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Sample records for cln5 support molecular

  1. Data on characterizing the gene expression patterns of neuronal ceroid lipofuscinosis genes: CLN1, CLN2, CLN3, CLN5 and their association to interneuron and neurotransmission markers: Parvalbumin and Somatostatin

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    Helena M. Minye

    2016-09-01

    Full Text Available The article contains raw and analyzed data related to the research article “Neuronal ceroid lipofuscinosis genes, CLN2, CLN3, CLN5 are spatially and temporally co-expressed in a developing mouse brain” (Fabritius et al., 2014 [1]. The processed data gives an understanding of the development of the cell types that are mostly affected by defective function of CLN proteins, timing of expression of CLN1, CLN2, CLN3 and CLN5 genes in a murine model. The data shows relationship between the expression pattern of these genes during neural development. Immunohistochemistry was used to identify known interneuronal markers for neurotransmission and cell proliferation: parvalbumin, somatostatin subpopulations of interneurons. Non-radioactive in-situ hybridization detected CLN5 mRNA in the hippocampus. Throughout the development strong expression of CLN genes were identified in the germinal epithelium and in ventricle regions, cortex, hippocampus, and cerebellum. This provides supportive evidence that CLN1, CLN2, CLN3 and CLN5 genes may be involved in synaptic pruning.

  2. Induced Pluripotent Stem Cells Derived from a CLN5 Patient Manifest Phenotypic Characteristics of Neuronal Ceroid Lipofuscinoses

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    Kristiina Uusi-Rauva

    2017-05-01

    Full Text Available Neuronal ceroid lipofuscinoses (NCLs are autosomal recessive progressive encephalopathies caused by mutations in at least 14 different genes. Despite extensive studies performed in different NCL animal models, the molecular mechanisms underlying neurodegeneration in NCLs remain poorly understood. To model NCL in human cells, we generated induced pluripotent stem cells (iPSCs by reprogramming skin fibroblasts from a patient with CLN5 (ceroid lipofuscinosis, neuronal, 5 disease, the late infantile variant form of NCL. These CLN5 patient-derived iPSCs (CLN5Y392X iPSCs harbouring the most common CLN5 mutation, c.1175_1176delAT (p.Tyr392X, were further differentiated into neural lineage cells, the most affected cell type in NCLs. The CLN5Y392X iPSC-derived neural lineage cells showed accumulation of autofluorescent storage material and subunit C of the mitochondrial ATP synthase, both representing the hallmarks of many forms of NCLs, including CLN5 disease. In addition, we detected abnormalities in the intracellular organelles and aberrations in neuronal sphingolipid transportation, verifying the previous findings obtained from Cln5-deficient mouse macrophages. Therefore, patient-derived iPSCs provide a suitable model to study the mechanisms of NCL diseases.

  3. Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity.

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    Yamashita, Arisa; Hiraki, Yuri; Yamazaki, Tetsuo

    2017-06-10

    αB-crystallin (αBC) is a small heat shock protein. Mutations in the αBC gene are linked to α-crystallinopathy, a hereditary myopathy histologically characterized by intracellular accumulation of protein aggregates. The disease-causing R120G αBC mutant, harboring an arginine-to-glycine replacement at position 120, is an aggregate-prone protein. We previously showed that the R120G mutant's aggregation in HeLa cells was prevented by enforced expression of αBC on the endoplasmic reticulum (ER). To elucidate the molecular nature of the preventive effect on the R120G mutant, we isolated proteins binding to ER-anchored αBC (TMαBC). The ER transmembrane CLN6 protein was identified as a TMαBC's binder. CLN6 knockdown in HeLa cells attenuated TMαBC's anti-aggregate activity against the R120G mutant. Conversely, CLN6 overexpression enhanced the activity, indicating that CLN6 operates as a downstream effector of TMαBC. CLN6 physically interacted with the R120G mutant, and repressed its aggregation in HeLa cells even when TMαBC was not co-expressed. Furthermore, CLN6's antagonizing effect on the R120G mutant was compromised upon treatment with a lysosomal inhibitor, suggesting CLN6 requires the intact autophagy-lysosome system to prevent the R120G mutant from aggregating. We hence conclude that CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMαBC, but also serves as a potential target of therapeutic interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

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    von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

    2009-05-01

    Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.

  5. Loss of Cln3 Function in the Social Amoeba Dictyostelium discoideum Causes Pleiotropic Effects That Are Rescued by Human CLN3

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    Huber, Robert J.

    2014-01-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL) is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3− cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3− cells was precocious and cln3− slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3− cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3− cells, strongly supports the use of this new model for JNCL research. PMID:25330233

  6. Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3.

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    Robert J Huber

    Full Text Available The neuronal ceroid lipofuscinoses (NCL are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3- cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3- cells was precocious and cln3- slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3- cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3- cells, strongly supports the use of this new model for JNCL research.

  7. A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs.

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    Melville, Scott A; Wilson, Carmen L; Chiang, Chiu S; Studdert, Virginia P; Lingaas, Frode; Wilton, Alan N

    2005-09-01

    Neuronal ceroid lipofuscinosis (NCL) is a neurodegenerative disease found in Border collie dogs, humans, and other animals. Disease gene studies in humans and animals provided candidates for the NCL gene in Border collies. A combination of linkage analysis and comparative genomics localized the gene to CFA22 in an area syntenic to HSA13q that contains the CLN5 gene responsible for the Finnish variant of human late infantile NCL. Sequencing of CLN5 revealed a nonsense mutation (Q206X) within exon 4 that correlated with NCL in Border collies. This truncation mutation should result in a protein product of a size similar to that of some mutations identified in human CLN5 and therefore the Border collie may make a good model for human NCL. A simple test was developed to enable screening of the Border collie population for carriers so the disease can be eliminated as a problem in the breed.

  8. Genetics Home Reference: CLN3 disease

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    ... age, and people with CLN3 disease are often blind by late childhood or adolescence. Also around age 4 to 8, children with CLN3 disease start to fall behind in school. They have difficulty learning new information and lose ...

  9. Loss of Cln3 impacts protein secretion in the social amoeba Dictyostelium.

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    Huber, Robert J

    2017-07-01

    Neuronal ceroid lipofuscinosis (NCL), also referred to as Batten disease, is the most common form of childhood neurodegeneration. Mutations in CLN3 cause the most prevalent subtype of the disease, which manifests during early childhood and is currently untreatable. The precise function of the CLN3 protein is still not known, which has inhibited the development of targeted therapies. In the social amoeba Dictyostelium discoideum, loss of the CLN3 homolog, Cln3, reduces adhesion during early development, which delays streaming and aggregation. The results of the present study indicate that this phenotype may be at least partly due to aberrant protein secretion in cln3 - cells. It is well-established that Cln3 localizes primarily to the contractile vacuole (CV) system in Dictyostelium, and to a lesser extent, compartments of the endocytic pathway. Intriguingly, the CV system has been linked to the secretion of proteins that do not contain a signal peptide for secretion (i.e., unconventional protein secretion). Proteins that do contain a signal peptide are secreted via a conventional mechanism involving the endoplasmic reticulum, transport through the Golgi, and secretion via vesicle release. In this study, Cln3 was observed to co-localize with the Golgi marker wheat germ agglutinin suggesting that Cln3 participates in both secretion mechanisms. Chimeras of wild-type (WT) and cln3 - cells displayed delayed streaming and aggregation, and interestingly, cln3 - cells starved in conditioned media (CM) harvested from starving WT cells showed near normal timing of streaming and aggregation suggesting aberrant protein secretion in Cln3-deficient cells. Based on these observations, LC-MS/MS was used to reveal the protein content of CM from starved cells (mass spectrometry data are available via ProteomeXchange with identifier PXD004897). A total of 450 proteins were detected in WT and cln3 - CM, of which 3 were absent in cln3 - CM. Moreover, 12 proteins that were present in

  10. Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease

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    Melanie A. Jones

    2014-04-01

    Full Text Available Wolfram syndrome (WFS is a progressive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. WFS1 and WFS2 are caused by recessive mutations in the genes Wolfram Syndrome 1 (WFS1 and CDGSH iron sulfur domain 2 (CISD2, respectively. To explore the function of CISD2, we performed genetic studies in flies with altered expression of its Drosophila orthologue, cisd2. Surprisingly, flies with strong ubiquitous RNAi-mediated knockdown of cisd2 had no obvious signs of altered life span, stress resistance, locomotor behavior or several other phenotypes. We subsequently found in a targeted genetic screen, however, that altered function of cisd2 modified the effects of overexpressing the fly orthologues of two lysosomal storage disease genes, palmitoyl-protein thioesterase 1 (PPT1 in humans, Ppt1 in flies and ceroid-lipofuscinosis, neuronal 3 (CLN3 in humans, cln3 in flies, on eye morphology in flies. We also found that cln3 modified the effects of overexpressing Ppt1 in the eye and that overexpression of cln3 interacted with a loss of function mutation in cisd2 to disrupt locomotor ability in flies. Follow-up multi-species bioinformatic analyses suggested that a gene network centered on CISD2, PPT1 and CLN3 might impact disease through altered carbohydrate metabolism, protein folding and endopeptidase activity. Human genetic studies indicated that copy number variants (duplications and deletions including CLN3, and possibly another gene in the CISD2/PPT1/CLN3 network, are over-represented in individuals with developmental delay. Our studies indicate that cisd2, Ppt1 and cln3 function in concert in flies, suggesting that CISD2, PPT1 and CLN3 might also function coordinately in humans. Further, our studies raise the possibility that WFS2 and some lysosomal storage disorders might be influenced by common mechanisms and that the underlying genes might have previously unappreciated effects on

  11. Osmotic stress changes the expression and subcellular localization of the Batten disease protein CLN3.

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    Amanda Getty

    Full Text Available Juvenile CLN3 disease (formerly known as juvenile neuronal ceroid lipofuscinosis is a fatal childhood neurodegenerative disorder caused by mutations in the CLN3 gene. CLN3 encodes a putative lysosomal transmembrane protein with unknown function. Previous cell culture studies using CLN3-overexpressing vectors and/or anti-CLN3 antibodies with questionable specificity have also localized CLN3 in cellular structures other than lysosomes. Osmoregulation of the mouse Cln3 mRNA level in kidney cells was recently reported. To clarify the subcellular localization of the CLN3 protein and to investigate if human CLN3 expression and localization is affected by osmotic changes we generated a stably transfected BHK (baby hamster kidney cell line that expresses a moderate level of myc-tagged human CLN3 under the control of the human ubiquitin C promoter. Hyperosmolarity (800 mOsm, achieved by either NaCl/urea or sucrose, dramatically increased the mRNA and protein levels of CLN3 as determined by quantitative real-time PCR and Western blotting. Under isotonic conditions (300 mOsm, human CLN3 was found in a punctate vesicular pattern surrounding the nucleus with prominent Golgi and lysosomal localizations. CLN3-positive early endosomes, late endosomes and cholesterol/sphingolipid-enriched plasma membrane microdomain caveolae were also observed. Increasing the osmolarity of the culture medium to 800 mOsm extended CLN3 distribution away from the perinuclear region and enhanced the lysosomal localization of CLN3. Our results reveal that CLN3 has multiple subcellular localizations within the cell, which, together with its expression, prominently change following osmotic stress. These data suggest that CLN3 is involved in the response and adaptation to cellular stress.

  12. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

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    Arsov, Todor

    2011-05-13

    The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.

  13. Management Strategies for CLN2 Disease.

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    Williams, Ruth E; Adams, Heather R; Blohm, Martin; Cohen-Pfeffer, Jessica L; de Los Reyes, Emily; Denecke, Jonas; Drago, Kristen; Fairhurst, Charlie; Frazier, Margie; Guelbert, Norberto; Kiss, Szilárd; Kofler, Annamaria; Lawson, John A; Lehwald, Lenora; Leung, Mary-Anne; Mikhaylova, Svetlana; Mink, Jonathan W; Nickel, Miriam; Shediac, Renée; Sims, Katherine; Specchio, Nicola; Topcu, Meral; von Löbbecke, Ina; West, Andrea; Zernikow, Boris; Schulz, Angela

    2017-04-01

    CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, autosomal recessive, pediatric-onset, rapidly progressive neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 (TPP1) enzyme deficiency, and is characterized by language delay, seizures, rapid cognitive and motor decline, blindness, and early death. No management guidelines exist and there is a paucity of published disease-specific evidence to inform clinical practice, which currently draws upon experience from the field of childhood neurodisability. Twenty-four disease experts were surveyed on CLN2 disease management and a subset met to discuss current practice. Management goals and strategies are consistent among experts globally and are guided by the principles of pediatric palliative care. Goals and interventions evolve as the disease progresses, with a shift in focus from maintenance of function early in the disease to maintenance of quality of life. A multidisciplinary approach is critical for optimal patient care. This work represents an initial step toward the development of consensus-based management guidelines for CLN2 disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

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    Wu, Dan, E-mail: danw@bjmu.edu.cn [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Liu, Jing; Wu, Baiyan [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Tu, Bo; Zhu, Weiguo [Department of Biochemistry and Molecular Biology, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Luo, Jianyuan, E-mail: jluo@som.umaryland.edu [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Department of Medical and Research Technology, School of Medicine, University of Maryland, Baltimore 21201 (United States)

    2014-04-25

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.

  15. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

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    Wu, Dan; Liu, Jing; Wu, Baiyan; Tu, Bo; Zhu, Weiguo; Luo, Jianyuan

    2014-01-01

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration

  16. Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a proteasome-dependent manner.

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    Oresic, Kristina; Mueller, Britta; Tortorella, Domenico

    2009-06-01

    NCLs (neuronal ceroid lipofuscinoses), a group of inherited neurodegenerative lysosomal storage diseases that predominantly affect children, are the result of autosomal recessive mutations within one of the nine cln genes. The wild-type cln gene products are composed of membrane and soluble proteins that localize to the lysosome or the ER (endoplasmic reticulum). However, the destiny of the Cln variants has not been fully characterized. To explore a possible link between ER quality control and processing of Cln mutants, we investigated the fate of two NCL-related Cln6 mutants found in patient samples (Cln6(G123D) and Cln6(M241T)) in neuronal-derived human cells. The point mutations are predicted to be in the putative transmembrane domains and most probably generate misfolded membrane proteins that are subjected to ER quality control. Consistent with this paradigm, both mutants underwent rapid proteasome-mediated degradation and complexed with components of the ER extraction apparatus, Derlin-1 and p97. In addition, knockdown of SEL1L [sel-1 suppressor of lin-12-like (Caenorhabditis elegans)], a member of an E3 ubiquitin ligase complex involved in ER protein extraction, rescued significant amounts of Cln6(G123D) and Cln6(M241T) polypeptides. The results implicate ER quality control in the instability of the Cln variants that probably contributes to the development of NCL.

  17. Using Patient-Specific Induced Pluripotent Stem Cells and Wild-Type Mice to Develop a Gene Augmentation-Based Strategy to Treat CLN3-Associated Retinal Degeneration.

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    Wiley, Luke A; Burnight, Erin R; Drack, Arlene V; Banach, Bailey B; Ochoa, Dalyz; Cranston, Cathryn M; Madumba, Robert A; East, Jade S; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2016-10-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is a childhood neurodegenerative disease with early-onset, severe central vision loss. Affected children develop seizures and CNS degeneration accompanied by severe motor and cognitive deficits. There is no cure for JNCL, and patients usually die during the second or third decade of life. In this study, independent lines of induced pluripotent stem cells (iPSCs) were generated from two patients with molecularly confirmed mutations in CLN3, the gene mutated in JNCL. Clinical-grade adeno-associated adenovirus serotype 2 (AAV2) carrying the full-length coding sequence of human CLN3 was generated in a U.S. Food and Drug Administration-registered cGMP facility. AAV2-CLN3 was efficacious in restoring full-length CLN3 transcript and protein in patient-specific fibroblasts and iPSC-derived retinal neurons. When injected into the subretinal space of wild-type mice, purified AAV2-CLN3 did not show any evidence of retinal toxicity. This study provides proof-of-principle for initiation of a clinical trial using AAV-mediated gene augmentation for the treatment of children with CLN3-associated retinal degeneration.

  18. Genetics Home Reference: CLN6 disease

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    ... the accumulation of proteins and other substances in lysosomes , which are cell structures that digest and recycle ... are involved in the buildup of substances in lysosomes in CLN6 disease . These accumulations occur in more ...

  19. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

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    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  20. Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease.

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    Kim Wager

    Full Text Available The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80-85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery.

  1. Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis.

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    Liliana Catherine Patiño

    Full Text Available The neuronal ceroid-lipofuscinoses (NCL is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14 have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8 and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg and c.1361T>C (p.Met454Thr MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease.

  2. Functional categorization of gene expression changes in the cerebellum of a Cln3-knockout mouse model for Batten disease.

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    Brooks, Andrew I; Chattopadhyay, Subrata; Mitchison, Hannah M; Nussbaum, Robert L; Pearce, David A

    2003-01-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten Disease) is the most common progressive neurodegenerative disorder of childhood. The disease is inherited in an autosomal recessive manner and is the result of mutations in the CLN3 gene. One brain region severely affected in Batten disease is the cerebellum. Using a mouse model for Batten disease which shares pathological similarities to the disease in humans we have used oligonucleotide arrays to profile approximately 19000 mRNAs in the cerebellum. We have identified reproducible changes of twofold or more in the expression of 756 gene products in the cerebellum of 10-week-old Cln3-knockout mice as compared to wild-type controls. We have subsequently divided these genes with altered expression into 14 functional categories. We report a significant alteration in expression of genes associated with neurotransmission, neuronal cell structure and development, immune response and inflammation, and lipid metabolism. An apparent shift in metabolism toward gluconeogenesis is also evident in Cln3-knockout mice. Further experimentation will be necessary to understand the contribution of these changes in expression to a disease state. Detailed analysis of the functional consequences of altered expression of genes in the cerebellum of the Cln3-knockout mice may provide valuable clues in understanding the molecular basis of the pathological mechanisms underlying Batten disease.

  3. Conjugated linolenic acids (CLnA, super CLA – natural sources and biological activity

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2014-11-01

    Full Text Available Polyunsaturated fatty acids (PUFA have a wide range of biological activity. Among them conjugated fatty acids are of great interest. Conjugated linoleic acids (CLA, which exert a multidirectional health-benefiting influence, and conjugated linolenic acids (CLnA, super CLA are examples of this group of fatty acids. CLnA are a group of positional and geometric isomers of octadecatrienoic acid (C18:3, which possess double bonds at positions 9, 11, 13 or 8, 10, 12 of their chain. Some vegetable oils are rich sources of CLnA, e.g. bitter melon oil (from Momordica charantia seeds and pomegranate oil (from Punica granatum seeds. The aim of this paper was to present information concerning natural sources and health-promoting activities of conjugated linolenic acids.The presented data reveal that conjugated linolenic acids may be very useful in prevention and treatment of many diseases, especially diabetes, arteriosclerosis , obesity and cancers (mammary, prostate and colon cancer. Among many potential mechanisms of their action, the fact that some CLnA are converted by oxidoreductases into CLA is very important. It seems to be very reasonable to conduct research concerning the possibility of CLnA use in prevention of many diseases.

  4. Production of a conjugated fatty acid by Bifidobacterium breve LMC520 from α-linolenic acid: conjugated linolenic acid (CLnA).

    Science.gov (United States)

    Park, Hui Gyu; Cho, Hyung Taek; Song, Myoung-Chong; Kim, Sang Bum; Kwon, Eung Gi; Choi, Nag Jin; Kim, Young Jun

    2012-03-28

    This study was performed to characterize natural CLnA isomer production by Bifidobacterium breve LMC520 of human origin in comparison to conjugated linoleic acid (CLA) production. B. breve LMC520 was found to be highly active in terms of CLnA production, of which the major portion was identified as cis-9,trans-11,cis-15 CLnA isomer by GC-MS and NMR analysis. B. breve LMC520 was incubated for 48 h using MRS medium (containing 0.05% L-cysteine · HCl) under different environmental conditions such as atmosphere, pH, and substrate concentration. The high conversion rate of α-linolenic acid (α-LNA) to CLnA (99%) was retained up to 2 mM α-LNA, and the production was proportionally increased nearly 7-fold with 8 mM by the 6 h of incubation under anaerobic conditions at a wide range of pH values (between 5 and 9). When α-LNA was compared with linoleic acid (LA) as a substrate for isomerization by B. breve LMC520, the conversion of α-LNA was higher than that of LA. These results demonstrated that specific CLnA isomer could be produced through active bacterial conversion at an optimized condition. Because many conjugated octadecatrienoic acids in nature are shown to play many positive roles, the noble isomer found in this study has potential as a functional source.

  5. Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation.

    Science.gov (United States)

    Pontikis, Charlie C; Cella, Claire V; Parihar, Nisha; Lim, Ming J; Chakrabarti, Shubhodeep; Mitchison, Hannah M; Mobley, William C; Rezaie, Payam; Pearce, David A; Cooper, Jonathan D

    2004-10-15

    Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.

  6. Thalamocortical neuron loss and localized astrocytosis in the Cln3Deltaex7/8 knock-in mouse model of Batten disease.

    Science.gov (United States)

    Pontikis, Charlie C; Cotman, Susan L; MacDonald, Marcy E; Cooper, Jonathan D

    2005-12-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is the result of mutations in the Cln3 gene. The Cln3 knock-in mouse (Cln3Deltaex7/8) reproduces the most common Cln3 mutation and we have now characterized the CNS of these mice at 12 months of age. With the exception of the thalamus, Cln3Deltaex7/8 homozygotes displayed no significant regional atrophy, but a range of changes in individual laminar thickness that resulted in variable cortical thinning across subfields. Stereological analysis revealed a pronounced loss of neurons within individual laminae of somatosensory cortex of affected mice and the novel finding of a loss of sensory relay thalamic neurons. These affected mice also exhibited profound astrocytic reactions that were most pronounced in the neocortex and thalamus, but diminished in other brain regions. These data provide the first direct evidence for neurodegenerative and reactive changes in the thalamocortical system in JNCL and emphasize the localized nature of these events.

  7. Modeling the mechanism of CLN025 beta-hairpin formation

    Science.gov (United States)

    McKiernan, Keri A.; Husic, Brooke E.; Pande, Vijay S.

    2017-09-01

    Beta-hairpins are substructures found in proteins that can lend insight into more complex systems. Furthermore, the folding of beta-hairpins is a valuable test case for benchmarking experimental and theoretical methods. Here, we simulate the folding of CLN025, a miniprotein with a beta-hairpin structure, at its experimental melting temperature using a range of state-of-the-art protein force fields. We construct Markov state models in order to examine the thermodynamics, kinetics, mechanism, and rate-determining step of folding. Mechanistically, we find the folding process is rate-limited by the formation of the turn region hydrogen bonds, which occurs following the downhill hydrophobic collapse of the extended denatured protein. These results are presented in the context of established and contradictory theories of the beta-hairpin folding process. Furthermore, our analysis suggests that the AMBER-FB15 force field, at this temperature, best describes the characteristics of the full experimental CLN025 conformational ensemble, while the AMBER ff99SB-ILDN and CHARMM22* force fields display a tendency to overstabilize the native state.

  8. Progressive retinal degeneration and glial activation in the CLN6 (nclf mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation.

    Directory of Open Access Journals (Sweden)

    Myriam Mirza

    Full Text Available Neuronal ceroid lipofuscinosis (NCL is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, and spontaneous seizures. Neuropathological analyses of autopsy material from NCL patients and animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss of retinal cells and reactive gliosis in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular phenotype of CLN6 (nclf mice, an established mouse model for variant-late infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking, electroretinography, and mRNA expression were used to characterize retinal morphology and function as well as the responses of Müller cells and microglia. Our histological data showed a severe and progressive degeneration in the CLN6 (nclf retina co-inciding with reactive Müller glia. Furthermore, a prominent phenotypic transformation of ramified microglia to phagocytic, bloated, and mislocalized microglial cells was identified in CLN6 (nclf retinas. These events overlapped with a rapid loss of visual perception and retinal function. Based on the strong microglia reactivity we hypothesized that dietary supplementation with immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA, could ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that treatment of three-week-old CLN6 (nclf mice with either 5% DHA or 0.6% curcumin for 30 weeks resulted in a reduced number of amoeboid reactive microglia and partially improved retinal function. DHA-treatment also improved the morphology of CLN6 (nclf retinas with a preserved thickness of the photoreceptor layer in most regions of the retina. Our results suggest that microglial reactivity closely accompanies disease progression in the CLN6 (nclf retina and both processes can be attenuated with dietary supplemented immuno-modulating compounds.

  9. Crystal structure of chlorido{[3-(eta(5)-cyclopenta-dienyl)-2,2,3-trimethyl-1-phenylbutylidene]azanido-kappa N}[eta(2)(N,O)-N,N-dimethylhydroxyl-aminato]titanium(IV), C20H27ClN2OTi

    Czech Academy of Sciences Publication Activity Database

    Večeřa, M.; Gyepes, R.; Lamač, Martin

    2017-01-01

    Roč. 232, č. 3 (2017), s. 457-459 ISSN 1433-7266 R&D Projects: GA ČR(CZ) GA14-08531S Institutional support: RVO:61388955 Keywords : crystal structure * C20H27ClN2OTi * physical chemistry Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 0.152, year: 2016

  10. Low-mass molecular dynamics simulation: A simple and generic technique to enhance configurational sampling

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Yuan-Ping, E-mail: pang@mayo.edu

    2014-09-26

    Highlights: • Reducing atomic masses by 10-fold vastly improves sampling in MD simulations. • CLN025 folded in 4 of 10 × 0.5-μs MD simulations when masses were reduced by 10-fold. • CLN025 folded as early as 96.2 ns in 1 of the 4 simulations that captured folding. • CLN025 did not fold in 10 × 0.5-μs MD simulations when standard masses were used. • Low-mass MD simulation is a simple and generic sampling enhancement technique. - Abstract: CLN025 is one of the smallest fast-folding proteins. Until now it has not been reported that CLN025 can autonomously fold to its native conformation in a classical, all-atom, and isothermal–isobaric molecular dynamics (MD) simulation. This article reports the autonomous and repeated folding of CLN025 from a fully extended backbone conformation to its native conformation in explicit solvent in multiple 500-ns MD simulations at 277 K and 1 atm with the first folding event occurring as early as 66.1 ns. These simulations were accomplished by using AMBER forcefield derivatives with atomic masses reduced by 10-fold on Apple Mac Pros. By contrast, no folding event was observed when the simulations were repeated using the original AMBER forcefields of FF12SB and FF14SB. The results demonstrate that low-mass MD simulation is a simple and generic technique to enhance configurational sampling. This technique may propel autonomous folding of a wide range of miniature proteins in classical, all-atom, and isothermal–isobaric MD simulations performed on commodity computers—an important step forward in quantitative biology.

  11. Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog.

    Science.gov (United States)

    Hirz, M; Drögemüller, M; Schänzer, A; Jagannathan, V; Dietschi, E; Goebel, H H; Hecht, W; Laubner, S; Schmidt, M J; Steffen, F; Hilbe, M; Köhler, K; Drögemüller, C; Herden, C

    2017-03-01

    Neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases that have been described in a variety of dog breeds, where they are caused by different mutations in different genes. However, the causative gene defect in the breed Alpenländische Dachsbracke remained unknown so far. Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene. Case 1, a 2-year-old male Alpenländische Dachsbracke was presented with neurological signs including disorientation, character changes including anxiety states and aggressiveness, sudden blindness and reduction of food intake. Magnetic resonance imaging (MRI) scans showed cerebral atrophy with dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci. Postmortem examination of the central nervous system (CNS) showed neuronal loss in the cerebral cortex, cerebellum and spinal cord with massive intracellular deposits of ceroid pigment. Additional ceroid-lipofuscin deposits were observed in the enteric nervous system and in macrophages within spleen, lymph nodes and lung. Ultrastructural analyses confirmed NCL with the presence of osmiophilic membrane bounded lamellar-like structures. Case 2, a 1,5-year old female Alpenländische Dachsbracke was presented with progressive generalized forebrain disease including mental changes such as fearful reactions to various kinds of external stimuli and disorientation. The dog also displayed seizures, absence of menace reactions and negative cotton-ball test with normal pupillary light reactions. The clinical and post mortem examination yielded similar results in the brain as in Case 1. Whole genome sequencing of Case 1 and PCR results of both cases revealed a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form

  12. A central role for TOR signalling in a yeast model for juvenile CLN3 disease

    Directory of Open Access Journals (Sweden)

    Michael E. Bond

    2015-11-01

    Full Text Available Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs or Batten disease in the fission yeast Schizosaccharomyces pombe. A global screen for genetic interactions with btn1 highlighted a conserved key signalling hub in which multiple components functionally relate to this conserved disease gene. This signalling hub includes two major mitogen-activated protein kinase (MAPK cascades, and centers on the Tor kinase complexes TORC1 and TORC2. We confirmed that yeast cells modelling CLN3 disease exhibit features consistent with dysfunction in the TORC pathways, and showed that modulating TORC function leads to a comprehensive rescue of defects in this yeast disease model. The same pathways may be novel targets in the development of therapies for the NCLs and related diseases.

  13. New Results from the NOAA CREST Lidar Network (CLN Observations in the US Eastcoast

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    Moshary Fred

    2016-01-01

    Full Text Available This paper presents coordinated ground-based observations by the NOAA-CREST Lidar Network (CLN for profiling of aerosols, cloud, water vapor, and wind along the US east coast including Caribbean region at Puerto Rico. The instrumentation, methodology and observation capability are reviewed. The applications to continental and intercontinental-scale transport of smoke and dust plumes, and their large scale regional impact are discussed.

  14. (3Z-5-Chloro-3-(hydroxyiminoindolin-2-one

    Directory of Open Access Journals (Sweden)

    Bianca Barreto Martins

    2016-10-01

    Full Text Available In the title compound, C8H5ClN2O2 (common name: 5-chloroisatin 3-oxime, the molecular structure deviates slightly from the ideal planarity, with a maximum deviation of 0.0478 (8 Å for the non-H atoms. In the crystal, molecules are linked by N—H...O interactions, building centrosymmetric dimers with graph-set motif R22(8. Additionally, the molecules are connected by pairs of O—H...O interactions into chains along [100] with a C(6 motif. The hydrogen-bonded dimers and chains build a two-dimensional network parallel to (100. The packing also features π–π stacking interactions between benzene rings [centroid–centroid distance = 3.748 (2 Å].

  15. Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

    Czech Academy of Sciences Publication Activity Database

    Kunická, T.; Procházka, Pavel; Krus, I.; Bendová, Petra; Protivová, M.; Susová, S.; Hlaváč, V.; Liška, V.; Novák, P.; Schneiderová, M.; Pitule, P.; Bruha, J.; Vyčítal, O.; Vodička, Pavel; Souček, P.

    2017-01-01

    Roč. 16, oct (2017), s. 795 ISSN 1471-2407 R&D Projects: GA MZd(CZ) NT14329; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : colorectal carcinoma * 5-fluorouracil * methylation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.288, year: 2016

  16. 2-Amino-5-chloropyridinium nitrate

    Directory of Open Access Journals (Sweden)

    Donia Zaouali Zgolli

    2009-11-01

    Full Text Available The title structure, C5H6ClN2+·NO3−, is held together by extensive hydrogen bonding between the NO3− ions and 2-amino-5-chloropyridinium H atoms. The cation–anion N—H...O hydrogen bonds link the ions into a zigzag- chain which develops parallel to the b axis. The structure may be compared with that of the related 2-amino-5-cyanopyridinium nitrate.

  17. The Networks of Genes Encoding Palmitoylated Proteins in Axonal and Synaptic Compartments Are Affected in PPT1 Overexpressing Neuronal-Like Cells

    Directory of Open Access Journals (Sweden)

    Francesco Pezzini

    2017-08-01

    Full Text Available CLN1 disease (OMIM #256730 is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product Palmitoyl-Protein Thioesterase 1 (PPT1 is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 expression is also linked to synaptic compartments. The aim of this study was to unravel molecular signatures connected to CLN1. We utilized SH-SY5Y neuroblastoma cells overexpressing wild type CLN1 (SH-p.wtCLN1 and five selected CLN1 patients’ mutations. The cellular distribution of wtPPT1 was consistent with regular processing of endogenous protein, partially detected inside Lysosomal Associated Membrane Protein 2 (LAMP2 positive vesicles, while the mutants displayed more diffuse cytoplasmic pattern. Transcriptomic profiling revealed 802 differentially expressed genes (DEGs in SH-p.wtCLN1 (as compared to empty-vector transfected cells, whereas the number of DEGs detected in the two mutants (p.L222P and p.M57Nfs*45 was significantly lower. Bioinformatic scrutiny linked DEGs with neurite formation and neuronal transmission. Specifically, neuritogenesis and proliferation of neuronal processes were predicted to be hampered in the wtCLN1 overexpressing cell line, and these findings were corroborated by morphological investigations. Palmitoylation survey identified 113 palmitoylated protein-encoding genes in SH-p.wtCLN1, including 25 ones simultaneously assigned to axonal growth and synaptic compartments. A remarkable decrease in the expression of palmitoylated proteins, functionally related to axonal elongation (GAP43, CRMP1 and NEFM and of the synaptic marker SNAP25, specifically in SH-p.wtCLN1 cells was confirmed by immunoblotting. Subsequent, bioinformatic network survey of DEGs assigned to the synaptic annotations linked 81 DEGs, including 23 ones encoding for palmitoylated proteins. Results obtained in this experimental setting outlined two affected functional modules (connected to

  18. An atypical case of neuronal ceroid lipofuscinosis with co-inheritance of a variably penetrant POLG1 mutation

    Directory of Open Access Journals (Sweden)

    Staropoli John F

    2012-06-01

    Full Text Available Abstract Background The neuronal ceroid lipofuscinoses (NCLs, or Batten disease comprise the most common Mendelian form of childhood-onset neurodegeneration, but the functions of the known underlying gene products remain poorly understood. The clinical heterogeneity of these disorders may shed light on genetic interactors that modify disease onset and progression. Case presentation We describe a proband with congenital hypotonia and an atypical form of infantile-onset, biopsy-proven NCL. Pathologic and molecular work-up of this patient identified CLN5 mutations as well as a mutation―previously described as incompletely penetrant or a variant of unknown significance―in POLG1, a nuclear gene essential for maintenance of mitochondrial DNA (mtDNA copy number. The congenital presentation of this patient is far earlier than that described for either CLN5 patients or affected carriers of the POLG1 variant (c.1550 G > T, p.Gly517Val. Assessment of relative mtDNA copy number and mitochondrial membrane potential in the proband and control subjects suggested a pathogenic effect of the POLG1 change as well as a possible functional interaction with CLN5 mutations. Conclusions These findings suggest that an incompletely penetrant variant in POLG1 may modify the clinical phenotype in a case of CLN5 and are consistent with emerging evidence of interactions between NCL-related genes and mitochondrial physiology.

  19. Broadening the horizon – level 2.5 of the HUPO-PSI format for molecular interactions

    Directory of Open Access Journals (Sweden)

    Cusick Michael E

    2007-10-01

    Full Text Available Abstract Background Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. Results The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. Conclusion The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel.

  20. 4-Chloro­selanyl-3,5-diethyl-1H-pyrazol-2-ium chloride

    Science.gov (United States)

    Seredyuk, Maksym; Znovjyak, Kateryna O.; Sliva, Tetyana Yu.; Haukka, Matti; Fritsky, Igor O.

    2011-01-01

    In the cation of the title compound, C7H12ClN2Se+·Cl−, the ethyl­ene groups and the Se–Cl fragment adopt a cis configuration with a C—Se—Cl angle of 96.09 (6)°. In the crystal, inter­molecular N—H⋯Cl hydrogen bonds link two cations and two chlorine anions into centrosymmetric clusters. π–π inter­actions between the pyrazole rings [centroid–centroid distance of 3.530 (2) Å] link these clusters into columns along [001] with short inter­molecular Se⋯Cl− contacts of 2.995 (1) Å. PMID:22220089

  1. 1-[3-(4-Chlorophenyl-5-(4-methoxyphenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2012-04-01

    Full Text Available In the title compound, C18H17ClN2O2, the benzene rings form dihedral angles of 6.69 (6 and 74.88 (5° with the 4,5-dihydro-1H-pyrazole ring. The benzene rings form a dihedral angle of 76.67 (5° with each other. In the crystal, molecules are linked via bifurcated (C,C–H...O hydrogen bonds into chains along [010]. The crystal structure is further consolidated by C—H...π interactions.

  2. Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

    Science.gov (United States)

    Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

    2016-05-01

    CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests

  3. Crystal structure of 4-aminopyridinium 5-(5-chloro-2,4-dinitrophenyl-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate hemihydrate

    Directory of Open Access Journals (Sweden)

    Manickkam Vaduganathan

    2014-10-01

    Full Text Available The title molecular salt, C5H7N2+·C12H8ClN4O7−·0.5H2O, crystallizes as a hemihydrate. The two rings in the barbiturate anion are not coplanar but make a dihedral angle of 43.17 (16°. The two nitro groups deviate from the ring to which they are attached; the nitro group ortho with respect to the ring junction is more deviated [39.3 (4°] than that in the para position [4.2 (5°], probably to overcome steric hindrance. As a result of this, the latter nitro group is more involved in delocalizing the negative charge of the anion than the former nitro group. In the crystal, the cations and anions are linked via N—H...O hydrogen bonds forming zigzag chains along [10-1]. The chains are linked by O—H...O and C—H...O hydrogen bonds, forming slabs lying parallel to (10-1. Further C—H...O hydrogen bonds link the slabs, forming a three-dimensional structure.

  4. Molecular phospholipid films on solid supports

    DEFF Research Database (Denmark)

    Czolkos, Ilja; Jesorka, Aldo; Orwar, Owe

    2011-01-01

    Phospholipid membranes are versatile structures for mimicking biological surfaces. Bilayer and monolayer membranes can be formed on solid supports, leading to enhanced stability and accessibility of the biomimetic molecular film. This has facilitated functional studies of membrane proteins and ai...

  5. Ethyl 13-(4-chlorophenyl-11-methyl-6-oxo-5-phenyl-8-thia-3,4,5,10-tetraazatricyclo[7.4.0.02,7]trideca-1(9,2(7,3,10,12-pentaene-12-carboxylate

    Directory of Open Access Journals (Sweden)

    Elham A. Al-Taifi

    2016-05-01

    Full Text Available In the title molecule, C24H17ClN4O3S, the central tricyclic moiety is twisted slightly, as indicated by the dihedral angles of 4.86 (5 and 0.97 (6°, respectively, between the five-membered ring and the C3N3 and pyridyl rings. Additionally, the chlorobenzene ring makes a dihedral angle of 65.80 (5° with the pyridyl ring. Weak C—H...O, C—Cl...N [3.0239 (13 Å] and π–π stacking interactions [inter-centroid distance between thienyl rings = 3.6994 (8 Å, and between thienyl and pyridyl rings = 3.7074 (8 Å] contribute to the molecular packing. The ethyl group in the ester moiety is disordered over two sets of sites, with the major component having an occupancy of 0.567 (11.

  6. The crystal structure of 6-(4-chlorophenyl-2-(4-methylbenzylimidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde

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    A. Sowmya

    2016-10-01

    Full Text Available In the title imidazo[2,1-b][1,3,4]thiadiazole derivative, C19H14ClN3OS, the 4-methylbenzyl and chlorophenyl rings are inclined to the planar imidazo[2,1-b][1,3,4]thiadiazole moiety (r.m.s. deviation = 0.012 Å by 64.5 (1 and 3.7 (1°, respectively. The molecular structure is primarily stabilized by a strong intramolecular C—H...O hydrogen bond, leading to the formation of a pseudo-seven-membered S(7 ring motif, and a short intramolecular C—H...N contact forming an S(5 ring motif. In the crystal, molecules are linked by pairs of C—H...S hydrogen bonds, forming inversion dimers. The dimers are linked by C—H...O and C—H...π interactions, forming chains propagating along [110].

  7. 2-Amino-5-chloropyridinium trifluoroacetate

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    Madhukar Hemamalini

    2010-04-01

    Full Text Available The asymmetric unit of the title salt, C5H6ClN2+·C2F3O2−, contains two independent 2-amino-5-chloropyridinium cations and two independent trifluoroacetate anions. The F atoms of both anions are disordered over two sets of positions, with occupancy ratios of 0.672 (12:0.328 (12 and 0.587 (15:0.413 (15. In the crystal, the cations and anions are linked via N—H...O and C—H...O hydrogen bonds, forming a two-dimensional network parallel to (001.

  8. Molecular dynamics simulation based on the multi-component molecular orbital method: Application to H5O2+,D5O2+,andT5O2+

    International Nuclear Information System (INIS)

    Ishimoto, Takayoshi; Koyama, Michihisa

    2012-01-01

    Graphical abstract: Molecular dynamics method based on multi-component molecular orbital method was applied to basic hydrogen bonding systems, H 5 O 2 + , and its isotopomers (D 5 O 2 + andT 5 O 2 + ). Highlights: ► Molecular dynamics method with nuclear quantum effect was developed. ► Multi-component molecular orbital method was used as ab initio MO calculation. ► Developed method applied to basic hydrogen bonding system, H 5 O 2 + , and isotopomers. ► O ⋯ O vibrational stretching reflected to the distribution of protonic wavefunctions. ► H/D/T isotope effect was also analyzed. - Abstract: We propose a molecular dynamics (MD) method based on the multi-component molecular orbital (MC M O) method, which takes into account the quantum effect of proton directly, for the detailed analyses of proton transfer in hydrogen bonding system. The MC M O based MD (MC M O-MD) method is applied to the basic structures, H 5 O 2 + (called “Zundel ion”), and its isotopomers (D 5 O 2 + andT 5 O 2 + ). We clearly demonstrate the geometrical difference of hydrogen bonded O ⋯ O distance induced by H/D/T isotope effect because the O ⋯ O in H-compound was longer than that in D- or T-compound. We also find the strong relation between stretching vibration of O ⋯ O and the distribution of hydrogen bonded protonic wavefunction because the protonic wavefunction tends to delocalize when the O ⋯ O distance becomes short during the dynamics. Our proposed MC M O-MD simulation is expected as a powerful tool to analyze the proton dynamics in hydrogen bonding systems.

  9. Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

    2016-09-01

    4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

  10. Molecular organization and comparative analysis of chromosome 5B of the wild wheat ancestor Triticum dicoccoides

    Czech Academy of Sciences Publication Activity Database

    Akpinar, B.A.; Yuce, M.; Lucas, S.; Vrána, Jan; Burešová, Veronika; Doležel, Jaroslav; Budak, H.

    2015-01-01

    Roč. 5, JUN 18 (2015) ISSN 2045-2322 R&D Projects: GA ČR GBP501/12/G090; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : TURGIDUM VAR. DICOCCOIDES * MARKER DEVELOPMENT * GENOME SEQUENCE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.228, year: 2015

  11. 4-({[6-(4-Chlorobenzyl-4-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl]sulfanyl}acetyl-3-phenylsydnone

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-04-01

    Full Text Available In the title syndone (1,2,3-oxadiazol-3-ylium-5-olate compound, C21H16ClN5O4S, the dihedral angle between the benzene and oxadiazole rings is 55.62 (11° and that between the triazine and the chloro-substituted phenyl rings is 82.45 (9°. There is an intramolecular C—H...S hydrogen bond, which generates an S(5 ring motif. In the crystal, inversion dimers linked by pairs of C—H...O hydrogen bonds generate R22(20 loops. The dimers are connected by C—H...N and C—H...O hydrogen bonds.

  12. Cold Water Vapor in the Barnard 5 Molecular Cloud

    Science.gov (United States)

    Wirstrom, E. S.; Charnley, S. B.; Persson, C. M.; Buckle, J. V.; Cordiner, M. A.; Takakuwa, S.

    2014-01-01

    After more than 30 yr of investigations, the nature of gas-grain interactions at low temperatures remains an unresolved issue in astrochemistry. Water ice is the dominant ice found in cold molecular clouds; however, there is only one region where cold ((is) approximately 10 K) water vapor has been detected-L1544. This study aims to shed light on ice desorption mechanisms under cold cloud conditions by expanding the sample. The clumpy distribution of methanol in dark clouds testifies to transient desorption processes at work-likely to also disrupt water ice mantles. Therefore, the Herschel HIFI instrument was used to search for cold water in a small sample of prominent methanol emission peaks. We report detections of the ground-state transition of o-H2O (J = 110-101) at 556.9360 GHz toward two positions in the cold molecular cloud, Barnard 5. The relative abundances of methanol and water gas support a desorption mechanism which disrupts the outer ice mantle layers, rather than causing complete mantle removal.

  13. COLD WATER VAPOR IN THE BARNARD 5 MOLECULAR CLOUD

    Energy Technology Data Exchange (ETDEWEB)

    Wirström, E. S.; Persson, C. M. [Department of Earth and Space Sciences, Chalmers University of Technology, Onsala Space Observatory, SE-439 92 Onsala (Sweden); Charnley, S. B.; Cordiner, M. A. [Astrochemistry Laboratory and The Goddard Center for Astrobiology, Mailstop 691, NASA Goddard Space Flight Center, 8800 Greenbelt Road, Greenbelt, MD 20770 (United States); Buckle, J. V. [Astrophysics Group, Cavendish Laboratory, J. J. Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Takakuwa, S., E-mail: eva.wirstrom@chalmers.se [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 106, Taiwan (China)

    2014-06-20

    After more than 30 yr of investigations, the nature of gas-grain interactions at low temperatures remains an unresolved issue in astrochemistry. Water ice is the dominant ice found in cold molecular clouds; however, there is only one region where cold (∼10 K) water vapor has been detected—L1544. This study aims to shed light on ice desorption mechanisms under cold cloud conditions by expanding the sample. The clumpy distribution of methanol in dark clouds testifies to transient desorption processes at work—likely to also disrupt water ice mantles. Therefore, the Herschel HIFI instrument was used to search for cold water in a small sample of prominent methanol emission peaks. We report detections of the ground-state transition of o-H{sub 2}O (J = 1{sub 10}-1{sub 01}) at 556.9360 GHz toward two positions in the cold molecular cloud, Barnard 5. The relative abundances of methanol and water gas support a desorption mechanism which disrupts the outer ice mantle layers, rather than causing complete mantle removal.

  14. 2-[(2-Chlorobenzylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2011-09-01

    Full Text Available In the title compound, C16H13ClN2S, the mean planes fitted through all non-H atoms of the heterocyclic five-membered and the benzene rings are oriented at a dihedral angle of 5.19 (7°. In the crystal, a weak C—H...π interaction occurs, along with weak π–π interactions [cenroid–centroid distance = 3.7698 (11 Å].

  15. Nanoparticle-Supported Molecular Polymerization Catalysts

    OpenAIRE

    Amgoune, Abderramane; Krumova, Marina; Mecking, Stefan

    2008-01-01

    Homogeneous molecular catalysts are immobilzed in a well-defined fashion on individual silica nanoparticles with a narrow particle size distribution by covalent attachment. This synthetic methodology is demonstrated with modified salicylaldiminato-substituted titanium(IV) complexes incorporating a trimethoxysilane-terminated linker: dichloro-bis[κ2-N,O-6-(3-(trimethoxysilyl)propoxyphenylimino)-2-tert-butyl-phenolato]titanium(IV) (3) and dichlorobis[κ2-N,O-6-(4-(trimethoxysilyl)propoxy-2,3,5,6...

  16. Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky disease correlate with advancing age and deteriorating neurological function.

    Directory of Open Access Journals (Sweden)

    Anton Orlin

    Full Text Available BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL, one form of Batten's disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described. METHODS: Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed. RESULTS: Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1. The mean ophthalmic severity score was 2.6 (range 1 to 5. The mean neurological severity score was 6.1 (range 2 to 11. Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005 and patients with more severe neurological findings (p<0.03. A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002. A direct association was also found between age and the ophthalmic manifestations (p<0.0002, with older children having more severe ophthalmic manifestations. CONCLUSIONS: Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.

  17. Ethyl 2-{3-[(2-chloro-1,3-thiazol-5-ylmethyl]-4-nitroimino-1,3,5-triazinan-1-yl}acetate

    Directory of Open Access Journals (Sweden)

    Chuan-wen Sun

    2010-06-01

    Full Text Available In the title compound, C11H15ClN6O4S, which belongs to the neonicotinoid class of insecticidally active heterocyclic compounds, the six-membered triazine ring adopts an opened envolope conformation. The planar nitro imine group [dihedral angle between nitro and imine groups = 1.07 (7°] and the thiazole ring are oriented at a dihedral angle of 69.62 (8°. A classical intramolecular N—H...O hydrogen bond is found in the molecular structure. Moreover, one classical intermolecular N—H...N and four non-classical C—H...O and C—H...N hydrogen bonds are also present in the crystal structure. Besides intermolecular hydrogen bonds, the Cl atom forms an intermolecular short contact [3.020 (2 Å] with one of the nitro O atoms.

  18. Synthesis of cerium oxide catalysts supported on MCM-41 molecular sieve

    International Nuclear Information System (INIS)

    Souza, E.L.S.; Barros, T.R.B.; Sousa, B.V. de

    2016-01-01

    Porous materials have been widely studied as catalysts and catalyst support. The MCM-41 structure is the one that has been most studied because of its application possibilities in chemical processes. This work aimed to obtain and characterize cerium oxide catalysts supported on MCM-41 molecular sieve. The molecular sieve was synthesized by the conventional method with the following molar composition: 1 SiO2: 0.30 CTABr: NH3 11: 144 H2O. Then, 25% w/w cerium was incorporated into the MCM-41 using the wet impregnation process and the material obtained was activated by calcination. From the XRD patterns was confirmed the structure of the molecular sieve, and were identified the cerium oxide phases in its structure. The textural catalysts characteristics were investigated by isotherms of N2 adsorption/desorption (BET method). (author)

  19. Evidence for aberrant astrocyte hemichannel activity in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL).

    Science.gov (United States)

    Burkovetskaya, Maria; Karpuk, Nikolay; Xiong, Juan; Bosch, Megan; Boska, Michael D; Takeuchi, Hideyuki; Suzumura, Akio; Kielian, Tammy

    2014-01-01

    Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have been implicated in CNS pathology by allowing the non-discriminant passage of molecules between the intracellular and extracellular milieus. Here we examined acute brain slices from CLN3 mutant mice (CLN3Δex7/8) to determine whether CLN3 loss alters the balance of GJ and HC activity. CLN3Δex7/8 mice displayed transient increases in astrocyte HC opening at postnatal day 30 in numerous brain regions, compared to wild type (WT) animals; however, HC activity steadily decreased at postnatal days 60 and 90 in CLN3Δex7/8 astrocytes to reach levels lower than WT cells. This suggested a progressive decline in astrocyte function, which was supported by significant reductions in glutamine synthetase, GLAST, and connexin expression in CLN3Δex7/8 mice compared to WT animals. Based on the early increase in astrocyte HC activity, CLN3Δex7/8 mice were treated with the novel carbenoxolone derivative INI-0602 to inhibit HCs. Administration of INI-0602 for a one month period significantly reduced lysosomal ceroid inclusions in the brains of CLN3Δex7/8 mice compared to WT animals, which coincided with significant increases in astrocyte GJ communication and normalization of astrocyte resting membrane potential to WT levels. Collectively, these findings suggest that alterations in

  20. Evidence for aberrant astrocyte hemichannel activity in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL.

    Directory of Open Access Journals (Sweden)

    Maria Burkovetskaya

    Full Text Available Juvenile Neuronal Ceroid Lipofuscinosis (JNCL is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ channels. In contrast, unopposed hemichannels (HCs have been implicated in CNS pathology by allowing the non-discriminant passage of molecules between the intracellular and extracellular milieus. Here we examined acute brain slices from CLN3 mutant mice (CLN3Δex7/8 to determine whether CLN3 loss alters the balance of GJ and HC activity. CLN3Δex7/8 mice displayed transient increases in astrocyte HC opening at postnatal day 30 in numerous brain regions, compared to wild type (WT animals; however, HC activity steadily decreased at postnatal days 60 and 90 in CLN3Δex7/8 astrocytes to reach levels lower than WT cells. This suggested a progressive decline in astrocyte function, which was supported by significant reductions in glutamine synthetase, GLAST, and connexin expression in CLN3Δex7/8 mice compared to WT animals. Based on the early increase in astrocyte HC activity, CLN3Δex7/8 mice were treated with the novel carbenoxolone derivative INI-0602 to inhibit HCs. Administration of INI-0602 for a one month period significantly reduced lysosomal ceroid inclusions in the brains of CLN3Δex7/8 mice compared to WT animals, which coincided with significant increases in astrocyte GJ communication and normalization of astrocyte resting membrane potential to WT levels. Collectively, these findings suggest that

  1. Crystal structure of 2-amino-4-(4-chlorophenyl-1-(4-methylphenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Shaaban K. Mohamed

    2015-12-01

    Full Text Available In the title compound, C23H20ClN3O, each of the cyclohexene and 1,4-dihydropyridine rings of the 1,4,5,6,7,8-hexahydroquinoline ring system adopts a twisted-boat conformation. The dihedral angle between the two benzene rings is 11.52 (7°. In the crystal, molecules are linked through a pair of amino–nitrile N—H...N hydrogen bonds, forming inversion dimers. These assemble into a three-dimensional network via C—H...O and C—H...π interactions.

  2. Synthesis and X-ray structure of the dysprosium(III complex derived from the ligand 5-chloro-1,3-diformyl-2-hydroxybenzene-bis-(2-hydroxybenzoylhydrazone [Dy2(C22H16ClN4O53](SCN 3.(H2O.(CH3OH

    Directory of Open Access Journals (Sweden)

    Aliou H. Barry

    2003-12-01

    Full Text Available The title compound [Dy2(C22H16ClN4O53](SCN 3.(H2O.(CH3OH has been synthesized and its crystal structure determined by single X-ray diffraction at room temperature. The two nine coordinated Dy(III are bound to three macromolecules ligand through the phenolic oxygens of the p-chlorophenol moieties, the nitrogen atoms and the carbonyl functions of the hydrazonic moieties. The phenolic oxygen atoms of the 2-hydroxybenzoyl groups are not bonded to the metal ions. In the bases of the coordination polyhedra the six Dy-N bonds are in the range 2.563(13-2.656(13 Å and the twelve Dy-O bonds are in the range 2.281(10-2.406(10 Å.

  3. Large-scale phenotyping of an accurate genetic mouse model of JNCL identifies novel early pathology outside the central nervous system.

    Directory of Open Access Journals (Sweden)

    John F Staropoli

    Full Text Available Cln3(Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL, an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3(Δex7/8 mice. Homozygous Cln3(Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10-14 weeks of age. Homozygous Cln3(Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12-13 week old homozygous Cln3(Δex7/8 mice, which were also seen to a lesser extent in heterozygous Cln3(Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15-16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV, and reticulocyte counts were reproducibly increased in homozygous Cln3(Δ (ex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3(Δ (ex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3(Δ (ex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3(Δ (ex7/8 mice that merit further study for JNCL biomarker development.

  4. Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas.

    Science.gov (United States)

    Murakami, Masanori; Yoshimoto, Takanobu; Nakabayashi, Kazuhiko; Nakano, Yujiro; Fukaishi, Takahiro; Tsuchiya, Kyoichiro; Minami, Isao; Bouchi, Ryotaro; Okamura, Kohji; Fujii, Yasuhisa; Hashimoto, Koshi; Hata, Ken-Ichiro; Kihara, Kazunori; Ogawa, Yoshihiro

    2017-10-01

    The pathophysiology of aldosterone-producing adenomas (APAs) has been investigated via genetic approaches and the pathogenic significance of a series of somatic mutations, including KCNJ5 , has been uncovered. However, how the mutational status of an APA is associated with its molecular characteristics, including its transcriptome and methylome, has not been fully understood. This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status. Cortisol-producing adenomas (CPAs) were used as reference. We conducted transcriptome and methylome analyses of 29 APAs with KCNJ5 mutations, 8 APAs without KCNJ5 mutations and 5 CPAs. Genome-wide gene expression and CpG methylation profiles were obtained from RNA and DNA samples extracted from these 42 adrenal tumors. Cluster analysis of the transcriptome and methylome revealed molecular heterogeneity in APAs depending on their mutational status. DNA hypomethylation and gene expression changes in Wnt signaling and inflammatory response pathways were characteristic of APAs with KCNJ5 mutations. Comparisons between transcriptome data from our APAs and that from normal adrenal cortex obtained from the Gene Expression Omnibus suggested similarities between APAs with KCNJ5 mutations and zona glomerulosa. The present study, which is based on transcriptome and methylome analyses, indicates the molecular heterogeneity of APAs depends on their mutational status. Here, we report the unique characteristics of APAs with KCNJ5 mutations. © 2017 Society for Endocrinology.

  5. Immobilization of molecular catalysts in supported ionic liquid phases.

    Science.gov (United States)

    Van Doorslaer, Charlie; Wahlen, Joos; Mertens, Pascal; Binnemans, Koen; De Vos, Dirk

    2010-09-28

    In a supported ionic liquid phase (SILP) catalyst system, an ionic liquid (IL) film is immobilized on a high-surface area porous solid and a homogeneous catalyst is dissolved in this supported IL layer, thereby combining the attractive features of homogeneous catalysts with the benefits of heterogeneous catalysts. In this review reliable strategies for the immobilization of molecular catalysts in SILPs are surveyed. In the first part, general aspects concerning the application of SILP catalysts are presented, focusing on the type of catalyst, support, ionic liquid and reaction conditions. Secondly, organic reactions in which SILP technology is applied to improve the performance of homogeneous transition-metal catalysts are presented: hydroformylation, metathesis reactions, carbonylation, hydrogenation, hydroamination, coupling reactions and asymmetric reactions.

  6. Strength order and nature of the π-hole bond of cyanuric chloride and 1,3,5-triazine with halide.

    Science.gov (United States)

    Wang, Hui; Li, Chen; Wang, Weizhou; Jin, Wei Jun

    2015-08-28

    The (13)C NMR chemical shift moving upfield indicates the main model of π-holeX(-) bond between cyanuric chloride/1,3,5-triazine (3ClN/3N), which possess both the π-hole and σ-hole, and X(-). (13)C NMR and UV absorption titration in acetonitrile confirmed that the bonding abilities of 3ClN/3N with X(-) follow the order I(-) > Br(-) > Cl(-), which is apparently the order of the charge transfer ability of halide to 3ClN/3N. Chemical calculations showed that the bonding abilities in solution were essentially consistent with those obtained by titration experiments. However, the results in the gas phase were the reverse, i.e., π-holeCl(-) > π-holeBr(-) > π-holeI(-) in bonding energy, which obeys the order of electrostatic interaction. In fact, the π-hole bond and σ-hole bond compete with solvation and possible anion-hydrogen bond between a solvent molecule and a halide in solution. An explanation is that the apparent charge transfer order of π-/σ-holeI(-) > π-/σ-holeBr(-) > π-/σ-holeCl(-) occurs for weak π-hole bonds and σ-hole bonds, whereas the order of electrostatic attraction of π-/σ-holeCl(-) > π-/σ-holeBr(-) > π-/σ-holeI(-) is valid for strong bonds. It can be concluded by combining energy decomposition analysis and natural bond orbital analysis that the π-holeX(-) bond and σ-holeX(-) bond are electrostatically attractive in nature regardless of whether the order is I(-) > Br(-) > Cl(-) or the reverse.

  7. Molecular metal catalysts on supports: organometallic chemistry meets surface science.

    Science.gov (United States)

    Serna, Pedro; Gates, Bruce C

    2014-08-19

    Recent advances in the synthesis and characterization of small, essentially molecular metal complexes and metal clusters on support surfaces have brought new insights to catalysis and point the way to systematic catalyst design. We summarize recent work unraveling effects of key design variables of site-isolated catalysts: the metal, metal nuclearity, support, and other ligands on the metals, also considering catalysts with separate, complementary functions on supports. The catalysts were synthesized with the goal of structural simplicity and uniformity to facilitate incisive characterization. Thus, they are essentially molecular species bonded to porous supports chosen for their high degree of uniformity; the supports are crystalline aluminosilicates (zeolites) and MgO. The catalytic species are synthesized in reactions of organometallic precursors with the support surfaces; the precursors include M(L)2(acetylacetonate)1-2, with M = Ru, Rh, Ir, or Au and the ligands L = C2H4, CO, or CH3. Os3(CO)12 and Ir4(CO)12 are used as precursors of supported metal clusters, and some such catalysts are made by ship-in-a-bottle syntheses to trap the clusters in zeolite cages. The simplicity and uniformity of the supported catalysts facilitate precise structure determinations, even in reactive atmospheres and during catalysis. The methods of characterizing catalysts in reactive atmospheres include infrared (IR), extended X-ray absorption fine structure (EXAFS), X-ray absorption near edge structure (XANES), and nuclear magnetic resonance (NMR) spectroscopies, and complementary methods include density functional theory and atomic-resolution aberration-corrected scanning transmission electron microscopy for imaging of individual metal atoms. IR, NMR, XANES, and microscopy data demonstrate the high degrees of uniformity of well-prepared supported species. The characterizations determine the compositions of surface metal complexes and clusters, including the ligands and the metal-support

  8. Radiative transitions from Υ(5S) to molecular bottomonium

    International Nuclear Information System (INIS)

    Voloshin, M. B.

    2011-01-01

    The heavy quark spin symmetry implies that in addition to the recently observed Z(10610) and Z(10650) molecular resonances with I G =1 + , there should exist two or four molecular bottomonium-like states with I G =1 - . Properties of these G-odd states are considered, including their production in the radiative transitions from Υ(5S), by applying the same symmetry to the Υ(5S) resonance and the transition amplitudes. The considered radiative processes can provide a realistic option for observing the yet hypothetical states.

  9. The Climate Literacy Network: Leveraging a Diverse Community to Broaden the Reach of Your Climate Literacy Efforts

    Science.gov (United States)

    Ledley, T. S.; Carley, S.; Niepold, F.; Duggan-Haas, D. A.; Hollweg, K.; McCaffrey, M. S.

    2012-12-01

    There are a wide range of programs, activities, and projects focused on improving the understanding of climate science by citizens in a multitude of contexts. While most of these are necessarily customized for the particular audiences, communities, or regions they address, they can learn a lot from each other by sharing their experiences, expertise, and materials. The Climate Literacy Network (CLN, http://cleanet.org/cln), established in 2008 to facilitate the implementation of the Climate Literacy Essential Principles of Climate Science, is a diverse group of over 370 stakeholders with a wide range of expertise in, for example, science, policy, media, arts, economics, psychology, education, and social sciences. The CLN meets virtually weekly to share information about ongoing activities and new resources, discuss controversial public issues and ways to address them, get input from this diverse community on directions individual efforts might take, organize climate literacy sessions at professional meetings, provide input on documents relevant to climate literacy, and address common needs of the individual members. The weekly CLN teleconferences are also a venue for presentations from climate change education efforts to extend their reach and potential impact. The teleconferences are supported by an active listserv that is archived on the CLN website along with recordings of past teleconference and the schedule of upcoming teleconferences (http://cleanet.org/clean/community/cln/telecon_schedule.html). In this presentation we will describe the details of these various activities, give examples of how discussions within the CLN has led to funded efforts and expanded partnerships, and identify ways you can participate in and leverage this very active community.

  10. Mesoporous molecular sieves as advanced supports for olefin metathesis catalysts

    Czech Academy of Sciences Publication Activity Database

    Balcar, Hynek; Čejka, Jiří

    2013-01-01

    Roč. 257, 21-22 (2013), s. 3107-3124 ISSN 0010-8545 R&D Projects: GA AV ČR IAA400400805; GA ČR GBP106/12/G015 Institutional support: RVO:61388955 Keywords : Olefin metathesis * mesoporous molecular sieves * Heterogeneous catalysts Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 12.098, year: 2013

  11. Electronic structure of surface-supported bis(phthalocyaninato) terbium(III) single molecular magnets.

    Science.gov (United States)

    Vitali, Lucia; Fabris, Stefano; Conte, Adriano Mosca; Brink, Susan; Ruben, Mario; Baroni, Stefano; Kern, Klaus

    2008-10-01

    The electronic structure of isolated bis(phthalocyaninato) terbium(III) molecules, a novel single-molecular-magnet (SMM), supported on the Cu(111) surface has been characterized by density functional theory and scanning tunneling spectroscopy. These studies reveal that the interaction with the metal surface preserves both the molecular structure and the large spin magnetic moment of the metal center. The 4f electron states are not perturbed by the adsorption while a strong molecular/metal interaction can induce the suppression of the minor spin contribution delocalized over the molecular ligands. The calculations show that the inherent spin magnetic moment of the molecule is only weakly affected by the interaction with the surface and suggest that the SMM character might be preserved.

  12. Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells.

    Science.gov (United States)

    Requena, Teresa; Gallego-Martinez, Alvaro; Lopez-Escamez, Jose A

    2018-01-01

    Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear.org/index.html) and obtained gene expression fold-change between ENHCs and non-epithelial cells (NECs) against HCs for each gene. Differentially expressed genes (DEG) with a log2 fold change between 1 and -1 were discarded. The remaining genes were selected to search for interactions using Ingenuity Pathway Analysis and STRING platform. Specific molecular networks for ENHCs in the cochlea and the vestibular organs were generated and significant pathways were identified. Results : Between 1723 and 1559 DEG were found in the mouse cochlear and vestibular tissues, respectively. Six main pathways showed enrichment in the supporting cells in both tissues: (1) "Inhibition of Matrix Metalloproteases"; (2) "Calcium Transport I"; (3) "Calcium Signaling"; (4) "Leukocyte Extravasation Signaling"; (5) "Signaling by Rho Family GTPases"; and (6) "Axonal Guidance Si". In the mouse cochlea, ENHCs showed a significant enrichment in 18 pathways highlighting "axonal guidance signaling (AGS)" ( p = 4.37 × 10 -8 ) and "RhoGDI Signaling" ( p = 3.31 × 10 -8 ). In the vestibular dataset, there were 20 enriched pathways in ENHCs, the most significant being "Leukocyte Extravasation Signaling" ( p = 8.71 × 10 -6 ), "Signaling by Rho Family GTPases" ( p = 1.20 × 10 -5 ) and "Calcium Signaling" ( p = 1.20 × 10 -5 ). Among the top ranked networks, the most biologically significant network contained the

  13. Adsorption properties of the SAPO-5 molecular sieve

    KAUST Repository

    Hu, Enping; Lai, Zhiping; Wang, Kean

    2010-01-01

    The adsorption properties of an aluminophosphate molecular sieve, SAPO-5, were measured for a number of gases and vapors, including N2, water, isopropanol, and xylenes. The data showed that SAPO-5 is quite hydrophobic and has a strong selectivity of o-xylene over its isomers m- and p-xylene. © 2010 American Chemical Society.

  14. Adsorption properties of the SAPO-5 molecular sieve

    KAUST Repository

    Hu, Enping

    2010-09-09

    The adsorption properties of an aluminophosphate molecular sieve, SAPO-5, were measured for a number of gases and vapors, including N2, water, isopropanol, and xylenes. The data showed that SAPO-5 is quite hydrophobic and has a strong selectivity of o-xylene over its isomers m- and p-xylene. © 2010 American Chemical Society.

  15. N′-Benzylidene-2-({5-[(4-chlorophenoxymethyl]-4-phenyl-4H-1,2,4-triazol-3-yl}sulfanylacetohydrazide hemihydrate

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2016-04-01

    Full Text Available The title compound, C24H20ClN5O2S·0.5H2O, has three independent molecules in the asymmetric unit and two water molecules of crystallization, one of which is equally disordered over two sites. The three unique organic molecules differ in the conformations of the substituents on the pyrazole ring. In the crystal, extensive O—H...O, O—H...N, N—H...O and C—H...O hydrogen bonding generates a three-dimensional network and C—H...π interactions are also observed.

  16. Molecular and genetic insights into an infantile epileptic encephalopathy-CDKL5 disorder

    Institute of Scientific and Technical Information of China (English)

    Ailing Zhou; Song Han; Zhaolan Joe Zhou

    2017-01-01

    BACKGROUND:The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder.Given the large number of literature published thus far,this review aims to summarize current genetic studies,draw a consensus on proposed molecular functions,and point to gaps of knowledge in CDKL5 research.METHODS:A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years.We analyzed these publications and summarized the findings into four sections:genetic studies,CDKL5 expression pattems,molecular functions,and animal models.We also discussed challenges and future directions in each section.RESULTS:On the clinical side,CDKL5 disorder is characterized by early onset epileptic seizures,intellectual disability,and stereotypical behaviors.On the research side,a series of molecular and genetic studies in human patients,cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy,and pointed to a key role for CDKL5 in regulating neuronal function in the brain.Mouse models of CDKL5 disorder have also been developed,and notably,manifest behavioral phenotypes,mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage.CONCLUSIONS:Given what we have leamed thus far,future identification of robust,quantitative,and sensitive outcome measures would be the key in animal model studies,particularly in heterozygous females.In the meantime,molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes.

  17. Molecular and genetic insights into an infantile epileptic encephalopathy - CDKL5 disorder.

    Science.gov (United States)

    Zhou, Ailing; Han, Song; Zhou, Zhaolan Joe

    2017-02-01

    The discovery that mutations in cyclin-dependent kinase-like 5 ( CDKL5 ) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes.

  18. Crystal structure of chlorido(2-{1-[2-(4-chlorophenylhydrazin-1-ylidene-κN]ethyl}pyridine-κN(η5-pentamethylcyclopentadienylrhodium(III chloride

    Directory of Open Access Journals (Sweden)

    Neelakandan Devika

    2015-03-01

    Full Text Available The cation of the title compound, [Rh(η5-C5Me5Cl(C13H12ClN3]Cl, adopts a typical piano-stool geometry. The complex is chiral at the metal and crystallizes as a racemate. Upon coordination, the hydrazinylidenepyridine ligand is non-planar, an angle of 54.42 (7° being observed between the pyridine ring and the aromatic ring of the [2-(4-chlorophenylhydrazin-1-ylidene]ethyl group. In the crystal, a weak interionic N—H...Cl hydrogen bond is observed.

  19. Photochemistry of framework-supported M(diimine)(CO)3X complexes in three-dimensional lithium carboxylate metal–organic frameworks: monitoring the effect of framework cations

    OpenAIRE

    Reade, Thomas J.; Murphy, Thomas S.; Calladine, James A.; Horvath, Raphael; Clark, Ian P.; Greetham, Gregory M.; Towrie, Michael; Lewis, William; George, Michael W.; Champness, Neil R.

    2017-01-01

    The structures and photochemical behaviour of two new metal–organic frameworks (MOFs) are reported. Reaction of Re(2,2′-bipy-5,5′-dicarboxylic acid)(CO)3Cl or Mn(2,2′-bipy-5,5′-dicarboxylic acid)(CO)3Br with LiCl or LiBr, respectively, produces single crystals of {Li2(DMF)2 [(2,2′-bipy-5,5′-dicarboxylate)Re(CO)3Cl]}n (ReLi) or {Li2(DMF)2[(2,2′-bipy-5,5′-dicarboxylate)Mn(CO)3Br]}n (MnLi). The structures formed by the two MOFs comprise one-dimensional chains of carboxylate-bridged Li(I) cations...

  20. 1-[1-(4-Chloro-phen-yl)ethyl-idene]carbono-hydrazide.

    Science.gov (United States)

    Du, Lingyun; Du, Lei; Wang, Shuhao

    2009-08-12

    The mol-ecular skeleton of the title mol-ecule, C(9)H(11)ClN(4)O, is essentially planar, the dihedral angle between the ring and the and N/N/C plane being 6.7 (3)°. In the crystal, inter-molecular N-H⋯O and N-H⋯N hydrogen bonds link the mol-ecules into ribbons propagated along [010].

  1. Leishmania infections: Molecular targets and diagnosis

    Czech Academy of Sciences Publication Activity Database

    Akhoundi, M.; Downing, T.; Votýpka, Jan; Kuhls, K.; Lukeš, Julius; Cannet, A.; Ravel, C.; Marty, P.; Delaunay, P.; Kasbari, M.; Granouillac, B.; Gradoni, L.; Sereno, D.

    2017-01-01

    Roč. 57, OCT (2017), s. 1-29 ISSN 0098-2997 Institutional support: RVO:60077344 Keywords : molecular markers * diagnostic methods * hybrid strains * sympatric species * genome-wide map Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 5.686, year: 2016

  2. The Radar Cross Sections of Hayes TRX-11, TPT-5A and TPT-5l Towed Targets

    Science.gov (United States)

    1992-08-01

    77 - na n f5 z -3- 0’ iC - 0- = . -a -- V 0’ ~ ~ ~ ~ ~ ~ ~ ~ o ,~C r- = on C4v~ W) 0,- . ,--a Ca a’ a a C - cCaC -7 C -7 - c...Cl~~~~~ C C’ tV e mata a-- e- acCA C C, ’aC ’.’. - Caý C I ’. Cl CA w t Cl- - - -- - - - - - -- - ,C -r laCa - - - wC 7 A;’ Va -.- C- ae o 0’ -CC Cln... F5 :’ In in m C .j~j’C’ .. 7 ’C o.C Cý " 2 C Cc r- C- C4 C nr-r----r----r-- X - - 0 0 0 0 ’ C at VtC t~0 C~atr C-C .a V~a~ *.at ate07 ate-~~~ 7

  3. Nasal Colivelin treatment ameliorates memory impairment related to Alzheimer's disease.

    Science.gov (United States)

    Yamada, Marina; Chiba, Tomohiro; Sasabe, Jumpei; Terashita, Kenzo; Aiso, Sadakazu; Matsuoka, Masaaki

    2008-07-01

    Humanin (HN) and its derivatives, such as Colivelin (CLN), suppress neuronal death induced by insults related to Alzheimer's disease (AD) by activating STAT3 in vitro. They also ameliorate functional memory impairment of mice induced by anticholinergic drugs or soluble toxic amyloid-beta (Abeta) in vivo when either is directly administered into the cerebral ventricle or intraperitoneally injected. However, the mechanism underlying the in vivo effect remains uncharacterized. In addition, from the standpoint of clinical application, drug delivery methods that are less invasive and specific to the central nervous system (CNS) should be developed. In this study, we show that intranasally (i.n.) administered CLN can be successfully transferred to CNS via the olfactory bulb. Using several behavioral tests, we have demonstrated that i.n. administered CLN ameliorates memory impairment of AD models in a dose-responsive manner. Attenuation of AD-related memory impairment by HN derivatives such as CLN appears to be correlated with an increase in STAT3 phosphorylation levels in the septohippocampal region, suggesting that anti-AD activities of HN derivatives may be mediated by activation of STAT3 in vivo as they are in vitro. We further demonstrate that CLN treatment inhibits an Abeta induced decrease in the number of choline acetyltransferase (ChAT)-positive neurons in the medial septum. Combined with the finding that HN derivatives upregulate mRNA expression of neuronal ChAT and vesicular acetylcholine transporter (VAChT) in vitro, it is assumed that CLN may ameliorate memory impairment of AD models by supporting cholinergic neurotransmission, which is at least partly mediated by STAT3-mediated transcriptional upregulation of ChAT and VAChT.

  4. Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease.

    Science.gov (United States)

    Micsenyi, Matthew C; Sikora, Jakub; Stephney, Gloria; Dobrenis, Kostantin; Walkley, Steven U

    2013-06-26

    Protein aggregates are a common pathological feature of neurodegenerative diseases and several lysosomal diseases, but it is currently unclear what aggregates represent for pathogenesis. Here we report the accumulation of intraneuronal aggregates containing the macroautophagy adapter proteins p62 and NBR1 in the neurodegenerative lysosomal disease late-infantile neuronal ceroid lipofuscinosis (CLN2 disease). CLN2 disease is caused by a deficiency in the lysosomal enzyme tripeptidyl peptidase I, which results in aberrant lysosomal storage of catabolites, including the subunit c of mitochondrial ATP synthase (SCMAS). In an effort to define the role of aggregates in CLN2, we evaluated p62 and NBR1 accumulation in the CNS of Cln2(-/-) mice. Although increases in p62 and NBR1 often suggest compromised degradative mechanisms, we found normal ubiquitin-proteasome system function and only modest inefficiency in macroautophagy late in disease. Importantly, we identified that SCMAS colocalizes with p62 in extra-lysosomal aggregates in Cln2(-/-) neurons in vivo. This finding is consistent with SCMAS being released from lysosomes, an event known as lysosomal membrane permeability (LMP). We predicted that LMP and storage release from lysosomes results in the sequestration of this material as cytosolic aggregates by p62 and NBR1. Notably, LMP induction in primary neuronal cultures generates p62-positive aggregates and promotes p62 localization to lysosomal membranes, supporting our in vivo findings. We conclude that LMP is a previously unrecognized pathogenic event in CLN2 disease that stimulates cytosolic aggregate formation. Furthermore, we offer a novel role for p62 in response to LMP that may be relevant for other diseases exhibiting p62 accumulation.

  5. Constrained Photophysics of 5,7-dimethoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one in the Bioenvironment of Serum Albumins: A Spectroscopic Endeavour Supported by Molecular Docking Analysis.

    Science.gov (United States)

    Mitra, Amrit Krishna; Sau, Abhishek; Pal, Uttam; Saha, Chandan; Basu, Samita

    2017-07-01

    This paper vividly indicates that steady state as well as time-resolved fluorescence techniques can serve as highly sensitive monitors to explore the interactions of 5,7-dimethoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one with model transport proteins, bovine serum albumin (BSA) and human serum albumin (HSA). Besides these, we have used fluorescence anisotropy study to assess the degree of restrictions imparted by the micro-environments of serum albumins. Again, to speculate the triplet excited state interaction between such fluorophore and albumin proteins (BSA& HSA), laser flash-photolysis experiments have been carried out. Molecular docking experiments have also been performed to support the conclusions obtained from steady state experiments.

  6. Molecular and genetic insights into an infantile epileptic encephalopathy – CDKL5 disorder

    Science.gov (United States)

    Zhou, Ailing; Han, Song

    2017-01-01

    Background The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. Methods A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. Results On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Conclusions Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes. PMID:28580010

  7. Molecular Interaction of a New Antibacterial Polymer with a Supported Lipid Bilayer Measured by an in situ Label-Free Optical Technique

    Directory of Open Access Journals (Sweden)

    Robert Horvath

    2013-05-01

    Full Text Available The interaction of the antibacterial polymer–branched poly(ethylene imine substituted with quaternary ammonium groups, PEO and alkyl chains, PEI25QI5J5A815–with a solid supported lipid bilayer was investigated using surface sensitive optical waveguide spectroscopy. The analysis of the optogeometrical parameters was extended developing a new composite layer model in which the structural and optical anisotropy of the molecular layers was taken into consideration. Following in situ the change of optical birefringence we were able to determine the composition of the lipid/polymer surface layer as well as the displacement of lipid bilayer by the antibacterial polymer without using additional labeling. Comparative assessment of the data of layer thickness and optical anisotropy helps to reveal the molecular mechanism of antibacterial effect of the polymer investigated.

  8. Synthesis of cerium oxide catalysts supported on MCM-41 molecular sieve; Sintese de catalisadores de oxido de cerio suportados na peneira molecular MCM-41

    Energy Technology Data Exchange (ETDEWEB)

    Souza, E.L.S.; Barros, T.R.B.; Sousa, B.V. de, E-mail: emylle.souza@gmail.com [Universidade Federal de Campina Grande (UFCG), PB (Brazil). Unidade Academica de Engenharia Quimica

    2016-07-01

    Porous materials have been widely studied as catalysts and catalyst support. The MCM-41 structure is the one that has been most studied because of its application possibilities in chemical processes. This work aimed to obtain and characterize cerium oxide catalysts supported on MCM-41 molecular sieve. The molecular sieve was synthesized by the conventional method with the following molar composition: 1 SiO2: 0.30 CTABr: NH3 11: 144 H2O. Then, 25% w/w cerium was incorporated into the MCM-41 using the wet impregnation process and the material obtained was activated by calcination. From the XRD patterns was confirmed the structure of the molecular sieve, and were identified the cerium oxide phases in its structure. The textural catalysts characteristics were investigated by isotherms of N2 adsorption/desorption (BET method). (author)

  9. 2-(5-Chloro-2-oxoindolin-3-ylidenehydrazinecarbothioamide

    Directory of Open Access Journals (Sweden)

    Viviane Conceição Duarte de Bittencourt

    2014-01-01

    Full Text Available The title molecule, C9H7ClN4OS, is almost planar, with an r.m.s. deviation of 0.034 (2 Å for the mean plane through all the non-H atoms. Intramolecular N—H...O and N—H...N hydrogen bonds form S(6 and S(5 ring motifs, respectively. In the crystal, molecules are assembled into inversion dimers through pairs of co-operative N—H...Cl interactions. These dimers are connected along the b axis by N—H...O and N—H...S hydrogen bonds, generating layers parallel to (103. The layers are further connected along the a axis into a three-dimensional network, through weak π–π stacking interactions [centroid–centroid distance = 3.849 (2 Å].

  10. Theoretical investigation of molecular structure and vibrational spectra of 4,5-bis-(2-isopropyl-5- methylphenoxy) phthalonitrile molecule

    International Nuclear Information System (INIS)

    Avci, D.

    2005-01-01

    The molecular geometry and vibrational frequencies of 4,5-bis-(2-isopropyl-5- methylphenoxy) phthalonitrile in the ground state have been calculated using the Hartree- Fock (HF) and density functional method (B3LYP) with 6-31G(d) basis set. The optimized geometric bond lengths and bond angles obtained by using HF and DFT (B3LYP) show the best agreement with the experimental data. Comparison of the observed fundamental vibrational frequencies of 4,5-bis-(2-isopropyl-5-methylphenoxy) phthalonitrile with calculated results by density functional B3LYP and Hartree-Fock methods indicate that B3LYP is superior to the scaled Hartree-Fock approach for molecular vibrational problems

  11. Solid phase extraction of penicillins from milk by using sacrificial silica beads as a support for a molecular imprint

    International Nuclear Information System (INIS)

    Giovannoli, Cristina; Anfossi, Laura; Biagioli, Flavia; Passini, Cinzia; Baggiani, Claudio

    2013-01-01

    We have prepared molecularly imprinted beads with molecular recognition capability for target molecules containing the penicillanic acid substructure. They were prepared by (a) grafting mesoporous silica beads with 6-aminopenicillanic acid as the mimic template, (b) filling the pores with a polymerized mixture of methacrylic acid and trimethylolpropane trimethacrylate, and (c) removing the silica support with ammonium fluoride. The resulting imprinted beads showed good molecular recognition capability for various penicillanic species, while antibiotics such as cephalosporins or chloramphenicol were poorly recognized. The imprinted beads were used to extract penicillin V, nafcillin, oxacillin, cloxacillin and dicloxacillin from skimmed and deproteinized milk in the concentration range of 5–100 μg·L −1 . The extracts were then analyzed by micellar electrokinetic chromatography by applying reverse polarity staking as an in-capillary preconcentration step, and this resulted in a fast and affordable method within the MRL levels, characterized by minimal pretreatment steps and recoveries of 64–90 %. (author)

  12. Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Usman Sumo Friend Tambunan

    2017-04-01

    Full Text Available Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5 methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl- l -methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S -adenosyl- l -homocysteine (SAH. The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity test. The 2 simulations were performed using Molecular Operating Environment (MOE 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356 based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.

  13. Proton-transfer compounds of 8-hydroxy-7-iodoquinoline-5-sulfonic acid (ferron) with 4-chloroaniline and 4-bromoaniline.

    Science.gov (United States)

    Smith, Graham; Wermuth, Urs D; Healy, Peter C

    2007-07-01

    The crystal structures of the proton-transfer compounds of ferron (8-hydroxy-7-iodoquinoline-5-sulfonic acid) with 4-chloroaniline and 4-bromoaniline, namely 4-chloroanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)ClN(+) x C(9)H(5)INO(4)S(-) x H(2)O, and 4-bromoanilinium 8-hydroxy-7-iodoquinoline-5-sulfonate monohydrate, C(6)H(7)BrN(+) x C(9)H(5)INO(4)S(-) x H(2)O, have been determined. The compounds are isomorphous and comprise sheets of hydrogen-bonded cations, anions and water molecules which are extended into a three-dimensional framework structure through centrosymmetric R(2)(2)(10) O-H...N hydrogen-bonded ferron dimer interactions.

  14. Productivity of determinate growth tomato lines tolerant to heat under the organic system Produtividade de linhagens de tomate rasteiro tolerantes ao calor sob o sistema orgânico

    Directory of Open Access Journals (Sweden)

    Cândido A da Costa

    2011-12-01

    Full Text Available The objective of the present work was to evaluate the productive response of heat tolerant lines of determinate growth tomato under the organic production system. The experiment was carried out in the Instituto de Ciências Agrárias of UFMG, Montes Claros, Minas Gerais state, Brazil. The experimental design was of randomized complete blocks with eight treatments and four replications. The treatments consisted of eight heat tolerant processing type tomato lines obtained from the Asian Vegetable Research and Development Center (AVRDC, China: CLN1621L, CLN1621F, CLN1621E, CLN1466P, CLN2026E, CLN2026D, CLN2026C and CLN2001C. There was an inverse relationship between the average weight of the fruits and the number of fruits per plant. The highest average fruit weight of some lines was compensated by the lowest quantity of fruits, in such a way that there were no significant differences among the lines. Symptoms of nutritional deficiency and incidences of pests and diseases were not verified in any of the studied lines. All lines presented potential for genetic improvement research and cultivation using organic production systems under higher temperature conditions.O objetivo do presente trabalho foi avaliar o desempenho produtivo de linhagens de tomate rasteiro tolerantes ao calor sob o sistema orgânico de produção. O experimento foi realizado no Núcleo de Ciências Agrárias da UFMG, Montes Claros-MG. Foi utilizado o delineamento em blocos casualizados com oito tratamentos e quatro repetições. Os tratamentos consistiram de oito linhagens de tomate do tipo rasteiro tolerantes ao calor obtidos na Asian Vegetable Research and Development Center (AVRDC, China: CLN1621L, CLN1621F, CLN1621E, CLN1466P, CLN2026E, CLN2026D, CLN2026C e CLN2001C. Houve uma relação inversa entre o peso médio dos frutos e o número de frutos produzidos por planta. O maior peso médio de frutos de algumas linhagens foi compensado pelo menor número de frutos, de tal

  15. Cryogenic adsorption of low-concentration hydrogen on charcoal, 5A molecular sieve, sodalite, ZSM-5 and Wessalith DAY

    International Nuclear Information System (INIS)

    Willms, R.S.

    1993-01-01

    The separation of low-concentration hydrogen isotopes from helium is a processing step that is required for ceramic lithium breeding blanket processing. Cryogenic adsorption is one method of effecting this separation. In this study live adsorbents were considered for this purpose: charcoal, 5A molecular sieve, UOP S-115, ZSM-5 and Wessalith DAY. The first two adsorbents exhibit good equilibrium loadings and are shown to be quite effective at adsorbing low-concentration hydrogen isotopes. The latter three adsorbents display considerably lower equilibrium loadings. This study concludes that by using either charcoal or 5A molecular sieve, cryogenic adsorption would be an effective means of separating hydrogen isotopes from helium

  16. Serum protein fractionation using supported molecular matrix electrophoresis.

    Science.gov (United States)

    Dong, Weijie; Matsuno, Yu-ki; Kameyama, Akihiko

    2013-08-01

    Supported molecular matrix electrophoresis (SMME), in which a hydrophilic polymer such as PVA serves as a support within a porous PVDF membrane, was recently developed. This method is similar to cellulose acetate membrane electrophoresis but differs in the compatibility to glycan analysis of the separated bands. In this report, we describe the first instance of the application of SMME to human serum fractionation, and demonstrate the differences with serum fractionation by cellulose acetate membrane electrophoresis. The SMME membrane exhibited almost no EOF during electrophoresis, unlike the cellulose acetate membrane, but afforded comparative results for serum fractionation. The visualization of each fraction was achieved by conventional staining with dye such as Direct Blue-71, and objective quantification was obtained by densitometry after inducing membrane transparency with 1-nonene. Immunostaining was also achieved. Moreover, mass spectrometric analysis of both N-linked and O-linked glycans from the separated bands was demonstrated. Serum fractionation and glycan profiling of each fraction using SMME will enable novel insights into the relationships between various glycosylation profiles and disease states. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Synthesis, characterization and molecular structure of a dinuclear uranyl complex supported by N,N',N'',N'''-tetra-(3,5-di-tert-butylsalicylidene)-1,2,4,5- phenylenetetraamine

    Energy Technology Data Exchange (ETDEWEB)

    Schnorr, Rene; Handke, Marcel; Kersting, Berthold [Leipzig Univ. (Germany). Inst. fuer Anorganische Chemie

    2015-07-01

    The preparation, characterization and the molecular structure of a dinuclear uranyl complex [(UO{sub 2}){sub 2}L(OCMe{sub 2}){sub 2}] supported by the bis-salophen ligand N,N',N'',N'''-tetra-(3,5-di-tert-butylsalicylidene)-1,2,4,5- phenylenetetraamine (L{sup 4-}) is described. [(UO{sub 2}){sub 2}L(OCMe{sub 2}){sub 2}] was prepared by reaction of uranyl nitrate with the neutral, protonated form of the ligand (H{sub 4}L) in acetone. From a saturated acetone solution [(UO{sub 2}){sub 2}L(OCMe{sub 2}){sub 2}] . 1.5(OCMe{sub 2}) crystallizes triclinically, space group P anti 1 with a = 1522.7(2), b = 1751.4(2), c = 1815.4(2) Aa, α = 109.16(1), β = 99.29(1), γ = 105.29(1) and Z = 2. Each uranium atom is surrounded in a distorted pentagonal bipyramidal fashion by two O and two N atoms of the salicylidene units, one O atom of an acetone ligand, and the two oxo groups. The cyclic voltammogram of [(UO{sub 2}){sub 2}L(OCMe{sub 2}){sub 2}] shows two quasi-reversible redox processes centered at +0.57 V and +0.82 V vs. Fc{sup +}/Fc attributed to the sequential oxidation of the coordinating phenolates to phenoxyl radicals. The crystal structure of an ethanol solvate of H{sub 4}L was also determined by X-ray crystallography. H{sub 4}L . 5EtOH: triclinic, space group P anti 1, a = 1003.4(3), b = 1187.7(3), c = 1905.1(5) Aa, α = 75.75(2), β = 78.74(2), γ = 66.66(2) , Z = 1.

  18. AVALIAÇÃO DE LINHAGENS DE TOMATE CEREJA TOLERANTES AO CALOR SOB SISTEMA ORGÂNICO DE PRODUÇÃO

    Directory of Open Access Journals (Sweden)

    ANDRÉ COSTA DA SILVA

    2011-01-01

    Full Text Available The aim of this paper was to evaluate the performance of lines of cherry tomato, heat tolerant under the organic system. The experiment was conducted at the Instituto de Ciências Agrárias da UFMG, Montes Claros - MG. The treatments consisted of eleven lines of cherry tomato, heat tolerant, obtained from the Asian Vegetable Research and Development Center, China: CLN1561A, CLN1555C, CLN1555B, CLN1555A, CLN1558B, CLN1558A, CH151, CH152, CH154, CH157, CH155 cultivated under organic system. We used a randomized block design with eleven treatments and four replications. There was an inverse relationship between the average fruit weight and number of fruits produced per plant. The lines CLN1561A and CH157 are indicated for the culture and commercialization of the cherry tomato organically produced, therefore to present greater productivity and greater total soluble solid content.

  19. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  20. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    International Nuclear Information System (INIS)

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-01-01

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  1. Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

    Directory of Open Access Journals (Sweden)

    Franco Alhaique

    2007-04-01

    Full Text Available The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs as a controlled release device for 5-fluorouracil (5-FU in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs. MIPs were synthesized using methacrylic acid (MAA as functional monomer and ethylene glycol dimethacrylate (EGDMA as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

  2. Molecular dynamics study of the vaporization of an ionic drop

    Science.gov (United States)

    Galamba, N.

    2010-09-01

    The melting of a microcrystal in vacuum and subsequent vaporization of a drop of NaCl were studied through molecular dynamics simulations with the Born-Mayer-Huggins-Tosi-Fumi rigid-ion effective potential. The vaporization was studied for a single isochor at increasing temperatures until the drop completely vaporized, and gaseous NaCl formed. Examination of the vapor composition shows that the vapor of the ionic drop and gaseous NaCl are composed of neutral species, the most abundant of which, ranging from simple NaCl monomers (ion pairs) to nonlinear polymers, (NanCln)n=2-4. The enthalpies of sublimation, vaporization, and dissociation of the different vapor species are found to be in reasonable agreement with available experimental data. The decrease of the enthalpy of vaporization of the vapor species, with the radius of the drop decrease, accounts for a larger fraction of trimers and tetramers than that inferred from experiments. Further, the rhombic dimer is significantly more abundant than its linear isomer although the latter increases with the temperature. The present results suggest that both trimers and linear dimers may be important to explain the vapor pressure of molten NaCl at temperatures above 1500 K.

  3. Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System.

    Science.gov (United States)

    Banjar, Haneen; Adelson, David; Brown, Fred; Chaudhri, Naeem

    2017-01-01

    The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.

  4. Fabrication variables affecting the structure and properties of supported carbon molecular sieve membranes for hydrogen separation

    KAUST Repository

    Briceño, Kelly

    2012-10-01

    A high molecular weight polyimide (Matrimid) was used as a precursor for fabricating supported carbon molecular sieve membranes without crack formation at 550-700°C pyrolysis temperature. A one-step polymer (polyimide) coating method as precursor of carbon layer was used without needing a prior modification of a TiO 2 macroporous support. The following fabrication variables were optimized and studied to determine their effect on the carbon structure: polymeric solution concentration, solvent extraction, heating rate and pyrolysis temperature. Two techniques (Thermogravimetric analysis and Raman spectroscopy) were used to determine these effects on final carbon structure. Likewise, the effect of the support was also reported as an additional and important variable in the design of supported carbon membranes. Atomic force microscopy and differential scanning calorimetry quantified the degree of influence. Pure gas permeation tests were performed using CH 4, CO, CO 2 and H 2. The presence of a molecular sieving mechanism was confirmed after defects were plugged with PDMS solution at 12wt%. Gas selectivities higher than Knudsen theoretical values were reached with membranes obtained over 650°C, showing as best values 4.46, 4.70 and 10.62 for H 2/N 2, H 2/CO and H 2/CH 4 ratio, respectively. Permeance values were over 9.82×10 -9mol/(m 2Pas)during pure hydrogen permeation tests. © 2012 Elsevier B.V.

  5. Fabrication variables affecting the structure and properties of supported carbon molecular sieve membranes for hydrogen separation

    KAUST Repository

    Briceñ o, Kelly; Montané , Daniel; Garcia-Valls, Ricard; Iulianelli, Adolfo; Basile, Angelo

    2012-01-01

    A high molecular weight polyimide (Matrimid) was used as a precursor for fabricating supported carbon molecular sieve membranes without crack formation at 550-700°C pyrolysis temperature. A one-step polymer (polyimide) coating method as precursor of carbon layer was used without needing a prior modification of a TiO 2 macroporous support. The following fabrication variables were optimized and studied to determine their effect on the carbon structure: polymeric solution concentration, solvent extraction, heating rate and pyrolysis temperature. Two techniques (Thermogravimetric analysis and Raman spectroscopy) were used to determine these effects on final carbon structure. Likewise, the effect of the support was also reported as an additional and important variable in the design of supported carbon membranes. Atomic force microscopy and differential scanning calorimetry quantified the degree of influence. Pure gas permeation tests were performed using CH 4, CO, CO 2 and H 2. The presence of a molecular sieving mechanism was confirmed after defects were plugged with PDMS solution at 12wt%. Gas selectivities higher than Knudsen theoretical values were reached with membranes obtained over 650°C, showing as best values 4.46, 4.70 and 10.62 for H 2/N 2, H 2/CO and H 2/CH 4 ratio, respectively. Permeance values were over 9.82×10 -9mol/(m 2Pas)during pure hydrogen permeation tests. © 2012 Elsevier B.V.

  6. N-(3-Chloro-4-ethoxy-1-methyl-1H-indazol-5-yl-4-methoxybenzenesulfonamide

    Directory of Open Access Journals (Sweden)

    Hakima Chicha

    2014-06-01

    Full Text Available The indazole ring system of the title compound, C17H18ClN3O4S, is almost planar (r.m.s. deviation = 0.0113 Å and forms dihedral angles of 32.22 (8 and 57.5 (3° with the benzene ring and the mean plane through the 4-ethoxy group, respectively. In the crystal, molecules are connected by pairs of N—H...O hydrogen bonds into inversion dimers, which are further linked by π–π interactions between the diazole rings [intercentroid distance = 3.4946 (11 Å], forming chains parallel to [101].

  7. 7-Chloro-11a-phenyl-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

    Directory of Open Access Journals (Sweden)

    Vahan Martirosyan

    2008-03-01

    Full Text Available The title compound, C18H15ClN2O2, is a potential human immunodeficiency virus type-1 (HIV-1 non-nucleoside reverse transcriptase inhibitor. The pyrrolidine ring adopts an envelope and the diazepine ring a boat conformation. In the crystal structure, two isomers (R and S form centrosymmetric dimers via N—H...O hydrogen bonds.

  8. Molecular-signature analyses support the establishment of the actinobacterial genus Sphaerimonospora (Mingma et al. 2016).

    Science.gov (United States)

    Meyers, Paul R

    2017-10-01

    The genera Microbispora and Sphaerimonospora were examined for GyrB and RecA amino-acid signatures to determine whether molecular-signature analyses support the recent establishment of the genus Sphaerimonospora. The creation of Sphaerimonospora was based mainly upon morphological differences between Microbispora and Sphaerimonospora and the clustering of the type strains of the two genera in phylogenetic trees based on a multilocus sequence analysis. The molecular-signature analyses showed that all members of Sphaerimonospora can be distinguished from all members of Microbispora at 14 amino acid positions in the GyrB protein and at four positions in the shorter RecA protein. These amino acid differences can be used as signatures to differentiate the members of these genera from each other and thus provide support for the establishment of the genus Sphaerimonospora. This is the first demonstration of the use of molecular signatures to support the establishment of a new genus in the family Streptosporangiaceae. Following the transfer of Microbispora mesophila and Microbispora thailandensis from Microbispora to Sphaerimonospora, all species in the genus Microbispora are characterised by the insertion of a small, hydrophobic amino acid after position 208 in the GyrB protein. This insertion is absent from the GyrB protein of members of the genus Sphaerimonospora. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Weimer, Jill M; Benedict, Jared W; Getty, Amanda L; Pontikis, Charlie C; Lim, Ming J; Cooper, Jonathan D; Pearce, David A

    2009-04-17

    Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is a neurodegenerative disease resulting from a mutation in CLN3, which presents clinically with visual deterioration, seizures, motor impairments, cognitive decline, hallucinations, loss of circadian rhythm, and premature death in the late-twenties to early-thirties. Using a Cln3 null (Cln3(-/-)) mouse, we report here several deficits in the cerebellum in the absence of Cln3, including cell loss and early onset motor deficits. Surprisingly, early onset glial activation and selective neuronal loss within the mature fastigial pathway of the deep cerebellar nuclei (DCN), a region critical for balance and coordination, are seen in many regions of the Cln3(-/-) cerebellum. Additionally, there is a loss of Purkinje cells (PC) in regions of robust Bergmann glia activation in Cln3(-/-) mice and human JNCL post-mortem cerebellum. Moreover, the Cln3(-/-) cerebellum had a mis-regulation in granule cell proliferation and maintenance of PC dendritic arborization and spine density. Overall, this study defines a novel multi-faceted, early-onset cerebellar disruption in the Cln3 null brain, including glial activation, cell loss, and aberrant cell proliferation and differentiation. These early alterations in the maturation of the cerebellum could underlie some of the motor deficits and pathological changes seen in JNCL patients.

  10. Interaction of light with impurities in lithium niobate crystals

    Energy Technology Data Exchange (ETDEWEB)

    Schwesyg, Judith Renate Marie-Luise

    2011-06-06

    Congruent lithium niobate (LiNbO{sub 3}) and 5-mol% MgO-doped LiNbO{sub 3} (MgO:LN) crystals are widely used as nonlinear-optical crystals in frequency-conversion devices due to their large nonlinear-optic coefficients. These devices usually require high optical pump powers, but absorption of photons by impurities limits their usability due to heat accumulation that leads to thermo-optic refractive index changes. These refractive index changes distort the beam shape and disturb the phase-matching condition. Furthermore pyroelectric fields can build up. In this thesis the residual optical absorption in congruent LiNbO{sub 3} (CLN) and MgO:LN crystals is studied. Absorption spectra of CLN and MgO:LN crystals between 400-2000 nm reveal a residual absorption up to 0.04 cm{sup -1}. This absorption is mainly caused by transition metal impurities. Between 2300-2800 nm unknown hydrogen absorption bands in CLN and MgO:LN are revealed on the order of 0.001 cm{sup -1}. High-temperature annealing is applied to the CLN and MgO:LN crystals, which decreases optical absorption by up to one order of magnitude. As an application, the operation of a 1550-nm pumped singly-resonant CW optical parametric oscillator, resonant around 2600 nm, using a low-loss, periodically-poled, annealed CLN crystal is demonstrated. Another issue that affects CLN is photorefractive damage (PRD), i.e. light-induced refractive index changes. In contrast, MgO:LN crystals do not suffer from PRD even at high optical intensities. However, it is shown in this thesis that PRD can occur within seconds in MgO:LN, using green laser light at light intensity levels as low as 100 mW/cm{sup 2}, if the crystal is heated by several degrees Celsius during or before illumination. Photorefractive damage does not occur in CLN crystals under the same conditions. We show that the pyroelectric effect together with an elevated photoconductivity compared to that of CLN causes this beam distortion and that this effect also

  11. Interaction of light with impurities in lithium niobate crystals

    International Nuclear Information System (INIS)

    Schwesyg, Judith Renate Marie-Luise

    2011-01-01

    Congruent lithium niobate (LiNbO 3 ) and 5-mol% MgO-doped LiNbO 3 (MgO:LN) crystals are widely used as nonlinear-optical crystals in frequency-conversion devices due to their large nonlinear-optic coefficients. These devices usually require high optical pump powers, but absorption of photons by impurities limits their usability due to heat accumulation that leads to thermo-optic refractive index changes. These refractive index changes distort the beam shape and disturb the phase-matching condition. Furthermore pyroelectric fields can build up. In this thesis the residual optical absorption in congruent LiNbO 3 (CLN) and MgO:LN crystals is studied. Absorption spectra of CLN and MgO:LN crystals between 400-2000 nm reveal a residual absorption up to 0.04 cm -1 . This absorption is mainly caused by transition metal impurities. Between 2300-2800 nm unknown hydrogen absorption bands in CLN and MgO:LN are revealed on the order of 0.001 cm -1 . High-temperature annealing is applied to the CLN and MgO:LN crystals, which decreases optical absorption by up to one order of magnitude. As an application, the operation of a 1550-nm pumped singly-resonant CW optical parametric oscillator, resonant around 2600 nm, using a low-loss, periodically-poled, annealed CLN crystal is demonstrated. Another issue that affects CLN is photorefractive damage (PRD), i.e. light-induced refractive index changes. In contrast, MgO:LN crystals do not suffer from PRD even at high optical intensities. However, it is shown in this thesis that PRD can occur within seconds in MgO:LN, using green laser light at light intensity levels as low as 100 mW/cm 2 , if the crystal is heated by several degrees Celsius during or before illumination. Photorefractive damage does not occur in CLN crystals under the same conditions. We show that the pyroelectric effect together with an elevated photoconductivity compared to that of CLN causes this beam distortion and that this effect also influences frequency conversion

  12. Doping chloro boron subnaphthalocyanines and chloro boron subphthalocyanine in simple OLED architectures yields warm white incandescent-like emissions

    Science.gov (United States)

    Plint, Trevor G.; Lessard, Benoît H.; Bender, Timothy P.

    2018-01-01

    We have incorporated chloro boron subphthalocyanine (Cl-BsubPc) and chloro boron subnapthalocyanines (Cl-ClnBsubNcs) into organic light emitting diodes (OLEDs) that enabled an overall warm white emission with CIE coordinates close to that of a 60 W incandescent lightbulb. More specifically, we have shown that Cl-BsubPc and Cl-ClnBsubNcs can be used as dopant emitters in a simple host-dopant architecture, and we have compared the use of NPB and Alq3 as potential hosts for these materials. When doped into Alq3, Cl-BsubPc shows a strong orange emission, and Cl-ClnBsubNcs shows a moderately strong red emission. We have further demonstrated that Cl-BsubPc and Cl-ClnBsubNcs can be co-doped into the same layer giving combined orange and red emission peaks. A "cascade" energy transfer mechanism of sequential absorption and re-emission is proposed. Device performance characteristics such as luminance, current efficiency, photoluminescence efficiency, and external quantum efficiency are tabulated. Additionally, in view of ongoing research into white emitting OLEDs for indoor lighting purposes, the Colour Rendering Index (CRI), R9 values, and CIE co-ordinates for these devices are also discussed. We conclude from this study that the BsubNc chromophore has potential application as a red dopant in OLEDs including for indoor lighting. Additionally, given the scope for axial and peripheral derivatization of the BsubNc motif, we believe that this chromophore has many unexplored molecular design handles that will affect its ultimate performance and application in OLEDs and other opto-electronic devices.

  13. Molecular dynamics simulations of ejecta production from sinusoidal tin surfaces under supported and unsupported shocks

    Science.gov (United States)

    Wu, Bao; Wu, FengChao; Zhu, YinBo; Wang, Pei; He, AnMin; Wu, HengAn

    2018-04-01

    Micro-ejecta, an instability growth process, occurs at metal/vacuum or metal/gas interface when compressed shock wave releases from the free surface that contains surface defects. We present molecular dynamics (MD) simulations to investigate the ejecta production from tin surface shocked by supported and unsupported waves with pressures ranging from 8.5 to 60.8 GPa. It is found that the loading waveforms have little effect on spike velocity while remarkably affect the bubble velocity. The bubble velocity of unsupported shock loading remains nonzero constant value at late time as observed in experiments. Besides, the time evolution of ejected mass in the simulations is compared with the recently developed ejecta source model, indicating the suppressed ejection of unmelted or partial melted materials. Moreover, different reference positions are chosen to characterize the amount of ejecta under different loading waveforms. Compared with supported shock case, the ejected mass of unsupported shock case saturates at lower pressure. Through the analysis on unloading path, we find that the temperature of tin sample increases quickly from tensile stress state to zero pressure state, resulting in the melting of bulk tin under decaying shock. Thus, the unsupported wave loading exhibits a lower threshold pressure causing the solid-liquid phase transition on shock release than the supported shock loading.

  14. Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation.

    Science.gov (United States)

    Tambunan, Usman Sumo Friend; Nasution, Mochammad Arfin Fardiansyah; Azhima, Fauziah; Parikesit, Arli Aditya; Toepak, Erwin Prasetya; Idrus, Syarifuddin; Kerami, Djati

    2017-01-01

    Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S -adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.

  15. Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

    Science.gov (United States)

    Arora, Shivani; Vohora, Divya

    2016-08-01

    As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated

  16. Cervical lymph node metastases from thyroid cancer: does thyroglobulin and calcitonin measurement in fine needle aspirates improve the diagnostic value of cytology?

    Directory of Open Access Journals (Sweden)

    Baldini Enke

    2013-02-01

    Full Text Available Abstract Background Measurement of thyroglobulin (Tg protein in the washout of the needle used for fine needle aspiration biopsy cytology (FNAB-C has been shown to increase the sensitivity of FNAB-C in identifying cervical lymph node (CLN metastasis from well-differentiated thyroid cancer (TC. In this study, we evaluated whether routine measurement of Tg protein (FNAB-Tgp, Tg mRNA (FNAB-Tgm and calcitonin (CT mRNA (FNAB-CTm in the FNAB washout of CLN increases the accuracy of FNAB-C in the diagnosis of suspicious metastatic CLN. Methods In this prospective study 35 CLN from 28 patients were examined. Histology showed metastatic papillary TC (PTC in 26 CLN, metastatic medullary TC (MTC in 3 CLN, metastatic anaplastic TC (ATC in 3 CLN and 3 metastatic CLN from extra-thyroidal cancers. Results The overall accuracy of FNAB-C was 84.4%, reaching 95.7% when the analysis was restricted to PTC. Both FNAB-Tgp and FNAB-Tgm compared favorably with FNAB-C and shown diagnostic performances not statistically different from that of FNAB-C. However, FNAB-Tgp and FNAB-Tgm/FNAB-CTm were found useful in cases in which cytology results were inadequate or provided diagnosis inconsistent with patient's clinical parameters. Conclusions We demonstrated that FNAB-C, Tg/CT mRNA and Tg protein determination in the fine-needle washout showed similar accuracy in the diagnosis of metastatic CLN from TC. The results of this study suggest that samples for Tg protein and Tg/CT mRNA measurements from CLN suspicious for metastatic TC should be collected, but their measurements should be restricted to cases in which FNAB-C provides uninformative or inconsistent diagnosis with respect to patient's clinical parameters.

  17. Cervical lymph node metastases from thyroid cancer: does thyroglobulin and calcitonin measurement in fine needle aspirates improve the diagnostic value of cytology?

    Science.gov (United States)

    2013-01-01

    Background Measurement of thyroglobulin (Tg) protein in the washout of the needle used for fine needle aspiration biopsy cytology (FNAB-C) has been shown to increase the sensitivity of FNAB-C in identifying cervical lymph node (CLN) metastasis from well-differentiated thyroid cancer (TC). In this study, we evaluated whether routine measurement of Tg protein (FNAB-Tgp), Tg mRNA (FNAB-Tgm) and calcitonin (CT) mRNA (FNAB-CTm) in the FNAB washout of CLN increases the accuracy of FNAB-C in the diagnosis of suspicious metastatic CLN. Methods In this prospective study 35 CLN from 28 patients were examined. Histology showed metastatic papillary TC (PTC) in 26 CLN, metastatic medullary TC (MTC) in 3 CLN, metastatic anaplastic TC (ATC) in 3 CLN and 3 metastatic CLN from extra-thyroidal cancers. Results The overall accuracy of FNAB-C was 84.4%, reaching 95.7% when the analysis was restricted to PTC. Both FNAB-Tgp and FNAB-Tgm compared favorably with FNAB-C and shown diagnostic performances not statistically different from that of FNAB-C. However, FNAB-Tgp and FNAB-Tgm/FNAB-CTm were found useful in cases in which cytology results were inadequate or provided diagnosis inconsistent with patient's clinical parameters. Conclusions We demonstrated that FNAB-C, Tg/CT mRNA and Tg protein determination in the fine-needle washout showed similar accuracy in the diagnosis of metastatic CLN from TC. The results of this study suggest that samples for Tg protein and Tg/CT mRNA measurements from CLN suspicious for metastatic TC should be collected, but their measurements should be restricted to cases in which FNAB-C provides uninformative or inconsistent diagnosis with respect to patient's clinical parameters. PMID:23421519

  18. Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells.

    Science.gov (United States)

    Sun, Bing; Bai, Yuxin; Zhang, Liyuan; Gong, Linlin; Qi, Xiaoyu; Li, Huizhen; Wang, Faming; Chi, Xinming; Jiang, Yulin; Shao, Shujuan

    Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.

  19. Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Bing Sun

    Full Text Available Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5 is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.

  20. Molecular isotopic tracing of carbon flow and trophic relationships in a methane supported microbial community

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Werne, J.; Baas, B.

    2002-01-01

    A molecular isotopic study in cold-seep sediments from Kazan mud volcano in the eastern Mediterranean Sea indicates that a significant proportion of methane released in this environment is incorporated into biomass in methane-supported chemosynthetic microbial communities. Furthermore, extremely

  1. Data supporting a molecular phylogeny of the hyper-diverse genus Brueelia

    Directory of Open Access Journals (Sweden)

    Sarah E. Bush

    2015-12-01

    Full Text Available Data is presented in support of a phylogenetic reconstruction of one of the largest, and most poorly understood, groups of lice: the Brueelia-complex (Bush et al., 2015 [1]. Presented data include the voucher information and molecular data (GenBank accession numbers of 333 ingroup taxa within the Brueelia-complex and 30 outgroup taxa selected from across the order Phthiraptera. Also included are phylogenetic reconstructions based on Bayesian inference analyses of combined COI and EF-1α sequences for Brueelia-complex species and outgroup taxa.

  2. Decreased T2 signal in the thalami may be a sign of lysosomal storage disease

    International Nuclear Information System (INIS)

    Autti, Taina; Joensuu, Raimo; Aaberg, Laura

    2007-01-01

    Lysosomal disorders are rare and are caused by genetically transmitted lysosomal enzyme deficiencies. A decreased T2 signal in the thalamus has occasionally been reported. Because the finding of bilateral abnormal signal intensity of the thalamus on T2-weighted images has not been systematically reviewed, and its value as a diagnostic tool critically evaluated, we carried out a systematic review of the literature. Articles in English with 30 trios of keywords were collected from PubMed. Exclusion criteria were lack of conventional T2-weighted images in the protocol and not being a human study. Finally, 111 articles were included. The thalamus was considered affected only if mentioned in the text or in the figure legends. Some 117 patients with various lysosomal diseases and five patients with ceruloplasmin deficiency were reported to have a bilateral decrease in T2 signal intensity. At least one article reported a bilateral decrease in signal intensity of the thalami on T2-weighted images in association with GM1 and GM2 gangliosidosis and with Krabbe's disease, aspartylglucosaminuria, mannosidosis, fucosidosis, and mucolipidosis IV. Furthermore, thalamic alteration was a consistent finding in several types of neuronal ceroid lipofuscinosis (NCL) including CLN1 (infantile NCL), CLN2 (classic late infantile NCL), CLN3 (juvenile NCL), CLN5 (Finnish variant late infantile NCL), and CLN7 (Turkish variant late infantile NCL). A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease. (orig.)

  3. Molecular dynamics simulations of ejecta production from sinusoidal tin surfaces under supported and unsupported shocks

    Directory of Open Access Journals (Sweden)

    Bao Wu

    2018-04-01

    Full Text Available Micro-ejecta, an instability growth process, occurs at metal/vacuum or metal/gas interface when compressed shock wave releases from the free surface that contains surface defects. We present molecular dynamics (MD simulations to investigate the ejecta production from tin surface shocked by supported and unsupported waves with pressures ranging from 8.5 to 60.8 GPa. It is found that the loading waveforms have little effect on spike velocity while remarkably affect the bubble velocity. The bubble velocity of unsupported shock loading remains nonzero constant value at late time as observed in experiments. Besides, the time evolution of ejected mass in the simulations is compared with the recently developed ejecta source model, indicating the suppressed ejection of unmelted or partial melted materials. Moreover, different reference positions are chosen to characterize the amount of ejecta under different loading waveforms. Compared with supported shock case, the ejected mass of unsupported shock case saturates at lower pressure. Through the analysis on unloading path, we find that the temperature of tin sample increases quickly from tensile stress state to zero pressure state, resulting in the melting of bulk tin under decaying shock. Thus, the unsupported wave loading exhibits a lower threshold pressure causing the solid-liquid phase transition on shock release than the supported shock loading.

  4. Forest fuel reduces the nitrogen load - calculations of nitrogen flows

    International Nuclear Information System (INIS)

    Burstroem, F.; Johansson, Jan.

    1995-12-01

    Nitrogen deposition in Sweden has increased strongly during recent decades, particularly in southern Sweden. Nitrogen appears to be largely accumulated in biomass and in the soil. It is therefore desirable to check the accumulation of nitrogen in the forest. The most suitable way of doing this is to remove more nitrogen-rich biomass from the forest, i.e., increase the removal of felling residues from final fellings and cleanings. An ecological condition for intensive removal of fuel is that the ashes are returned. The critical load for nitrogen, CL(N), indicates the level of nitrogen deposition that the forest can withstand without leading to ecological changes. Today, nitrogen deposition is higher than the CL(N) in almost all of Sweden. CL(N) is calculated in such a manner that nitrogen deposition should largely be balanced by nitrogen losses through harvesting during a forest rotation. The value of CL(N) thus largely depends on how much nitrogen is removed with the harvested biomass. When both stems and felling residues are harvested, the CL(N) is about three times higher than in conventional forestry. The increase is directly related to the amount of nitrogen in the removed biofuel. Use of biofuel also causes a certain amount of nitrogen emissions. From the environmental viewpoint there is no difference between the sources of the nitrogen compounds. An analysis of the entire fuel chain shows that, compared with the amount of nitrogen removed from the forest with the fuel, about 5 % will be emitted as nitrogen oxides or ammonia during combustion, and a further ca 5 % during handling and transports. A net amount of about 90 % of biomass nitrogen is removed from the system and becomes inert nitrogen (N 2 ). 60 refs, 3 figs, 4 tabs, 11 appendices

  5. Involvement of the mitochondrial compartment in human NCL fibroblasts

    International Nuclear Information System (INIS)

    Pezzini, Francesco; Gismondi, Floriana; Tessa, Alessandra; Tonin, Paola; Carrozzo, Rosalba; Mole, Sara E.; Santorelli, Filippo M.; Simonati, Alessandro

    2011-01-01

    Highlights: ► Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. ► Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. ► Enhanced caspase-mediated apoptosis occurs following STS treatment in CLN1 fibroblasts. -- Abstract: Neuronal ceroid lipofuscinosis (NCL) are a group of progressive neurodegenerative disorders of childhood, characterized by the endo-lysosomal storage of autofluorescent material. Impaired mitochondrial function is often associated with neurodegeneration, possibly related to the apoptotic cascade. In this study we investigated the possible effects of lysosomal accumulation on the mitochondrial compartment in the fibroblasts of two NCL forms, CLN1 and CLN6. Fragmented mitochondrial reticulum was observed in all cells by using the intravital fluorescent marker Mitotracker, mainly in the perinuclear region. This was also associated with intense signal from the lysosomal markers Lysotracker and LAMP2. Likewise, mitochondria appeared to be reduced in number and shifted to the cell periphery by electron microscopy; moreover the mitochondrial markers VDCA and COX IV were reduced following quantitative Western blot analysis. Whilst there was no evidence of increased cell death under basal condition, we observed a significant increase in apoptotic nuclei following Staurosporine treatment in CLN1 cells only. In conclusion, the mitochondrial compartment is affected in NCL fibroblasts invitro, and CLN1 cells seem to be more vulnerable to the negative effects of stressed mitochondrial membrane than CLN6 cells.

  6. Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans.

    Science.gov (United States)

    Chen, Zhuo; Wang, Zhengfei; Xu, Shixia; Zhou, Kaiya; Yang, Guang

    2013-02-09

    Hair is one of the main distinguishing characteristics of mammals and it has many important biological functions. Cetaceans originated from terrestrial mammals and they have evolved a series of adaptations to aquatic environments, which are of evolutionary significance. However, the molecular mechanisms underlying their aquatic adaptations have not been well explored. This study provided insights into the evolution of hair loss during the transition from land to water by investigating and comparing two essential regulators of hair follicle development and hair follicle cycling, i.e., the Hairless (Hr) and FGF5 genes, in representative cetaceans and their terrestrial relatives. The full open reading frame sequences of the Hr and FGF5 genes were characterized in seven cetaceans. The sequence characteristics and evolutionary analyses suggested the functional loss of the Hr gene in cetaceans, which supports the loss of hair during their full adaptation to aquatic habitats. By contrast, positive selection for the FGF5 gene was found in cetaceans where a series of positively selected amino acid residues were identified. This is the first study to investigate the molecular basis of the hair loss in cetaceans. Our investigation of Hr and FGF5, two indispensable regulators of the hair cycle, provide some new insights into the molecular basis of hair loss in cetaceans. The results suggest that positive selection for the FGF5 gene might have promoted the termination of hair growth and early entry into the catagen stage of hair follicle cycling. Consequently, the hair follicle cycle was disrupted and the hair was lost completely due to the loss of the Hr gene function in cetaceans. This suggests that cetaceans have evolved an effective and complex mechanism for hair loss.

  7. Synthesis and characterization of alumina-supported vanadium oxide catalysts prepared by the molecular designed dispersion of VO(acac)2 complexes

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Baltes, M.; Voort, P. van der; Ramachandra Rao, R.; Catana, Gabriela; Schoonheydt, R.A.; Vansant, E.F.

    2000-01-01

    Alumina-supported vanadium oxide catalysts have been prepared by the molecular designed dispersion method, using the vanadyl acetylacetonate complex (VO(acac)2). The complex has been adsorbed on the support from solution, followed by thermal conversion into the corresponding supported vanadium oxide

  8. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  9. Crystal structure of 1-[2-(4-chlorophenyl-4,5-diphenyl-1H-imidazol-1-yl]propan-2-ol

    Directory of Open Access Journals (Sweden)

    Shaaban K. Mohamed

    2017-01-01

    Full Text Available The title compound, C24H21ClN2O, crystallizes with two unique molecules in the asymmetric unit. In each molecule, the central imidazole ring is substituted at the 2-, 4- and 5-positions by benzene rings. The 2-substituted ring carries a Cl atom at the 4-position. One of the imidazole N atoms in each molecule has a propan-2-ol substituent. In the crystal, a series of O—H...N, C—H...O and C—H...Cl hydrogen bonds, augmented by several C—H...π(ring interactions, generate a three-dimensional network of molecules stacked along the a-axis direction.

  10. 5-Chloro-5′′-[4-(dimethylaminobenzylidene]-4′-[4-(dimethylaminophenyl]-1′,1′′-dimethyldispiro[indoline-3,2′-pyrrolidine-3′,3′′-piperidine]-2,4′′-dione

    Directory of Open Access Journals (Sweden)

    I. S. Ahmed Farag

    2014-01-01

    Full Text Available The title compound, C34H38ClN5O2, has spiro links connecting the pyrrolidine ring and indole residue, as well as the piperidine and pyrrolidine rings. A half-chair conformation is found for the piperidine ring with the C atom connected to the spiro-C atom lying 0.738 (4 Å out of the plane of the remaining five atoms (r.m.s. deviation = 0.0407 Å. The methylene C atom is the flap in the envelope conformation for the pyrrolidine ring. In the crystal, supramolecular chains are sustained by alternating eight-membered {...HNCO}2 and 14-membered {...HC5O}2 synthons. Chains are connected into a three-dimensional network by (pyrrolidine-bound phenyl-methylC—H...π(pyrrolidine-bound phenyl edge-to-face interactions.

  11. Molecular analyses of dinosaur osteocytes support the presence of endogenous molecules.

    Science.gov (United States)

    Schweitzer, Mary Higby; Zheng, Wenxia; Cleland, Timothy P; Bern, Marshall

    2013-01-01

    The discovery of soft, transparent microstructures in dinosaur bone consistent in morphology with osteocytes was controversial. We hypothesize that, if original, these microstructures will have molecular features in common with extant osteocytes. We present immunological and mass spectrometry evidence for preservation of proteins comprising extant osteocytes (Actin, Tubulin, PHEX, Histone H4) in osteocytes recovered from two non-avian dinosaurs. Furthermore, antibodies to DNA show localized binding to these microstructures, which also react positively with DNA intercalating stains propidium iodide (PI) and 4',6'-diamidino-2-phenylindole dihydrochloride (DAPI). Each antibody binds dinosaur cells in patterns similar to extant cells. These data are the first to support preservation of multiple proteins and to present multiple lines of evidence for material consistent with DNA in dinosaurs, supporting the hypothesis that these structures were part of the once living animals. We propose mechanisms for preservation of cells and component molecules, and discuss implications for dinosaurian cellular biology. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Molecular and Silica-Supported Molybdenum Alkyne Metathesis Catalysts: Influence of Electronics and Dynamics on Activity Revealed by Kinetics, Solid-State NMR, and Chemical Shift Analysis.

    Science.gov (United States)

    Estes, Deven P; Gordon, Christopher P; Fedorov, Alexey; Liao, Wei-Chih; Ehrhorn, Henrike; Bittner, Celine; Zier, Manuel Luca; Bockfeld, Dirk; Chan, Ka Wing; Eisenstein, Odile; Raynaud, Christophe; Tamm, Matthias; Copéret, Christophe

    2017-12-06

    Molybdenum-based molecular alkylidyne complexes of the type [MesC≡Mo{OC(CH 3 ) 3-x (CF 3 ) x } 3 ] (MoF 0 , x = 0; MoF 3 , x = 1; MoF 6 , x = 2; MoF 9 , x = 3; Mes = 2,4,6-trimethylphenyl) and their silica-supported analogues are prepared and characterized at the molecular level, in particular by solid-state NMR, and their alkyne metathesis catalytic activity is evaluated. The 13 C NMR chemical shift of the alkylidyne carbon increases with increasing number of fluorine atoms on the alkoxide ligands for both molecular and supported catalysts but with more shielded values for the supported complexes. The activity of these catalysts increases in the order MoF 0 molecular and supported species. Detailed solid-state NMR analysis of molecular and silica-supported metal alkylidyne catalysts coupled with DFT/ZORA calculations rationalize the NMR spectroscopic signatures and discernible activity trends at the frontier orbital level: (1) increasing the number of fluorine atoms lowers the energy of the π*(M≡C) orbital, explaining the more deshielded chemical shift values; it also leads to an increased electrophilicity and higher reactivity for catalysts up to MoF 6 , prior to a sharp decrease in reactivity for MoF 9 due to the formation of stable metallacyclobutadiene intermediates; (2) the silica-supported catalysts are less active than their molecular analogues because they are less electrophilic and dynamic, as revealed by their 13 C NMR chemical shift tensors.

  13. Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer.

    Science.gov (United States)

    Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Suemoto, Yuko; Meyerhardt, Jeffrey A; Fuchs, Charles S

    2007-11-01

    The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer. In contrast, a phenotype with less widespread promoter methylation (CIMP-low) has not been well characterised. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and silencing have been associated with G>A mutations and microsatellite instability-low (MSI-low). To examine molecular correlates with MGMT methylation/silencing in colorectal cancer. Utilising MethyLight technology, we quantified DNA methylation in MGMT and eight other markers (a CIMP-diagnostic panel; CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) in 920 population-based colorectal cancers. Tumours with both MGMT methylation and loss were correlated positively with MSI-low (p = 0.02), CIMP-high (>or=6/8 methylated CIMP markers, p = 0.005), CIMP-low (1/8-5/8 methylated CIMP markers, p = 0.002, compared to CIMP-0 with 0/8 methylated markers), KRAS G>A mutation (p = 0.02), and inversely with 18q loss of heterozygosity (p = 0.0002). Tumours were classified into nine MSI/CIMP subtypes. Among the CIMP-low group, tumours with both MGMT methylation and loss were far more frequent in MSI-low tumours (67%, 12/18) than MSI-high tumours (5.6%, 1/18; p = 0.0003) and microsatellite stable (MSS) tumours (33%, 52/160; p = 0.008). However, no such relationship was observed among the CIMP-high or CIMP-0 groups. The relationship between MGMT methylation/silencing and MSI-low is limited to only CIMP-low tumours, supporting the suggestion that CIMP-low in colorectal cancer may be a different molecular phenotype from CIMP-high and CIMP-0. Our data support a molecular difference between MSI-low and MSS in colorectal cancer, and a possible link between CIMP-low, MSI-low, MGMT methylation/loss and KRAS mutation.

  14. CRYSTAL AND MOLECULAR STRUCTURE OF 5-NITROPIRIDINE PIPERIDINE-SULFENAMIDE

    OpenAIRE

    Brito, Iván; León, Yasna; Arias, Mauricio; Vargas, Danitza; Carmona, Francisco; Ramírez, Eduardo; Restovic, Ambrosio; Cárdenas, Alejandro; Wittke, Oscar; López-Rodríguez, Matías

    2002-01-01

    The crystal and molecular structure of 5-nitropiridine piperidine-sulfenamide, C10H13N3O2 S is described and compared with other sulfenamides and with other similar compounds. This structure belongs to a type of divalent sulphur compound and crystallizes in the orthorhombic space group Pnma with a= 27.810(4), b=6.797(1), c=6.110(1)Å, and Dx =1.376 g cm-3 with Z=4. The S-N bond distance of 1.699(4) Å is shorter than a single S-N bond [1.74 Å]. The NO2-(C6H3N)-S-N(C 5H10) molecule lies on a cry...

  15. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    International Nuclear Information System (INIS)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    2012-01-01

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of “fluorine as a probe in medicinal chemistry” an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells. - Highlights: ► Development of HR-CS MAS for quantification of fluorine bound to organic molecules ► Measuring as molecular absorption of gallium monofluoride ► Quantification of organic-bound fluorine in biological material ► The concept of “fluorine as a probe in medicinal chemistry” could be established

  16. 5 CFR 870.803 - Child incapable of self-support.

    Science.gov (United States)

    2010-01-01

    .... The certificate must include the name of the child, the type of disability, how long it has existed... certificate stating that the child is incapable of self-support because of a physical or mental disability... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Child incapable of self-support. 870.803...

  17. Synthesis and chemistry of chromium in CrAPO-5 molecular sieves

    NARCIS (Netherlands)

    Weckhuysen, B.M.; Schoonheydt, R.A.

    1994-01-01

    CrAPO-5 molecular sieves were synthesized hydrothermally starting with different Cr precursors and Cr and template contents. The behavior of Cr was investigated spectroscopically by diffuse reflectance spectroscopy (d.r.s.) and electron spin resonance (e.s.r.). In the gels, Cr 3+ and Cr 8+ are

  18. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    Science.gov (United States)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of "fluorine as a probe in medicinal chemistry" an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells.

  19. Preparation of self-supporting molecularly imprinted films via transition layer construction and RAFT polymerization, and their use in HPLC

    International Nuclear Information System (INIS)

    Ding, Peng; Tang, Shengfu; Shi, Liyi; Li, Zongzhou; Song, Na

    2013-01-01

    Molecularly imprinted films with self-supporting property (SS-MIFs) have been prepared by using the strategy of transition layer construction followed by reversible addition-fragmentation chain transfer (RAFT) polymerization. The structure, composition and selectivity of the SS-MIFs as well as the mechanism of mass transfer were characterized by scanning electron microscopy, X-ray diffraction, Fourier transform IR spectrometry, specific surface area analysis, thermogravimetric analysis, and HPLC. Surface area analysis showed the samples possessed specific surface areas as high as 80.5 m 2 .g −1 . This is almost 9 times more than that of the original porous anodic aluminum oxide substrate. Thermogravimetric analysis also showed the samples to be thermally stable up to 350 °C. The separating power was investigated by HPLC and revealed a selective separation effect for the target molecules theobromine. The separation factor is 5.37. (author)

  20. Commentary: Biochemistry and Molecular Biology Educators Launch National Network

    Science.gov (United States)

    Bailey, Cheryl; Bell, Ellis; Johnson, Margaret; Mattos, Carla; Sears, Duane; White, Harold B.

    2010-01-01

    The American Society of Biochemistry and Molecular Biology (ASBMB) has launched an National Science Foundation (NSF)-funded 5 year project to support biochemistry and molecular biology educators learning what and how students learn. As a part of this initiative, hundreds of life scientists will plan and develop a rich central resource for…

  1. Theoretical studies on molecular and explosive properties of 4,4',5,5'-Tetranitro-2,2'-bi-1H-imidazole (TNBI)

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Soo Gyeong; Goh, Eun Mee; Cho, Jin Rai; Kim, Jeong Kook [High Explosives Team, Agency for Defense Development, P. O. Box 35-5, Yuseong, Daejeon, 305-600 (Korea)

    2006-02-15

    We performed theoretical studies to predict the molecular structure, molecular properties, and explosive performance of 4,4',5,5'-tetranitro-2,2'-bi-1H-imidazole (TNBI). High levels of ab initio and density functional theories were employed to predict the molecular structure of TNBI. Predicted TNBI structure was in good agreement with that observed by X-ray crystallography. Heat of formation in the solid phase at 298 K was predicted to be 270.3 kJ/mol. Density of TNBI was predicted to be 1.919-1.956 g/cm{sup 3} depending upon the parameter sets of group additivity method. By using these values as input data, we estimated detonation velocity and C-J pressure to be 8.69-8.80 km/s and 34.5-36.1 GPa, respectively. Impact sensitivity of TNBI was predicted to be 33 cm. (Abstract Copyright [2006], Wiley Periodicals, Inc.)

  2. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Magnus [Freie Universitaet Berlin, Institut fuer Pharmazie, Pharmazeutische Chemie, Koenigin-Luise-Str. 2-4, 14195 Berlin (Germany); Huang, Mao-Dong; Becker-Ross, Helmut; Florek, Stefan [Leibniz Institut fuer Analytische Wissenschaften, ISAS-e.V., Department Berlin, Albert-Einstein-Str. 9, 12489 Berlin (Germany); Ott, Ingo [Technische Universitaet Carolo Wilhelmina zu Braunschweig, Institut fuer Medizinische und Pharmazeutische Chemie, Beethovenstr. 55, 38106 Braunschweig (Germany); Gust, Ronald, E-mail: ronald.gust@uibk.ac.at [Universitaet Innsbruck, Institut fuer Pharmazie, Pharmazeutische Chemie, Innrain 80/82, 6020 Innsbruck (Austria)

    2012-03-15

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of 'fluorine as a probe in medicinal chemistry' an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells. - Highlights: Black-Right-Pointing-Pointer Development of HR-CS MAS for quantification of fluorine bound to organic molecules Black-Right-Pointing-Pointer Measuring as molecular absorption of gallium monofluoride Black-Right-Pointing-Pointer Quantification of organic-bound fluorine in biological material Black-Right-Pointing-Pointer The concept of 'fluorine as a probe in medicinal chemistry' could be established.

  3. How Dynamic Visualization Technology Can Support Molecular Reasoning

    Science.gov (United States)

    Levy, Dalit

    2013-01-01

    This paper reports the results of a study aimed at exploring the advantages of dynamic visualization for the development of better understanding of molecular processes. We designed a technology-enhanced curriculum module in which high school chemistry students conduct virtual experiments with dynamic molecular visualizations of solid, liquid, and…

  4. Photoassociation spectroscopy of 87Rb2 (5s1/2+5p1/2)0u+ long-range molecular states: Coupling with the (5s1/2+5p3/2)0u+ series analyzed using the Lu-Fano approach

    International Nuclear Information System (INIS)

    Jelassi, H.; Viaris de Lesegno, B.; Pruvost, L.

    2006-01-01

    We report on photoassociation of cold 87 Rb atoms providing the spectroscopy of (5s 1/2 +5p 1/2 )0 u + long-range molecular states, in the energy range of [-12.5, -0.7 cm -1 ] below the dissociation limit. A Lu-Fano approach coupled to the LeRoy-Bernstein formula is used to analyze the data. The Lu-Fano graph exhibits the coupling of the molecular series with the (5s 1/2 +5p 3/2 )0 u + one, which is due to spin effects in the molecule. A two-channel model involving an improved LeRoy-Bernstein formula allows us to characterize the molecular series, to localize (5s 1/2 +5p 3/2 )0 u + levels, to evaluate the coupling, and to predict the energy and width of the first predissociated level of (5s 1/2 +5p 3/2 )0 u + series. An experimental spectrum confirms the prediction

  5. 1-[5-(2-Chlorophenyl-3-(4-methylphenyl-4,5-dihydro-1H-pyrazol-1-yl]ethan-1-one

    Directory of Open Access Journals (Sweden)

    Farook Adam

    2016-01-01

    Full Text Available The title compound, C18H17ClN2O, crystallized with two independent molecules (the S and R enantiomers in the asymmetric unit. The molecules are V-shaped with the two aromatic rings inclined to one another by 78.78 (11 and 81.23 (11°. In the crystal, molecules are linked via C—H...O hydrogen bonds, forming chains along the c-axis direction. The chains are linked via C—H...π interactions, forming a three-dimensional framework. The crystal structure was refined as a two-component twin.

  6. Analysis of neonicotinoids by gas chromatography coupled to nuclide 63Ni - Electron Capture Detector - GC/ECD

    International Nuclear Information System (INIS)

    Amaral, Priscila O.; Leao, Claudio; Redigolo, Marcelo M.; Crepaldi, Caike; Bustillos, Oscar V.

    2015-01-01

    Recently, several reports have been published discussing reduction in bee population which polymerizes cultures around the world this phenomenon is known as Colony Collapse Disorder (CCD). The phenomenon describes the lack of worker honeybees in the colony despite having pups and food. The causes of this problem are unknown but there are studies that claim that reduction of population of bees is linked to poisoning through insecticides specifically neonicotinoids. Among this type of pesticide are imidacloprid (C 9 H 10 ClN 5 O 2 ), clothianidin (C 6 H 8 ClN 5 O 2 S) and thiamethoxam (C 8 H 10 ClN 5 O 3 S). This paper presents the analysis of neonicotinoids - clothianidin, imidacloprid and thiamethoxam - by the technique of gas chromatography coupled to nuclide 63 Ni electron capture detector (GC/ECD). The electron capture detector (ECD) is a gas chromatography detector that has been used for the detection of organic halogens, nitriles, nitrates and organometallic compounds. The ECD detector ionizes the analytes by the beta particles from the nuclide sources 63 Ni within carrier gas N 2 . The electrons produced in this process are collected and create a current that are amplified and generates a chromatographic peak. Methodology and details of the analysis are present in this work. (author)

  7. Negative differential resistance and switch behavior of T-BxNy (x, y = 5, 6, 11) molecular junctions

    Science.gov (United States)

    Wang, Shi-Liang; Yang, Chuan-Lu; Wang, Mei-Shan; Ma, Xiao-Guang; Xin, Jian-Guo

    2017-05-01

    The electronic transport properties of T-BxNy (x, y = 5, 6, 11) molecular junction are investigated based on first-principle density functional theory and non-equilibrium Green's function method. Strong negative differential resistance (NDR) behavior is observed for T-B5N6 molecule under negative and positive bias voltages, with an obvious switch effect for T-B6N5. However, only small NDR is shown for the complex of the two molecules. The projected device density of states, the spatial distribution of molecular orbitals, and the effect of transmission spectra under various bias voltages on the electronic transport properties are analyzed. The obvious effect of bias voltage on the changes in the electronic distribution of frontier molecular orbitals is responsible for the NDR or switch behavior. Therefore, different functional molecular devices can be obtained with different structures of T-BxNy.

  8. Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys.

    Science.gov (United States)

    Mei, Davide; Darra, Francesca; Barba, Carmen; Marini, Carla; Fontana, Elena; Chiti, Laura; Parrini, Elena; Dalla Bernardina, Bernardo; Guerrini, Renzo

    2014-11-01

    Mutations involving the cyclin-dependent kinase-like 5 (CDKL5) gene cause an early onset epileptic encephalopathy (EE) with severe neurologic impairment and a skewed 12:1 female-to-male ratio. To date, 18 mutations have been described in boys. We analyzed our cohort of boys with early onset EE to assess the diagnostic yield of our molecular approach. We studied 74 boys who presented early onset severe seizures, including infantile spasms and developmental delay, in the setting of EE, using Sanger sequencing, next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). We identified alterations involving CDKL5 in four boys (5.4%) using NGS in one and MLPA in three. Three of four mutations were indicative of somatic mosaicism. CDKL5 gene mutations accounted for 5.4% of boys with early onset EE. Somatic mosaic mutations might be even more represented than germline mutations, probably because their less deleterious effect enhances viability of the male embryo. The molecular approach used for CDKL5 screening remarkably influences the diagnostic yield in boys. Diagnosis is optimized by Sanger sequencing combined with array-based methods or MLPA; alternatively, NGS targeted resequencing designed to also detect copy number alterations, may be performed. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  9. In situ synthesis of molecularly imprinted nanoparticles in porous support membranes using high-viscosity polymerization solvents.

    Science.gov (United States)

    Renkecz, Tibor; László, Krisztina; Horváth, Viola

    2012-06-01

    There is a growing need in membrane separations for novel membrane materials providing selective retention. Molecularly imprinted polymers (MIPs) are promising candidates for membrane functionalization. In this work, a novel approach is described to prepare composite membrane adsorbers incorporating molecularly imprinted microparticles or nanoparticles into commercially available macroporous filtration membranes. The polymerization is carried out in highly viscous polymerization solvents, and the particles are formed in situ in the pores of the support membrane. MIP particle composite membranes selective for terbutylazine were prepared and characterized by scanning electron microscopy and N₂ porosimetry. By varying the polymerization solvent microparticles or nanoparticles with diameters ranging from several hundred nanometers to 1 µm could be embedded into the support. The permeability of the membranes was in the range of 1000 to 20,000 Lm⁻²  hr⁻¹  bar⁻¹. The imprinted composite membranes showed high MIP/NIP (nonimprinted polymer) selectivity for the template in organic media both in equilibrium-rebinding measurements and in filtration experiments. The solid phase extraction of a mixture of the template, its analogs, and a nonrelated compound demonstrated MIP/NIP selectivity and substance selectivity of the new molecularly imprinted membrane. The synthesis technique offers a potential for the cost-effective production of selective membrane adsorbers with high capacity and high throughput. Copyright © 2012 John Wiley & Sons, Ltd.

  10. [Analysis of hot spots and trend of molecular pharmacognosy research based on project supported by National Natural Science Foundation of 1995-2014].

    Science.gov (United States)

    Wang, Jun-Wen; Liu, Yang; Tong, Yuan-Yuan; Yang, Ce; Li, Hai-Yan

    2016-05-01

    This study collected 1995-2014 molecular pharmacognosy study, a total of 595 items, funded by Natural Science Foundation of China (NSFC). TDA and Excel software were used to analyze the data of the projects about general situation, hot spots of research with rank analytic and correlation analytic methods. Supported by NSFC molecular pharmacognosy projects and funding a gradual increase in the number of, the proportion of funds for pharmaceutical research funding tends to be stable; mainly supported by molecular biology methods of genuine medicinal materials, secondary metabolism and Germplasm Resources Research; hot drugs including Radix Salviae Miltiorrhizae, Radix Rehmanniae, Cordyceps sinensis, hot contents including tanshinone biosynthesis, Rehmannia glutinosa continuous cropping obstacle. Copyright© by the Chinese Pharmaceutical Association.

  11. Effects of water vapor on the radiolysis of methane over molecular sieve 5A

    International Nuclear Information System (INIS)

    Shimizu, Y.; Nagai, S.

    1989-01-01

    Effects of the addition of H 2 O on the radiation-induced chemical reaction of methane over molecular sieve 5A at 460 0 C have been studied by product analysis. Hydrogen, carbon monoxide, carbon dioxide and hydrocarbons consisting mainly of C 2 and C 3 alkanes and alkenes were produced from CH 4 + H 2 O mixtures at high conversion levels. The yields of hydrocarbons from 3:1 and 3:2 CH 4 + H 2 O mixtures decreased slightly with time but those from 3:4 mixture showed no decrease with time. When the molecular sieve 5A that had been irradiated in flowing methane was reirradiated in the presence of H 2 O, carbonaceous solid produced from methane on molecular sieve 5A was readily decomposed to carbon dioxide, carbon monoxide, hydrogen and hydrocarbons, mainly alkanes. Therefore, it is concluded that the suppression of decrease of product yields with time by the addition of H 2 O is mainly ascribed to decomposition of the carbonaceous solid by H 2 O under electron beam irradiation. The role of added H 2 O is also discussed in connection with the conventional methane-steam reforming reaction. (author)

  12. Insight into the molecular switch mechanism of human Rab5a from molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing-Fang, E-mail: jfwang@gordonlifescience.org [Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shanghai Center for Bioinformation Technology, 100 Qinzhou Road, Shanghai 200235 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States); Chou, Kuo-Chen [Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States)

    2009-12-18

    Rab5a is currently a most interesting target because it is responsible for regulating the early endosome fusion in endocytosis and possibly the budding process. We utilized longtime-scale molecular dynamics simulations to investigate the internal motion of the wild-type Rab5a and its A30P mutant. It was observed that, after binding with GTP, the global flexibility of the two proteins is increasing, while the local flexibility in their sensitive sites (P-loop, switch I and II regions) is decreasing. Also, the mutation of Ala30 to Pro30 can cause notable flexibility variations in the sensitive sites. However, this kind of variations is dramatically reduced after binding with GTP. Such a remarkable feature is mainly caused by the water network rearrangements in the sensitive sites. These findings might be of use for revealing the profound mechanism of the displacements of Rab5a switch regions, as well as the mechanism of the GDP dissociation and GTP association.

  13. Preparation of Ultrahigh Molecular Weight Polyethylene/Graphene Nanocomposite In situ Polymerization via Spherical and Sandwich Structure Graphene/Sio2 Support

    Science.gov (United States)

    Su, Enqi; Gao, Wensheng; Hu, Xinjun; Zhang, Caicai; Zhu, Bochao; Jia, Junji; Huang, Anping; Bai, Yongxiao

    2018-04-01

    Reduced graphene oxide/SiO2 (RGO/SiO2) serving as a novel spherical support for Ziegler-Natta (Z-N) catalyst is reported. The surface and interior of the support has a porous architecture formed by RGO/SiO2 sandwich structure. The sandwich structure is like a brick wall coated with a graphene layer of concreted as skeleton which could withstand external pressures and endow the structure with higher support stabilities. After loading the Z-N catalyst, the active components anchor on the surface and internal pores of the supports. When the ethylene molecules meet the active centers, the molecular chains grow from the surface and internal catalytic sites in a regular and well-organized way. And the process of the nascent molecular chains filled in the sandwich structure polymerization could ensure the graphene disperse uniformly in the polymer matrix. Compared with traditional methods, the porous spherical graphene support of this strategy has far more advantages and could maintain an intrinsic graphene performance in the nanocomposites.

  14. 1-[1-(4-Chloro­phen­yl)ethyl­idene]carbono­hydrazide

    Science.gov (United States)

    Du, Lingyun; Du, Lei; Wang, Shuhao

    2009-01-01

    The mol­ecular skeleton of the title mol­ecule, C9H11ClN4O, is essentially planar, the dihedral angle between the ring and the and N/N/C plane being 6.7 (3)°. In the crystal, inter­molecular N—H⋯O and N—H⋯N hydrogen bonds link the mol­ecules into ribbons propagated along [010]. PMID:21577542

  15. Synthesis, crystal structure, vibrational spectra and theoretical calculations of quantum chemistry of a potential antimicrobial Meldrum's acid derivative

    Science.gov (United States)

    Campelo, M. J. M.; Freire, P. T. C.; Mendes Filho, J.; de Toledo, T. A.; Teixeira, A. M. R.; da Silva, L. E.; Bento, R. R. F.; Faria, J. L. B.; Pizani, P. S.; Gusmão, G. O. M.; Coutinho, H. D. M.; Oliveira, M. T. A.

    2017-10-01

    A new derivative of Meldrum's acid 5-((5-chloropyridin-2-ylamino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (CYMM) of molecular formula C12H11ClN2O4 was synthesized and structurally characterized using single crystal X-ray diffraction technique. The vibrational properties of the crystal were studied by Fourier Transform infrared (FT-IR), Fourier Transform Raman (FT-Raman) techniques and theoretical calculations of quantum chemistry using Density functional theory (DFT) and Density functional perturbation theory (DFPT). A comparison with experimental spectra allowed the assignment of all the normal modes. The descriptions of the normal modes were carried by means of potential energy distribution (PED). Additionally, analysis of the antimicrobial activity and antibiotic resistance modulatory activity was carried out to evaluate the antibacterial potential of the CYMM.

  16. Lysosomal-associated transmembrane protein 5 (LAPTM5 is a molecular partner of CD1e.

    Directory of Open Access Journals (Sweden)

    Catherine Angénieux

    Full Text Available The CD1e protein participates in the presentation of lipid antigens in dendritic cells. Its transmembrane precursor is transported to lysosomes where it is cleaved into an active soluble form. In the presence of bafilomycin, which inhibits vacuolar ATPase and consequently the acidification of endosomal compartments, CD1e associates with a 27 kD protein. In this work, we identified this molecular partner as LAPTM5. The latter protein and CD1e colocalize in trans-Golgi and late endosomal compartments. The quantity of LAPTM5/CD1e complexes increases when the cells are treated with bafilomycin, probably due to the protection of LAPTM5 from lysosomal proteases. Moreover, we could demonstrate that LAPTM5/CD1e association occurs under physiological conditions. Although LAPTM5 was previously shown to act as a platform recruiting ubiquitin ligases and facilitating the transport of receptors to lysosomes, we found no evidence that LATPM5 controls either CD1e ubiquitination or the generation of soluble lysosomal CD1e proteins. Notwithstanding these last observations, the interaction of LAPTM5 with CD1e and their colocalization in antigen processing compartments both suggest that LAPTM5 might influence the role of CD1e in the presentation of lipid antigens.

  17. Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.

    Directory of Open Access Journals (Sweden)

    Birgit Piater

    Full Text Available The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF. Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX. CLN64 and a previously described single-stranded DNA (ssDNA aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.

  18. Gemfibrozil, food and drug administration-approved lipid-lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Ghosh, Arunava; Rangasamy, Suresh Babu; Modi, Khushbu K; Pahan, Kalipada

    2017-05-01

    Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL. Therefore, we administered gemfibrozil (gem), an food and drug administration (FDA)-approved lipid-lowering drug, which has been shown to stimulate lysosomal biogenesis and induce anti-inflammation, orally, at a dose of 7.5 mg/kg body wt/day to Cln2 (-/-) mice. We observed that gem-fed Cln2 (-/-) mice lived longer by more than 10 weeks and had better motor activity compared to vehicle (0.1% Methyl cellulose) treatment. Gem treatment lowered the burden of storage materials, increased anti-inflammatory factors like SOCS3 and IL-1Ra, up-regulated anti-apoptotic molecule like phospho-Bad, and reduced neuronal apoptosis in the brain of Cln2 (-/-) mice. Collectively, this study reinforces a neuroprotective role of gem that may be of therapeutic interest in improving the quality of life in LINCL patients. © 2017 International Society for Neurochemistry.

  19. Energy Storage Analysis of a Mixed R161/MOF-5 Nanoparticle Nanofluid Based on Molecular Simulations.

    Science.gov (United States)

    Wang, Qiang; Tang, Shengli; Li, Leilei

    2018-05-20

    The thermal properties of refrigerants can be modified by adding porous nanoparticles into them. Here, molecular simulations, including molecular dynamics and grand canonical Monte Carlo, were employed to study the thermal energy storage properties of an R161/MOF-5 nanofluid. The results show that the thermodynamic energy change of MOF-5 nanoparticles is linear to the temperature. The adsorption heat calculated by grand canonical Monte Carlo is close to that calculated by the Clausius⁻Clapeyron equation. Additionally, a negative enhancement of the thermal energy storage capacity of the R161/MOF-5 nanofluid is found near the phase transition area.

  20. Three-site mechanism and molecular weight: Time dependency in liquid propylene batch polymerization using a MgCl2-supported Ziegler-Natta catalyst

    NARCIS (Netherlands)

    Shimizu, Fumihiko; Pater, J.T.M.; Weickert, G.

    2001-01-01

    This article demonstrates that the molecular weight of propylene homopolymer decreases with time, and that the molecular weight distribution (MWD) narrows when a highly active MgCl2-supported catalyst is used in a liquid pool polymerization at constant H2 concentration and temperature. To track the

  1. Cardiovascular molecular imaging of apoptosis

    International Nuclear Information System (INIS)

    Wolters, S.L.; Reutelingsperger, C.P.M.; Corsten, M.F.; Hofstra, L.; Narula, J.

    2007-01-01

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  2. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

    2007-06-15

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  3. Study of the chemical binding effect on the molecular stopping power of V2O5

    International Nuclear Information System (INIS)

    Eisenbarth, S.R.

    1981-01-01

    The stopping powers of V and V 2 O 5 have been measured for helium ions with energies from 0.3 to 2.0 MeV and probable errors of 2.2 and 3.0%, respectively. The vanadium stopping power was 12 and 14% lower than the previous measurement of Chu and Powers (1969) and 2 to 5% lower than the semi-empirical values of Chu and Zeigler (1974) in this energy range. The V 2 O 5 stopping power was found to be 2 to 3.5% lower than the Bragg rule curve calculated with the molecular oxygen values of Bourland, Chu, and Powers (1971) and the present vanadium stopping power. The use of Bragg's rule to extract the oxygen contribution to the molecular stopping power of V 2 O 5 results in a solid oxygen stopping power which is in good agreement with the solid molecular oxygen measurement of Chu, Braun, Davies, Matsunami, and Thompson (1978) and approximately 5% higher than Feng's value (1974) obtained from metal oxides which have wide energy band gaps. The present experiment cautions against the use of a common stopping power for oxygen in Bragg rule calculations for solid compounds as purposed by Feng and by Zeigler and Chu (1976)

  4. Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine

    Science.gov (United States)

    Oldiges, Daiane P.; Laughery, Jacob M.; Tagliari, Nelson Junior; Leite Filho, Ronaldo Viana; Davis, William C.; da Silva Vaz, Itabajara; Termignoni, Carlos; Knowles, Donald P.; Suarez, Carlos E.

    2016-01-01

    The Rhipicephalus microplus tick is a notorious blood-feeding ectoparasite of livestock, especially cattle, responsible for massive losses in animal production. It is the main vector for transmission of pathogenic bacteria and parasites, including Babesia bovis, an intraerythrocytic apicomplexan protozoan parasite responsible for bovine Babesiosis. This study describes the development and testing of a live B. bovis vaccine expressing the protective tick antigen glutathione-S-transferase from Haemaphysalis longicornis (HlGST). The B. bovis S74-T3B parasites were electroporated with a plasmid containing the bidirectional Ef-1α (elongation factor 1 alpha) promoter of B. bovis controlling expression of two independent genes, the selectable marker GFP-BSD (green fluorescent protein–blasticidin deaminase), and HlGST fused to the MSA-1 (merozoite surface antigen 1) signal peptide from B. bovis. Electroporation followed by blasticidin selection resulted in the emergence of a mixed B. bovis transfected line (termed HlGST) in in vitro cultures, containing parasites with distinct patterns of insertion of both exogenous genes, either in or outside the Ef-1α locus. A B. bovis clonal line termed HlGST-Cln expressing intracellular GFP and HlGST in the surface of merozoites was then derived from the mixed parasite line HlGST using a fluorescent activated cell sorter. Two independent calf immunization trials were performed via intravenous inoculation of the HlGST-Cln and a previously described control consisting of an irrelevant transfected clonal line of B. bovis designated GFP-Cln. The control GFP-Cln line contains a copy of the GFP-BSD gene inserted into the Ef-1α locus of B. bovis in an identical fashion as the HIGST-Cln parasites. All animals inoculated with the HlGST-Cln and GFP-Cln transfected parasites developed mild babesiosis. Tick egg fertility and fully engorged female tick weight was reduced significantly in R. microplus feeding on HlGST-Cln-immunized calves

  5. Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine.

    Directory of Open Access Journals (Sweden)

    Daiane P Oldiges

    2016-12-01

    Full Text Available The Rhipicephalus microplus tick is a notorious blood-feeding ectoparasite of livestock, especially cattle, responsible for massive losses in animal production. It is the main vector for transmission of pathogenic bacteria and parasites, including Babesia bovis, an intraerythrocytic apicomplexan protozoan parasite responsible for bovine Babesiosis. This study describes the development and testing of a live B. bovis vaccine expressing the protective tick antigen glutathione-S-transferase from Haemaphysalis longicornis (HlGST. The B. bovis S74-T3B parasites were electroporated with a plasmid containing the bidirectional Ef-1α (elongation factor 1 alpha promoter of B. bovis controlling expression of two independent genes, the selectable marker GFP-BSD (green fluorescent protein-blasticidin deaminase, and HlGST fused to the MSA-1 (merozoite surface antigen 1 signal peptide from B. bovis. Electroporation followed by blasticidin selection resulted in the emergence of a mixed B. bovis transfected line (termed HlGST in in vitro cultures, containing parasites with distinct patterns of insertion of both exogenous genes, either in or outside the Ef-1α locus. A B. bovis clonal line termed HlGST-Cln expressing intracellular GFP and HlGST in the surface of merozoites was then derived from the mixed parasite line HlGST using a fluorescent activated cell sorter. Two independent calf immunization trials were performed via intravenous inoculation of the HlGST-Cln and a previously described control consisting of an irrelevant transfected clonal line of B. bovis designated GFP-Cln. The control GFP-Cln line contains a copy of the GFP-BSD gene inserted into the Ef-1α locus of B. bovis in an identical fashion as the HIGST-Cln parasites. All animals inoculated with the HlGST-Cln and GFP-Cln transfected parasites developed mild babesiosis. Tick egg fertility and fully engorged female tick weight was reduced significantly in R. microplus feeding on HlGST-Cln

  6. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

    Science.gov (United States)

    Staquicini, Fernanda I; Qian, Ming D; Salameh, Ahmad; Dobroff, Andrey S; Edwards, Julianna K; Cimino, Daniel F; Moeller, Benjamin J; Kelly, Patrick; Nunez, Maria I; Tang, Ximing; Liu, Diane D; Lee, J Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R M; Lobb, Roy R; Edelman, Martin J; Sidman, Richard L; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

    International Nuclear Information System (INIS)

    Asafi, M S; Tekpinar, M; Yildirim, A

    2016-01-01

    Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated. (paper)

  8. Editorial: Molecular Organization of Membranes: Where Biology Meets Biophysics

    Czech Academy of Sciences Publication Activity Database

    Cebecauer, Marek; Holowka, D.

    2017-01-01

    Roč. 5, č. 113 (2017), s. 1-3 ISSN 2296-634X Institutional support: RVO:61388955 Keywords : nanodomains * membrane properties * cell membrane Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology

  9. Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5).

    Science.gov (United States)

    Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav; Daugvilaite, Viktorija; Steen, Anne; Brvar, Matjaž; Pui, Aurel; Frimurer, Thomas Michael; Ulven, Trond; Rosenkilde, Mette Marie

    2016-12-23

    The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn 2+ (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site using computational modeling, binding, and functional studies on WT and mutated CCR5. The metal ion Zn 2+ is anchored to the chemokine receptor-conserved Glu-283 VII:06/7.39 Both chelators interact with aromatic residues in the transmembrane receptor domain. The additional pyridine ring of ZnTerp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248 VI:13/6.48 microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism but maintained positive allosteric modulation of CCL3 binding. Despite a similar overall binding mode of all three metal ion chelator complexes, the pyridine ring of ZnClTerp blocks the conformational switch of Trp-248 required for receptor activation, thereby explaining its lack of activity. Importantly, ZnClTerp becomes agonist to the same extent as ZnTerp upon Ala mutation of Ile-116 III:16/3.40 , a residue that constrains the Trp-248 microswitch in its inactive conformation. Binding studies with 125 I-CCL3 revealed an allosteric interface between the chemokine and the small molecule binding site, including residues Tyr-37 I:07/1.39 , Trp-86 II:20/2.60 , and Phe-109 III:09/3.33 The small molecules and CCL3 approach this interface from opposite directions, with some residues being mutually exploited. This study provides new insight into the molecular mechanism of CCR5 activation and paves the way for future allosteric drugs for chemokine receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Slow neutron scattering in molecular crystals. 5-4

    International Nuclear Information System (INIS)

    Inoue, Kazuhiko

    1976-01-01

    The utilization of incoherent inelastic neutron scattering (INS) as a probe for molecular crystals is reviewed. In particular, some typical examples of the measurement of incoherent inelastic neutron scattering spectra (INSS) in molecular crystals are presented in the first section of this report. The results of measurement are shown for theta-xylene, benzene, polypropylene oxide, deuteride, and formic acid. The second section presents an equation for the incoherent scattering cross section of a crystal by dividing the molecular motion into the outer and inner modes. Phonon expansion is also used for the easy understanding of the relation between the INSS and the dynamic characteristics of molecular crystals. In the third section, the measured results are analyzed on the basis of the theory presented in the previous section. And the difference between the van der Waals bond and the hydrogen bond is shortly discussed. (Aoki, K.)

  11. The crystal structures of three pyrazine-2,5-dicarb-oxamides: three-dimensional supra-molecular structures.

    Science.gov (United States)

    Cati, Dilovan S; Stoeckli-Evans, Helen

    2017-05-01

    The complete mol-ecules of the title compounds, N 2 , N 5 -bis-(pyridin-2-ylmeth-yl)pyrazine-2,5-dicarboxamide, C 18 H 16 N 6 O 2 (I), 3,6-dimethyl- N 2 , N 5 -bis-(pyridin-2-yl-meth-yl)pyrazine-2,5-dicarboxamide, C 20 H 20 N 6 O 2 (II), and N 2 , N 5 -bis-(pyridin-4-ylmeth-yl)pyrazine-2,5-dicarboxamide, C 18 H 16 N 6 O 2 (III), are generated by inversion symmetry, with the pyrazine rings being located about centres of inversion. Each mol-ecule has an extended conformation with the pyridine rings inclined to the pyrazine ring by 89.17 (7)° in (I), 75.83 (8)° in (II) and by 82.71 (6)° in (III). In the crystal of (I), mol-ecules are linked by N-H⋯N hydrogen bonds, forming layers lying parallel to the bc plane. The layers are linked by C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure. In the crystal of (II), mol-ecules are also linked by N-H⋯N hydrogen bonds, forming layers lying parallel to the (10-1) plane. As in (I), the layers are linked by C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure. In the crystal of (III), mol-ecules are again linked by N-H⋯N hydrogen bonds, but here form corrugated sheets lying parallel to the bc plane. Within the sheets, neighbouring pyridine rings are linked by offset π-π inter-actions [inter-centroid distance = 3.739 (1) Å]. The sheets are linked by C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure. Compound (I) crystallizes in the monoclinic space group P 2 1 / c . Another monoclinic polymorph, space group C 2/ c , has been reported on by Cockriel et al. [ Inorg. Chem. Commun. (2008), 11 , 1-4]. The mol-ecular structures of the two polymorphs are compared.

  12. Preparation, Characterization, and UV Irradiation of Mars Soil Analogues Under Simulated Martian Conditions to Support Detection of Molecular Biomarkers

    Science.gov (United States)

    Fornaro, T.; Brucato, J. R.; ten Kate, I. L.; Siljeström, S.; Steele, A.; Cody, G. D.; Hazen, R. M.

    2018-04-01

    We present laboratory activities of preparation, characterization, and UV irradiation processing of Mars soil analogues, which are key to support both in situ exploration and sample return missions devoted to detection of molecular biomarkers on Mars.

  13. Molecular Modeling of Adsorption of 5-Aminosalicylic Acid in the Halloysite Nanotube

    Directory of Open Access Journals (Sweden)

    Ana Borrego-Sánchez

    2018-02-01

    Full Text Available Halloysite nanotubes are becoming interesting materials for drug delivery. The knowledge of surface interactions is important for optimizing this application. The aim of this work is to perform a computational study of the interaction between 5-aminosalicylic acid (5-ASA drug and halloysite nanotubes for the development of modified drug delivery systems. The optimization of this nanotube and the adsorption of different conformers of the 5-ASA drug on the internal surface of halloysite in the presence and absence of water were performed using quantum mechanical calculations by using Density Functional Theory (DFT and methods based on atomistic force fields for molecular modeling, respectively.

  14. 33 original article infections a pseudomonas aeruginosa dans un

    African Journals Online (AJOL)

    boaz

    COPYRIGHT 2014. AFR. J. CLN. EXPER. .... Effective management of P. aeruginosa infections requires good ... a guide for doctors managing patients with. Pseudomonas .... Principles and practice of infectious diseases.5th edition. Edited by ...

  15. Peltier cooling in molecular junctions

    Science.gov (United States)

    Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod

    2018-02-01

    The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.

  16. Cdc42 and Tks5: a minimal and universal molecular signature for functional invadosomes.

    Science.gov (United States)

    Di Martino, Julie; Paysan, Lisa; Gest, Caroline; Lagrée, Valérie; Juin, Amélie; Saltel, Frédéric; Moreau, Violaine

    2014-01-01

    Invadosomes are actin-based structures involved in extracellular-matrix degradation. Invadosomes, either known as podosomes or invadopodia, are found in an increasing number of cell types. Moreover, their overall organization and molecular composition may vary from one cell type to the other. Some are constitutive such as podosomes in hematopoietic cells whereas others are inducible. However, they share the same feature, their ability to interact and to degrade the extracellular matrix. Based on the literature and our own experiments, the aim of this study was to establish a minimal molecular definition of active invadosomes. We first highlighted that Cdc42 is the key RhoGTPase involved in invadosome formation in all described models. Using different cellular models, such as NIH-3T3, HeLa, and endothelial cells, we demonstrated that overexpression of an active form of Cdc42 is sufficient to form invadosome actin cores. Therefore, active Cdc42 must be considered not only as an inducer of filopodia, but also as an inducer of invadosomes. Depending on the expression level of Tks5, these Cdc42-dependent actin cores were endowed or not with a proteolytic activity. In fact, Tks5 overexpression rescued this activity in Tks5 low expressing cells. We thus described the adaptor protein Tks5 as a major actor of the invadosome degradation function. Surprisingly, we found that Src kinases are not always required for invadosome formation and function. These data suggest that even if Src family members are the principal kinases involved in the majority of invadosomes, it cannot be considered as a common element for all invadosome structures. We thus define a minimal and universal molecular signature of invadosome that includes Cdc42 activity and Tks5 presence in order to drive the actin machinery and the proteolytic activity of these invasive structures.

  17. X-ray crystal and molecular structure of (eta/sup 5/C/sub 5/H/sub 5/)UCl/sub 3/. 2PPh/sub 3/O thf: trichloro (eta/sup 5/cyclopentadienyl)bis(triphenylphosphine oxide) uranium(IV). thf

    Energy Technology Data Exchange (ETDEWEB)

    Bombieri, G; De Paoli, G [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi; Del Pra, A; Bagnall, K W

    1978-01-01

    Following reports of the preparation of (eta/sup 5/C/sub 5/H/sub 5/)UCl/sub 3/.xL (x = 1, L = dimethoxyethane and x = 2, L = tetrahydrofuran (thf), a series of analogous oxygen-donor complexes were isolated. This paper describes the crystal and molecular structure of one of them, ((eta/sup 5/C/sub 5/H/sub 5/)UCl/sub 3/.2PPh/sub 3/O)thf.

  18. Calcifying/ossifying synovial sarcoma: A clinicopathologic and molecular study of 5 cases

    Directory of Open Access Journals (Sweden)

    Nasir Ud Din

    2015-01-01

    Full Text Available Background: Synovial sarcoma (SS is a soft tissue sarcoma with a generally aggressive behavior. Calcifying/ossifying SS is a rare variant associated with a favorable prognosis. Aim: The aim was to report clinicopathological features and molecular analysis of 5 cases of calcifying/ossifying SS. Materials and Methods: Record of 370 cases of SS reported in the section of Histopathology, of a tertiary care Hospital, between 2002 and 2011 were retrieved. Five cases exhibiting extensive calcification and ossification were identified. Immunohistochemistry was performed using Flex technique. Molecular analysis of these 5 cases was performed later at the collaborative Hospital abroad, by reverse transcription polymerase chain reaction. Results and Conclusions: The ages of the patients ranged from 13 to 44 years (mean age 27 years; female to male ratio 1.6:1. The duration of symptoms ranged from 5 months to 5 years. Histologically, 4 were monophasic, and 1 was biphasic. Three cases exhibited extensive calcification and two extensive ossification. Immunohistochemical stain (epithelial membrane antigen was positive in all 5 cases, CKAE1/AE3 (3/4, Bcl2 (4/4, S100 (4/4, CK7 (2/2, CD99 (1/3 and vimentin (2/2. Intact RNA was obtained from 3 cases, all of which were positive for the SYT/SSX fusion transcript. Follow-up was available in 4 cases and ranged from 19 months to 85 months (mean 50 months. Local recurrence was seen in 2 cases. In conclusions, we report clinicopathologic features of 5 cases of calcifying/ossifying SS. The duration of symptoms and mean age of patients is similar to the literature. A slight female predominance was seen in contrast to a male predominance described in the literature. The clinical course of our cases validates the favorable prognosis of this rare type of SS.

  19. Cervical Lymph Nodes as a Selective Niche for Brucella during Oral Infections

    Science.gov (United States)

    von Bargen, Kristine; Gagnaire, Aurélie; Arce-Gorvel, Vilma; de Bovis, Béatrice; Baudimont, Fannie; Chasson, Lionel; Bosilkovski, Mile; Papadopoulos, Alexia; Martirosyan, Anna; Henri, Sandrine; Mège, Jean-Louis; Malissen, Bernard; Gorvel, Jean-Pierre

    2015-01-01

    Cervical lymph nodes (CLN) are the first lymph nodes encountered by material taking the oral route. To study their role in orally acquired infections, we analyzed 307 patients of up to 14 years treated in the university clinic of Skopje, Macedonia, for brucellosis, a zoonotic bacterial disease frequently acquired by ingestion of contaminated dairy products. From these children, 36% had lymphadenopathy. Among orally infected children, lymphadenopathy with CLN being the only lymph nodes affected was significantly more frequent as compared to those infected by contact with animals (83% vs. 63%), suggesting a possible involvement of CLN during orally acquired human brucellosis. Using a murine model where bacteria are delivered into the oral cavity, we show that Brucella quickly and selectively colonize the CLN where they proliferate and persist over long periods of time for up to 50 days post-infection. A similar efficient though less specific drainage to CLN was found for Brucella, Salmonella typhimurium and fluorescent microspheres delivered by gavage, a pathway likely representing a mixed infection mode of intragastric and oral infection, suggesting a central pathway of drained material. Microspheres as well as bacteria drained to CLN predominately reside in cells expressing CD68 and no or low levels of CD11c. Even though no systemic response could be detected, Brucella induced a locally restricted inflammatory reaction with increased expression levels of interferon γ, interleukin (IL)-6, IL-12, granzyme B and a delayed induction of Nos2. Inflammation led to pronounced lymphadenopathy, infiltration of macrophages/monocytes expressing high levels of major histocompatibility complex II and to formation of epitheloid granulomas. Together, these results highlight the role of CLN in oral infections as both, an initial and efficient trap for bacterial invaders and as possible reservoir for chronic pathogens. They likewise cast a new light on the significance of oral

  20. Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis

    Directory of Open Access Journals (Sweden)

    Aleksandra Somogyi

    2018-02-01

    Full Text Available Juvenile neuronal ceroid lipofuscinosis (JNCL is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase, which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis.

  1. Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis

    Science.gov (United States)

    Somogyi, Aleksandra; Petcherski, Anton; Beckert, Benedikt; Huebecker, Mylene; Priestman, David A.; Banning, Antje; Cotman, Susan L.; Platt, Frances M.; Ruonala, Mika O.

    2018-01-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis. PMID:29470438

  2. Porous rod-like MgO complex membrane with good anti-bacterial activity directed by conjugated linolenic acid polymer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hua-Jie, E-mail: wanghuajie972001@163.com; Chen, Meng [Henan Normal University, College of Chemistry and Chemical Engineering (China); Mi, Li-Wei, E-mail: mlwzzu@163.com [Zhongyuan University of Technology, Center for Advanced Materials Research (China); Shi, Li-Hua [Anyang 101 Education Center (China); Cao, Ying, E-mail: caoying1130@sina.com [Zhongyuan University of Technology, Center for Advanced Materials Research (China)

    2016-02-15

    The problem of infection in the tissue engineering substitutes is driving us to seek new coating materials. We previously found that conjugated linolenic acid (CLnA) has well biocompatibility and excellent membrane-forming property. The objective of this study is to endow the anti-bacterial activity to CLnA membra ne by linking with MgO. The results showed that the CLnA polymer membrane can be loaded with porous rod-like MgO and such complex membrane showed anti-bacterial sensitivity against gram-positive bacteria (Staphylococcus aureus) even at the low concentration (0.15 μg/mm{sup 2}). In the present study, the best zone of inhibition got to 18.2 ± 0.8 mm when the amount of MgO reach 2.42 ± 0.58 μg/mm{sup 2}. It was deduced that the porous rod-like structure of MgO was directed by CLnA in its polymerization process. Such CLnA/MgO complex membrane can be helpful in the tissue engineering, medicine, food engineering, food preservation, etc. on the basis of its good anti-bacterial activity.

  3. Incorporation and profile of fatty acids in tilapia fillets (Oreochromis niloticus fed with tung oil

    Directory of Open Access Journals (Sweden)

    Elton Guntendorfer Bonafé

    2013-02-01

    Full Text Available The acceptance of tung oil enriched diet and the incorporation of conjugated linolenic acid - CLnA into fillets of Genetically Improved Farmed Tilapia (GIFT were investigated. The diet was well accepted, and after 10 days CLnA was incorporated into the fillets with a 1.02% content of total fatty acids (FA. In addition, biosynthesis of the conjugated linoleic acid isomers - CLA (0.31% of fillet total FA content from CLnA, and the presence of alpha-linolenic acid - LNA (1.08% of fillet total FA content, eicosapentaenoic acid - EPA (2.85% of fillet total FA content and docosahexaenoic acid - DHA (3.08% of fillet total FA content were observed. Therefore, the consumption of this fish can increase the intake of different FA (CLnA, CLA, LNA, EPA and DHA, which play an important role in human metabolism.

  4. A 5′P degradation hot spot influences molecular farming of anticancerogenic nuclease TBN1 in tobacco cells

    Czech Academy of Sciences Publication Activity Database

    Týcová, Anna; Piernikarczyk, R.J.J.; Kugler, M.; Lipovová, P.; Podzimek, T.; Steger, G.; Matoušek, Jaroslav

    2016-01-01

    Roč. 127, č. 2 (2016), s. 347-358 ISSN 0167-6857 Institutional support: RVO:60077344 Keywords : mRNA quantification * Nicotiana benthamiana * Nicotiana tabacum * Post-transcriptional gene silencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.002, year: 2016

  5. Support for Synchrotron Access by Environmental Scientists

    International Nuclear Information System (INIS)

    Daly, Michael; Madden, Andrew; Palumbo, Anthony; Qafoku, N.

    2006-01-01

    To support ERSP-funded scientists in all aspects of synchrotron-based research at the Advanced Photon Source (APS). This support comes in one or more of the following forms: (1) writing proposals to the APS General User (GU) program, (2) providing time at MRCAT/EnviroCAT beamlines via the membership of the Molecular Environmental Science (MES) Group in MRCAT/EnviroCAT, (3) assistance in experimental design and sample preparation, (4) support at the beamline during the synchrotron experiment, (5) analysis and interpretation of the synchrotron data, and (6) integration of synchrotron experimental results into manuscripts

  6. Adsorption properties of a molecular 5 A sieve for 85Kr

    International Nuclear Information System (INIS)

    Wardaszko, T.; Nidecka, J.

    1978-01-01

    The enrichment processes which are necessary at low-level 85 Kr determinations in the atmospheric air require the knowledge of adsorption properties of appropriate sorbing agents, such as a molecular 5A sieve. Following low-temperature adsorption, under specified conditions, of known amounts of 85 Kr diluted in the air, desorption was carried out and then the 85 Kr content in the temperature fraction as well as their total volume were determined. Distribution curves for the above quantities in fractions are presented. (author)

  7. Molecular-beam epitaxy growth and characterization of 5-μm quantum cascade laser

    International Nuclear Information System (INIS)

    Mamutin, V V; Ustinov, V M; Ilyinskaya, N D; Baydakova, M V; Ber, B Ya; Kasantsev, D Yu

    2011-01-01

    Molecular-beam epitaxy growth of 5 μm emitting strain-compensated quantum semiconductor laser (QCL) is reported. The QCL structure is characterized by complementary techniques: high-resolution X-ray diffraction and dynamical secondary-ion mass-spectrometry, that reveal the high quality of QCL structure and in-depth distribution of chemical composition, respectively.

  8. Permanent genetic resources added to molecular ecology resources database 1 February 2013-31 March 2013

    Czech Academy of Sciences Publication Activity Database

    Arias, M. C.; Atteke, C.; Augusto, S. C.; Bailey, J.; Bazaga, P.; Beheregaray, L. B.; Benoit, L.; Blatrix, R.; Born, C.; Brito, R. M.; Chen, H.-K.; Covarrubias, S.; de Vega, C.; Djiéto-Lordon, C.; Dubois, M.-P.; Francisco, F. O.; García, C.; Concalves, P. H. P.; González, C.; Gutiérrez-Rodríguez, C.; Hammer, M. P.; Herrera, C. M.; Itoh, H.; Kamimura, S.; Karaoglu, H.; Kojima, S.; Li, S.-L.; Ling, H. J.; Matos Maravi, Pavel F.; McKey, D.; Mezui-M’Eko, J.; Ornelas, J. F.; Park, R. F.; Pozo, M. I.; Ramula, S.; Rigueiro, C.; Sandoval-Castillo, J.; Santiago, L. R.; Seino, M. M.; Song, C.-B.; Takeshima, H.; Vasemägi, A.; Wellings, C. R.; Yan, J.; Du, Y.-Z.; Zhang, C.-R.; Zhang, T.-Y.

    2013-01-01

    Roč. 13, č. 4 (2013), s. 760-762 ISSN 1755-098X Institutional support: RVO:60077344 Keywords : molecular ecology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.626, year: 2013 http://onlinelibrary.wiley.com/doi/10.1111/1755-0998.12121/pdf

  9. Theoretical investigation of molecular hydrogen reactions with active centres in B6H5- and AlB6H5- clusters

    International Nuclear Information System (INIS)

    Mebel', A.M.; Charkin, O.P.

    1991-01-01

    Nonempirical calculations of sections of potential surface (PS) along the shortest way of reaction of hydrogen interaction with different active centres in AlB 5 H 5 - cluster were conducted. Mechanisms of reactions of valent-saturated hydrides (BH, AlH) and clusters (B 6 H 5 - , AlB 5 H 5 - ) with molecular hydrogen are correlated. Qualitative model enabling to form an opinion about the presence or the absence of barrier on PS of the shortest way of reactions of breaking σ-bond of H-H type on the active centre of cluster, is suggested. The model is based on analysis of the character of canonical MO reagents and products

  10. (E-2-(5-Chloro-2-hydroxybenzylidene-N-cyclohexylhydrazine-1-carbothioamide

    Directory of Open Access Journals (Sweden)

    Md. Azharul Arafath

    2017-01-01

    Full Text Available In the title compound, C14H18ClN3OS, the phenol ring is almost coplanar with the hydrazinecarbothioamide moiety, making a dihedral angle of 6.92 (8°. The cyclohexane ring has a chair conformation and the conformation about the C=N bond is E. In the crystal, molecules are linked by N—H...O and O—H...S hydrogen bonds, forming inversion dimers with an R22(14 ring motif flanked by two R22(6 ring motifs. The dimers are linked by short Cl...Cl interactions, forming layers parallel to the ab plane.

  11. Designing molecular printboards: a photolithographic platform for recodable surfaces

    Czech Academy of Sciences Publication Activity Database

    Abt, D.; Schmidt, B. V. K. J.; Pop-Georgievski, Ognen; Quick, A. S.; Danilov, D.; Kostina, Nina Yu.; Bruns, M.; Wenzel, W.; Wegener, M.; Rodriguez-Emmenegger, Cesar; Barner-Kowollik, C.

    2015-01-01

    Roč. 21, č. 38 (2015), s. 13186-13190 ISSN 0947-6539 R&D Projects: GA ČR(CZ) GJ15-09368Y Institutional support: RVO:61389013 Keywords : cyclodextrin * molecular printboard * photoconjugation Subject RIV: BO - Biophysics Impact factor: 5.771, year: 2015

  12. Influence of pyrolysis conditions on the CO2/CH4 and O2/N2 perm selectivity of supported carbon molecular sieve membranes

    International Nuclear Information System (INIS)

    Mohd Fikri Abdul Rahman; Wan Mohd Hafiz Faizal Wan Harun; Mohd Azmier Ahmad

    2010-01-01

    This work focused on the effect of pyrolysis conditions onto supported carbon molecular sieve membranes performance in pure gas permeation and perm selectivity. The membrane support was synthesis by carbonization of titania mixed with cellulose acetate at temperature of 125 degree Celsius. The molecular sieving membrane layer was obtained by coating the polyvinyl alcohol-glutaraldehyde solution onto the membrane support before heated at various pyrolysis temperatures and holding times. The optimum preparation conditions were found at pyrolysis temperature and holding time of 400 degree Celsius and 30 minutes, respectively. At this point, the CO 2 and O 2 permeation flux were 2.63 ml/ min and 2.67 ml/ min, respectively. Meanwhile, the perm selectivities of CO 2 / CH 4 and O 2 / N 2 were 1.87 and 1.92, respectively. (author)

  13. Non-adiabatic molecular dynamic simulations of opening reaction of molecular junctions

    Czech Academy of Sciences Publication Activity Database

    Zobač, Vladimír; Lewis, J.P.; Jelínek, Pavel

    2016-01-01

    Roč. 27, č. 28 (2016), 1-8, č. článku 285202. ISSN 0957-4484 R&D Projects: GA ČR(CZ) GA14-02079S Institutional support: RVO:68378271 Keywords : non-adiabatic molecular dynamics * molecular junctions * molecular switches * DFT Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.440, year: 2016

  14. Theoretical and experimental approach on the molecular interactions of the DL-Alanine with an electrolytic environment

    Science.gov (United States)

    Cantero-López, Plinio; Yañez-Osses, Osvaldo; Páez-Meza, Manuel Silvestre; López, Johana E.; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro

    2017-11-01

    The molecular interactions that promote the stability of proteins and amino acids in saline solutions is a central topic of molecular biophysics. However, a well-supported molecular picture of the phenomena has not been established yet. In this paper, we studied as model system the mix between DL-Alanine in aqueous solutions of STP (Na2S2O3·5H2O) at different temperatures, from volumetric and viscometric properties. The thermophysical properties obtained indicate the presence of a strong preferential solvation, structure-making action and a possible salt in effect. Quantum chemical calculations and molecular dynamic (MD) simulations provide a new insight to support these arguments.

  15. Molecular Outflow and Feedback in an Obscured Quasar at z˜1.5 Revealed by ALMA

    Science.gov (United States)

    Brusa, Marcella

    2017-11-01

    We imaged with ALMA and ARGOS/LUCI the molecular gas and the dust and stellar continuum in XID2028, an obscured QSO at z=1.593, where the presence of a massive outflow in the ionized gas component traced by the [O III]5007 emission has been resolved up to 10 kpc. This target does represent a unique test case to study QSO 'feedback in action' at the peak epoch of AGN- galaxy coevolution. The QSO has been detected both in the CO(5-4) transition and in the 1.3mm continuum, with emissions confined in the central ( consumption conditions in XID2028, possibly due to feedback effects on the host galaxy. Finally, we observe an asymmetric profile of the CO(5-4) line, which suggests the presence of high velocity gas up to 700 km/s. An image of the blueshfited and redshifted CO wings provides the first detection of a spatially resolved, galaxy-scale molecular outflow at high-z, extended in opposite directions with the approaching component spatially coincident with the ionised gas outflow. The resolved, molecular outflow appear to be cospatial with the component observed int the ionised gas. XID2028 therefore represents the first example of molecular and ionised kpc scales outflows at high-z.

  16. Prevalence and molecular characteristics of urinary and intestinal microsporidia infections in renal transplant recipients

    Czech Academy of Sciences Publication Activity Database

    Kicia, M.; Wesolowska, M.; Kopacz, Z.; Jakuszko, K.; Sak, Bohumil; Květoňová, Dana; Krajewska, M.; Kváč, Martin

    2016-01-01

    Roč. 22, č. 5 (2016), 462.e5-462.e9 ISSN 1198-743X Institutional support: RVO:60077344 Keywords : Encephalitozoon cuniculi * Enterocytozoon bieneusi * immunosuppression * renal transplant recipients * urinary tract Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.292, year: 2016

  17. Larval anatomy of the pterobranch Cephalodiscus gracilis supports secondarily derived sessility concordant with molecular phylogenies

    Science.gov (United States)

    Stach, Thomas

    2013-12-01

    Pterobranchs have been interpreted as "missing links" combining primitive invertebrate features with advanced vertebrate-like characteristics. The first detailed morphological description of an ontogenetic stage of a pterobranch, based on digital 3D-reconstruction at electron microscopic resolution, reveals a triploblastic animal with monociliated epithelia, an extensive coelomic cavity, a through gut with an asymmetrically developed gill slit but no signs of planktonic specializations, such as ciliated bands. Therefore, this crawling larva supports the hypothesis proposed in previous molecular phylogenetic studies that pterobranchs could be derived within enteropneusts rather than being "missing links".

  18. Silica-supported, single-site titanium catalysts for olefin epoxidation. A molecular precursor strategy for control of catalyst structure.

    Science.gov (United States)

    Jarupatrakorn, Jonggol; Don Tilley, T

    2002-07-17

    A molecular precursor approach involving simple grafting procedures was used to produce site-isolated titanium-supported epoxidation catalysts of high activity and selectivity. The tris(tert-butoxy)siloxy titanium complexes Ti[OSi(O(t)Bu)(3)](4) (TiSi4), ((i)PrO)Ti[OSi(O(t)Bu)(3)](3) (TiSi3), and ((t)BuO)(3)TiOSi(O(t)Bu)(3) (TiSi) react with the hydroxyl groups of amorphous Aerosil, mesoporous MCM-41, and SBA-15 via loss of HO(t)Bu and/or HOSi(O(t)Bu)(3) and introduction of titanium species onto the silica surface. Powder X-ray diffraction, nitrogen adsorption/desorption, infrared, and diffuse reflectance ultraviolet spectroscopies were used to investigate the structures and chemical natures of the surface-bound titanium species. The titanium species exist mainly in isolated, tetrahedral coordination environments. Increasing the number of siloxide ligands in the molecular precursor decreases the amount of titanium that can be introduced this way, but also enhances the catalytic activity and selectivity for the epoxidation of cyclohexene with cumene hydroperoxide as oxidant. In addition, the high surface area mesoporous silicas (MCM-41 and SBA-15) are more effective than amorphous silica as supports for these catalysts. Supporting TiSi3 on the SBA-15 affords highly active cyclohexene epoxidation catalysts (0.25-1.77 wt % Ti loading) that provide turnover frequencies (TOFs) of 500-1500 h(-1) after 1 h (TOFs are reduced by about half after calcination). These results demonstrate that oxygen-rich siloxide complexes of titanium are useful as precursors to supported epoxidation catalysts.

  19. Quantum chemical calculations and molecular docking studies of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione(CTD) and its mannich product 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD)

    Science.gov (United States)

    Fatma, Shaheen; Bishnoi, Abha; Verma, Anil Kumar; Singh, Vineeta; Srivastava, Krishna

    2018-04-01

    This work presents the synthesis of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione (CTD) by Claisen condensation of thiazolidine-2,4-dione and mannich product of CTD, 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD). The static first hyperpolarizability values for thiazolidine-2,4-dione derivatives have been calculated as 10.28 × 10-30 esu for CTD and 19.42 × 10-30 esu for CMTD. The gradual increase in hyperpolarizability values of synthesized thiazolidine-2,4-dione derivatives from CTD to CMTD is due to the blockage of sbnd NH group on CTD by mannich reaction. The structures of these compounds have been derived by spectroscopic(IR, UV, Mass, 1H and 13C NMR) analysis as well as with the help of theoretical studies. The high values of first static hyperpolarizability indicate that the synthesized derivatives are suitable as non-linear optical (NLO) material. CTD with MIC value of 12.5 μg/mL can be developed as an alternative drug for the treatment of enteric fever. Calculated frontier orbital gap values suggest that the CMTD is a soft molecule with high chemical reactivity and is more polarizable as compared to the CTD. Molecular electrostatic potential is calculated for the optimized geometry of the molecules to estimate their chemical reactivity. The inhibitor CTD forms a stable complex with 3-dehydroquinase enzyme of Salmonella typhi. It is evident from the ligand receptor interactions and a binding affinity value of -5.88 kcal/mol and an inhibition constant of 49.22 μM. This is further confirmed by the experimental biological data. The molecular docking studies are supportive of the antibacterial activity of CTD exhibiting high inhibition constant and binding energy.

  20. Synthesis and characterization of molecular materials from N-trifluoromethanesulfonyl-1-azahexa-1,3,5-trieno derivates

    International Nuclear Information System (INIS)

    Rodriguez Gomez, A; Ortiz Rebollo, A; Sanchez Vergara, M.E

    2008-01-01

    Molecular materials have been developed recently for their diverse electrical properties, such as insulation, semiconductors, conductors and superconductors and they can also be used in diodes, transistors, solar cells and electronic switches among other things. The molecular materials are formed by condensation and organization of molecular units that can be organic, organometallic, or metal-organic and whose properties are individually characterized later. Because of their true nature, the properties of molecular materials can be derived from the characteristics of the molecular units that form them. For this study molecular materials were synthesized from electronic donors and acceptors: Cu (TAAB) +2 , Ni (TAAB) +2 and the NTrifluoromethanesulfonyl-1-azahexa-1,3,5-trieno derivatives that are especially attractive from the structural point of view, since in their neutral from they have an extensive electronic dislocation which gives them a very specific chemical behavior. The synthesized materials were chemically and structurally characterized by IR spectroscopy, scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and mass spectrometry. Thin films of the different materials were deposited and the optical activation energy was evaluated, using techniques like profilometry and UV-vis spectroscopy

  1. WMe6 tamed by silica: Si-O-WMe5 as an efficient, well-defined species for alkane metathesis, leading to the observation of a supported W-methyl/methylidyne species

    KAUST Repository

    Samantaray, Manoja

    2014-01-22

    The synthesis and full characterization of a well-defined silica-supported ≡Si-O-W(Me)5 species is reported. Under an inert atmosphere, it is a stable material at moderate temperature, whereas the homoleptic parent complex decomposes above -20 °C, demonstrating the stabilizing effect of immobilization of the molecular complex. Above 70 °C the grafted complex converts into the two methylidyne surface complexes [(≡SiO-)W(≡CH) Me2] and [(≡SiO-)2W(≡CH)Me]. All of these silica-supported complexes are active precursors for propane metathesis reactions. © 2013 American Chemical Society.

  2. WMe6 tamed by silica: Si-O-WMe5 as an efficient, well-defined species for alkane metathesis, leading to the observation of a supported W-methyl/methylidyne species

    KAUST Repository

    Samantaray, Manoja; Callens, Emmanuel; Abou-Hamad, Edy; Rossini, Aaron J.; Widdifield, Cory M.; Dey, Raju; Emsley, Lyndon; Basset, Jean-Marie

    2014-01-01

    The synthesis and full characterization of a well-defined silica-supported ≡Si-O-W(Me)5 species is reported. Under an inert atmosphere, it is a stable material at moderate temperature, whereas the homoleptic parent complex decomposes above -20 °C, demonstrating the stabilizing effect of immobilization of the molecular complex. Above 70 °C the grafted complex converts into the two methylidyne surface complexes [(≡SiO-)W(≡CH) Me2] and [(≡SiO-)2W(≡CH)Me]. All of these silica-supported complexes are active precursors for propane metathesis reactions. © 2013 American Chemical Society.

  3. Porcine ubiquitin-like 5 (UBL5) gene: genomic organization, polymorphisms, mRNA cloning, splicing variants and association study

    Czech Academy of Sciences Publication Activity Database

    Masopust, Martin; Weisz, Filip; Bartenschlager, H.; Knoll, A.; Vykoukalová, Z.; Geldermann, H.; Čepica, Stanislav

    2014-01-01

    Roč. 41, č. 4 (2014), s. 2353-2362 ISSN 0301-4851 R&D Projects: GA ČR GAP502/10/1216 Institutional support: RVO:67985904 Keywords : pig * UBL5 * PCR cloning Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.024, year: 2014

  4. Molecular Recognition of PTS-1 Cargo Proteins by Pex5p: Implications for Protein Mistargeting in Primary Hyperoxaluria

    Directory of Open Access Journals (Sweden)

    Noel Mesa-Torres

    2015-02-01

    Full Text Available Peroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1, where alanine:glyoxylate aminotransferase (AGT undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3–4 orders of magnitude reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.

  5. Molecular Gas in a Submillimeter Galaxy at z = 4.5: Evidence for a Major Merger at 1 Billion Years after the Big Bang

    Science.gov (United States)

    Schinnerer, E.; Carilli, C. L.; Capak, P.; Martinez-Sansigre, A.; Scoville, N. Z.; Smolčić, V.; Taniguchi, Y.; Yun, M. S.; Bertoldi, F.; Le Fevre, O.; de Ravel, L.

    2008-12-01

    We report the detection of CO molecular line emission in the z = 4.5 millimeter-detected galaxy COSMOS J100054+023436 (hereafter J1000+0234) using the IRAM Plateau de Bure interferometer (PdBI) and NRAO's Very Large Array (VLA). The 12CO(4-3) line as observed with PdBI has a full line width of ~1000 km s-1, an integrated line flux of 0.66 Jy km s-1, and a CO luminosity of 3.2 × 1010 L⊙. Comparison to the 3.3 σ detection of the CO(2-1) line emission with the VLA suggests that the molecular gas is likely thermalized to the J = 4-3 transition level. The corresponding molecular gas mass is 2.6 × 1010 M⊙ assuming an ULIRG-like conversion factor. From the spatial offset of the red- and blueshifted line peaks and the line width a dynamical mass of 1.1 × 1011 M⊙ is estimated assuming a merging scenario. The molecular gas distribution coincides with the rest-frame optical and radio position of the object while being offset by 0.5'' from the previously detected Lyα emission. J1000+0234 exhibits very typical properties for lower redshift (z ~ 2) submillimeter galaxies (SMGs) and thus is very likely one of the long sought after high-redshift (z > 4) objects of this population. The large CO(4-3) line width taken together with its highly disturbed rest-frame UV geometry suggest an ongoing major merger about a billion years after the big bang. Given its large star formation rate (SFR) of >1000 M⊙ yr-1 and molecular gas content this object could be the precursor of a "red and dead" elliptical observed at a redshift of z = 2. Based on observations carried out with the IRAM Plateau de Bure Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain).

  6. New molecular settings to support in vivo anti-malarial assays.

    Science.gov (United States)

    Bahamontes-Rosa, Noemí; Alejandre, Ane Rodriguez; Gomez, Vanesa; Viera, Sara; Gomez-Lorenzo, María G; Sanz-Alonso, Laura María; Mendoza-Losana, Alfonso

    2016-03-08

    Quantitative real-time PCR (qPCR) is now commonly used as a method to confirm diagnosis of malaria and to differentiate recrudescence from re-infection, especially in clinical trials and in reference laboratories where precise quantification is critical. Although anti-malarial drug discovery is based on in vivo murine efficacy models, use of molecular analysis has been limited. The aim of this study was to develop qPCR as a valid methodology to support pre-clinical anti-malarial models by using filter papers to maintain material for qPCR and to compare this with traditional methods. FTA technology (Whatman) is a rapid and safe method for extracting nucleic acids from blood. Peripheral blood samples from mice infected with Plasmodium berghei, P. yoelii, or P. falciparum were kept as frozen samples or as spots on FTA cards. The extracted genetic material from both types of samples was assessed for quantification by qPCR using sets of specific primers specifically designed for Plasmodium 18S rRNA, LDH, and CytB genes. The optimal conditions for nucleic acid extraction from FTA cards and qPCR amplification were set up, and were confirmed to be suitable for parasite quantification using DNA as template after storage at room temperature for as long as 26 months in the case of P. berghei samples and 52 months for P. falciparum and P. yoelii. The quality of DNA extracted from the FTA cards for gene sequencing and microsatellite amplification was also assessed. This is the first study to report the suitability of FTA cards and qPCR assay to quantify parasite load in samples from in vivo efficacy models to support the drug discovery process.

  7. 1-[(6-Chloro-3-pyridylmethyl]-N-(4-ethoxyphenyl-3-phenyl-1H-pyrazole-5-carboxamide

    Directory of Open Access Journals (Sweden)

    Zheng Tang

    2009-04-01

    Full Text Available In the title compound, C24H21ClN4O2, the pyrazole ring makes dihedral angles of 7.70 (11, 89.17 (11 and 40.68 (11° with the phenyl, pyridine and ethoxyphenyl rings, respectively. There are some intramolecular C—H...O and C—H...π bonds giving rigidity to the molecule, while weak intermolecular N—H...N and C—H...π hydrogen bonds link the molecules into a two-dimensional structure.

  8. Drug: D08391 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08391 Drug Pirlimycin (INN); Pirsue [veterinary] (TN) ... C17H31ClN2O5S D08391.gif ... ... ... Antibacterial ... DG01578 ... Lincosamide antibiotic Chemical group: DG01577 ... Lincosamide Target: 50S ribosomal subunit (veterinary

  9. 4-Chloroselanyl-3,5-diethyl-1H-pyrazol-2-ium chloride

    Directory of Open Access Journals (Sweden)

    Maksym Seredyuk

    2011-11-01

    Full Text Available In the cation of the title compound, C7H12ClN2Se+·Cl−, the ethylene groups and the Se–Cl fragment adopt a cis configuration with a C—Se—Cl angle of 96.09 (6°. In the crystal, intermolecular N—H...Cl hydrogen bonds link two cations and two chlorine anions into centrosymmetric clusters. π–π interactions between the pyrazole rings [centroid–centroid distance of 3.530 (2 Å] link these clusters into columns along [001] with short intermolecular Se...Cl− contacts of 2.995 (1 Å.

  10. Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells

    OpenAIRE

    Sun, Bing; Bai, Yuxin; Zhang, Liyuan; Gong, Linlin; Qi, Xiaoyu; Li, Huizhen; Wang, Faming; Chi, Xinming; Jiang, Yulin; Shao, Shujuan

    2016-01-01

    Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer...

  11. 6-Chloro-3-[5-(3-methoxy-8-methyl-4-quinolyl-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]-2-methyl-4-phenylquinoline

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2009-11-01

    Full Text Available In the title compound, C36H29ClN4O, the dihydropyrazole ring adopts an envelope conformation. The two quinoline ring systems (r.m.s. deviations = 0.029 and 0.018 Å are oriented at a dihedral angle of 71.43 (4°. One of the quinoline rings makes a dihedral angle of 65.40 (7° with the phenyl substituent. In the crystal, molecules are linked into chains along the b axis by intermolecular C—H...N hydrogen bonds. In addition, C—H...π and π–π [centroid–centroid distance = 3.7325 (8 Å] interactions are observed.

  12. Tunable Push-Pull Interactions in 5-Nitrosopyrimidines

    Czech Academy of Sciences Publication Activity Database

    Procházková, Eliška; Čechová, Lucie; Tarábek, Ján; Janeba, Zlatko; Dračínský, Martin

    2016-01-01

    Roč. 81, č. 9 (2016), s. 3780-3789 ISSN 0022-3263 R&D Projects: GA ČR GA15-11223S Institutional support: RVO:61388963 Keywords : polysubstituted 5-nitrosopyrimidines * molecular dynamics * NMR spectroscopy Subject RIV: CC - Organic Chemistry Impact factor: 4.849, year: 2016

  13. Dense molecular clumps associated with the Large Magellanic Cloud supergiant shells LMC 4 and LMC 5

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Kosuke; Mizuno, Norikazu [Department of Astronomy, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 133-0033 (Japan); Minamidani, Tetsuhiro [Nobeyama Radio Observatory, 462-2 Nobeyama Minamimaki-mura, Minamisaku-gun, Nagano 384-1305 (Japan); Onishi, Toshikazu; Muraoka, Kazuyuki [Department of Physical Science, Osaka Prefecture University, Gakuen 1-1, Sakai, Osaka 599-8531 (Japan); Kawamura, Akiko; Muller, Erik; Tatematsu, Ken' ichi; Hasegawa, Tetsuo; Miura, Rie E.; Ezawa, Hajime [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Dawson, Joanne [Australia Telescope National Facility, CSIRO Astronomy and Space Science, P.O. Box 76, Epping, NSW 1710 (Australia); Tosaki, Tomoka [Joetsu University of Education, Yamayashiki-machi, Joetsu, Niigata 943-8512 (Japan); Sakai, Takeshi [Graduate School of Informatics and Engineering, The University of Electro-Communications, Chofu, Tokyo 182-8585 (Japan); Tsukagoshi, Takashi [College of Science, Ibaraki University, Bunkyo 2-1-1, Mito 310-8512 (Japan); Tanaka, Kunihiko [Department of Physics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama, Kanagawa 223-8522 (Japan); Fukui, Yasuo, E-mail: kosuke.fujii@nao.ac.jp [Department of Astrophysics, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan)

    2014-12-01

    We investigate the effects of supergiant shells (SGSs) and their interaction on dense molecular clumps by observing the Large Magellanic Cloud (LMC) star-forming regions N48 and N49, which are located between two SGSs, LMC 4 and LMC 5. {sup 12}CO (J = 3-2, 1-0) and {sup 13}CO(J = 1-0) observations with the ASTE and Mopra telescopes have been carried out toward these regions. A clumpy distribution of dense molecular clumps is revealed with 7 pc spatial resolution. Large velocity gradient analysis shows that the molecular hydrogen densities (n(H{sub 2})) of the clumps are distributed from low to high density (10{sup 3}-10{sup 5} cm{sup –3}) and their kinetic temperatures (T {sub kin}) are typically high (greater than 50 K). These clumps seem to be in the early stages of star formation, as also indicated from the distribution of Hα, young stellar object candidates, and IR emission. We found that the N48 region is located in the high column density H I envelope at the interface of the two SGSs and the star formation is relatively evolved, whereas the N49 region is associated with LMC 5 alone and the star formation is quiet. The clumps in the N48 region typically show high n(H{sub 2}) and T {sub kin}, which are as dense and warm as the clumps in LMC massive cluster-forming areas (30 Dor, N159). These results suggest that the large-scale structure of the SGSs, especially the interaction of two SGSs, works efficiently on the formation of dense molecular clumps and stars.

  14. Dr Jekyll and Mr Hyde: a strange case of 5-ethynyl-2 '-deoxyuridine and 5-ethynyl-2 '- deoxycytidine

    Czech Academy of Sciences Publication Activity Database

    Ligasová, A.; Liboska, Radek; Friedecký, D.; Mičová, K.; Adam, T.; Oždian, T.; Rosenberg, Ivan; Koberna, K.

    2016-01-01

    Roč. 6, č. 1 (2016), č. článku 150172. ISSN 2046-2441 R&D Projects: GA MZd NV15-31604A Institutional support: RVO:61388963 Keywords : cytidine deaminase * dCMP deaminase * 5-ethynyl-2 '-deoxyuridine * 5-ethynyl-2 '-deoxycytidine * DNA replication Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.481, year: 2016 http://rsob.royalsocietypublishing.org/content/6/1/150172

  15. Re-emergence of Chikungunya in India: Molecular studies

    Indian Academy of Sciences (India)

    Re-emergence of Chikungunya in India: Molecular studies · PowerPoint Presentation · CHIKUNGUNYA virus · Slide 4 · Slide 5 · CHIKV Genotypes · Slide 7 · In view of long absence of CHIK epidemics, it was postulated that CHIK virus has disappeared from India and South-East Asia. Serological surveys supported this view.

  16. Synthesis and Characterization of Nanocrystalline Aluminophosphate AlPO4-5 Molecular Sieve

    Directory of Open Access Journals (Sweden)

    Asir Alnaama

    2018-03-01

    Full Text Available Nanocrystalline aluminophosphate AlPO4-5 molecular sieves were synthesized by hydrothermal method (HTS. Synthesis parameters like time and temperature of crystallization were investigated. Type of template (R and ratio of R/P2O5 were studied also. Characterization of the synthesized AlPO4-5 were done by powder X-ray diffraction (XRD, scanning electron microscopy (SEM/EDX, Fourier transform infrared (FTIR, differential scanning calorimetry-thermogravimetry analysis (DSC-TGA, and N2 adsorption-desorption BET analysis. XRD patterns results showed excellent crystallinity for two types of templates, di-n-propylamine (DPA and tetrapropyl ammonium hydroxide (TPAOH for alumminophosphate five (AFI structure. Nano-level for particle size of 66 nm was revealed by AFM test. Good thermal stability was obtained in DSC-TGA results. Best time and temperature of crystallization of 24h and 190 O C were got. Optimum R/P2O5 for two kind of template was established.

  17. Carbon Support Surface Effects in the Gold-Catalyzed Oxidation of 5-Hydroxymethylfurfural

    NARCIS (Netherlands)

    Donoeva, Baira; Masoud, Nazila; De Jongh, Petra E.

    2017-01-01

    Oxidation of 5-hydroxymethylfurfural into 2,5-furandicarboxylic acid is an important transformation for the production of bio-based polymers. Carbon-supported gold catalysts hold great promise for this transformation. Here we demonstrate that the activity, selectivity, and stability of the

  18. [Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].

    Science.gov (United States)

    Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J

    2018-02-07

    Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in

  19. Theoretical Studies Of Molecular Structure And Vibrational Spectra Of 5-Aminolevulinic Acid Hexyl Ester

    International Nuclear Information System (INIS)

    Comert, H.

    2010-01-01

    The molecular geometry and vibrational frequencies of The 5-Aminolevulinic acid's hexyl ester (ALA-H) in the ground state have been calculated using Hartree-Fock (HF) and Density functional method (B3LYP) with 6-31++G(d) basis set. The calculated vibrational spectra and geometric parameters of title compound were compered with experimental ones.

  20. CeCo5 thin films with perpendicular anisotropy grown by molecular beam epitaxy

    Science.gov (United States)

    Sharma, S.; Hildebrandt, E.; Major, M.; Komissinskiy, P.; Radulov, I.; Alff, L.

    2018-04-01

    Buffer-free, highly textured (0 0 1) oriented CeCo5 thin films showing perpendicular magnetic anisotropy were synthesized on (0 0 1) Al2O3 substrates by molecular beam epitaxy. Ce exists in a mixture of Ce3+ and Ce4+ valence states as shown by X-ray photoelectron spectroscopy. The first anisotropy constant, K1, as measured by torque magnetometry was 0.82 MJ/m3 (8.2 ×106erg /cm3) . A maximum coercivity of 5.16 kOe with a negative temperature coefficient of -0.304%K-1 and a magnetization of 527.30 emu/cm3 was measured perpendicular to the film plane at 5 K. In addition, a large anisotropy of the magnetic moment of 15.5% was observed. These magnetic parameters make CeCo5 a potential candidate material for spintronic and magnetic recording applications.

  1. The 5S rDNA in two Abracris grasshoppers (Ommatolampidinae: Acrididae): molecular and chromosomal organization.

    Science.gov (United States)

    Bueno, Danilo; Palacios-Gimenez, Octavio Manuel; Martí, Dardo Andrea; Mariguela, Tatiane Casagrande; Cabral-de-Mello, Diogo Cavalcanti

    2016-08-01

    The 5S ribosomal DNA (rDNA) sequences are subject of dynamic evolution at chromosomal and molecular levels, evolving through concerted and/or birth-and-death fashion. Among grasshoppers, the chromosomal location for this sequence was established for some species, but little molecular information was obtained to infer evolutionary patterns. Here, we integrated data from chromosomal and nucleotide sequence analysis for 5S rDNA in two Abracris species aiming to identify evolutionary dynamics. For both species, two arrays were identified, a larger sequence (named type-I) that consisted of the entire 5S rDNA gene plus NTS (non-transcribed spacer) and a smaller (named type-II) with truncated 5S rDNA gene plus short NTS that was considered a pseudogene. For type-I sequences, the gene corresponding region contained the internal control region and poly-T motif and the NTS presented partial transposable elements. Between the species, nucleotide differences for type-I were noticed, while type-II was identical, suggesting pseudogenization in a common ancestor. At chromosomal point to view, the type-II was placed in one bivalent, while type-I occurred in multiple copies in distinct chromosomes. In Abracris, the evolution of 5S rDNA was apparently influenced by the chromosomal distribution of clusters (single or multiple location), resulting in a mixed mechanism integrating concerted and birth-and-death evolution depending on the unit.

  2. Molecular structure, vibrational spectra and photochemistry of 5-mercapto-1-methyltetrazole

    Science.gov (United States)

    Gómez-Zavaglia, A.; Reva, I. D.; Frija, L.; Cristiano, M. L.; Fausto, R.

    2006-04-01

    In this work, 5-mercapto-1-methyltetrazole was studied by low temperature matrix-isolation and solid-state infrared spectroscopy, DFT(B3LYP)/6-311++G(d,p) calculations and photochemical methods. In the low temperature neat solid phase and isolated in an argon matrix, the compound was found to exist in the 1-methyl-1,4-dihydro-5 H-tetrazole-5-thione tautomeric form. The infrared spectra of the compound were fully assigned and correlated with structural properties. In situ UV-irradiation ( λ>235 nm) of the matrix-isolated monomer is shown to induce different photochemical processes, all of them involving cleavage of the tetrazole ring: e.g. (1) molecular nitrogen expulsion, with production of 1-methyl-1 H-diazirene-3-thiol, which is produced in two different conformers; (2) ring cleavage leading to production of methyl isothiocyanate and azide; (3) simultaneous elimination of nitrogen and sulphur with production of N-methylcarbodiimide. Following these photoprocesses, subsequent reactions occur, leading to production of methyl diazene, carbon monosulphide and nitrogen hydride. Spectroscopic evidence of the production of the above-mentioned chemical species is provided.

  3. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    Science.gov (United States)

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  4. Bidimensional ZSM-5 zeolites probed as catalysts for polyethylene cracking

    Czech Academy of Sciences Publication Activity Database

    Peral, A.; Escola, J. M.; Serrano, D. P.; Přech, Jan; Ochoa-Hernández, Cristina; Čejka, Jiří

    2016-01-01

    Roč. 6, č. 8 (2016), s. 2754-2765 ISSN 2044-4753 R&D Projects: GA ČR(CZ) GAP106/12/0189 Institutional support: RVO:61388955 Keywords : PILLARED MOLECULAR -SIEVE * NANOCRYSTALLINE ZSM-5 * PROTOZEOLITIC UNITS Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.773, year: 2016

  5. Data supporting characterization of CLIC1, CLIC4, CLIC5 and DmCLIC antibodies and localization of CLICs in endoplasmic reticulum of cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Devasena Ponnalagu

    2016-06-01

    Full Text Available Chloride intracellular channel (CLICs proteins show 60–70% sequence identity to each other, and exclusively localize to the intracellular organelle membranes and cytosol. In support of our recent publication, “Molecular identity of cardiac mitochondrial chloride intracellular channel proteins” (Ponnalagu et al., 2016 [1], it was important to characterize the specificity of different CLIC paralogs/ortholog (CLIC1, CLIC4, CLIC5 and DmCLIC antibodies used to decipher their localization in cardiac cells. In addition, localization of CLICs in the other organelles such as endoplasmic reticulum (ER of cardiomyocytes was established. This article also provides data on the different primers used to show the relative abundance of CLIC paralogs in cardiac tissue and the specificity of the various CLIC antibodies used. We demonstrate that the predominant CLICs in the heart, namely CLIC1, CLIC4 and CLIC5, show differential distribution in endoplasmic reticulum. CLIC1 and CLIC4 both show co-localization to the endoplasmic reticulum whereas CLIC5 does not.

  6. Measuring NH3 and other molecular abundance profiles from 5 microns ground-based spectroscopy in support of JUNO investigations

    Science.gov (United States)

    Blain, Doriann; Fouchet, Thierry; Greathouse, Thomas K.; Bézard, Bruno; Encrenaz, Therese; Lacy, John H.; Drossart, Pierre

    2017-10-01

    We report on results of an observational campaign to support the Juno mission. At the beginning of 2016, using TEXES (Texas Echelon cross-dispersed Echelle Spectrograph), mounted on the NASA Infrared Telescope Facility (IRTF), we obtained data cubes of Jupiter in the 1930--1943 cm-1 and 2135--2153 cm-1 spectral ranges (around 5 μm), which probe the atmosphere in the 1--4 bar region, with a spectral resolution of ≈0.3 cm-1 (R≈7000) and an angular resolution of ≈1.5''.This dataset is analyzed by a code that combines a line-by-line radiative transfer model with a non-linear optimal estimation inversion method. The inversion retrieves the abundance profiles of NH3 and PH3, which are the main conbtributors at these wavelengths, as well as the cloud transmittance. This retrieval is performed over more than one thousand pixels of our data cubes, producing effective maps of the disk, where all the major belts are visible (NEB, SEB, NTB, STB, NNTB and SSTB).We will present notably our retrieved NH3 abundance maps which can be compared with the unexpected latitudinal distribution observed by Juno's MWR (Bolton et al., 2017 and Li et al. 2017), as well as our other species retrieved abundance maps and discuss on their significance for the understanding of Jupiter's atmospheric dynamics.References:Bolton, S., et al. (2017), Jupiter’s interior and deep atmosphere: The first close polar pass with the Juno spacecraft, Science, doi:10.1126/science.aal2108, in press.Li, C., A. P. Ingersoll, S. Ewald, F. Oyafuso, and M. Janssen (2017), Jupiter’s global ammonia distribution from inversion of Juno Microwave Radiometer observations, Geophys. Res. Lett., doi:10.1002/2017GL073159, in press.

  7. Molecular Modeling

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 5. Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking. Rama Rao Nadendla. General Article Volume 9 Issue 5 May 2004 pp 51-60. Fulltext. Click here to view fulltext PDF. Permanent link:

  8. Supporting English Language Learners in Math Class, Grades 3-5

    Science.gov (United States)

    Bresser, Rusty; Melanese, Kathy; Sphar, Christine

    2009-01-01

    More than 10 percent of the students in our nation's public schools are English language learners, and this number grows each year. Many of these students are falling behind in math. "Supporting English Language Learners in Math Class, Grades 3-5" outlines the challenges ELL students face when learning math and provides a wealth of specific…

  9. Altair Lander Life Support: Design Analysis Cycles 4 and 5

    Science.gov (United States)

    Anderson, Molly; Curley, Su; Rotter, Henry; Stambaugh, Imelda; Yagoda, Evan

    2011-01-01

    Life support systems are a critical part of human exploration beyond low earth orbit. NASA s Altair Lunar Lander team is pursuing efficient solutions to the technical challenges of human spaceflight. Life support design efforts up through Design Analysis Cycle (DAC) 4 focused on finding lightweight and reliable solutions for the Sortie and Outpost missions within the Constellation Program. In DAC-4 and later follow on work, changes were made to add functionality for new requirements accepted by the Altair project, and to update the design as knowledge about certain issues or hardware matured. In DAC-5, the Altair project began to consider mission architectures outside the Constellation baseline. Selecting the optimal life support system design is very sensitive to mission duration. When the mission goals and architecture change several trade studies must be conducted to determine the appropriate design. Finally, several areas of work developed through the Altair project may be applicable to other vehicle concepts for microgravity missions. Maturing the Altair life support system related analysis, design, and requirements can provide important information for developers of a wide range of other human vehicles.

  10. MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods

    Science.gov (United States)

    Tamura, Koichiro; Peterson, Daniel; Peterson, Nicholas; Stecher, Glen; Nei, Masatoshi; Kumar, Sudhir

    2011-01-01

    Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net. PMID:21546353

  11. N-(2-Chlorophenyl-2-({5-[4-(methylsulfanylbenzyl]-4-phenyl-4H-1,2,4-triazol-3-yl}sulfanylacetamide

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-08-01

    Full Text Available In the title molecule, C24H21ClN4OS2, the central 1,2,4-triazole ring forms dihedral angles of 89.05 (9, 86.66 (9 and 82.70 (10° with the chloro-substituted benzene ring, the methylsulfanyl-substituted benzene ring and the phenyl ring, respectively. In the crystal, molecules are linked into sheets parallel to (100 by intermolecular N—H...N and weak C—H...O hydrogen bonds.

  12. Hydration effects on the molecular structure of silica-supported vanadium oxide catalysts: A combined IR, Raman, UV–vis and EXAFS study

    NARCIS (Netherlands)

    Keller, D.E.; Visser, T.; Soulimani, F.; Koningsberger, D.C.; Weckhuysen, B.M.

    2007-01-01

    The effect of hydration on the molecular structure of silica-supported vanadium oxide catalysts with loadings of 1–16 wt.% V has been systematically investigated by infrared, Raman, UV–vis and EXAFS spectroscopy. IR and Raman spectra recorded during hydration revealed the formation of V–OH groups,

  13. GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit

    Energy Technology Data Exchange (ETDEWEB)

    Pronk, Sander [Science for Life Lab., Stockholm (Sweden); KTH Royal Institute of Technology, Stockholm (Sweden); Pall, Szilard [Science for Life Lab., Stockholm (Sweden); KTH Royal Institute of Technology, Stockholm (Sweden); Schulz, Roland [Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Larsson, Per [Univ. of Virginia, Charlottesville, VA (United States); Bjelkmar, Par [Science for Life Lab., Stockholm (Sweden); Stockholm Univ., Stockholm (Sweden); Apostolov, Rossen [Science for Life Lab., Stockholm (Sweden); KTH Royal Institute of Technology, Stockholm (Sweden); Shirts, Michael R. [Univ. of Virginia, Charlottesville, VA (United States); Smith, Jeremy C. [Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kasson, Peter M. [Univ. of Virginia, Charlottesville, VA (United States); van der Spoel, David [Science for Life Lab., Stockholm (Sweden); Uppsala Univ., Uppsala (Sweden); Hess, Berk [Science for Life Lab., Stockholm (Sweden); KTH Royal Institute of Technology, Stockholm (Sweden); Lindahl, Erik [Science for Life Lab., Stockholm (Sweden); KTH Royal Institute of Technology, Stockholm (Sweden); Stockholm Univ., Stockholm (Sweden)

    2013-02-13

    In this study, molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. As a result, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations.

  14. Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry.

    Science.gov (United States)

    Gray, Lesley-Ann; D'Antoine, Heather A; Tong, Steven Y C; McKinnon, Melita; Bessarab, Dawn; Brown, Ngiare; Reményi, Bo; Steer, Andrew; Syn, Genevieve; Blackwell, Jenefer M; Inouye, Michael; Carapetis, Jonathan R

    2017-12-12

    Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single-nucleotide polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P = 1.86 × 10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.09-1.90; P = 9.56 × 10-3) and HLA-DQA1*0103_DQB1*0601 (OR, 1.27; 95% CI, 1.07-1.52; P = 7.15 × 10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P = 2.36 × 10-3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the 2-risk haplotypes than the protective haplotype. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  15. Molecular Diagnosis of 5α-Reductase Type II Deficiency in Brazilian Siblings with 46,XY Disorder of Sex Development

    Directory of Open Access Journals (Sweden)

    Maricilda Palandi de Mello

    2011-12-01

    Full Text Available The steroid 5α-reductase type II enzyme catalyzes the conversion of testosterone (T to dihydrotestosterone (DHT, and its deficiency leads to undervirilization in 46,XY individuals, due to an impairment of this conversion in genital tissues. Molecular analysis in the steroid 5α-reductase type II gene (SRD5A2 was performed in two 46,XY female siblings. SRD5A2 gene sequencing revealed that the patients were homozygous for p.Gln126Arg missense mutation, which results from the CGA > CAA nucleotide substitution. The molecular result confirmed clinical diagnosis of 46,XY disorder of sex development (DSD for the older sister and directed the investigation to other family members. Studies on SRD5A2 protein structure showed severe changes at NADPH binding region indicating that structural modeling analysis can be useful to evaluate the deleterious role of a mutation as causing 5α-reductase type II enzyme deficiency.

  16. Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

    Directory of Open Access Journals (Sweden)

    Rossana L. Sanchez

    2016-12-01

    Conclusions: and Importance: Pathogenic variants in CLN8 account for the retinitis pigmentosa and seizures in our patients however, currently, they do not have regression or neurocognitive decline. The presentation of NCL can be very diverse and it is important for ophthalmologists to consider this in the differential diagnosis of retinal disorders with seizures or other neurological features. Molecular genetic testing of multiple genes causing isolated and syndromic eye disorders using NGS panels and aCGH along with additional complementary testing may often be required to arrive at a definitive diagnosis.

  17. Imaging Multi-Particle Atomic and Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Landers, Allen [Auburn Univ., AL (United States)

    2016-02-12

    Final Report for Grant Number: DE- FG02-10ER16146 This grant supported research in basic atomic, molecular and optical physics related to the interactions of atoms and molecules with photons and electrons. The duration of the grant was the 5 year period from 4/1/2010 – 10/31/2015. All of the support from the grant was used to pay salaries of the PI, graduate students, and undergraduates and travel to conferences and meetings. The results were in the form of publications in peer reviewed journals. There were 20 peer reviewed publications over these 5 years with 2 of the publications in Physical Review Letters and 1 in Nature; all of the other articles were in respected peer reviewed journals (Physical Review A, New Journal of Physics, Journal of Physics B ...).

  18. Catalytic Performance of Zeolite-Supported Vanadia in the Aerobic Oxidation of 5-hydroxymethylfurfural to 2,5- diformylfuran

    DEFF Research Database (Denmark)

    Sádaba, Irantzu; Gorbanev, Yury; Kegnæs, Søren

    2013-01-01

    on the four different zeolite supports H-beta, H-Y, H-mordenite, and H-ZSM-5 with 1–10 wt% vanadia loading were prepared and characterized by nitrogen physisorption, X-ray powder diffraction, scanning electron  microscopy, ammonia temperature-programmed desorption, Raman spectroscopy and UV...

  19. Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5

    Directory of Open Access Journals (Sweden)

    Inger Lindin

    2014-03-01

    Full Text Available The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD simulations of: (1 MK5 alone; (2 MK5 in complex with an inhibitor; and (3 MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. Electrostatic Potential Surface (EPS calculations of MK5 and p38α showed that electrostatic interactions are important for recognition and binding.

  20. Molecular structure, spectral studies, NBO, HOMO-LUMO profile, MEP and Mulliken analysis of 3β,6β-dichloro-5α-hydroxy-5α-cholestane

    Science.gov (United States)

    Alam, Mahboob; Park, Soonheum

    2018-05-01

    The synthesis of 3β,6β-dichloro-5α-hydroxy-5α-cholestane (in general, steroidal chlorohydrin or steroidal halohydrin) and theoretical study of the structure are reported in this paper. The individuality of chlorohydrin was confirmed by FT-IR, NMR, MS, CHN microanalysis and X-ray crystallography. DFT calculations on the titled molecule have been performed. The molecular structure and spectra explained by Gaussian hybrid computational analysis theory (B3LYP) are found to be in correlation with the experimental data obtained from the various spectrophotometric techniques. The theoretical geometry optimization data were compared with the X-ray data. The vibrational bands appearing in the FT-IR are assigned with accuracy using harmonic frequencies along with intensities and animated modes. Molecular properties like NBO, HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping and dipole moment have been dealt at same level of theory. The calculated electronic spectrum of chlorohydrin is interpreted on the basis of TD-DFT calculations.

  1. Molecular systematics and biodiversity of the Cryptotis mexicanus group (Eulipotyphla: Soricidae): two new species from Honduras supported

    Science.gov (United States)

    Baird, Amy B.; McCarthy, Timothy J.; Trujillo, Robert G.; Kang, Yuan Yuan; Esmaeiliyan, Mehdi; Valdez, Joselyn; Woodman, Neal; Bickham, John W.

    2018-01-01

    Small-eared shrews of the genus Cryptotis (Mammalia: Eulipotyphla: Soricidae) are widespread in the northern Neotropics. Systematic studies of these shrews over the past two decades have revealed previously undocumented morphological and species diversity, resulting in a quadrupling of the number of recognized species. Unfortunately, a small proportion of the species in the genus have been included in molecular phylogenetic studies, and evolutionary relationships within the genus are incompletely known. Traditionally, species have been assigned to four or five morphologically defined ‘species groups’, but tests of the monophyly of some of these groups show weak support and relationships amongst species groups remain somewhat speculative. The largest species group is the C. mexicanus group inhabiting Mexico and northern Central America. We studied sequences from mitochondrial cytochrome-b and 16S genes, as well as nuclear ApoB and BRCA1 genes from 22 species of Cryptotis, including 15 species in the C. mexicanus group. Our combined analysis shows that the C. goldmani subgroup is very weakly supported as monophyletic; however, the C. mexicanus group as a whole is not monophyletic. Our molecular phylogenetic analyses confirm the distinctiveness of two newly described species (C. celaque and C. mccarthyi) from isolated highlands of western Honduras and illustrate their relationship with other species formerly considered part of a widespread C. goodwini.

  2. Molecular detection of Rickettsia species in Amblyomma ticks collected from snakes in Thailand

    Czech Academy of Sciences Publication Activity Database

    Sumrandee, C.; Hirunkanokpun, S.; Doornbos, K.; Kitthawee, S.; Baimai, V.; Grubhoffer, Libor; Trinachartvanit, W.; Ahantarig, A.

    2014-01-01

    Roč. 5, č. 6 (2014), s. 632-640 ISSN 1877-959X Institutional support: RVO:60077344 Keywords : Tick * Rickettsia spp. * Amblyomma varanense * Amblyomma helvolum * Snake * Thailand Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.718, year: 2014

  3. Synthesis and catalytic performance of ZSM-5/MCM-41 composite molecular sieve from palygorskite

    Science.gov (United States)

    Jiang, Jinlong; Wu, Mei; Yang, Yong; Duanmu, Chuansong; Chen, Jing; Gu, Xu

    2017-10-01

    ZSM-5/MCM-41 composite molecular sieve has been hydrothermally synthesized through a two-step crystallization process using palygorskite (PAL) as silicon and aluminum source. The products were characterized by various means and their catalytic properties for acetalization of cyclohexanone and esterification of acetic acid and n-butanol were also investigated. In the first step ZSM-5 zeolite could be formed from the acid-treated PAL after hydrothermal treatment using tetrapropylammonium bromide as template. XRD patterns, N2 adsorption and desorption data, and TEM images show that the composite obtained in the secondary step had a well-ordered mesoporous MCM-41 phase and a microporous ZSM-5 zeolite phase. Compared with ZSM-5, ZSM-5/MCM-41 composite possessed more total acid amount, weak acid sites and large pore structure due to the formation of MCM-41 and exhibited higher catalytic activity for the acetalization and esterification reaction.

  4. Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae.

    Science.gov (United States)

    Chen, Ming-Chyuan; Cheng, Ying-Min; Hong, Min-Chang; Fang, Lee-Shing

    2004-11-19

    The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts.

  5. Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae

    International Nuclear Information System (INIS)

    Chen, M.-C.; Cheng, Y.-M; Hong, M.-C.; Fang, L.-S.

    2004-01-01

    The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts

  6. Synthesis, Crystal Structure and Anti-ischaemic Activity of (E)-1-{4 ...

    African Journals Online (AJOL)

    chloro- phenyl)prop-2-en-1-one (C28H29ClN2O3, Mr = 476.98) (5) was synthesized and studied by the single crystal X-ray diffraction method. Its structure was confirmed by 1HNMR, 13CNMR,HRMSand X-ray single crystal structure ...

  7. Study of the structural role of gallium and aluminum in 45S5 bioactive glasses by molecular dynamics simulations.

    Science.gov (United States)

    Malavasi, Gianluca; Pedone, Alfonso; Menziani, Maria Cristina

    2013-04-18

    The structural properties of phosphosilicate glasses based on the 45S5 Bioglass doped with gallium and aluminum (46.2 SiO2·24.3Na2O·26.9CaO·2.6P2O5·1.0X2O3, X = Ga or Al) are investigated by means of classical molecular dynamics simulations. Structural features of the two compositions are compared with those of the original 45S5 Bioglass in order to relate them to the different known bioactivities of these materials. Differences in the coordination environments of Ga and Al, network connectivity, and ion aggregation reveal a microscopic model of these glasses which supports the interpretation of the experimental data and provides new insight into the different biological behaviors of Ga- and Al-containing phosphosilicate glasses. Although Ga is found predominantly in a 4-fold coordination environment, small amounts of 5- and 6-fold coordinated atoms have been detected depending on the interatomic potential model employed. This suggests its possible intermediate role in phosphosilicate glasses. On the contrary, Al plays a network former role and leads to glasses with a more polymerized structure. Interestingly, the results show an increased propensity for aggregation of the Ca(2+) and PO4(3-) ions in the Al-containing phosphosilicate glasses with respect to the Ga-containing ones. This leads to insoluble calcium-phosphate-rich regions not detected in the bioactive glasses.

  8. Study of the glass forming ability of Cu{sub 60}Zr{sub 32,5}Ti{sub 7,5} alloy by molecular dynamics; Formacao de fase amorfa na liga Cu{sub 60}Zr{sub 32,5}Ti{sub 7,5} por dinamica molecular

    Energy Technology Data Exchange (ETDEWEB)

    Schimidt, C.S.; Lima, L.V.; Bastos, I.N.; Aliaga, L.C.R., E-mail: camilaschimidt17@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), Nova Friburgo, RJ (Brazil). Departamento de Materiais

    2016-07-01

    This article presents the results of molecular dynamics simulation of Cu{sub 60}Zr{sub 32.5}Ti{sub 7.5} alloy through the open source code LAMMPS. Amorphous samples were produced by quenching the metallic molten from 2300K to 200K at cooling rates of 50, 5 and 0.5K/ps. The pair distribution functions of both the liquid and solid were calculated and compared at different temperatures. The topology of short-range order was analyzed using the Voronoi tessellation method, which determined the presence of Cu-centered icosahedral clusters as the prevailing in the amorphous state at 300K. Moreover, the sample was submitted to uniaxial tensile tests at strain rate of 10ps{sup -1}, in order to investigate the mechanical behavior of the metallic glass. The result of the stress-strain curve showed that applied loads lead to the plastic regime. However, the presences of shear bands, typical in the experimental testing, were not observed. Moreover, the evolution of the viscosity above the glass transition temperature and the fragility of the alloy were determined. The solidus and liquidus temperatures were determined and a good agreement with experimental data was found. (author)

  9. RELAP5 analyses and support of Oconee-1 PTS studies

    International Nuclear Information System (INIS)

    Charlton, T.R.

    1983-01-01

    The integrity of a reactor vessel during a severe overcooling transient with primary system pressurization is a current safety concern and has been identified as an Unresolved Safety Issue(USI) A-49 by the US Nuclear Regulatory Commission (NRC). Resolution of USI A-49, denoted as Pressurized Thermal Shock (PTS), is being examined by the US NRC sponsored PTS integration study. In support of this study, the Idaho National Engineering Laboratory (INEL) has performed RELAP5/MOD1.5 thermal-hydraulic analyses of selected overcooling transients. These transient analyses were performed for the Oconee-1 pressurized water reactor (PWR), which is Babcock and Wilcox designed nuclear steam supply system

  10. Molecular characterization and expression analysis of a GTP-binding protein (MiRab5) in Mangifera indica.

    Science.gov (United States)

    Liu, Zhao-liang; Luo, Cong; Dong, Long; Van Toan, Can; Wei, Peng-xiao; He, Xin-hua

    2014-04-25

    The Rab family, the largest branch of Ras small GTPases, plays a crucial role in the vesicular transport in plants. The members of Rab family act as molecular switches that regulate the fusion of vesicles with target membranes through conformational changes. However, little is known about the Rab5 gene involved in fruit ripening and stress response. In this study, the MiRab5 gene was isolated from stress-induced Mangifera indica. The full-length cDNA sequence was 984bp and contained an open reading frame of 600bp, which encoded a 200 amino acid protein with a molecular weight of 21.83kDa and a theoretical isoelectric point of 6.99. The deduced amino acid sequence exhibited high homology with tomato (91% similarity) and contains all five characteristic Rab motifs. Real-time quantitative RT-PCR analysis demonstrated that MiRab5 was ubiquitously expressed in various mango tree tissues at different levels. The expression of MiRab5 was up-regulated during later stages of fruit ripening. Moreover, MiRab5 was generally up-regulated in response to various abiotic stresses (cold, salinity, and PEG treatments). Recombinant MiRab5 protein was successfully expressed and purified. SDS-PAGE and western blot analysis indicated that the expressed protein was recognized by the anti-6-His antibody. These results provide insights into the role of the MiRab5 gene family in fruit ripening and stress responses in the mango plant. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. CHEMICAL AND PHYSICAL CONDITIONS IN MOLECULAR CLOUD CORE DC 000.4-19.5 (SL42) IN CORONA AUSTRALIS

    Energy Technology Data Exchange (ETDEWEB)

    Hardegree-Ullman, E.; Whittet, D. C. B. [New York Center for Astrobiology and Department of Physics, Applied Physics, and Astronomy, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180 (United States); Harju, J. [Finnish Centre for Astronomy with ESO (FINCA), University of Turku, Vaeisaelaentie 20, FI-21500, Piikkioe (Finland); Juvela, M.; Sipilae, O. [Department of Physics, P.O. Box 64, FI-00014, University of Helsinki (Finland); Hotzel, S., E-mail: hardee@rpi.edu [Observatory, FI-00014, University of Helsinki (Finland)

    2013-01-20

    Chemical reactions in starless molecular clouds are heavily dependent on interactions between gas phase material and solid phase dust and ices. We have observed the abundance and distribution of molecular gases in the cold, starless core DC 000.4-19.5 (SL42) in Corona Australis using data from the Swedish ESO Submillimeter Telescope. We present column density maps determined from measurements of C{sup 18}O (J = 2-1, 1-0) and N{sub 2}H{sup +} (J = 1-0) emission features. Herschel data of the same region allow a direct comparison to the dust component of the cloud core and provide evidence for gas phase depletion of CO at the highest extinctions. The dust color temperature in the core calculated from Herschel maps ranges from roughly 10.7 to 14.0 K. This range agrees with the previous determinations from Infrared Space Observatory and Planck observations. The column density profile of the core can be fitted with a Plummer-like density distribution approaching n(r) {approx} r {sup -2} at large distances. The core structure deviates clearly from a critical Bonnor-Ebert sphere. Instead, the core appears to be gravitationally bound and to lack thermal and turbulent support against the pressure of the surrounding low-density material: it may therefore be in the process of slow contraction. We test two chemical models and find that a steady-state depletion model agrees with the observed C{sup 18}O column density profile and the observed N(C{sup 18}O) versus A{sub V} relationship.

  12. Spectroscopic investigations (FT-IR & FT-Raman) and molecular docking analysis of 6-[1-methyl-4-nitro-1H-imidazol-5-yl) sulfonyl]-7H-purine

    Science.gov (United States)

    Prasath, M.; Govindammal, M.; Sathya, B.

    2017-10-01

    The Azathioprine is used as anticancer agent. Azathioprine is chemically called 6-[1-methyl-4-nitro-1H-imidazol-5-yl) sulfonyl]-7H-purine (6M4N5P). The vibrational analysis of the 6M4N5P compound was carried out by using FT-IR and FT-Raman spectroscopic techniques and compared with aspects. The optimized geometry, frequency and intensity of the vibrational bands of 6M4N5P were obtained from the HF and DFT methods with 6-31G (d,p) basis set. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FT-IR and FT-Raman spectra. The calculated Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energies show that charge transfer occur within the molecule. MEP (Molecular Electrostatic Potential) is very useful in the investigation of the charge distributions and molecular structure. The molecule orbital contributions were determined by using the total density of states (TDOS). A molecular docking analysis has been carried out to understand the conformational change and electrostatic properties of 6M4N5P in the active site of Rac1-Receptor.

  13. Large-Scale Molecular Simulations on the Mechanical Response and Failure Behavior of a defective Graphene: Cases of 5-8-5 Defects

    Science.gov (United States)

    Wang, Shuaiwei; Yang, Baocheng; Yuan, Jinyun; Si, Yubing; Chen, Houyang

    2015-10-01

    Understanding the effect of defects on mechanical responses and failure behaviors of a graphene membrane is important for its applications. As examples, in this paper, a family of graphene with various 5-8-5 defects are designed and their mechanical responses are investigated by employing molecular dynamics simulations. The dependence of fracture strength and strain as well as Young’s moduli on the nearest neighbor distance and defect types is examined. By introducing the 5-8-5 defects into graphene, the fracture strength and strain become smaller. However, the Young’s moduli of DL (Linear arrangement of repeat unit 5-8-5 defect along zigzag-direction of graphene), DS (a Slope angle between repeat unit 5-8-5 defect and zigzag direction of graphene) and DZ (Zigzag-like 5-8-5 defects) defects in the zigzag direction become larger than those in the pristine graphene in the same direction. A maximum increase of 11.8% of Young’s modulus is obtained. Furthermore, the brittle cracking mechanism is proposed for the graphene with 5-8-5 defects. The present work may provide insights in controlling the mechanical properties by preparing defects in the graphene, and give a full picture for the applications of graphene with defects in flexible electronics and nanodevices.

  14. Modeling of amorphous SiCxO6/5 by classical molecular dynamics and first principles calculations

    Science.gov (United States)

    Liao, Ningbo; Zhang, Miao; Zhou, Hongming; Xue, Wei

    2017-02-01

    Polymer-derived silicon oxycarbide (SiCO) presents excellent performance for high temperature and lithium-ion battery applications. Current experiments have provided some information on nano-structure of SiCO, while it is very challenging for experiments to take further insight into the molecular structure and its relationship with properties of materials. In this work, molecular dynamics (MD) based on empirical potential and first principle calculation were combined to investigate amorphous SiCxO6/5 ceramics. The amorphous structures of SiCO containing silicon-centered mix bond tetrahedrons and free carbon were successfully reproduced. The calculated radial distribution, angular distribution and Young’s modulus were validated by current experimental data, and more details on molecular structure were discussed. The change in the slope of Young’s modulus is related to the glass transition temperature of the material. The proposed modeling approach can be used to predict the properties of SiCO with different compositions.

  15. ATS drugs molecular structure representation using refined 3D geometric moment invariants

    Czech Academy of Sciences Publication Activity Database

    Pratama, S. F.; Muda, A. K.; Choo, J. H.; Flusser, Jan; Abraham, A.

    2017-01-01

    Roč. 55, č. 10 (2017), s. 1951-1963 ISSN 0259-9791 R&D Projects: GA ČR GA15-16928S Institutional support: RVO:67985556 Keywords : 3D moment invariants * Geometric moment invariants * ATS drugs * Molecular similarity * Molecular descriptors Subject RIV: JD - Computer Applications, Robotics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 1.308, year: 2016 http://library.utia.cas.cz/separaty/2017/ZOI/flusser-0479217.pdf

  16. Molecular systematics of Barbatosphaeria (Sordariomycetes): multigene phylogeny and secondary ITS structure

    Czech Academy of Sciences Publication Activity Database

    Réblová, Martina; Réblová, K.; Štěpánek, Václav

    2015-01-01

    Roč. 35, December 2015 (2015), s. 21-38 ISSN 0031-5850 R&D Projects: GA ČR GAP506/12/0038 Institutional support: RVO:67985939 ; RVO:61388971 Keywords : Barbatosphaeria * molecular systematic * ITS secondary structures Subject RIV: EF - Botanics; EE - Microbiology, Virology (MBU-M) Impact factor: 5.725, year: 2015

  17. Molecular modeling of the human eukaryotic translation initiation factor 5A (eIF5A) based on spectroscopic and computational analyses

    International Nuclear Information System (INIS)

    Costa-Neto, Claudio M.; Parreiras-e-Silva, Lucas T.; Ruller, Roberto; Oliveira, Eduardo B.; Miranda, Antonio; Oliveira, Laerte; Ward, Richard J.

    2006-01-01

    The eukaryotic translation initiation factor 5A (eIF5A) is a protein ubiquitously present in archaea and eukarya, which undergoes a unique two-step post-translational modification called hypusination. Several studies have shown that hypusination is essential for a variety of functional roles for eIF5A, including cell proliferation and synthesis of proteins involved in cell cycle control. Up to now neither a totally selective inhibitor of hypusination nor an inhibitor capable of directly binding to eIF5A has been reported in the literature. The discovery of such an inhibitor might be achieved by computer-aided drug design based on the 3D structure of the human eIF5A. In this study, we present a molecular model for the human eIF5A protein based on the crystal structure of the eIF5A from Leishmania brasiliensis, and compare the modeled conformation of the loop bearing the hypusination site with circular dichroism data obtained with a synthetic peptide of this loop. Furthermore, analysis of amino acid variability between different human eIF5A isoforms revealed peculiar structural characteristics that are of functional relevance

  18. Study of the glass forming ability of Cu60Zr32,5Ti7,5 alloy by molecular dynamics

    International Nuclear Information System (INIS)

    Schimidt, C.S.; Lima, L.V.; Bastos, I.N.; Aliaga, L.C.R.

    2016-01-01

    This article presents the results of molecular dynamics simulation of Cu 60 Zr 32.5 Ti 7.5 alloy through the open source code LAMMPS. Amorphous samples were produced by quenching the metallic molten from 2300K to 200K at cooling rates of 50, 5 and 0.5K/ps. The pair distribution functions of both the liquid and solid were calculated and compared at different temperatures. The topology of short-range order was analyzed using the Voronoi tessellation method, which determined the presence of Cu-centered icosahedral clusters as the prevailing in the amorphous state at 300K. Moreover, the sample was submitted to uniaxial tensile tests at strain rate of 10ps -1 , in order to investigate the mechanical behavior of the metallic glass. The result of the stress-strain curve showed that applied loads lead to the plastic regime. However, the presences of shear bands, typical in the experimental testing, were not observed. Moreover, the evolution of the viscosity above the glass transition temperature and the fragility of the alloy were determined. The solidus and liquidus temperatures were determined and a good agreement with experimental data was found. (author)

  19. Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2012 - 31 January 2013

    Czech Academy of Sciences Publication Activity Database

    Mendel, Jan; Urbánková, Soňa; Vyskočilová, M.

    2013-01-01

    Roč. 13, č. 3 (2013), s. 546-549 ISSN 1755-098X Institutional support: RVO:68081766 Keywords : genetic database * microsatellite marker loci Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.626, year: 2013

  20. YCo5±x thin films with perpendicular anisotropy grown by molecular beam epitaxy

    Science.gov (United States)

    Sharma, S.; Hildebrandt, E.; Sharath, S. U.; Radulov, I.; Alff, L.

    2017-06-01

    The synthesis conditions of buffer-free (00l) oriented YCo5 and Y2Co17 thin films onto Al2O3 (0001) substrates have been explored by molecular beam epitaxy (MBE). The manipulation of the ratio of individual atomic beams of Yttrium, Y and Cobalt, Co, as well as growth rate variations allows establishing a thin film phase diagram. Highly textured YCo5±x thin films were stabilized with saturation magnetization of 517 emu/cm3 (0.517 MA/m), coercivity of 4 kOe (0.4 T), and anisotropy constant, K1, equal to 5.34 ×106 erg/cm3 (0.53 MJ/m3). These magnetic parameters and the perpendicular anisotropy obtained without additional underlayers make the material system interesting for application in magnetic recording devices.

  1. Supported high-risk percutaneous coronary intervention with the Impella 2.5 device the Europella registry

    DEFF Research Database (Denmark)

    Sjauw, Krischan D; Konorza, Thomas; Erbel, Raimund

    2009-01-01

    OBJECTIVES: This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). BACKGROUND: Patients with complex or high-risk coronary...... with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. METHODS: The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points.......5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. CONCLUSIONS: This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2...

  2. New perspectives in the Fischer-Tropsch synthesis using cobalt supported on mesoporous molecular sieves; Novas perspectivas na sintese de Fischer-Tropsch usando cobalto suportado em peneiras moleculares mesoporosas

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.J.B.; Silva, A.O.S. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Engenharia Quimica; Fernandes Junior, V.J.; Araujo, A.S. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Quimica

    2004-07-01

    The conversion of synthesis gas to liquid products via Fischer-Tropsch synthesis (FTS) is an important process in the generation of clean fuels of sulfur and nitrogen compounds. Catalysts based on iron are very used in the conventional process due its cheap manufacture price. Recently the use of cobalt as promoter gave good results. MCM-41 mesoporous materials were discovered by Mobil scientists in the nineties and ever since they have great successes as support and catalyst in several processes of the oil industry as catalytic cracking, reformer and hydrotreating. In this work are presented new alternatives for FTS with the use of cobalt supported on molecular sieves of the type MCM-41. A comparative study with the usual catalysts based on silica was accomplished with different levels of cobalt. (author)

  3. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit.

    Science.gov (United States)

    Pronk, Sander; Páll, Szilárd; Schulz, Roland; Larsson, Per; Bjelkmar, Pär; Apostolov, Rossen; Shirts, Michael R; Smith, Jeremy C; Kasson, Peter M; van der Spoel, David; Hess, Berk; Lindahl, Erik

    2013-04-01

    Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. GROMACS is an open source and free software available from http://www.gromacs.org. Supplementary data are available at Bioinformatics online.

  4. High-Flux Carbon Molecular Sieve Membranes for Gas Separation.

    Science.gov (United States)

    Richter, Hannes; Voss, Hartwig; Kaltenborn, Nadine; Kämnitz, Susanne; Wollbrink, Alexander; Feldhoff, Armin; Caro, Jürgen; Roitsch, Stefan; Voigt, Ingolf

    2017-06-26

    Carbon membranes have great potential for highly selective and cost-efficient gas separation. Carbon is chemically stable and it is relative cheap. The controlled carbonization of a polymer coating on a porous ceramic support provides a 3D carbon material with molecular sieving permeation performance. The carbonization of the polymer blend gives turbostratic carbon domains of randomly stacked together sp 2 hybridized carbon sheets as well as sp 3 hybridized amorphous carbon. In the evaluation of the carbon molecular sieve membrane, hydrogen could be separated from propane with a selectivity of 10 000 with a hydrogen permeance of 5 m 3 (STP)/(m 2 hbar). Furthermore, by a post-synthesis oxidative treatment, the permeation fluxes are increased by widening the pores, and the molecular sieve carbon membrane is transformed from a molecular sieve carbon into a selective surface flow carbon membrane with adsorption controlled performance and becomes selective for carbon dioxide. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Using support vector regression to predict PM10 and PM2.5

    International Nuclear Information System (INIS)

    Weizhen, Hou; Zhengqiang, Li; Yuhuan, Zhang; Hua, Xu; Ying, Zhang; Kaitao, Li; Donghui, Li; Peng, Wei; Yan, Ma

    2014-01-01

    Support vector machine (SVM), as a novel and powerful machine learning tool, can be used for the prediction of PM 10 and PM 2.5 (particulate matter less or equal than 10 and 2.5 micrometer) in the atmosphere. This paper describes the development of a successive over relaxation support vector regress (SOR-SVR) model for the PM 10 and PM 2.5 prediction, based on the daily average aerosol optical depth (AOD) and meteorological parameters (atmospheric pressure, relative humidity, air temperature, wind speed), which were all measured in Beijing during the year of 2010–2012. The Gaussian kernel function, as well as the k-fold crosses validation and grid search method, are used in SVR model to obtain the optimal parameters to get a better generalization capability. The result shows that predicted values by the SOR-SVR model agree well with the actual data and have a good generalization ability to predict PM 10 and PM 2.5 . In addition, AOD plays an important role in predicting particulate matter with SVR model, which should be included in the prediction model. If only considering the meteorological parameters and eliminating AOD from the SVR model, the prediction results of predict particulate matter will be not satisfying

  6. ANÁLISE SENSORIAL E FÍSICO-QUÍMICA DE FRUTOS TOMATE CEREJA ORGÂNICOS

    Directory of Open Access Journals (Sweden)

    DENILSON DE OLIVEIRA GUILHERME

    2014-01-01

    Full Text Available The study assessed sensorial aspects and physicochemical characteristics of two non- commercial genotypes of cherry tomato, CH152 and CLN1561, and compared them to the genotype Carolina, all grown organically. Ripened fruits of the three varieties were harvested at the same time, selected, cleaned and subjected to sensorial analysis by 50 adult testers. They used a 9-point hedonic scale to classify the fruits in terms of aroma, flavor, flesh color and general appearance. The physicochemical analyses determined pH, solu- ble solids (SS and titratable acidity (AT. For the aspects aroma and general appearance, the 3 varieties ob- tained mean scores of 7.0 to 7.9, which corresponds to “like moderately”; and scored 8.0 to 8.9 to the attribute flesh color, which represents “like very much”. For the attribute flavor, the scores of “Carolina” tomatoes and CLN1561A corresponded to “like moderately, and for CH152 it was “like very much”. The mean values of physicochemical parameters (pH = 4.41 to 4.61; SS = 4.03 to 5.06; and AT = 335.13 to 369.23 were similar among the genotypes (ANOVA, P>0.05. In conclusion, both the varieties tested, CH152 and CLN1561, pro- duce fruits of high sensorial and physicochemical quality, showing potential for commercial exploitation.

  7. 3D-QSAR (CoMFA, CoMSIA), molecular docking and molecular dynamics simulations study of 6-aryl-5-cyano-pyrimidine derivatives to explore the structure requirements of LSD1 inhibitors.

    Science.gov (United States)

    Ding, Lina; Wang, Zhi-Zheng; Sun, Xu-Dong; Yang, Jing; Ma, Chao-Ya; Li, Wen; Liu, Hong-Min

    2017-08-01

    Recently, Histone Lysine Specific Demethylase 1 (LSD1) was regarded as a promising anticancer target for the novel drug discovery. And several small molecules as LSD1 inhibitors in different structures have been reported. In this work, we carried out a molecular modeling study on the 6-aryl-5-cyano-pyrimidine fragment LSD1 inhibitors using three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to generate 3D-QSAR models. The results show that the best CoMFA model has q 2 =0.802, r 2 ncv =0.979, and the best CoMSIA model has q 2 =0.799, r 2 ncv =0.982. The electrostatic, hydrophobic and H-bond donor fields play important roles in the models. Molecular docking studies predict the binding mode and the interactions between the ligand and the receptor protein. Molecular dynamics simulations results reveal that the complex of the ligand and the receptor protein are stable at 300K. All the results can provide us more useful information for our further drug design. Copyright © 2017. Published by Elsevier Ltd.

  8. Identification of a 5-protein biomarker molecular signature for predicting Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Martín Gómez Ravetti

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a progressive brain disease with a huge cost to human lives. The impact of the disease is also a growing concern for the governments of developing countries, in particular due to the increasingly high number of elderly citizens at risk. Alzheimer's is the most common form of dementia, a common term for memory loss and other cognitive impairments. There is no current cure for AD, but there are drug and non-drug based approaches for its treatment. In general the drug-treatments are directed at slowing the progression of symptoms. They have proved to be effective in a large group of patients but success is directly correlated with identifying the disease carriers at its early stages. This justifies the need for timely and accurate forms of diagnosis via molecular means. We report here a 5-protein biomarker molecular signature that achieves, on average, a 96% total accuracy in predicting clinical AD. The signature is composed of the abundances of IL-1alpha, IL-3, EGF, TNF-alpha and G-CSF. METHODOLOGY/PRINCIPAL FINDINGS: Our results are based on a recent molecular dataset that has attracted worldwide attention. Our paper illustrates that improved results can be obtained with the abundance of only five proteins. Our methodology consisted of the application of an integrative data analysis method. This four step process included: a abundance quantization, b feature selection, c literature analysis, d selection of a classifier algorithm which is independent of the feature selection process. These steps were performed without using any sample of the test datasets. For the first two steps, we used the application of Fayyad and Irani's discretization algorithm for selection and quantization, which in turn creates an instance of the (alpha-beta-k-Feature Set problem; a numerical solution of this problem led to the selection of only 10 proteins. CONCLUSIONS/SIGNIFICANCE: the previous study has provided an extremely

  9. Fundamental Studies of Butane Oxidation over Model-Supported Vanadium Oxide Catalysts: Molecular Structure-Reactivity Relationships

    NARCIS (Netherlands)

    Wachs, I.E.; Jehng, J.M.; Deo, G.; Weckhuysen, B.M.; Guliants, V.V.; Benziger, J.B.; Sundaresan, S.

    1997-01-01

    The oxidation of n-butane to maleic anhydride was investigated over a series of model-supported vanadia catalysts where the vanadia phase was present as a two-dimensional metal oxide overlayer on the different oxide supports (TiO2, ZrO2, CeO2, Nb2O5, Al2O3, and SiO2). No correlation was found

  10. Molecular characterization of adenosine 5'-monophosphate deaminase--the key enzyme responsible for the umami taste of nori (Porphyra yezoensis Ueda, Rhodophyta).

    Science.gov (United States)

    Minami, Seiko; Sato, Minoru; Shiraiwa, Yoshihiro; Iwamoto, Koji

    2011-12-01

    The enzyme adenosine 5'-monophosphate deaminase (AMPD, EC 3.5.4.6) catalyzes the conversion of adenosine 5'-monophosphate to inosine 5'-mononucleotide (IMP). IMP is generally known as the compound responsible for the umami taste of the edible red alga Porphyra yezoensis Ueda that is known in Japan as nori. Therefore, we suspect that AMPD plays a key role in providing a favorable nori taste. In this study, we undertake the molecular characterization of nori-derived AMPD. The nori AMPD protein has a molecular mass of 55 kDa as estimated from both gel filtration and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The calculated molecular mass from the amino acid sequence deduced from cDNA is 57.1 kDa. The isoelectric point is 5.71. The coding region of AMPD consists of 1,566 bp encoding 522 amino acids and possesses a transmembrane domain and two N-glycosylation sites. The sequence identity of nori AMPD in human and yeast AMPDs was found to be less than 50% and 20% in DNA and amino acid sequences, respectively. Proline in the conserved motif of [SA]-[LIVM]-[NGS]-[STA]-D-D-P was found to be converted to glutamate. These results indicate that nori AMPD is a novel type of AMPD.

  11. PARTIAL SUPPORT OF THE COMMITTEE OF ATOMIC, MOLECULAR, AND OPTICAL SCIENCES Final Report for the period September 30, 2008 to June 30, 2014

    Energy Technology Data Exchange (ETDEWEB)

    Lancaster, James

    2015-06-29

    This report is the final report for the 2008-2014 cycle of DOE support for the Committee on Atomic, Molecular, and Optical Sciences. Highlights of the committee’s activities over this period included: • Meetings of the committee were held semiannually (Washington, DC in April and Irvine, CA in October) for four of the six years and annually the last two years (Washington, DC in April). • Committee meetings included half-day focus sessions on each of the areas identified in the last AMO decadal survey as having great scientific promise and short summaries of the focus session were prepared and delivered to sponsoring agencies. • CAMOS initiated a study that has been funded on high intensity lasers. DOE support for CAMOS has been of central importance to the committee’s ability to continue to fulfill its mandate to the Board on Physics and Astronomy and to the wider atomic, molecular, and optical sciences research community.

  12. [Analysis on research projects for acupuncture and moxibustion supported by NSFC during the 11th 5-year-plan].

    Science.gov (United States)

    Zhao, Chang-Long; Jing, Xiang-Hong; Li, Yu-Qing; Li, Liang; Rong, Pei-Jing; Wang, Chang-En

    2012-08-01

    In the present paper, the authors introduce the approved and finished research projects for acupuncture and moxibustion therapies supported by the National Natural Science Foundation of China (NSFC) during the 11th 5-year-plan. A total of 194 research projects were subsidized by NSFC from 2006 to 2010. These projects include 6 aspects: meridian-collaterals, acupoint theory, acupuncture analgesia, mechanisms underlying improvement of different clinical problems, clinical trials, and moxibustion therapy. The research on acupoints has been becoming a new hotspot in recent years. Majority of the research projects focus on the mechanism of acu-moxibustion underlying improvement of different clinical problems, while fewer projects on clinical trials. During the 11th 5-year-plan, 119 projects were completed; most of them involved meridian-collateral theory, acupoint theory, mechanism of acu-moxibustion underlying improvement of clinical problems and acupuncture manipulations. Following analysis of the finished research projects, we find that 1) many neurobiological methods and techniques are commonly used in the research on meridian-collateral theory; 2) the research on acupoint theory is changing from observing the local morphological structure to identifying characteristics of the regional activated receptors, particularly under the circumstances of visceral pathological conditions and efficacies of acupoints; 3) researches on the underlying mechanism of acu-moxibusiton for improving clinical disorders mainly focused on its cerebral protective effects against cerebral ischemia, in addition, researches about other diseases on clinical conditions have been also carried out, but the related mechanisms are far from understanding; 4) In many research projects, various new methods and techniques, such as fMRI, position emission tomography, genomics, proteomics, molecular biology, nerve stem cell, etc. were widely used; 5) Randomized controlled multi-center clinical trials are

  13. Information engineering for molecular diagnostics.

    Science.gov (United States)

    Sorace, J. M.; Ritondo, M.; Canfield, K.

    1994-01-01

    Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field. PMID:7949937

  14. The Effect of 5E-Learning Model Supported with Webquest Media on Students' Achievement and Satisfaction

    Science.gov (United States)

    Sahin, Semsettin M. S.; Baturay, Meltem Huri

    2016-01-01

    The purpose of this research study is to investigate the effect of the 5E-learning model supported with WebQuest media on the achievement and satisfaction of students. Therefore, two groups of students were compared in an experimental research design model. The experimental group was exposed to the 5E-learning model supported with WebQuest media;…

  15. Highly pathogenic avian influenza virus subtype H5N1 in Africa: a comprehensive phylogenetic analysis and molecular characterization of isolates.

    Directory of Open Access Journals (Sweden)

    Giovanni Cattoli

    Full Text Available Highly pathogenic avian influenza virus A/H5N1 was first officially reported in Africa in early 2006. Since the first outbreak in Nigeria, this virus spread rapidly to other African countries. From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries. At present, little is known of the epidemiology and molecular evolution of A/H5N1 viruses in Africa. We have generated 494 full gene sequences from 67 African isolates and applied molecular analysis tools to a total of 1,152 A/H5N1 sequences obtained from viruses isolated in Africa, Europe and the Middle East between 2006 and early 2008. Detailed phylogenetic analyses of the 8 gene viral segments confirmed that 3 distinct sublineages were introduced, which have persisted and spread across the continent over this 2-year period. Additionally, our molecular epidemiological studies highlighted the association between genetic clustering and area of origin in a majority of cases. Molecular signatures unique to strains isolated in selected areas also gave us a clearer picture of the spread of A/H5N1 viruses across the continent. Mutations described as typical of human influenza viruses in the genes coding for internal proteins or associated with host adaptation and increased resistance to antiviral drugs have also been detected in the genes coding for transmembrane proteins. These findings raise concern for the possible human health risk presented by viruses with these genetic properties and highlight the need for increased efforts to monitor the evolution of A/H5N1 viruses across the African continent. They further stress how imperative it is to implement sustainable control strategies to improve animal and public health at a global level.

  16. Mechanical tuning of conductance and thermopower in helicene molecular junctions

    Czech Academy of Sciences Publication Activity Database

    Vacek, Jaroslav; Vacek Chocholoušová, Jana; Stará, Irena G.; Starý, Ivo; Dubi, Y.

    2015-01-01

    Roč. 7, č. 19 (2015), s. 8793-8802 ISSN 2040-3364 R&D Projects: GA ČR(CZ) GAP207/10/2207 Institutional support: RVO:61388963 Keywords : helicene molecular junctions * quantum interference * stereoselective syntheses * nonlinear optical properties Subject RIV: CC - Organic Chemistry Impact factor: 7.760, year: 2015 http://pubs.rsc.org/en/content/articlepdf/2015/nr/c5nr01297j

  17. Workplace Lactation Support in Milwaukee County 5 Years After the Affordable Care Act.

    Science.gov (United States)

    Lennon, Tyler; Willis, Earnestine

    2017-02-01

    Workplace lactation support has become increasingly important because returning to work is associated with discontinuing breastfeeding and women in the workforce are increasing. Research aim: This study examined workplace lactation support among Milwaukee County businesses 5 years after implementation of the Affordable Care Act's Break Time for Nursing Mothers provision. A cross-sectional survey of Milwaukee County businesses was conducted in the summer of 2015 that inquired about workplace policies, lactation spaces, and other lactation resources offered. Business supports were stratified based on employer sizes: large (> 500 employees), medium (50-499 employees), and small (20-49 employees). A lactation amenity score was calculated for each business based on lactation resources available. Three hundred surveys were distributed and 71 businesses voluntarily completed the survey. Small employers were excluded from statistical analysis due to fewer responses ( n = 8). Overall, 87.3% ( n = 55) of respondents reported providing access to a multiuser space for lactation and 65.1% ( n = 41) reported providing a designated lactation space. Large employers ( n = 30) were more likely than medium employers ( n = 33) to provide a designated lactation space for breastfeeding or expressing (86.7% vs. 45.5%, p increase additional lactation support for women in the workplace.

  18. Electrosíntesis y caracterización de materiales moleculares a partir de derivados n-trifluorometansulfonil-1-azahexa-1,3,5-trienos. // Electrosintesis and characterization of molecular materials starting from having derived.

    Directory of Open Access Journals (Sweden)

    M. E. Sánchez Vergara

    2008-01-01

    Full Text Available Actualmente existe un interés creciente en los Materiales Moleculares, ya que estos pueden presentar diferentescomportamientos eléctricos que van desde aislantes, semiconductores o bien conductores. En el presente estudio fueronsintetizados materiales de este tipo, a partir de derivados N-Trifluorometansulfonil-1-azahexa-1,3,5-trienos yK3[Cr(C2O43]•3H2O debido a que estos compuestos representan un gran interés por sus variadas aplicaciones en camposcomo la química analítica, además los derivados N-Trifluorometansulfonil-1-azahexa-1,3,5-trienos resultan especialmenteatractivos desde el punto de vista estructural ya que en su forma neutra presentan una extensa deslocalización electrónica locual les confiere un comportamiento químico muy particular. En esta comunicación, se forman mediante electrosíntesisconvencional y mediante electrosíntesis en el módulo de electrocristalización del microscopio de fuerza atómica (AFM,algunos materiales moleculares. Una vez obtenidos dichos materiales, se caracterizan por análisis elemental sobresuperficies (SEM-EDS.Palabras claves: Materiales moleculares, anisotropía, electrocristalización._____________________________________________________________________________Abstract.Recently, molecular materials have been developed because of their electrical properties which give conductor,semiconductor, or superconductor behavior. In this work, the synthesis of new materials formed from Ntrifluoromethanesulfonyl-1-azahexa-1, 3, 5-triene species and K3[Cr(C2O43]•3H2O is reported. NTrifluoromethanesulfonyl-1-azahexa-1,3,5-trienes compounds, which are highly functionalised pentametines, have alsobeen studied due to its interesting physical and chemical properties. These compounds are especially interesting from astructural point of view for some reasons; in a neutral form, they show an extensive electronic delocalisation, which confersthem a very particular chemical behaviour. This study is focused on

  19. Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics Simulations

    Czech Academy of Sciences Publication Activity Database

    Meliá, C.; Ferrer, S.; Řezáč, Jan; Parisel, O.; Reinaud, O.; Moliner, V.; de la Lande, A.

    2013-01-01

    Roč. 19, č. 51 (2013), s. 17328-17337 ISSN 0947-6539 Institutional support: RVO:61388963 Keywords : ab initio calculations * copper * electron transfer * enzymes * molecular dynamics * reaction mechanisms Subject RIV: CC - Organic Chemistry Impact factor: 5.696, year: 2013

  20. High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.

    Science.gov (United States)

    Sato, Eiichi; Ando, Takashi; Ichikawa, Jiro; Okita, Genki; Sato, Nobutaka; Wako, Masanori; Ohba, Tetsuro; Ochiai, Satoshi; Hagino, Tetsuo; Jacobson, Richard; Haro, Hirotaka

    2014-12-01

    Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Carbon/H-ZSM-5 composites as supports for bi-functional Fischer-Tropsch synthesis catalysts

    NARCIS (Netherlands)

    Valero-Romero, M.J.; Sartipi, S.; Sun, X.; Rodríguez-Mirasol, J.; Cordero, T.; Kapteijn, F.; Gascon, J.

    2016-01-01

    Mesoporous H-ZSM-5–carbon composites, prepared via tetrapropylammonium hydroxide (TPAOH) post treatment of H-ZSM-5 followed by deposition of pyrolytic carbon, have been used as the support for the preparation of Co-based Fischer–Tropsch catalysts. The resulting catalysts display an improved

  2. Primary complement C5 deficiencies – Molecular characterization and clinical review of two families

    DEFF Research Database (Denmark)

    Schejbel, Lone; Fadnes, Dag; Permin, Henrik

    2013-01-01

    of the Norwegian patient, previously diagnosed as homozygous C5 deficient and suffering four Neisseria infections, an additional case of C5 deficiency was discovered, who had experienced one episode of Neisseria infections. Detailed review of the clinical history of the patients and their healthy relatives did...... infections, which is not covered by the current vaccines. These data support the clinical guidelines for patients treated with C5 inhibitors, who are functional C5 deficient by the treatment....

  3. The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Lorant Janosi

    Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

  4. Hydrodeoxygenation of Methyl Laurate over Ni Catalysts Supported on Hierarchical HZSM-5 Zeolite

    Directory of Open Access Journals (Sweden)

    Nana Li

    2017-12-01

    Full Text Available The hierarchical HZSM-5 zeolite was prepared successfully by a simple NaOH treatment method. The concentration of NaOH solution was carefully tuned to optimal the zeolite acidity and pore structure. Under NaOH treatment conditions, a large number of mesopores, which interconnected with the retained micropores, were created to facilitate mass transfer performance. There are very good correlations between the decline of the relative zeolite crystallinity and the loss of micropores volume. The Ni nanoclusters were uniformly confined in the mesopores of hierarchical HZSM-5 by the excessive impregnation method. The direct deoxygenation in N2 and hydrodeoxygenation in H2 of the methyl laurate were compared respectively over the Ni/HZSM-5 catalysts. In the N2 atmosphere, the deoxygenation rate of the methyl laurate on the Ni/HZSM-5 catalyst is relatively slow. In the presence of H2, the synergistic effect between the hydrogenation function of the metal and the acid function of the zeolite supports can make the deoxygenation level more obvious. The yield of hydrocarbon products gradually reached the maximum with the appropriate treatment concentration of 1M NaOH, which could be attributed to the improved mass transfer in the hierarchical HZSM-5 supports.

  5. Density functional theory analysis and molecular docking evaluation of 1-(2, 5-dichloro-4-sulfophenyl)-3-methyl-5-pyrazolone as COX2 inhibitor against inflammatory diseases

    Science.gov (United States)

    Kavitha, T.; Velraj, G.

    2017-08-01

    The molecular structure of 1-(2, 5-Dichloro-4-Sulfophenyl)-3-Methyl-5-Pyrazolone (DSMP) was optimized using DFT/B3LYP/6-31++G(d,p) level and its corresponding experimental as well as theoretical FT-IR, FT-Raman vibrational frequencies and UV-Vis spectral analysis were carried out. The vibrational assignments and total energy distributions of each vibration were presented with the aid of Veda 4xx software. The molecular electrostatic potential, HOMO-LUMO energies, global and local reactivity descriptors and natural bond orbitals were analyzed in order to find the most possible reactive sites of the molecule and it was found that DSMP molecule possess enhanced nucleophilic activity. One of the common known COX2 inhibitor, celecoxib (CXB) was also found to exhibit similar reactivity properties and hence DSMP was also expected to inhibit COX enzymes. In order to detect the COX inhibition nature of DSMP, molecular docking analysis was carried out with the help of Autodock software. For that, the optimized structure was in turn used for docking DSMP with COX enzymes. The binding energy scores and inhibitory constant values reveal that the DSMP molecule possess good binding affinity and low inhibition constant towards COX2 enzyme and hence it can be used as an anti-inflammatory drug after carrying out necessary biological tests.

  6. Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions

    Czech Academy of Sciences Publication Activity Database

    Dračínský, Martin; Möller, H. M.; Exner, T. E.

    2013-01-01

    Roč. 9, č. 8 (2013), s. 3806-3815 ISSN 1549-9618 R&D Projects: GA ČR GA13-24880S Institutional support: RVO:61388963 Keywords : ab initio molecular dynamics * NMR spectroscopy * DFT calculations * hydration Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.310, year: 2013

  7. Integration of a zebrafish research project into a molecular biology course to support critical thinking and course content goals.

    Science.gov (United States)

    Felzien, Lisa K

    2016-11-12

    Engaging undergraduates in research is essential for teaching them to think like scientists, and it has become a desired component of classroom and laboratory instruction. Research projects that span an entire semester expose students to a variety of concepts and techniques and allow students to use experiments to learn scientific principles, understand why specific techniques are applicable, critically analyze varied data, and examine how experimentation leads to acquiring knowledge. To provide an experience with these features, a semester long research project was integrated into a combined lecture and laboratory course, Molecular Biology. The project utilized the zebrafish model to examine gene expression during embryonic development and required students to develop and test hypotheses about the timing of expression of previously uncharacterized genes. The main goals for the project were to provide opportunities for students to develop critical thinking skills required for conducting research and to support the content goals of the course. To determine whether these goals were met, student performance on the steps of the project and related pre-test and post-test questions was examined. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):565-573, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

  8. Assessment of knowledge of participants on basic molecular biology techniques after 5-day intensive molecular biology training workshops in Nigeria.

    Science.gov (United States)

    Yisau, J I; Adagbada, A O; Bamidele, T; Fowora, M; Brai, B I C; Adebesin, O; Bamidele, M; Fesobi, T; Nwaokorie, F O; Ajayi, A; Smith, S I

    2017-07-08

    The deployment of molecular biology techniques for diagnosis and research in Nigeria is faced with a number of challenges, including the cost of equipment and reagents coupled with the dearth of personnel skilled in the procedures and handling of equipment. Short molecular biology training workshops were conducted at the Nigerian Institute of Medical Research (NIMR), to improve the knowledge and skills of laboratory personnel and academics in health, research, and educational facilities. Five-day molecular biology workshops were conducted annually between 2011 and 2014, with participants drawn from health, research facilities, and the academia. The courses consisted of theoretical and practical sessions. The impact of the workshops on knowledge and skill acquisition was evaluated by pre- and post-tests which consisted of 25 multiple choice and other questions. Sixty-five participants took part in the workshops. The mean knowledge of molecular biology as evaluated by the pre- and post-test assessments were 8.4 (95% CI 7.6-9.1) and 13.0 (95 CI 11.9-14.1), respectively. The mean post-test score was significantly greater than the mean pre-test score (p biology workshop significantly increased the knowledge and skills of participants in molecular biology techniques. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):313-317, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  9. Effect of intermolecular hydrogen bonding, vibrational analysis and molecular structure of a biomolecule: 5-Hydroxymethyluracil

    Science.gov (United States)

    Çırak, Çağrı; Sert, Yusuf; Ucun, Fatih

    2014-06-01

    In the present work, the experimental and theoretical vibrational spectra of 5-hydroxymethyluracil were investigated. The FT-IR (4000-400 cm-1) spectrum of the molecule in the solid phase was recorded. The geometric parameters (bond lengths and bond angles), vibrational frequencies, Infrared intensities of the title molecule in the ground state were calculated using density functional B3LYP and M06-2X methods with the 6-311++G(d,p) basis set for the first time. The optimized geometric parameters and theoretical vibrational frequencies were found to be in good agreement with the corresponding experimental data, and with the results found in the literature. The vibrational frequencies were assigned based on the potential energy distribution using the VEDA 4 program. The dimeric form of 5-hydroxymethyluracil molecule was also simulated to evaluate the effect of intermolecular hydrogen bonding on its vibrational frequencies. It was observed that the Nsbnd H stretching modes shifted to lower frequencies, while its in-plane and out-of-plane bending modes shifted to higher frequencies due to the intermolecular Nsbnd H⋯O hydrogen bond. Also, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies and diagrams were presented.

  10. Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds

    International Nuclear Information System (INIS)

    Yonezawa, Tetsu; Asano, Takashi; Fujino, Tatsuya; Nishihara, Hiroshi

    2013-01-01

    Highlights: ► MALDI-MS applications for drug identification in forensic science is investigated. ► Cyclodextrin-supported organic matrices strongly suppress the obstacle peaks of organic matrix compounds. ► Cyclodextrin-supported organic matrices also suppress the alkali adducted molecule peaks. ► Sugar units of cyclodextrins work for this specific features. - Abstract: A mass measurement technique for detecting low-molecular-weight drugs with a cyclodextrin-supported organic matrix was investigated. By using cyclodextrin-supported 2,4,6-trihydroxyacetophenone (THAP), the matrix-related peaks of drugs were suppressed. The peaks of protonated molecules of the sample and THAP were mainly observed, and small fragments were detected in a few cases. Despite the Na + and K + peaks were observed in the spectrum, Na + or K + adduct sample molecules were undetected, owing to the sugar units of cyclodextrin. The advantages of MALDI-MS with cyclodextrin-supported matrices as an analytical tool for forensic samples are discussed. The suppression of alkali adducted molecules and desorption process are also discussed

  11. Risk factors and the preoperative assessment of right para-oesophageal lymph node metastasis in right lobe papillary thyroid carcinoma: A case series.

    Science.gov (United States)

    Qu, You; Zhang, Hao; Zhang, Ping; Dong, Wenwu; He, Liang; Sun, Wei; Liu, Jinhao

    2017-06-01

    Right para-oesophageal lymph nodes (RPELN) are included among the right central compartment lymph nodes (rCLN) and located behind right recurrent laryngeal nerve (rRLN). However, due to the likelihood of increasing postoperative complications, and the extremely difficulties of RPELN dissection, the decision to perform RPELN dissection remains controversial. The aim of this study was to explore the risk factors of RPELN metastasis and evaluate RPELN metastasis by preoperative examination. We reviewed the medical records of 163 consecutive papillary thyroid carcinoma (PTC) patients (125 females and 38 males) who underwent right lobe plus isthmic resection (91 patients) or total thyroidectomy (72 patients) with right or bilateral central compartment lymph node dissection. The RPELN dissections were performed in all patients and were individually dissected and recorded intraoperatively. All patients underwent thyroid ultrasound and enhanced neck computed tomography (CT) routinely during preoperative examination. RPELN metastasis was detected in 20 patients (12.3%), among whom 6 (3.7%) had RPELN metastasis without rCLN metastasis. Total rCLN metastasis and lateral compartment lymph node metastasis were confirmed in 57 (35.0%) and 24 (14.7%) patients, respectively. The tumour diameter, number of metastatic rCLN and lateral compartment lymph nodes, RPELN visible on CT, and enhanced CT value of RPELN were confirmed significantly associated with RPELN metastasis by univariate analysis (P 1 cm) in the right lobe or suspected rCLN metastasis were recommended to undergo prophylactic RPELN dissection, particularly in those with a high enhanced CT value (>132) of RPELN or those with the copresence of lateral compartment lymph node metastasis. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Fatigue assessment of central support structure coil jacket of 4.5 MJ SMES

    International Nuclear Information System (INIS)

    Akhter, Javed; Bhunia, Uttam; Mondal, Bidhan Chandra; Nandi, Chinmay; Pal, Gautam; Saha, Subimal

    2013-01-01

    The Superconducting coil of 4.5 SMES will be of sector-toroidal type with 8 sectors. The maximum coil current will be 1200 Amperes. During its life time the SMES will be subjected to several cycles of charging and discharging. Thus the structural assessment of coil central support structure and the Liquid Helium Jacket, which comprises of the stress analysis and the fatigue life assessment, is a critical part of the design. In this paper fatigue life assessment of the 4.5 MJ SMES coil central support structure and the Liquid Helium Jacket together with the related stress analysis is presented. Coupled electromagnetic and Structural analysis using the commercial finite element analysis package ANSYS is performed. Considering the cyclic symmetry of the coil assembly, only 1/8th of the assembly is modelled. (author)

  13. Computational Biology Support: RECOMB Conference Series (Conference Support)

    Energy Technology Data Exchange (ETDEWEB)

    Michael Waterman

    2006-06-15

    This funding was support for student and postdoctoral attendance at the Annual Recomb Conference from 2001 to 2005. The RECOMB Conference series was founded in 1997 to provide a scientific forum for theoretical advances in computational biology and their applications in molecular biology and medicine. The conference series aims at attracting research contributions in all areas of computational molecular biology. Typical, but not exclusive, the topics of interest are: Genomics, Molecular sequence analysis, Recognition of genes and regulatory elements, Molecular evolution, Protein structure, Structural genomics, Gene Expression, Gene Networks, Drug Design, Combinatorial libraries, Computational proteomics, and Structural and functional genomics. The origins of the conference came from the mathematical and computational side of the field, and there remains to be a certain focus on computational advances. However, the effective use of computational techniques to biological innovation is also an important aspect of the conference. The conference had a growing number of attendees, topping 300 in recent years and often exceeding 500. The conference program includes between 30 and 40 contributed papers, that are selected by a international program committee with around 30 experts during a rigorous review process rivaling the editorial procedure for top-rate scientific journals. In previous years papers selection has been made from up to 130--200 submissions from well over a dozen countries. 10-page extended abstracts of the contributed papers are collected in a volume published by ACM Press and Springer, and are available at the conference. Full versions of a selection of the papers are published annually in a special issue of the Journal of Computational Biology devoted to the RECOMB Conference. A further point in the program is a lively poster session. From 120-300 posters have been presented each year at RECOMB 2000. One of the highlights of each RECOMB conference is a

  14. IAEA advisory group meeting on atomic and molecular data for fusion, Culham Laboratory, UK, 1 - 5 November 1976

    International Nuclear Information System (INIS)

    Lorenz, A.

    1977-02-01

    The IAEA Nuclear Data Section convened an Advisory Group Meeting on Atomic and Molecular Data for Fusion at the UKAEA Laboratory at Culham, from 1-5 November 1976. Three detailed working group reports identifying requirements and availability of atomic collision data, atomic structure data, and surface interaction data in fusion research are presented. The meeting recommended the formation of an international network of data centres for the compilation and dissemination of atomic and molecular data required for fusion, and recommended that the IAEA Nuclear Data Section be given the responsibility to establish and coordinate this network

  15. Quantum mechanics/molecular mechanics simulation of the ligand vibrations of the water-oxidizing Mn4CaO5 cluster in photosystem II.

    Science.gov (United States)

    Nakamura, Shin; Noguchi, Takumi

    2016-10-11

    During photosynthesis, the light-driven oxidation of water performed by photosystem II (PSII) provides electrons necessary to fix CO 2 , in turn supporting life on Earth by liberating molecular oxygen. Recent high-resolution X-ray images of PSII show that the water-oxidizing center (WOC) is composed of an Mn 4 CaO 5 cluster with six carboxylate, one imidazole, and four water ligands. FTIR difference spectroscopy has shown significant structural changes of the WOC during the S-state cycle of water oxidation, especially within carboxylate groups. However, the roles that these carboxylate groups play in water oxidation as well as how they should be properly assigned in spectra are unresolved. In this study, we performed a normal mode analysis of the WOC using the quantum mechanics/molecular mechanics (QM/MM) method to simulate FTIR difference spectra on the S 1 to S 2 transition in the carboxylate stretching region. By evaluating WOC models with different oxidation and protonation states, we determined that models of high-oxidation states, Mn(III) 2 Mn(IV) 2 , satisfactorily reproduced experimental spectra from intact and Ca-depleted PSII compared with low-oxidation models. It is further suggested that the carboxylate groups bridging Ca and Mn ions within this center tune the reactivity of water ligands bound to Ca by shifting charge via their π conjugation.

  16. Molecular-Based Mechanisms of Mendelian Forms of Salt-Dependent Hypertension Questioning the Prevailing Theory

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Dominiczak, A. F.; DiCarlo, S. E.; Pravenec, Michal; Morris Jr., R. C.

    2015-01-01

    Roč. 65, č. 5 (2015), s. 932-941 ISSN 0194-911X R&D Projects: GA ČR(CZ) GAP301/12/0696 Institutional support: RVO:67985823 Keywords : Mendelian * salt sensitive hypertension * vasodysfunction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.350, year: 2015

  17. [Adsorption characteristics of acetone and butanone onto honeycomb ZSM-5 molecular sieve].

    Science.gov (United States)

    Du, Juan; Luan, Zhi-Qiang; Xie, Qiang; Ye, Ping-Wei; Li, Kai; Wang, Xi-Qin

    2013-12-01

    Adsorption capacity of acetone and acetone-butanone mixture onto honeycomb ZSM-5 molecular sieve was measured in this paper, and the influences of relative humidity, initial adsorbate concentration and airflow velocity on the adsorption process were investigated. Besides, adsorption performance parameters were calculated by Wheeler's equation. The results showed that relative humidity had no obvious influence on the acetone adsorption performance, which suggests that this material has good hydrophobic ability; in the low concentration range, the dynamic saturated adsorption capacity of acetone increased with the increase of initial concentration, but in the occasion of high concentration of acetone gas (more than 9 mg x L(-1)), the dynamic saturated adsorption capacity maintained at a certain level and did not vary with the increase of initial concentration; the increase of air flow velocity resulted in significant increase of acetone adsorption rate constant, at the same time the critical layer thickness of the adsorbent bed also increased significantly. In the cases of acetone-butanone mixture, the adsorption capacity of butanone onto ZSM-5 was clearly higher than that of acetone.

  18. Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses.

    Science.gov (United States)

    Sima, Ni; Li, Rong; Huang, Wei; Xu, Miao; Beers, Jeanette; Zou, Jizhong; Titus, Steven; Ottinger, Elizabeth A; Marugan, Juan J; Xie, Xing; Zheng, Wei

    2018-04-10

    Infantile and late infantile neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases affecting the central nervous system (CNS). The infantile NCL (INCL) is caused by mutations in the PPT1 gene and late-infantile NCL (LINCL) is due to mutations in the TPP1 gene. Deficiency in PPT1 or TPP1 enzyme function results in lysosomal accumulation of pathological lipofuscin-like material in the patient cells. There is currently no small-molecular drug treatment for NCLs. We have generated induced pluripotent stem cells (iPSC) from three patient dermal fibroblast lines and further differentiated them into neural stem cells (NSCs). Using these new disease models, we evaluated the effect of δ-tocopherol (DT) and hydroxypropyl-β-cyclodextrin (HPBCD) with the enzyme replacement therapy as the control. Treatment with the relevant recombinant enzyme or DT significantly ameliorated the lipid accumulation and lysosomal enlargement in the disease cells. A combination therapy of δ-tocopherol and HPBCD further improved the effect compared to that of either drug used as a single therapy. The results demonstrate that these patient iPSC derived NCL NSCs are valid cell- based disease models with characteristic disease phenotypes that can be used for study of disease pathophysiology and drug development.

  19. 2-Chloroquinazolin-4(3H-one

    Directory of Open Access Journals (Sweden)

    Dong-Lei Cao

    2012-06-01

    Full Text Available In the title compound, C8H5ClN2O, the quinazoline system is approximately planar with a maximum deviation from the least-squares plane of 0.034 (2 Å. In the crystal, classical N—H...O and weak non-classical C—H...N hydrogen bonds link the molecules.

  20. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  1. 8-{(E-[(4-Chlorophenylimino]methyl}-1,1,7,7-tetramethyl-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-9-ol

    Directory of Open Access Journals (Sweden)

    Esen Nur Kantar

    2013-06-01

    Full Text Available The title Schiff base, C23H27ClN2O adopts the phenol–imine tautomeric form, with an intramolecular O—H...N hydrogen bond, which generates an S(6 ring motif. Three C atoms of the heterocyclic moiety of the hexahydropyridoquinoline unit, as well as the two methyl groups bonded to one of these C atoms, are disordered over two set of sites, with anoccupancy ratio of 0.740 (4:0.260 (4.

  2. The molecular environment of the pillar-like features in the H II region G46.5-0.2

    Science.gov (United States)

    Paron, S.; Celis Peña, M.; Ortega, M. E.; Fariña, C.; Petriella, A.; Rubio, M.; Ashley, R. P.

    2017-10-01

    At the interface of H II regions and molecular gas, peculiar structures appear, some of them with pillar-like shapes. Understanding their origin is important for characterizing triggered star formation and the impact of massive stars on the interstellar medium. In order to study the molecular environment and influence of radiation on two pillar-like features related to the H II region G46.5-0.2, we performed molecular line observations with the Atacama Submillimeter Telescope Experiment and spectroscopic optical observations with the Isaac Newton Telescope. From the optical observations, we identified the star that is exciting the H II region as spectral type O4-6. The molecular data allowed us to study the structure of the pillars and an HCO+ cloud lying between them. In this HCO+ cloud, which has no well-defined 12CO counterpart, we found direct evidence of star formation: two molecular outflows and two associated near-IR nebulosities. The outflow axis orientation is perpendicular to the direction of the radiation flow from the H II region. Several Class I sources are also embedded in this HCO+ cloud, showing that it is usual that young stellar objects (YSOs) form large associations occupying a cavity bounded by pillars. On the other hand, it was confirmed that the radiation-driven implosion (RDI) process is not occurring in one of the pillar tips.

  3. Structural analysis of CYP2C9 and CYP2C5 and an evaluation of commonly used molecular modeling techniques

    DEFF Research Database (Denmark)

    Afzelius, Lovisa; Raubacher, Florian; Karlén, Anders

    2004-01-01

    , newly built homology models, and repeated molecular dynamics simulations. The CPCA was based on molecular interaction fields focused on the active site regions of the proteins and include detailed amino acid analysis. The comparison of the CYP2C9 and CYP2C5 crystal structures revealed differences...... improved the similarity to the crystal target in some cases and could be recommended even though it requires a careful manual alignment process. The application of molecular dynamics simulations to highly flexible proteins such as cytochromes P450 is also explored and the information is extracted...... in the flexible regions such as the B-C and F-G loop and the N and C termini. Cross homology models of CYP2C9 and CYP2C5, using their respective crystal structures as templates, indicated that such models were more similar to their templates than to their target proteins. Inclusion of multiple templates slightly...

  4. Implant-supported mandibular overdentures retained with ball or bar attachments: a randomized prospective 5-year study

    DEFF Research Database (Denmark)

    Gotfredsen, K; Holm, B

    2001-01-01

    PURPOSE: The aim of the present study was to evaluate the periimplant conditions and the maintenance requirements for implant-supported overdentures in the mandible retained with ball or bar attachments during a 5-year period. MATERIALS AND METHODS: Twenty-six completely edentulous patients had two...... differences were registered. The mean frequency of complications/repairs per patient per year was 1.0 in the bar group and 0.6 in the ball group during the 5-year observation period. CONCLUSION: Two implants with ball or bar attachment supported an overdenture in the mandible for 5 years with a 100% survival...

  5. Looking for inhibitors of the dengue virus NS5 RNA-dependent RNA-polymerase using a molecular docking approach

    Directory of Open Access Journals (Sweden)

    Galiano V

    2016-10-01

    Full Text Available Vicente Galiano,1 Pablo Garcia-Valtanen,2 Vicente Micol,3,4 José Antonio Encinar3 1Physics and Computer Architecture Department, Miguel Hernández University (UMH, Elche, Spain; 2Experimental Therapeutics Laboratory, Hanson and Sansom Institute for Health Research, School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia; 3Molecular and Cell Biology Institute, Miguel Hernández University (UMH, Elche, Spain; 4CIBER: CB12/03/30038, Physiopathology of the Obesity and Nutrition, CIBERobn, Instituto de Salud Carlos III, Palma de Mallorca, Spain Abstract: The dengue virus (DENV nonstructural protein 5 (NS5 contains both an N-terminal methyltransferase domain and a C-terminal RNA-dependent RNA polymerase domain. Polymerase activity is responsible for viral RNA synthesis by a de novo initiation mechanism and represents an attractive target for antiviral therapy. The incidence of DENV has grown rapidly and it is now estimated that half of the human population is at risk of becoming infected with this virus. Despite this, there are no effective drugs to treat DENV infections. The present in silico study aimed at finding new inhibitors of the NS5 RNA-dependent RNA polymerase of the four serotypes of DENV. We used a chemical library comprising 372,792 nonnucleotide compounds (around 325,319 natural compounds to perform molecular docking experiments against a binding site of the RNA template tunnel of the virus polymerase. Compounds with high negative free energy variation (ΔG <-10.5 kcal/mol were selected as putative inhibitors. Additional filters for favorable druggability and good absorption, distribution, metabolism, excretion, and toxicity were applied. Finally, after the screening process was completed, we identified 39 compounds as lead DENV polymerase inhibitor candidates. Potentially, these compounds could act as efficient DENV polymerase inhibitors in vitro and in vivo. Keywords: virtual screening, molecular

  6. The Molecular Structures of the Local Arm and Perseus Arm in the Galactic Region of l  = [139.°75, 149.°75], b  = [−5.°25, 5.°25

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xinyu; Xu, Ye; Yang, Ji; Sun, Yan, E-mail: xydu@pmo.ac.cn, E-mail: xuye@pmo.ac.cn [Purple Mountain Observatory, Chinese Academy of Science, Nanjing 210008 (China)

    2017-04-01

    Using the Purple Mountain Observatory Delingha (PMODLH) 13.7 m telescope, we report a 96 deg{sup 2} {sup 12}CO/{sup 13}CO/C{sup 18}O mapping observation toward the Galactic region of l  = [139.°75,149.°75], b  = [−5.°25, 5.°25]. The molecular structures of the Local Arm and Perseus Arm are presented. Combining H i data and part of the Outer Arm results, we obtain that the warp structure of both atomic and molecular gas is obvious, while the flare structure only exists in atomic gas in this observing region. In addition, five filamentary giant molecular clouds on the Perseus Arm are identified. Among them, four are newly identified. Their relations with the Milky Way large-scale structure are discussed.

  7. HIV-1 entry inhibition by small-molecule CCR5 antagonists: A combined molecular modeling and mutant study using a high-throughput assay

    International Nuclear Information System (INIS)

    Labrecque, Jean; Metz, Markus; Lau, Gloria; Darkes, Marilyn C.; Wong, Rebecca S.Y.; Bogucki, David; Carpenter, Bryon; Chen Gang; Li Tongshuang; Nan, Susan; Schols, Dominique; Bridger, Gary J.; Fricker, Simon P.; Skerlj, Renato T.

    2011-01-01

    Based on the attrition rate of CCR5 small molecule antagonists in the clinic the discovery and development of next generation antagonists with an improved pharmacology and safety profile is necessary. Herein, we describe a combined molecular modeling, CCR5-mediated cell fusion, and receptor site-directed mutagenesis approach to study the molecular interactions of six structurally diverse compounds (aplaviroc, maraviroc, vicriviroc, TAK-779, SCH-C and a benzyloxycarbonyl-aminopiperidin-1-yl-butane derivative) with CCR5, a coreceptor for CCR5-tropic HIV-1 strains. This is the first study using an antifusogenic assay, a model of the interaction of the gp120 envelope protein with CCR5. This assay avoids the use of radioactivity and HIV infection assays, and can be used in a high throughput mode. The assay was validated by comparison with other established CCR5 assays. Given the hydrophobic nature of the binding pocket several binding models are suggested which could prove useful in the rational drug design of new lead compounds.

  8. Confinement and the Glass Transition Temperature in Supported Polymer Films: Molecular Weight, Repeat Unit Modification, and Cooperativity Length Scale Investigations

    Science.gov (United States)

    Mundra, Manish K.

    2005-03-01

    It is well known that the glass transition temperatures, Tgs, of supported polystyrene (PS) films decrease dramatically with decreasing film thickness below 60-80 nm. However, a detailed understanding of the cause of this effect is lacking. We have investigated the impact of several parameters, including polymer molecular weight (MW), repeat unit structure, and the length scale of cooperatively rearranging regions in bulk. There is no significant effect of PS MW on the Tg-confinement effect over a range of 5,000 to 3,000,000 g/mol. In contrast, the strength of the Tg reduction and the onset of the confinement effect increase dramatically upon changing the polymer from PS to poly(4-tert-butylstyrene) (PTBS), with PTBS exhibiting a Tg reduction relative to bulk at a thickness of 300-400 nm. PTBS also shows a Tg reduction relative to bulk of 47 K in a 21-nm-thick film, more than twice that observed in a PS film of identical thickness. Characterization of the length scale of cooperatively rearranging regions has been done by differential scanning calorimetry but reveals at best a limited correlation with the confinement effect.

  9. Polyphosphoric acid supported on Ni0.5Zn0.5Fe2O4 nanoparticles as a magnetically-recoverable green catalyst for the synthesis of pyranopyrazoles

    Directory of Open Access Journals (Sweden)

    Farid Moeinpour

    2017-05-01

    Full Text Available Polyphosphoric acid supported on silica coated Ni0.5Zn0.5Fe2O4 nanoparticles was found to be magnetically separable, highly efficient, eco-friendly, green and recyclable heterogeneous catalyst. This new catalyst at first was fully characterized by TEM, SEM, FTIR and XRD techniques and then catalytic activity of this catalyst was investigated in the synthesis of 5-cyano-1,4-dihydropyrano[2,3-c]pyrazoles. Also the Ni0.5Zn0.5Fe2O4 magnetic nanoparticle-supported polyphosphoric acid could be reused at least six times without significant loss of activity. It could be recovered easily by applying an external magnet.

  10. Molecular aspects of the interaction between Mason-Pfizer monkey virus matrix protein and artificial phospholipid membrane

    Czech Academy of Sciences Publication Activity Database

    Junková, P.; Prchal, J.; Spiwok, V.; Pleskot, Roman; Kadlec, Jan; Krásný, L.; Hynek, R.; Hrabal, R.; Ruml, T.

    2016-01-01

    Roč. 84, č. 11 (2016), s. 1717-1727 ISSN 0887-3585 Institutional support: RVO:61388963 Keywords : covalent labelling * mass spectrometry * multiscale molecular dynamics * protein-membrane interaction * phosphatidylinositol-(4,5)-bisphosphate * liposomes Subject RIV: CE - Biochemistry Impact factor: 2.289, year: 2016

  11. In vitro comparison of support capabilities of intra-aortic balloon pump and Impella 2.5 left percutaneous.

    Science.gov (United States)

    Schampaert, Stéphanie; van't Veer, Marcel; van de Vosse, Frans N; Pijls, Nico H J; de Mol, Bas A; Rutten, Marcel C M

    2011-09-01

    The Impella 2.5 left percutaneous (LP), a relatively new transvalvular assist device, challenges the position of the intra-aortic balloon pump (IABP), which has a long record in supporting patients after myocardial infarction and cardiac surgery. However, while more costly and more demanding in management, the advantages of the Impella 2.5 LP are yet to be established. The aim of this study was to evaluate the benefits of the 40 cc IABP and the Impella 2.5 LP operating at 47,000 rpm in vitro, and compare their circulatory support capabilities in terms of cardiac output, coronary flow, cardiac stroke work, and arterial blood pressure. Clinical scenarios of cardiogenic preshock and cardiogenic shock (CS), with blood pressure depression, lowered cardiac output, and constant heart rate of 80 bpm, were modeled in a model-controlled mock circulation, featuring a systemic, pulmonary, and coronary vascular bed. The ventricles, represented by servomotor-operated piston pumps, included the Frank-Starling mechanism. The systemic circulation was modeled with a flexible tube having close-to-human aortic dimensions and compliance properties. Proximally, it featured a branch mimicking the brachiocephalic arteries and a physiological correct coronary flow model. The rest of the systemic and pulmonary impedance was modeled by four-element Windkessel models. In this system, the enhancement of coronary flow and blood pressure was tested with both support systems under healthy and pathological conditions. Hemodynamic differences between the IABP and the Impella 2.5 LP were small. In our laboratory model, both systems approximately yielded a 10% cardiac output increase and a 10% coronary flow increase. However, since the Impella 2.5 LP provided significantly better left ventricular unloading, the circulatory support capabilities were slightly in favor of the Impella 2.5 LP. On the other hand, pulsatility was enhanced with the IABP and lowered with the Impella 2.5 LP. The support

  12. Effects of Quantum Nuclear Delocalisation on NMR Parameters from Path Integral Molecular Dynamics

    Czech Academy of Sciences Publication Activity Database

    Dračínský, Martin; Hodgkinson, P.

    2014-01-01

    Roč. 20, č. 8 (2014), s. 2201-2207 ISSN 0947-6539 Grant - others:Seventh Framework Programme of the European Union(XE) FP7-299242 People Institutional support: RVO:61388963 Keywords : density functional calculations * isotope effects * NMR spectroscopy * nuclear delocalisation * path integral molecular dynamics Subject RIV: CC - Organic Chemistry Impact factor: 5.731, year: 2014

  13. Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds

    Energy Technology Data Exchange (ETDEWEB)

    Yonezawa, Tetsu, E-mail: tetsu@eng.hokudai.ac.jp [Division of Materials Science and Engineering, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628 (Japan); Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Asano, Takashi [Division of Materials Science and Engineering, Faculty of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628 (Japan); Criminal Investigation Laboratory, Metropolitan Police Department, 2-1-1 Kasumigaseki, Chiyoda-ku, Tokyo 100-8929 (Japan); Fujino, Tatsuya [Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397 (Japan); Nishihara, Hiroshi [Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2013-06-20

    Highlights: ► MALDI-MS applications for drug identification in forensic science is investigated. ► Cyclodextrin-supported organic matrices strongly suppress the obstacle peaks of organic matrix compounds. ► Cyclodextrin-supported organic matrices also suppress the alkali adducted molecule peaks. ► Sugar units of cyclodextrins work for this specific features. - Abstract: A mass measurement technique for detecting low-molecular-weight drugs with a cyclodextrin-supported organic matrix was investigated. By using cyclodextrin-supported 2,4,6-trihydroxyacetophenone (THAP), the matrix-related peaks of drugs were suppressed. The peaks of protonated molecules of the sample and THAP were mainly observed, and small fragments were detected in a few cases. Despite the Na{sup +} and K{sup +} peaks were observed in the spectrum, Na{sup +} or K{sup +} adduct sample molecules were undetected, owing to the sugar units of cyclodextrin. The advantages of MALDI-MS with cyclodextrin-supported matrices as an analytical tool for forensic samples are discussed. The suppression of alkali adducted molecules and desorption process are also discussed.

  14. Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2017-03-01

    One molecular-based approach that increases potency and reduces dose-limited sequela is the implementation of selective 'targeted' delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine-monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine-reactive gemcitabine-(5'-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with gemcitabine-(5'-phosphorylimidazolide) resulting in the synthetic formation of gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]. The gemcitabine molar incorporation index for gemcitabine-(5'-phosphoramidate)-[anti-IGF-R1] was 2.67:1. Cytotoxicity Analysis - dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine-equivalent concentrations of 10 -9  M and 10 -7  M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine-reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non-dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

  15. The transcription factor Swi4 is target for PKA regulation of cell size at the G1 to S transition in Saccharomyces cerevisiae.

    Science.gov (United States)

    Amigoni, Loredana; Colombo, Sonia; Belotti, Fiorella; Alberghina, Lilia; Martegani, Enzo

    2015-08-03

    To investigate the specific target of PKA in the regulation of cell cycle progression and cell size we developed a new approach using the yeast strain GG104 bearing a deletion in adenylate cyclase gene and permeable to cAMP ( cyr1Δ, pde2Δ, msn2Δ, msn4Δ). In this strain the PKA activity is absent and can be activated by addition of cAMP in the medium, without any other change of the growth conditions. In the present work we show that the activation of PKA by exogenous cAMP in the GG104 strain exponentially growing in glucose medium caused a marked increase of cell size and perturbation of cell cycle with a transient arrest of cells in G1, followed by an accumulation of cells in G2/M phase with a minimal change in the growth rate. Deletion of CLN1 gene, but not of CLN2, abolished the transient G1 phase arrest. Consistently we found that PKA activation caused a transcriptional repression of CLN1 gene. Transcription of CLN1 is controlled by SBF and MBF dual-regulated promoter. We found that also the deletion of SWI4 gene abolished the transient G1 arrest suggesting that Swi4 is a target responsible for PKA modulation of G1/S phase transition. We generated a SWI4 allele mutated in the consensus site for PKA (Swi4(S159A)) and we found that expression of Swi4(S159A) protein in the GG104-Swi4Δ strain did not restore the transient G1 arrest induced by PKA activation, suggesting that Swi4 phosphorylation by PKA regulates CLN1 gene expression and G1/S phase transition.

  16. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  17. The linear interplay of intrinsic and extrinsic noises ensures a high accuracy of cell fate selection in budding yeast

    Science.gov (United States)

    Li, Yongkai; Yi, Ming; Zou, Xiufen

    2014-01-01

    To gain insights into the mechanisms of cell fate decision in a noisy environment, the effects of intrinsic and extrinsic noises on cell fate are explored at the single cell level. Specifically, we theoretically define the impulse of Cln1/2 as an indication of cell fates. The strong dependence between the impulse of Cln1/2 and cell fates is exhibited. Based on the simulation results, we illustrate that increasing intrinsic fluctuations causes the parallel shift of the separation ratio of Whi5P but that increasing extrinsic fluctuations leads to the mixture of different cell fates. Our quantitative study also suggests that the strengths of intrinsic and extrinsic noises around an approximate linear model can ensure a high accuracy of cell fate selection. Furthermore, this study demonstrates that the selection of cell fates is an entropy-decreasing process. In addition, we reveal that cell fates are significantly correlated with the range of entropy decreases. PMID:25042292

  18. Synthesis, vibrational spectroscopic investigations, molecular docking, antibacterial studies and molecular dynamics study of 5-[(4-nitrophenyl)acetamido]-2-(4-tert-butylphenyl)benzoxazole

    Science.gov (United States)

    Sheena Mary, Y.; Al-Shehri, Mona M.; Jalaja, K.; Al-Omary, Fatmah A. M.; El-Emam, Ali A.; Yohannan Panicker, C.; Armaković, Stevan; Armaković, Sanja J.; Temiz-Arpaci, Ozlem; Van Alsenoy, C.

    2017-04-01

    Antimicrobial active 5-[(4-nitrophenyl)acetamido]-2-(4-tert-butylphenyl)benzoxazole (NATPB) was synthesized and observed IR, Raman bands are compared with the theoretically predicted wave numbers. In the IR spectrum the NH stretching wave number splits into a doublet with a noted difference and is red shifted from the computed value, which indicates the weakening of NH bond resulting in proton transfer to the neighbouring oxygen atom. The HOMO-LUMO plots reveal the charge transfer in the molecular system through the conjugated paths. The electrophilic and nucleophilic reactive sites are identified from the MEP plot. Mapping of average local ionization energy (ALIE) values to the electron density surface served us as a tool for prediction of molecule sites possibly prone to electrophilic attacks. Other important reactive centres of the title molecule were detected by calculations of Fukui functions. Calculations of bond dissociation energies (BDE) for hydrogen abstraction were used in order to assess whether the NATPB molecules is prone to autoxidation mechanism or not, while BDE of the remaining single acyclic bonds were used in order to determine the weakest bond. Interaction properties with water were investigated by molecular dynamics (MD) simulations and calculations of radial distribution functions (RDFs). The compound possessed broad spectrum activity against all of the tested Gram-positive and Gram-negative bacteria and yeasts, their minimum inhibitory concentrations (MICs) ranging between 32 and 128 μg/ml. The compound exhibited significant antibacterial activity (32 μg/ml) against an antibiotic resistant E. faecalis isolate, at same potency with the compared standard drugs vancomycin and gentamycin sulfate. The molecular docking studies show that the compound might exhibit inhibitory activity against CDK inhibitors.

  19. Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine

    Czech Academy of Sciences Publication Activity Database

    Moudrá, Alena; Hubáčková, Soňa; Machalová, Veronika; Vančurová, Markéta; Bartek, Jiří; Reiniš, Milan; Hodný, Zdeněk; Jonasova, A.

    2016-01-01

    Roč. 5, č. 10 (2016), č. článku e1183860. ISSN 2162-402X R&D Projects: GA MZd NT14174 Institutional support: RVO:68378050 Keywords : 5-azacyatidine * bone marrow plasma * cytokines * DNA damage * inflammation * myelodysplastic syndromes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.719, year: 2016

  20. Next-Generation Survey Sequencing and the Molecular Organization of Wheat Chromosome 6B

    Czech Academy of Sciences Publication Activity Database

    Tanaka, T.; Kobayashi, F.; Joshi, G.P.; Šimková, Hana; Nasuda, S.; Doležel, Jaroslav; Handa, H.

    2014-01-01

    Roč. 21, č. 2 (2014), s. 103-114 ISSN 1340-2838 R&D Projects: GA ČR GBP501/12/G090 Grant - others:GA MŠk(CZ) ED0007/01/01 Program:ED Institutional support: RVO:61389030 Keywords : wheat * chromosome 6B * genome sequencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.477, year: 2014

  1. Crystal structures of 5-amino-N-phenyl-3H-1,2,4-di-thia-zol-3-iminium chloride and 5-amino-N-(4-chloro-phen-yl)-3H-1,2,4-di-thia-zol-3-iminium chloride monohydrate.

    Science.gov (United States)

    Yeo, Chien Ing; Tan, Yee Seng; Tiekink, Edward R T

    2015-10-01

    The crystal and mol-ecular structures of the title salt, C8H8N3S2 (+)·Cl(-), (I), and salt hydrate, C8H7ClN3S2 (+)·Cl(-)·H2O, (II), are described. The heterocyclic ring in (I) is statistically planar and forms a dihedral angle of 9.05 (12)° with the pendant phenyl ring. The comparable angle in (II) is 15.60 (12)°, indicating a greater twist in this cation. An evaluation of the bond lengths in the H2N-C-N-C-N sequence of each cation indicates significant delocalization of π-electron density over these atoms. The common feature of the crystal packing in (I) and (II) is the formation of charge-assisted amino-N-H⋯Cl(-) hydrogen bonds, leading to helical chains in (I) and zigzag chains in (II). In (I), these are linked by chains mediated by charge-assisted iminium-N(+)-H⋯Cl(-) hydrogen bonds into a three-dimensional architecture. In (II), the chains are linked into a layer by charge-assisted water-O-H⋯Cl(-) and water-O-H⋯O(water) hydrogen bonds with charge-assisted iminium-N(+)-H⋯O(water) hydrogen bonds providing the connections between the layers to generate the three-dimensional packing. In (II), the chloride anion and water mol-ecules are resolved into two proximate sites with the major component being present with a site occupancy factor of 0.9327 (18).

  2. Crystal structures of 5-amino-N-phenyl-3H-1,2,4-dithiazol-3-iminium chloride and 5-amino-N-(4-chlorophenyl-3H-1,2,4-dithiazol-3-iminium chloride monohydrate

    Directory of Open Access Journals (Sweden)

    Chien Ing Yeo

    2015-10-01

    Full Text Available The crystal and molecular structures of the title salt, C8H8N3S2+·Cl−, (I, and salt hydrate, C8H7ClN3S2+·Cl−·H2O, (II, are described. The heterocyclic ring in (I is statistically planar and forms a dihedral angle of 9.05 (12° with the pendant phenyl ring. The comparable angle in (II is 15.60 (12°, indicating a greater twist in this cation. An evaluation of the bond lengths in the H2N—C—N—C—N sequence of each cation indicates significant delocalization of π-electron density over these atoms. The common feature of the crystal packing in (I and (II is the formation of charge-assisted amino-N—H...Cl− hydrogen bonds, leading to helical chains in (I and zigzag chains in (II. In (I, these are linked by chains mediated by charge-assisted iminium-N+—H...Cl− hydrogen bonds into a three-dimensional architecture. In (II, the chains are linked into a layer by charge-assisted water-O—H...Cl− and water-O—H...O(water hydrogen bonds with charge-assisted iminium-N+—H...O(water hydrogen bonds providing the connections between the layers to generate the three-dimensional packing. In (II, the chloride anion and water molecules are resolved into two proximate sites with the major component being present with a site occupancy factor of 0.9327 (18.

  3. First hydrothermal synthesis of Bi{sub 5}O{sub 7}Br and its photocatalytic properties for molecular oxygen activation and RhB degradation

    Energy Technology Data Exchange (ETDEWEB)

    Su, Yurong; Ding, Chenghua; Dang, Yuanlin [College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061 (China); Wang, Hui [CAS Key Laboratory of Nuclear Radiation and Nuclear Energy Techniques, and Multidisciplinary Initiative Center, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Ye, Liqun, E-mail: yeliquny@163.com [College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061 (China); Jin, Xiaoli [College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061 (China); Xie, Haiquan, E-mail: Xie-hq@163.com [College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061 (China); Liu, Chao [College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061 (China)

    2015-08-15

    Graphical abstract: Bi{sub 5}O{sub 7}Br was firstly synthesized by via hydromel method and showed good photocatalytic properties for molecular oxygen activation and RhB degradation. - Highlights: • Bi{sub 5}O{sub 7}Br, a new Bi{sub x}O{sub y}X{sub z} semiconductor photocatalyst was firstly synthesized by via hydromel method. • As-synthesized Bi{sub 5}O{sub 7}Br can effectively activate molecular oxygen under UV–vis light irradiation. • The appearance of Bi{sub 5}O{sub 7}Br photocatalysis enriched the Bi-O-X photocatalysts. - Abstract: Comparing with BiOX (X = Cl, Br, I), Bi{sub x}O{sub y}X{sub z} as the newest bismuth-based photocatalysts have more appropriate conduction band position. And so, they can be used to active molecular oxygen. In this paper, Bi{sub 5}O{sub 7}Br, a new Bi{sub x}O{sub y}X{sub z} semiconductor photocatalyst was firstly synthesized by via hydromel method. It was characterized by X-ray diffraction (XRD), UV–visible diffused reflectance spectra (DRS), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM) and the corresponding selected-area electron diffraction (SAED) pattern. It can be found that the crystal structure and morphology are same with Bi{sub 5}O{sub 7}I. The size of a single rod is about 2 μm in width and 50 μm in length. As-synthesized Bi{sub 5}O{sub 7}Br can effectively activate molecular oxygen to generate superoxide radical (O{sub 2}{sup •} {sup −}) and hydroxyl radical (• OH) under UV–vis light irradiation. And it also showed high photocatalytic activity than BiOBr for the degradation of dyes. Thus, it can be seen, the appearance of Bi{sub 5}O{sub 7}Br photocatalysis enriched the bismuth-rich strategy of Bi-O-X photocatalysts.

  4. Preparation and application of zirconium sulfate supported on SAPO-34 molecular sieve as solid acid catalyst for esterification

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Dongyan, E-mail: xdy0156@sina.com; Ma, Hong; Cheng, Fei

    2014-05-01

    Graphical abstract: - Highlights: • SAPO-34 supported zirconium sulfate solid acid catalyst was prepared. • Esterification of acetic acid with ethanol can be catalyzed by ZS/SAPO-34. • The hydration of ZS is vital to the acidic property and catalytic performance. • The ZS/SAPO-34 catalyst treated at 200 °C shows good reusability. - Abstract: Zirconium sulfate (ZS) was supported on SAPO-34 molecular sieve by using an incipient wetness impregnation method with zirconium sulfate as the precursor. The as-prepared catalysts were used as solid acid catalyst for esterification reaction of acetic acid with ethanol. The influence of calcination temperature on the acidic property, catalytic activity, and reusability of ZS/SAPO-34 catalysts were mainly investigated. FT-IR, SEM, EDS and TG analysis have been carried out to demonstrate the characteristics of ZS/SAPO-34 catalysts. It was found that the 30 wt%ZS/SAPO-34 catalysts display the property of superacid irrespective of calcination temperature. The ZS/SAPO-34 catalyst treated at 200 °C can enhance the interaction between the supported ZS and SAPO-34 and keep the catalyst remaining substantially active after several reaction cycles. However, further increasing calcination temperature will cause the transfer of ZS from hydrate to anhydrous phase, and thus the decrease of activity.

  5. Preparation and application of zirconium sulfate supported on SAPO-34 molecular sieve as solid acid catalyst for esterification

    International Nuclear Information System (INIS)

    Xu, Dongyan; Ma, Hong; Cheng, Fei

    2014-01-01

    Graphical abstract: - Highlights: • SAPO-34 supported zirconium sulfate solid acid catalyst was prepared. • Esterification of acetic acid with ethanol can be catalyzed by ZS/SAPO-34. • The hydration of ZS is vital to the acidic property and catalytic performance. • The ZS/SAPO-34 catalyst treated at 200 °C shows good reusability. - Abstract: Zirconium sulfate (ZS) was supported on SAPO-34 molecular sieve by using an incipient wetness impregnation method with zirconium sulfate as the precursor. The as-prepared catalysts were used as solid acid catalyst for esterification reaction of acetic acid with ethanol. The influence of calcination temperature on the acidic property, catalytic activity, and reusability of ZS/SAPO-34 catalysts were mainly investigated. FT-IR, SEM, EDS and TG analysis have been carried out to demonstrate the characteristics of ZS/SAPO-34 catalysts. It was found that the 30 wt%ZS/SAPO-34 catalysts display the property of superacid irrespective of calcination temperature. The ZS/SAPO-34 catalyst treated at 200 °C can enhance the interaction between the supported ZS and SAPO-34 and keep the catalyst remaining substantially active after several reaction cycles. However, further increasing calcination temperature will cause the transfer of ZS from hydrate to anhydrous phase, and thus the decrease of activity

  6. Fundamental Roles of the Golgi-Associated Toxoplasma Aspartyl Protease, ASP5, at the Host-Parasite Interface

    Czech Academy of Sciences Publication Activity Database

    Hammoudi, P.-M.; Jacot, D.; Mueller, C.; Di Cristina, M.; Dogga, S.K.; Marq, J.-B.; Romano, J.; Tosetti, N.; Dubrot, J.; Emre, Y.; Lunghi, M.; Coppens, I.; Yamamoto, M.; Sojka, Daniel; Pino, P.; Soldati-Favre, D.

    2015-01-01

    Roč. 11, č. 10 (2015), e1005211 E-ISSN 1553-7374 Institutional support: RVO:60077344 Keywords : Toxoplasma gondii * Plasmodium proteins * ASP5 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.003, year: 2015

  7. Why are carbon molecular sieves interesting?

    Directory of Open Access Journals (Sweden)

    Oliveira Erica C. de

    2006-01-01

    Full Text Available This paper describes the production methods and the prospective uses of carbon molecular sieves. The main route to these materials is replication synthesis, where a silica or aluminosilicate molecular sieve is used as template to grow the carbonaceous phase in the voids. These materials may have applications as varied as in separation, adsorption and storage of gases, as electrodes in batteries, and as catalyst supports, all of them highly dependent on the molecular sieve porosity.

  8. Application of support vector machine to three-dimensional shape-based virtual screening using comprehensive three-dimensional molecular shape overlay with known inhibitors.

    Science.gov (United States)

    Sato, Tomohiro; Yuki, Hitomi; Takaya, Daisuke; Sasaki, Shunta; Tanaka, Akiko; Honma, Teruki

    2012-04-23

    In this study, machine learning using support vector machine was combined with three-dimensional (3D) molecular shape overlay, to improve the screening efficiency. Since the 3D molecular shape overlay does not use fingerprints or descriptors to compare two compounds, unlike 2D similarity methods, the application of machine learning to a 3D shape-based method has not been extensively investigated. The 3D similarity profile of a compound is defined as the array of 3D shape similarities with multiple known active compounds of the target protein and is used as the explanatory variable of support vector machine. As the measures of 3D shape similarity for our new prediction models, the prediction performances of the 3D shape similarity metrics implemented in ROCS, such as ShapeTanimoto and ScaledColor, were validated, using the known inhibitors of 15 target proteins derived from the ChEMBL database. The learning models based on the 3D similarity profiles stably outperformed the original ROCS when more than 10 known inhibitors were available as the queries. The results demonstrated the advantages of combining machine learning with the 3D similarity profile to process the 3D shape information of plural active compounds.

  9. Protein Based Molecular Markers Provide Reliable Means to Understand Prokaryotic Phylogeny and Support Darwinian Mode of Evolution

    Directory of Open Access Journals (Sweden)

    Vaibhav eBhandari

    2012-07-01

    Full Text Available The analyses of genome sequences have led to the proposal that lateral gene transfers (LGTs among prokaryotes are so widespread that they disguise the interrelationships among these organisms. This has led to questioning whether the Darwinian model of evolution is applicable to the prokaryotic organisms. In this review, we discuss the usefulness of taxon-specific molecular markers such as conserved signature indels (CSIs and conserved signature proteins (CSPs for understanding the evolutionary relationships among prokaryotes and to assess the influence of LGTs on prokaryotic evolution. The analyses of genomic sequences have identified large numbers of CSIs and CSPs that are unique properties of different groups of prokaryotes ranging from phylum to genus levels. The species distribution patterns of these molecular signatures strongly support a tree-like vertical inheritance of the genes containing these molecular signatures that is consistent with phylogenetic trees. Recent detailed studies in this regard on Thermotogae and Archaea, which are reviewed here, have identified large numbers of CSIs and CSPs that are specific for the species from these two taxa and a number of their major clades. The genetic changes responsible for these CSIs (and CSPs initially likely occurred in the common ancestors of these taxa and then vertically transferred to various descendants. Although some CSIs and CSPs in unrelated groups of prokaryotes were identified, their small numbers and random occurrence has no apparent influence on the consistent tree-like branching pattern emerging from other markers. These results provide evidence that although LGT is an important evolutionary force, it does not mask the tree-like branching pattern of prokaryotes or understanding of their evolutionary relationships. The identified CSIs and CSPs also provide novel and highly specific means for identification of different groups of microbes and for taxonomical and biochemical

  10. Protein based molecular markers provide reliable means to understand prokaryotic phylogeny and support Darwinian mode of evolution.

    Science.gov (United States)

    Bhandari, Vaibhav; Naushad, Hafiz S; Gupta, Radhey S

    2012-01-01

    The analyses of genome sequences have led to the proposal that lateral gene transfers (LGTs) among prokaryotes are so widespread that they disguise the interrelationships among these organisms. This has led to questioning of whether the Darwinian model of evolution is applicable to prokaryotic organisms. In this review, we discuss the usefulness of taxon-specific molecular markers such as conserved signature indels (CSIs) and conserved signature proteins (CSPs) for understanding the evolutionary relationships among prokaryotes and to assess the influence of LGTs on prokaryotic evolution. The analyses of genomic sequences have identified large numbers of CSIs and CSPs that are unique properties of different groups of prokaryotes ranging from phylum to genus levels. The species distribution patterns of these molecular signatures strongly support a tree-like vertical inheritance of the genes containing these molecular signatures that is consistent with phylogenetic trees. Recent detailed studies in this regard on the Thermotogae and Archaea, which are reviewed here, have identified large numbers of CSIs and CSPs that are specific for the species from these two taxa and a number of their major clades. The genetic changes responsible for these CSIs (and CSPs) initially likely occurred in the common ancestors of these taxa and then vertically transferred to various descendants. Although some CSIs and CSPs in unrelated groups of prokaryotes were identified, their small numbers and random occurrence has no apparent influence on the consistent tree-like branching pattern emerging from other markers. These results provide evidence that although LGT is an important evolutionary force, it does not mask the tree-like branching pattern of prokaryotes or understanding of their evolutionary relationships. The identified CSIs and CSPs also provide novel and highly specific means for identification of different groups of microbes and for taxonomical and biochemical studies.

  11. Artificial liver support with the molecular adsorbent recirculating system: activation of coagulation and bleeding complications.

    Science.gov (United States)

    Bachli, Esther B; Schuepbach, Reto A; Maggiorini, Marco; Stocker, Reto; Müllhaupt, Beat; Renner, Eberhard L

    2007-05-01

    Numerous, mostly uncontrolled, observations suggest that artificial liver support with the Molecular Adsorbent Recirculating System (MARS) improves pathophysiologic sequelae and outcome of acute and acute-on-chronic liver failure. MARS is felt to be safe, but extracorporeal circuits may activate coagulation. To assess the frequency of and risk factors for activation of coagulation during MARS treatment. Retrospective analysis of coagulopathy/bleeding complications observed during 83 consecutive MARS sessions in 21 patients (11 men; median age 46 years; median three sessions per patient; median duration of session 8 h). Nine clinically relevant episodes of coagulopathy/bleeding were observed in eight patients, forced to premature cessation of MARS in seven and ended lethal in four. Four complications occurred during the first, five during later (third to seventh) MARS sessions and two bleeders tolerated further sessions without complications. Coagulation parameters worsened significantly also during MARS sessions not associated with bleeding (PMARS therapy, potentially leading to bleeding complications and mortality.

  12. Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy-substituted phenyl-3-((phenylaminomethyl-1,3,4-oxadiazole-2(3H-thiones

    Directory of Open Access Journals (Sweden)

    Urja D. Nimbalkar

    2016-05-01

    Full Text Available A novel series of 5-(4-(benzyloxysubstituted phenyl-3-((phenyl aminomethyl-1,3,4-oxadiazole-2(3H-thione Mannich bases 6a–o were synthesized in good yield from the key compound 5-(4-(benzyloxyphenyl-1,3,4-oxadiazole-2(3H-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 α-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs.

  13. Electron Transport through Porphyrin Molecular Junctions

    Science.gov (United States)

    Zhou, Qi

    level broadening and shifting may significantly affect the electron transport through molecular junctions. The second factor studied, that is, the deprotection of the porphyrin end groups (acetylthio, -SCOCH3), was completed in-situ for the free base porphyrin through the reaction of the acetylthio with sulfuric acid at 35° Celsius for 3 hours. MALDI spectroscopy confirms that two additional deprotected porphyrin species are formed by deprotection, with protonated (MH+) molecular masses of 721 and 679, corresponding to a partially deprotected porphyrin (i.e. only one of the two end groups deprotected), and a fully deprotected porphyrin molecule. Along with the un-reacted acetyl protected porphyrin, a total of 3 porphyrin species are in the solution. This solution is used for self-assembly on a gold/mica surface. The thickness of the in-situ deprotected SAM is determined to be ˜1.7 nm, confirming a relatively upright molecular orientation (54.0°-63.5° between the substrate surface and the molecule), compared to a thickness of ˜1.5 nm for the protected SAM that has a more flat-lying molecular orientation (˜45.6° between the substrate surface and the molecule). From G-S measurements on SAMs prepared by in-situ deprotection, junctions with lower conductance steps at mid 10-5 G0 and junctions with higher conductance steps around 10-4 G 0 are observed. Supported by computational modeling from our collaborating research group, we associate the lower conductance steps to junctions based on the protected form of thiols at the tip-molecule interface, and the higher conductance steps to the deprotected form of the thiol contacts. We suggest that the reduced conductance in the protected porphyrin originates from the presence of the acetyl end groups (-COCH3), rather than from the elongation of the sulfur-gold (S-Au) bonds at the tip-molecule interface. By studying these two factors, I expect this work to provide insights into electron transport through molecules or metal

  14. The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein.

    Directory of Open Access Journals (Sweden)

    Kenrick A Vassall

    Full Text Available The classic isoforms of myelin basic protein (MBP are essential for the formation and maintenance of myelin in the central nervous system of higher vertebrates. The protein is involved in all facets of the development, compaction, and stabilization of the multilamellar myelin sheath, and also interacts with cytoskeletal and signaling proteins. The predominant 18.5-kDa isoform of MBP is an intrinsically-disordered protein that is a candidate auto-antigen in the human demyelinating disease multiple sclerosis. A highly-conserved central segment within classic MBP consists of a proline-rich region (murine 18.5-kDa sequence -T92-P93-R94-T95-P96-P97-P98-S99- containing a putative SH3-ligand, adjacent to a region that forms an amphipathic α-helix (P82-I90 upon interaction with membranes, or under membrane-mimetic conditions. The T92 and T95 residues within the proline-rich region can be post-translationally modified through phosphorylation by mitogen-activated protein (MAP kinases. Here, we have investigated the structure of the α-helical and proline-rich regions in dilute aqueous buffer, and have evaluated the effects of phosphorylation at T92 and T95 on the stability and dynamics of the α-helical region, by utilizing four 36-residue peptides (S72-S107 with differing phosphorylation status. Nuclear magnetic resonance spectroscopy reveals that both the α-helical as well as the proline-rich regions are disordered in aqueous buffer, whereas they are both structured in a lipid environment (cf., Ahmed et al., Biochemistry 51, 7475-9487, 2012. Thermodynamic analysis of trifluoroethanol-titration curves monitored by circular dichroism spectroscopy reveals that phosphorylation, especially at residue T92, impedes formation of the amphipathic α-helix. This conclusion is supported by molecular dynamics simulations, which further illustrate that phosphorylation reduces the folding reversibility of the α-helix upon temperature perturbation and affect the

  15. A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells.

    Science.gov (United States)

    Xiao, Hui; Bid, Hemant Kumar; Jou, David; Wu, Xiaojuan; Yu, Wenying; Li, Chenglong; Houghton, Peter J; Lin, Jiayuh

    2015-02-06

    Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells. LY5 inhibited persistent STAT3 phosphorylation and induced apoptosis in human medulloblastoma cell lines expressing constitutive STAT3 phosphorylation. The inhibition of STAT3 signaling by LY5 was confirmed by down-regulating the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21. LY5 also inhibited the induction of STAT3 phosphorylation by interleukin-6 (IL-6), insulin-like growth factor (IGF)-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but did not inhibit STAT1 and STAT5 phosphorylation stimulated by interferon-γ (IFN-γ) and EGF, respectively. In addition, LY5 blocked the STAT3 nuclear localization induced by IL-6, but did not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively. A combination of LY5 with cisplatin or x-ray radiation also showed more potent effects than single treatment alone in the inhibition of cell viability in human medulloblastoma cells. Furthermore, LY5 demonstrated a potent inhibitory activity on cell migration and angiogenesis. Taken together, these findings indicate LY5 inhibits persistent and inducible STAT3 phosphorylation and suggest that LY5 is a promising therapeutic drug candidate for medulloblastoma by inhibiting persistent STAT3 signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Portable Life Support System 2.5 Fan Design and Development

    Science.gov (United States)

    Quinn, Gregory; Carra, Michael; Converse, David; Chullen, Cinda

    2016-01-01

    NASA is building a high-fidelity prototype of an advanced Portable Life Support System (PLSS) as part of the Advanced Exploration Systems Program. This new PLSS, designated as PLSS 2.5, will advance component technologies and systems knowledge to inform a future flight program. The oxygen ventilation loop of its predecessor, PLSS 2.0, was driven by a centrifugal fan developed using specifications from the Constellation Program. PLSS technology and system parameters have matured to the point where the existing fan will not perform adequately for the new prototype. In addition, areas of potential improvement were identified with the PLSS 2.0 fan that could be addressed in a new design. As a result, a new fan was designed and tested for the PLSS 2.5. The PLSS 2.5 fan is a derivative of the one used in PLSS 2.0, and it uses the same nonmetallic, canned motor, with a larger volute and impeller to meet the higher pressure drop requirements of the PLSS 2.5 ventilation loop. The larger impeller allows it to operate at rotational speeds that are matched to rolling element bearings, and which create reasonably low impeller tip speeds consistent with prior, oxygen-rated fans. Development of the fan also considered a shrouded impeller design that could allow larger clearances for greater oxygen safety, assembly tolerances and particle ingestion. This paper discusses the design, manufacturing and performance testing of the new fans.

  17. Assessment of Knowledge of Participants on Basic Molecular Biology Techniques after 5-Day Intensive Molecular Biology Training Workshops in Nigeria

    Science.gov (United States)

    Yisau, J. I.; Adagbada, A. O.; Bamidele, T.; Fowora, M.; Brai, B. I. C.; Adebesin, O.; Bamidele, M.; Fesobi, T.; Nwaokorie, F. O.; Ajayi, A.; Smith, S. I.

    2017-01-01

    The deployment of molecular biology techniques for diagnosis and research in Nigeria is faced with a number of challenges, including the cost of equipment and reagents coupled with the dearth of personnel skilled in the procedures and handling of equipment. Short molecular biology training workshops were conducted at the Nigerian Institute of…

  18. Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

    Science.gov (United States)

    Cheng, Cheng; Guo, Luo; Lu, Ling; Xu, Xiaochen; Zhang, ShaSha; Gao, Junyan; Waqas, Muhammad; Zhu, Chengwen; Chen, Yan; Zhang, Xiaoli; Xuan, Chuanying; Gao, Xia; Tang, Mingliang; Chen, Fangyi; Shi, Haibo; Li, Huawei; Chai, Renjie

    2017-01-01

    Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein-protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

  19. Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    Haibo Shi

    2017-04-01

    Full Text Available Cochlear supporting cells (SCs have been shown to be a promising resource for hair cell (HC regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

  20. Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea

    Science.gov (United States)

    Cheng, Cheng; Guo, Luo; Lu, Ling; Xu, Xiaochen; Zhang, ShaSha; Gao, Junyan; Waqas, Muhammad; Zhu, Chengwen; Chen, Yan; Zhang, Xiaoli; Xuan, Chuanying; Gao, Xia; Tang, Mingliang; Chen, Fangyi; Shi, Haibo; Li, Huawei; Chai, Renjie

    2017-01-01

    Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein–protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration. PMID:28491023

  1. Efficient Aerobic Oxidation of 5-Hydroxymethylfurfural in Aqueous Media with Au-Pd Supported on Zinc Hydroxycarbonate

    DEFF Research Database (Denmark)

    Gui, Zhenyou; Cao, Wenrong; Shunmugavel, Saravanamurugan

    2016-01-01

    Bimetallic catalysts with Au–Pd supported on zinc hydroxycarbonate (ZOC) were synthesized by a simple deposition–precipitation method and analyzed by transmission electron microscopy to have a narrow-size distribution of predominantly 1–2 nm. The prepared Au–Pd/ZOC catalysts exhibited excellent...... activity towards 5-hydoxymethylfurfural (HMF) oxidation in water in the presence of the base NaHCO3 at benign conditions of 80 °C and 3 bar O2, resulting in quantitative yield of 2,5-furandicarboxylic acid (FDCA). The addition of base not only enhanced the yield of FDCA but also stabilized the support ZOC...

  2. Molecular organization of the 5S rDNA gene type II in elasmobranchs.

    Science.gov (United States)

    Castro, Sergio I; Hleap, Jose S; Cárdenas, Heiber; Blouin, Christian

    2016-01-01

    The 5S rDNA gene is a non-coding RNA that can be found in 2 copies (type I and type II) in bony and cartilaginous fish. Previous studies have pointed out that type II gene is a paralog derived from type I. We analyzed the molecular organization of 5S rDNA type II in elasmobranchs. Although the structure of the 5S rDNA is supposed to be highly conserved, our results show that the secondary structure in this group possesses some variability and is different than the consensus secondary structure. One of these differences in Selachii is an internal loop at nucleotides 7 and 112. These mutations observed in the transcribed region suggest an independent origin of the gene among Batoids and Selachii. All promoters were highly conserved with the exception of BoxA, possibly due to its affinity to polymerase III. This latter enzyme recognizes a dT4 sequence as stop signal, however in Rajiformes this signal was doubled in length to dT8. This could be an adaptation toward a higher efficiency in the termination process. Our results suggest that there is no TATA box in elasmobranchs in the NTS region. We also provide some evidence suggesting that the complexity of the microsatellites present in the NTS region play an important role in the 5S rRNA gene since it is significantly correlated with the length of the NTS.

  3. G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations

    DEFF Research Database (Denmark)

    Ísberg, Vignir; Balle, Thomas; Sander, Tommy

    2011-01-01

    molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability......A 5-HT(2A) receptor model was constructed by homology modeling based on the ß(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered...

  4. Molecular Electronics

    DEFF Research Database (Denmark)

    Jennum, Karsten Stein

    This thesis includes the synthesis and characterisation of organic compounds designed for molecular electronics. The synthesised organic molecules are mainly based on two motifs, the obigo(phenyleneethynylenes) (OPE)s and tetrathiafulvalene (TTF) as shown below. These two scaffolds (OPE and TTF......) are chemically merged together to form cruciform-like structures that are an essential part of the thesis. The cruciform molecules were subjected to molecular conductance measurements to explore their capability towards single-crystal field-effect transistors (Part 1), molecular wires, and single electron......, however, was obtained by a study of a single molecular transistor. The investigated OPE5-TTF compound was captured in a three-terminal experiment, whereby manipulation of the molecule’s electronic spin was possible in different charge states. Thus, we demonstrated how the cruciform molecules could...

  5. Impact of nanoconfinement on the diisopropylammonium chloride (C6H16ClN) organic ferroelectric

    Science.gov (United States)

    Baryshnikov, S. V.; Charnaya, E. V.; Milinskiy, A. Yu.; Parfenov, V. A.; Egorova, I. V.

    2018-03-01

    The dielectric studies of diisopropylammonium chloride (DIPAC) nanoparticles embedded into opal and MCM-41 silica matrices are presented. It is shown that the ferroelectric phase transition shifts to low temperatures and broadens for DIPAC within the opal pores compared to bulk. The thermal hysteresis of the transition increases under opal nanoconfinement. No anomalies of the permittivity relevant to the ferroelectric transition are observed for DIPAC within the MCM-41 molecular sieves likely due to formation of the amorphous phase.

  6. THE FAR-INFRARED, UV, AND MOLECULAR GAS RELATION IN GALAXIES UP TO z = 2.5

    International Nuclear Information System (INIS)

    Nordon, R.; Lutz, D.; Saintonge, A.; Berta, S.; Wuyts, S.; Förster Schreiber, N. M.; Genzel, R.; Magnelli, B.; Poglitsch, A.; Popesso, P.; Rosario, D.; Sturm, E.; Tacconi, L. J.

    2013-01-01

    We use the infrared excess (IRX) FIR/UV luminosity ratio to study the relation between the effective UV attenuation (A IRX ) and the UV spectral slope (β) in a sample of 450 1 * ) > 9.3. Thus, we are able to study galaxies on and even below the main SFR-stellar mass relation (main sequence). We find that main-sequence galaxies form a tight sequence in the IRX-β plane, which has a flatter slope than commonly used relations. This slope favors a Small-Magellanic-Cloud-like UV extinction curve, though the interpretation is model dependent. The scatter in the A IRX -β plane correlates with the position of the galaxies in the SFR-M * plane. Using a smaller sample of galaxies with CO gas masses, we study the relation between the UV attenuation and the molecular gas content. We find a very tight relation between the scatter in the IRX-β plane and the specific attenuation S A , a quantity that represents the attenuation contributed by the molecular gas mass per young star. S A is sensitive to both the geometrical arrangement of stars and dust and to the compactness of the star-forming regions. We use this empirical relation to derive a method for estimating molecular gas masses using only widely available integrated rest-frame UV and FIR photometry. The method produces gas masses with an accuracy between 0.12 and 0.16 dex in samples of normal galaxies between z ∼ 0 and z ∼ 1.5. Major mergers and submillimeter galaxies follow a different S A relation.

  7. Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism

    Science.gov (United States)

    Liberato, Marcelo V.; Silveira, Rodrigo L.; Prates, Érica T.; de Araujo, Evandro A.; Pellegrini, Vanessa O. A.; Camilo, Cesar M.; Kadowaki, Marco A.; Neto, Mario De O.; Popov, Alexander; Skaf, Munir S.; Polikarpov, Igor

    2016-04-01

    Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials. Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity. Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms. The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite. This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.

  8. Molecular structure, vibrational, UV, NMR, HOMO-LUMO, MEP, NLO, NBO analysis of 3,5 di tert butyl 4 hydroxy benzoic acid

    Science.gov (United States)

    Mathammal, R.; Sangeetha, K.; Sangeetha, M.; Mekala, R.; Gadheeja, S.

    2016-09-01

    In this study, we report a combined experimental and theoretical study on molecular structure and vibrational spectra of 3,5 di tert butyl 4 hydroxy benzoic acid. The properties of title compound have been evaluated by quantum chemical calculation (DFT) using B3LYP functional and 6-31 + G (d, p) as basis set. IR Spectra has been recorded using Fourier transform infrared spectroscopy (FT-IR) in the region 4000-400 cm-1. The vibrational assignment of the calculated normal modes has been made on the basis set. The isotropic chemical shifts computed by 13C and 1H NMR (Nuclear Magnetic Resonance) analyses also show good agreement with experimental observations. The theoretical UV-Vis spectrum of the compound are used to study the visible absorption maxima (λ max). The structure activity relationship have been interpreted by mapping electrostatic potential surface (MEP), which is valuable information for the quality control of medicines and drug receptor interactions. The Mullikan charges, HOMO (Highest Occupied Molecular Orbital) - LUMO (Lowest Unoccupied Molecular Orbital) energy are analyzed. HOMO-LUMO energy gap and other related molecular properties are also calculated. The Natural Bond Orbital (NBO) analysis is carried out to investigate the various intra and inter molecular interactions of molecular system. The Non-linear optical properties such as dipole moment (μ), polarizability (αtot) and molecular first order hyperpolarizability (β) of the title compound are computed with B3LYP/6-31 + G (d,p) level of theory.

  9. Nonadiabatic ab initio molecular dynamics of photoisomerization reaction between 1,3-cyclohexadiene and 1,3,5-cis-hexatriene

    International Nuclear Information System (INIS)

    Ohta, Ayumi; Kobayashi, Osamu; Danielache, Sebastian O.; Nanbu, Shinkoh

    2015-01-01

    Highlights: • The photoisomerization between cyclohexadiene and hexatriene was simulated. • Nonadiabatic ab initio MD simulations were employed to elucidate the mechanism. • Each excitations to S_1 and S_2 were simulated using full-dimensional model. • Specific molecular motions at CoIns and molecular vibrations on S_1 PES were found. • The one-sided product branching ratio was obtained at the photoexcitation to S_2. - Abstract: The photoisomerization process between 1,3-cyclohexadiene (CHD) and 1,3,5-cis-hexatriene (HT) has been studied by nonadiabatic ab initio molecular dynamics based on trajectory surface-hopping approach with a full-dimensional reaction model. The quantum chemical calculations were treated at MS-MR-CASPT2 level for 8 electrons in 8 orbitals with the cc-pVDZ basis set. The Zhu–Nakamura formula was employed to evaluate nonadiabatic transition probabilities. S_1 and S_2 states were included in the photoisomerization dynamics. Lifetimes and CHD:HT branching ratios were computationally estimated on the basis of statistical analysis of multiple executed trajectories. The analysis of trajectories suggested that the nonadiabatic transitions at the S_0/S_1 and S_1/S_2 conical intersections (CoIn) are correlated to the Kekulé-type vibration and the C3–C4–C5 bending motion, respectively. The one-sided branching ratio was obtained by excitations to the S_2 state; 70:30. The critical branching process was found to be dominated by the location of CoIn in potential energy hypersurface of the excited state.

  10. EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

    Science.gov (United States)

    Weinelt, Martin; von Oppen, Felix

    2012-10-01

    metal surfaces, focusing on electronic and vibrational spectroscopy in one case and scanning tunneling microscopy studies in the other. Original research articles describe results in many aspects of the field, including: Self-assembly, self-organization, and controlled growth of molecular layers on various substrates. Highly-ordered arrays provide model systems with extraordinary structural properties, allowing one to adjust interactions between molecules and between molecule and substrate, and can be robustly prepared from solution, an essential prerequisite for applications. Conformational or electronic switching of molecules adsorbed at metal and semiconductor surfaces. These studies highlight the elementary processes governing molecular switching at surfaces as well as the wide range of possible stimuli. Carbon-based substrates such as graphene or carbon nanotubes. These substrates are attractive due to their effective two-dimensionality which implies that switching of adsorbed molecules can effect a significant back-action on the substrate. Mechanisms of conformational switching. Several contributions study the role of electron-vibron coupling and heating in current-induced conformational switching. We hope that the collection of articles presented here will stimulate and encourage researchers in surface physics and interfacial chemistry to contribute to the still emerging field of molecular switches at surfaces. We wish to acknowledge the support and input from many colleagues in preparing this special section. A significant part of this work has been conducted in the framework of the Sonderforschungsbereich 658 Elementary Processes in Molecular Switches at Surfaces of the Deutsche Forschungsgemeinschaft, to which we are grateful for financial support. Molecular surfaces at switches contents Molecular switches at surfacesMartin Weinelt and Felix von Oppen Optically and thermally induced molecular switching processes at metal surfacesPetra Tegeder Effects of

  11. Comparison of Separation of Seed Oil Triglycerides Containing Isomeric Conjugated Octadecatrienoic Acid Moieties by Reversed-Phase HPLC

    Directory of Open Access Journals (Sweden)

    Anh Van Nguyen

    2017-12-01

    Full Text Available Relative retention analysis and increment approach were applied for the comparison of triglycerides (TGs retention of a broad set of plant seed oils with isomeric conjugated octadecatrienoic acids (CLnA by reversed-phase HPLC for “propanol-2-acetonitrile” mobile phases and Kromasil 100-5C18 stationary phase with diode array detection (DAD and mass spectrometric (MS detection. The subjects of investigation were TGs of seed oils: Calendula officinalis, Catalpa ovata, Jacaranda mimosifolia, Centranthus ruber, Momordica charantia, Trichosanthes anguina, Punica granatum, Thladiantha dubia, Valeriana officinalis, and Vernicia montana. It was found that a sequence of elution of TGs of the same types is the same without any inversions for full range of mobile phase compositions: punicic (C18:39Z11E13Z < jacaric (C18:38Z10E12Z < catalpic (C18:39E11E13Z < α-eleostearic (C18:39Z11E13E < calendic (C18:38E10E12Z < β-eleostearic (C18:39E11E13E < all-E calendic (C18:38E10E12E acids. TGs and fatty acid compositions were calculated for all oil samples. Regularities of solute retentions as a function of isomeric conjugated octadecatrienoic acid moiety structure are discussed. Thus, it was proven that it is possible to differentiate TGs of complex composition with moieties of all natural CLnA by retention control accomplished by electronic spectra comparison, even though there are only three types of electronic-vibration spectra for seven isomeric CLnA.

  12. The value of metaphorical reasoning in bioethics: An empirical-ethical study.

    Science.gov (United States)

    Olsman, Erik; Veneberg, Bert; van Alfen, Claudia; Touwen, Dorothea

    2017-01-01

    Metaphors are often used within the context of ethics and healthcare but have hardly been explored in relation to moral reasoning. To describe a central set of metaphors in one case and to explore their contribution to moral reasoning. Semi-structured interviews were conducted with 16 parents of a child suffering from the neurodegenerative disease CLN3. The interviews were recorded, transcribed, and metaphors were analyzed. The researchers wrote memos and discussed about their analyses until they reached consensus. Ethical considerations: Participants gave oral and written consent and their confidentiality and anonymity were respected. A central set of metaphors referred to the semantic field of the hands and arms and consisted of two central metaphors that existed in a dialectical relationship: grasping versus letting go. Participants used these metaphors to describe their child's experiences, who had to "let go" of abilities, while "clinging" to structures and the relationship with their parent(s). They also used it to describe their own experiences: participants tried to "grab" the good moments with their child and had to "let go" of their child when (s)he approached death. Participants, in addition, "held" onto caring for their child while being confronted with the necessity to "let go" of this care, leaving it to professional caregivers. The ethical analysis of the findings shows that thinking in terms of the dialectical relationship between "grasping" and "letting go" helps professional caregivers to critically think about images of good care for children with CLN3. It also helps them to bear witness to the vulnerable, dependent, and embodied nature of the moral self of children with CLN3 and their parents. Metaphorical reasoning may support the inclusion of marginalized perspectives in moral reasoning. Future studies should further explore the contribution of metaphorical reasoning to moral reasoning in other cases.

  13. Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

    Science.gov (United States)

    Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

    2015-02-01

    To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

  14. Carbon cluster formation during thermal decomposition of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine and 1,3,5-triamino-2,4,6-trinitrobenzene high explosives from ReaxFF reactive molecular dynamics simulations.

    Science.gov (United States)

    Zhang, Luzheng; Zybin, Sergey V; van Duin, Adri C T; Dasgupta, Siddharth; Goddard, William A; Kober, Edward M

    2009-10-08

    We report molecular dynamics (MD) simulations using the first-principles-based ReaxFF reactive force field to study the thermal decomposition of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) at various densities and temperatures. TATB is known to produce a large amount (15-30%) of high-molecular-weight carbon clusters, whereas detonation of nitramines such as HMX and RDX (1,3,5-trinitroperhydro-1,3,5-triazine) generate predominantly low-molecular-weight products. In agreement with experimental observation, these simulations predict that TATB decomposition quickly (by 30 ps) initiates the formation of large carbonaceous clusters (more than 4000 amu, or approximately 15-30% of the total system mass), and HMX decomposition leads almost exclusively to small-molecule products. We find that HMX decomposes readily on this time scale at lower temperatures, for which the decomposition rate of TATB is about an order of magnitude slower. Analyzing the ReaxFF MD results leads to the detailed atomistic structure of this carbon-rich phase of TATB and allows characterization of the kinetics and chemistry related to this phase and their dependence on system density and temperature. The carbon-rich phase formed from TATB contains mainly polyaromatic rings with large oxygen content, leading to graphitic regions. We use these results to describe the initial reaction steps of thermal decomposition of HMX and TATB in terms of the rates for forming primary and secondary products, allowing comparison to experimentally derived models. These studies show that MD using the ReaxFF reactive force field provides detailed atomistic information that explains such macroscopic observations as the dramatic difference in carbon cluster formation between TATB and HMX. This shows that ReaxFF MD captures the fundamental differences in the mechanisms of such systems and illustrates how the ReaxFF may be applied to model complex chemical phenomena

  15. Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

    Directory of Open Access Journals (Sweden)

    Sugimoto Yuka

    2012-03-01

    Full Text Available Abstract Background While lenalidomide (LEN shows high efficacy in myelodysplastic syndromes (MDS with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. Design and methods We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN, MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML without del[5q] by metaphase cytogenetics (MC who underwent therapy with LEN. Results Fluorescence in situ hybridization (FISH or single nucleotide polymorphism array (SNP-A-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8% additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08 and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11. However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Conclusions Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.

  16. Structure-based design of a bisphosphonate 5 '(3 ')-deoxyribonucleotidase inhibitor

    Czech Academy of Sciences Publication Activity Database

    Pachl, Petr; Šimák, Ondřej; Řezáčová, Pavlína; Fábry, Milan; Buděšínský, Miloš; Rosenberg, Ivan; Brynda, Jiří

    2015-01-01

    Roč. 6, č. 9 (2015), s. 1635-1638 ISSN 2040-2503 R&D Projects: GA ČR GA203/09/0820; GA ČR GA13-26526S; GA ČR GA13-24880S Institutional support: RVO:61388963 ; RVO:68378050 Keywords : mitochondrial deoxyribonucleotidase * crystal structures * 5'-nucleotidases Subject RIV: CE - Biochemistry; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 2.319, year: 2015

  17. Molecular dynamics studies of displacement cascades in Fe-Y{sub 2}TiO{sub 5} system

    Energy Technology Data Exchange (ETDEWEB)

    Dholakia, Manan, E-mail: manan@igcar.gov.in; Chandra, Sharat; Jaya, S. Mathi [Materials Physics Division, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102, TN (India)

    2016-05-23

    The effect of displacement cascade on Fe-Y{sub 2}TiO{sub 5} bilayer is studied using classical molecular dynamics simulations. Different PKA species – Fe, Y, Ti and O – with the same PKA energy of 8 keV are used to produce displacement cascades that encompass the interface. It is shown that Ti atom has the highest movement in the ballistic regime of cascades which can lead to Ti atoms moving out of the oxide clusters into the Fe matrix in ODS alloys.

  18. From beta-relaxation to alpha-decay: Atomistic picture from molecular dynamics simulations for glass-forming Ni0.5Zr0.5 melt

    Energy Technology Data Exchange (ETDEWEB)

    Teichler, Helmar [Inst. Materialphysik, Univ Goettingen (Germany)

    2013-07-01

    In glass-forming melts the decay of structural fluctuation shows the well known transition from beta-relaxation (von-Schweidler law with exponent b) to alpha-decay (KWW law with exponent beta). Here we present results from molecular dynamics simulations for a metallic glass forming Ni0.5Zr0.5 model aimed at giving an understanding of this transition on the atomistic scale. At the considered temperature below mode coupling Tc, the dynamics of the system can be interpreted by residence of the particles in their neighbour cages and escape from the cages as rare processes. Our analysis yields that the fraction of residing particles is characterized by a hierarchical law in time, with von-Schweidler b explicitly related to the exponent of this law. In the alpha-decay regime the stretching exponent reflects, in addition, floating of the cages due to strain effects of escaped particles. Accordingly, the change from beta-relaxation to alpha-decay indicates the transition from low to large fraction of escaped particles.

  19. Conformational analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) by NMR and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Marcelle de S.; Figueroa-Villar, Jose D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Quimica. Grupo de Medicina Quimica

    2014-05-15

    2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-ones) with para and ortho-R groups on the benzene ring were prepared and studied by nuclear magnetic resonance (NMR) and molecular modeling to determine their conformational exchanges. Experimental and calculated results indicated conformational interconversions in these compounds by rotation of benzene ring and slow movement of dimedone rings, leading to intramolecular hydrogen bond length variation. The presence of one R group at the ortho position on the benzene ring modifies conformational exchange, leading to disappearance of one intramolecular hydrogen bond and superposition of diverse NMR signals. The correlation of σ{sub p} values with chemical shifts, angles and atomic charges confirms that para-R groups electronic properties are involved in conformational exchange and chemical shift variance. These results will be used to study the interaction of these compounds with bio-molecules and their use as starting materials for design and synthesis of new bioactive agents. (author)

  20. Novel 1,5,7-trihydroxy-3-hydroxy methyl anthraquinone isolated from terrestrial Streptomyces sp. (eri-26) with antimicrobial and molecular docking studies.

    Science.gov (United States)

    Duraipandiyan, V; Al-Dhabi, N A; Balachandran, C; Raj, M Karunai; Arasu, M Valan; Ignacimuthu, S

    2014-11-01

    Streptomyces sp. isolate ERI-26 was obtained from the Nilgiris forest soil of Western Ghats, Tamil Nadu, India. Novel anthraquinone compound was isolated from the active fraction 5; it was identified by spectroscopical data using UV, IR, NMR and MASS. The isolated compound 1,5,7-trihydroxy-3-hydroxy methyl anthraquinone was tested against bacteria and fungi at minimum inhibitory concentration level. The compound showed significant antimicrobial activity against bacteria, Staphylococcus aureus at 125 μg/ml, Staphylococcus epidermidis at 62.5 μg/m, Bacillus subtilis at 31.25 μg/ml, fungi; Epidermophyton floccosum at 62.5 μg/ml, Aspergillus niger at 31.25 μg/ml, Aspergiller flavus at 31.25 μg/ml, Trichophyton rubrum at 62.5 μg/ml and Botrytis cinerea at 62.5 μg/ml. The isolated compound was subjected to molecular docking studies for the inhibition of TtgR, topoisomerase IV and AmpC β-lactamase enzymes which are targets for antimicrobials. Docking studies of the compound showed low docking energy indicating its usefulness as antimicrobial agent. 1,5,7-Trihydroxy-3-hydroxy methyl anthraquinone is new, and its antimicrobial and molecular docking properties are reported for the first time.

  1. Structural and Molecular Characterization of meso-Substituted Zinc Porphyrins: A DFT Supported Study

    Directory of Open Access Journals (Sweden)

    Giuseppe Mele

    2011-12-01

    Full Text Available Structural parameters of a range of over 100 meso-substituted zinc porphyrins were reviewed and compared to show how far the nature of the functional group may affect the interatomic distances and bond angles within the porphyrin core. It was proved that even despite evident deformations of the molecular structure, involving twisting of the porphyrin's central plane, the coupled π-bonding system remains flexible and stable. DFT calculations were applied to a number of selected porphyrins representative for the reviewed compounds to emphasize the relevance of theoretical methods in structural investigations of complex macrocyclic molecular systems. Experimental and DFT-simulated IR spectral data were reported and analyzed in context of the individual molecular features introduced by the meso substituents into the porphyrin moiety base. Raw experimental spectral data, including 1H- and 13C-NMR, UV-Vis, FTIR, XRD, and other relevant physicochemical details have been provided for a specially chosen reference zinc porphyrin functionalized by tert-butylphenyl groups.

  2. Observations of HC3N, HC5N, and HC7N in molecular clouds

    International Nuclear Information System (INIS)

    Snell, R.L.; Schloerb, F.P.; Young, J.S.; Hjalmarson, A.; Friberg, P.

    1981-01-01

    We present observations of HC 3 N, HC 5 N, and HC 7 N in five molecular clouds. Statistical equilibrium calculations have been performed for HC 5 N and HC 7 N and compared with our data and data on other transitions of these molecules reported in the literature to derive the densities and the column densities of the cyanopolyynes in these clouds. We derive densities for TMC 1, TMC 2, and L1544 of between 1 and 4 x 10 4 cm -3 . We have found that the ratios of the cyanopolyynes in these three clouds are the following: HC 3 N/HC 5 Nroughly-equal1.4 and HC 5 N/HC 7 Nroughly-equal3. In L134 N and DR 21(OH) we have measured limits on the HC 5 N emission and find the HC 3 N/HC 5 N ratio to be substantially greater than in the three Taurus clouds. We have also compared the cyanopolyyne column densities with those of 13 CO and find that the abundance of HC 3 N in L134 N and DR 21(OH) is an order of magnitude smaller than that found in the Taurus clouds. The chemical differences between L134 N and the Taurus clouds are particularly interesting in view of their similar physical properties

  3. The physical map of wheat chromosome 5DS revealed gene duplications and small rearrangements

    Czech Academy of Sciences Publication Activity Database

    Akpinar, B.A.; Magni, F.; Yuce, M.; Lucas, S. J.; Šimková, Hana; Šafář, Jan; Vautrin, S.; Berges, H.; Cattonaro, F.; Doležel, Jaroslav; Budak, H.

    2015-01-01

    Roč. 16, JUN 13 (2015) ISSN 1471-2164 R&D Projects: GA ČR GBP501/12/G090; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Triticum aestivum * 5DS * Hexaploid wheat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.867, year: 2015

  4. Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.

    Science.gov (United States)

    Mariño-Enríquez, Adrián; Bovée, Judith V M G

    2016-09-01

    Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. H ii REGION G46.5-0.2: THE INTERPLAY BETWEEN IONIZING RADIATION, MOLECULAR GAS, AND STAR FORMATION

    International Nuclear Information System (INIS)

    Paron, S.; Ortega, M. E.; Dubner, G.; Petriella, A.; Giacani, E.; Yuan, Jing-Hua; Li, Jin Zeng; Liu, Hongli; Huang, Ya Fang; Zhang, Si-Ju; Wu, Yuefang

    2015-01-01

    H ii regions are particularly interesting because they can generate dense layers of gas and dust, elongated columns or pillars of gas pointing toward the ionizing sources, and cometary globules of dense gas where triggered star formation can occur. Understanding the interplay between the ionizing radiation and the dense surrounding gas is very important to explain the origin of these peculiar structures, and hence to characterize triggered star formation. G46.5-0.2 (G46), a poorly studied galactic H ii region located at about 4 kpc, is an excellent target for performing this kind of study. Using public molecular data extracted from the Galactic Ring Survey ( 13 CO J = 1–0) and from the James Clerk Maxwell Telescope data archive ( 12 CO, 13 CO, C 18 O J = 3–2, HCO + , and HCN J = 4–3), and infrared data from the GLIMPSE and MIPSGAL surveys, we perform a complete study of G46, its molecular environment, and the young stellar objects (YSOs) placed around it. We found that G46, probably excited by an O7V star, is located close to the edge of the GRSMC G046.34-00.21 molecular cloud. It presents a horse-shoe morphology opening in the direction of the cloud. We observed a filamentary structure in the molecular gas likely related to G46 and not considerable molecular emission toward its open border. We found that about 10′ to the southwest of G46 there are some pillar-like features, shining at 8 μm and pointing toward the H ii region open border. We propose that the pillar-like features were carved and sculpted by the ionizing flux from G46. We found several YSOs likely embedded in the molecular cloud grouped in two main concentrations: one, closer to the G46 open border consisting of Class II type sources, and another mostly composed of Class I type YSOs located just ahead of the pillar-like features, strongly suggesting an age gradient in the YSO distribution

  6. H II Region G46.5-0.2: The Interplay between Ionizing Radiation, Molecular Gas, and Star Formation

    Science.gov (United States)

    Paron, S.; Ortega, M. E.; Dubner, G.; Yuan, Jing-Hua; Petriella, A.; Giacani, E.; Zeng Li, Jin; Wu, Yuefang; Liu, Hongli; Huang, Ya Fang; Zhang, Si-Ju

    2015-06-01

    H ii regions are particularly interesting because they can generate dense layers of gas and dust, elongated columns or pillars of gas pointing toward the ionizing sources, and cometary globules of dense gas where triggered star formation can occur. Understanding the interplay between the ionizing radiation and the dense surrounding gas is very important to explain the origin of these peculiar structures, and hence to characterize triggered star formation. G46.5-0.2 (G46), a poorly studied galactic H ii region located at about 4 kpc, is an excellent target for performing this kind of study. Using public molecular data extracted from the Galactic Ring Survey (13CO J = 1-0) and from the James Clerk Maxwell Telescope data archive (12CO, 13CO, C18O J = 3-2, HCO+, and HCN J = 4-3), and infrared data from the GLIMPSE and MIPSGAL surveys, we perform a complete study of G46, its molecular environment, and the young stellar objects (YSOs) placed around it. We found that G46, probably excited by an O7V star, is located close to the edge of the GRSMC G046.34-00.21 molecular cloud. It presents a horse-shoe morphology opening in the direction of the cloud. We observed a filamentary structure in the molecular gas likely related to G46 and not considerable molecular emission toward its open border. We found that about 10‧ to the southwest of G46 there are some pillar-like features, shining at 8 μm and pointing toward the H ii region open border. We propose that the pillar-like features were carved and sculpted by the ionizing flux from G46. We found several YSOs likely embedded in the molecular cloud grouped in two main concentrations: one, closer to the G46 open border consisting of Class II type sources, and another mostly composed of Class I type YSOs located just ahead of the pillar-like features, strongly suggesting an age gradient in the YSO distribution.

  7. Quantitative structure–activity relationship model for amino acids as corrosion inhibitors based on the support vector machine and molecular design

    International Nuclear Information System (INIS)

    Zhao, Hongxia; Zhang, Xiuhui; Ji, Lin; Hu, Haixiang; Li, Qianshu

    2014-01-01

    Highlights: • Nonlinear quantitative structure–activity relationship (QSAR) model was built by the support vector machine. • Descriptors for QSAR model were selected by principal component analysis. • Binding energy was taken as one of the descriptors for QSAR model. • Acidic solution and protonation of the inhibitor were considered. - Abstract: The inhibition performance of nineteen amino acids was studied by theoretical methods. The affection of acidic solution and protonation of inhibitor were considered in molecular dynamics simulation and the results indicated that the protonated amino-group was not adsorbed on Fe (1 1 0) surface. Additionally, a nonlinear quantitative structure–activity relationship (QSAR) model was built by the support vector machine. The correlation coefficient was 0.97 and the root mean square error, the differences between predicted and experimental inhibition efficiencies (%), was 1.48. Furthermore, five new amino acids were theoretically designed and their inhibition efficiencies were predicted by the built QSAR model

  8. Daughter-specific transcription factors regulate cell size control in budding yeast.

    Science.gov (United States)

    Di Talia, Stefano; Wang, Hongyin; Skotheim, Jan M; Rosebrock, Adam P; Futcher, Bruce; Cross, Frederick R

    2009-10-01

    In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1 phase of the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it has been proposed that daughter-specific, Ace2-dependent repression of expression of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted to reconcile these two divergent perspectives on the origin of long daughter G1 times. We quantified size control using single-cell time-lapse imaging of fluorescently labeled budding yeast, in the presence or absence of the daughter-specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required for efficient size control, but they shift the domain of efficient size control to larger cell size, thus increasing cell size requirement for Start in daughters. Microarray and chromatin immunoprecipitation experiments show that Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3. Quantification of cell size control in cells expressing titrated levels of Cln3 from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can account for the differential regulation of Start in response to cell size in mothers and daughters. We show how daughter-specific transcriptional programs can interact with intrinsic cell size control to differentially regulate Start in mother and daughter cells. This work demonstrates mechanistically how asymmetric localization of cell fate determinants results in cell-type-specific regulation of the cell cycle.

  9. Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast

    Science.gov (United States)

    Di Talia, Stefano; Wang, Hongyin; Skotheim, Jan M.; Rosebrock, Adam P.; Futcher, Bruce; Cross, Frederick R.

    2009-01-01

    In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1 phase of the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it has been proposed that daughter-specific, Ace2-dependent repression of expression of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted to reconcile these two divergent perspectives on the origin of long daughter G1 times. We quantified size control using single-cell time-lapse imaging of fluorescently labeled budding yeast, in the presence or absence of the daughter-specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required for efficient size control, but they shift the domain of efficient size control to larger cell size, thus increasing cell size requirement for Start in daughters. Microarray and chromatin immunoprecipitation experiments show that Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3. Quantification of cell size control in cells expressing titrated levels of Cln3 from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can account for the differential regulation of Start in response to cell size in mothers and daughters. We show how daughter-specific transcriptional programs can interact with intrinsic cell size control to differentially regulate Start in mother and daughter cells. This work demonstrates mechanistically how asymmetric localization of cell fate determinants results in cell-type-specific regulation of the cell cycle. PMID:19841732

  10. Daughter-specific transcription factors regulate cell size control in budding yeast.

    Directory of Open Access Journals (Sweden)

    Stefano Di Talia

    2009-10-01

    Full Text Available In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1 phase of the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it has been proposed that daughter-specific, Ace2-dependent repression of expression of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted to reconcile these two divergent perspectives on the origin of long daughter G1 times. We quantified size control using single-cell time-lapse imaging of fluorescently labeled budding yeast, in the presence or absence of the daughter-specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required for efficient size control, but they shift the domain of efficient size control to larger cell size, thus increasing cell size requirement for Start in daughters. Microarray and chromatin immunoprecipitation experiments show that Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3. Quantification of cell size control in cells expressing titrated levels of Cln3 from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can account for the differential regulation of Start in response to cell size in mothers and daughters. We show how daughter-specific transcriptional programs can interact with intrinsic cell size control to differentially regulate Start in mother and daughter cells. This work demonstrates mechanistically how asymmetric localization of cell fate determinants results in cell-type-specific regulation of the cell cycle.

  11. Selective Aerobic Oxidation of 5-Hydroxymethylfurfural in Water Over Solid Ruthenium Hydroxide Catalysts with Magnesium-Based Supports

    DEFF Research Database (Denmark)

    Gorbanev, Yury; Kegnæs, Søren; Riisager, Anders

    2011-01-01

    Solid catalyst systems comprised of ruthenium hydroxide supported on magnesium-based carrier materials (spinel, magnesium oxide and hydrotalcite) were investigated for the selective, aqueous aerobic oxidation of the biomass-derived chemical 5-hydroxymethylfurfural into 2,5-furandicarboxylic acid...

  12. The spectroscopic (FT-IR, FT-Raman, dispersive Raman and NMR) study of ethyl-6-chloronicotinate molecule by combined density functional theory.

    Science.gov (United States)

    Karabacak, Mehmet; Calisir, Zuhre; Kurt, Mustafa; Kose, Etem; Atac, Ahmet

    2016-01-15

    In this study, ethyl-6-chloronicotinate (E-6-ClN) molecule is recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1) (FT-IR, FT-Raman and dispersive Raman, respectively) in the solid phase. ((1))H and ((13))C nuclear magnetic resonance (NMR) spectra are recorded in DMSO solution. The structural and spectroscopic data of the molecule are obtained for two possible isomers (S1 and S2) from DFT (B3LYP) with 6-311++G(d,p) basis set calculations. The geometry of the molecule is fully optimized, vibrational spectra are calculated and fundamental vibrations are assigned on the basis of the potential energy distribution (PED) of the vibrational modes. ((1))H and ((13))C NMR chemical shifts are calculated by using the gauge-invariant atomic orbital (GIAO) method. The electronic properties, such as excitation energies, oscillator strengths, wavelengths, HOMO and LUMO energies, are performed by time-dependent density functional theory (TD-DFT). Total and partial density of state and overlap population density of state diagrams analysis are presented for E-6-ClN molecule. Furthermore, frontier molecular orbitals (FMO), molecular electrostatic potential, and thermodynamic features are performed. In addition to these, reduced density gradient of the molecule is performed and discussed. As a conclusion, the calculated results are compared with the experimental spectra of the title compound. The results of the calculations are applied to simulate the vibrational spectra of the molecule, which show excellent agreement with the observed ones. The theoretical and tentative results will give us a detailed description of the structural and physicochemical properties of the molecule. Natural bond orbital analysis is done to have more information stability of the molecule arising from charge delocalization, and to reveal the information regarding charge transfer within the molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Molecular active plasmonics: controlling plasmon resonances with molecular machines

    KAUST Repository

    Zheng, Yue Bing

    2009-08-26

    The paper studies the molecular-level active control of localized surface plasmon resonances (LSPRs) of Au nanodisk arrays with molecular machines. Two types of molecular machines - azobenzene and rotaxane - have been demonstrated to enable the reversible tuning of the LSPRs via the controlled mechanical movements. Azobenzene molecules have the property of trans-cis photoisomerization and enable the photo-induced nematic (N)-isotropic (I) phase transition of the liquid crystals (LCs) that contain the molecules as dopant. The phase transition of the azobenzene-doped LCs causes the refractive-index difference of the LCs, resulting in the reversible peak shift of the LSPRs of the embedded Au nanodisks due to the sensitivity of the LSPRs to the disks\\' surroundings\\' refractive index. Au nanodisk array, coated with rotaxanes, switches its LSPRs reversibly when it is exposed to chemical oxidants and reductants alternatively. The correlation between the peak shift of the LSPRs and the chemically driven mechanical movement of rotaxanes is supported by control experiments and a time-dependent density functional theory (TDDFT)-based, microscopic model.

  14. Molecular active plasmonics: controlling plasmon resonances with molecular machines

    KAUST Repository

    Zheng, Yue Bing; Yang, Ying-Wei; Jensen, Lasse; Fang, Lei; Juluri, Bala Krishna; Flood, Amar H.; Weiss, Paul S.; Stoddart, J. Fraser; Huang, Tony Jun

    2009-01-01

    The paper studies the molecular-level active control of localized surface plasmon resonances (LSPRs) of Au nanodisk arrays with molecular machines. Two types of molecular machines - azobenzene and rotaxane - have been demonstrated to enable the reversible tuning of the LSPRs via the controlled mechanical movements. Azobenzene molecules have the property of trans-cis photoisomerization and enable the photo-induced nematic (N)-isotropic (I) phase transition of the liquid crystals (LCs) that contain the molecules as dopant. The phase transition of the azobenzene-doped LCs causes the refractive-index difference of the LCs, resulting in the reversible peak shift of the LSPRs of the embedded Au nanodisks due to the sensitivity of the LSPRs to the disks' surroundings' refractive index. Au nanodisk array, coated with rotaxanes, switches its LSPRs reversibly when it is exposed to chemical oxidants and reductants alternatively. The correlation between the peak shift of the LSPRs and the chemically driven mechanical movement of rotaxanes is supported by control experiments and a time-dependent density functional theory (TDDFT)-based, microscopic model.

  15. Light-Powered Molecular Engineering

    DEFF Research Database (Denmark)

    Neves Petersen, Teresa; Crookshanks, Meg; Skovsen, Esben

    2007-01-01

    We present a new photonic technology and demonstrate that it allows for precise immobilisation of biomolecules to sensor surfaces. The technology secures spatially controlled molecular immobilisation since immobilisation of each molecule to a support surface can be limited to the focal point of t...

  16. Molecular Simulation and Biochemical Studies Support an Elevator-type Transport Mechanism in EIIC.

    Science.gov (United States)

    Lee, Jumin; Ren, Zhenning; Zhou, Ming; Im, Wonpil

    2017-06-06

    Enzyme IIC (EIIC) is a membrane-embedded sugar transport protein that is part of the phosphoenolpyruvate-dependent phosphotransferases. Crystal structures of two members of the glucose EIIC superfamily, bcChbC in the inward-facing conformation and bcMalT in the outward-facing conformation, were previously solved. Comparing the two structures led us to the hypothesis that sugar translocation could be achieved by an elevator-type transport mechanism in which a transport domain binds to the substrate and, through rigid body motions, transports it across the membrane. To test this hypothesis and to obtain more accurate descriptions of alternate conformations of the two proteins, we first performed collective variable-based steered molecular dynamics (CVSMD) simulations starting with the two crystal structures embedded in model lipid bilayers, and steered their transport domain toward their own alternative conformation. Our simulations show that large rigid-body motions of the transport domain (55° in rotation and 8 Å in translation) lead to access of the substrate binding site to the alternate side of the membrane. H-bonding interactions between the sugar and the protein are intact, although the side chains of the binding-site residues were not restrained in the simulation. Pairs of residues in bcMalT that are far apart in the crystal structure become close to each other in the simulated model. Some of these pairs can be cross-linked by a mercury ion when mutated to cysteines, providing further support for the CVSMD-generated model. In addition, bcMalT binds to maltose with similar affinities before and after the cross-linking, suggesting that the binding site is preserved after the conformational change. In combination, these results support an elevator-type transport mechanism in EIIC. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. A Coupling Tool for Parallel Molecular Dynamics-Continuum Simulations

    KAUST Repository

    Neumann, Philipp; Tchipev, Nikola

    2012-01-01

    We present a tool for coupling Molecular Dynamics and continuum solvers. It is written in C++ and is meant to support the developers of hybrid molecular - continuum simulations in terms of both realisation of the respective coupling algorithm

  18. Lambda hyperon production and polarization in collisions of p(3.5 GeV)+Nb

    Czech Academy of Sciences Publication Activity Database

    Agakishiev, G.; Arnold, O.; Balanda, A.; Belver, D.; Belyaev, A. V.; Berger-Chen, J. C.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Chernenko, S.; Dybczak, A.; Epple, E.; Fabbietti, L.; Krása, Antonín; Křížek, Filip; Kugler, Andrej; Sobolev, Yuri, G.; Tlustý, Pavel; Wagner, Vladimír

    2014-01-01

    Roč. 50, č. 5 (2014), s. 81 ISSN 1434-6001 R&D Projects: GA ČR GA13-06759S; GA MŠk LG14004 Institutional support: RVO:61389005 Keywords : heavy ion collisions * HADES * spectrometer Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.736, year: 2014

  19. Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

    Science.gov (United States)

    Röser, Claudia; Jordan, Nadine; Balfanz, Sabine; Baumann, Arnd; Walz, Bernd; Baumann, Otto; Blenau, Wolfgang

    2012-01-01

    Secretion in blowfly (Calliphora vicina) salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT), which activates both inositol 1,4,5-trisphosphate (InsP(3))/Ca(2+) and cyclic adenosine 3',5'-monophosphate (cAMP) signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7) that share high similarity with mammalian 5-HT(2) and 5-HT(7) receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+)] in a dose-dependent manner (EC(50) = 24 nM). In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i) (EC(50) = 4 nM). We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α) or Cv5-HT(7) in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM) activates only the Cv5-HT(2α) receptor, 5-carboxamidotryptamine (300 nM) activates only the Cv5-HT(7) receptor, and clozapine (1 µM) antagonizes the effects of 5-HT via Cv5-HT(7) in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+)- and cAMP-signalling cascades.

  20. Molecular and pharmacological characterization of serotonin 5-HT2α and 5-HT7 receptors in the salivary glands of the blowfly Calliphora vicina.

    Directory of Open Access Journals (Sweden)

    Claudia Röser

    Full Text Available Secretion in blowfly (Calliphora vicina salivary glands is stimulated by the biogenic amine serotonin (5-hydroxytryptamine, 5-HT, which activates both inositol 1,4,5-trisphosphate (InsP(3/Ca(2+ and cyclic adenosine 3',5'-monophosphate (cAMP signalling pathways in the secretory cells. In order to characterize the signal-inducing 5-HT receptors, we cloned two cDNAs (Cv5-ht2α, Cv5-ht7 that share high similarity with mammalian 5-HT(2 and 5-HT(7 receptor genes, respectively. RT-PCR demonstrated that both receptors are expressed in the salivary glands and brain. Stimulation of Cv5-ht2α-transfected mammalian cells with 5-HT elevates cytosolic [Ca(2+] in a dose-dependent manner (EC(50 = 24 nM. In Cv5-ht7-transfected cells, 5-HT produces a dose-dependent increase in [cAMP](i (EC(50 = 4 nM. We studied the pharmacological profile for both receptors. Substances that appear to act as specific ligands of either Cv5-HT(2α or Cv5-HT(7 in the heterologous expression system were also tested in intact blowfly salivary gland preparations. We observed that 5-methoxytryptamine (100 nM activates only the Cv5-HT(2α receptor, 5-carboxamidotryptamine (300 nM activates only the Cv5-HT(7 receptor, and clozapine (1 µM antagonizes the effects of 5-HT via Cv5-HT(7 in blowfly salivary glands, providing means for the selective activation of each of the two 5-HT receptor subtypes. This study represents the first comprehensive molecular and pharmacological characterization of two 5-HT receptors in the blowfly and permits the analysis of the physiological role of these receptors, even when co-expressed in cells, and of the modes of interaction between the Ca(2+- and cAMP-signalling cascades.

  1. High molecular weight FGF2 isoforms demonstrate canonical receptor-mediated activity and support human embryonic stem cell self-renewal

    Directory of Open Access Journals (Sweden)

    Denis Kole

    2017-05-01

    Full Text Available Basic fibroblast growth factor (FGF2 is a highly pleiotropic member of a large family of growth factors with a broad range of activities, including mitogenesis and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006, and it is known to be essential for maintenance of balance between survival, proliferation, and self-renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon et al., 2011. A single FGF2 transcript can be translated into five FGF2 protein isoforms, an 18 kDa low molecular weight (LMW isoform and four larger high molecular weight (HMW isoforms (Arese et al., 1999; Arnaud et al., 1999. As they are not generally secreted, high molecular weight (HMW FGF2 isoforms have predominantly been investigated intracellularly; only a very limited number of studies have investigated their activity as extracellular factors. Here we report over-expression, isolation, and biological activity of all recombinant human FGF2 isoforms. We show that HMW FGF2 isoforms can support self-renewal of human embryonic stem cells (hESCs in vitro. Exogenous supplementation with HMW FGF2 isoforms also activates the canonical FGFR/MAPK pathway and induces mitogenic activity in a manner similar to that of the 18 kDa FGF2 isoform. Though all HMW isoforms, when supplemented exogenously, are able to recapitulate LMW FGF2 activity to some degree, it appears that certain isoforms tend to do so more poorly, demonstrating a lesser functional response by several measures. A better understanding of isoform-specific FGF2 effects will lead to a better understanding of developmental and pathological FGF2 signaling.

  2. Activation of p53 pathway by Nutlin-3a inhibits the expression of the therapeutic target alpha 5 integrin in colon cancer cells

    Czech Academy of Sciences Publication Activity Database

    Janoušková, Hana; Ray, A.M.; Noulet, F.; Lelong-Rebel, I.; Choulier, L.; Schaffner, F.; Lehmann, M.; Martin, S.; Teisinger, Jan; Dontenwill, M.

    2013-01-01

    Roč. 336, č. 2 (2013), s. 307-318 ISSN 0304-3835 Institutional support: RVO:67985823 Keywords : colon cancer * integrin alpha 5 beta 1 * p53 * Nutlin-3a Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.016, year: 2013

  3. A molecular phylogenetic appraisal of the acanthostomines Acanthostomum and Timoniella and their position within Cryptogonimidae (Trematoda: Opisthorchioidea).

    Science.gov (United States)

    Martínez-Aquino, Andrés; Vidal-Martínez, Victor M; Aguirre-Macedo, M Leopoldina

    2017-01-01

    The phylogenetic position of three taxa from two trematode genera, belonging to the subfamily Acanthostominae (Opisthorchioidea: Cryptogonimidae), were analysed using partial 28S ribosomal DNA (Domains 1-2) and internal transcribed spacers (ITS1-5.8S-ITS2). Bayesian inference and Maximum likelihood analyses of combined 28S rDNA and ITS1 + 5.8S + ITS2 sequences indicated the monophyly of the genus Acanthostomum ( A. cf. americanum and A. burminis ) and paraphyly of the Acanthostominae . These phylogenetic relationships were consistent in analyses of 28S alone and concatenated 28S + ITS1 + 5.8S + ITS2 sequences analyses. Based on molecular phylogenetic analyses, the subfamily Acanthostominae is therefore a paraphyletic taxon, in contrast with previous classifications based on morphological data. Phylogenetic patterns of host specificity inferred from adult stages of other cryptogonimid taxa are also well supported. However, analyses using additional genera and species are necessary to support the phylogenetic inferences from this study. Our molecular phylogenetic reconstruction linked two larval stages of A. cf. americanum cercariae and metacercariae. Here, we present the evolutionary and ecological implications of parasitic infections in freshwater and brackish environments.

  4. A molecular phylogenetic appraisal of the acanthostomines Acanthostomum and Timoniella and their position within Cryptogonimidae (Trematoda: Opisthorchioidea

    Directory of Open Access Journals (Sweden)

    Andrés Martínez-Aquino

    2017-12-01

    Full Text Available The phylogenetic position of three taxa from two trematode genera, belonging to the subfamily Acanthostominae (Opisthorchioidea: Cryptogonimidae, were analysed using partial 28S ribosomal DNA (Domains 1–2 and internal transcribed spacers (ITS1–5.8S–ITS2. Bayesian inference and Maximum likelihood analyses of combined 28S rDNA and ITS1 + 5.8S + ITS2 sequences indicated the monophyly of the genus Acanthostomum (A. cf. americanum and A. burminis and paraphyly of the Acanthostominae. These phylogenetic relationships were consistent in analyses of 28S alone and concatenated 28S + ITS1 + 5.8S + ITS2 sequences analyses. Based on molecular phylogenetic analyses, the subfamily Acanthostominae is therefore a paraphyletic taxon, in contrast with previous classifications based on morphological data. Phylogenetic patterns of host specificity inferred from adult stages of other cryptogonimid taxa are also well supported. However, analyses using additional genera and species are necessary to support the phylogenetic inferences from this study. Our molecular phylogenetic reconstruction linked two larval stages of A. cf. americanum cercariae and metacercariae. Here, we present the evolutionary and ecological implications of parasitic infections in freshwater and brackish environments.

  5. Isotopic and molecular fractionation in combustion; three routes to molecular marker validation, including direct molecular 'dating' (GC/AMS)

    Science.gov (United States)

    Currie, L. A.; Klouda, G. A.; Benner, B. A.; Garrity, K.; Eglinton, T. I.

    The identification of unique isotopic, elemental, and molecular markers for sources of combustion aerosol has growing practical importance because of the potential effects of fine particle aerosol on health, visibility and global climate. It is urgent, therefore, that substantial efforts be directed toward the validation of assumptions involving the use of such tracers for source apportionment. We describe here three independent routes toward carbonaceous aerosol molecular marker identification and validation: (1) tracer regression and multivariate statistical techniques applied to field measurements of mixed source, carbonaceous aerosols; (2) a new development in aerosol 14C metrology: direct, pure compound accelerator mass spectrometry (AMS) by off-line GC/AMS ('molecular dating'); and (3) direct observation of isotopic and molecular source emissions during controlled laboratory combustion of specific fuels. Findings from the combined studies include: independent support for benzo( ghi)perylene as a motor vehicle tracer from the first (statistical) and second (direct 'dating') studies; a new indication, from the third (controlled combustion) study, of a relation between 13C isotopic fractionation and PAH molecular fractionation, also linked with fuel and stage of combustion; and quantitative data showing the influence of both fuel type and combustion conditions on the yields of such species as elemental carbon and PAH, reinforcing the importance of exercising caution when applying presumed conservative elemental or organic tracers to fossil or biomass burning field data as in the first study.

  6. Library of molecular associations: curating the complex molecular basis of liver diseases

    Directory of Open Access Journals (Sweden)

    Maass Thorsten

    2010-03-01

    Full Text Available Abstract Background Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. Results We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Conclusion Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

  7. Report of the workshop on accelerator-based atomic and molecular science

    International Nuclear Information System (INIS)

    Meyerhof, W.E.

    1981-01-01

    This Workshop, held in New London, NH on July 27-30, 1980, had a registration of 43, representing an estimated one-third of all principal investigators in the United States in this research subfield. The workshop was organized into 5 working groups for the purpose of (1) identifying some vital physics problems which experimental and theoretical atomic and molecular science can address with current and projected techniques; (2) establishing facilities and equipment needs required to realize solutions to these problems; (3) formulating suggestions for a coherent national policy concerning this discipline; (4) assessing and projecting the manpower situation; and (5) evaluating the relations of this interdisciplinary science to other fields. Recommedations deal with equipment and operating costs for small accelerator laboratories, especially at universities; instrumentation of ion beam lines dedicated to atomic and molecular science at some large accelerators; development of low-velocity, high charge-state ion sources; synchrotron light sources; improvement or replacement of tandem van de Graaff accelerators; high-energy beam lines for atomic physics; the needs for postdoctoral support in this subfield; new accelerator development; need for representatives from atomic and molecular science on program committees for large national accelerator facilities; and the contributions the field can make to applied physics problems

  8. Exploring Ion-Ion Interactions in Aqueous Solutions by a Combination of Molecular Dynamics and Neutron Scattering

    Czech Academy of Sciences Publication Activity Database

    Kohagen, Miriam; Pluhařová, E.; Mason, Philip E.; Jungwirth, Pavel

    2015-01-01

    Roč. 6, č. 9 (2015), s. 1563-1567 ISSN 1948-7185 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : ion pairing * molecular dynamics * neutron scattering Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 8.539, year: 2015 http://pubs.acs.org/doi/pdf/10.1021/acs.jpclett.5b00060

  9. Parallel variable selection of molecular dynamics clusters as a tool for calculation of spectroscopic properties

    Czech Academy of Sciences Publication Activity Database

    Kessler, Jiří; Dračínský, Martin; Bouř, Petr

    2013-01-01

    Roč. 34, č. 5 (2013), s. 366-371 ISSN 0192-8651 R&D Projects: GA ČR GAP208/11/0105; GA MŠk(CZ) LH11033 Grant - others:GA MŠk(CZ) LM2010005 Institutional support: RVO:61388963 Keywords : molecular dynamics * clusters * density functional theory * Raman optical activity * NMR Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.601, year: 2013

  10. Paramecium putrinum (Ciliophora, Protozoa): the first insight into the variation of two DNA fragments - molecular support for the existence of cryptic species.

    Science.gov (United States)

    Tarcz, Sebastian; Rautian, Maria; Potekhin, Alexey; Sawka, Natalia; Beliavskaya, Alexandra; Kiselev, Andrey; Nekrasova, Irina; Przyboś, Ewa

    2014-04-01

    Paramecium putrinum (Claparede & Lachmann 1858) is one of the smallest (80-140 μm long) species of the genus Paramecium. Although it commonly occurs in freshwater reservoirs, no molecular studies of P. putrinum have been conducted to date. Herein we present an assessment of molecular variation in 27 strains collected from widely separated populations by using two selected DNA fragments (ITS1-5.8S-ITS2-5'LSU rDNA and COI mtDNA). Both the trees and haplotype networks reconstructed for both genome fragments show that the studied strains of P. putrinum form five main haplogroups. The mean distance between the studied strains is p-distance=0.007/0.068 (rDNA/COI) and exhibits similar variability as that between P. bursaria syngens. Based on these data, one could hypothesize that the clusters revealed in the present study may correspond to previously reported syngens and that there are at least five cryptic species within P. putrinum. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

    Science.gov (United States)

    Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

    2015-01-01

    The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

  12. New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is).

    Science.gov (United States)

    Ribaudo, Giovanni; Pagano, Mario Angelo; Bova, Sergio; Zagotto, Giuseppe

    2016-01-01

    Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). In addition to this, sildenafil and tadalafil, have also been approved for the treatment of pulmonary arterial hypertension. Due to its expression and localization in many tissues, PDE5 and its regulation has been reported to be involved in several other diseases. We aim to provide an updated overview of the emerging therapeutic applications of PDE5-Is besides ED, taking into account the latest ongoing research reports. We searched online databases (Pubmed, Reaxys, Scopus) to lay the bases for an accurate, quality criteria-based literature update. We focused our attention on most recent research reports, in particular when supported by pre-clinical and clinical data. The regulation of PDE5 may influence pathological conditions such as, among the others, heart failure, cystic fibrosis, cancer, CNS-related diseases, diabetes and dysfunctions affecting male urinary/reproductive system. Sildenafil, vardenafil, tadalafil and the other chemical entities considered PDE5-Is showed overall positive results and significant improvements in the studied disease, thus some discordant results, in particular when comparing pre-clinical and clinical data, have to be pointed out, suggesting that further insights are needed especially to assess the exact molecular pathway underlying.

  13. Photoresponsive surface molecularly imprinted polymer on ZnO nanorods for uric acid detection in physiological fluids

    International Nuclear Information System (INIS)

    Tang, Qian; Li, Zai-yong; Wei, Yu-bo; Yang, Xia; Liu, Lan-tao; Gong, Cheng-bin; Ma, Xue-bing; Lam, Michael Hon-wah; Chow, Cheuk-fai

    2016-01-01

    A photoresponsive surface molecularly imprinted polymer for uric acid in physiological fluids was fabricated through a facile and effective method using bio-safe and biocompatible ZnO nanorods as a support. The strategy was carried out by introducing double bonds on the surface of the ZnO nanorods with 3-methacryloxypropyltrimethoxysilane. The surface molecularly imprinted polymer on ZnO nanorods was then prepared by surface polymerization using uric acid as template, water-soluble 5-[(4-(methacryloyloxy)phenyl)diazenyl]isophthalic acid as functional monomer, and triethanolamine trimethacryl ester as cross-linker. The surface molecularly imprinted polymer on ZnO nanorods showed good photoresponsive properties, high recognition ability, and fast binding kinetics toward uric acid, with a dissociation constant of 3.22 × 10"−"5 M in aqueous NaH_2PO_4 buffer at pH = 7.0 and a maximal adsorption capacity of 1.45 μmol g"−"1. Upon alternate irradiation at 365 and 440 nm, the surface molecularly imprinted polymer on ZnO nanorods can quantitatively uptake and release uric acid. - Highlights: • Novel surface molecularly imprinted polymer on ZnO nanorods was synthesized. • ZnO-SMIP showed good selectivity toward uric acid in physiological fluids. • ZnO-SMIP displayed good photoresponsive properties.

  14. Photoresponsive surface molecularly imprinted polymer on ZnO nanorods for uric acid detection in physiological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Qian [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Department of Science and Environmental Studies, The Hong Kong Institute of Education (Hong Kong); Li, Zai-yong; Wei, Yu-bo; Yang, Xia; Liu, Lan-tao [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Gong, Cheng-bin, E-mail: gongcbtq@swu.edu.cn [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Ma, Xue-bing [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Lam, Michael Hon-wah [Department of Biology and Chemistry, City University of Hong Kong (Hong Kong); Chow, Cheuk-fai, E-mail: cfchow@ied.edu.hk [Department of Science and Environmental Studies, The Hong Kong Institute of Education (Hong Kong)

    2016-09-01

    A photoresponsive surface molecularly imprinted polymer for uric acid in physiological fluids was fabricated through a facile and effective method using bio-safe and biocompatible ZnO nanorods as a support. The strategy was carried out by introducing double bonds on the surface of the ZnO nanorods with 3-methacryloxypropyltrimethoxysilane. The surface molecularly imprinted polymer on ZnO nanorods was then prepared by surface polymerization using uric acid as template, water-soluble 5-[(4-(methacryloyloxy)phenyl)diazenyl]isophthalic acid as functional monomer, and triethanolamine trimethacryl ester as cross-linker. The surface molecularly imprinted polymer on ZnO nanorods showed good photoresponsive properties, high recognition ability, and fast binding kinetics toward uric acid, with a dissociation constant of 3.22 × 10{sup −5} M in aqueous NaH{sub 2}PO{sub 4} buffer at pH = 7.0 and a maximal adsorption capacity of 1.45 μmol g{sup −1}. Upon alternate irradiation at 365 and 440 nm, the surface molecularly imprinted polymer on ZnO nanorods can quantitatively uptake and release uric acid. - Highlights: • Novel surface molecularly imprinted polymer on ZnO nanorods was synthesized. • ZnO-SMIP showed good selectivity toward uric acid in physiological fluids. • ZnO-SMIP displayed good photoresponsive properties.

  15. Plantago lagopus B Chromosome Is Enriched in 5S rDNA-Derived Satellite DNA

    Czech Academy of Sciences Publication Activity Database

    Kumke, K.; Macas, Jiří; Fuchs, J.; Altschmied, L.; Kour, J.; Dhar, M.K.; Houben, A.

    2016-01-01

    Roč. 148, č. 1 (2016), s. 68-73 ISSN 1424-8581 R&D Projects: GA ČR GBP501/12/G090 Institutional support: RVO:60077344 Keywords : Polymorhpic A chromosome segment * Satellite repeat * Supernumerary chromosome * 5S rDNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.354, year: 2016

  16. Electric conductivity of PCl5-ZrCl4, PCl5-TaCl5, and PCl5-MoCl5 molten mixtures

    International Nuclear Information System (INIS)

    Salyulev, A.B.; Red'kin, A.A.; Moskalenko, N.I.

    1997-01-01

    When mixing individual molecular melts of PCl 5 with ZrCl 4 , TaCl 5 or with MoCl 5 , an essential (by several orders) increase in electric conductivity (up to 0.02-0.1 Ohm -1 ·cm -1 ), which stems, in all probability, from the appearance of complex ions PCl 4 + , ZrCl 5 - , ZrCl 6 2- , TaCl 5 - and MoCl 6 - in the molten mixtures as a result of chemical interaction

  17. Wood burning pollution in southern Chile: PM2.5 source apportionment using CMB and molecular markers.

    Science.gov (United States)

    Villalobos, Ana M; Barraza, Francisco; Jorquera, Héctor; Schauer, James J

    2017-06-01

    Temuco is a mid-size city representative of severe wood smoke pollution in southern Chile; i.e., ambient 24-h PM 2.5 concentrations have exceeded 150 μg/m 3 in the winter season and the top concentration reached 372 μg/m 3 in 2010. Annual mean concentrations have decreased but are still above 30 μg/m 3 . For the very first time, a molecular marker source apportionment of ambient organic carbon (OC) and PM 2.5 was conducted in Temuco. Primary resolved sources for PM 2.5 were wood smoke (37.5%), coal combustion (4.4%), diesel vehicles (3.3%), dust (2.2%) and vegetative detritus (0.7%). Secondary inorganic PM 2.5 (sulfates, nitrates and ammonium) contributed 4.8% and unresolved organic aerosols (generated from volatile emissions from incomplete wood combustion), including secondary organic aerosols, contributed 47.1%. Adding the contributions of unresolved organic aerosols to those from primary wood smoke implies that wood burning is responsible for 84.6% of the ambient PM 2.5 in Temuco. This predominance of wood smoke is ultimately due to widespread poverty and a lack of efficient household heating methods. The government has been implementing emission abatement policies but achieving compliance with ambient air quality standards for PM 2.5 in southern Chile remains a challenge. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Prediction of hourly PM2.5 using a space-time support vector regression model

    Science.gov (United States)

    Yang, Wentao; Deng, Min; Xu, Feng; Wang, Hang

    2018-05-01

    Real-time air quality prediction has been an active field of research in atmospheric environmental science. The existing methods of machine learning are widely used to predict pollutant concentrations because of their enhanced ability to handle complex non-linear relationships. However, because pollutant concentration data, as typical geospatial data, also exhibit spatial heterogeneity and spatial dependence, they may violate the assumptions of independent and identically distributed random variables in most of the machine learning methods. As a result, a space-time support vector regression model is proposed to predict hourly PM2.5 concentrations. First, to address spatial heterogeneity, spatial clustering is executed to divide the study area into several homogeneous or quasi-homogeneous subareas. To handle spatial dependence, a Gauss vector weight function is then developed to determine spatial autocorrelation variables as part of the input features. Finally, a local support vector regression model with spatial autocorrelation variables is established for each subarea. Experimental data on PM2.5 concentrations in Beijing are used to verify whether the results of the proposed model are superior to those of other methods.

  19. TPR investigations on the reducibility of Cu supported on Al2O3, zeolite Y and SAPO-5

    International Nuclear Information System (INIS)

    Hoang, Dang Lanh; Dang, Thi Thuy Hanh; Engeldinger, Jana; Schneider, Matthias; Radnik, Joerg; Richter, Manfred; Martin, Andreas

    2011-01-01

    Reducibility of Cu supported on Al 2 O 3 , zeolite Y and silicoaluminophosphate SAPO-5 has been investigated in dependence on the Cu content using a method combining conventional temperature programmed reduction (TPR) by hydrogen with reoxidation in N 2 O followed by a second the so-called surface-TPR (s-TPR). The method enables discrimination and a quantitative estimation of the Cu oxidation states +2, +1 and 0. The quantitative results show that the initial oxidation state of Cu after calcination in air at 400 deg. C, independent on the nature of the support, is predominantly +2. Cu 2+ supported on Al 2 O 3 is quantitatively reduced by hydrogen to metallic Cu 0 . Comparing the TPR of the samples calcined in air and that of samples additionally pre-treated in argon reveals that in zeolite Y and SAPO-5 Cu 2+ cations are stabilized as weakly and strongly forms. In both systems, strongly stabilized Cu 2+ ions are not auto-reduced by pre-treatment in argon at 650 deg. C, but are reduced in hydrogen to form Cu + . The weakly stabilized Cu 2+ ions, in contrast, may be auto-reduced by pre-treatment in argon at 650 deg. C forming Cu + but are reduced in hydrogen to metallic Cu 0 . - Graphical Abstract: TPR, TPR-(act), s-TPR and s-TPR-(act) profiles of (1.36)Cu/SAPO-5 (A), (4.55)Cu/SAPO-5 (B) and (9.19)Cu/SAPO-5 (C) samples. The intensities of TCD signals in (A) and (B) are multiplied by 4.5 and 2, respectively. Highlights: → Cu supported on SAPO-5, alumina and zeolite Y was investigated by TPR and s-TPR. → Cu oxidation states can be discriminated and quantitatively determined. → In zeolite Y and SAPO-5 Cu 2+ cations are stabilized at weak and strong forms. → Strongly stabilized Cu 2+ cannot be auto-reduced in argon at 650 deg. C.

  20. Novel mechanism for Fc epsilon RI-mediated signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation and the selective influence of STAT5B over mast cell cytokine production

    Czech Academy of Sciences Publication Activity Database

    Pullen, N.A.; Barnstein, B.O.; Falanga, Y.T.; Wang, Z.Q.; Suzuki, R.; Tamang, T.D.L.; Khurana, M.C.; Harry, E.A.; Dráber, Petr; Bunting, K.D.; Mizuno, K.; Wilson, B.S.; Ryan, J.J.

    2012-01-01

    Roč. 287, č. 3 (2012), s. 2045-2054 ISSN 0021-9258 R&D Projects: GA MŠk 1M0506; GA ČR GAP302/10/1759; GA ČR GA301/09/1826 Grant - others:NIH(US) 1R01AI59638; NIH(US) R01DK059380; NIH(US) AI051575; NIH(US) GM065794; VCU(US) U19A1077435 Institutional support: RVO:68378050 Keywords : cytokine induction * STAT transcription factor * mast cell * Fyn kinase * STAT5 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.651, year: 2012

  1. Centrality dependence of charged jet production in p–Pb collisions at root s(NN)=5.02 TeV

    Czech Academy of Sciences Publication Activity Database

    Adam, J.; Adamová, Dagmar; Bielčík, J.; Bielčíková, Jana; Čepila, J.; Contreras, J. G.; Eyyubova, G.; Ferencei, Jozef; Horák, D.; Křížek, Filip; Kučera, Vít; Mareš, Jiří A.; Petráček, V.; Pospíšil, Jan; Schulc, M.; Špaček, M.; Šumbera, Michal; Vaňát, Tomáš; Závada, Petr

    2016-01-01

    Roč. 76, č. 5 (2016), s. 271 ISSN 1434-6044 R&D Projects: GA MŠk(CZ) LG15052 Institutional support: RVO:68378271 ; RVO:61389005 Keywords : ALICE collaboration * heavy ion collisions * production Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders; BF - Elementary Particles and High Energy Physics (FZU-D) Impact factor: 5.331, year: 2016

  2. Outcome of childhood lupus nephritis in Saudi children

    Directory of Open Access Journals (Sweden)

    Sulaiman Mohammed Al-Mayouf

    2017-01-01

    Full Text Available Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE. All patients with childhood lupus nephritis (cLN proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD. Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI, and death related to SLE was determined. A total of 84 (72 females cLN patients with follow-up duration of 9.3 years (±5.2 were included in this study. The mean current age was 19.4 years (±5.5 and mean age at onset was 9.2 years (±2.4. The most frequent histopathological class was proliferative glomerulonephritis (64.3% followed by membranous nephritis (27.4%. The mean activity and chronicity indices were 5.9 (±3.9 and 2.9 (±2.2, respectively. Renal microthrombosis was found in 9 (10.7% patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197 and the mean protein/ creatinine ratio was 0.8 (± 1.1 while the mean total pSDI was 1.9 (±1.9 and mean renal SDI was 0.7 (±1.1. Sixteen (19% patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more

  3. H ii REGION G46.5-0.2: THE INTERPLAY BETWEEN IONIZING RADIATION, MOLECULAR GAS, AND STAR FORMATION

    Energy Technology Data Exchange (ETDEWEB)

    Paron, S.; Ortega, M. E.; Dubner, G.; Petriella, A.; Giacani, E. [Instituto de Astronomía y Física del Espacio (IAFE, CONICET-UBA), CC 67, Suc. 28, 1428 Buenos Aires (Argentina); Yuan, Jing-Hua; Li, Jin Zeng; Liu, Hongli; Huang, Ya Fang; Zhang, Si-Ju [National Astronomical Observatories, Chinese Academy of Sciences, 20 A Datun Road, Chaoyang District, Beijing 100012 (China); Wu, Yuefang, E-mail: sparon@iafe.uba.ar [Department of Astronomy, Peking University, 100871 Beijing (China)

    2015-06-15

    H ii regions are particularly interesting because they can generate dense layers of gas and dust, elongated columns or pillars of gas pointing toward the ionizing sources, and cometary globules of dense gas where triggered star formation can occur. Understanding the interplay between the ionizing radiation and the dense surrounding gas is very important to explain the origin of these peculiar structures, and hence to characterize triggered star formation. G46.5-0.2 (G46), a poorly studied galactic H ii region located at about 4 kpc, is an excellent target for performing this kind of study. Using public molecular data extracted from the Galactic Ring Survey ({sup 13}CO J = 1–0) and from the James Clerk Maxwell Telescope data archive ({sup 12}CO, {sup 13}CO, C{sup 18}O J = 3–2, HCO{sup +}, and HCN J = 4–3), and infrared data from the GLIMPSE and MIPSGAL surveys, we perform a complete study of G46, its molecular environment, and the young stellar objects (YSOs) placed around it. We found that G46, probably excited by an O7V star, is located close to the edge of the GRSMC G046.34-00.21 molecular cloud. It presents a horse-shoe morphology opening in the direction of the cloud. We observed a filamentary structure in the molecular gas likely related to G46 and not considerable molecular emission toward its open border. We found that about 10′ to the southwest of G46 there are some pillar-like features, shining at 8 μm and pointing toward the H ii region open border. We propose that the pillar-like features were carved and sculpted by the ionizing flux from G46. We found several YSOs likely embedded in the molecular cloud grouped in two main concentrations: one, closer to the G46 open border consisting of Class II type sources, and another mostly composed of Class I type YSOs located just ahead of the pillar-like features, strongly suggesting an age gradient in the YSO distribution.

  4. Molecular dosimetry based on radiation induced degradation of polyisobutylene

    International Nuclear Information System (INIS)

    Joerkov Thomsen, Kristina

    1999-01-01

    This project investigates the possibility of qualitative measurement of radiation doses through detection of changes in the average molecular weight in the polymer Polyisobutylene (PIB). Changes in molecular weight and molecular weight distribution is detected by Gel Permeation Chromatography (GPC). The aim of the project is to decide whether or not it is possible to determine a quality difference between α-radiation ( 241 Am, 5,5 MeV) and γ-radiation ( 60 Co, 1,25 MeV) in the dose range 0,5 to 10 kGy by irradiation of PIB. Irradiation with 60 Co changes the average number molecular weight M n by 12% per kGy and the average weight molecular weight M w by 23% per kGy. The presence of antioxidant in the irradiated sample inhibits a change in average molecular weight by 5% and 16% for M n and M w respectively. (au)

  5. Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice

    Czech Academy of Sciences Publication Activity Database

    Kazerounian, S.; Ciarlini, P.D.S.C.; Yuan, D.; Ghazvinian, R.; Alberich-Jorda, Meritxell; Joshi, M.; Zhang, H.; Beggs, A.H.; Gazda, H.T.

    2016-01-01

    Roč. 7, č. 1 (2016), s. 32-36 ISSN 1837-9664 R&D Projects: GA MŠk LK21307 Institutional support: RVO:68378050 Keywords : Ribosomal proteins RPL5 and RPS24 * Diamond-Blackfan anemia * Soft tissue sarcoma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.916, year: 2016

  6. Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for α₂- versus α₁-GABA(A-receptor complexes.

    Directory of Open Access Journals (Sweden)

    Henrik Sindal Jensen

    Full Text Available Clobazam (CLB, a 1,5-benzodiazepine (BZD, was FDA-approved in October 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS in patients 2 years and older. BZDs exert various CNS effects through allosteric modulation of GABAA receptors. The structurally distinct, 1,4-BZD clonazepam (CLN is also approved to treat LGS. The precise mechanisms of action and clinical efficacy of both are unknown. Data show that the GABAA α₁-subunit-selective compound zolpidem [ZOL] exhibits hypnotic/sedative effects. Conversely, data from knock-in mice carrying BZD binding site mutations suggest that the α₂ subunit mediates anticonvulsant effects, without sedative actions. Hence, the specific pattern of interactions across the GABAA receptor complexes of BZDs might be reflected in their clinical efficacies and adverse effect profiles. In this study, GABAA-receptor binding affinities of CLB, N-desmethylclobazam (N-CLB, the major metabolite of CLB, CLN, and ZOL were characterized with native receptors from rat-brain homogenates and on cloned receptors from HEK293 cells transfected with combinations of α (α₁, α₂, α₃, or α₅, β₂, and γ₂ subtypes. Our results demonstrate that CLB and N-CLB have significantly greater binding affinities for α₂- vs. α₁-receptor complexes, a difference not observed for CLN, for which no distinction between α₂ and α₁ receptors was observed. Our experiments with ZOL confirmed the high preference for α₁ receptors. These results provide potential clues to a new understanding of the pharmacologic modes of action of CLB and N-CLB.

  7. Uncovering the molecular organization of unusual highly scattered 5S rDNA: The case of Chariesterus armatus (Heteroptera).

    Science.gov (United States)

    Bardella, Vanessa Bellini; Cabral-de-Mello, Diogo Cavalcanti

    2018-03-10

    One cluster of 5S rDNA per haploid genome is the most common pattern among Heteroptera. However, in Chariesterus armatus, highly scattered signals were noticed. We isolated and characterized the entire 5S rDNA unit of C. armatus aiming to a deeper knowledge of molecular organization of the 5S rDNA among Heteroptera and to understand possible causes and consequences of 5S rDNA chromosomal spreading. For a comparative analysis, we performed the same approach in Holymenia histrio with 5S rDNA restricted to one bivalent. Multiple 5S rDNA variants were observed in both species, though they were more variable in C. armatus, with some of variants corresponding to pseudogenes. These pseudogenes suggest birth-and-death mechanism, though homogenization was also observed (concerted evolution), indicating evolution through mixed model. Association between transposable elements and 5S rDNA was not observed, suggesting spreading of 5S rDNA through other mechanisms, like ectopic recombination. Scattered organization is a rare example for 5S rDNA, and such organization in C. armatus genome could have led to the high diversification of sequences favoring their pseudogenization. Copyright © 2017. Published by Elsevier B.V.

  8. Molecularly Imprinted Polymer Waveguides for Direct Optical Detection of Low-Molecular-Weight Analytes

    Czech Academy of Sciences Publication Activity Database

    Sharma, N.; Petri, C.; Jonas, U.; Bach, M.; Tovar, G.; Mrkvová, Kateřina; Vala, Milan; Homola, Jiří; Knoll, W.; Dostálek, J.

    2014-01-01

    Roč. 215, č. 23 (2014), s. 2295-2304 ISSN 1022-1352 R&D Projects: GA ČR GBP205/12/G118 Institutional support: RVO:67985882 Keywords : Label-free biosensors * Molecularly imprinted polymers * Hydrogels Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 2.616, year: 2014

  9. Molecular and serological detection of Ehrlichia canis and Babesia vogeli in dogs in Colombia.

    Science.gov (United States)

    Vargas-Hernández, G; André, M R; Faria, J L M; Munhoz, T D; Hernandez-Rodriguez, M; Machado, R Z; Tinucci-Costa, M

    2012-05-25

    Ehrlichiosis and babesiosis are tick-borne diseases, caused mainly by Ehrlichia canis and Babesia canis, respectively, with a worldwide occurrence in dogs, whose main vector is the brown-dog tick, Rhipicephalus sanguineus. The present work aimed to detect the presence of E. canis and Babesia sp. in 91 dog blood samples in Colombia, by molecular and serological techniques. We also performed sequence alignment to indicate the identity of the parasite species infecting these animals. The present work shows the first molecular detection of E. canis and B. vogeli in dogs from Colombia. Immunoglobulin-G (IgG) antibodies to E. canis and Babesia vogeli were found in 75 (82.4%) and 47 (51.6%) sampled dogs, respectively. Thirty-seven (40.6%) and 5 (5.5%) dogs were positive in PCR for E. canis and Babesia sp., respectively. After sequencing, amplicons showed 99% of identity with isolates of E. canis and B. vogeli. The phylogenetic trees based on 16S rRNA-Anaplasmataceae sequences and 18S rRNA-piroplasmid sequences supported the identity of the found E. canis and B. vogeli DNAs, respectively. The present work shows the first molecular detection of E. canis and B. vogeli in dogs in Colombia. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Rapid and recent diversification patterns in Anseriformes birds: Inferred from molecular phylogeny and diversification analyses.

    Science.gov (United States)

    Sun, Zhonglou; Pan, Tao; Hu, Chaochao; Sun, Lu; Ding, Hengwu; Wang, Hui; Zhang, Chenling; Jin, Hong; Chang, Qing; Kan, Xianzhao; Zhang, Baowei

    2017-01-01

    The Anseriformes is a well-known and widely distributed bird order, with more than 150 species in the world. This paper aims to revise the classification, determine the phylogenetic relationships and diversification patterns in Anseriformes by exploring the Cyt b, ND2, COI genes and the complete mitochondrial genomes (mito-genomes). Molecular phylogeny and genetic distance analyses suggest that the Dendrocygna species should be considered as an independent family, Dendrocygnidae, rather than a member of Anatidae. Molecular timescale analyses suggests that the ancestral diversification occurred during the Early Eocene Climatic Optimum (58 ~ 50 Ma). Furthermore, diversification analyses showed that, after a long period of constant diversification, the median initial speciation rate was accelerated three times, and finally increased to approximately 0.3 sp/My. In the present study, both molecular phylogeny and diversification analyses results support that Anseriformes birds underwent rapid and recent diversification in their evolutionary history, especially in modern ducks, which show extreme diversification during the Plio-Pleistocene (~ 5.3 Ma). Therefore, our study support that the Plio-Pleistocene climate fluctuations are likely to have played a significant role in promoting the recent diversification for Anseriformes.

  11. Rapid and recent diversification patterns in Anseriformes birds: Inferred from molecular phylogeny and diversification analyses.

    Directory of Open Access Journals (Sweden)

    Zhonglou Sun

    Full Text Available The Anseriformes is a well-known and widely distributed bird order, with more than 150 species in the world. This paper aims to revise the classification, determine the phylogenetic relationships and diversification patterns in Anseriformes by exploring the Cyt b, ND2, COI genes and the complete mitochondrial genomes (mito-genomes. Molecular phylogeny and genetic distance analyses suggest that the Dendrocygna species should be considered as an independent family, Dendrocygnidae, rather than a member of Anatidae. Molecular timescale analyses suggests that the ancestral diversification occurred during the Early Eocene Climatic Optimum (58 ~ 50 Ma. Furthermore, diversification analyses showed that, after a long period of constant diversification, the median initial speciation rate was accelerated three times, and finally increased to approximately 0.3 sp/My. In the present study, both molecular phylogeny and diversification analyses results support that Anseriformes birds underwent rapid and recent diversification in their evolutionary history, especially in modern ducks, which show extreme diversification during the Plio-Pleistocene (~ 5.3 Ma. Therefore, our study support that the Plio-Pleistocene climate fluctuations are likely to have played a significant role in promoting the recent diversification for Anseriformes.

  12. Two Models of Magnetic Support for Photoevaporated Molecular Clouds

    International Nuclear Information System (INIS)

    Ryutov, D; Kane, J; Mizuta, A; Pound, M; Remington, B

    2004-01-01

    The thermal pressure inside molecular clouds is insufficient for maintaining the pressure balance at an ablation front at the cloud surface illuminated by nearby UV stars. Most probably, the required stiffness is provided by the magnetic pressure. After surveying existing models of this type, we concentrate on two of them: the model of a quasi-homogeneous magnetic field and the recently proposed model of a ''magnetostatic turbulence''. We discuss observational consequences of the two models, in particular, the structure and the strength of the magnetic field inside the cloud and in the ionized outflow. We comment on the possible role of reconnection events and their observational signatures. We mention laboratory experiments where the most significant features of the models can be tested

  13. Adolescent Loneliness and the Interaction between the Serotonin Transporter Gene (5-HTTLPR and Parental Support: A Replication Study.

    Directory of Open Access Journals (Sweden)

    Annette W M Spithoven

    Full Text Available Gene-by-environment interaction (GxEs studies have gained popularity over the last decade, but the robustness of such observed interactions has been questioned. The current study contributes to this debate by replicating the only study on the interaction between the serotonin transporter gene (5-HTTLPR and perceived parental support on adolescents' peer-related loneliness. A total of 1,111 adolescents (51% boys with an average age of 13.70 years (SD = 0.93 participated and three annual waves of data were collected. At baseline, adolescent-reported parental support and peer-related loneliness were assessed and genetic information was collected. Assessment of peer-related loneliness was repeated at Waves 2 and 3. Using a cohort-sequential design, a Latent Growth Curve Model was estimated. Overall, a slight increase of loneliness over time was found. However, the development of loneliness over time was found to be different for boys and girls: girls' levels of loneliness increased over time, whereas boys' levels of loneliness decreased. Parental support was inversely related to baseline levels of loneliness, but unrelated to change of loneliness over time. We were unable to replicate the main effect of 5-HTTLPR or the 5-HTTLPR x Support interaction effect. In the Discussion, we examine the implications of our non-replication.

  14. Crystallography and Molecular Arrangement of Polymorphic Monolayer J-Aggregates of a Cyanine Dye: Multiangle Polarized Light Fluorescence Optical Microscopy Study.

    Science.gov (United States)

    Prokhorov, Valery V; Pozin, Sergey I; Perelygina, Olga M; Mal'tsev, Eugene I

    2018-04-24

    The molecular orientation in monolayer J-aggregates of 3,3-di(γ-sulfopropyl)-5,5-dichlorotiamonomethinecyanine dye has been precisely estimated using improved linear polarization measurements in the fluorescence microscope in which a multiangle set of polarization data is obtained using sample rotation. The estimated molecular orientation supplemented with the previously established crystallographic constraints based on the analysis of the well-developed two-dimensional J-aggregate shapes unambiguously indicate the staircase type of molecular arrangement for striplike J-aggregates with the staircases oriented along strips. The molecular transition dipoles are inclined at an angle of ∼25° to the strip direction, whereas the characteristic strip vertex angle ∼45° is formed by the [100] and [1-10] directions of the monoclinic unit cell. Measurements of the geometry of partially unwound tubes and their polarization properties support the model of tube formation by close-packed helical winding of flexible monolayer strips. In the tubes, the long molecular axes are oriented at a small angle in the range of 5-15° to the normal to the tube axis providing low bending energy. At a nanoscale, high-resolution atomic force microscopy imaging of J-aggregate monolayers reveals a complex quasi-one-dimensional organization.

  15. [Towards a molecular psychiatry].

    Science.gov (United States)

    de la Fuente, J R

    1988-06-01

    Recent research data from psychopharmacology, brain imaging and molecular genetics support the notion of a new psychiatric frontier: that of molecular psychiatry. Identification of different subtypes of neurotransmitter receptors and their changes in density and sensitivity in response to endogenous ligands and/or psychotropic drugs may account for the clinical expression of various behavioral phenomena, including some psychiatric disorders. Brain imaging, in particular positron-emission tomographic evaluations, are likely to change psychiatric nosology. New diagnostic elements derived from these scanners will allow to associate psychotic states to neuroreceptor changes. Molecular genetics has shown that bipolar affective disorder can be caused by a single gene. A strong linkage seems to exist between a gene locus on chromosome 11 and bipolar illness. An amyloid gene located on chromosome 21 has also been shown to be strongly related to familial Alzheimer's disease. While genetic heterogeneity limits the screening value of these findings, the powerful techniques of molecular biology have entered the field of psychiatry. Ethical issues regarding DNA immortality, gene cloning and gene therapy will strengthen this relationship.

  16. Comparison of the performance of different DFT methods in the calculations of the molecular structure and vibration spectra of serotonin (5-hydroxytryptamine, 5-HT)

    Science.gov (United States)

    Yang, Yue; Gao, Hongwei

    2012-04-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter which plays an important role in treating acute or clinical stress. The comparative performance of different density functional theory (DFT) methods at various basis sets in predicting the molecular structure and vibration spectra of serotonin was reported. The calculation results of different methods including mPW1PW91, HCTH, SVWN, PBEPBE, B3PW91 and B3LYP with various basis sets including LANL2DZ, SDD, LANL2MB, 6-31G, 6-311++G and 6-311+G* were compared with the experimental data. It is remarkable that the SVWN/6-311++G and SVWN/6-311+G* levels afford the best quality to predict the structure of serotonin. The results also indicate that PBEPBE/LANL2DZ level show better performance in the vibration spectra prediction of serotonin than other DFT methods.

  17. Characteristics of supported nano-TiO2/ZSM-5/silica gel (SNTZS): Photocatalytic degradation of phenol

    International Nuclear Information System (INIS)

    Zainudin, Nor Fauziah; Abdullah, Ahmad Zuhairi; Mohamed, Abdul Rahman

    2010-01-01

    Photocatalytic degradation of phenol was investigated using the supported nano-TiO 2 /ZSM-5/silica gel (SNTZS) as a photocatalyst in a batch reactor. The prepared photocatalyst was characterized using XRD, TEM, FT-IR and BET surface area analysis. The synthesized photocatalyst composition was developed using nano-TiO 2 as the photoactive component and zeolite (ZSM-5) as the adsorbents, all supported on silica gel using colloidal silica gel binder. The optimum formulation of SNTZS catalyst was observed to be (nano-TiO 2 :ZSM-5:silica gel:colloidal silica gel = 1:0.6:0.6:1) which giving about 90% degradation of 50 mg/L phenol solution in 180 min. The SNTZS exhibited higher photocatalytic activity than that of the commercial Degussa P25 which only gave 67% degradation. Its high photocatalytic activity was due to its large specific surface area (275.7 m 2 /g), small particle size (8.1 nm), high crystalline quality of the synthesized catalyst and low electron-hole pairs recombination rate as ZSM-5 adsorbent was used. The SNTZS photocatalyst synthesized in this study also has been proven to have an excellent adhesion and reusability.

  18. Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.

    Science.gov (United States)

    Chin, Kathleen; Wieslander, Cecilia; Shi, Haolin; Balgobin, Sunil; Montoya, T Ignacio; Yanagisawa, Hiromi; Word, R Ann

    2016-01-01

    Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6-8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during

  19. Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall.

    Directory of Open Access Journals (Sweden)

    Kathleen Chin

    Full Text Available Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5 during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO mice were generated in which doxycycline (dox treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO. Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-. In controls, perineal body length (PBL and bulge increased significantly after delivery but declined to baseline values within 6-8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5

  20. Pelvic Organ Support in Animals with Partial Loss of Fibulin-5 in the Vaginal Wall

    Science.gov (United States)

    Shi, Haolin; Balgobin, Sunil; Montoya, T. Ignacio; Yanagisawa, Hiromi; Word, R. Ann

    2016-01-01

    Compromise of elastic fiber integrity in connective tissues of the pelvic floor is most likely acquired through aging, childbirth-associated injury, and genetic susceptibility. Mouse models of pelvic organ prolapse demonstrate systemic deficiencies in proteins that affect elastogenesis. Prolapse, however, does not occur until several months after birth and is thereby acquired with age or after parturition. To determine the impact of compromised levels of fibulin-5 (Fbln5) during adulthood on pelvic organ support after parturition and elastase-induced injury, tissue-specific conditional knockout (cKO) mice were generated in which doxycycline (dox) treatment results in deletion of Fbln5 in cells that utilize the smooth muscle α actin promoter-driven reverse tetracycline transactivator and tetracycline responsive element-Cre recombinase (i.e., Fbln5f/f/SMA++-rtTA/Cre+, cKO). Fbln5 was decreased significantly in the vagina of cKO mice compared with dox-treated wild type or controls (Fbln5f/f/SMA++-rtTA/Cre-/-). In controls, perineal body length (PBL) and bulge increased significantly after delivery but declined to baseline values within 6–8 weeks. Although overt prolapse did not occur in cKO animals, these transient increases in PBL postpartum were amplified and, unlike controls, parturition-induced increases in PBL (and bulge) did not recover to baseline but remained significantly increased for 12 wks. This lack of recovery from parturition was associated with increased MMP-9 and nondetectable levels of Fbln5 in the postpartum vagina. This predisposition to prolapse was accentuated by injection of elastase into the vaginal wall in which overt prolapse occurred in cKO animals, but rarely in controls. Taken together, our model system in which Fbln5 is conditionally knock-downed in stromal cells of the pelvic floor results in animals that undergo normal elastogenesis during development but lose Fbln5 as adults. The results indicate that vaginal fibulin-5 during

  1. Molecular cogs of the insect circadian clock.

    Science.gov (United States)

    Shirasu, Naoto; Shimohigashi, Yasuyuki; Tominaga, Yoshiya; Shimohigashi, Miki

    2003-08-01

    During the last five years, enormous progress has been made in understanding the molecular basis of circadian systems, mainly by molecular genetic studies using the mouse and fly. Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. These participate in transcriptional/translational feedback loops and many homologous clock-components in the fruit fly Drosophila are also expressed in mammalian clock tissues with circadian rhythms. Thus, the mechanisms of the central clock seem to be conserved across animal kingdom. However, some recent studies imply that the present widely accepted molecular models of circadian clocks may not always be supported by the experimental evidence.

  2. Involvement of phosphatidylinositol 4,5-bisphosphate in RNA polymerase I transcription

    Czech Academy of Sciences Publication Activity Database

    Yildirim, Sukriye; Castano, Enrique; Sobol, Margaryta; Philimonenko, Vlada; Dzijak, Rastislav; Venit, Tomáš; Hozák, Pavel

    2013-01-01

    Roč. 126, č. 12 (2013), s. 2730-2739 ISSN 0021-9533 R&D Projects: GA ČR GAP305/11/2232; GA ČR(CZ) GD204/09/H084; GA MŠk LC545; GA MŠk(CZ) LC06063 Grant - others:CONACYT(MX) 176598 Institutional support: RVO:68378050 Keywords : nucleolus * transcription * PIP2 * UBF * fibrillarin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.325, year: 2013

  3. Cortical GABA markers identify a molecular subtype of psychotic and bipolar disorders.

    Science.gov (United States)

    Volk, D W; Sampson, A R; Zhang, Y; Edelson, J R; Lewis, D A

    2016-09-01

    Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a 'low GABA marker' (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders. Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects. Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype. These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

  4. Influence of incorporation method of sulfated zirconia in MCM-41 molecular sieve; Influencia do metodo de incorporacao da zirconia sulfatada na peneira molecular MCM-41

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, C.E.; Santos, J.S.B.; Cavalcante, J.N.A.; Andrade, M.R.A.; Sousa, B.V., E-mail: eduardopereira.eq@gmail.com [Universidade Federal de Campina Grande (UFCG), PB (Brazil). Centro de Ciencia e Tecnologia

    2016-07-01

    Sulfated metal oxides and sulfated zirconia have attracted great attention in recent years due to its high catalytic activity. The sulfated zirconia has the function of assigning the acidic material, through the formation of Bronsted acids and Lewis sites. The incorporation of sulfated zirconia in MCM-41 molecular sieve was carried out through the techniques: dry and wet. The wet process involves the use of an excess of solution on the volume of the support pores. Therefore, the concentration of the metal precursor on the support depends on the solution concentration and the pore volume of the support. In the process of incorporating by dry, the volume of the solution containing the precursor does not exceed the pore volume of the support. After either procedure, the impregnated support must be dried in order to allow the precursor compound can be converted into a catalytically active phase. This study aims to evaluate two methods of incorporation of sulfated zirconia in the mesoporous molecular sieve MCM-41. The process of merger took for wet and dry impregnation. Through the XRD patterns it was possible to identify the presence of the hexagonal structure of the molecular sieve, as well as the tetragonal and monoclinic phases of zirconia. From the spectroscopic analysis in the infrared region to the method the wet, it was possible to identify the vibrational frequencies related to the merger of sulfated zirconia in the MCM-41 structure of the molecular sieve. (author)

  5. Deuteron NMR resolved mesogen vs. crosslinker molecular order and reorientational exchange in liquid single crystal elastomers

    Czech Academy of Sciences Publication Activity Database

    Milavec, J.; Domenici, V.; Zupančič, B.; Rešetič, A.; Bubnov, Alexej; Zalar, B.

    2016-01-01

    Roč. 18, č. 5 (2016), s. 4071-4077 ISSN 1463-9076 R&D Projects: GA ČR GA15-02843S; GA MŠk(CZ) LD14007 Grant - others:EU - ICT(XE) COST Action IC1208 Institutional support: RVO:68378271 Keywords : liquid single crystal elastomer * NMR * liquid crystal * molecular order * monomers Subject RIV: JJ - Other Materials Impact factor: 4.123, year: 2016

  6. Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient.

    Science.gov (United States)

    Talbott, Vanessa A; Yeo, Charles J; Brody, Jonathan R; Witkiewicz, Agnieszka K

    2012-07-01

    Pancreatic ductal adenocarcinoma (PDA) is rarely a survivable disease. In rare cases, separate synchronous tumors are discovered at the time of resection, while in others, patients present with a metachronous cancer after prior surgical resection. Studying molecular markers of synchronous and metachronous lesions may aid to clarify the biology of this often deadly disease. Two patients presented with synchronous tumors (each one with a tumor in the pancreatic head/neck and the other in the tail, designated patients A and B). An additional patient (patient C) underwent an R0 resection for PDA of the head and recurred 1.5 y later with PDA in the tail. Genomic DNA was laser capture microdissected (LCM) from the tumor and molecular analysis was performed. K-ras status and loss of heterozygosity (LOH) were determined from multiple specimens for each case. All samples from each patient harbored identical K-ras mutations. In patient A, the tumor at the head of the pancreas had more clonal genetic instability as reflected by LOH analysis over multiple LCM samples. Patient B had more genetic instability in the tail lesion compared with the neck. Patient C had virtually the identical molecular profile in both tumors, supporting the notion that both tumors were related. We conclude that the synchronous and metachronous tumors likely are initiated from identical precursor lesions and/or events (i.e., K-ras mutations). Future studies will need to investigate if these tumors will respond similarly to adjuvant therapies targeted against the clonal molecular events in the tumor. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Molecular-nuclear transitions

    International Nuclear Information System (INIS)

    Belyaev, V.B.; Miller, M.B.

    2007-01-01

    Full text: The spectra in some light nuclei have one interesting property. For example, in the closed vicinity of some resonance states of such nuclei as 5 He, 8 Be, 18 F, 18 Ne the thresholds exist for two- or three-body decay of those nuclei. Let us consider the lightest of the above nuclei, 5 He. The energy threshold for 5 He > d+t decay is ∼50 keV lower than the energy of 3/2 + state of 5 He nucleus. However, due to a rather large width of this state, ∼70 keV, the nuclear capture of deuterons by tritons in dtm-molecule is highly enhanced in comparison with the process of dd capture in the ddm molecule. The physical reason for the enhancement of the probability of the capture into the resonant state can be associated with a long tail of wave function of the resonant state and, accordingly, with the large value of the overlap integral determining in general the probability of the transition between two systems. Thus, one can expect the enhancement of the molecular-nuclear transitions, and this was indeed observed experimentally for the case of dtm molecule. Now, let us consider some other molecular-nuclear combinations: 18 Ne - H 2 O, 18 F - 17 OH, and 8 Be - 6 LiD molecule. With the high accuracy the energies of the above molecular systems coincide with the energies of the resonant states in the appropriate nuclei. Due to the uncertainty in the experimental nuclear data it is not known at present whether the energies of these thresholds are lower or higher of the corresponding energies of the nuclear resonances. Let us assume that the molecular energy is few keV over the energy of the nuclear resonance. Then, we will deal with a very interesting phenomenon: the molecular-nuclear complex constitutes a two level system, which in some sense is analogous to the two-level atomic system, as in a laser. The crucial difference between this one and the two-level atomic systems consists in a fact that in the molecular-nuclear case no special procedure of pumping up

  8. Electrosíntesis y caracterización de materiales moleculares a partir de derivados n-trifluorometansulfonil-1-azahexa-1,3,5-trienos.

    Directory of Open Access Journals (Sweden)

    M. E. Sánchez Vergara

    2008-01-01

    Full Text Available Actualmente existe un interés creciente en los Materiales Moleculares, ya que estos pueden presentar diferentes comportamientos eléctricos que van desde aislantes, semiconductores o bien conductores. En el presente estudio fueron sintetizados materiales de este tipo, a partir de derivados N-Trifluorometansulfonil-1-azahexa-1,3,5-trienos y K3[Cr(C2O43]•3H2O debido a que estos compuestos representan un gran interés por sus variadas aplicaciones en campos como la química analítica, además los derivados N-Trifluorometansulfonil-1-azahexa-1,3,5-trienos resultan especialmente atractivos desde el punto de vista estructural ya que en su forma neutra presentan una extensa deslocalización electrónica lo cual les confiere un comportamiento químico muy particular. En esta comunicación, se forman mediante electrosíntesis convencional y mediante electrosíntesis en el módulo de electrocristalización del microscopio de fuerza atómica (AFM, algunos materiales moleculares. Una vez obtenidos dichos materiales, se caracterizan por análisis elemental sobre superficies (SEM-EDS.Recently, molecular materials have been developed because of their electrical properties which give conductor, semiconductor, or superconductor behaviour. In this work, the synthesis of new materials formed from Ntrifluoromethanesulfonyl-1-azahexa-1, 3, 5-triene species and K3[Cr(C2O43]•3H2O is reported. NTrifluoromethanesulfonyl-1-azahexa-1,3,5-trienes compounds, which are highly functionalised pentametines, have also been studied due to its interesting physical and chemical properties. These compounds are especially interesting from a structural point of view for some reasons; in a neutral form, they show an extensive electronic delocalisation, which confers them a very particular chemical behaviour. This study is focused on the Molecular Materials preparation by means of two different electrosynthesis techniques: electrocrystallization in conventional cells, and

  9. Experimental and computational study on molecular structure and vibrational analysis of a modified biomolecule: 5-Bromo-2'-deoxyuridine

    Science.gov (United States)

    Çırak, Çağrı; Sert, Yusuf; Ucun, Fatih

    In the present study, the experimental and theoretical vibrational spectra of 5-bromo-2'-deoxyuridine were investigated. The experimental FT-IR (400-4000 cm-1) and μ-Raman spectra (100-4000 cm-1) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths and bond angles) were calculated using ab initio Hartree Fock (HF) and density functional B3LYP method with 6-31G(d), 6-31G(d,p), 6-311++G(d) and 6-311++G(d,p) basis sets by Gaussian program, for the first time. The assignments of vibrational frequencies were performed by potential energy distribution by using VEDA 4 program. The optimized geometric parameters and theoretical vibrational frequencies are compared with the corresponding experimental data and they were seen to be in a good agreement with the each other. Also, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were found.

  10. Analisis Perbandingan Teknik Support Vector Regression (SVR) Dan Decision Tree C4.5 Dalam Data Mining

    OpenAIRE

    Astuti, Yuniar Andi

    2011-01-01

    This study examines techniques Support Vector Regression and Decision Tree C4.5 has been used in studies in various fields, in order to know the advantages and disadvantages of both techniques that appear in Data Mining. From the ten studies that use both techniques, the results of the analysis showed that the accuracy of the SVR technique for 59,64% and C4.5 for 76,97% So in this study obtained a statement that C4.5 is better than SVR 097038020

  11. Experimental testing of a new integrated model of the budding yeast Start transition.

    Science.gov (United States)

    Adames, Neil R; Schuck, P Logan; Chen, Katherine C; Murali, T M; Tyson, John J; Peccoud, Jean

    2015-11-05

    The cell cycle is composed of bistable molecular switches that govern the transitions between gap phases (G1 and G2) and the phases in which DNA is replicated (S) and partitioned between daughter cells (M). Many molecular details of the budding yeast G1-S transition (Start) have been elucidated in recent years, especially with regard to its switch-like behavior due to positive feedback mechanisms. These results led us to reevaluate and expand a previous mathematical model of the yeast cell cycle. The new model incorporates Whi3 inhibition of Cln3 activity, Whi5 inhibition of SBF and MBF transcription factors, and feedback inhibition of Whi5 by G1-S cyclins. We tested the accuracy of the model by simulating various mutants not described in the literature. We then constructed these novel mutant strains and compared their observed phenotypes to the model's simulations. The experimental results reported here led to further changes of the model, which will be fully described in a later article. Our study demonstrates the advantages of combining model design, simulation, and testing in a coordinated effort to better understand a complex biological network. © 2015 Adames et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  12. Comparison of Separation of Seed Oil Triglycerides Containing Isomeric Conjugated Octadecatrienoic Acid Moieties by Reversed-Phase HPLC

    OpenAIRE

    Anh Van Nguyen; Victor Deineka; Lumila Deineka; Anh Vu Thi Ngoc

    2017-01-01

    Relative retention analysis and increment approach were applied for the comparison of triglycerides (TGs) retention of a broad set of plant seed oils with isomeric conjugated octadecatrienoic acids (CLnA) by reversed-phase HPLC for “propanol-2-acetonitrile” mobile phases and Kromasil 100-5C18 stationary phase with diode array detection (DAD) and mass spectrometric (MS) detection. The subjects of investigation were TGs of seed oils: Calendula officinalis, Catalpa ovata, Jacaranda mimosifolia, ...

  13. Drug: D07284 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07284 Drug Butanilicaine (INN) ... C13H19ClN2O D07284.gif ... Neuropsychiatric agent ... DG02030 ... Anesthetic...s ... DG01675 ... Local anesthetic ... DG01673 ... Amide type local anesthetic ... DG01675 ... Local anesthetic... ... DG01673 ... Amide type local anesthetic ATC code: N01BB05 ... CAS: 3785-21-5 PubChem: 51091621 ChEBI: 55518 ChEMBL: CHEMBL2104238 LigandBox: D07284 NIKKAJI: J8.254F ...

  14. Tick-Pathogen Ensembles: Do Molecular Interactions Lead Ecological Innovation?

    Czech Academy of Sciences Publication Activity Database

    Cabezas Cruz, Alejandro; Estrada-Peňa, A.; Rego, Ryan O. M.; de la Fuente, J.

    2017-01-01

    Roč. 7, 13 March (2017), č. článku 74. ISSN 2235-2988 Institutional support: RVO:60077344 Keywords : tick-pathogen interactions * transcriptional reprogramming * epigenetics * ecological adaptation * Anaplasma phagocytophilum Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.300, year: 2016

  15. Molecular weight characterisation of synthetic polymers

    CERN Document Server

    Holding, Steve R

    1995-01-01

    The report comprises a state-of-the-art overview of the subject of molecular weight characterisation, supported by an extensive, indexed bibliography. The bibliography contains over 400 references and abstracts, compiled from the Polymer Library.

  16. EDITORIAL: Molecular Imaging Technology

    Science.gov (United States)

    Asai, Keisuke; Okamoto, Koji

    2006-06-01

    'Molecular Imaging Technology' focuses on image-based techniques using nanoscale molecules as sensor probes to measure spatial variations of various species (molecular oxygen, singlet oxygen, carbon dioxide, nitric monoxide, etc) and physical properties (pressure, temperature, skin friction, velocity, mechanical stress, etc). This special feature, starting on page 1237, contains selected papers from The International Workshop on Molecular Imaging for Interdisciplinary Research, sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, which was held at the Sendai Mediatheque, Sendai, Japan, on 8 9 November 2004. The workshop was held as a sequel to the MOSAIC International Workshop that was held in Tokyo in 2003, to summarize the outcome of the 'MOSAIC Project', a five-year interdisciplinary project supported by Techno-Infrastructure Program, the Special Coordination Fund for Promotion of Science Technology to develop molecular sensor technology for aero-thermodynamic research. The workshop focused on molecular imaging technology and its applications to interdisciplinary research areas. More than 110 people attended this workshop from various research fields such as aerospace engineering, automotive engineering, radiotechnology, fluid dynamics, bio-science/engineering and medical engineering. The purpose of this workshop is to stimulate intermixing of these interdisciplinary fields for further development of molecular sensor and imaging technology. It is our pleasure to publish the seven papers selected from our workshop as a special feature in Measurement and Science Technology. We will be happy if this issue inspires people to explore the future direction of molecular imaging technology for interdisciplinary research.

  17. Crystal and molecular structures of benzo[4,5]imidazo[1,2-c]quinazolin-6-one and 10-carboxybenzo[4,5]imidazo[1,2-c]quinazolin-6-one: A quantum-chemical study of their tautomerism

    International Nuclear Information System (INIS)

    Koval’chukova, O. V.; Stash, A. I.; Strashnov, P. V.; Neborak, E. V.; Strashnova, S. B.; Zaitsev, B. E.

    2011-01-01

    Benzo[4,5]imidazo[1,2-c]quinazolin-6-one and 10-carboxybenzo[4,5]imidazo[1,2-c]quinazolin-6-one were isolated in the crystalline state and studied by X-ray diffraction. The crystal and molecular structures of these compounds were determined by X-ray diffraction. The energy characteristics of the tautomeric and ionic forms were calculated by the quantum-chemical PM3 method.

  18. Quantum mechanics/molecular mechanics studies on the mechanism of action of cofactor pyridoxal 5'-phosphate in ornithine 4,5-aminomutase.

    Science.gov (United States)

    Pang, Jiayun; Scrutton, Nigel S; Sutcliffe, Michael J

    2014-09-01

    A computational study was performed on the experimentally elusive cyclisation step in the cofactor pyridoxal 5'-phosphate (PLP)-dependent D-ornithine 4,5-aminomutase (OAM)-catalysed reaction. Calculations using both model systems and a combined quantum mechanics/molecular mechanics approach suggest that regulation of the cyclic radical intermediate is achieved through the synergy of the intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The captodative effect of PLP is balanced by an enzyme active site that controls the deprotonation of both the pyridine nitrogen atom (N1) and the Schiff-base nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal carboxylate and amino groups of the substrate and Arg297 and Glu81 impose substantial "strain" energy on the orientation of the cyclic intermediate to control its trajectory. In addition the "strain" energy, which appears to be sensitive to both the number of carbon atoms in the substrate/analogue and the position of the radical intermediates, may play a key role in controlling the transition of the enzyme from the closed to the open state. Our results provide new insights into several aspects of the radical mechanism in aminomutase catalysis and broaden our understanding of cofactor PLP-dependent reactions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Kinetic and structural characterization of an alternatively spliced variant of human mitochondrial 5'(3')-deoxyribonucleotidase

    Czech Academy of Sciences Publication Activity Database

    Pachl, Petr; Fábry, Milan; Veverka, Václav; Brynda, Jiří; Řezáčová, Pavlína

    2015-01-01

    Roč. 30, č. 1 (2015), 63-68 ISSN 1475-6366 R&D Projects: GA ČR GA203/09/0820; GA MŠk(CZ) LK11205 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : 5'(3')-deoxyribonucleotidase * alternative splicing * crystal structure * hydrolase * mitochondria Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.428, year: 2015

  20. TH-AB-BRA-02: Automated Triplet Beam Orientation Optimization for MRI-Guided Co-60 Radiotherapy

    International Nuclear Information System (INIS)

    Nguyen, D; Thomas, D; Cao, M; O’Connor, D; Lamb, J; Sheng, K

    2016-01-01

    Purpose: MRI guided Co-60 provides daily and intrafractional MRI soft tissue imaging for improved target tracking and adaptive radiotherapy. To remedy the low output limitation, the system uses three Co-60 sources at 120° apart, but using all three sources in planning is considerably unintuitive. We automate the beam orientation optimization using column generation, and then solve a novel fluence map optimization (FMO) problem while regularizing the number of MLC segments. Methods: Three patients—1 prostate (PRT), 1 lung (LNG), and 1 head-and-neck boost plan (H&NBoost)—were evaluated. The beamlet dose for 180 equally spaced coplanar beams under 0.35 T magnetic field was calculated using Monte Carlo. The 60 triplets were selected utilizing the column generation algorithm. The FMO problem was formulated using an L2-norm minimization with anisotropic total variation (TV) regularization term, which allows for control over the number of MLC segments. Our Fluence Regularized and Optimized Selection of Triplets (FROST) plans were compared against the clinical treatment plans (CLN) produced by an experienced dosimetrist. Results: The mean PTV D95, D98, and D99 differ by −0.02%, +0.12%, and +0.44% of the prescription dose between planning methods, showing same PTV dose coverage. The mean PTV homogeneity (D95/D5) was at 0.9360 (FROST) and 0.9356 (CLN). R50 decreased by 0.07 with FROST. On average, FROST reduced Dmax and Dmean of OARs by 6.56% and 5.86% of the prescription dose. The manual CLN planning required iterative trial and error runs which is very time consuming, while FROST required minimal human intervention. Conclusions: MRI guided Co-60 therapy needs the output of all sources yet suffers from unintuitive and laborious manual beam selection processes. Automated triplet orientation optimization is shown essential to overcome the difficulty and improves the dosimetry. A novel FMO with regularization provides additional controls over the number of MLC segments

  1. TH-AB-BRA-02: Automated Triplet Beam Orientation Optimization for MRI-Guided Co-60 Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, D; Thomas, D; Cao, M; O’Connor, D; Lamb, J; Sheng, K [Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA (United States)

    2016-06-15

    Purpose: MRI guided Co-60 provides daily and intrafractional MRI soft tissue imaging for improved target tracking and adaptive radiotherapy. To remedy the low output limitation, the system uses three Co-60 sources at 120° apart, but using all three sources in planning is considerably unintuitive. We automate the beam orientation optimization using column generation, and then solve a novel fluence map optimization (FMO) problem while regularizing the number of MLC segments. Methods: Three patients—1 prostate (PRT), 1 lung (LNG), and 1 head-and-neck boost plan (H&NBoost)—were evaluated. The beamlet dose for 180 equally spaced coplanar beams under 0.35 T magnetic field was calculated using Monte Carlo. The 60 triplets were selected utilizing the column generation algorithm. The FMO problem was formulated using an L2-norm minimization with anisotropic total variation (TV) regularization term, which allows for control over the number of MLC segments. Our Fluence Regularized and Optimized Selection of Triplets (FROST) plans were compared against the clinical treatment plans (CLN) produced by an experienced dosimetrist. Results: The mean PTV D95, D98, and D99 differ by −0.02%, +0.12%, and +0.44% of the prescription dose between planning methods, showing same PTV dose coverage. The mean PTV homogeneity (D95/D5) was at 0.9360 (FROST) and 0.9356 (CLN). R50 decreased by 0.07 with FROST. On average, FROST reduced Dmax and Dmean of OARs by 6.56% and 5.86% of the prescription dose. The manual CLN planning required iterative trial and error runs which is very time consuming, while FROST required minimal human intervention. Conclusions: MRI guided Co-60 therapy needs the output of all sources yet suffers from unintuitive and laborious manual beam selection processes. Automated triplet orientation optimization is shown essential to overcome the difficulty and improves the dosimetry. A novel FMO with regularization provides additional controls over the number of MLC segments

  2. [Screen potential CYP450 2E1 inhibitors from Chinese herbal medicine based on support vector regression and molecular docking method].

    Science.gov (United States)

    Chen, Xi; Lu, Fang; Jiang, Lu-di; Cai, Yi-Lian; Li, Gong-Yu; Zhang, Yan-Ling

    2016-07-01

    Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use. Copyright© by the Chinese Pharmaceutical Association.

  3. Progress in the molecular diagnosis of Lyme disease.

    Science.gov (United States)

    Ružić-Sabljić, Eva; Cerar, Tjaša

    2017-01-01

    Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

  4. Molecular catalysts structure and functional design

    CERN Document Server

    Gade, Lutz H

    2014-01-01

    Highlighting the key aspects and latest advances in the rapidly developing field of molecular catalysis, this book covers new strategies to investigate reaction mechanisms, the enhancement of the catalysts' selectivity and efficiency, as well as the rational design of well-defined molecular catalysts. The interdisciplinary author team with an excellent reputation within the community discusses experimental and theoretical studies, along with examples of improved catalysts, and their application in organic synthesis, biocatalysis, and supported organometallic catalysis. As a result, readers wil

  5. Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium.

    Directory of Open Access Journals (Sweden)

    Kate Lawrenson

    Full Text Available The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses.We studied 10 cases of MT-EC (containing endometrioid and serous differentiation, 5 pure low-grade endometrioid adenocarcinoma (EAC and 5 pure uterine serous carcinoma (USC. Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006, H19 (P = 0.010, HOMER2 (P = 0.009 and TNNT1 (P = 0.006. Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035.Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future.

  6. Graphene–poly(5-aminoindole) composite film as Pt catalyst support for methanol electrooxidation in alkaline medium

    International Nuclear Information System (INIS)

    Yue, Ruirui; Zhang, Qiang; Wang, Caiqin; Du, Yukou; Yang, Ping; Xu, Jingkun

    2013-01-01

    Highlights: • Electropolymerization of 5-aminoindole (AIn) in the presence of graphene (GE). • Significant catalytic effect of GE on the polymerization of AIn. • PAIn/GE/GC used as Pt catalyst support. • The enhanced catalytic activity of Pt/PAIn/GE/GC for methanol electrooxidation. -- Abstract: 5-Aminoindole (AIn) was electropolymerized on graphene (GE) modified glass carbon (GC) electrode in 0.5 M H 2 SO 4 aqueous solution containing 0.01 M AIn. Because of the catalytic effect of GE, the polymerization efficiency of AIn and the electrochemical activity of as-formed poly(5-aminoindole) (PAIn) were significantly improved on GE/GC electrode as compared to that on the bare GC electrode. The prepared PAIn/GE/GC electrode was used as substrate for Pt particle electrodeposition. SEM, EDX and Raman spectral were used to characterize the prepared electrodes. Electrocatalytic experiments demonstrate that the Pt/PAIn/GE/GC electrode possesses high catalytic activity toward methanol electrooxidation in alkaline medium, due to the good dispersion of Pt particles on PAIn/GE/GC and the electronic interactions between the metal particles and the polymer matrixes. Thus, PAIn can be a promising alternative for polymeric catalyst support in direct alcohol fuel cells

  7. Molecular pathology of bone tumours: diagnostic implications.

    Science.gov (United States)

    Puls, Florian; Niblett, Angela J; Mangham, D Chas

    2014-03-01

    Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

  8. NGLview-interactive molecular graphics for Jupyter notebooks.

    Science.gov (United States)

    Nguyen, Hai; Case, David A; Rose, Alexander S

    2018-04-01

    NGLview is a Jupyter/IPython widget to interactively view molecular structures as well as trajectories from molecular dynamics simulations. Fast and scalable molecular graphics are provided through the NGL Viewer. The widget supports showing data from the file-system, online data bases and from objects of many popular analysis libraries including mdanalysis, mdtraj, pytraj, rdkit and more. The source code is freely available under the MIT license at https://github.com/arose/nglview. Python packages are available from PyPI and bioconda. NGLview uses Python on the server-side and JavaScript on the client. The integration with Jupyter is done through the ipywidgets package. The NGL Viewer is embedded client-side to provide WebGL accelerated molecular graphics. asr.moin@gmail.com.

  9. 34 CFR 380.5 - What activities may the Secretary fund under community-based supported employment projects?

    Science.gov (United States)

    2010-07-01

    ... development, including work site modification and use of advanced learning technology for skills training. (3) On-the-job training. (4) Job placement. (5) Application of rehabilitation technology in providing... EDUCATION SPECIAL PROJECTS AND DEMONSTRATIONS FOR PROVIDING SUPPORTED EMPLOYMENT SERVICES TO INDIVIDUALS...

  10. The T. brucei TRM5 methyltransferase plays an essential role in mitochondrial protein synthesis and function

    Czech Academy of Sciences Publication Activity Database

    Paris, Z.; Horáková, Eva; Rubio, M.A.T.; Sample, P.; Fleming, I.M.C.; Armocida, S.; Lukeš, Julius; Alfonzo, J. D.

    2013-01-01

    Roč. 19, č. 5 (2013), s. 649-658 ISSN 1355-8382 R&D Projects: GA ČR(CZ) GAP305/11/2179; GA MŠk LH12104 Institutional support: RVO:60077344 Keywords : Trypanosoma * tRNA * methylation * tRNA import * mitochondrion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.622, year: 2013

  11. Inclusive dielectron spectra in p plus p collisions at 3.5 GeV kinetic beam energy

    Czech Academy of Sciences Publication Activity Database

    Agakishiev, G.; Balanda, A.; Belyaev, A.; Finocchiaro, P.; Guber, F.; Karavicheva, T.; Krása, Antonín; Křížek, Filip; Kugler, Andrej; Lapidus, K.; Markert, J.; Michel, J.; Pechenova, O.; Rustamov, A.; Sobolev, Yuri, G.; Strobele, H.; Tarantola, A.; Teilab, K.; Tlustý, Pavel; Wagner, Vladimír

    2012-01-01

    Roč. 48, č. 5 (2012), s. 1-11 ISSN 1434-6001 R&D Projects: GA MŠk LC07050; GA AV ČR IAA100480803 Institutional support: RVO:61389005 Keywords : relativistic collisions * nuclear matter * dielectron spectra * HADES Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.043, year: 2012

  12. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847 as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells

    Directory of Open Access Journals (Sweden)

    Karsono AH

    2014-06-01

    Full Text Available Agung Heru Karsono, Olivia Mayasari Tandrasasmita, Raymond R TjandrawinataSection of Molecular Pharmacology, Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, IndonesiaAbstract: DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell number. The observation revealed that DLBS4847 inhibited the growth of PC3 cells through downregulation of the 5α-reductase (5AR pathway. At the transcription level, 5AR1 and androgen-receptor gene expressions were downregulated in a dose-dependent manner. Furthermore, 5AR-1 and dihydrotestosterone expression were also downregulated at the protein level. A microarray study was also performed to see the effects of DLBS4847 on differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847 downregulated genes related to prostate growth and hypertrophy. Our results suggested that DLBS4847 could potentially become an alternative treatment for prostate disorders, such as benign prostatic hyperplasia. In this regard, DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR pathway.Keywords: DLBS4847, Curcuma mangga, 5α-reductase inhibitor, benign prostatic hyperplasia (BPH, prostate cancer

  13. Sentinel lymph node concept in oral cancer

    International Nuclear Information System (INIS)

    Hasegawa, Shogo; Omura, Ken; Harada, Hiroyuki; Shimamoto, Hiroaki; Yoshida, Yoshihiko; Uekusa, Masaru; Togawa, Takashi

    2005-01-01

    The cervical lymph node (CLN) status is one of the most important prognostic factors in oral cancer. However, the main method of addressing the CLN depends on diagnostic imaging. Sentinel lymph node (SN) biopsy combined with lymphoscintigraphy may be a minimally invasive technique that samples first-echelon lymph node to predict the need for neck dissection. Focused analysis of the SN is highly accurate in identifying metastases. In this study, we investigate the possibility of identifying the SN in oral cancer and the detection of metastases in SN by HE stain, cytokeratin IHC and cytokeratin 17 reverse transcription polymerase chain reaction (RT-PCR). Twenty-four consecutive patients who had clinically negative CLN underwent SN biopsy, followed by elective neck dissection. SNs were detected by means of mapping with isotope labeling 99m Tc-phytate. All lymph nodes were examined by conventional HE staining for evaluating metastasis. In addition, each SN was cut into multiple sections for cytokeratin IHC staining and for RT-PCR for cytokeratin 17. SNs were identified in 24 (100%) of 24 patients by lymphoscintigraphy and gamma probe. One to seven SNs were identified in each patient. Both HE and immunohistochemical staining of SN identified metastasis in 7 patients (29.2%), and the expression of cytokeratin 17 by RT-PCR of SN was positive in 8 patients (34.8%). No metastases were identified using HE, cytokeratin IHC staining in non-SNs. Neck failure has not developed in 23 (95.8%) of 24 patients. The results strongly suggest the usefulness of the SN concept in oral cancer and for better assessing the status of the CLN. (author)

  14. Structural Magnetic Resonance Imaging Data Do Not Help Support DSM-5 Autism Spectrum Disorder Category

    Science.gov (United States)

    Pina-Camacho, Laura; Villero, Sonia; Boada, Leticia; Fraguas, David; Janssen, Joost; Mayoral, Maria; Llorente, Cloe; Arango, Celso; Parellada, Mara

    2013-01-01

    This systematic review aims to determine whether or not structural magnetic resonance imaging (sMRI) data support the DSM-5 proposal of an autism spectrum disorder (ASD) diagnostic category, and whether or not classical DSM-IV autistic disorder (AD) and Asperger syndrome (AS) categories should be subsumed into it. The most replicated sMRI findings…

  15. Synthesis, physico-chemical characterization and biological activity of copper(ii and nickel(ii complexes with l-benzoyl-2-methylbenzimidazole derivatives

    Directory of Open Access Journals (Sweden)

    Podunavac-Kuzmanović Sanja O.

    2002-01-01

    Full Text Available Chlorides of copper(II and nickel(ll react with 1-benzoyl-2-methylbenzimidazole or 1-(4-chlorobenzoyl-2-methylbenzimidazole to give complexes of the type [M(LnCln(H20∙Cln (M = Cu or Ni; L = (1-benzoyl-2-methylbenzimidazole or 1-(4-chlorobenzoyl-2-methylbenzimidazole; n=O, 1 or 2. The complexes were synthesized and characterized by elemental analysis, molar conductivity magnetic susceptibility measurements and IR spectra. These studies suggest that all the complexes possess an octahedral stereochemistry. The antibacterial activity of (1-benzoyl-2-methylbenzimidazole or 1-(4-chlorobenzoyl-2-methylbenzimidazole and their complexes was evaluated against Escherichia coli and Bacillus sp.

  16. PAX5О± and PAX5ОІ mRNA expression in breast Cancer: Relation ...

    African Journals Online (AJOL)

    Manal Basyouni Ahmed

    mRNA expression of PAX5a and PAX5b in breast cancer and assessing their underlying pathological roles through ... the molecular alterations that contribute to disease initiation and ... ring growth and survival of cancer cells [3]. PAX5 is ..... and CA15-3 are prognostic parameters for different molecular subtypes of · breast ...

  17. Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

    Science.gov (United States)

    Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.

    2015-01-01

    Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906

  18. Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents.

    Science.gov (United States)

    Kumar, Parvin; Kadyan, Kulbir; Duhan, Meenakshi; Sindhu, Jayant; Singh, Vineeta; Saharan, Baljeet Singh

    2017-11-14

    Acyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively. The present work involves the design and synthesis of some novel acyl hydrazone based molecular hybrids of 1,4-dihydropyridine and pyrazole (5a-g). These molecular hybrids were synthesised by condensation of 1,4-dihydropyridin-4-yl-phenoxyacetohydrazides with differently substituted pyrazole carbaldehyde. The final compound (5) showed two conformations (the major, E, s-cis and the minor, E, s-trans) as revealed by NMR spectral data and further supported by the energy calculations (MOPAC2016 using PM7 method). All the synthesised compounds were screened for their in vitro antimalarial activities against chloroquine-sensitive malaria parasite Plasmodium falciparum (3D7) and antimicrobial activity against Gram positive bacteria i.e. Bacillus cereus, Gram negative bacteria i.e. Escherichia coli and antifungal activity against one yeast i.e. Aspergillus niger. All these compounds were found more potent than chloroquine and clotrimazole, the standard drugs. In vitro antiplasmodial IC 50 value of the most potent compound 5d was found to be 4.40 nM which is even less than all the three reference drugs chloroquine (18.7 nM), pyrimethamine (11 nM) and artimisinin (6 nM). In silico binding study of compound 5d with plasmodial cysteine protease falcipain-2 indicated the inhibition of falcipain-2 as the probable reason for the antimalarial potency of compound 5d. All the compounds had shown good to excellent antimicrobial and antifungal activities.

  19. Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China.

    Science.gov (United States)

    Du, Yingying; Chen, Mingyue; Yang, Jiayun; Jia, Yane; Han, Shufang; Holmes, Edward C; Cui, Jie

    2017-06-15

    H5N6 avian influenza virus (AIV) has posed a potential threat to public health since its emergence in China in 2013. To understand the evolution and emergence of H5N6 AIV in the avian population, we performed molecular surveillance of live poultry markets (LPMs) in Wugang Prefecture, Hunan Province, in central China, during 2014 and 2015. Wugang Prefecture is located on the Eastern Asian-Australian migratory bird flyway, and a human death due to an H5N6 virus was reported in the prefecture on 21 November 2016. In total, we sampled and sequenced the complete genomes of 175 H5N6 AIVs. Notably, our analysis revealed that H5N6 AIVs contain at least six genotypes arising from segment reassortment, including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2 and a novel NP gene that has its origins with H7N3 viruses. In addition, phylogenetic analysis revealed that genetically similar H5N6 AIVs tend to cluster according to their geographic regions of origin. These results help to reveal the evolutionary behavior of influenza viruses prior to their emergence in humans. IMPORTANCE The newly emerged H5N6 influenza A virus has caused more than 10 human deaths in China since 2013. In November 2016, a human death due to an H5N6 virus, in Wugang Prefecture, Hunan Province, was confirmed by the WHO. To better understand the evolution and emergence of H5N6 viruses, we surveyed live poultry markets (LPMs) in Wugang Prefecture before the reported human death, with a focus on revealing the diversity and genomic origins of H5N6 in birds during 2014 and 2015. In general, H5N6 viruses in this region were most closely related to H5N1 clade 2.3.4.4, with the exception of one virus with an HA gene derived from clade 2.3.2 such that it represents a novel reassortant. Clearly, the ongoing surveillance of LPMs is central to monitoring the emergence of pathogenic influenza viruses. Copyright © 2017 American Society for Microbiology.

  20. A molecular map of CQR in Mali

    Science.gov (United States)

    Djimde, Abdoulaye A.; Barger, Breanna; Kone, Aminatou; Beavogui, Abdoul H.; Tekete, Mamadou; Fofana, Bakary; Dara, Antoine; Maiga, Hamma; Dembele, Demba; Toure, Sekou; Dama, Souleymane; Ouologuem, Dinkorma; Sangare, Cheick Papa Oumar; Dolo, Amagana; Sogoba, Nofomo; Nimaga, Karamoko; Kone, Yacouba; Doumbo, Ogobara K.

    2009-01-01

    Plasmodium falciparum CQR transporter point mutation (PfCRT76T) is known to be the key determinant of CQR. Molecular detection of PfCRT76T in field samples may be used for the surveillance of CQR in the malaria endemic countries. The genotype-resistance index (GRI) which is obtained as the ratio of the prevalence of PfCRT 76T to the incidence of CQR in a clinical trial was proposed as a simple andpractical molecular-based addition to the tools currently available for monitoring CQR in the field. In order to validate the GRI model across populations, time, and resistance patterns, we compiled data from the literature and generated new data from a dozen of sites across Mali. We found a mean PfCRT76T mutation prevalence of 84.5% (range 60.9%–95.1%) across all sites. CQR rates predicted from the GRI model was extrapolated onto a map of Mali to show the patterns of resistance throughout the participating regions. We present a comprehensive map of CQR in Mali, which strongly supports recent changes in drug policy away from chloroquine. PMID:20041947

  1. Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches

    Science.gov (United States)

    Almutairi, Maha S.; Zakaria, Azza S.; Ignasius, P. Primsa; Al-Wabli, Reem I.; Joe, Isaac Hubert; Attia, Mohamed I.

    2018-02-01

    Indole-isatin molecular hybrids 5a-i have been synthesized and characterized by different spectroscopic methods to be evaluated as new antimicrobial agents against a panel of Gram positive bacteria, Gram negative bacteria, and moulds. Compound 5h was selected as a representative example of the prepared compounds 5a-i to perform computational investigations. Its vibrational properties have been studied using FT-IR and FT-Raman with the aid of density functional theory approach. The natural bond orbital analysis as well as HOMO and LUMO molecular orbitals investigations of compound 5h were carried out to explore its possible intermolecular delocalization or hyperconjugation and its possible interactions with the target protein. Molecular docking of compound 5h predicted its binding mode with the fungal target protein.

  2. Maxillary implant-supported overdentures opposed by (partial) natural dentitions : A 5-year prospective case series study

    NARCIS (Netherlands)

    Boven, G. C.; Slot, J. W. A.; Raghoebar, G. M.; Vissink, A.; Meijer, H. J. A.

    2017-01-01

    The aim of this study was to assess the 5-year treatment outcome of maxillary implant-retained overdentures opposed by natural antagonistic teeth. Fifty consecutive patients received maxillary overdentures supported by six dental implants. Implants were placed in the anterior region, if enough bone

  3. Brief Report: DSM-5 "Levels of Support:" A Comment on Discrepant Conceptualizations of Severity in ASD

    Science.gov (United States)

    Weitlauf, Amy S.; Gotham, Katherine O.; Vehorn, Alison C.; Warren, Zachary E.

    2014-01-01

    Proposed DSM-5 revisions to the diagnosis of autism spectrum disorder (ASD) include a "severity" marker based on degree of impairment. Although qualitative differences between support levels are described, quantitative methods or practice recommendations for differentiating between levels remain undetermined. This leaves the field…

  4. Molecular phylogenetic analysis supports a Gondwanan origin of the Hyriidae (Mollusca: Bivalvia: Unionida) and the paraphyly of Australasian taxa.

    Science.gov (United States)

    Graf, Daniel L; Jones, Hugh; Geneva, Anthony J; Pfeiffer, John M; Klunzinger, Michael W

    2015-04-01

    The freshwater mussel family Hyriidae (Mollusca: Bivalvia: Unionida) has a disjunct trans-Pacific distribution in Australasia and South America. Previous phylogenetic analyses have estimated the evolutionary relationships of the family and the major infra-familial taxa (Velesunioninae and Hyriinae: Hyridellini in Australia; Hyriinae: Hyriini, Castaliini, and Rhipidodontini in South America), but taxon and character sampling have been too incomplete to support a predictive classification or allow testing of biogeographical hypotheses. We sampled 30 freshwater mussel individuals representing the aforementioned hyriid taxa, as well as outgroup species representing the five other freshwater mussel families and their marine sister group (order Trigoniida). Our ingroup included representatives of all Australian genera. Phylogenetic relationships were estimated from three gene fragments (nuclear 28S, COI and 16S mtDNA) using maximum parsimony, maximum likelihood, and Bayesian inference, and we applied a Bayesian relaxed clock model calibrated with fossil dates to estimate node ages. Our analyses found good support for monophyly of the Hyriidae and the subfamilies and tribes, as well as the paraphyly of the Australasian taxa (Velesunioninae, (Hyridellini, (Rhipidodontini, (Castaliini, Hyriini)))). The Hyriidae was recovered as sister to a clade comprised of all other Recent freshwater mussel families. Our molecular date estimation supported Cretaceous origins of the major hyriid clades, pre-dating the Tertiary isolation of South America from Antarctica/Australia. We hypothesize that early diversification of the Hyriidae was driven by terrestrial barriers on Gondwana rather than marine barriers following disintegration of the super-continent. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Charge carrier transport on molecular wire controlled by dipolar species: towards light-driven molecular switch

    Czech Academy of Sciences Publication Activity Database

    Nešpůrek, Stanislav; Toman, Petr; Sworakowski, J.

    438-439, - (2003), s. 268-278 ISSN 0040-6090. [International Conference on Nano- Molecular Electronics /5./. Kobe, 10.12.2002-12.12.2002] R&D Projects: GA AV ČR KSK4050111 Keywords : molecular electronics * polymers * quantum effects Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.598, year: 2003

  6. Characteristics of supported nano-TiO{sub 2}/ZSM-5/silica gel (SNTZS): Photocatalytic degradation of phenol

    Energy Technology Data Exchange (ETDEWEB)

    Zainudin, Nor Fauziah; Abdullah, Ahmad Zuhairi [School of Chemical Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300 Nibong Tebal, Penang (Malaysia); Mohamed, Abdul Rahman, E-mail: chrahman@eng.usm.my [School of Chemical Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300 Nibong Tebal, Penang (Malaysia)

    2010-02-15

    Photocatalytic degradation of phenol was investigated using the supported nano-TiO{sub 2}/ZSM-5/silica gel (SNTZS) as a photocatalyst in a batch reactor. The prepared photocatalyst was characterized using XRD, TEM, FT-IR and BET surface area analysis. The synthesized photocatalyst composition was developed using nano-TiO{sub 2} as the photoactive component and zeolite (ZSM-5) as the adsorbents, all supported on silica gel using colloidal silica gel binder. The optimum formulation of SNTZS catalyst was observed to be (nano-TiO{sub 2}:ZSM-5:silica gel:colloidal silica gel = 1:0.6:0.6:1) which giving about 90% degradation of 50 mg/L phenol solution in 180 min. The SNTZS exhibited higher photocatalytic activity than that of the commercial Degussa P25 which only gave 67% degradation. Its high photocatalytic activity was due to its large specific surface area (275.7 m{sup 2}/g), small particle size (8.1 nm), high crystalline quality of the synthesized catalyst and low electron-hole pairs recombination rate as ZSM-5 adsorbent was used. The SNTZS photocatalyst synthesized in this study also has been proven to have an excellent adhesion and reusability.

  7. Aerobic Oxidation of 5-(Hydroxymethyl)furfural Cyclic Acetal Enables Selective Furan-2,5-dicarboxylic Acid Formation with CeO2 -Supported Gold Catalyst.

    Science.gov (United States)

    Kim, Minjune; Su, Yaqiong; Fukuoka, Atsushi; Hensen, Emiel J M; Nakajima, Kiyotaka

    2018-05-14

    The utilization of 5-(hydroxymethyl)furfural (HMF) for the large-scale production of essential chemicals has been largely limited by the formation of solid humin as a byproduct, which prevents the operation of stepwise batch-type and continuous flow-type processes. The reaction of HMF with 1,3-propanediol produces an HMF acetal derivative that exhibits excellent thermal stability. Aerobic oxidation of the HMF acetal with a CeO 2 -supported Au catalyst and Na 2 CO 3 in water gives a 90-95 % yield of furan 2,5-dicarboxylic acid, an increasingly important commodity chemical for the biorenewables industry, from concentrated solutions (10-20 wt %) without humin formation. The six-membered acetal ring suppresses thermal decomposition and self-polymerization of HMF in concentrated solutions. Kinetic studies supported by DFT calculations identify two crucial steps in the reaction mechanism, that is, the partial hydrolysis of the acetal into 5-formyl-2-furan carboxylic acid involving OH - and Lewis acid sites on CeO 2 , and subsequent oxidative dehydrogenation of the in situ generated hemiacetal involving Au nanoparticles. These results represent a significant advance over the current state of the art, overcoming an inherent limitation of the oxidation of HMF to an important monomer for biopolymer production. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Molecular marker-assisted selection for resistance to pathogens in tomato

    International Nuclear Information System (INIS)

    Barone, A.; Frusciante, L.

    2007-01-01

    Since the 1980s, the use of molecular markers has been suggested to improve the efficiency of releasing resistant varieties, thus overcoming difficulties met with classical breeding. For tomato, a high-density molecular map is available in which more than 40 resistance genes are localized. Markers linked to these genes can be used to speed up gene transfer and pyramiding. Suitable PCR markers targeting resistance genes were constructed directly on the sequences of resistance genes or on restriction fragment length polymorphisms (RFLPs) tightly linked to them, and used to select resistant genotypes in backcross schemes. In some cases, the BC 5 generation was reached, and genotypes that cumulated two homozygous resistant genes were also obtained. These results supported the feasibility of using marker-assisted selection (MAS) in tomato and reinforcing the potential of this approach for other genes, which is today also driven by the development of new techniques and increasing knowledge about the tomato genome. (author)

  9. Characterizing and sourcing ambient PM2.5 over key emission regions in China II: Organic molecular markers and CMB modeling

    Science.gov (United States)

    Zhou, Jiabin; Xiong, Ying; Xing, Zhenyu; Deng, Junjun; Du, Ke

    2017-08-01

    From November 2012 to July 2013, a sampling campaign was completed for comprehensive characterization of PM2.5 over four key emission regions in China: Beijing-Tianjin-Hebei (BTH), Yangzi River Delta (YRD), Pearl River Delta (PRD), and Sichuan Basin (SB). A multi-method approach, adopting different analytical and receptor modeling methods, was employed to determine the relative abundances of region-specific air pollution constituents and contributions of emission sources. This paper is focused on organic molecular marker based source apportionment using chemical mass balance (CMB) receptor modeling. Analyses of the organic molecular markers revealed that vehicle emission, coal combustion, biomass burning, meat cooking and natural gas combustion were the major contributors to organic carbon (OC) in PM2.5. The vehicle emission dominated the sources contributing to OC in spring at four sampling sites. During wintertime, the coal combustion had highest contribution to OC at BTH site, while the major source contributing to OC at YRD and PRD sites was vehicle emission. In addition, the relative contributions of different emission sources to PM2.5 mass at a specific location site and in a specific season revealed seasonal and spatial variations across all four sampling locations. The largest contributor to PM2.5 mass was secondary sulfate (14-17%) in winter at the four sites. The vehicle emission was found to be the major source (14-21%) for PM2.5 mass at PRD site. The secondary ammonium has minor variation (4-5%) across the sites, confirming the influences of regional emission sources on these sites. The distinct patterns of seasonal and spatial variations of source apportionment observed in this study were consistent with the findings in our previous paper based upon water-soluble ions and carbonaceous fractions. This makes it essential for the local government to make season- and region-specific mitigation strategies for abating PM2.5 pollution in China.

  10. A new species of Cacatuocotyle (Monogenea, Dactylogyridae) parasitizing Astyanax spp. (Characiformes, Characidae) from Brazil, including molecular data and a key to species identification.

    Science.gov (United States)

    Zago, Aline Cristina; Franceschini, Lidiane; Müller, Maria Isabel; Silva, Reinaldo José da

    2018-06-26

    The present study describes Cacatuocotyle papilionis n. sp. (Monogenea, Dactylogyridae) from the skin of the characid fishes Astyanax lacustris (Lütken, 1875) (=Astyanax altiparanae Garutti & Britski, 2000) and Astyanax fasciatus (Cuvier, 1819) (Characiformes, Characidae) from the Southeast of Brazil, supported by morphological and molecular data. The new species differs from all congeners, mainly due to the morphology of the ventral bar (resembling a butterfly), accessory piece, and the number of rings of the male copulatory organ (MCO), comprising a coiled tube with 4.5-5.5 counterclockwise rings. The first molecular data for this monogenean genus is provided in this study, using the partial sequences of the ribosomal gene (28S), as well as providing an identification key to the species.

  11. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Indrová, Marie; Vlková, Veronika; Bieblová, Jana; Šímová, Jana; Paračková, Zuzana; Pajtasz-Piasecka, E.; Rossowska, J.; Reiniš, Milan

    2014-01-01

    Roč. 95, č. 5 (2014), s. 743-753 ISSN 0741-5400 R&D Projects: GA ČR(CZ) GPP301/11/P220; GA ČR GAP301/10/2174 Institutional support: RVO:68378050 Keywords : arginase-1 * immunosuppression * microenvironment Subject RIV: EB - Gene tics ; Molecular Biology Impact factor: 4.289, year: 2014

  12. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Indrová, Marie; Vlková, Veronika; Bieblová, Jana; Šímová, Jana; Paračková, Zuzana; Pajtasz-Piasecka, E.; Rossowska, J.; Reiniš, Milan

    2014-01-01

    Roč. 95, č. 5 (2014), s. 743-753 ISSN 0741-5400 R&D Projects: GA ČR(CZ) GPP301/11/P220; GA ČR GAP301/10/2174 Institutional support: RVO:68378050 Keywords : arginase-1 * immunosuppression * microenvironment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.289, year: 2014

  13. Molecular robots with sensors and intelligence.

    Science.gov (United States)

    Hagiya, Masami; Konagaya, Akihiko; Kobayashi, Satoshi; Saito, Hirohide; Murata, Satoshi

    2014-06-17

    CONSPECTUS: What we can call a molecular robot is a set of molecular devices such as sensors, logic gates, and actuators integrated into a consistent system. The molecular robot is supposed to react autonomously to its environment by receiving molecular signals and making decisions by molecular computation. Building such a system has long been a dream of scientists; however, despite extensive efforts, systems having all three functions (sensing, computation, and actuation) have not been realized yet. This Account introduces an ongoing research project that focuses on the development of molecular robotics funded by MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan). This 5 year project started in July 2012 and is titled "Development of Molecular Robots Equipped with Sensors and Intelligence". The major issues in the field of molecular robotics all correspond to a feedback (i.e., plan-do-see) cycle of a robotic system. More specifically, these issues are (1) developing molecular sensors capable of handling a wide array of signals, (2) developing amplification methods of signals to drive molecular computing devices, (3) accelerating molecular computing, (4) developing actuators that are controllable by molecular computers, and (5) providing bodies of molecular robots encapsulating the above molecular devices, which implement the conformational changes and locomotion of the robots. In this Account, the latest contributions to the project are reported. There are four research teams in the project that specialize on sensing, intelligence, amoeba-like actuation, and slime-like actuation, respectively. The molecular sensor team is focusing on the development of molecular sensors that can handle a variety of signals. This team is also investigating methods to amplify signals from the molecular sensors. The molecular intelligence team is developing molecular computers and is currently focusing on a new photochemical technology for accelerating DNA

  14. Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hua; Carney, Paul J.; Mishin, Vasiliy P.; Guo, Zhu; Chang, Jessie C.; Wentworth, David E.; Gubareva, Larisa V.; Stevens, James; Schultz-Cherry, S.

    2016-04-06

    ABSTRACT

    During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015, the virus was detected in wild birds in Canada and the United States, and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North American lineages. In particular, viruses were found with N1, N2, and N8 neuraminidase vRNAs, and these are collectively referred to as H5Nx viruses. In the United States, more than 48 million domestic birds have been affected. Here we present a detailed structural and biochemical analysis of the surface antigens of H5N1, H5N2, and H5N8 viruses in addition to those of a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA-approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses and to continually assess future changes that may increase their pandemic potential.

    IMPORTANCEThe H5Nx viruses emerging in North America, Europe, and Asia pose a great public health concern. Here we report a molecular and structural study of the major surface proteins of several H5Nx influenza viruses. Our results improve the understanding of these new viruses and provide important information on their receptor preferences and susceptibilities to antivirals, which are central to pandemic risk assessment.

  15. 5-Isopropylidene-1,3-dithiolo[4,5-d][1,3]dithiole-2-thione

    Directory of Open Access Journals (Sweden)

    Yoshiro Yamashita

    2009-05-01

    Full Text Available The title compound, C7H6S5, contains a 5-ylidene-1,3-dithiolo[4,5-d][1,3]dithiole-2-thione framework, which is an important synthetic precursor of multi-dimensional organic superconductors and conductors. The molecular framework is planar with an r.m.s. deviation of 0.012 Å for the non-H atoms. In the crystal structure, molecules are linked by short intermolecular S...S interactions [3.501 (5 and 3.581 (4 Å], constructing a zigzag molecular tape network along the c axis.

  16. Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

    Science.gov (United States)

    Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

    2015-11-18

    Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Genetics Home Reference: CLN1 disease

    Science.gov (United States)

    ... a palmitoyl-protein thioesterase 1 enzyme that has a reduced level of normal function; however, protein function in these ... Uusi-Rauva K, Scifo E, Tyynelä J, Jalanko A, Braulke T. Cell biology and function of neuronal ceroid lipofuscinosis-related proteins. ...

  18. Genetics Home Reference: CLN4 disease

    Science.gov (United States)

    ... are compartments in the cell that digest and recycle materials. These accumulations occur in cells throughout the ... development. These cases occur in people with no history of the disorder in their family. Related Information ...

  19. Genetics Home Reference: CLN2 disease

    Science.gov (United States)

    ... 2016 Sep;119(1-2):160-7. doi: 10.1016/j.ymgme.2016.07.011. Epub 2016 Jul ... 2013 Mar 1;516(1):114-21. doi: 10.1016/j.gene.2012.12.058. Epub 2012 Dec ... Acta. 2013 Nov;1832(11):1801-6. doi: 10.1016/j.bbadis.2013.04.008. Epub 2013 Apr ...

  20. Coordination polyhedra CsCln in crystals

    International Nuclear Information System (INIS)

    Serezhkin, V.N.; Serezhkina, L.B.

    1999-01-01

    Characteristics of the Voronoi-Dirichlet polyhedrons are estimated for 133 crystallographic cesium atoms in chlorides Cs x M y Cl z (M=Cd, Sc, V, Nb, Mo, W, Ru, Re, etc.). It is found that cesium atoms have coordination numbers 6,8,9,10, 11 and 12 as regards the chlorine atoms. The results of cesium atom coordination sphere examination by the crossing spheres method are presented. Metal-metal interactions (including Cs-Cs) in the structure of certain chlorides are revealed

  1. Genetics Home Reference: CLN8 disease

    Science.gov (United States)

    ... about four to six times per year. By middle age, seizures become even less frequent. In addition to ... What is precision medicine? What is newborn screening? New Pages RAB18 deficiency Depression Pelizaeus-Merzbacher-like disease ...

  2. Genetics Home Reference: CLN10 disease

    Science.gov (United States)

    ... Foundation CLIMB: Children Living with Inherited Metabolic Diseases March of Dimes: Neonatal Death The ... Sources for This Page Anderson GW, Goebel HH, Simonati A. Human pathology in NCL. Biochim Biophys Acta. 2013 Nov;1832( ...

  3. Pre-clinical evaluation of AAV5-miHTT gene therapy of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Konstantinová, P.; Miniarikova, J.; Blits, B.; Zimmer, V.; Spoerl, A.; Southwell, A.; Hayden, M.; van Deventer, S.; Deglon, N.; Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Richard, Ch.; Petry, H.

    2015-01-01

    Roč. 78, Supl 2 (2015), s. 8-8 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * gene therapy * AAV5-miHTT Subject RIV: EB - Genetics ; Molecular Biology

  4. Polypropylene obtained through zeolite supported catalysts

    Directory of Open Access Journals (Sweden)

    Queli C. Bastos

    2004-01-01

    Full Text Available Propylene polymerizations were carried out with f2C(Flu(CpZrCl2 and SiMe2(Ind2ZrCl2 catalysts supported on silica, zeolite sodic mordenite (NaM and acid mordenite (HM. The polymerizations were performed at different temperatures and varying aluminium/zirconium molar ratios ([Al]/[Zr]. The effect of these reaction parameters on the catalyst activity was investigated using a proposed statistical experimental planning. In the case of f2C(Flu(CpZrCl2, SiO2 and NaM were used as support and the catalyst performance evaluated using toluene and pentane as polymerization solvent. The molecular weight, molecular weight distribution, melting point and crystallinity of the polymers were examined. The results indicate very high activities for the syndiospecific heterogeneous system. Also, the polymers obtained had superior Mw and stereoregularity.

  5. Polypropylene obtained through zeolite supported catalysts

    International Nuclear Information System (INIS)

    Bastos, Queli C.; Marques, Maria de Fatima V.

    2004-01-01

    Propylene polymerizations were carried out with φ 2 C(Flu)(Cp)ZrCl 2 and SiMe 2 (Ind)2ZrCl 2 catalysts supported on silica, zeolite sodic mordenite (NaM) and acid mordenite (HM). The polymerizations were performed at different temperatures and varying aluminium/zirconium molar ratios ([Al]/[Zr]). The effect of these reaction parameters on the catalyst activity was investigated using a proposed statistical experimental planning. In the case of f 2 C(Flu)(Cp)ZrCl 2 , SiO 2 and NaM were used as support and the catalyst performance evaluated using toluene and pentane as polymerization solvent. The molecular weight, molecular weight distribution, melting point and crystallinity of the polymers were examined. The results indicate very high activities for the syndiospecific heterogeneous system. Also, the polymers obtained had superior Mw and stereo regularity. (author)

  6. Evolutional dynamics of 45S and 5S ribosomal DNA in ancient allohexaploid Atropa belladonna.

    Science.gov (United States)

    Volkov, Roman A; Panchuk, Irina I; Borisjuk, Nikolai V; Hosiawa-Baranska, Marta; Maluszynska, Jolanta; Hemleben, Vera

    2017-01-23

    Polyploid hybrids represent a rich natural resource to study molecular evolution of plant genes and genomes. Here, we applied a combination of karyological and molecular methods to investigate chromosomal structure, molecular organization and evolution of ribosomal DNA (rDNA) in nightshade, Atropa belladonna (fam. Solanaceae), one of the oldest known allohexaploids among flowering plants. Because of their abundance and specific molecular organization (evolutionarily conserved coding regions linked to variable intergenic spacers, IGS), 45S and 5S rDNA are widely used in plant taxonomic and evolutionary studies. Molecular cloning and nucleotide sequencing of A. belladonna 45S rDNA repeats revealed a general structure characteristic of other Solanaceae species, and a very high sequence similarity of two length variants, with the only difference in number of short IGS subrepeats. These results combined with the detection of three pairs of 45S rDNA loci on separate chromosomes, presumably inherited from both tetraploid and diploid ancestor species, example intensive sequence homogenization that led to substitution/elimination of rDNA repeats of one parent. Chromosome silver-staining revealed that only four out of six 45S rDNA sites are frequently transcriptionally active, demonstrating nucleolar dominance. For 5S rDNA, three size variants of repeats were detected, with the major class represented by repeats containing all functional IGS elements required for transcription, the intermediate size repeats containing partially deleted IGS sequences, and the short 5S repeats containing severe defects both in the IGS and coding sequences. While shorter variants demonstrate increased rate of based substitution, probably in their transition into pseudogenes, the functional 5S rDNA variants are nearly identical at the sequence level, pointing to their origin from a single parental species. Localization of the 5S rDNA genes on two chromosome pairs further supports uniparental

  7. Cooperative effect by monopodal silica-supported niobium com-plexes pairs enhancing catalytic cyclic carbonate production

    KAUST Repository

    D'Elia, Valerio

    2015-05-07

    Recent discoveries highlighted the activity and the intriguing mechanistic features of NbCl5 as a molecular catalyst for the cycloaddition of CO2 and epoxides under ambient conditions. This has inspired the preparation of novel silica supported Nb-species by reacting a molecular niobium precursor [NbCl5•OEt2] with silica dehydroxylated at 700 °C (SiO2-700) or at 200 oC (SiO2-200) to generate diverse surface complexes. The product of the reaction between SiO2-700 and [NbCl5•OEt2] was identified as a monopodal supported surface species [≡SiONbCl4•OEt2] (1a). The reactions of SiO2-200 with the niobium precursor, according to two different protocols, generated surface complexes 2a and 3a presenting significant, but different, populations of the monopodal surface complex along with bipodal [(≡SiO)2NbCl3•OEt2]. 93Nb SSNMR spectra of 1a-3a and 31P SSNMR on their PMe3 derivatives (1b-3b) led to the unambiguous assignment of 1a as a single site, monopodal Nb-species while 2a and 3a were found to present two distinct surface-supported components, with 2a being mostly monopodal [≡SiONbCl4•OEt2] and 3a being mostly bipodal [≡S ONbCl3•OEt2]. Double-quantum/single-quantum 31P NMR correlation experiment carried out on 2b supported the existence of vicinal Nb centers on the silica surface for this species. 1a-3a were active heterogeneous catalysts for the synthesis of propylene carbonate from CO2 and propylene oxide under mild catalytic conditions; the performance of 2a was found to significantly surpass that of 1a and 3a. With the support of a systematic DFT study carried out on model silica surfaces, the observed differences in catalytic efficiency were correlated with an unprece-dented cooperative effect between two neighboring Nb centers on the surface of 2a. This is in an excellent agreement with our previous discoveries regarding the mechanism of the NbCl5 catalyzed cycloaddition in the homogeneous phase.

  8. Cooperative effect by monopodal silica-supported niobium com-plexes pairs enhancing catalytic cyclic carbonate production

    KAUST Repository

    D'Elia, Valerio; Dong, Hailin; Rossini, Aaron J; Widdifield, Cory M.; Vummaleti, Sai V. C.; Minenkov, Yury; Poater, Albert; Abou-Hamad, Edy; Pelletier, Jeremie D. A.; Cavallo, Luigi; Emsley, Lyndon; Basset, Jean-Marie

    2015-01-01

    Recent discoveries highlighted the activity and the intriguing mechanistic features of NbCl5 as a molecular catalyst for the cycloaddition of CO2 and epoxides under ambient conditions. This has inspired the preparation of novel silica supported Nb-species by reacting a molecular niobium precursor [NbCl5•OEt2] with silica dehydroxylated at 700 °C (SiO2-700) or at 200 oC (SiO2-200) to generate diverse surface complexes. The product of the reaction between SiO2-700 and [NbCl5•OEt2] was identified as a monopodal supported surface species [≡SiONbCl4•OEt2] (1a). The reactions of SiO2-200 with the niobium precursor, according to two different protocols, generated surface complexes 2a and 3a presenting significant, but different, populations of the monopodal surface complex along with bipodal [(≡SiO)2NbCl3•OEt2]. 93Nb SSNMR spectra of 1a-3a and 31P SSNMR on their PMe3 derivatives (1b-3b) led to the unambiguous assignment of 1a as a single site, monopodal Nb-species while 2a and 3a were found to present two distinct surface-supported components, with 2a being mostly monopodal [≡SiONbCl4•OEt2] and 3a being mostly bipodal [≡S ONbCl3•OEt2]. Double-quantum/single-quantum 31P NMR correlation experiment carried out on 2b supported the existence of vicinal Nb centers on the silica surface for this species. 1a-3a were active heterogeneous catalysts for the synthesis of propylene carbonate from CO2 and propylene oxide under mild catalytic conditions; the performance of 2a was found to significantly surpass that of 1a and 3a. With the support of a systematic DFT study carried out on model silica surfaces, the observed differences in catalytic efficiency were correlated with an unprece-dented cooperative effect between two neighboring Nb centers on the surface of 2a. This is in an excellent agreement with our previous discoveries regarding the mechanism of the NbCl5 catalyzed cycloaddition in the homogeneous phase.

  9. Observation of divergent La3+ ion dilute effect in two series of 3-D fluorescent lanthanide-MOFs-based molecular alloys RExLa1−x–EBTC (RE3+=Eu3+ or Tb3+; EBTC4−=1,1′-ethynebenzene-3,3′,5,5′-etracarboxylate)

    International Nuclear Information System (INIS)

    Zhai, Lu; Zhang, Wen-Wei; Ren, Xiao-Ming; Zuo, Jing-Lin

    2015-01-01

    The lanthanide metal-organic frameworks (MOFs) [Ln 2 (EBTC) 1.5 (CH 3 OH) 4 ]·6H 2 O are isostructural to each other, where EBTC 4− =1,1′-ethynebenzene-3,3′,5,5′-tetracarboxylate; Ln 3+ =La 3+ , Eu 3+ and Tb 3+ ; and the corresponding MOF is abbreviated as Ln–EBTC. MOFs Eu–EBTC and Tb–EBTC emit intense red and green luminescence (visible by bare eyes), respectively. The molecular alloys of Eu x La 1−x –EBTC and Tb x La 1−x –EBTC have been successfully prepared by mixing Eu 3+ /Tb 3+ and La 3+ salts with the desired molar ratio in the starting material. Two series of Eu x La 1−x –EBTC and Tb x La 1−x –EBTC molecular alloys are isomorphic to the parent Ln–EBTC MOFs, while exhibit divergent La 3+ ion diluting effect, namely, with increasing the relative amount of La 3+ , the intensity of characteristic emission arising from Tb 3+ ion monotonely increases in Tb x La 1−x –EBTC molecular alloys, whereas that of Eu 3+ ion shows non-monotone decrease in Eu x La 1−x –EBTC molecular alloys. The possible origin is discussed for such a divergent behavior between Eu x La 1−x –EBTC and Tb x La 1−x –EBTC molecular alloys. - Graphical abstract: Two series of 3-D fluorescent lanthanide-MOFs-based molecular alloys RE x La 1−x –EBTC (RE 3+ =Eu 3+ or Tb 3+ ; EBTC 4− =1,1′-ethynebenzene-3,3′,5,5′-tetracarboxylate) have been successfully prepared by mixing Eu 3+ /Tb 3+ and La 3+ salts with the desired molar ratio in the starting material and showed photoluminescence property with divergent La 3+ ion dilute effect. - Highlights: • 3-D molecular alloys of Eu x La 1−x –EBTC and Tb x La 1−x –EBTC were prepared. • They are isomorphic to the parent Ln–EBTC MOFs. • They show photoluminescence property with divergent La 3+ ion diluting effect. • The possible origin is discussed for such a divergent behavior

  10. Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps.

    Science.gov (United States)

    Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan; Stone, John E; Zhao, Jianhua; Schulten, Klaus

    2016-07-07

    Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.2 Å and 3.4 Å resolution, respectively. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the macromolecules studied, captured by means of local root mean square fluctuations. The MDFF tools described are available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services.

  11. Role of Au-C Interactions on the Catalytic Activity of Au Nanoparticles Supported on TiC(001) toward Molecular Oxygen Dissociation

    International Nuclear Information System (INIS)

    Rodriguez, J.; Feria, L.; Jirsak, T.; Takahashi, Y.; Nakamura, K.; Illas, F.

    2010-01-01

    High-resolution photoemission and density functional calculations on realistic slab surface models were used to study the interaction and subsequent dissociation of O 2 with Au nanoparticles supported on TiC(001). The photoemission results indicate that at 150 K O 2 adsorbs molecularly on the supported gold nanoparticles, and upon heating to temperatures above 200 K the O 2 → 2O reaction takes place with migration of atomic oxygen to the TiC(001) substrate. The addition of Au to TiC(001) substantially enhances the rate of O 2 dissociation at room temperature. The reactivity of Au nanoparticles supported on TiC(001) toward O 2 dissociation is much larger than that of similar nanoparticles supported either on TiO 2 (110) or MgO(001) surfaces, where the cleavage of O-O bonds is very difficult. Density functional calculations carried out on large supercells show that the contact of Au with TiC(001) is essential for charge polarization and an enhancement in the chemical activity of Au. Small two-dimensional particles which expose Au atoms in contact with TiC(001) are the most reactive. While O 2 prefers binding to Au sites, the O atoms interact more strongly with the TiC(001) surface. The oxygen species active during the low-temperature ( 2 . Once atomic O binds to TiC(001), the chemisorption bond is so strong that temperatures well above 400 K are necessary to remove the O adatoms from the TiC(001) substrate by direct reaction with CO. The high reactivity of Au/TiC(001) toward O 2 at low-temperature opens the route for the transformation of alcohols and amines on the supported Au nanoparticles.

  12. Determination of the molecular structure via the medium energy electrons (500 eV-1,5 KeV) Ar, N2, Co e HCl

    International Nuclear Information System (INIS)

    Nogueira, J.C.

    1977-01-01

    Elastic Differential and Total Differential Cross Sections are measured for electron collision in medium-energy range (500 eV - 1,5 KeV) with argon, nitrogen, carbon monoxide and hydrogen chloride, all in their electronic ground state. Theoretical calculation for the Elastic Differential Cross Sections by atoms were done employing Hartree-Fock-Clementy wave function, and making use of Partial Wave and WKBJ Methods. Exchange effect is included in the case of argon. Independent Atom Model, Half Molecule Model and a new model, the Ionic Model were utilized for the molecular calculations. The Ionic Model is suggested for the interaction between HCl and electrons. Inelastic Differential Cross Section were also computed, making use of the First Born Approximation and Hartree-Fock-Clementi wave function. It is also demonstrated, for the first time, that medium energy electrons (500 eV - 1,5 Kev) can be used to determine molecular structure parameters, in gas phase [pt

  13. Improved energy of the 21.5 keV M1+E2 nuclear transition in Eu-151

    Czech Academy of Sciences Publication Activity Database

    Inoyatov, A. K.; Kovalík, Alojz; Filosofov, D. V.; Ryšavý, Miloš; Perevoshchikov, L. L.; Baimukhanova, A.

    2016-01-01

    Roč. 52, č. 5 (2016), s. 133 ISSN 1434-6001 R&D Projects: GA ČR(CZ) GAP203/12/1896; GA MŠk LG14004 Institutional support: RVO:61389005 Keywords : electron binding energies * internal conversion * Gd-151 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 2.833, year: 2016

  14. Molecular characterization of the llama FGF5 gene and identification of putative loss of function mutations.

    Science.gov (United States)

    Daverio, M S; Vidal-Rioja, L; Frank, E N; Di Rocco, F

    2017-12-01

    Llama, the most numerous domestic camelid in Argentina, has good fiber-production ability. Although a few genes related to other productive traits have been characterized, the molecular genetic basis of fiber growth control in camelids is still poorly understood. Fibroblast growth factor 5 (FGF5) is a secreted signaling protein that controls hair growth in humans and other mammals. Mutations in the FGF5 gene have been associated with long-hair phenotypes in several species. Here, we sequenced the llama FGF5 gene, which consists of three exons encoding 813 bp. cDNA analysis from hair follicles revealed the expression of two FGF5 alternative spliced transcripts, in one of which exon 2 is absent. DNA variation analysis showed four polymorphisms in the coding region: a synonymous SNP (c.210A>G), a single base deletion (c.348delA), a 12-bp insertion (c.351_352insCATATAACATAG) and a non-sense mutation (c.499C>T). The deletion was always found together with the insertion forming a haplotype and producing a putative truncated protein of 123 amino acids. The c.499C>T mutation also leads to a premature stop codon at position 168. In both cases, critical functional domains of FGF5, including one heparin binding site, are lost. All animals analyzed were homozygous for one of the deleterious mutations or compound heterozygous for both (i.e. c.348delA, c.351_352insCATATAACATAG/c.499T). Sequencing of guanaco samples showed that the FGF5 gene encodes a full-length 270-amino acid protein. These results suggest that FGF5 is likely functional in short-haired wild species and non-functional in the domestic fiber-producing species, the llama. © 2017 Stichting International Foundation for Animal Genetics.

  15. Influence of incorporation method of sulfated zirconia in MCM-41 molecular sieve

    International Nuclear Information System (INIS)

    Pereira, C.E.; Santos, J.S.B.; Cavalcante, J.N.A.; Andrade, M.R.A.; Sousa, B.V.

    2016-01-01

    Sulfated metal oxides and sulfated zirconia have attracted great attention in recent years due to its high catalytic activity. The sulfated zirconia has the function of assigning the acidic material, through the formation of Bronsted acids and Lewis sites. The incorporation of sulfated zirconia in MCM-41 molecular sieve was carried out through the techniques: dry and wet. The wet process involves the use of an excess of solution on the volume of the support pores. Therefore, the concentration of the metal precursor on the support depends on the solution concentration and the pore volume of the support. In the process of incorporating by dry, the volume of the solution containing the precursor does not exceed the pore volume of the support. After either procedure, the impregnated support must be dried in order to allow the precursor compound can be converted into a catalytically active phase. This study aims to evaluate two methods of incorporation of sulfated zirconia in the mesoporous molecular sieve MCM-41. The process of merger took for wet and dry impregnation. Through the XRD patterns it was possible to identify the presence of the hexagonal structure of the molecular sieve, as well as the tetragonal and monoclinic phases of zirconia. From the spectroscopic analysis in the infrared region to the method the wet, it was possible to identify the vibrational frequencies related to the merger of sulfated zirconia in the MCM-41 structure of the molecular sieve. (author)

  16. Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

    Science.gov (United States)

    Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

    2009-12-01

    The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

  17. Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yi; Han, Gye Won; Abagyan, Ruben; Wu, Beili; Stevens, Raymond C.; Cherezov, Vadim; Kufareva, Irina; Handel, Tracy M. (USC); (Chinese Aca. Sci.); (UCSD)

    2017-06-01

    CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc. Molecular modeling indicated that HIV gp120 mimicked the chemokine interaction with CCR5, providing an explanation for the ability of CCR5 to recognize diverse ligands and gp120 variants. Our findings reveal that structural plasticity facilitates receptor-chemokine specificity and enables exploitation by HIV, and provide insight into the design of small molecule and protein inhibitors for HIV and other CCR5-mediated diseases.

  18. Orthonormal Wavelet Bases for Quantum Molecular Dynamics

    International Nuclear Information System (INIS)

    Tymczak, C.; Wang, X.

    1997-01-01

    We report on the use of compactly supported, orthonormal wavelet bases for quantum molecular-dynamics (Car-Parrinello) algorithms. A wavelet selection scheme is developed and tested for prototypical problems, such as the three-dimensional harmonic oscillator, the hydrogen atom, and the local density approximation to atomic and molecular systems. Our method shows systematic convergence with increased grid size, along with improvement on compression rates, thereby yielding an optimal grid for self-consistent electronic structure calculations. copyright 1997 The American Physical Society

  19. Crystal structures of N-(4-chlorophenyl-2-[(4,6-diaminopyrimidin-2-ylsulfanyl]acetamide and N-(3-chlorophenyl-2-[(4,6-diaminopyrimidin-2-ylsulfanyl]acetamide

    Directory of Open Access Journals (Sweden)

    S. Subasri

    2017-04-01

    Full Text Available The title compounds, C12H12ClN5OS, (I, and C12H12ClN5OS, (II, are 2-[(diaminopyrimidin-2-ylsulfanyl]acetamides. Compound (II, crystallizes with two independent molecules (A and B in the asymmetric unit. In each of the molecules, in both (I and (II, an intramolecular N—H...N hydrogen bond forms an S(7 ring motif. The pyrimidine ring is inclined to the benzene ring by 42.25 (14° in (I, and by 59.70 (16 and 62.18 (15° in molecules A and B, respectively, of compound (II. In the crystal of (I, molecules are linked by pairs of N—H...N hydrogen bonds, forming inversion dimers with an R22(8 ring motif. The dimers are linked via bifurcated N—H...O and C—H...O hydrogen bonds, forming corrugated layers parallel to the ac plane. In the crystal of (II, the A molecules are linked through N—H...O and N—H...Cl hydrogen bonds, forming layers parallel to (100. The B molecules are also linked by N—H...O and N—H...Cl hydrogen bonds, also forming layers parallel to (100. The parallel layers of A and B molecules are linked via N—H...N hydrogen bonds, forming a three-dimensional structure.

  20. Mass loading and episodic variation of molecular markers in PM2.5 aerosols over a rural area in eastern central India

    Science.gov (United States)

    Nirmalkar, Jayant; Deshmukh, Dhananjay K.; Deb, Manas K.; Tsai, Ying I.; Sopajaree, Khajornsak

    2015-09-01

    The impact of biomass burning in atmospheric aerosols load is poorly known. We investigated the impact of biomass burning through molecular markers on the concentration of PM2.5 aerosol samples collected from a rural site in eastern central India during three episodic periods from October to November 2011. The collected PM2.5 samples were chemically quantified for potassium as well as sugars and dicarboxylic acids using ion chromatography. Levoglucosan and glucose were found as the most abundant sugar compounds and sugar-alcohols showed the predominance of mannitol whereas oxalic acid was the most abundant diacid followed by maleic acid in PM2.5 aerosols. Substantially enhanced concentrations of K+ as well as levoglucosan and glucose were observed in eastern central India. Analysis of the source specific molecular markers and ratios of sugars and diacids infer that combustion of biomass was the major emission sources of organic compounds associated with PM2.5 aerosols over eastern central India. We applied Spearman correlation analysis and principal component analysis to further investigate the sources of measured sugars and diacids. The concentrations of K+ and levoglucosan were significantly correlated with sugars and diacids that verifying their common sources from biomass burning emission. This study demonstrates that biomass burning for domestic heating and cooking purposes and agricultural activities significantly influence the air quality of eastern central India during the investigation period. The obtained data in this research is helpful for the global scientific community to assessments and remedial of air quality parameters in rural areas of developing countries under similar atmospheric circumstances.