its own genes. This review presents a view on the transcriptional regulation mechanisms of bacteriophages, and its contribution to phage diversity and classification. Through this review, we aim to broaden the understanding of phage-host interactions while providing a reference source for researchers studying the regulation of phage transcription. PMID:25482231

  18. Sigma Factors for Cyanobacterial Transcription

    Directory of Open Access Journals (Sweden)

    Sousuke Imamura

    2009-04-01

    Full Text Available Cyanobacteria are photosynthesizing microorganisms that can be used as a model for analyzing gene expression. The expression of genes involves transcription and translation. Transcription is performed by the RNA polymerase (RNAP holoenzyme, comprising a core enzyme and a sigma (σ factor which confers promoter selectivity. The unique structure, expression, and function of cyanobacterial σ factors (and RNAP core subunits are summarized here based on studies, reported previously. The types of promoter recognized by the σ factors are also discussed with regard to transcriptional regulation.

  19. Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells

    Science.gov (United States)

    Joshi, Anagha; Pooley, Christopher; Freeman, Tom C.; Lennartsson, Andreas; Babina, Magda; Schmidl, Christian; Geijtenbeek, Teunis; Michoel, Tom; Severin, Jessica; Itoh, Masayoshi; Lassmann, Timo; Kawaji, Hideya; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R. R.; Rehli, Michael; Hume, David A.

    2015-01-01

    The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity. PMID:25717144

  20. Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells.

    Science.gov (United States)

    Joshi, Anagha; Pooley, Christopher; Freeman, Tom C; Lennartsson, Andreas; Babina, Magda; Schmidl, Christian; Geijtenbeek, Teunis; Michoel, Tom; Severin, Jessica; Itoh, Masayoshi; Lassmann, Timo; Kawaji, Hideya; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Rehli, Michael; Hume, David A

    2015-05-01

    The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity.

  1. Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Padmesh S Rajput

    Full Text Available BACKGROUND: Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5. METHODS AND FINDINGS: To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice. CONCLUSIONS: This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the

  2. Peptide mimics of a major lupus epitope of SmB/B'.

    Science.gov (United States)

    Kaufman, Kenneth M; Kirby, Monica Y; Harley, John B; James, Judith A

    2003-04-01

    One of the most distinguishing features of systemic lupus erythematosus is the presence of high concentrations of autoantibodies that recognize a limited number of self-antigens. Even though many lupus autoantigens have been identified, the inciting triggers of these abnormal immune responses are not fully understood. One mechanism that could generate these autoantibodies is a normal immune response toward a foreign epitope that mimics a common antigenic target of an autoantigen. Antibody generated toward the foreign epitope could also bind the autoantigen. This "cross-reactivity" would result in the presentation of the autoantigen to the immune system. Under autoimmune-prone conditions, tolerance toward the native protein is broken and an autoimmune response is initiated. Previously, it was suggested that Epstein-Barr virus might use such a mechanism to initiate an autoimmune response. Cross-reactive epitopes may have a similar amino acid sequence or a similar tertiary structure that is independent of amino acid sequence. A major, and likely initial, target of the lupus anti-SmB' response is a repeated, proline-rich sequence, PPPGMRPP. To identify potential cross-reactive targets, we used affinity-purified autoantibodies specific for PPPGMRPP to screen a random heptapeptide phage display library. Eighty-five clones were isolated and sequenced with eleven distinct sequence motifs being identified. Two of these motifs were homologous to the SmB' epitope, while the other nine were not. Interestingly, one of the peptide motifs that mimicked the SmB' epitope is identical to a peptide sequence found in the Epstein-Barr virus major DNA binding protein.

  3. Irregular-shaped platinum nanoparticles as peroxidase mimics for highly efficient colorimetric immunoassay.

    Science.gov (United States)

    Gao, Zhuangqiang; Xu, Mingdi; Hou, Li; Chen, Guonan; Tang, Dianping

    2013-05-01

    Enzyme-linked immunosorbent assay (ELISA) methods based on natural enzyme-labeled probes have been applied in the immunoassays, but most have some inevitable limitations (e.g. harsh preparation, purification and storage) and are unsuitable for routine use. Herein we synthesized a new class of irregular-shaped platinum nanoparticles (ISPtNP) with a mean length of 7.0 nm and a narrowing width from 2.0 to 5.0 nm along the longitudinal axes, which were utilized as peroxidase-like mimics for the development of colorimetric immunoassays. Compared with bioactive horseradish peroxidase (HRP), the synthesized ISPtNP exhibited a low Km value (~0.12 mM) and a high Kcat value (~2.27×10(4)s(-1)) for 3,3',5,5'-tetramethylbenzidine (TMB) with strong thermal stability and pH tolerance. The catalytic mechanism of the ISPtNP toward TMB/H2O2 was for the first time discussed and deliberated in this work. Based on a sandwich-type assay format, two types of colorimetric immunoassay protocols were designed and developed for the detection of rabbit IgG (RIgG, as a model) by using the synthesized ISPtNP and conventional HRP as the labeling of detection antibodies, respectively. Similar detection limits (LODs) of 2.5 ng mL(-1) vs. 1.0 ng mL(-1) were obtained toward RIgG with the ISPtNP labeling compared to HRP format. Intra- and inter-assay coefficients of variation were less than 13%. Importantly, the ISPtNP-based assay system could be suitable for use in a mass production of miniaturized lab-on-a-chip devices and open new opportunities for protein diagnostics and biosecurity.

  4. An athymic mouse model to mimic cobalt-60 cutaneous radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Mosca, Rodrigo Crespo; Ferreira, Danilo Cardenuto; Napolitano, Celia Marina; Santin, Stefany Plumeri; Dornelles, Leonardo Dalla Porta; Alvarenga, Eluara Ortigoso; Mathor, Monica Beatriz, E-mail: rcmosca@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Propose: Cutaneous wound from irradiation is the most common complication in radiotherapy treatment, and can be lead to mortality. We describe an athymic mouse model to mimic cutaneous radiation injury by Cobalt-60. Methods: A protocol was including dosimetry with silicon diodes,10x10x5 cm arrangement made by four lead bricks and PVC pipe designed to immobilize the athymic mouse in order to irradiate one clamped back skin point that was subdivided in four parts. To get the measurements of dose rates on the arrangement in Panoramic Irradiator, it was used a silicon diode encased in an opaque protection for ambient light and connected to an electric cable, forming a dosing probe. The currents generated in diode sensitive volume as a function of time of exposure to gamma radiation coming from the radiator, with dose rate of 0,015 Gy/min in positions 1, 0,021 Gy/min in position 2, 0,55 Gy/min in position 3 and 1,45 Gy/min in position four. After the dosimetry, each athymic mouse was anesthetized using Xylazine and Ketamine dilution and entered into a PVC pipe and a small portion of skin (1 cm{sup 3}) was clamped. This tube was then fixed to arrangement and the athymic mouse was irradiate for 60 min, than it was being returned to its cage. Results: The wound was visualized in all animals and photographed after 5 days of irradiation, with the emergence of ulceration after 9 days. No systemic or lethal sequelae occurred or visualized in any animals. Late clinical signs included a wound healing after 22 days. Conclusion: While still being a baseline study, we created a new functional preclinical animal model that can be used for new therapies and may improve radiotherapy management. (author)

  5. A peptide mimic blocks the cross-reaction of anti-DNA antibodies with glomerular antigens.

    Science.gov (United States)

    Xia, Y; Eryilmaz, E; Der, E; Pawar, R D; Guo, X; Cowburn, D; Putterman, C

    2016-03-01

    Anti-DNA antibodies play a pivotal role in the pathogenesis of lupus nephritis by cross-reacting with renal antigens. Previously, we demonstrated that the binding affinity of anti-DNA antibodies to self-antigens is isotype-dependent. Furthermore, significant variability in renal pathogenicity was seen among a panel of anti-DNA isotypes [derived from a single murine immunoglobulin (Ig)G3 monoclonal antibody, PL9-11] that share identical variable regions. In this study, we sought to select peptide mimics that effectively inhibit the binding of all murine and human anti-DNA IgG isotypes to glomerular antigens. The PL9-11 panel of IgG anti-DNA antibodies (IgG1, IgG2a, IgG2b and IgG3) was used for screening a 12-mer phage display library. Binding affinity was determined by surface plasmon resonance. Enzyme-linked immunosorbent assay (ELISA), flow cytometry and glomerular binding assays were used for the assessment of peptide inhibition of antibody binding to nuclear and kidney antigens. We identified a 12 amino acid peptide (ALWPPNLHAWVP, or 'ALW') which binds to all PL9-11 IgG isotypes. Preincubation with the ALW peptide reduced the binding of the PL9-11 anti-DNA antibodies to DNA, laminin, mesangial cells and isolated glomeruli significantly. Furthermore, we confirmed the specificity of the amino acid sequence in the binding of ALW to anti-DNA antibodies by alanine scanning. Finally, ALW inhibited the binding of murine and human lupus sera to dsDNA and glomeruli significantly. In conclusion, by inhibiting the binding of polyclonal anti-DNA antibodies to autoantigens in vivo, the ALW peptide (or its derivatives) may potentially be a useful approach to block anti-DNA antibody binding to renal tissue.

  6. Fluorescent competitive assay for melamine using dummy molecularly imprinted polymers as antibody mimics

    Institute of Scientific and Technical Information of China (English)

    DU Xin-wei; JIN Mao-jun; ZHENG Lu-fei; ZHANG Yan-xin; SHE Yong-xin; LIU Guang-yang; ZHAO Feng-nian; WANG Jing; WANG Shan-shan; JIN Fen; SHAO Hua

    2016-01-01

    A lfuorescent competitive assay for melamine was ifrst developed utilizing dummy molecularly imprinted polymers (DMIPs) as artiifcial antibodies. This method is based on the competition between lfuorescent substances and the unlabeled analyte for binding sites in synthesized DMIPs and the decreased binding of lfuorescent substances to DMIPs due to increased concentrations of melamine in the solutions. DMIPs for melamine were synthesized under a hot water bath in the pres-ence of the initiator azobisisobutyronitrile (AIBN) using 2,4-diamino-6-methyl-1,3,5-triazine (DAMT) as a dummy template, methacrylic acid (MAA) as a functional monomer, and ethylene glycol dimethacrylate (EGDMA) as a crosslinking agent. The adsorption capacity and selectivity of DMIPs for melamine were evaluated by the isothermal adsorption curve and Scatchard analysis. The evaluation results showed that the synthesized DMIPs had speciifc recognition sites for melamine and the maximum adsorption amount was 1066.33 μg g–1. Later, 5-(4,6-dichlorotriazinyl) amino lfuorescein (DTAF) with a triazine ring, which slightly resembles melamine, was selected as the lfuorescent substance. The lfuorescent competitive assay using DMIPs as the antibody mimics was ifnaly established by selecting and optimizing the reaction solvents, DMIPs amount, DTAF concentration, and incubation time. The optimal detection system showed a linear response within range of 0.05–40 mg L–1 and the limit of detection (LOD) was 1.23 μg L–1. It was successfuly applied to the detection of melamine in spiked milk samples with satisfactory recoveries (71.9 to 86.3%). According to the comparative analysis, the result of optimized lfuorescent competitive assay revealed excelent agreement with the HPLC-MS/MS result for melamine.

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

    Science.gov (United States)

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

    2017-04-01

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

  8. Phosphatase-inert glucosamine 6-phosphate mimics serve as actuators of the glmS riboswitch.

    Science.gov (United States)

    Fei, Xiang; Holmes, Thomas; Diddle, Julianna; Hintz, Lauren; Delaney, Dan; Stock, Alex; Renner, Danielle; McDevitt, Molly; Berkowitz, David B; Soukup, Juliane K

    2014-12-19

    The glmS riboswitch is unique among gene-regulating riboswitches and catalytic RNAs. This is because its own metabolite, glucosamine-6-phosphate (GlcN6P), binds to the riboswitch and catalytically participates in the RNA self-cleavage reaction, thereby providing a novel negative feedback mechanism. Given that a number of pathogens harbor the glmS riboswitch, artificial actuators of this potential RNA target are of great interest. Structural/kinetic studies point to the 2-amino and 6-phosphate ester functionalities in GlcN6P as being crucial for this actuation. As a first step toward developing artificial actuators, we have synthesized a series of nine GlcN6P analogs bearing phosphatase-inert surrogates in place of the natural phosphate ester. Self-cleavage assays with the Bacillus cereus glmS riboswitch give a broad SAR. Two analogs display significant activity, namely, the 6-deoxy-6-phosphonomethyl analog (5) and the 6-O-malonyl ether (13). Kinetic profiles show a 22-fold and a 27-fold higher catalytic efficiency, respectively, for these analogs vs glucosamine (GlcN). Given their nonhydrolyzable phosphate surrogate functionalities, these analogs are arguably the most robust artificial glmS riboswitch actuators yet reported. Interestingly, the malonyl ether (13, extra O atom) is much more effective than the simple malonate (17), and the "sterically true" phosphonate (5) is far superior to the chain-truncated (7) or chain-extended (11) analogs, suggesting that positioning via Mg coordination is important for activity. Docking results are consistent with this view. Indeed, the viability of the phosphonate and 6-O-malonyl ether mimics of GlcN6P points to a potential new strategy for artificial actuation of the glmS riboswitch in a biological setting, wherein phosphatase-resistance is paramount.

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

    Science.gov (United States)

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

    2013-12-15

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

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

    Science.gov (United States)

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

    2011-12-01

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

  11. Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans

    Directory of Open Access Journals (Sweden)

    Denny Christine A

    2006-05-01

    Full Text Available Abstract Background Caloric restriction (CR has long been recognized as a dietary therapy that improves health and increases longevity. Little is known about the persistent effects of CR on plasma biomarkers (glucose, ketone bodies, and lipids following re-feeding in mice. It is also unclear how these biomarker changes in calorically restricted mice relate to those observed previously in calorically restricted humans. Results Three groups of individually housed adult female C57BL/6J (B6 mice (n = 4/group were fed a standard rodent chow diet either: (1 unrestricted (UR; (2 restricted for three weeks to reduce body weight by approximately 15–20% (R; or (3 restricted for three weeks and then re-fed unrestricted (ad libitum for an additional three weeks (R-RF. Body weight and food intake were measured throughout the study, while plasma lipids and levels of glucose and ketone bodies (β-hydroxybutyrate were measured at the termination of the study. Plasma glucose, phosphatidylcholine, cholesterol, and triglycerides were significantly lower in the R mice than in the UR mice. In contrast, plasma fatty acids and β-hydroxybutyrate were significantly higher in the R mice than in the UR mice. CR had no effect on plasma phosphatidylinositol levels. While body weight and plasma lipids of the R-RF mice returned to unrestricted levels upon re-feeding, food intake and glucose levels remained significantly lower than those prior to the initiation of CR. Conclusion CR establishes a new homeostatic state in B6 mice that persists for at least three weeks following ad libitum re-feeding. Moreover, the plasma biomarker changes observed in B6 mice during CR mimic those reported in humans on very low calorie diets or during therapeutic fasting.

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

    Science.gov (United States)

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

    2015-12-11

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

  13. Functionalized hybrid nanofibers to mimic native ECM for tissue engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Karuppuswamy, Priyadharsini [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore); Department Physics and Nanotechnology, SRM University, Kattankulathur, Chennai (India); Department of Engineering and System Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Venugopal, Jayarama Reddy, E-mail: nnijrv@nus.edu.sg [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore); Navaneethan, Balchandar [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore); Department Physics and Nanotechnology, SRM University, Kattankulathur, Chennai (India); Laiva, Ashang Luwang; Sridhar, Sreepathy; Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore)

    2014-12-15

    Highlights: • Functionalized hybrid polymer mats fabricated for tissue engineering. • Hybrid polymer mats showed high surface area, high porosity and good wettability. • Incorporation of natural polymers modified the properties of nanofiber mats more biologically favorable for biomedical applications. - Abstract: Nanotechnology being one of the most promising technologies today shows an extremely huge potential in the field of tissue engineering to mimic the porous topography of natural extracellular matrix (ECM). Natural polymers are incorporated into the synthetic polymers to fabricate functionalized hybrid nanofibrous scaffolds, which improve cell and tissue compatibility. The present study identified the biopolymers – aloe vera, silk fibroin and curcumin incorporated into polycaprolactone (PCL) as suitable substrates for tissue engineering. Different combinations of PCL with natural polymers – PCL/aloe vera, PCL/silk fibroin, PCL/aloe vera/silk fibroin, PCL/aloe vera/silk fibroin/curcumin were electrospun into nanofibrous scaffolds. The fabricated two dimensional nanofibrous scaffolds showed high surface area, appropriate mechanical properties, hydrophilicity and porosity, required for the regeneration of diseased tissues. The nanofibrous scaffolds were characterized by Scanning electron microscope (SEM), porometry, Instron tensile tester, VCA optima contact angle measurement and FTIR to analyze the fiber diameter and morphology, porosity and pore size distribution, mechanical strength, wettability, chemical bonds and functional groups, respectively. The average fiber diameter of obtained fibers ranged from 250 nm to 350 nm and the tensile strength of PCL scaffolds at 4.49 MPa increased upto 8.3 MPa for PCL/silk fibroin scaffolds. Hydrophobicity of PCL decreased with the incorporation of natural polymers, especially for PCL/aloe vera scaffolds. The properties of as-spun nanofiber scaffolds showed their potential as promising scaffold materials in

  14. Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity.

    Science.gov (United States)

    Dickey, Jennifer S; Baird, Brandon J; Redon, Christophe E; Avdoshina, Valeriya; Palchik, Guillermo; Wu, Junfang; Kondratyev, Alexei; Bonner, William M; Martin, Olga A

    2012-11-01

    Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by γ-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-β and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo.

  15. Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity

    Science.gov (United States)

    Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Avdoshina, Valeriya; Palchik, Guillermo; Wu, Junfang; Kondratyev, Alexei; Bonner, William M.; Martin, Olga A.

    2012-01-01

    Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by γ-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-β and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo. PMID:22941641

  16. Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

    Science.gov (United States)

    Deatly, Anne M.; Lin, Yen-Huei; McCarthy, Maureen; Chen, Wei; Miller, Lynn Z.; Quiroz, Jorge; Nowak, Becky M.; Lerch, Robert A.; Udem, Stephen A.; Goodwin, Thomas J.

    2012-01-01

    Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse

  17. Integrating phosphorylation network with transcriptional network reveals novel functional relationships.

    Directory of Open Access Journals (Sweden)

    Lin Wang

    Full Text Available Phosphorylation and transcriptional regulation events are critical for cells to transmit and respond to signals. In spite of its importance, systems-level strategies that couple these two networks have yet to be presented. Here we introduce a novel approach that integrates the physical and functional aspects of phosphorylation network together with the transcription network in S.cerevisiae, and demonstrate that different network motifs are involved in these networks, which should be considered in interpreting and integrating large scale datasets. Based on this understanding, we introduce a HeRS score (hetero-regulatory similarity score to systematically characterize the functional relevance of kinase/phosphatase involvement with transcription factor, and present an algorithm that predicts hetero-regulatory modules. When extended to signaling network, this approach confirmed the structure and cross talk of MAPK pathways, inferred a novel functional transcription factor Sok2 in high osmolarity glycerol pathway, and explained the mechanism of reduced mating efficiency upon Fus3 deletion. This strategy is applicable to other organisms as large-scale datasets become available, providing a means to identify the functional relationships between kinases/phosphatases and transcription factors.

  18. RNA-guided transcriptional regulation

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  19. The eukaryotic gene transcription machinery.

    Science.gov (United States)

    Kornberg, R D

    2001-08-01

    Seven purified proteins may be combined to reconstitute regulated, promoter-dependent RNA polymerase II transcription: five general transcription factors, Mediator, and RNA polymerase II. The entire system has been conserved across species from yeast to humans. The structure of RNA polymerase II, consisting of 10 polypeptides with a mass of about 500 kDa, has been determined at atomic resolution. On the basis of this structure, that of an actively transcribing RNA polymerase II complex has been determined as well.

  20. Gyrase-dependent stabilization of pSC101 plasmid inheritance by transcriptionally active promoters.

    Science.gov (United States)

    Beaucage, S L; Miller, C A; Cohen, S N

    1991-09-01

    The pSC101 plasmid encodes a cis-acting genetic locus termed par that ensures the stable inheritance of plasmids in a population of dividing cells. In the absence of selection, par-defective plasmids are lost rapidly from the bacterial population. We report here that the stability of par-deleted pSC101 derivatives is restored by introducing certain adventitious bacterial promoters onto the plasmid. Stabilization requires active transcription from the inserted promoter and is affected by the site and orientation of the insertion, the length of the nascent transcript and DNA gyrase activity. While a promotor-associated overall increase in negative superhelicity of plasmid DNA was observed, stabilized inheritance appeared to be dependent on localized rather than generalized supercoiling. Our demonstration that promoter-induced DNA supercoiling can mimic the effects of the pSC101 par locus provides evidence that the previously reported superhelicity-generating effects of par are intrinsic to its function.

  1. Transcription, translation, and the evolution of specialists and generalists.

    Science.gov (United States)

    Zhong, Shaobin; Miller, Stephen P; Dykhuizen, Daniel E; Dean, Antony M

    2009-12-01

    We used DNA microarrays to measure transcription and iTRAQ 2D liquid chromatography-mass spectrometry/mass spectrometry (a mass-tag labeling proteomic technique) to measure protein expression in 14 strains of Escherichia coli adapted for hundreds of generations to growth-limiting concentrations of either lactulose, methylgalactoside, or a 72:28 mixture of the two. The two ancestors, TD2 and TD10, differ only in their lac operons and have similar transcription and protein expression profiles. Changes in transcription and protein expression are observed at 30-250 genes depending on the evolved strain. Lactulose specialists carry duplications of the lac operon and show increased transcription and translation at lac. Methylgalactoside specialists are galS(-) and so constitutively transcribe and translate mgl, which encodes a transporter of methylgalactoside. However, there are two strains that carry lac duplications, are galS(-), and show increased transcription and translation at both operons. One is a generalist, the other a lactulose specialist. The generalist fails to sweep to fixation because its lac(+), galS(+) competitor expresses the csg adhesin and sticks to the chemostat wall, thereby preventing complete washout. Transcription and translation are sometimes decoupled. Lactulose-adapted strains show increased protein expression at fru, a fructose transporter, without evidence of increased transcription. This suggests that fructose, produced by the action of beta-galactosidase on lactulose, may leach from cells before being recouped. Reduced expression, at "late" flagella genes and the constitutive gat operon, is an adaptation to starvation. A comparison with two other long-term evolution experiments suggests that certain aspects of adaptation are predictable, some are characteristic of an experimental system, whereas others seem erratic.

  2. Transcription inactivation through local refolding of the RNA polymerase structure

    Energy Technology Data Exchange (ETDEWEB)

    Belogurov, Georgiy A.; Vassylyeva, Marina N.; Sevostyanova, Anastasiya; Appleman, James R.; Xiang, Alan X.; Lira, Ricardo; Webber, Stephen E.; Klyuyev, Sergiy; Nudler, Evgeny; Artsimovitch, Irina; Vassylyev, Dmitry G.; (OSU); (UAB); (Anadys); (NYUSM)

    2009-02-12

    Structural studies of antibiotics not only provide a shortcut to medicine allowing for rational structure-based drug design, but may also capture snapshots of dynamic intermediates that become 'frozen' after inhibitor binding. Myxopyronin inhibits bacterial RNA polymerase (RNAP) by an unknown mechanism. Here we report the structure of dMyx - a desmethyl derivative of myxopyronin B - complexed with a Thermus thermophilus RNAP holoenzyme. The antibiotic binds to a pocket deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble. Notably, binding of dMyx stabilizes refolding of the {beta}'-subunit switch-2 segment, resulting in a configuration that might indirectly compromise binding to, or directly clash with, the melted template DNA strand. Consistently, footprinting data show that the antibiotic binding does not prevent nucleation of the promoter DNA melting but instead blocks its propagation towards the active site. Myxopyronins are thus, to our knowledge, a first structurally characterized class of antibiotics that target formation of the pre-catalytic transcription initiation complex - the decisive step in gene expression control. Notably, mutations designed in switch-2 mimic the dMyx effects on promoter complexes in the absence of antibiotic. Overall, our results indicate a plausible mechanism of the dMyx action and a stepwise pathway of open complex formation in which core enzyme mediates the final stage of DNA melting near the transcription start site, and that switch-2 might act as a molecular checkpoint for DNA loading in response to regulatory signals or antibiotics. The universally conserved switch-2 may have the same role in all multisubunit RNAPs.

  3. Thermodynamic and Kinetic Modeling of Transcriptional Pausing

    National Research Council Canada - National Science Library

    Vasisht R. Tadigotla; Dáibhid Ó. Maoiléidigh; Anirvan M. Sengupta; Vitaly Epshtein; Richard H. Ebright; Evgeny Nudler; Andrei E. Ruckenstein

    2006-01-01

    We present a statistical mechanics approach for the prediction of backtracked pauses in bacterial transcription elongation derived from structural models of the transcription elongation complex (EC...

  4. National Capital Planning Commission Meeting Transcripts

    Data.gov (United States)

    National Capital Planning Commission — Transcripts of the monthly (with the exception of August) National Capital Planning Commission meeting transcripts are provided for research to confirm actions taken...

  5. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL.

    Science.gov (United States)

    Hagner, Patrick R; Man, Hon-Wah; Fontanillo, Celia; Wang, Maria; Couto, Suzana; Breider, Mike; Bjorklund, Chad; Havens, Courtney G; Lu, Gang; Rychak, Emily; Raymon, Heather; Narla, Rama Krishna; Barnes, Leo; Khambatta, Gody; Chiu, Hsiling; Kosek, Jolanta; Kang, Jian; Amantangelo, Michael D; Waldman, Michelle; Lopez-Girona, Antonia; Cai, Ti; Pourdehnad, Michael; Trotter, Matthew; Daniel, Thomas O; Schafer, Peter H; Klippel, Anke; Thakurta, Anjan; Chopra, Rajesh; Gandhi, Anita K

    2015-08-06

    Cereblon (CRBN), a substrate receptor of the Cullin 4 RING E3 ubiquitin ligase complex, is the target of the immunomodulatory drugs lenalidomide and pomalidomide. Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of 2 common substrates, transcription factors Aiolos and Ikaros. Here we report that CC-122, a new chemical entity termed pleiotropic pathway modifier, binds CRBN and promotes degradation of Aiolos and Ikaros in diffuse large B-cell lymphoma (DLBCL) and T cells in vitro, in vivo, and in patients, resulting in both cell autonomous as well as immunostimulatory effects. In DLBCL cell lines, CC-122-induced degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros correlates with increased transcription of interferon (IFN)-stimulated genes independent of IFN-α, -β, and -γ production and/or secretion and results in apoptosis in both activated B-cell (ABC) and germinal center B-cell DLBCL cell lines. Our results provide mechanistic insight into the cell-of-origin independent antilymphoma activity of CC-122, in contrast to the ABC subtype selective activity of lenalidomide.

  6. Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

    Science.gov (United States)

    Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

    2011-08-01

    Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

  7. [Psychological aspects of induced abortion].

    Science.gov (United States)

    Sz Makó, Hajnalka; Veszprémi, Béla

    2011-01-01

    The present paper, based on the results of international studies, is focused on the reconsideration of the psychological aspects of induced abortion. By presenting a narrow cross-section of the Hungarian demographic data, we would like to emphasise the necessity and the significance of a deeper understanding of the subject. Factors behind the decision-making, short- and long term outcomes of the intervention influencing primarily the mental health of women and partner-relationship aspects are discussed in details. While acknowledging the complexity of the subject deriving from the legal, ethical, moral, religious, medical, social and sociological concerns, our aim is to call attention to the psychological aspects of induced abortion and the importance of psychological care of women undergoing surgical operation.

  8. Dynamic aspects of musical imagery.

    Science.gov (United States)

    Halpern, Andrea R

    2012-04-01

    Auditory imagery can represent many aspects of music, such as the starting pitches of a tune or the instrument that typically plays it. In this paper, I concentrate on more dynamic, or time-sensitive aspects of musical imagery, as demonstrated in two recently published studies. The first was a behavioral study that examined the ability to make emotional judgments about both heard and imagined music in real time. The second was a neuroimaging study on the neural correlates of anticipating an upcoming tune, after hearing a cue tune. That study found activation of several sequence-learning brain areas, some of which varied with the vividness of the anticipated musical memory. Both studies speak to the ways in which musical imagery allows us to judge temporally changing aspects of the represented musical experience. These judgments can be quite precise, despite the complexity of generating the rich internal representations of imagery. © 2012 New York Academy of Sciences.

  9. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation

    Science.gov (United States)

    Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E.; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D.; Asano, Katsura

    2016-01-01

    ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila. The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. PMID:27325740

  10. Thiazolidinediones mimic glucose starvation in facilitating Sp1 degradation through the up-regulation of beta-transducin repeat-containing protein.

    Science.gov (United States)

    Wei, Shuo; Chuang, Hsiao-Ching; Tsai, Wan-Chi; Yang, Hsiao-Ching; Ho, Shiuh-Rong; Paterson, Andrew J; Kulp, Samuel K; Chen, Ching-Shih

    2009-07-01

    This study investigated the mechanism by which the transcription factor Sp1 is degraded in prostate cancer cells. We recently developed a thiazolidinedione derivative, (Z)-5-(4-hydroxy-3-trifluoromethylbenzylidene)-3-(1-methylcyclohexyl)-thiazolidine-2,4-dione (OSU-CG12), that induces Sp1 degradation in a manner paralleling that of glucose starvation. Based on our finding that thiazolidinediones suppress beta-catenin and cyclin D1 by up-regulating the E3 ligase SCF(beta-TrCP), we hypothesized that beta-transducin repeat-containing protein (beta-TrCP) targets Sp1 for proteasomal degradation in response to glucose starvation or OSU-CG12. Here we show that either treatment of LNCaP cells increased specific binding of Sp1 with beta-TrCP. This direct binding was confirmed by in vitro pull-down analysis with bacterially expressed beta-TrCP. Although ectopic expression of beta-TrCP enhanced the ability of OSU-CG12 to facilitate Sp1 degradation, suppression of endogenous beta-TrCP function by a dominant-negative mutant or small interfering RNA-mediated knockdown blocked OSU-CG12-facilitated Sp1 ubiquitination and/or degradation. Sp1 contains a C-terminal conventional DSG destruction box ((727)DSGAGS(732)) that mediates beta-TrCP recognition and encompasses a glycogen synthase kinase 3beta (GSK3beta) phosphorylation motif (SXXXS). Pharmacological and molecular genetic approaches and mutational analyses indicate that extracellular signal-regulated kinase-mediated phosphorylation of Thr739 and GSK3beta-mediated phosphorylation of Ser728 and Ser732 were critical for Sp1 degradation. The ability of OSU-CG12 to mimic glucose starvation to activate beta-TrCP-mediated Sp1 degradation has translational potential to foster novel strategies for cancer therapy.

  11. Synthesis and Kinetics of a Novel Mimic with Glutathione Peroxidase Activity-Tellurium-containing Hyaluronic Acid (TeHA)

    Institute of Scientific and Technical Information of China (English)

    Zhi Bo CHEN; Lan Ying LIU; Bo Xun ZHANG; Zhong Xiu HUANG; Qing Lin PENG; Jia CHEN; Yu WANG; Jian Guo ZHANG; Guang Zhi JIANG; Wen Shu LI

    2006-01-01

    A novel mimic was synthesized by modifying hyaluronic acid (HA) with tellurium,whose function is similar to that of glutathione peroxidase (GPX). The structure of TeHA was characterized by means of IR and NMR, the target-Te was located at -CH2OH of the N-acetyl-D-glucosamine of HA. The H2O2 reducing activity of TeHA, by glutathione (GSH), was 163.6U/μmol according to Wilson's method. In contrast to other mimics, TeHA displayed the highest activity. Moreover, TeHA accepted many hydroperoxides as its substrates, such as H2O2, cumenyl hydroperoxide (CuOOH) and tert-butyl hydroperoxide (t-BuOOH), and CuOOH was the optimal substrate of TeHA. A ping-pong mechanism was observed in the steady-state kinetic studies of the reactions catalyzed by TeHA.

  12. Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

    Science.gov (United States)

    Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

    2017-01-03

    Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

  13. Practical Aspects of CMOS Layout

    DEFF Research Database (Denmark)

    Stassen, Flemming

    1996-01-01

    The topics covered in these notes are the practical aspects and limitations of layout, when random process variations result in electrical parameters, which are not constant but rather statistically distributed.The focus is on design methods for reducing or eliminating the effects. The notes cover...... three aspects:1) to introduce layout structures robust to process variations2) to present simplistic models for analog building blocks with the aim of analysing consequences of parameter variations3) to present the basic noise considerations which guide the layout of supply structures etc....

  14. Technical aspects of data communication

    CERN Document Server

    MacNamara, John E

    1988-01-01

    Technical Aspects of Data Communication, Third Edition provides information pertinent to the technical aspects of data communication. This book discusses a simple asynchronous interface implemented with a specialized integrated circuit called a UART.Organized into 28 chapters, this edition begins with an overview of the interface standards ranging from the classic EIA-232-D to the EIA-530. This text then describes modems and modem control, with material on high-speed modems and error-correcting modems. Other chapters discuss hardware and software methods. This book discusses as well digital tr

  15. Mathematical aspects of natural dynamos

    CERN Document Server

    Dormy, Emmanuel

    2007-01-01

    Although the origin of Earth's and other celestial bodies' magnetic fields remains unknown, we do know that the motion of electrically conducting fluids generates and maintains these fields, forming the basis of magnetohydrodynamics (MHD) and, to a larger extent, dynamo theory. Answering the need for a comprehensive, interdisciplinary introduction to this area, ""Mathematical Aspects of Natural Dynamos"" provides a foundation in dynamo theory before moving on to modeling aspects of natural dynamos.Bringing together eminent international contributors, the book first introduces governing equatio

  16. SPAM -- Technological and Legal Aspects

    CERN Document Server

    Banday, M Tariq

    2011-01-01

    In this paper an attempt is made to review technological, economical and legal aspects of the spam in detail. The technical details will include different techniques of spam control e.g., filtering techniques, Genetic Algorithm, Memory Based Classifier, Support Vector Machine Method, etc. The economic aspect includes Shaping/Rate Throttling Approach/Economic Filtering and Pricing/Payment based spam control. Finally, the paper discusses the legal provisions for the control of spam. The scope of the legal options is limited to USA, European Union, New Zealand, Canada, Britain and Australia.

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

    Science.gov (United States)

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

    2013-11-18

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

  18. Deiodination of thyroid hormones by iodothyronine deiodinase mimics: does an increase in the reactivity alter the regioselectivity?

    Science.gov (United States)

    Manna, Debasish; Mugesh, Govindasamy

    2011-07-06

    Organoselenium compounds as functional mimics of iodothyronine deiodinase are described. The naphthyl-based compounds having two selenol groups are remarkably efficient in the inner-ring deiodination of thyroxine. The introduction of a basic amino group in close proximity to one of the selenol moieties enhances the deiodination. This study suggests that an increase in the nucleophilic reactivity of the conserved Cys residue at the active site of deiodinases is very important for effective deiodination.

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

    CERN Document Server

    Adler, Stephen L

    2016-01-01

    A frame dependent effective action motivated by the postulates of three-space general coordinate invariance and Weyl scaling invariance exactly mimics a cosmological constant in Robertson-Walker spacetimes. However, in a static spherically symmetric Schwarzschild-like geometry it modifies the black hole horizon structure within microscopic distances of the nominal horizon, in such a way that $g_{00}$ never vanishes. This could have important implications for the black hole "information paradox".

  20. Endogenous target mimics down-regulate miR160 mediation of ARF10, -16 and -17 cleavage during somatic embryogenesis in Dimocarpus longan Lour.

    Directory of Open Access Journals (Sweden)

    yuling elin

    2015-11-01

    Full Text Available MicroRNA160 plays a critical role in plant development by negatively regulating the auxin response factors ARF10, -16 and -17. However, the ways in which miR160 expression is regulated at the transcriptional level, and how miR160 interacts with its targets during plant embryo development, remain unknown. Here, we studied the regulatory relationships among endogenous target mimics (eTMs, and miR160 and its targets, and their involvement in hormone signaling and somatic embryogenesis (SE in Dimocarpus longan. We identified miR160 family members and isolated the miR160 precursor, primary transcript, and promoter. The promoter contained cis-acting elements responsive to stimuli such as light, abscisic acid, salicylic acid and heat stress. The pri-miR160 was down-regulated in response to salicylic acid but up-regulated by gibberellic acid, ethylene, and methyl jasmonate treatment, suggesting that pri-miR160 was associated with hormone transduction. Dlo-miR160a, -a* and -d* reached expression peaks in torpedo-shaped embryos, globular embryos and cotyledonary embryos, respectively, but were barely detectable in embryogenic callus. This suggests that they have expression-related and functional diversity, especially during the middle and later developmental stages of SE. Four potential eTMs for miR160 were identified. Two of them, glucan endo-1,3-beta- glucosidase-like protein 2-like and calpain-type cysteine protease DEK1, were confirmed to control the corresponding dlo-miR160a* expression level. This suggests that they may function to abolish the binding between dlo-miR160a* and its targets. These two eTMs also participated in auxin and ABA signal transduction. DlARF10, -16, and -17 targeting by dlo-miR160a was confirmed; their expression levels were higher in friable-embryogenic callus and incomplete compact pro-embryogenic cultures and responded to 2,4-D, suggesting they may play a major role in the early stages of longan SE dependent on 2,4-D. The e

  1. In vitro transcription accurately predicts lac repressor phenotype in vivo in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Matthew Almond Sochor

    2014-07-01

    Full Text Available A multitude of studies have looked at the in vivo and in vitro behavior of the lac repressor binding to DNA and effector molecules in order to study transcriptional repression, however these studies are not always reconcilable. Here we use in vitro transcription to directly mimic the in vivo system in order to build a self consistent set of experiments to directly compare in vivo and in vitro genetic repression. A thermodynamic model of the lac repressor binding to operator DNA and effector is used to link DNA occupancy to either normalized in vitro mRNA product or normalized in vivo fluorescence of a regulated gene, YFP. An accurate measurement of repressor, DNA and effector concentrations were made both in vivo and in vitro allowing for direct modeling of the entire thermodynamic equilibrium. In vivo repression profiles are accurately predicted from the given in vitro parameters when molecular crowding is considered. Interestingly, our measured repressor–operator DNA affinity differs significantly from previous in vitro measurements. The literature values are unable to replicate in vivo binding data. We therefore conclude that the repressor-DNA affinity is much weaker than previously thought. This finding would suggest that in vitro techniques that are specifically designed to mimic the in vivo process may be necessary to replicate the native system.

  2. A latex agglutination test for the field determination of abnormal vitellogenin production in male fishes contaminated by estrogen mimics

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, Ilizabete [Laboratoire d' Immunologie-Microbiologie (LIM/ESE-CNRS, unite FRE2635), IUT de Thionville-Yutz, 1, Impasse A Kastler, F-57970 Yutz (France); Pihan, Jean-Claude [Laboratoire de Production des Ecosystemes et Ecotoxicologie (LBFE), UFR SciFa, campus Bridoux, rue du G Delestraint, F-57070 Metz (France); Falla, Jairo [Laboratoire d' Immunologie-Microbiologie (LIM/ESE-CNRS, unite FRE2635), IUT de Thionville-Yutz, 1, Impasse A Kastler, F-57970 Yutz (France)

    2004-06-09

    Estrogen mimics are pollutants present in the aquatic environment. These compounds induce abnormalities in the reproductive system of male fishes, which lead to a total or partial male feminization, or to their demasculinization. Ultimately, these alterations could lead to a disappearance of the total contaminated fish population. Moreover, these toxic substances possess the capacity to mimic endogenous estrogens and to induce the abnormal production of vitellogenin (VTG) in male and immature fishes. The purpose of this research was to develop an easy, specific, cheap and fast method for diagnosing the contamination of male fishes by estrogen mimics, using VTG as biomarker. The selected method is based on a reverse latex agglutination test (rLAT), developed with monoclonal antibodies specific of this biomarker. The development of this VTG-rLAT has involved, firstly, the purification of carp VTG to produce monoclonal antibodies, specifics of this protein. One of these antibodies was selected to recover latex particles (diameter: 1 {mu}m). Finally, the immunoreactivity of the VTG-rLAT was verified with different fish plasma samples from males treated with 17{beta}-estradiol and non-treated males or females in vitellogenesis.

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

    Science.gov (United States)

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

    2015-01-26

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

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

    Science.gov (United States)

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

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with high mortality. Many disorders can mimic CCHF. It is important to recognize the condition and to perform differential diagnosis in endemic countries. Twenty-one children aged 18 years or less with a preliminary diagnosis of CCHF were retrospectively evaluated. Real-time PCR and a confirmatory indirect immunofluorescence assay for negative results were performed. The diagnoses determined that 9 patients had (42.9%) CCHF; 7 patients had (33.3%) viral upper respiratory tract infections (URTI); 2 patients had (9.5%) brucellosis; 1 patients had (4.7%) periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome episode; 1 patient had (4.7%) cerebral palsy, diabetes insipidus, acute gastroenteritis, and hypernatremic dehydration; and 1 patient had (4.7%) cellulitis after a tick bite. The mean age of patients with CCHF was greater than that of the other patients (116.1±53.6 vs. 94.1±52.1 months, p=0.02). Seventeen (81%) of the children included had a history of tick bites, 2 (9.5%) had a history of contact with a patient with CCHF, and 2 (9.5%) had no exposure, but were living in an endemic region. Three patients had an underlying disorder: cerebral palsy and diabetes insipidus, epilepsy, or PFAPA. All of the children experienced fever. Other frequent symptoms were malaise, diarrhea, vomiting, and abdominal pain, but none of these differed statistically between the patient groups. CCHF patients had a longer mean duration of symptoms (10.56±1.42 vs. 6.75±3.62 days, p=0.008) and a longer mean length of hospitalization (8.00±2.08 vs. 3.58±1.56 days, pnon-infectious causes may resemble CCHF. Although they are not pathognomonic, some indicators, including a longer symptom duration and hospitalization, cytopenia, elevated liver enzymes, creatine kinase and prolonged coagulation parameters, were found to be in favor of CCHF.

  5. Probabilistic aspects of ocean waves

    NARCIS (Netherlands)

    Battjes, J.A.

    1977-01-01

    Background material for a special lecture on probabilistic aspects of ocean waves for a seminar in Trondheim. It describes long term statistics and short term statistics. Statistical distributions of waves, directional spectra and frequency spectra. Sea state parameters, response peaks, encounter

  6. Psychosocial Aspects of Heart Transplantation.

    Science.gov (United States)

    Suszycki, Lee H.

    1988-01-01

    Presents an overview of medical and psychosocial aspects of heart transplantation, with a focus on the program at Columbia-Presbyterian Medical Center. Describes social workers' interventions which help patients and families to achieve optimal psychosocial functioning before and after transplantation. (Author/ABL)

  7. Probabilistic aspects of ocean waves

    NARCIS (Netherlands)

    Battjes, J.A.

    1977-01-01

    Background material for a special lecture on probabilistic aspects of ocean waves for a seminar in Trondheim. It describes long term statistics and short term statistics. Statistical distributions of waves, directional spectra and frequency spectra. Sea state parameters, response peaks, encounter pr

  8. Hispathologic aspects of Lyme Borreliosis.

    NARCIS (Netherlands)

    Koning, Johannes de

    1994-01-01

    As a result of the recent interest in Lyme disease a large number of papers has been published on its different aspects. The purpose of this thesis is to present a comprehensive study of the most important histopathological manifestations based on the experience obtained during the last 11 years. In

  9. Coal mining in socioeconomic aspect

    OpenAIRE

    ZALOZNOVA YU. S.

    2014-01-01

    The article investigate the correlation of economic and social factors in the development of coal mining on example of vertically integrated companies with both domestic and foreign assets. The effect of socioeconomic aspects which have led to the American paradox of coal is studied to understand the essence of the coal mining industry at the present stage of the global economic management.

  10. Transcriptional Crosstalk between Nuclear Receptors and Cytokine Signal Transduction Pathways in Immunity

    Institute of Scientific and Technical Information of China (English)

    Lihua Wang; Xiaohu Zhang; William L. Farrar; Xiaoyi Yang

    2004-01-01

    The nuclear receptor superfamily and the transcriptional factors associated with cytokines are inherently different families of signaling molecules and activate gene transcription by binding to their respective responsive element. However, it has become increasingly clear from our works and others that nuclear receptors are important regulators of cytokine production and function through complex and varied interactions between these distinct transcriptional factors. This review provides a general overview of the mechanism of action of nuclear receptors and their transcriptional crosstalk with transcriptional factors associated with cytokine transduction pathways. One of the most important mechanistic aspects is protein to protein interaction through a direct or co-regulator-mediated indirect manner. Such crosstalk is crucially involved in physiological and therapeutic roles of nuclear receptors and their ligands in immunity,inflammation and cytokine-related tumors. Cellular & Molecular Immunology. 2004;1(6):416-424.

  11. Computational Approaches to Understand Transcriptional Regulation and Alternative Promoter Usage in Mammals

    DEFF Research Database (Denmark)

    Jørgensen, Mette

    understand and cure diseases. The focus of this thesis is transcriptional regulation. The main aim was to gain new insight into transcriptional regulation but a secondary goal was to develop new bioinformatic methods to facilitate future research. Three di erent studies are presented each focusing on di...... into proteins. All cells need di erent proteins in di erent amounts to function properly. The transcription and translation are therefore highly regulated and the regulation is not fully understood. It is important to learn as much as possible about both transcriptional and translational regulation to better...... erent aspects of transcriptional regulation. In the rst study we develop a machine learning framework to predict mRNA production, stalling and elongation of RNA polymerase II using publicly available histone modi cation data. The study reveals new pieces of information about the histone code. Besides...

  12. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal.

    Science.gov (United States)

    Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Bucris, Efrat; Ziv-Av, Amotz; Xiang, Cunli; Bobbitt, Kevin; Rempel, Sandra A; Hasselbach, Laura; Mikkelsen, Tom; Slavin, Shimon; Brodie, Chaya

    2013-02-01

    MicroRNAs (miRNAs) have emerged as potential cancer therapeutics; however, their clinical use is hindered by lack of effective delivery mechanisms to tumor sites. Mesenchymal stem cells (MSCs) have been shown to migrate to experimental glioma and to exert anti-tumor effects by delivering cytotoxic compounds. Here, we examined the ability of MSCs derived from bone marrow, adipose tissue, placenta and umbilical cord to deliver synthetic miRNA mimics to glioma cells and glioma stem cells (GSCs). We examined the delivery of miR-124 and miR-145 mimics as glioma cells and GSCs express very low levels of these miRNAs. Using fluorescently labeled miRNA mimics and in situ hybridization, we demonstrated that all the MSCs examined delivered miR-124 and miR-145 mimics to co-cultured glioma cells and GSCs via gap junction- dependent and independent processes. The delivered miR-124 and miR-145 mimics significantly decreased the luciferase activity of their respected reporter target genes, SCP-1 and Sox2, and decreased the migration of glioma cells and the self-renewal of GSCs. Moreover, MSCs delivered Cy3-miR-124 mimic to glioma xenografts when administered intracranially. These results suggest that MSCs can deliver synthetic exogenous miRNA mimics to glioma cells and GSCs and may provide an efficient route of therapeutic miRNA delivery in vivo.

  13. Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

    Science.gov (United States)

    Egi, H; Hattori, M; Tokunaga, M; Suzuki, T; Kawaguchi, K; Sawada, H; Ohdan, H

    2013-01-01

    The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery. © 2013 S. Karger AG, Basel.

  14. Structural basis of transcription initiation.

    Science.gov (United States)

    Zhang, Yu; Feng, Yu; Chatterjee, Sujoy; Tuske, Steve; Ho, Mary X; Arnold, Eddy; Ebright, Richard H

    2012-11-23

    During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 and 3.0 Å resolution of functional transcription initiation complexes comprising Thermus thermophilus RNA polymerase, σ(A), and a promoter DNA fragment corresponding to the transcription bubble and downstream double-stranded DNA of the RNAP-promoter open complex. The structures show that σ recognizes the -10 element and discriminator element through interactions that include the unstacking and insertion into pockets of three DNA bases and that RNAP recognizes the -4/+2 region through interactions that include the unstacking and insertion into a pocket of the +2 base. The structures further show that interactions between σ and template-strand single-stranded DNA (ssDNA) preorganize template-strand ssDNA to engage the RNAP active center.

  15. Transcription factors - Methods and protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2011-03-01

    Full Text Available A hearty wellcome to prof. Higgins editorial toil: a necessary tool for those colleagues (young and older fighting each day with the transcription factor they are involved with. In fact, the book is a full coverage compendium of state of the art papers dealing with practical thecniques and theoretical concepts about transcription factors. Each of the chapters (twenty-four is written by colleagues already working with one of the many trascription factors we become acquainted with. For the sake of the reader the volume is divided in four parts: Part I is a brief (when compared to the others three ! introductory presentation of the shuttling (i.e., transcription factor nuclear-cytoplasmic trafficking achieved by three reviews presentation of this biologically critical phenomenon. Part II (nine chapters is devoted to the necessary techniques to study nuclear translocation ...............

  16. Pervasive transcription: detecting functional RNAs in bacteria.

    Science.gov (United States)

    Lybecker, Meghan; Bilusic, Ivana; Raghavan, Rahul

    2014-01-01

    Pervasive, or genome-wide, transcription has been reported in all domains of life. In bacteria, most pervasive transcription occurs antisense to protein-coding transcripts, although recently a new class of pervasive RNAs was identified that originates from within annotated genes. Initially considered to be non-functional transcriptional noise, pervasive transcription is increasingly being recognized as important in regulating gene expression. The function of pervasive transcription is an extensively debated question in the field of transcriptomics and regulatory RNA biology. Here, we highlight the most recent contributions addressing the purpose of pervasive transcription in bacteria and discuss their implications.

  17. On Transcription and Other Aspects of the Craft of Qualitative Research

    OpenAIRE

    2005-01-01

    El artículo procura contribuir a salvar la brecha entre el discurso oral y sus versiones escritas. Examina las formas de llevar a cabo la grabación y transcripción, no sólo para prevenir distorsiones importantes, sino también para destacar el carácter inevitablemente interpretativo de toda transcripción. Enfatiza especiamente los procedimientos artesanales por cuanto muchos estudiantes e investigadores en países no industrializados tienen poco acceso a la tecnología específica (tanto por razo...

  18. On Transcription and Other Aspects of the Craft of Qualitative Research

    Directory of Open Access Journals (Sweden)

    Levy Farías

    2005-03-01

    Full Text Available El artículo procura contribuir a salvar la brecha entre el discurso oral y sus versiones escritas. Examina las formas de llevar a cabo la grabación y transcripción, no sólo para prevenir distorsiones importantes, sino también para destacar el carácter inevitablemente interpretativo de toda transcripción. Enfatiza especiamente los procedimientos artesanales por cuanto muchos estudiantes e investigadores en países no industrializados tienen poco acceso a la tecnología específica (tanto por razones económicas como de idioma, que aunque no elimina totalmente la intervención humana, ciertamente simplifica las tareas a ejecutar. Además describe una forma accesible de hacer tablas discursivas usando un conocido procesador de palabras y discute los grados y limitaciones de la edición o intervención del texto transcrito.

  19. Aspects on Aspect : Theory and Applications of Grammatical Aspect in Spanish

    NARCIS (Netherlands)

    González González, P.

    2003-01-01

    This thesis provides an overview of disciplines related to the grammatical phenomenon of aspect. There are several claims advocated in this thesis, according to the different disciplines dealt with in each chapter. Chapter 1 claims that intra-sentential semantic structure contains three potential le

  20. Aspects on Aspect : Theory and Applications of Grammatical Aspect in Spanish

    NARCIS (Netherlands)

    González González, P.

    2003-01-01

    This thesis provides an overview of disciplines related to the grammatical phenomenon of aspect. There are several claims advocated in this thesis, according to the different disciplines dealt with in each chapter. Chapter 1 claims that intra-sentential semantic structure contains three potential le