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Sample records for unique hypusine modification

Biochemical quantitation of the eIF5A hypusination in Arabidopsis thaliana uncovers ABA-dependent regulation

PubMed Central

Belda-Palazón, Borja; Nohales, María A.; Rambla, José L.; Aceña, José L.; Delgado, Oscar; Fustero, Santos; Martínez, M. Carmen; Granell, Antonio; Carbonell, Juan; Ferrando, Alejandro

2014-01-01

The eukaryotic translation elongation factor eIF5A is the only protein known to contain the unusual amino acid hypusine which is essential for its biological activity. This post-translational modification is achieved by the sequential action of the enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The crucial molecular function of eIF5A during translation has been recently elucidated in yeast and it is expected to be fully conserved in every eukaryotic cell, however the functional description of this pathway in plants is still sparse. The genetic approaches with transgenic plants for either eIF5A overexpression or antisense have revealed some activities related to the control of cell death processes but the molecular details remain to be characterized. One important aspect of fully understanding this pathway is the biochemical description of the hypusine modification system. Here we have used recombinant eIF5A proteins either modified by hypusination or non-modified to establish a bi-dimensional electrophoresis (2D-E) profile for the three eIF5A protein isoforms and their hypusinated or unmodified proteoforms present in Arabidopsis thaliana. The combined use of the recombinant 2D-E profile together with 2D-E/western blot analysis from whole plant extracts has provided a quantitative approach to measure the hypusination status of eIF5A. We have used this information to demonstrate that treatment with the hormone abscisic acid produces an alteration of the hypusine modification system in Arabidopsis thaliana. Overall this study presents the first biochemical description of the post-translational modification of eIF5A by hypusination which will be functionally relevant for future studies related to the characterization of this pathway in Arabidopsis thaliana. PMID:24904603
Expression of Eukaryotic Initiation Factor 5A and Hypusine Forming Enzymes in Glioblastoma Patient Samples: Implications for New Targeted Therapies

PubMed Central

Preukschas, Michael; Hagel, Christian; Schulte, Alexander; Weber, Kristoffer; Lamszus, Katrin; Sievert, Henning; Pällmann, Nora; Bokemeyer, Carsten; Hauber, Joachim; Braig, Melanie; Balabanov, Stefan

2012-01-01

Glioblastomas are highly aggressive brain tumors of adults with poor clinical outcome. Despite a broad range of new and more specific treatment strategies, therapy of glioblastomas remains challenging and tumors relapse in all cases. Recent work demonstrated that the posttranslational hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is a crucial regulator of cell proliferation, differentiation and an important factor in tumor formation, progression and maintenance. Here we report that eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient samples. Importantly, targeting eIF-5A and its hypusine modification with GC7, a specific DHS-inhibitor, showed a strong antiproliferative effect in glioblastoma cell lines in vitro, while normal human astrocytes were not affected. Furthermore, we identified p53 dependent premature senescence, a permanent cell cycle arrest, as the primary outcome in U87-MG cells after treatment with GC7. Strikingly, combined treatment with clinically relevant alkylating agents and GC7 had an additive antiproliferative effect in glioblastoma cell lines. In addition, stable knockdown of eIF-5A and DHS by short hairpin RNA (shRNA) could mimic the antiproliferative effects of GC7. These findings suggest that pharmacological inhibition of eIF-5A may represent a novel concept to treat glioblastomas and may help to substantially improve the clinical course of this tumor entity. PMID:22927971
Relevance of the Axis Spermidine/eIF5A for Plant Growth and Development

PubMed Central

Belda-Palazón, Borja; Almendáriz, Carla; Martí, Esmeralda; Carbonell, Juan; Ferrando, Alejandro

2016-01-01

One key role of the essential polyamine spermidine in eukaryotes is to provide the 4-aminobutyl moiety group destined to the post-translational modification of a lysine in the highly conserved translation factor eIF5A. This modification is catalyzed by two sequential enzymatic steps leading to the activation of eIF5A by the conversion of one conserved lysine to the unusual amino acid hypusine. The active translation factor facilitates the sequence-specific translation of polyproline sequences that otherwise cause ribosome stalling. In spite of the well-characterized involvement of active eIF5A in the translation of proline repeat-rich proteins, its biological role has been recently elucidated only in mammals, and it is poorly described at the functional level in plants. Here we describe the alterations in plant growth and development caused by RNAi-mediated conditional genetic inactivation of the hypusination pathway in Arabidopsis thaliana by knocking-down the enzyme deoxyhypusine synthase. We have uncovered that spermidine-mediated activation of eIF5A by hypusination is involved in several aspects of plant biology such as the control of flowering time, the aerial and root architecture, and root hair growth. In addition this pathway is required for adaptation to challenging growth conditions such as high salt and high glucose medium and to elevated concentrations of the plant hormone ABA. We have also performed a bioinformatic analysis of polyproline-rich containing proteins as putative eIF5A targets to uncover their organization in clusters of protein networks to find molecular culprits for the disclosed phenotypes. This study represents a first attempt to provide a holistic view of the biological relevance of the spermidine-dependent hypusination pathway for plant growth and development. PMID:26973686
DOE Office of Scientific and Technical Information (OSTI.GOV)

Tariq, Mohammad; Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570; Ito, Akihiro, E-mail: akihiro-i@riken.jp

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNAmore » oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.« less
Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis

PubMed Central

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki

2017-01-01

Abstract Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. PMID:28637321
Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis.

PubMed

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki; Dever, Thomas E

2017-08-21

Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.
Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A

PubMed Central

Aksu, Metin; Trakhanov, Sergei; Görlich, Dirk

2016-01-01

Xpo4 is a bidirectional nuclear transport receptor that mediates nuclear export of eIF5A and Smad3 as well as import of Sox2 and SRY. How Xpo4 recognizes such a variety of cargoes is as yet unknown. Here we present the crystal structure of the RanGTP·Xpo4·eIF5A export complex at 3.2 Å resolution. Xpo4 has a similar structure as CRM1, but the NES-binding site is occluded, and a new interaction site evolved that recognizes both globular domains of eIF5A. eIF5A contains hypusine, a unique amino acid with two positive charges, which is essential for cell viability and eIF5A function in translation. The hypusine docks into a deep, acidic pocket of Xpo4 and is thus a critical element of eIF5A's complex export signature. This further suggests that Xpo4 recognizes other cargoes differently, and illustrates how Xpo4 suppresses – in a chaperone-like manner – undesired interactions of eIF5A inside nuclei. PMID:27306458
Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea

PubMed Central

Graf, Michael; Blaby, Ian K.; Makkay, Andrea M.; Starosta, Agata L.; Papke, R. Thane; Oshima, Tairo; Wilson, Daniel N.

2016-01-01

Translation initiation factor 5A (IF5A) is essential and highly conserved in Eukarya (eIF5A) and Archaea (aIF5A). The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced in Haloferax volcanii in minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification in Hfx. volcanii that was experimentally tested. Analysis of aIF5A from Hfx. volcanii by LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene (HVO_1958) in agmatine synthesis. The agmatinase-like gene (HVO_2299) was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS) from S. cerevisiae was shown to transfer 4-aminobutyl moiety from spermidine to aIF5A from Hfx. volcanii in vitro. However, at least under conditions tested, this transfer was not observed with the Hfx. volcanii DHS. Furthermore, the growth of Hfx. volcanii was not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis in Hfx. volcanii that differs from the canonical eukaryotic pathway, paving the way for further studies. PMID:28053595
Polyamines and Hypusination Are Required for Ebolavirus Gene Expression and Replication

PubMed Central

Olsen, Michelle E.; Filone, Claire Marie; Rozelle, Dan; Mire, Chad E.; Agans, Krystle N.; Hensley, Lisa

2016-01-01

ABSTRACT Ebolavirus (EBOV) is an RNA virus that is known to cause severe hemorrhagic fever in humans and other primates. EBOV successfully enters and replicates in many cell types. This replication is dependent on the virus successfully coopting a number of cellular factors. Many of these factors are currently unidentified but represent potential targets for antiviral therapeutics. Here we show that cellular polyamines are critical for EBOV replication. We found that small-molecule inhibitors of polyamine synthesis block gene expression driven by the viral RNA-dependent RNA polymerase. Short hairpin RNA (shRNA) knockdown of the polyamine pathway enzyme spermidine synthase also resulted in reduced EBOV replication. These findings led us to further investigate spermidine, a polyamine that is essential for the hypusination of eukaryotic initiation factor 5A (eIF5A). Blocking the hypusination of eIF5A (and thereby inhibiting its function) inhibited both EBOV gene expression and viral replication. The mechanism appears to be due to the importance of hypusinated eIF5A for the accumulation of VP30, an essential component of the viral polymerase. The same reduction in hypusinated eIF5A did not alter the accumulation of other viral polymerase components. This action makes eIF5A function an important gate for proper EBOV polymerase assembly and function through the control of a single virus protein. PMID:27460797
Bifunctional activity of deoxyhypusine synthase/hydroxylase from Trichomonas vaginalis.

PubMed

Quintas-Granados, Laura Itzel; Carvajal Gamez, Bertha Isabel; Villalpando, Jose Luis; Ortega-Lopez, Jaime; Arroyo, Rossana; Azuara-Liceaga, Elisa; Álvarez-Sánchez, María Elizbeth

2016-04-01

The Trichomonas vaginalis genome analysis suggested the presence of a putative deoxyhypusine synthase (TvDHS) that catalyzes the posttranslational modification of eIF-5A. Herein, we expressed and purified the recombinant TvDHS (rTvDHS) protein (43 kDa) and the recombinant TveIF-5A (rTveIF-5A) precursor protein (46 kDa). A 41 kDa band of the native TvDHS was recognized by western blot analysis in T. vaginalis total protein extract by a mouse polyclonal anti-rTvDHS antibody. The enzymatic activity of rTvDHS was determined by in vitro rTveIF-5A precursor modification. The modification reaction was performed by using ((3)H)-spermidine, and the biochemical analysis showed that rTvDHS exhibited Km value of 0.6 μM. The rTvDHS activity was inhibited by the spermidine analog, N″-guanyl-1,7-diamino-heptane (GC7). Native gel electrophoresis analysis showed two bands corresponding to an rTvDHS-rTveIF-5A complex and an intermediate form of rTveIF-5A. The two forms were subsequently separated by ion exchange chromatography to identify the hypusine residue by MS/MS analysis. Moreover, mutations in TvDHS showed that the putative HE motif present in this enzyme is involved in the hydroxylation of TveIF-5A. We observed that only hypusine-containing TveIF-5A was bound to an RNA hairpin ERE structure from the cox-2 gene, which contains the AAAUGUCACAC consensus sequence. Interestingly, 2DE-WB assays, using parasites that were grown in DAB-culture conditions and transferred to exogenous putrescine, showed the new isoform of TveIF-5A. In summary, our results indicate that T. vaginalis contains an active TvDHS capable of modifying the precursor TveIF-5A protein, which subsequently exhibits RNA binding activity. Copyright © 2015. Published by Elsevier B.V.
Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell.

PubMed

Miller-Fleming, Leonor; Olin-Sandoval, Viridiana; Campbell, Kate; Ralser, Markus

2015-10-23

The polyamines (PAs) spermidine, spermine, putrescine and cadaverine are an essential class of metabolites found throughout all kingdoms of life. In this comprehensive review, we discuss their metabolism, their various intracellular functions and their unusual and conserved regulatory features. These include the regulation of translation via upstream open reading frames, the over-reading of stop codons via ribosomal frameshifting, the existence of an antizyme and an antizyme inhibitor, ubiquitin-independent proteasomal degradation, a complex bi-directional membrane transport system and a unique posttranslational modification-hypusination-that is believed to occur on a single protein only (eIF-5A). Many of these features are broadly conserved indicating that PA metabolism is both concentration critical and evolutionary ancient. When PA metabolism is disrupted, a plethora of cellular processes are affected, including transcription, translation, gene expression regulation, autophagy and stress resistance. As a result, the role of PAs has been associated with cell growth, aging, memory performance, neurodegenerative diseases, metabolic disorders and cancer. Despite comprehensive studies addressing PAs, a unifying concept to interpret their molecular role is missing. The precise biochemical function of polyamines is thus one of the remaining mysteries of molecular cell biology. Copyright © 2015. Published by Elsevier Ltd.
Fertility and polarized cell growth depends on eIF5A for translation of polyproline-rich formins in Saccharomyces cerevisiae.

PubMed

Li, Tianlu; Belda-Palazón, Borja; Ferrando, Alejandro; Alepuz, Paula

2014-08-01

eIF5A is an essential and evolutionary conserved translation elongation factor, which has recently been proposed to be required for the translation of proteins with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its activation by hypusination, a modification that requires spermidine, an essential factor for mammalian fertility that also promotes yeast mating. We show that in response to pheromone, hypusinated eIF5A is required for shmoo formation, localization of polarisome components, induction of cell fusion proteins, and actin assembly in yeast. We also show that eIF5A is required for the translation of Bni1, a proline-rich formin involved in polarized growth during shmoo formation. Our data indicate that translation of the polyproline motifs in Bni1 is eIF5A dependent and this translation dependency is lost upon deletion of the polyprolines. Moreover, an exogenous increase in Bni1 protein levels partially restores the defect in shmoo formation seen in eIF5A mutants. Overall, our results identify eIF5A as a novel and essential regulator of yeast mating through formin translation. Since eIF5A and polyproline formins are conserved across species, our results also suggest that eIF5A-dependent translation of formins could regulate polarized growth in such processes as fertility and cancer in higher eukaryotes. Copyright © 2014 by the Genetics Society of America.
Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva.

PubMed

Cracchiolo, Bernadette M; Heller, Debra S; Clement, Paul M J; Wolff, Edith C; Park, Myung-Hee; Hanauske-Abel, Hartmut M

2004-07-01

The mature eukaryotic translation initiation factor 5A contains the unusual amino acid hypusine, formed post-translationally from a specific lysine residue and essential for proliferation of eukaryotic cells. We hypothesized that the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH-353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was used to test this proposal in biopsies of vulvar high-grade intraepithelial neoplasia (VIN), characterized by the presence of proliferating cells throughout the thickness of the epithelium. Methods. Formalin-fixed and paraffin-embedded archival samples with an independently established diagnosis of VIN 3 were stained immunohistochemically after antigen retrieval, employing NIH-353 and, for comparison, the standard Ki-67 antibody. NIH-353 labeled neoplastic keratinocytes throughout the thickness of the epithelium in all VIN 3 samples. Malignant cells in a case of focally invasive squamous cell carcinoma also stained strongly for mature, hypusine-containing eIF5A-1. Epithelium adjacent to these lesions, though still of apparently normal morphology, was immunoreactive throughout its full thickness. At inflammatory foci of lesional sites, solitary reactive lymphocytes were positive, as were individual proliferating cells within dermal appendages. The submucosal stroma lacked reactive cells. NIH-353 identifies mature eIF5A-1 as an in situ biomarker for proliferation. Like Ki-67, this immunoreagent promises broad applicability in histopathological diagnosis and may be helpful in outcome prediction. In contrast to Ki-67, NIH-353 visualizes a molecular target for antineoplastic therapy, and thus may guide the development and clinical testing of drugs that, like the fungicide ciclopirox, inhibit hypusine formation and cell proliferation.
Target evaluation of deoxyhypusine synthase from Theileria parva the neglected animal parasite and its relationship to Plasmodium.

PubMed

Njuguna, James T; von Koschitzky, Imke; Gerhardt, Heike; Lämmerhofer, Michael; Choucry, Ali; Pink, Mario; Schmitz-Spahnke, Simone; Bakheit, Mohammed A; Strube, Christina; Kaiser, Annette

2014-08-01

East Coast fever (ECF) is a tick-borne disease caused by the parasite Theileria parva which infects cattle. In Sub-Saharan Africa it leads to enormous economic costs. After a bite of a tick, sporozoites invade the host lymphocytes and develop into schizonts. At this stage the parasite transforms host lymphocytes resulting in the clonal expansion of infected lymphocytes. Animals develop a lymphoma like disorder after infection which is rapidly fatal. Hitherto, a few drugs of the quinone type can cure the disease. However, therapy can only be successful after early diagnosis. The genera Theileria and Plasmodium, which includes the causative agent of human malaria, are closely related apicomplexan parasites. Enzymes of the hypusine pathway, a posttranslational modification in eukaryotic initiation factor EIF-5A, have shown to be druggable targets in Plasmodium. We identified the first enzyme of the hypusine pathway from T. parva, the deoxyhypusine synthase (DHS), which is located on chromosome 2 of the Muguga strain. Transcription is significantly increased in schizonts. The expressed T. parva DHS reveals an open reading frame (ORF) of 370 amino acids after expression in Escherichia coli Rosetta cells with a molecular size of 41.26 kDa and a theoretical pI of 5.26. Screening of the Malaria Box which consists of 400 active compounds resulted in a novel heterocyclic compound with a guanyl spacer which reduced the activity of T. parva DHS to 45%. In sum, the guanyl residue seems to be an important lead structure for inhibition of Theileria DHS. Currently, more different guanyl analogues from the Malaria Box are tested in inhibitor experiments to determine their efficacy. Copyright © 2014 Elsevier Ltd. All rights reserved.
The guanylhydrazone CNI-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase.

PubMed

Specht, Sabine; Sarite, Salem Ramadan; Hauber, Ilona; Hauber, Joachim; Görbig, Ulf F; Meier, Chris; Bevec, Dorian; Hoerauf, Achim; Kaiser, Annette

2008-05-01

Malaria is still a major cause of death in the tropics. There is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. Over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5A (eIF-5A) in Plasmodium. Hypusine biosynthesis involves catalysis of deoxyhypusine synthase (DHS) in the first step of post-translational modification. In a screen for new inhibitors of purified plasmodium DHS, CNI-1493, a novel selective pro-inflammatory cytokine inhibitor used in clinical phase II for the treatment of Crohn's disease, inhibited the enzyme of the parasite 3-fold at a concentration of 2 microM. In vitro experiments with 200 microM CNI-1493 in Plasmodium-infected erythrocytes, which lack nuclei and DHS protein, showed a parasite clearance within 2 days. This can presumably be attributed to an anti-proliferating effect because of the inhibition of DHS by the parasite. The determined IC50 of CNI-1493 was 135.79 microM after 72 h. In vivo application of this substance in Plasmodium berghei ANKA-infected C57BL/6 mice significantly reduced parasitemia after dosage of 1 mg/kg or 4 mg/kg/body weight and prevented death of mice with cerebral malaria. This effect was paralleled by a decrease in serum TNF levels of the mice. We suggest that the new mechanism of CNI-1493 is caused by a decrease in modified eIF-5A biosynthesis with a downstream effect on the TNF synthesis of the host. From the current data, we consider CNI-1493 to be a promising drug for anti-malarial therapy because of its combined action, i.e., the decrease in eIF-5A biosynthesis of the parasite and host cell TNF biosynthesis.
Hypusine modification in eukaryotic initiation factor 5A in rodent cells selected for resistance to growth inhibition by ornithine decarboxylase-inhibiting drugs.

PubMed Central

Tome, M E; Gerner, E W

1996-01-01

Selection of HTC cells in drugs that inhibit ornithine decarboxylase (ODC) has produced two cell lines, HMOA and DH23A/b, that contain increased amounts of more stable ODC. In addition to alterations in ODC, these cells appear to produce modified eukaryotic initiation factor 5A (eIF-5A) at different rates, a reaction that both requires spermidine and is essential for proliferation. Alterations to the modification of eIF-5A by spermidine cannot be accounted for by changes in eIF-5A protein or modified eIF-5A turnover. Deoxyhypusine synthetase activity is similar in the parental and variant cell lines and is unaltered by growth into plateau phase or by spermidine depletion. The increased rate of eIF-5A modification in DH23A/b cells is due to an increased accumulation of the unmodified eIF-5A precursor. Increased precursor accumulation is not due to increased eIF-5A transcription, but rather it can be attributed to a metabolic accumulation caused by growth under conditions of chronically limiting spermidine. Selection using drugs that inhibit ODC apparently does not cause alterations in the eIF-5A modification pathway. These data support the hypothesis that one of the main effects of spermidine depletion is depletion of the modified eIF-5A pool, and that this is a critical factor in the cytostasis often observed after depletion of cellular polyamines. PMID:8947467
Assessment of deoxyhypusine hydroxylase as a putative, novel drug target.

PubMed

Kerscher, B; Nzukou, E; Kaiser, A

2010-02-01

Antimalarial drug resistance has nowadays reached each drug class on the market for longer than 10 years. The focus on validated, classical targets has severe drawbacks. If resistance is arising or already present in the field, a target-based High-Throughput-Screening (HTS) with the respective target involves the risk of identifying compounds to which field populations are also resistant. Thus, it appears that a rewarding albeit demanding challenge for target-based drug discovery is to identify novel drug targets. In the search for new targets for antimalarials, we have investigated the biosynthesis of hypusine, present in eukaryotic initiation factor 5A (eIF5A). Deoxyhypusine hydroxylase (DOHH), which has recently been cloned and expressed from P. falciparum, completes the modification of eIF5A through hydroxylation. Here, we assess the present druggable data on Plasmodium DOHH and its human counterpart. Plasmodium DOHH arose from a cyanobacterial phycobilin lyase by loss of function. It has a low FASTA score of 27 to its human counterpart. The HEAT-like repeats present in the parasite DOHH differ in number and amino acid identity from its human ortholog and might be of considerable interest for inhibitor design.
SNPs detection in DHPS-WDR83 overlapping genes mapping on porcine chromosome 2 in a QTL region for meat pH.

PubMed

Zambonelli, Paolo; Davoli, Roberta; Bigi, Mila; Braglia, Silvia; De Paolis, Luigi Francesco; Buttazzoni, Luca; Gallo, Maurizio; Russo, Vincenzo

2013-10-08

The pH is an important parameter influencing technological quality of pig meat, a trait affected by environmental and genetic factors. Several quantitative trait loci associated to meat pH are described on PigQTL database but only two genes influencing this parameter have been so far detected: Ryanodine receptor 1 and Protein kinase, AMP-activated, gamma 3 non-catalytic subunit. To search for genes influencing meat pH we analyzed genomic regions with quantitative effect on this trait in order to detect SNPs to use for an association study. The expressed sequences mapping on porcine chromosomes 1, 2, 3 in regions associated to pork pH were searched in silico to find SNPs. 356 out of 617 detected SNPs were used to genotype Italian Large White pigs and to perform an association analysis with meat pH values recorded in semimembranosus muscle at about 1 hour (pH1) and 24 hours (pHu) post mortem.The results of the analysis showed that 5 markers mapping on chromosomes 1 or 3 were associated with pH1 and 10 markers mapping on chromosomes 1 or 2 were associated with pHu. After False Discovery Rate correction only one SNP mapping on chromosome 2 was confirmed to be associated to pHu. This polymorphism was located in the 3'UTR of two partly overlapping genes, Deoxyhypusine synthase (DHPS) and WD repeat domain 83 (WDR83). The overlapping of the 3'UTRs allows the co-regulation of mRNAs stability by a cis-natural antisense transcript method of regulation. DHPS catalyzes the first step in hypusine formation, a unique amino acid formed by the posttranslational modification of the protein eukaryotic translation initiation factor 5A in a specific lysine residue. WDR83 has an important role in the modulation of a cascade of genes involved in cellular hypoxia defense by intensifying the glycolytic pathway and, theoretically, the meat pH value. The involvement of the SNP detected in the DHPS/WDR83 genes on meat pH phenotypic variability and their functional role are suggestive of molecular and biological processes related to glycolysis increase during post-mortem phase. This finding, after validation, can be applied to identify new biomarkers to be used to improve pig meat quality.
Modulation of protein synthesis by polyamines.

PubMed

Igarashi, Kazuei; Kashiwagi, Keiko

2015-03-01

Polyamines are ubiquitous small basic molecules that play important roles in cell growth and viability. Since polyamines mainly exist as a polyamine-RNA complex, we looked for proteins whose synthesis is preferentially stimulated by polyamines at the level of translation, and thus far identified 17 proteins in Escherichia coli and 6 proteins in eukaryotes. The mechanisms of polyamine stimulation of synthesis of these proteins were investigated. In addition, the role of eIF5A, containing hypusine formed from spermidine, on protein synthesis is described. These results clearly indicate that polyamines and eIF5A contribute to cell growth and viability through modulation of protein synthesis. © 2015 International Union of Biochemistry and Molecular Biology.
Genome-Wide Analyses and Functional Classification of Proline Repeat-Rich Proteins: Potential Role of eIF5A in Eukaryotic Evolution

PubMed Central

Mandal, Ajeet; Mandal, Swati; Park, Myung Hee

2014-01-01

The eukaryotic translation factor, eIF5A has been recently reported as a sequence-specific elongation factor that facilitates peptide bond formation at consecutive prolines in Saccharomyces cerevisiae, as its ortholog elongation factor P (EF-P) does in bacteria. We have searched the genome databases of 35 representative organisms from six kingdoms of life for PPP (Pro-Pro-Pro) and/or PPG (Pro-Pro-Gly)-encoding genes whose expression is expected to depend on eIF5A. We have made detailed analyses of proteome data of 5 selected species, Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, Mus musculus and Homo sapiens. The PPP and PPG motifs are low in the prokaryotic proteomes. However, their frequencies markedly increase with the biological complexity of eukaryotic organisms, and are higher in newly derived proteins than in those orthologous proteins commonly shared in all species. Ontology classifications of S. cerevisiae and human genes encoding the highest level of polyprolines reveal their strong association with several specific biological processes, including actin/cytoskeletal associated functions, RNA splicing/turnover, DNA binding/transcription and cell signaling. Previously reported phenotypic defects in actin polarity and mRNA decay of eIF5A mutant strains are consistent with the proposed role for eIF5A in the translation of the polyproline-containing proteins. Of all the amino acid tandem repeats (≥3 amino acids), only the proline repeat frequency correlates with functional complexity of the five organisms examined. Taken together, these findings suggest the importance of proline repeat-rich proteins and a potential role for eIF5A and its hypusine modification pathway in the course of eukaryotic evolution. PMID:25364902

Modification of NASA Langley 8 foot high temperature tunnel to provide a unique national research facility for hypersonic air-breathing propulsion systems

NASA Technical Reports Server (NTRS)

Kelly, H. N.; Wieting, A. R.

1984-01-01

A planned modification of the NASA Langley 8-Foot High Temperature Tunnel to make it a unique national research facility for hypersonic air-breathing propulsion systems is described, and some of the ongoing supporting research for that modification is discussed. The modification involves: (1) the addition of an oxygen-enrichment system which will allow the methane-air combustion-heated test stream to simulate air for propulsion testing; and (2) supplemental nozzles to expand the test simulation capability from the current nominal Mach number to 7.0 include Mach numbers 3.0, 4.5, and 5.0. Detailed design of the modifications is currently underway and the modified facility is scheduled to be available for tests of large scale propulsion systems by mid 1988.
Reproductive cloning combined with genetic modification.

PubMed

Strong, C

2005-11-01

Although there is widespread opposition to reproductive cloning, some have argued that its use by infertile couples to have genetically related children would be ethically justifiable. Others have suggested that lesbian or gay couples might wish to use cloning to have genetically related children. Most of the main objections to human reproductive cloning are based on the child's lack of unique nuclear DNA. In the future, it may be possible safely to create children using cloning combined with genetic modifications, so that they have unique nuclear DNA. The genetic modifications could be aimed at giving such children genetic characteristics of both members of the couple concerned. Thus, cloning combined with genetic modification could be appealing to infertile, lesbian, or gay couples who seek genetically related children who have genetic characteristics of both members. In such scenarios, the various objections to human reproductive cloning that are based on the lack of genetic uniqueness would no longer be applicable. The author argues that it would be ethically justifiable for such couples to create children in this manner, assuming these techniques could be used safely.
Small nucleolar RNAs that guide modification in trypanosomatids: repertoire, targets, genome organisation, and unique functions.

PubMed

Uliel, Shai; Liang, Xue-hai; Unger, Ron; Michaeli, Shulamit

2004-03-29

Small nucleolar RNAs constitute a family of newly discovered non-coding small RNAs, most of which function in guiding RNA modifications. Two prevalent types of modifications are 2'-O-methylation and pseudouridylation. The modification is directed by the formation of a canonical small nucleolar RNA-target duplex. Initially, RNA-guided modification was shown to take place on rRNA, but recent studies suggest that small nuclear RNA, mRNA, tRNA, and the trypanosome spliced leader RNA also undergo guided modifications. Trypanosomes contain more modifications and potentially more small nucleolar RNAs than yeast, and the increased number of modifications may help to preserve ribosome function under adverse environmental conditions during the cycling between the insect and mammalian host. The genome organisation in clusters carrying the two types of small nucleolar RNAs, C/D and H/ACA-like RNAs, resembles that in plants. However, the trypanosomatid H/ACA RNAs are similar to those found in Archaea and are composed of a single hairpin that may represent the primordial H/ACA RNA. In this review we summarise this new field of trypanosome small nucleolar RNAs, emphasising the open questions regarding the number of small nucleolar RNAs, the repertoire, genome organisation, and the unique function of guided modifications in these protozoan parasites.
tRNA modification profiles of the fast-proliferating cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Chao; Niu, Leilei; Song, Wei

Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In additionmore » to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.« less
Genetic modification and genetic determinism

PubMed Central

Resnik, David B; Vorhaus, Daniel B

2006-01-01

In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884
Optimization of Process Conditions for Enzymatic Modification of Alternan using Dextranase from Chaetomium erraticum

USDA-ARS?s Scientific Manuscript database

Alternan is a unique branched glucan with alternating a-(1 ' 6) and a-(1 ' 3) backbone linkages. We previously described the modification of alternan to a reduced molecular weight form using dextranase from Penicillium sp. The solution viscosity properties of this modified alternan resemble those ...
Outstanding effects on antithrombin activity of modified TBA diastereomers containing an optically pure acyclic nucleotide analogue.

PubMed

Scuotto, M; Persico, M; Bucci, M; Vellecco, V; Borbone, N; Morelli, E; Oliviero, G; Novellino, E; Piccialli, G; Cirino, G; Varra, M; Fattorusso, C; Mayol, L

2014-07-28

Herein, we report optically pure modified acyclic nucleosides as ideal probes for aptamer modification. These new monomers offer unique advantages in exploring the role played in thrombin inhibition by a single residue modification at key positions of the TBA structure.
Using Chromatin Immunoprecipitation in Toxicology: A Step-by-Step Guide to Increasing Efficiency, Reducing Variability, and Expanding Applications

EPA Science Inventory

Histone modifications work in concert with DNA methylation to regulate cellular structure, function, and the response to environmental stimuli. More than 130 unique histone modifications have been described to date and chromatin immunoprecipitation (ChIP) allows for the explorat...
Hierarchical layered double hydroxides with Ag nanoparticle modification for ethanol sensing

NASA Astrophysics Data System (ADS)

Qin, Yuxiang; Wang, Liping; Wang, Xiaofei

2018-07-01

Layered double hydroxides (LDHs) have recently been revealed to be promising in gas sensor applications due to their compositional flexibility and unique 2D-interlayer channel for gas diffusion and adsorption. This work demonstrates highly porous hierarchical LDHs containing Mg2+ and Al3+ (MgAl-LDHs) for ethanol sensing at room temperature. These MgAl-LDHs, with unique flower-like hierarchical structure and mesoporous interlayer, were synthesized hydrothermally using sodium dodecyl sulfate as soft template as well as intercalating agent. Further modification by discrete Ag nanoparticles (NPs) was achieved via an environmentally friendly glucose-reduction method to improve the gas-sensing response of the LDH-based sensor. It is found that the hierarchical MgAl-LDHs show potential in sensing ethanol gas with rapid dynamic characteristics at room temperature; their response magnitude towards ethanol can be enhanced significantly by Ag NP modification. The gas-response value of the Ag-modified MgAl-LDH sensor is about twice that of pristine MgAl-LDH sensors, towards 5–200 ppm ethanol at room temperature. Meanwhile, rapid response-recovery characteristics are achieved, with response and recovery times shorter than 10 and 50 s, respectively. The satisfactory sensing performance and remarkable response enhancement by Ag NP modification are demonstrated in terms of the unique microstructure of the hierarchical MgAl-LDHs and a constructed conductive effect model of Ag functionalized LDHs.
Hierarchical layered double hydroxides with Ag nanoparticle modification for ethanol sensing.

PubMed

Qin, Yuxiang; Wang, Liping; Wang, Xiaofei

2018-07-06

Layered double hydroxides (LDHs) have recently been revealed to be promising in gas sensor applications due to their compositional flexibility and unique 2D-interlayer channel for gas diffusion and adsorption. This work demonstrates highly porous hierarchical LDHs containing Mg 2+ and Al 3+ (MgAl-LDHs) for ethanol sensing at room temperature. These MgAl-LDHs, with unique flower-like hierarchical structure and mesoporous interlayer, were synthesized hydrothermally using sodium dodecyl sulfate as soft template as well as intercalating agent. Further modification by discrete Ag nanoparticles (NPs) was achieved via an environmentally friendly glucose-reduction method to improve the gas-sensing response of the LDH-based sensor. It is found that the hierarchical MgAl-LDHs show potential in sensing ethanol gas with rapid dynamic characteristics at room temperature; their response magnitude towards ethanol can be enhanced significantly by Ag NP modification. The gas-response value of the Ag-modified MgAl-LDH sensor is about twice that of pristine MgAl-LDH sensors, towards 5-200 ppm ethanol at room temperature. Meanwhile, rapid response-recovery characteristics are achieved, with response and recovery times shorter than 10 and 50 s, respectively. The satisfactory sensing performance and remarkable response enhancement by Ag NP modification are demonstrated in terms of the unique microstructure of the hierarchical MgAl-LDHs and a constructed conductive effect model of Ag functionalized LDHs.
Synthetic Proteins and Peptides for the Direct Interrogation of α-Synuclein Posttranslational Modifications

PubMed Central

Pratt, Matthew R.; Abeywardana, Tharindumala; Marotta, Nicholas P.

2015-01-01

α-Synuclein is the aggregation-prone protein associated with Parkinson’s disease (PD) and related neurodegenerative diseases. Complicating both its biological functions and toxic aggregation are a variety of posttranslational modifications. These modifications have the potential to either positively or negatively affect α-synuclein aggregation, raising the possibility that the enzymes that add or remove these modifications could be therapeutic targets in PD. Synthetic protein chemistry is uniquely positioned to generate site-specifically and homogeneously modified proteins for biochemical study. Here, we review the application of synthetic peptides and proteins towards understanding the effects of α-synuclein posttranslational modifications. PMID:26120904
Making the Mark: The Role of Adenosine Modifications in the Lifecycle of RNA Viruses

PubMed Central

Gonzales-van Horn, Sarah R.; Sarnow, Peter

2017-01-01

Summary Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating lifecycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral lifecycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2′ O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies. PMID:28618265
Recent progress in plasma-assisted synthesis and modification of 2D materials

NASA Astrophysics Data System (ADS)

Han, Zhao Jun; Murdock, Adrian T.; Seo, Dong Han; Bendavid, Avi

2018-07-01

Plasma represents an important technique for both the synthesis and modification of two-dimensional (2D) materials, owing to the unique plasma-material interactions which can enable effective energy transfer at the nanoscale. Non-equilibrium and non-thermal plasma techniques have been widely applied on various 2D materials, including graphene, silicene, germanene, phosphorene, hexagonal boron nitride (h-BN), and transition metal dichalcogenides such as MoS2 and WS2. Here, we review the recent progress in plasma-assisted synthesis and modification (e.g. functionalisation, doping and etching) of 2D materials and discuss the potential applications of this unique branch of 2D materials. Challenges and future research opportunities in the relevant research field are also discussed. The primary aim of this Review is to provide a better understanding of the plasma-assisted processes and to promote the utilization of 2D materials for advanced electronic, optoelectronic, sensing and energy storage applications.
Ambient response of a unique performance-based design building with dynamic response modification features

USGS Publications Warehouse

Çelebi, Mehmet; Huang, Moh; Shakal, Antony; Hooper, John; Klemencic, Ron

2012-01-01

A 64-story, performance-based design building with reinforced concrete core shear-walls and unique dynamic response modification features (tuned liquid sloshing dampers and buckling-restrained braces) has been instrumented with a monitoring array of 72 channels of accelerometers. Ambient vibration data recorded are analyzed to identify modes and associated frequencies and damping. The low-amplitude dynamic characteristics are considerably different than those computed from design analyses, but serve as a baseline against which to compare with future strong shaking responses. Such studies help to improve our understanding of the effectiveness of the added features to the building and help improve designs in the future.
Transcriptomic sequencing reveals a set of unique genes activated by butyrate-induced histone modification

USDA-ARS?s Scientific Manuscript database

Butyrate is a nutritional element with strong epigenetic regulatory activity as an inhibitor of histone deacetylases (HDACs). Based on the analysis of differentially expressed genes induced by butyrate in the bovine epithelial cell using deep RNA-sequencing technology (RNA-seq), a set of unique gen...
Rapid End-Group Modification of Polysaccharides for Biomaterial Applications in Regenerative Medicine.

PubMed

Bondalapati, Somasekhar; Ruvinov, Emil; Kryukov, Olga; Cohen, Smadar; Brik, Ashraf

2014-09-15

Polysaccharides have emerged as important functional materials because of their unique properties such as biocompatibility, biodegradability, and availability of reactive sites for chemical modifications to optimize their properties. The overwhelming majority of the methods to modify polysaccharides employ random chemical modifications, which often improve certain properties while compromising others. On the other hand, the employed methods for selective modifications often require excess of coupling partners, long reaction times and are limited in their scope and wide applicability. To circumvent these drawbacks, aniline-catalyzed oxime formation is developed for selective modification of a variety of polysaccharides through their reducing end. Notably, it is found that for efficient oxime formation, different conditions are required depending on the composition of the specific polysaccharide. It is also shown how our strategy can be applied to improve the physical and functional properties of alginate hydrogels, which are widely used in tissue engineering and regenerative medicine applications. While the randomly and selectively modified alginate exhibits similar viscoelastic properties, the latter forms significantly more stable hydrogel and superior cell adhesive and functional properties. Our results show that the developed conjugation reaction is robust and should open new opportunities for preparing polysaccharide-based functional materials with unique properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Posttranscriptional modification of tRNA in thermophilic archaea (Archaebacteria).

PubMed Central

Edmonds, C G; Crain, P F; Gupta, R; Hashizume, T; Hocart, C H; Kowalak, J A; Pomerantz, S C; Stetter, K O; McCloskey, J A

1991-01-01

Nucleoside modification has been studied in unfractionated tRNA from 11 thermophilic archaea (archaebacteria), including phylogenetically diverse representatives of thermophilic methanogens and sulfur-metabolizing hyperthermophiles which grow optimally in the temperature range of 56 (Thermoplasma acidophilum) to 105 degrees C (Pyrodictium occultum), and for comparison from the most thermophilic bacterium (eubacterium) known, Thermotoga maritima (80 degrees C). Nine nucleosides are found to be unique to the archaea, six of which are structurally novel in being modified both in the base and by methylation in ribose and occur primarily in tRNA from the extreme thermophiles in the Crenarchaeota of the archaeal phylogenetic tree. 2-Thiothymine occurs in tRNA from Thermococcus sp., and constitutes the only known occurrence of the thymine moiety in archaeal RNA, in contrast to its near-ubiquitous presence in tRNA from bacteria and eukarya. A total of 33 modified nucleosides are rigorously characterized in archaeal tRNA in the present study, demonstrating that the structural range of posttranscriptional modifications in archaeal tRNA is more extensive than previously known. From a phylogenetic standpoint, certain tRNA modifications occur in the archaea which are otherwise unique to either the bacterial or eukaryal domain, although the overall patterns of modification are more typical of eukaryotes than bacteria. PMID:1708763
Making the Mark: The Role of Adenosine Modifications in the Life Cycle of RNA Viruses.

PubMed

Gonzales-van Horn, Sarah R; Sarnow, Peter

2017-06-14

Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating life cycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral life cycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2' O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies. Copyright © 2017 Elsevier Inc. All rights reserved.
Modification of quantum dots with nucleic acids

NASA Astrophysics Data System (ADS)

Kocherginskaya, P. B.; Romanova, A. V.; Prokhorenko, I. A.; Itkis, Daniil M.; Korshun, V. A.; Goodilin, Eugene A.; Tretyakov, Yuri D.

2011-12-01

The key principles and modern approaches to targeted modification of semiconductor colloidal nanoparticles, quantum dots, which exhibit unique photophysical properties and are a promising class of luminescent markers, are discussed. Attention is given to the preparation of their bioconjugates with nucleic acids, promising tools for biological microchips and resonance energy transfer sensors. The bibliography includes 80 references.
Body Modifications in College Students: Considering Gender, Self-Esteem, Body Appreciation, and Reasons for Tattoos

ERIC Educational Resources Information Center

Hill, Brittany M.; Ogletree, S. M.; McCrary, K. M.

2016-01-01

Body modifications are becoming mainstream as more individuals are becoming tattooed. Using a convenience sample of college students, participants with and without tattoos were compared on measures of body appreciation, self-esteem, and need for uniqueness. Among these central Texas students 44% had at least one tattoo. Women, compared to men,…

Comparative analyses of Xanthomonas and Xylella complete genomes.

PubMed

Moreira, Leandro M; De Souza, Robson F; Digiampietri, Luciano A; Da Silva, Ana C R; Setubal, João C

2005-01-01

Computational analyses of four bacterial genomes of the Xanthomonadaceae family reveal new unique genes that may be involved in adaptation, pathogenicity, and host specificity. The Xanthomonas genus presents 3636 unique genes distributed in 1470 families, while Xylella genus presents 1026 unique genes distributed in 375 families. Among Xanthomonas-specific genes, we highlight a large number of cell wall degrading enzymes, proteases, and iron receptors, a set of energy metabolism genes, second copy of the type II secretion system, type III secretion system, flagella and chemotactic machinery, and the xanthomonadin synthesis gene cluster. Important genes unique to the Xylella genus are an additional copy of a type IV pili gene cluster and the complete machinery of colicin V synthesis and secretion. Intersections of gene sets from both genera reveal a cluster of genes homologous to Salmonella's SPI-7 island in Xanthomonas axonopodis pv citri and Xylella fastidiosa 9a5c, which might be involved in host specificity. Each genome also presents important unique genes, such as an HMS cluster, the kdgT gene, and O-antigen in Xanthomonas axonopodis pv citri; a number of avrBS genes and a distinct O-antigen in Xanthomonas campestris pv campestris, a type I restriction-modification system and a nickase gene in Xylella fastidiosa 9a5c, and a type II restriction-modification system and two genes related to peptidoglycan biosynthesis in Xylella fastidiosa temecula 1. All these differences imply a considerable number of gene gains and losses during the divergence of the four lineages, and are associated with structural genome modifications that may have a direct relation with the mode of transmission, adaptation to specific environments and pathogenicity of each organism.
Dealing with an Unconventional Genetic Code in Mitochondria: The Biogenesis and Pathogenic Defects of the 5-Formylcytosine Modification in Mitochondrial tRNAMet.

PubMed

Van Haute, Lindsey; Powell, Christopher A; Minczuk, Michal

2017-03-02

Human mitochondria contain their own genome, which uses an unconventional genetic code. In addition to the standard AUG methionine codon, the single mitochondrial tRNA Methionine (mt-tRNAMet) also recognises AUA during translation initiation and elongation. Post-transcriptional modifications of tRNAs are important for structure, stability, correct folding and aminoacylation as well as decoding. The unique 5-formylcytosine (f5C) modification of position 34 in mt-tRNAMet has been long postulated to be crucial for decoding of unconventional methionine codons and efficient mitochondrial translation. However, the enzymes responsible for the formation of mitochondrial f5C have been identified only recently. The first step of the f5C pathway consists of methylation of cytosine by NSUN3. This is followed by further oxidation by ABH1. Here, we review the role of f5C, the latest breakthroughs in our understanding of the biogenesis of this unique mitochondrial tRNA modification and its involvement in human disease.
Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes

PubMed Central

2017-01-01

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that display a wide variety of biological activities, from antimicrobial to antiallodynic. Lanthipeptides that display antimicrobial activity are called lantibiotics. The post-translational modification reactions of lanthipeptides include dehydration of Ser and Thr residues to dehydroalanine and dehydrobutyrine, a transformation that is carried out in three unique ways in different classes of lanthipeptides. In a cyclization process, Cys residues then attack the dehydrated residues to generate the lanthionine and methyllanthionine thioether cross-linked amino acids from which lanthipeptides derive their name. The resulting polycyclic peptides have constrained conformations that confer their biological activities. After installation of the characteristic thioether cross-links, tailoring enzymes introduce additional post-translational modifications that are unique to each lanthipeptide and that fine-tune their activities and/or stability. This review focuses on studies published over the past decade that have provided much insight into the mechanisms of the enzymes that carry out the post-translational modifications. PMID:28135077
The ethics of molecular memory modification.

PubMed

Hui, Katrina; Fisher, Carl E

2015-07-01

Novel molecular interventions have recently shown the potential to erase, enhance and alter specific long-term memories. Unique features of this form of memory modification call for a close examination of its possible applications. While there have been discussions of the ethics of memory modification in the literature, molecular memory modification (MMM) can provide special insights. Previously raised ethical concerns regarding memory enhancement, such as safety issues, the 'duty to remember', selfhood and personal identity, require re-evaluation in light of MMM. As a technology that exploits the brain's updating processes, MMM helps correct the common misconception that memory is a static entity by demonstrating how memory is plastic and subject to revision even in the absence of external manipulation. Furthermore, while putatively safer than other speculative technologies because of its high specificity, MMM raises notable safety issues, including potential insidious effects on the agent's emotions and personal identity. Nonetheless, MMM possesses characteristics of a more permissible form of modification, not only because it is theoretically safer, but because its unique mechanism of action requires a heightened level of cooperation from the agent. Discussions of memory modification must consider the specific mechanisms of action, which can alter the weight and relevance of various ethical concerns. MMM also highlights the need for conceptual accuracy regarding the term 'enhancement'; this umbrella term will have to be differentiated as new technologies are applied to a widening array of purposes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
The Expanding Landscape of the Thiol Redox Proteome*

PubMed Central

Yang, Jing; Carroll, Kate S.; Liebler, Daniel C.

2016-01-01

Cysteine occupies a unique place in protein chemistry. The nucleophilic thiol group allows cysteine to undergo a broad range of redox modifications beyond classical thiol-disulfide redox equilibria, including S-sulfenylation (-SOH), S-sulfinylation (-SO2H), S-sulfonylation (-SO3H), S-nitrosylation (-SNO), S-sulfhydration (-SSH), S-glutathionylation (-SSG), and others. Emerging evidence suggests that these post-translational modifications (PTM) are important in cellular redox regulation and protection against oxidative damage. Identification of protein targets of thiol redox modifications is crucial to understanding their roles in biology and disease. However, analysis of these highly labile and dynamic modifications poses challenges. Recent advances in the design of probes for thiol redox forms, together with innovative mass spectrometry based chemoproteomics methods make it possible to perform global, site-specific, and quantitative analyses of thiol redox modifications in complex proteomes. Here, we review chemical proteomic strategies used to expand the landscape of thiol redox modifications. PMID:26518762
On Time Delay Margin Estimation for Adaptive Control and Optimal Control Modification

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2011-01-01

This paper presents methods for estimating time delay margin for adaptive control of input delay systems with almost linear structured uncertainty. The bounded linear stability analysis method seeks to represent an adaptive law by a locally bounded linear approximation within a small time window. The time delay margin of this input delay system represents a local stability measure and is computed analytically by three methods: Pade approximation, Lyapunov-Krasovskii method, and the matrix measure method. These methods are applied to the standard model-reference adaptive control, s-modification adaptive law, and optimal control modification adaptive law. The windowing analysis results in non-unique estimates of the time delay margin since it is dependent on the length of a time window and parameters which vary from one time window to the next. The optimal control modification adaptive law overcomes this limitation in that, as the adaptive gain tends to infinity and if the matched uncertainty is linear, then the closed-loop input delay system tends to a LTI system. A lower bound of the time delay margin of this system can then be estimated uniquely without the need for the windowing analysis. Simulation results demonstrates the feasibility of the bounded linear stability method for time delay margin estimation.
Modification degrees at specific sites on heparan sulphate: an approach to measure chemical modifications on biological molecules with stable isotope labelling

PubMed Central

Wu, Zhengliang L.; Lech, Miroslaw

2005-01-01

Chemical modification of biological molecules is a general mechanism for cellular regulation. A quantitative approach has been developed to measure the extent of modification on HS (heparan sulphates). Sulphation on HS by sulphotransferases leads to variable sulphation levels, which allows cells to tune their affinities to various extracellular proteins, including growth factors. With stable isotope labelling and HPLC-coupled MS, modification degrees at various O-sulphation sites could be determined. A bovine kidney HS sample was first saturated in vitro with 34S by an OST (O-sulphotransferase), then digested with nitrous acid and analysed with HPLC-coupled MS. The 34S-labelled oligosaccharides were identified based on their unique isotope clusters. The modification degrees at the sulphotransferase recognition sites were obtained by calculating the intensities of isotopic peaks in the isotope clusters. The modification degrees at 3-OST-1 and 6-OST-1 sites were examined in detail. This approach can also be used to study other types of chemical modifications on biological molecules. PMID:15743272
Germline Modification and Engineering in Avian Species

PubMed Central

Lee, Hong Jo; Lee, Hyung Chul; Han, Jae Yong

2015-01-01

Production of genome-edited animals using germline-competent cells and genetic modification tools has provided opportunities for investigation of biological mechanisms in various organisms. The recently reported programmed genome editing technology that can induce gene modification at a target locus in an efficient and precise manner facilitates establishment of animal models. In this regard, the demand for genome-edited avian species, which are some of the most suitable model animals due to their unique embryonic development, has also increased. Furthermore, germline chimera production through long-term culture of chicken primordial germ cells (PGCs) has facilitated research on production of genome-edited chickens. Thus, use of avian germline modification is promising for development of novel avian models for research of disease control and various biological mechanisms. Here, we discuss recent progress in genome modification technology in avian species and its applications and future strategies. PMID:26333275
Epigenetics Mechanisms in Alzheimer’s disease

PubMed Central

Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul D.; Rogers, Joseph

2011-01-01

Epigenetic modifications help orchestrate sweeping developmental, aging, and disease-causing changes in phenotype by altering transcriptional activity in multiple genes spanning multiple biologic pathways. Although previous epigenetic research has focused primarily on dividing cells, particularly in cancer, recent studies have shown rapid, dynamic, and persistent epigenetic modifications in neurons that have significant neuroendocrine, neurophysiologic, and neurodegenerative consequences. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and Alzheimer’s disease (AD). Because of their reach across the genome, epigenetic mechanisms may provide a unique integrative framework for the pathologic diversity and complexity of AD. PMID:21482442
Where systems biology meets postharvest

USDA-ARS?s Scientific Manuscript database

Interpreting fruit metabolism, particularly tree fruit metabolism, presents unique challenges. Long periods from tree establishment to fruiting render techniques directed towards reducing the complexity of metabolic mechanisms, such as genomic modification, relatively difficult. Consequently, holi...
Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity.

PubMed Central

Basu, S; Mandal, C; Allen, A K

1988-01-01

A unique sialic acid-binding lectin, achatininH (ATNH) was purified in single step from the haemolymph of the snail Achatina fulica by affinity chromatography on sheep submaxillary-gland mucin coupled to Sepharose 4B. The homogeneity was checked by alkaline gel electrophoresis, immunodiffusion and immunoelectrophoresis. Amino acid analysis showed that the lectin has a fairly high content of acidic amino acid residues (22% of the total). About 1.3% of the residues are half-cystine. The glycoprotein contains 21% carbohydrate. The unusually high content of xylose (6%) and fucose (2.7%) in this snail lectin is quite interesting. The protein was subjected to various chemical modifications in order to detect the amino acid residues and carbohydrate residues present in its binding sites. Modification of tyrosine and arginine residues did not affect the binding activity of ATNH; however, modification of tryptophan and histidine residues led to a complete loss of its biological activity. A marked decrease in the fluorescence emission was found as the tryptophan residues of ATNH were modified. The c.d. data showed the presence of an identical type of conformation in the native and modified agglutinin. The modification of lysine and carboxy residues partially diminished the biological activity. The activity was completely lost after a beta-elimination reaction, indicating that the sugars are O-glycosidically linked to the glycoprotein's protein moiety. This result confirms that the carbohydrate moiety also plays an important role in the agglutination property of this lectin. Images Fig. 3. PMID:3140796
Soft Cysteine Signaling Network: The Functional Significance of Cysteine in Protein Function and the Soft Acids/Bases Thiol Chemistry That Facilitates Cysteine Modification.

PubMed

Wible, Ryan S; Sutter, Thomas R

2017-03-20

The unique biophysical and electronic properties of cysteine make this molecule one of the most biologically critical amino acids in the proteome. The defining sulfur atom in cysteine is much larger than the oxygen and nitrogen atoms more commonly found in the other amino acids. As a result of its size, the valence electrons of sulfur are highly polarizable. Unique protein microenvironments favor the polarization of sulfur, thus increasing the overt reactivity of cysteine. Here, we provide a brief overview of the endogenous generation of reactive oxygen and electrophilic species and specific examples of enzymes and transcription factors in which the oxidation or covalent modification of cysteine in those proteins modulates their function. The perspective concludes with a discussion of cysteine chemistry and biophysics, the hard and soft acids and bases model, and the proposal of the Soft Cysteine Signaling Network: a hypothesis proposing the existence of a complex signaling network governed by layered chemical reactivity and cross-talk in which the chemical modification of reactive cysteine in biological networks triggers the reorganization of intracellular biochemistry to mitigate spikes in endogenous or exogenous oxidative or electrophilic stress.
ASPOD modifications of 1993-1994

NASA Technical Reports Server (NTRS)

Jackson, Jennifer J. (Editor); Fogarty, Paul W.; Muller, Matthew; Martucci, Thomas A., III; Williams, Daniel; Rowney, David A.

1994-01-01

ASPOD, Autonomous Space Processors for Orbital Debris, provides a unique way of collecting the space debris that has built up over the past 37 years. For the past several years, ASPOD has gone through several different modifications. This year's concentrations were on the solar cutting array, the solar tracker, the earth based main frame/tilt table, the controls for the two robotic arms, and accurate autocad drawings of ASPOD. This final report contains the reports written by the students who worked on the ASPOD project this year.
Plasma technologies application for building materials surface modification

NASA Astrophysics Data System (ADS)

Volokitin, G. G.; Skripnikova, N. K.; Volokitin, O. G.; Shehovtzov, V. V.; Luchkin, A. G.; Kashapov, N. F.

2016-01-01

Low temperature arc plasma was used to process building surface materials, such as silicate brick, sand lime brick, concrete and wood. It was shown that building surface materials modification with low temperature plasma positively affects frost resistance, water permeability and chemical resistance with high adhesion strength. Short time plasma processing is rather economical than traditional processing thermic methods. Plasma processing makes wood surface uniquely waterproof and gives high operational properties, dimensional and geometrical stability. It also increases compression resistance and decreases inner tensions level in material.
Surface modification of ferritic steels using MEVVA and duoplasmatron ion sources

NASA Astrophysics Data System (ADS)

Kulevoy, Timur V.; Chalyhk, Boris B.; Fedin, Petr A.; Sitnikov, Alexey L.; Kozlov, Alexander V.; Kuibeda, Rostislav P.; Andrianov, Stanislav L.; Orlov, Nikolay N.; Kravchuk, Konstantin S.; Rogozhkin, Sergey V.; Useinov, Alexey S.; Oks, Efim M.; Bogachev, Alexey A.; Nikitin, Alexander A.; Iskandarov, Nasib A.; Golubev, Alexander A.

2016-02-01

Metal Vapor Vacuum Arc (MEVVA) ion source (IS) is a unique tool for production of high intensity metal ion beam that can be used for material surface modification. From the other hand, the duoplasmatron ion source provides the high intensity gas ion beams. The MEVVA and duoplasmatron IS developed in Institute for Theoretical and Experimental Physics were used for the reactor steel surface modification experiments. Response of ferritic-martensitic steel specimens on titanium and nitrogen ions implantation and consequent vacuum annealing was investigated. Increase in microhardness of near surface region of irradiated specimens was observed. Local chemical analysis shows atom mixing and redistribution in the implanted layer followed with formation of ultrafine precipitates after annealing.
Modifications and integration of the electronic tracking board in a pediatric emergency department.

PubMed

Dexheimer, Judith W; Kennebeck, Stephanie

2013-07-01

Electronic health records (EHRs) are used for data storage; provider, laboratory, and patient communication; clinical decision support; procedure and medication orders; and decision support alerts. Clinical decision support is part of any EHR and is designed to help providers make better decisions. The emergency department (ED) poses a unique environment to the use of EHRs and clinical decision support. Used effectively, computerized tracking boards can help improve flow, communication, and the dissemination of pertinent visit information between providers and other departments in a busy ED. We discuss the unique modifications and decisions made in the implementation of an EHR and computerized tracking board in a pediatric ED. We discuss the changing views based on provider roles, customization to the user interface including the layout and colors, decision support, tracking board best practices collected from other institutions and colleagues, and a case study of using reminders on the electronic tracking board to drive pain reassessments.
Meditope-Fab interaction: threading the hole.

PubMed

Bzymek, Krzysztof P; Ma, Yuelong; Avery, Kendra N; Horne, David A; Williams, John C

2017-12-01

Meditope, a cyclic 12-residue peptide, binds to a unique binding side between the light and heavy chains of the cetuximab Fab. In an effort to improve the affinity of the interaction, it was sought to extend the side chain of Arg8 in the meditope, a residue that is accessible from the other side of the meditope binding site, in order to increase the number of interactions. These modifications included an n-butyl and n-octyl extension as well as hydroxyl, amine and carboxyl substitutions. The atomic structures of the complexes and the binding kinetics for each modified meditope indicated that each extension threaded through the Fab `hole' and that the carboxyethylarginine substitution makes a favorable interaction with the Fab, increasing the half-life of the complex by threefold compared with the unmodified meditope. Taken together, these studies provide a basis for the design of additional modifications to enhance the overall affinity of this unique interaction.
In situ and ex situ modifications of bacterial cellulose for applications in tissue engineering.

PubMed

Stumpf, Taisa Regina; Yang, Xiuying; Zhang, Jingchang; Cao, Xudong

2018-01-01

Bacterial cellulose (BC) is secreted by a few strains of bacteria and consists of a cellulose nanofiber network with unique characteristics. Because of its excellent mechanical properties, outstanding biocompatibilities, and abilities to form porous structures, BC has been studied for a variety of applications in different fields, including the use as a biomaterial for scaffolds in tissue engineering. To extend its applications in tissue engineering, native BC is normally modified to enhance its properties. Generally, BC modifications can be made by either in situ modification during cell culture or ex situ modification of existing BC microfibers. In this review we will first provide a brief introduction of BC and its attributes; this will set the stage for in-depth and up-to-date discussions on modified BC. Finally, the review will focus on in situ and ex situ modifications of BC and its applications in tissue engineering, particularly in bone regeneration and wound dressing. Copyright © 2016. Published by Elsevier B.V.
Internal and external 2-d boundary layer flows

NASA Technical Reports Server (NTRS)

Crawford, M. E.; Kays, W. M.

1978-01-01

Computer program computes general two dimensional turbulent boundary-layer flow using finite-difference techniques. Structure allows for user modification to accommodate unique problems. Program should prove useful in many applications where accurate boundary-layer flow calculations are required.
Detection and quantification of RNA 2′-O-methylation and pseudouridylation

PubMed Central

Karijolich, John

2016-01-01

RNA-guided RNA modification is a naturally occurring process that introduces 2′-O-methylation and pseudouridylation into rRNA, spliceosomal snRNA and several other types of RNA. The Box C/D ribonucleoproteins (RNP) and Box H/ACA RNP, each containing one unique guide RNA (Box C/D RNA or Box H/ACA RNA) and a set of core proteins, are responsible for 2′-O-methylation and pseudouridylation respectively. Box C/D RNA and Box H/ACA RNA provide the modification specificity through base pairing with their RNA substrate. These post-transcriptional modifications could profoundly alter the properties and functions of substrate RNAs. Thus it is desirable to establish reliable and standardized modification methods to study biological functions of modified nucleotides in RNAs. Here, we present several sensitive and efficient methods and protocols for detecting and quantifying post-transcriptional 2′-O-methylation and pseudouridylation. PMID:26853326

Surface Modification of Nonwoven fabrics by Atmospheric Brush Plasma

NASA Astrophysics Data System (ADS)

Oksuz, Lutfi; Uygun, Emre; Bozduman, Ferhat; Yurdabak Karaca, Gozde; Asan, Orkun Nuri; Uygun Oksuz, Aysegul

2017-10-01

Polypropylene nonwoven fabrics (PPNF) are used in disposable absorbent articles, such as diapers, feminine care products, wipes. PPNF need to be wettable by water or aqueous-based liquid. Plasma surface treatment/modification has turned out to be a well-accepted method since it offers superior surface property enhancement than other chemical methods. The cold plasma brush can most efficiently use the discharge power as well as the plasma gas for material and surface treatment. The very low power consumption of such an atmospheric argon plasma brush provides many unique advantages in practical application. The purpose of this study was to reveal the effectiveness of non-thermal atmospheric plasma brush in surface wettability and modification of two different nonwoven surfaces.
Synergistic prevention of biofouling in seawater desalination by zwitterionic surfaces and low-level chlorination.

PubMed

Yang, Rong; Jang, Hongchul; Stocker, Roman; Gleason, Karen K

2014-03-19

Smooth, durable, ultrathin antifouling layers are deposited onto commercial reverse osmosis membranes without damaging them and they exhibit a fouling reduction. A new synergistic approach to antifouling, by coupling surface modification and drinking-water-level chlorination is enabled by the films' unique resistance against chlorine degradation. This approach substantially enhances longer-term fouling resistance compared with surface modification or chlorination alone, and can reduce freshwater production cost and its collateral toxicity to marine biota. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The Modification of Biocellular Chemical Reactions by Environmental Physicochemicals

NASA Astrophysics Data System (ADS)

Ishido, M.

Environmental risk factors affect human biological system to different extent from modification of biochemical reaction to cellular catastrophe. There are considerable public concerns about electromagnetic fields and endocrine disruptors. Their risk assessments have not been fully achieved because of their scientific uncertainty: electromagnetic fields just modify the bioreaction in the restricted cells and endocrine disruptors are quite unique in that their expression is dependent on the exposure periods throughout a life. Thus, we here describe their molecular characterization to establish the new risk assessments for environmental physicochemicals.
Characterization of Tyrosine Nitration and Cysteine Nitrosylation Modifications by Metastable Atom-Activation Dissociation Mass Spectrometry

NASA Astrophysics Data System (ADS)

Cook, Shannon L.; Jackson, Glen P.

2011-02-01

The fragmentation behavior of nitrated and S-nitrosylated peptides were studied using collision induced dissociation (CID) and metastable atom-activated dissociation mass spectrometry (MAD-MS). Various charge states, such as 1+, 2+, 3+, 2-, of modified and unmodified peptides were exposed to a beam of high kinetic energy helium (He) metastable atoms resulting in extensive backbone fragmentation with significant retention of the post-translation modifications (PTMs). Whereas the high electron affinity of the nitrotyrosine moiety quenches radical chemistry and fragmentation in electron capture dissociation (ECD) and electron transfer dissociation (ETD), MAD does produce numerous backbone cleavages in the vicinity of the modification. Fragment ions of nitrosylated cysteine modifications typically exhibit more abundant neutral losses than nitrated tyrosine modifications because of the extremely labile nature of the nitrosylated cysteine residues. However, compared with CID, MAD produced between 66% and 86% more fragment ions, which preserved the labile -NO modification. MAD was also able to differentiate I/L residues in the modified peptides. MAD is able to induce radical ion chemistry even in the presence of strong radical traps and therefore offers unique advantages to ECD, ETD, and CID for determination of PTMs such as nitrated and S-nitrosylated peptides.
Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi.

PubMed

de Jesus, Teresa Cristina Leandro; Nunes, Vinícius Santana; Lopes, Mariana de Camargo; Martil, Daiana Evelin; Iwai, Leo Kei; Moretti, Nilmar Silvio; Machado, Fabrício Castro; de Lima-Stein, Mariana L; Thiemann, Otavio Henrique; Elias, Maria Carolina; Janzen, Christian; Schenkman, Sergio; da Cunha, Julia Pinheiro Chagas

2016-06-03

Histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, DNA damage repair, and chromosome condensation. In early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based processes. Here, by using high-resolution mass spectrometry, we identified and quantified histone post-translational modifications in two life cycle stages of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. We detected 44 new modifications, namely: 18 acetylations, seven monomethylations, seven dimethylations, seven trimethylations, and four phosphorylations. We found that replicative (epimastigote stage) contains more histone modifications than nonreplicative and infective parasites (trypomastigote stage). Acetylations of lysines at the C-terminus of histone H2A and methylations of lysine 23 of histone H3 were found to be enriched in trypomastigotes. In contrast, phosphorylation in serine 23 of H2B and methylations of lysine 76 of histone H3 predominates in proliferative states. The presence of one or two methylations in the lysine 76 was found in cells undergoing mitosis and cytokinesis, typical of proliferating parasites. Our findings provide new insights into the role of histone modifications related to the control of gene expression and cell-cycle regulation in an early divergent organism.
Comprehensive Analysis of Protein Modifications by Top-down Mass Spectrometry

PubMed Central

Zhang, Han; Ge, Ying

2012-01-01

Mass spectrometry (MS)-based proteomics is playing an increasingly important role in cardiovascular research. Proteomics includes not only identification and quantification of proteins, but also the characterization of protein modifications such as post-translational modifications and sequence variants. The conventional bottom-up approach, involving proteolytic digestion of proteins into small peptides prior to MS analysis, is routinely used for protein identification and quantification with high throughput and automation. Nevertheless, it has limitations in the analysis of protein modifications mainly due to the partial sequence coverage and loss of connections among modifications on disparate portions of a protein. An alternative approach, top-down MS, has emerged as a powerful tool for the analysis of protein modifications. The top-down approach analyzes whole proteins directly, providing a “bird’s eye” view of all existing modifications. Subsequently, each modified protein form can be isolated and fragmented in the mass spectrometer to locate the modification site. The incorporation of the non-ergodic dissociation methods such as electron capture dissociation (ECD) greatly enhances the top-down capabilities. ECD is especially useful for mapping labile post-translational modifications which are well-preserved during the ECD fragmentation process. Top-down MS with ECD has been successfully applied to cardiovascular research with the unique advantages in unraveling the molecular complexity, quantifying modified protein forms, complete mapping of modifications with full sequence coverage, discovering unexpected modifications, and identifying and quantifying positional isomers and determining the order of multiple modifications. Nevertheless, top-down MS still needs to overcome some technical challenges to realize its full potential. Herein, we reviewed the advantages and challenges of top-down methodology with a focus on its application in cardiovascular research. PMID:22187450
Modification of Alternan by Dextranase

USDA-ARS?s Scientific Manuscript database

Alternan is a unique glucan with a backbone structure of alternating alpha-(1=-6) and alpha-(1=-3) linkages. Previously, we isolated strains of Penicillium sp. that modify native, high molecular weight alternan in a novel bioconversion process to a lower molecular weight form with solution viscosit...
Development of Scaffolds for Light Harvesting and Photocatalysis from the Coat Protein of Tobacco Mosaic Virus

NASA Astrophysics Data System (ADS)

Dedeo, Michel Toussaint

The utility of a previously developed TMV-based light harvesting system has been dramatically expanded through the introduction of reactive handles for the site-specific modification of the interior and exterior surfaces. Further experiments to reengineer the coat protein have produced structures with unique, unexpected, and useful assembly properties that complement the newly available surface modifications. Energy transfer from chromophores in the RNA channel of self-assembled TMV structures to the exterior was made possible by conjugation of acceptor dyes and porphyrins to the N-terminus. By repositioning the N-terminus to the pore through circular permutation, this process was repeated to create structures that mimic the light harvesting 1 complex of photosynthetic bacteria. To study and improve upon natural photosynthesis, closely packed chromophore arrays and gold nanoparticles were tethered to the pore of stabilized TMV disks through introduction of a uniquely reactive lysine. Finally, a dimeric TMV coat protein was produced to control the distribution and arrangement of synthetic groups with synergistic activity.
Primetime for Learning Genes.

PubMed

Keifer, Joyce

2017-02-11

Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene ( BDNF ), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.
Identification of the Phosphorylated Residues in TveIF5A by Mass Spectrometry

PubMed Central

Quintas-Granados, Laura Itzel; López-Camarillo, César; Armas, Jesús Fandiño; Mendoza Hernandez, Guillermo; Alvarez-Sánchez, María Elizbeth

2013-01-01

The initiation factor eIF5A in Trichomonas vaginalis (TveIF5A) is previously shown to undergo hypusination, phosphorylation and glycosylation. Three different pI isoforms of TveIF5A have been reported. The most acidic isoform (pI 5.2) corresponds to the precursor TveIF5A, whereas the mature TveIF5A appears to be the most basic isoform (pI 5.5). In addition, the intermediary isoform (pI 5.3) is found only under polyamine-depleted conditions and restored with exogenous putrescine. We propose that differences in PI are due to phosphorylation of the TveIF5A isoforms. Here, we have identified phosphorylation sites using mass spectrometry. The mature TveIF5A contains four phosphorylated residues (S3, T55, T78 and T82). Phosphorylation at S3 and T82 is also identified in the intermediary TveIF5A, while no phosphorylated residues are found in the precursor TveIF5A. It has been demonstrated that eIF5A proteins from plants and yeast are phosphorylated by a casein kinase 2 (CK2). Interestingly, a gene encoding a protein highly similar to CK2 (TvCK2) is found in T. vaginalis, which might be involved in the phosphorylation of TveIF5A in T. vaginalis. PMID:24308916
Microlabels For Auto Parts

NASA Technical Reports Server (NTRS)

Ash, John P.

1993-01-01

Proposed method of unique labeling and identification of automotive parts greatly simplifies recall campaigns and reduces effort and expense associated. Compressed symbols fully characterize each part by type and manufacturing history. Manufacturers notify only those owners whose cars need repairs or modifications. Similar compressed symbology developed for possible use on spacecraft.
Options for pest and disease control in organic pecan

USDA-ARS?s Scientific Manuscript database

Although organic pecans typically command a higher wholesale and retail price, their production presents a unique set of challenges. Among these are issues of pest and disease management - it is not simply a modification of the conventional, pest and disease management paradigm. Despite these pest ...
New facility for ion beam materials characterization and modification at Los Alamos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tesmer, J.R.; Maggiore, C.J.; Parkin, D.M.

1988-01-01

The Ion Beam Materials Laboratory (IBML) is a new Los Alamos laboratory devoted to the characterization and modification of the near surfaces of materials. The primary instruments of the IBML are a tandem electrostatic accelerator, a National Electrostatics Corp. Model 9SDH, coupled with a Varian CF-3000 ion implanter. The unique organizational structure of the IBML as well as the operational characteristics of the 9SDH (after approximately 3000 h of operation) and the laboratories' research capabilities will be discussed. Examples of current research results will also be presented. 5 refs., 2 figs.
Dermal carbonyl modification is related to the yellowish color change of photo-aged Japanese facial skin.

PubMed

Ogura, Yuki; Kuwahara, Tomohiro; Akiyama, Minoru; Tajima, Shingo; Hattori, Kazuhisa; Okamoto, Kouhei; Okawa, Shinpei; Yamada, Yukio; Tagami, Hachiro; Takahashi, Motoji; Hirao, Tetsuji

2011-10-01

The photo-aged facial skin is characterized by various unique features such as dark spots, wrinkles, and sagging. Elderly people, particularly Asians, tend to show a yellowish skin color change with photo-aging. However, there has been no analytical study conducted on this unique skin color change of the aged facial skin. The purpose of the present study is to examine whether the carbonyl modification in the dermal protein is involved in the yellowish color change that occurs in the photo-aged skin. Normal skin samples excised from the face, abdomen and buttock of variously aged Japanese were separated into the epidermal and the dermal portions. These skin samples were histologically examined for carbonyl modification. Moreover, an in vitro constructed dermis model composed of a contracted collagen gel was treated with acrolein or 4-hydroxynonenal. All these samples were also studied colorimetrically. The dermal samples obtained from the photo-aged facial skin exhibited an appearance of yellowish color, whereas neither the facial epidermis nor the dermis obtained from the abdomen or buttock showed such a yellowish discoloration. The upper layer of the dermis that revealed the yellowish color showed elastosis whose elastic fibers were found to colocalize with carbonyl protein as detected by a labeled hydrazide, as well as by an immunohistochemical examination using the antibody against acrolein adduct. Experimental induction of carbonyl modification in a dermis model in vitro by a long-term treatment with acrolein or 4-hydroxynonenal was found to show the appearance of the yellowish change which was also proven by an increase in b* value of colorimetry. It was more pronounced than that induced by glycation. Our present results strongly suggest that carbonyl modification of the dermal protein is involved in the production of the yellowish color change that is noted in the photo-aged facial skin. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Serving Exceptional Children. A Report to the Idaho Legislature, January 2004.

ERIC Educational Resources Information Center

Idaho State Department of Education, 2004

2004-01-01

This report provides information on 2002-2003 school year activities involving exceptional students. The term "exceptional students" refers to individuals with disabilities or gifts and talents who have unique needs that require specially designed instruction, administrative accommodations, or curriculum modifications in order to receive an…
Planning Lessons for Students with Significant Disabilities in High School English Classes

ERIC Educational Resources Information Center

Apitz, Megan; Ruppar, Andrea; Roessler, Karli; Pickett, Kelly J.

2017-01-01

Students with significant disabilities have intellectual disability and require individualized modifications, adaptations, and supports to access grade-level content (National Center on Educational Outcomes, 2013). This group of students presents a unique challenge for literacy instruction, particularly at the high school level. Teachers must…
Literacy Instruction in the Wake of Common Core State Standards

ERIC Educational Resources Information Center

Barrett-Mynes, Jennifer

2013-01-01

As teachers modify their instruction to meet English Language Arts (ELA) Common Core State Standards (CCSS), how do these modifications influence literacy instruction and learning opportunities afforded to students? While the CCSS standardized objectives for literacy instruction, the enacted curriculum is uniquely shaped by teachers and their…
78 FR 5565 - Modifications to the HIPAA Privacy, Security, Enforcement, and Breach Notification Rules Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... certain health information, such as standards for certain health care transactions conducted electronically and code sets and unique identifiers for health care providers and employers. The HIPAA... HIPAA apply to three types of entities, which are known as ``covered entities'': health care providers...
Plasticity during Childhood and Adolescence: Innovative Approaches to Investigating Neurocognitive Development

ERIC Educational Resources Information Center

Cohen Kadosh, Kathrin; Linden, David E. J.; Lau, Jennifer Y. F.

2013-01-01

Adolescence is a period of profound change, which holds substantial developmental milestones, but also unique challenges to the individual. In this opinion paper, we highlight the potential of combining two recently developed behavioural and neural training techniques (cognitive bias modification and functional magnetic neuroimaging-based…
Nano-organocatalyst: Magnetically retrievable ferrite-anchored glutathione for microwave-assisted Paal-Knorr reaction, Aza-Michael addition and pyrazole synthesis

EPA Science Inventory

Postsynthetic surface modification of magnetic nanoparticles by glutathione imparts desirable chemical functionality and enables the generation of catalytic sites on the surfaces of ensuing organocatalysts. In this article, we discuss the developments, unique activity and high s...

Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy.

PubMed

Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

2016-06-01

Despite remarkable advancements, clinical evaluations of adenovirus (Ad)-mediated cancer gene therapies have highlighted the need for improved delivery and targeting. Genetic modification of Ad capsid proteins has been extensively attempted. Although genetic modification enhances the therapeutic potential of Ad, it is difficult to successfully incorporate extraneous moieties into the capsid and the engineering process is laborious. Recently, chemical modification of the Ad surface with nanomaterials and targeting moieties has been found to enhance Ad internalization into the target by both passive and active mechanisms. Alternatively, external stimulus-mediated targeting can result in selective accumulation of Ad in the tumor and prevent dissemination of Ad into surrounding nontarget tissues. In the present review, we discuss various genetic, chemical, and mechanical engineering strategies for overcoming the challenges that hinder the therapeutic efficacy of Ad-based approaches. Surface modification of Ad by genetic, chemical, or mechanical engineering strategies enables Ad to overcome the shortcomings of conventional Ad and enhances delivery efficiency through distinct and unique mechanisms that unmodified Ad cannot mimic. However, although the therapeutic potential of Ad-mediated gene therapy has been enhanced by various surface modification strategies, each strategy still possesses innate limitations that must be addressed, requiring innovative ideas and designs.
A systematic review of recommended modifications of CBT for people with cognitive impairments following brain injury.

PubMed

Gallagher, Melanie; McLeod, Hamish J; McMillan, Thomas M

2016-11-22

Due to diverse cognitive, emotional and interpersonal changes that can follow brain injury, psychological therapies often need to be adapted to suit the complex needs of this population. The aims of the study were to synthesise published recommendations for therapy modifications following brain injury from non-progressive traumatic, vascular, or metabolic causes and to determine how often such modifications have been applied to cognitive behavioural therapy (CBT) for post-injury emotional adjustment problems. A systematic review and narrative synthesis of therapy modifications recommended in review articles and reported in intervention studies was undertaken. Database and manual searches identified 688 unique papers of which eight review articles and 16 intervention studies met inclusion criteria. The review articles were thematically analysed and a checklist of commonly recommended modifications composed. The checklist items clustered under themes of: therapeutic education and formulation; attention; communication; memory; and executive functioning. When this checklist was applied to the intervention studies, memory aids and an emphasis on socialising patients to the CBT model were most frequently reported as adaptations. It was concluded that the inconsistent reporting of psychological therapy adaptations for people with brain injury is a barrier to developing effective and replicable therapies. We present a comprehensive account of potential modifications that should be used to guide future research and practice.
Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

PubMed

Sen, Dilara; Keung, Albert J

2018-01-01

The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.
Genome engineering via homologous recombination in mouse embryonic stem (ES) cells: an amazingly versatile tool for the study of mammalian biology.

PubMed

Babinet, C; Cohen-Tannoudji, M

2001-09-01

The ability to introduce genetic modifications in the germ line of complex organisms has been a long-standing goal of those who study developmental biology. In this regard, the mouse, a favorite model for the study of the mammals, is unique: indeed not only is it possible since the late seventies, to add genes to the mouse genome like in several other complex organisms but also to perform gene replacement and modification. This has been made possible via two technological breakthroughs: 1) the isolation and culture of embryonic stem cells (ES), which have the unique ability to colonize all the tissues of an host embryo including its germ line; 2) the development of methods allowing homologous recombination between an incoming DNA and its cognate chromosomal sequence (gene "targeting"). As a result, it has become possible to create mice bearing null mutations in any cloned gene (knock-out mice). Such a possibility has revolutionized the genetic approach of almost all aspects of the biology of the mouse. In recent years, the scope of gene targeting has been widened even more, due to the refinement of the knock-out technology: other types of genetic modifications may now be created, including subtle mutations (point mutations, micro deletions or insertions, etc.) and chromosomal rearrangements such as large deletions, duplications and translocations. Finally, methods have been devised which permit the creation of conditional mutations, allowing the study of gene function throughout the life of an animal, when gene inactivation entails embryonic lethality. In this paper, we present an overview of the methods and scenarios used for the programmed modification of mouse genome, and we underline their enormous interest for the study of mammalian biology.
Structural basis of ubiquitin modification by the Legionella effector SdeA.

PubMed

Dong, Yanan; Mu, Yajuan; Xie, Yongchao; Zhang, Yupeng; Han, Youyou; Zhou, Yu; Wang, Wenhe; Liu, Zihe; Wu, Mei; Wang, Hao; Pan, Man; Xu, Ning; Xu, Cong-Qiao; Yang, Maojun; Fan, Shilong; Deng, Haiteng; Tan, Tianwei; Liu, Xiaoyun; Liu, Lei; Li, Jun; Wang, Jiawei; Fang, Xianyang; Feng, Yue

2018-05-01

Protein ubiquitination is a multifaceted post-translational modification that controls almost every process in eukaryotic cells. Recently, the Legionella effector SdeA was reported to mediate a unique phosphoribosyl-linked ubiquitination through successive modifications of the Arg42 of ubiquitin (Ub) by its mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains. However, the mechanisms of SdeA-mediated Ub modification and phosphoribosyl-linked ubiquitination remain unknown. Here we report the structures of SdeA in its ligand-free, Ub-bound and Ub-NADH-bound states. The structures reveal that the mART and PDE domains of SdeA form a catalytic domain over its C-terminal region. Upon Ub binding, the canonical ADP-ribosyltransferase toxin turn-turn (ARTT) and phosphate-nicotinamide (PN) loops in the mART domain of SdeA undergo marked conformational changes. The Ub Arg72 might act as a 'probe' that interacts with the mART domain first, and then movements may occur in the side chains of Arg72 and Arg42 during the ADP-ribosylation of Ub. Our study reveals the mechanism of SdeA-mediated Ub modification and provides a framework for further investigations into the phosphoribosyl-linked ubiquitination process.
Dramatic colour changes in a bird of paradise caused by uniquely structured breast feather barbules.

PubMed

Stavenga, Doekele G; Leertouwer, Hein L; Marshall, N Justin; Osorio, Daniel

2011-07-22

The breast-plate plumage of male Lawes' parotia (Parotia lawesii) produces dramatic colour changes when this bird of paradise displays on its forest-floor lek. We show that this effect is achieved not solely by the iridescence--that is an angular-dependent spectral shift of the reflected light--which is inherent in structural coloration, but is based on a unique anatomical modification of the breast-feather barbule. The barbules have a segmental structure, and in common with many other iridescent feathers, they contain stacked melanin rodlets surrounded by a keratin film. The unique property of the parotia barbules is their boomerang-like cross section. This allows each barbule to work as three coloured mirrors: a yellow-orange reflector in the plane of the feather, and two symmetrically positioned bluish reflectors at respective angles of about 30°. Movement during the parotia's courtship displays thereby achieves much larger and more abrupt colour changes than is possible with ordinary iridescent plumage. To our knowledge, this is the first example of multiple thin film or multi-layer reflectors incorporated in a single structure (engineered or biological). It nicely illustrates how subtle modification of the basic feather structure can achieve novel visual effects. The fact that the parotia's breast feathers seem to be specifically adapted to give much stronger colour changes than normal structural coloration implies that colour change is important in their courtship display.
[Methods of quantitative proteomics].

PubMed

Kopylov, A T; Zgoda, V G

2007-01-01

In modern science proteomic analysis is inseparable from other fields of systemic biology. Possessing huge resources quantitative proteomics operates colossal information on molecular mechanisms of life. Advances in proteomics help researchers to solve complex problems of cell signaling, posttranslational modification, structure and functional homology of proteins, molecular diagnostics etc. More than 40 various methods have been developed in proteomics for quantitative analysis of proteins. Although each method is unique and has certain advantages and disadvantages all these use various isotope labels (tags). In this review we will consider the most popular and effective methods employing both chemical modifications of proteins and also metabolic and enzymatic methods of isotope labeling.
Recent advances of molecular toolbox construction expand Pichia pastoris in synthetic biology applications.

PubMed

Kang, Zhen; Huang, Hao; Zhang, Yunfeng; Du, Guocheng; Chen, Jian

2017-01-01

Pichia pastoris: (reclassified as Komagataella phaffii), a methylotrophic yeast strain has been widely used for heterologous protein production because of its unique advantages, such as readily achievable high-density fermentation, tractable genetic modifications and typical eukaryotic post-translational modifications. More recently, P. pastoris as a metabolic pathway engineering platform has also gained much attention. In this mini-review, we addressed recent advances of molecular toolboxes, including synthetic promoters, signal peptides, and genome engineering tools that established for P. pastoris. Furthermore, the applications of P. pastoris towards synthetic biology were also discussed and prospected especially in the context of genome-scale metabolic pathway analysis.
UPTAKE, DISTRIBUTION, AND BIOCONVERSION OF FLUORESCENT LIPID ANALOGS IN THE OYSTER PROTOZOAN PARASITE, PERKINSUS MARINUS

EPA Science Inventory

It has been established that host lipids play a unique role for long term survival and life cycle completion in endogenous parasites. Parasites exploit fatty acids and lipids from the host, not only for membrane synthesis, but also for modification of their surface integrity to a...
On Precipitation Modification by Major Urban Areas: A New Perspective from TRMM

NASA Technical Reports Server (NTRS)

Pierce, Harold; Shepherd, J. Marshall; Starr, David OC. (Technical Monitor)

2001-01-01

By year 2025, 80% of the world's population will live in cities, according to a 1999 United Nation's report. As cities continue to grow, urban sprawl creates unique challenges related to land use planning, transportation, agriculture, housing, pollution, and development. Urban expansion also has measurable impact on environmental process.
On Selected Phonological Patterns in Saudi Arabian Sign Language

ERIC Educational Resources Information Center

Tomita, Nozomi; Kozak, Viola

2012-01-01

This paper focuses on two selected phonological patterns that appear unique to Saudi Arabian Sign Language (SASL). For both sections of this paper, the overall methodology is the same as that discussed in Stephen and Mathur (this volume), with some additional modifications tailored to the specific studies discussed here, which will be expanded…
Adaptive Physical Education and Aquatics for Students with Disabilities: A Teacher's Unique Experience

ERIC Educational Resources Information Center

Blassingame, Jennifer Cheryl

2011-01-01

Students with the most severe disabilities have special needs that cannot be addressed with general education curriculum modifications in a traditional prekindergarten-12th grade environment (Heward, 2006). It is essential that expert teachers with specialized educational background and training are prepared to adapt daily lessons to accommodate…
Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein,more » we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.« less
High-pressure polymorphism of As2S3 and new AsS2 modification with layered structure

NASA Astrophysics Data System (ADS)

Bolotina, N. B.; Brazhkin, V. V.; Dyuzheva, T. I.; Katayama, Y.; Kulikova, L. F.; Lityagina, L. V.; Nikolaev, N. A.

2014-01-01

At normal pressure, the As2S3 compound is the most stable equilibrium modification with unique layered structure. The possibility of high-pressure polymorphism of this substance remains questionable. Our research showed that the As2S3 substance was metastable under pressures P > 6 GPa decomposing into two high-pressure phases: As2S3 → AsS2 + AsS. New AsS2 phase can be conserved in the single crystalline form in metastable state at room pressure up to its melting temperature (470 K). This modification has the layered structure with P1211 monoclinic symmetry group; the unit-cell values are a = 7.916(2) Å, b = 9.937(2) Å, c = 7.118(1) Å, β = 106.41° ( Z = 8, density 3.44 g/cm3). Along with the recently studied AsS high-pressure modification, the new AsS2 phase suggests that high pressure polymorphism is a very powerful tool to create new layered-structure phases with "wrong" stoichiometry.
The RNA polymerase II CTD coordinates transcription and RNA processing

PubMed Central

Hsin, Jing-Ping; Manley, James L.

2012-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit consists of multiple heptad repeats (consensus Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7), varying in number from 26 in yeast to 52 in vertebrates. The CTD functions to help couple transcription and processing of the nascent RNA and also plays roles in transcription elongation and termination. The CTD is subject to extensive post-translational modification, most notably phosphorylation, during the transcription cycle, which modulates its activities in the above processes. Therefore, understanding the nature of CTD modifications, including how they function and how they are regulated, is essential to understanding the mechanisms that control gene expression. While the significance of phosphorylation of Ser2 and Ser5 residues has been studied and appreciated for some time, several additional modifications have more recently been added to the CTD repertoire, and insight into their function has begun to emerge. Here, we review findings regarding modification and function of the CTD, highlighting the important role this unique domain plays in coordinating gene activity. PMID:23028141
Nanoscale surface modification of Li-rich layered oxides for high-capacity cathodes in Li-ion batteries

NASA Astrophysics Data System (ADS)

Lan, Xiwei; Xin, Yue; Wang, Libin; Hu, Xianluo

2018-03-01

Li-rich layered oxides (LLOs) have been developed as a high-capacity cathode material for Li-ion batteries, but the structural complexity and unique initial charging behavior lead to several problems including large initial capacity loss, capacity and voltage fading, poor cyclability, and inferior rate capability. Since the surface conditions are critical to electrochemical performance and the drawbacks, nanoscale surface modification for improving LLO's properties is a general strategy. This review mainly summarizes the surface modification of LLOs and classifies them into three types of surface pre-treatment, surface gradient doping, and surface coating. Surface pre-treatment usually introduces removal of Li2O for lower irreversible capacity while surface doping is aimed to stabilize the structure during electrochemical cycling. Surface coating layers with different properties, protective layers to suppress the interface side reaction, coating layers related to structural transformation, and electronic/ionic conductive layers for better rate capability, can avoid the shortcomings of LLOs. In addition to surface modification for performance enhancement, other strategies can also be investigated to achieve high-performance LLO-based cathode materials.
Key advances in the chemical modification of nanocelluloses.

PubMed

Habibi, Youssef

2014-03-07

Nanocelluloses, including nanocrystalline cellulose, nanofibrillated cellulose and bacterial cellulose nanofibers, have become fascinating building blocks for the design of new biomaterials. Derived from the must abundant and renewable biopolymer, they are drawing a tremendous level of attention, which certainly will continue to grow in the future driven by the sustainability trend. This growing interest is related to their unsurpassed quintessential physical and chemical properties. Yet, owing to their hydrophilic nature, their utilization is restricted to applications involving hydrophilic or polar media, which limits their exploitation. With the presence of a large number of chemical functionalities within their structure, these building blocks provide a unique platform for significant surface modification through various chemistries. These chemical modifications are prerequisite, sometimes unavoidable, to adapt the interfacial properties of nanocellulose substrates or adjust their hydrophilic-hydrophobic balance. Therefore, various chemistries have been developed aiming to surface-modify these nano-sized substrates in order to confer to them specific properties, extending therefore their use to highly sophisticated applications. This review collocates current knowledge in the research and development of nanocelluloses and emphasizes more particularly on the chemical modification routes developed so far for their functionalization.
Decoding the Effect of Isobaric Substitutions on Identifying Missing Proteins and Variant Peptides in Human Proteome.

PubMed

Choong, Wai-Kok; Lih, Tung-Shing Mamie; Chen, Yu-Ju; Sung, Ting-Yi

2017-12-01

To confirm the existence of missing proteins, we need to identify at least two unique peptides with length of 9-40 amino acids of a missing protein in bottom-up mass-spectrometry-based proteomic experiments. However, an identified unique peptide of the missing protein, even identified with high level of confidence, could possibly coincide with a peptide of a commonly observed protein due to isobaric substitutions, mass modifications, alternative splice isoforms, or single amino acid variants (SAAVs). Besides unique peptides of missing proteins, identified variant peptides (SAAV-containing peptides) could also alternatively map to peptides of other proteins due to the aforementioned issues. Therefore, we conducted a thorough comparative analysis on data sets in PeptideAtlas Tiered Human Integrated Search Proteome (THISP, 2017-03 release), including neXtProt (2017-01 release), to systematically investigate the possibility of unique peptides in missing proteins (PE2-4), unique peptides in dubious proteins, and variant peptides affected by isobaric substitutions, causing doubtful identification results. In this study, we considered 11 isobaric substitutions. From our analysis, we found <5% of the unique peptides of missing proteins and >6% of variant peptides became shared with peptides of PE1 proteins after isobaric substitutions.
Setting Adolescents up for Success: Promoting a Policy to Delay High School Start Times

ERIC Educational Resources Information Center

Barnes, Margaux; Davis, Krista; Mancini, Mackenzie; Ruffin, Jasmine; Simpson, Tina; Casazza, Krista

2016-01-01

Background: A unique biological shift in sleep cycles occurs during adolescence causing later sleep and wake times. This shift is not matched by a concurrent modification in school start times, resulting in sleep curtailment for a large majority of adolescents. Chronic inadequate sleep is associated with poor academic performance including…
Modifications to a LATE MERISTEM IDENTITY-1 gene are responsible for the major leaf shapes of Upland cotton (Gossypium hirsutum L.)

USDA-ARS?s Scientific Manuscript database

Leaf shape varies spectacularly among plants. Leaves are the primary source of photo-assimilate in crop plants and understanding the genetic basis of variation in leaf morphology is critical to improving agricultural productivity. Leaf shape played a unique role in cotton improvement, as breeders ha...

Chemically Patterned Inverse Opal Created by a Selective Photolysis Modification Process.

PubMed

Tian, Tian; Gao, Ning; Gu, Chen; Li, Jian; Wang, Hui; Lan, Yue; Yin, Xianpeng; Li, Guangtao

2015-09-02

Anisotropic photonic crystal materials have long been pursued for their broad applications. A novel method for creating chemically patterned inverse opals is proposed here. The patterning technique is based on selective photolysis of a photolabile polymer together with postmodification on released amine groups. The patterning method allows regioselective modification within an inverse opal structure, taking advantage of selective chemical reaction. Moreover, combined with the unique signal self-reporting feature of the photonic crystal, the fabricated structure is capable of various applications, including gradient photonic bandgap and dynamic chemical patterns. The proposed method provides the ability to extend the structural and chemical complexity of the photonic crystal, as well as its potential applications.
Immobilization Techniques in the Fabrication of Nanomaterial-Based Electrochemical Biosensors: A Review

PubMed Central

Putzbach, William; Ronkainen, Niina J.

2013-01-01

The evolution of 1st to 3rd generation electrochemical biosensors reflects a simplification and enhancement of the transduction pathway. However, in recent years, modification of the transducer with nanomaterials has become increasingly studied and imparts many advantages. The sensitivity and overall performance of enzymatic biosensors has improved tremendously as a result of incorporating nanomaterials in their fabrication. Given the unique and favorable qualities of gold nanoparticles, graphene and carbon nanotubes as applied to electrochemical biosensors, a consolidated survey of the different methods of nanomaterial immobilization on transducer surfaces and enzyme immobilization on these species is beneficial and timely. This review encompasses modification of enzymatic biosensors with gold nanoparticles, carbon nanotubes, and graphene. PMID:23580051
Instrumentation and methodology for simultaneous excitation/detection of ions in an FTICR mass spectrometer

PubMed

Schmidt; Fiorentino; Arkin; Laude

2000-08-01

A method for direct and continuous detection of ion motion during different perturbation events of the fourier transform ion cyclotron resonance (FTICR) experiment is demonstrated. The modifications necessary to convert an ordinary FTICR cell into one capable of performing simultaneous excitation/detection (SED) using a capacitive network are outlined. With these modifications, a 200-fold reduction in the detection of the coupled excitation signal is achieved. This allows the unique ability not only to observe the response to the perturbation but to observe the perturbation event itself. SED is used successfully to monitor the ion cyclotron transient during single-frequency excitation, remeasurement and exciter-excite experiments.
Immobilization techniques in the fabrication of nanomaterial-based electrochemical biosensors: a review.

PubMed

Putzbach, William; Ronkainen, Niina J

2013-04-11

The evolution of 1st to 3rd generation electrochemical biosensors reflects a simplification and enhancement of the transduction pathway. However, in recent years, modification of the transducer with nanomaterials has become increasingly studied and imparts many advantages. The sensitivity and overall performance of enzymatic biosensors has improved tremendously as a result of incorporating nanomaterials in their fabrication. Given the unique and favorable qualities of gold nanoparticles, graphene and carbon nanotubes as applied to electrochemical biosensors, a consolidated survey of the different methods of nanomaterial immobilization on transducer surfaces and enzyme immobilization on these species is beneficial and timely. This review encompasses modification of enzymatic biosensors with gold nanoparticles, carbon nanotubes, and graphene.
The Chemical Biology of HNO Signaling

PubMed Central

Bianco, Christopher L.; Toscano, John P.; Bartberger, Michael D.; Fukuto, Jon M.

2016-01-01

Nitroxyl (HNO) is a simple molecule with significant potential as a pharmacological agent. For example, its use in the possible treatment of heart failure has received recent attention due to its unique therapeutic properties. Recent progress has been made on the elucidation of the mechanisms associated with its biological signaling. Importantly, the biochemical mechanisms described for HNO bioactivity are consistent with its unique and novel chemical properties/reactivity. To date, much of the biology of HNO can be associated with interactions and modification of important regulatory thiol proteins. Herein will be provided a description of HNO chemistry and how this chemistry translates to some of its reported biological effects. PMID:27555493
Quantitative PCR measurement of tRNA 2-methylthio modification for assessing type 2 diabetes risk.

PubMed

Xie, Peiyu; Wei, Fan-Yan; Hirata, Shoji; Kaitsuka, Taku; Suzuki, Tsutomu; Suzuki, Takeo; Tomizawa, Kazuhito

2013-11-01

Genetic variants in the human CDKAL1 (CDK5 regulatory subunit associated protein 1-like 1) gene have been associated with reduced insulin secretion and type 2 diabetes (T2D). CDKAL1 is a methylthiotransferase that catalyzes 2-methylthio (ms(2)) modification of the adenine at position 37 (A37) of cytoplasmic tRNA(Lys)(UUU). We investigated the ms(2)-modification level of tRNA(Lys)(UUU) as a direct readout of CDKAL1 enzyme activity in human samples. We developed a quantitative PCR (qPCR)-based method to measure ms(2) modification. tRNA(Lys)(UUU) was reverse-transcribed with 2 unique primers: Reverse primer r1 was designed to anneal to the middle of this tRNA, including the nucleotide at A37, and reverse primer r2 was designed to anneal to the region downstream (3') of A37. Subsequent qPCR was performed to detect the corresponding transcribed cDNAs. The efficiency of reverse transcription of tRNA(Lys)(UUU) was ms(2)-modification dependent. The relative difference in threshold cycle number obtained with the r1 or r2 primer yielded the ms(2)-modification level in tRNA(Lys)(UUU) precisely as predicted by an original mathematical model. The method was capable of measuring ms(2)-modification levels in tRNA(Lys)(UUU) in total RNA isolated from human peripheral blood samples, revealing that the ms(2)-modification rate in tRNA(Lys)(UUU) was decreased in individuals carrying the CDKAL1 genotype associated with T2D. In addition, the ms(2)-modification level was correlated with insulin secretion. The results point to the critical role of ms(2) modification in T2D and to a potential clinical use of a simple and high-throughput method for assessing T2D risk.
Dramatic colour changes in a bird of paradise caused by uniquely structured breast feather barbules

PubMed Central

Stavenga, Doekele G.; Leertouwer, Hein L.; Marshall, N. Justin; Osorio, Daniel

2011-01-01

The breast-plate plumage of male Lawes' parotia (Parotia lawesii) produces dramatic colour changes when this bird of paradise displays on its forest-floor lek. We show that this effect is achieved not solely by the iridescence—that is an angular-dependent spectral shift of the reflected light—which is inherent in structural coloration, but is based on a unique anatomical modification of the breast-feather barbule. The barbules have a segmental structure, and in common with many other iridescent feathers, they contain stacked melanin rodlets surrounded by a keratin film. The unique property of the parotia barbules is their boomerang-like cross section. This allows each barbule to work as three coloured mirrors: a yellow-orange reflector in the plane of the feather, and two symmetrically positioned bluish reflectors at respective angles of about 30°. Movement during the parotia's courtship displays thereby achieves much larger and more abrupt colour changes than is possible with ordinary iridescent plumage. To our knowledge, this is the first example of multiple thin film or multi-layer reflectors incorporated in a single structure (engineered or biological). It nicely illustrates how subtle modification of the basic feather structure can achieve novel visual effects. The fact that the parotia's breast feathers seem to be specifically adapted to give much stronger colour changes than normal structural coloration implies that colour change is important in their courtship display. PMID:21159676
Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology-Veterinary (STROBE-Vet) Statement.

PubMed

Sargeant, J M; O'Connor, A M; Dohoo, I R; Erb, H N; Cevallos, M; Egger, M; Ersbøll, A K; Martin, S W; Nielsen, L R; Pearl, D L; Pfeiffer, D U; Sanchez, J; Torrence, M E; Vigre, H; Waldner, C; Ward, M P

2016-12-01

Reporting of observational studies in veterinary research presents challenges that often are not addressed in published reporting guidelines. Our objective was to develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. We conducted a consensus meeting with 17 experts in Mississauga, Canada. Experts completed a premeeting survey about whether items in the STROBE statement should be modified or added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. During the meeting, each STROBE item was discussed to determine whether or not rewording was recommended, and whether additions were warranted. Anonymous voting was used to determine consensus. Six items required no modifications or additions. Modifications or additions were made to the STROBE items 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources and measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). The methods and processes used were similar to those used for other extensions of the STROBE statement. The use of this STROBE statement extension should improve reporting of observational studies in veterinary research by recognizing unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife.
Using concept maps in a modified team-based learning exercise.

PubMed

Knollmann-Ritschel, Barbara E C; Durning, Steven J

2015-04-01

Medical school education has traditionally been driven by single discipline teaching and assessment. Newer medical school curricula often implement an organ-based approach that fosters integration of basic science and clinical disciplines. Concept maps are widely used in education. Through diagrammatic depiction of a variety of concepts and their specific connections with other ideas, concept maps provide a unique perspective into learning and performance that can complement other assessment methods commonly used in medical schools. In this innovation, we describe using concepts maps as a vehicle for a modified a classic Team-Based Learning (TBL) exercise. Modifications to traditional TBL in our innovation included replacing an individual assessment using multiple-choice questions with concept maps as well as combining the group assessment and application exercise whereby teams created concept maps. These modifications were made to further assess understanding of content across the Fundamentals module (the introductory module of the preclerkship curriculum). While preliminary, student performance and feedback from faculty and students support the use of concept maps in TBL. Our findings suggest concept maps can provide a unique means of determining assessment of learning and generating feedback to students. Concept maps can also demonstrate knowledge acquisition, organization of prior and new knowledge, and synthesis of that knowledge across disciplines in a unique way providing an additional means of assessment in addition to traditional multiple-choice questions. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.
Apparent sixth sense in theropod evolution: The making of a Cretaceous weathervane.

PubMed

Rothschild, Bruce M; Naples, Virginia

2017-01-01

Two separate and distinctive skills are necessary to find prey: Detection of its presence and determination of its location. Surface microscopy of the dentary of albertosaurines revealed a previously undescribed sensory modification, as will be described here. While dentary "foramina" were previously thought to contain tactile sensory organs, the potential function of this theropod modification as a unique localizing system is explored in this study. Dentary surface perforations were examined by surface epi-illumination microscopy in tyrannosaurine and albertosaurine dinosaurs to characterize their anatomy. Fish lateral lines were examined as potentially comparable structures. In contrast to the subsurface vascular bifurcation noted in tyrannosaurines (which lack a lateral dentary surface groove), the area subjacent to the apertures in albertosaurine grooves has the appearance of an expanded chamber. That appearance seemed to be indistinguishable from the lateral line of fish. Dentary groove apertures in certain tyrannosaurid lines (specifically albertosaurines) not only have a unique appearance, but one with significant functional and behavior implications. The appearance of the perforations in the dentary groove of albertosaurines mirrors that previously noted only with specialized neurologic structures accommodating derived sensory functions, as seen in the lateral line of fish. The possibility that this specialized morphology could also represent a unique function in albertosaurine theropods for interacting with the environment or facilitating prey acquisition cannot be ignored. It is suggested that these expanded chambers function in perceiving and aligning the body relative to the direction of wind, perhaps a Cretaceous analogue of the contemporary midwestern weathervane.
A Tyrosine-Reactive Irreversible Inhibitor for Glutathione S-Transferase Pi (GSTP1)

PubMed Central

Crawford, L. A.; Weerapana, E.

2016-01-01

Glutathione S-Transferase Pi (GSTP1) mediates cellular defense against reactive electrophiles. Here, we report LAS17, a dichlorotriazine-containing compound that irreversibly inhibits GSTP1 and is selective for GSTP1 within cellular proteomes. Mass spectrometry and mutational studies identified Y108 as the site of modification, providing a unique mode of GSTP1 inhibition. PMID:27113843
A tyrosine-reactive irreversible inhibitor for glutathione S-transferase Pi (GSTP1).

PubMed

Crawford, L A; Weerapana, E

2016-05-24

Glutathione S-transferase Pi (GSTP1) mediates cellular defense against reactive electrophiles. Here, we report LAS17, a dichlorotriazine-containing compound that irreversibly inhibits GSTP1 and is selective for GSTP1 within cellular proteomes. Mass spectrometry and mutational studies identified Y108 as the site of modification, providing a unique mode of GSTP1 inhibition.
Centres of Specialization & Program Suspensions/Modifications. Final Recommendations [and] Proposed Centres of Specialization & Other Academic Initiatives.

ERIC Educational Resources Information Center

Sir Sandford Fleming Coll., Peterborough (Ontario).

In November 1995, Sir Sandford Fleming College, in Ontario, Canada, developed a proposal to establish centers of specialization, or clusters of related curricula or programs that are unique in a region, and to suspend or curtail existing programs due to funding shortages. Feedback was requested from the college community, with college-wide staff…
77 FR 19691 - Notice of Inventory Completion: Sam Noble Oklahoma Museum of Natural History, Norman, OK

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... mastodon tooth fragment, 1 fossil, 20 mica, 7 quartz, and 1,126 non-cultural rocks. The burial lots from... Arkansas River drainage are also absent in the temporally subsequent Red River sites (such as a unique form... that the Tula encountered by DeSoto practiced an extreme form of cranial modification similar to that...
The XFV-12A Thrust-Augmented Wing (TAW) prototype aircraft

NASA Technical Reports Server (NTRS)

Murphy, R.; Lewis, E. L.

1979-01-01

The XFV-12A, a unique V/STOL technology prototype aircraft being developed for the Navy, is described. The innovative design features a thrust augmented wing and a canard ejector. Structural, functional, and control test performances are discussed. Static tether test results are also discussed. Assessment of test results are given along with projections for future modification areas.
The Availability of Instructional Media for Teaching Mentally Retarded Students in Nyanza Region, Kenya

ERIC Educational Resources Information Center

Odero, Orao Remi

2016-01-01

Learners with mental retardation pose a unique problem to the education system, one not presented by any other exceptionality. In view of the challenges and limitations of these learners, modification of both social and educational environment is fundamental in-order to attain effective schooling for them. One of the best proven medium of teaching…
Treatment of Individuals with Borderline Personality Disorder Using Dialectical Behavior Therapy in a Community Mental Health Setting: Clinical Application and a Preliminary Investigation

ERIC Educational Resources Information Center

Ben-Porath, Denise D.; Peterson, Gregory A.; Smee, Jacqueline

2004-01-01

This article describes an effort to implement and examine dialectical behavior therapy's (DBT) effectiveness in a community mental health setting. Modifications made to address unique aspects of community mental health settings are described. Barriers encountered in implementation of DBT treatment in community mental health settings, such as staff…
RESEARCH INVESTIGATIONS ON THE PROTEOME: 1. MECHANISMS OF REGULATING PROTEIN SYNTHESIS, AND 2. GLOBAL CHARACTERIZATION OF PROTEOMIC RESPONSES TO ARSENIC EXPOSURES

EPA Science Inventory

Eukaryotic Elongation Factor 2 (eEF2) mediates translocation in protein synthesis. eEF2 is modified by two post-translational modifications: the phosphorylation of Thr57 in the G domain and a unique conversion of His699 to diphthamide at the tip of domain IV. Diphthamide is the t...
Technical Considerations for Reduced Representation Bisulfite Sequencing with Multiplexed Libraries

PubMed Central

Chatterjee, Aniruddha; Rodger, Euan J.; Stockwell, Peter A.; Weeks, Robert J.; Morison, Ian M.

2012-01-01

Reduced representation bisulfite sequencing (RRBS), which couples bisulfite conversion and next generation sequencing, is an innovative method that specifically enriches genomic regions with a high density of potential methylation sites and enables investigation of DNA methylation at single-nucleotide resolution. Recent advances in the Illumina DNA sample preparation protocol and sequencing technology have vastly improved sequencing throughput capacity. Although the new Illumina technology is now widely used, the unique challenges associated with multiplexed RRBS libraries on this platform have not been previously described. We have made modifications to the RRBS library preparation protocol to sequence multiplexed libraries on a single flow cell lane of the Illumina HiSeq 2000. Furthermore, our analysis incorporates a bioinformatics pipeline specifically designed to process bisulfite-converted sequencing reads and evaluate the output and quality of the sequencing data generated from the multiplexed libraries. We obtained an average of 42 million paired-end reads per sample for each flow-cell lane, with a high unique mapping efficiency to the reference human genome. Here we provide a roadmap of modifications, strategies, and trouble shooting approaches we implemented to optimize sequencing of multiplexed libraries on an a RRBS background. PMID:23193365
Rare Earth Ion-Doped Upconversion Nanocrystals: Synthesis and Surface Modification

PubMed Central

Chang, Hongjin; Xie, Juan; Zhao, Baozhou; Liu, Botong; Xu, Shuilin; Ren, Na; Xie, Xiaoji; Huang, Ling; Huang, Wei

2014-01-01

The unique luminescent properties exhibited by rare earth ion-doped upconversion nanocrystals (UCNPs), such as long lifetime, narrow emission line, high color purity, and high resistance to photobleaching, have made them widely used in many areas, including but not limited to high-resolution displays, new-generation information technology, optical communication, bioimaging, and therapy. However, the inherent upconversion luminescent properties of UCNPs are influenced by various parameters, including the size, shape, crystal structure, and chemical composition of the UCNPs, and even the chosen synthesis process and the surfactant molecules used. This review will provide a complete summary on the synthesis methods and the surface modification strategies of UCNPs reported so far. Firstly, we summarize the synthesis methodologies developed in the past decades, such as thermal decomposition, thermal coprecipitation, hydro/solvothermal, sol-gel, combustion, and microwave synthesis. In the second part, five main streams of surface modification strategies for converting hydrophobic UCNPs into hydrophilic ones are elaborated. Finally, we consider the likely directions of the future development and challenges of the synthesis and surface modification, such as the large-scale production and actual applications, stability, and so on, of the UCNPs. PMID:28346995

The Modification of Carbon with Iron Oxide Synthesized in Electrolysis Using the Arc Discharge Method

NASA Astrophysics Data System (ADS)

Endah Saraswati, Teguh; Dewi Indah Prasiwi, Oktaviana; Masykur, Abu; Handayani, Nestri; Anwar, Miftahul

2017-02-01

The modification of carbon-based nanomaterials with metals is widely studied due to its unique properties. Here, the modification of carbon nanomaterial with iron oxide has been successfully carried out. This modification was achieved using arc discharge in 50% ethanol liquid media. The anode used in the arc discharge was prepared from a mixture of carbon and iron oxide that was synthesized in electrolysis and was then calcined at 250°C with silicon binder with a mass ratio of 3:1:1, and the cathode used was graphite rod. Both electrodes were set in the nearest gap that could provide an arc during arc-discharging, leading to carbon-based nanoparticle formation. The diffractogram pattern of the X-ray diffraction of the fabricated nanoparticles confirmed the typical peak of carbon, iron oxide and iron. The magnetization value of the result analysis of the vibrating sample magnetometer was 9.9 emu/g. The bandgap energy measurement using diffuse reflectance ultra violet was estimated to be 2.18 eV. Using the transmission electron microscopy, the structure of the nanomaterial produced was observed as carbon-encapsulated iron compound nanoparticles.
The deposition of thin titanium-nitrogen coatings on the surface of PCL-based scaffolds for vascular tissue engineering

NASA Astrophysics Data System (ADS)

Kudryavtseva, Valeriya; Stankevich, Ksenia; Kibler, Elina; Golovkin, Alexey; Mishanin, Alexander; Bolbasov, Evgeny; Choynzonov, Evgeny; Tverdokhlebov, Sergei

2018-04-01

Biodegradable polymer scaffolds for tissue engineering is a promising technology for therapies of patients suffering from the loss of tissue or its function including cardiac tissues. However, limitations such as hydrophobicity of polymers prevent cell attachment, cell conductivity, and endothelialization. Plasma modification of polymers allows producing materials for an impressive range of applications due to their unique properties. Here, we demonstrate the possibility of bioresorbable electrospun polycaprolacton (PCL) scaffold surface modification by reactive magnetron sputtering of the titanium target in a nitrogen atmosphere. The influence of the plasma treatment time on the structure and properties of electrospun PCL scaffolds was studied. We show that the plasma treatment does not change the physico-mechanical properties of electrospun PCL scaffolds, leads to an increase in PCL scaffold biocompatibility, and, simultaneously, increases their hydrophilicity. In conclusion, this modification method opens a route to producing scaffolds with enhanced biocompatibility for tissue engineered vascular grafts.
Improving CRISPR-Cas specificity with chemical modifications in single-guide RNAs.

PubMed

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Bruhn, Laurakay; Dellinger, Douglas J

2018-01-25

CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence ('guide sequence') and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2'-O-methyl-3'-phosphonoacetate, or 'MP') incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Improving CRISPR–Cas specificity with chemical modifications in single-guide RNAs

PubMed Central

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Dellinger, Douglas J

2018-01-01

Abstract CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2′-O-methyl-3′-phosphonoacetate, or ‘MP’) incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. PMID:29216382
Structure of Hydrophobically Modified Phytoglycogen Nanoparticles

NASA Astrophysics Data System (ADS)

Atkinson, John; Nickels, Jonathan; Dutcher, John; Katsaras, John

Phytoglycogen is a highly branched, polysaccharide nanoparticle produced by some varieties of plants including sweet corn. These particles are attractive candidates for cosmetic, industrial and biomedical applications. Many of these applications result from phytoglycogen's unique interaction with water: (1) high solubility; (2) low viscosity and high stability in aqueous dispersions; and (3) a remarkable capacity to sequester and retain water. Neutron scattering measurements of native phytoglycogen revealed that the particles have uniform size, uniform radial particle density, and a high level of hydration. Hydrophobically modifying the outer surface of the hydrophilic nanoparticles opens up new applications in food and biomedicine, such as solubilizing and stabilizing bioactive compounds. One such modification is octenyl succinate anhydride (OSA), where the hydrophobicity can be tuned by adjusting the degree of substitution. I will present the results of small angle neutron scattering (SANS) measurements of aqueous dispersions of OSA-modified phytoglycogen with two different degrees of modification. Contrast series SANS measurements have yielded information about the radial density profile, providing insight into the nature of the chemical modification of the particles.
Planetary/DOD entry technology flight experiments. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Christensen, H. E.; Krieger, R. J.; Mcneilly, W. R.; Vetter, H. C.

1976-01-01

The feasibility of using the space shuttle to launch planetary and DoD entry flight experiments was examined. The results of the program are presented in two parts: (1) simulating outer planet environments during an earth entry test, the prediction of Jovian and earth radiative heating dominated environments, mission strategy, booster performance and entry vehicle design, and (2) the DoD entry test needs for the 1980's, the use of the space shuttle to meet these DoD test needs, modifications of test procedures as pertaining to the space shuttle, modifications to the space shuttle to accommodate DoD test missions and the unique capabilities of the space shuttle. The major findings of this program are summarized.
Scalable human ES culture for therapeutic use: propagation, differentiation, genetic modification and regulatory issues.

PubMed

Rao, M

2008-01-01

Embryonic stem cells unlike most adult stem cell populations can replicate indefinitely while preserving genetic, epigenetic, mitochondrial and functional profiles. ESCs are therefore an excellent candidate cell type for providing a bank of cells for allogenic therapy and for introducing targeted genetic modifications for therapeutic intervention. This ability of prolonged self-renewal of stem cells and the unique advantages that this offers for gene therapy, discovery efforts, cell replacement, personalized medicine and other more direct applications requires the resolution of several important manufacturing, gene targeting and regulatory issues. In this review, we assess some of the advance made in developing scalable culture systems, improvement in vector design and gene insertion technology and the changing regulatory landscape.
Recent applications of carbon nanomaterials in fluorescence biosensing and bioimaging.

PubMed

Wen, Jia; Xu, Yongqian; Li, Hongjuan; Lu, Aiping; Sun, Shiguo

2015-07-21

Carbon-based nanomaterials as important agents for biological applications have emerged in the past few years due to their unique optical, electronic, mechanical, and chemical properties. Many of these applications rely on successful surface modifications. This review article comprises two main parts. In the first part, we briefly review the properties and surface modifications of several classes of carbon nanomaterials, mainly carbon nanotubes (CNTs), graphene and its derivatives, carbon dots (CDs) and graphene quantum dots (GQDs), as well as some other forms of carbon-based nanomaterials such as fullerene, carbon nanohorns (CNHs) and carbon nanoonions (CNOs). In the second part, we focus on the biological applications of these carbon nanomaterials, in particular their applications for fluorescence biosensing as well as bioimaging.
Demonstrating the effect of forensic firearm countermeasures: Bullet characteristics generated due to barrel modifications.

PubMed

O'Keeffe, C; Champion, S; Allsop, D

2015-12-01

Forensic awareness and the declining availability of firearms have resulted in an increase in the use of modified and re-activated firearms in crime. Although some modifications are undertaken to simply acquire a functioning firearm, others are perpetrated as a direct forensic countermeasure to prevent the association between a firearm and a crime. This article describes the effects of these modifications on bullet striation patterns imparted from the barrel to a fired bullet. The key results indicated that the investigated modifications display assessable characteristics. The use of an oversized barrel imparted striations consistent with firing with the absence of typical rifling. Subsequent or consecutively fired bullets possessed striation variations, with the first showing the least evidence of striations. The application of a choke resulted in more obvious bullet elongation compared to a smoothbore barrel. The restriction caused merging of lands and groves of the imparted rifling and obscured their usual definition. Effects of breech adaption were also characterised by observing the buckling and enlargement of the cartridge case. This deformity of the cartridge case was most evident when the barrel pressure increased due to the presence of the choke. From this study it was evident that unique characteristic impressions associated with different modifications most commonly found in criminal investigations can be utilised by a forensic expert and impart significant intelligence to an investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
BuD, a helix–loop–helix DNA-binding domain for genome modification

PubMed Central

Stella, Stefano; Molina, Rafael; López-Méndez, Blanca; Juillerat, Alexandre; Bertonati, Claudia; Daboussi, Fayza; Campos-Olivas, Ramon; Duchateau, Phillippe; Montoya, Guillermo

2014-01-01

DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific protein–DNA interactions in protein scaffolds is key to providing ‘toolkits’ for precise genome modification or regulation of gene expression. In a search for putative DNA-binding domains, BurrH, a protein that recognizes a 19 bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helix–loop–helix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin β (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing. PMID:25004980
Multifunctional transparent ZnO nanorod films.

PubMed

Kwak, Geunjae; Jung, Sungmook; Yong, Kijung

2011-03-18

Transparent ZnO nanorod (NR) films that exhibit extreme wetting states (either superhydrophilicity or superhydrophobicity through surface chemical modification), high transmittance, UV protection and antireflection have been prepared via the facile ammonia hydrothermal method. The periodic 1D ZnO NR arrays showed extreme wetting states as well as antireflection properties due to their unique surface structure and prevented the UVA region from penetrating the substrate due to the unique material property of ZnO. Because of the simple, time-efficient and low temperature preparation process, ZnO NR films with useful functionalities are promising for fabrication of highly light transmissive, antireflective, UV protective, antifogging and self-cleaning optical materials to be used for optical devices and photovoltaic energy devices.
Ensuring the Quality of Outreach: The Critical Role of Evaluating Individual and Collective Initiatives and Performance

ERIC Educational Resources Information Center

Lynton, Ernest A.

2016-01-01

New knowledge is created in the course of the application of outreach. Each complex problem in the real world is likely to have unique aspects and thus it requires some modification of standard approaches. Hence, each engagement in outreach is likely to have an element of inquiry and discovery, leading to new knowledge. The flow of knowledge is in…
Self-Disinfection and Decontaminating Interior Surfaces Based on Photocatalytic Titania/Easy-Release Coatings

DTIC Science & Technology

2002-01-01

DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release, distribution unlimited 13. SUPPLEMENTARY NOTES This article is from ADA409494 Proceedings of...been shown to be independently capable, respectively, of diminishing viability and minimizing bioburdens on interior surfaces. Unique combinations of...active bacterial bioburdens and total retained biomass can be significantly reduced by these surface modifications. Interior surface coatings of TiO2
Electronics for a focal plane crystal spectrometer

NASA Technical Reports Server (NTRS)

Goeke, R. F.

1978-01-01

The HEAO-B program forced the usual constraints upon the spacecraft experiment electronics: high reliability, low power consumption, and tight packaging at reasonable cost. The programmable high voltage power supplies were unique in both application and simplicity of manufacture. The hybridized measurement chain is a modification of that used on the SAS-C program; the charge amplifier design in particular shows definite improvement in performance over previous work.
Early assessment of the trees of the Luquillo Mountains

Treesearch

Frank H. Wadsworth

2009-01-01

This is a description of the composition of a forest in Puerto Rico almost unique in that it probably had not received human modification. It comes from a 1948 inventory of 4,570 hectares of what today is the El Yunque National Forest in the Luquillo Mountains. The inventory, preparatory to a forest management plan, was a search for sustainable level of timber volume...
Apparent sixth sense in theropod evolution: The making of a Cretaceous weathervane

PubMed Central

Naples, Virginia

2017-01-01

Objective Two separate and distinctive skills are necessary to find prey: Detection of its presence and determination of its location. Surface microscopy of the dentary of albertosaurines revealed a previously undescribed sensory modification, as will be described here. While dentary “foramina” were previously thought to contain tactile sensory organs, the potential function of this theropod modification as a unique localizing system is explored in this study. Method Dentary surface perforations were examined by surface epi-illumination microscopy in tyrannosaurine and albertosaurine dinosaurs to characterize their anatomy. Fish lateral lines were examined as potentially comparable structures. Result In contrast to the subsurface vascular bifurcation noted in tyrannosaurines (which lack a lateral dentary surface groove), the area subjacent to the apertures in albertosaurine grooves has the appearance of an expanded chamber. That appearance seemed to be indistinguishable from the lateral line of fish. Conclusion Dentary groove apertures in certain tyrannosaurid lines (specifically albertosaurines) not only have a unique appearance, but one with significant functional and behavior implications. The appearance of the perforations in the dentary groove of albertosaurines mirrors that previously noted only with specialized neurologic structures accommodating derived sensory functions, as seen in the lateral line of fish. The possibility that this specialized morphology could also represent a unique function in albertosaurine theropods for interacting with the environment or facilitating prey acquisition cannot be ignored. It is suggested that these expanded chambers function in perceiving and aligning the body relative to the direction of wind, perhaps a Cretaceous analogue of the contemporary midwestern weathervane. PMID:29095949
Global profiling of alternative RNA splicing events provides insights into molecular differences between various types of hepatocellular carcinoma.

PubMed

Tremblay, Marie-Pier; Armero, Victoria E S; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S; Bisaillon, Martin

2016-08-26

Dysregulations in alternative splicing (AS) patterns have been associated with many human diseases including cancer. In the present study, alterations to the global RNA splicing landscape of cellular genes were investigated in a large-scale screen from 377 liver tissue samples using high-throughput RNA sequencing data. Our study identifies modifications in the AS patterns of transcripts encoded by more than 2500 genes such as tumor suppressor genes, transcription factors, and kinases. These findings provide insights into the molecular differences between various types of hepatocellular carcinoma (HCC). Our analysis allowed the identification of 761 unique transcripts for which AS is misregulated in HBV-associated HCC, while 68 are unique to HCV-associated HCC, 54 to HBV&HCV-associated HCC, and 299 to virus-free HCC. Moreover, we demonstrate that the expression pattern of the RNA splicing factor hnRNPC in HCC tissues significantly correlates with patient survival. We also show that the expression of the HBx protein from HBV leads to modifications in the AS profiles of cellular genes. Finally, using RNA interference and a reverse transcription-PCR screening platform, we examined the implications of cellular proteins involved in the splicing of transcripts involved in apoptosis and demonstrate the potential contribution of these proteins in AS control. This study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in hepatocellular carcinoma. Moreover, these data allowed us to identify unique signatures of genes for which AS is misregulated in the different types of HCC.
Structural conversion of the transformer protein RfaH: new insights derived from protein structure prediction and molecular dynamics simulations.

PubMed

Balasco, Nicole; Barone, Daniela; Vitagliano, Luigi

2015-01-01

Recent structural investigations have shown that the C-terminal domain (CTD) of the transcription factor RfaH undergoes unique structural modifications that have a profound impact into its functional properties. These modifications cause a complete change in RfaH(CTD) topology that converts from an α-hairpin to a β-barrel fold. To gain insights into the determinants of this major structural conversion, we here performed computational studies (protein structure prediction and molecular dynamics simulations) on RfaH(CTD). Although these analyses, in line with literature data, suggest that the isolated RfaH(CTD) has a strong preference for the β-barrel fold, they also highlight that a specific region of the protein is endowed with a chameleon conformational behavior. In particular, the Leu-rich region (residues 141-145) has a good propensity to adopt both α-helical and β-structured states. Intriguingly, in the RfaH homolog NusG, whose CTD uniquely adopts the β-barrel fold, the corresponding region is rich in residues as Val or Ile that present a strong preference for the β-structure. On this basis, we suggest that the presence of this Leu-rich element in RfaH(CTD) may be responsible for the peculiar structural behavior of the domain. The analysis of the sequences of RfaH family (PfamA code PF02357) unraveled that other members potentially share the structural properties of RfaH(CTD). These observations suggest that the unusual conformational behavior of RfaH(CTD) may be rare but not unique.
Deoxyribonucleic acid restriction and modification systems in Salmonella: chromosomally located systems of different serotypes.

PubMed Central

Bullas, L R; Colson, C; Neufeld, B

1980-01-01

With the use of four different phages, Salmonella strains representing 85 different serotypes were examined to determine their restriction-modification phenotype. They fell into one of three groups on this basis: group 1, those which lacked the common LT system; group 2, those in which only the LT system could be recognized; and group 3. those which possessed the LT system and at least one other system shown with some serotypes to be closely linked to serB. The specificity of the serB-linked restriction-modification system was unique for each serotype, but different strains of the same serotype expressed the same specificity. Two of the systems were shown to behave in genetic crosses as functional alleles of the S. typhimurium SB system. It is possible that these serB-linked restriction-modification systems constitute a large multiallelic series of genes extending throughout the Salmonella genus and Escherichia coli. We suggest that the division of the Salmonella into the three restriction-modification groups may be significant in defining a "biological grouping" of the different serotypes within the genus which may ultimately be useful in describing the Salmonella species. From the genetic relatedness between the genes of some of the Salmonella restriction-modification systems with those of the E. coli systems, we deduce that the restriction endonuclases produced by the Salmonella serB-linked systems are of type 1. Determination of the nucleotide sequences of the recognition sites of the restriction endonucleases of selected Salmonella systems should further our understanding of specificity with these enzymes. PMID:6243623
Cigar Product Modification Among High School Youth.

PubMed

Trapl, Erika S; Koopman Gonzalez, Sarah J; Cofie, Leslie; Yoder, Laura D; Frank, Jean; Sterling, Kymberle L

2018-02-07

Prevalence of cigar use has been increasing among youth. Research indicates that youth are modifying cigar products either by "freaking" (ie, removing the filter paper) or "blunting" (removing the tobacco and supplementing or replacing with marijuana), yet little is known about youth who engage in this behavior. Thus, this study examines demographic and concurrent substance use behaviors of youth who modify cigars. Data from the 2013 Cuyahoga County Youth Risk Behavior survey were examined (n = 16 855). The survey collected data on demographics, cigar product use, cigar modification behaviors, and current cigarette, hookah and marijuana use. Responses to cigar product use items were used to create a composite to classify youth in one of eight unique user categories. Univariate and bivariate statistics were calculated using SPSS complex samples procedures. Overall, 15.2% reported current cigar product use, 11.0% reported current freaking, and 18.5% reported current blunt use; taken together, 25.3% of respondents reported any current use of a cigar product. When examined by user category, of those who endorsed any cigar product use, cigars, cigarillos, and little cigars use only was most endorsed (26.3%), followed by Blunt only (25.2%) and all three (ie, cigars, cigarillos, and little cigars, freaking, and blunting; 17.4%). A substantial proportion of high school youth who report using cigar products are modifying them in some way, with nearly half freaking and nearly two-thirds blunting. Given the FDA Center for Tobacco products recent extension of its regulatory authority to include cigar products, it is imperative to understand more about the prevalence of and reasons for cigar modification behaviors. Although the FDA has recently enacted regulatory authority over cigar products, little is known about cigar product modification. This is the first study to concurrently examine two unique cigar modification behaviors, "freaking" (ie, removing the filter paper) and "blunting" (removing the tobacco and supplementing or replacing with marijuana). A significant proportion of high school youth are modifying cigar products to be used as a tobacco product and as a mechanism to smoke marijuana. More research is needed to understand these behaviors to prevent and reduce the use of cigar products among youth. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Independent roles of eIF5A and polyamines in cell proliferation

PubMed Central

2004-01-01

To examine the roles of active hypusinated eIF5A (eukaryotic translation initiation factor 5A) and polyamines in cell proliferation, mouse mammary carcinoma FM3A cells were treated with an inhibitor of deoxyhypusine synthase, GC7 (N1-guanyl-1, 7-diaminoheptane), or with an inhibitor of ornithine decarboxylase, DFMO (α-difluoromethylornithine), or with DFMO plus an inhibitor of spermine synthase, APCHA [N1-(3-aminopropyl)-cyclohexylamine]. Treatment with GC7 decreased the level of active eIF5A on day 1 without affecting cellular polyamine content, and inhibition of cell growth occurred from day 2. This delay reflects the fact that eIF5A was present in excess and was very stable in these cells. Treatment with DFMO or with DFMO plus APCHA inhibited cell growth on day 1. DFMO considerably decreased the levels of putrescine and spermidine, and the formation of active eIF5A began to decrease when the level of spermidine fell below 8 nmol/mg of protein after 12 h of incubation with DFMO. The combination of DFMO and APCHA markedly decreased the levels of putrescine and spermine and significantly decreased the level of spermidine, but did not affect the level of active eIF5A until day 3 when spermidine level decreased to 7 nmol/mg of protein. The results show that a decrease in either active eIF5A or polyamines inhibits cell growth, indicating that eIF5A and polyamines are independently involved in cell growth. PMID:15377278
Oral medicine modification for older adults: a qualitative study of nurses

PubMed Central

Crean, Abina M; Kelly, Maria; Sahm, Laura

2017-01-01

Objective Oral medicines are frequently modified (eg, tablets crushed) for older adults. However, these modifications can have clinical, legal and/or ethical implications. Nurses bear responsibility for medicine administration and hence, perform these modifications. The aim of this study was to investigate the knowledge, attitudes and beliefs of nurses about oral medicine modification for older adults. Design A qualitative study was conducted using semi-structured, face-to-face interviews with nurses providing care to older adults in acute and long-term care settings. Interviews were audio-recorded, transcribed verbatim and analysed thematically. Settings Sixteen purposively selected care settings; 4 acute-care and 12 long-term care settings were included. Nurses were recruited by convenience sampling at these sites. Participants Eighteen nurses participated (83% female, 67% long-term care, 33% acute-care, median age (IQR) 38 years (32.5–52.0)). Results Three major themes: modifying—a necessary evil, nurses’ role as patient advocate and modifying—we are working very much as a team and two minor themes: fractional dosing, and covert administration emerged from the data. Nurses viewed oral medicine modifications as being a routine and necessary occurrence in geriatric patient care due to limitations of available formulations and the presence of age-related challenges in drug administration. Nurses’ knowledge of residents’ requirements ensured that they advocate for those with individualised formulation needs, however, nurses rely on pharmacists for information about modifications. Nurses expressed a desire for supports including increased education and ward-specific, pharmacist-developed recommendations on common modifications. Conclusions This study has provided useful insights into the views of nurses regarding oral medicine modification for older adults. The unique and varied formulation requirements of older adults must be acknowledged. Increased engagement by healthcare professionals, the pharmaceutical industry, regulatory agencies and policy-makers is required to facilitate the development of age-appropriate formulations. In the interim, practical interventions, informed by the findings of this study, are required. PMID:29247094
Modification to the Langley 8-foot high temperature tunnel for hypersonic propulsion testing

NASA Technical Reports Server (NTRS)

Reubush, D. E.; Puster, R. L.; Kelly, H. N.

1987-01-01

Described are the modifications currently under way to the Langley 8-Foot High Temperature Tunnel to produce a new, unique national resource for testing hypersonic air-breathing propulsion systems. The current tunnel, which has been used for aerothermal loads and structures research since its inception, is being modified with the addition of a LOX system to bring the oxygen content of the test medium up to that of air, the addition of alternate Mach number capability (4 and 5) to augment the current M=7 capability, improvements to the tunnel hardware to reduce maintenance downtime, the addition of a hydrogen system to allow the testing of hydrogen powered engines, and a new data system to increase both the quantity and quality of the data obtained.
Zinc Oxide—From Synthesis to Application: A Review

PubMed Central

Kołodziejczak-Radzimska, Agnieszka; Jesionowski, Teofil

2014-01-01

Zinc oxide can be called a multifunctional material thanks to its unique physical and chemical properties. The first part of this paper presents the most important methods of preparation of ZnO divided into metallurgical and chemical methods. The mechanochemical process, controlled precipitation, sol-gel method, solvothermal and hydrothermal method, method using emulsion and microemulsion enviroment and other methods of obtaining zinc oxide were classified as chemical methods. In the next part of this review, the modification methods of ZnO were characterized. The modification with organic (carboxylic acid, silanes) and inroganic (metal oxides) compounds, and polymer matrices were mainly described. Finally, we present possible applications in various branches of industry: rubber, pharmaceutical, cosmetics, textile, electronic and electrotechnology, photocatalysis were introduced. This review provides useful information for specialist dealings with zinc oxide. PMID:28788596
Specialized (iso)eugenol-4-O-methyltransferases (s-IEMTs) and methods of making and using the same

DOEpatents

Liu, Chang-Jun; Cai, Yuanheng

2017-01-31

Specialized (iso)eugenol 4-O-methyltransferase (s-IEMT) enzymes having increased capacity for methylation of monolignols are disclosed. The s-IEMTs have unique activity favoring methylation of coniferyl alcohol versus sinapyl alcohol. Various s-IEMTs methylate ferulic acid. Means for producing the various s-IEMTs are provided. The s-IEMTs are useful for modification of lignin content and production of aromatic compounds.
A multi-stimuli responive, self-assembling, boronic acid dipeptide

DOE PAGES

Jones, Brad Howard; Martinez, Alina Marissa; Wheeler, Jill S.; ...

2015-08-11

Modification of the dipeptide of phenylalanine, FF, with a boronic acid (BA) functionality imparts unique aqueous self-assembly behavior that responds to multiple stimuli. Changes in pH and ionic strength are used to trigger hydrogelation via the formation of nanoribbon networks. Thus, we show for the first time that the binding of polyols to the BA functionality can modulate a peptide between its assembled and disassembled states.
Childbirth Education for Parents Experiencing Pregnancy after Perinatal Loss

PubMed Central

Wright, Patricia Moyle

2005-01-01

Expectant parents who have experienced previous perinatal loss have special concerns, which can be partially addressed by modifying prepared childbirth education courses. This article presents a review of current literature, highlighting the unique needs of expectant parents who have experienced previous pregnancy loss. Modifications to traditional childbirth education courses are suggested, which include addressing parents' grief, managing anxiety, and facilitating communication with health-care providers and others. PMID:17273448
Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin

PubMed Central

André, Pascale; Spertini, Olivier; Guia, Sophie; Rihet, Pascal; Dignat-George, Françoise; Brailly, Hervé; Sampol, José; Anderson, Paul J.; Vivier, Eric

2000-01-01

Natural killer (NK) cells are components of the innate immune system that can recognize and kill virally infected cells, tumor cells, and allogeneic cells without prior sensitization. NK cells also elaborate cytokines (e.g., interferon-γ and tumor necrosis factor-α) and chemokines (e.g., macrophage inflammatory protein-1α) that promote the acquisition of antigen-specific immunity. NK cell differentiation is accompanied by the cell surface expression of a mucin-like glycoprotein bearing an NK cell-restricted keratan sulfate-related lactosamine carbohydrate, the PEN5 epitope. Here, we report that PEN5 is a post-translational modification of P-selectin glycoprotein ligand-1 (PSGL-1). The PEN5 epitope creates on PSGL-1 a unique binding site for L-selectin, which is independent of PSGL-1 tyrosine sulfation. On the surface of NK cells, the expression of PEN5 is coordinated with the disappearance of L-selectin and the up-regulation of Killer cell Ig-like Receptors (KIR). These results indicate that NK cell differentiation is accompanied by the acquisition of a unique carbohydrate, PEN5, that can serve as part of a combination code to deliver KIR+ NK cells to specific tissues. PMID:10725346
Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia

PubMed Central

Mota, Roberto; Rodríguez, Jessica E; Bonetto, Andrea; O’Connell, Thomas M; Asher, Scott A; Parry, Traci L; Lockyer, Pamela; McCudden, Christopher R; Couch, Marion E; Willis, Monte S

2017-01-01

Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation. Up to 80% of cancer patients experience cachexia, with 20-30% of cancer-related deaths directly linked to cachexia. Despite efforts to identify early cachexia and cancer relapse, clinically useful markers are lacking. Recently, we identified the role of muscle-specific ubiquitin ligases Atrogin-1 (MAFbx, FBXO32) and Muscle Ring Finger-1 in the pathogenesis of cardiac atrophy and hypertrophy. We hypothesized that during cachexia, the Atrogin-1 and MuRF1 ubiquitin ligases are released from muscle and migrate to the circulation where they could be detected and serve as a cachexia biomarker. To test this, we induced cachexia in mice using the C26 adenocarcinoma cells or vehicle (control). Body weight, tumor volume, and food consumption were measured from inoculation until ~day 14 to document cachexia. Western blot analysis of serum identified the presence of Atrogin-1 and MuRF1 with unique post-translational modifications consistent with mono- and poly- ubiquitination of Atrogin-1 and MuRF1 found only in cachectic serum. These findings suggest that both increased Atrogin-1 and the presence of unique post-translational modifications may serve as a surrogate marker specific for cachexia. PMID:28979816
Enzymatic modification of a model homogalacturonan with the thermally tolerant pectin methylesterase from Citrus: 1. Nanostructural characterization, enzyme mode of action, and effect of pH.

PubMed

Cameron, Randall G; Luzio, Gary A; Vasu, Prasanna; Savary, Brett J; Williams, Martin A K

2011-03-23

Methyl ester distribution in pectin homogalacturonan has a major influence on functionality. Enzymatic engineering of the pectin nanostructure for tailoring functionality can expand the role of pectin as a food-formulating agent and the use of in situ modification in prepared foods. We report on the mode of action of a unique citrus thermally tolerant pectin methylesterase (TT-PME) and the nanostructural modifications that it produces. The enzyme was used to produce a controlled demethylesterification series from a model homogalacturonan. Oligogalacturonides released from the resulting demethylesterified blocks introduced by TT-PME using a limited endopolygalacturonase digestion were separated and quantified by high-pressure anion-exchange chromatography (HPAEC) coupled to an evaporative light-scattering detector (ELSD). The results were consistent with the predictions of a numerical simulation, which assumed a multiple-attack mechanism and a degree of processivity ∼10, at both pH 4.5 and 7.5. The average demethylesterified block size (0.6-2.8 nm) and number of average-sized blocks per molecule (0.8-1.9) differed, depending upon pH of the enzyme treatment. The mode of action of this enzyme and consequent nanostructural modifications of pectin differ from a previously characterized citrus salt-independent pectin methylesterase (SI-PME).
Variation of the chemical reactivity of Thermus thermophilus HB8 ribosomal proteins as a function of pH.

PubMed

Running, William E; Reilly, James P

2010-10-01

Ribosomes occupy a central position in cellular metabolism, converting stored genetic information into active cellular machinery. Ribosomal proteins modulate both the intrinsic function of the ribosome and its interaction with other cellular complexes, such as chaperonins or the signal recognition particle. Chemical modification of proteins combined with mass spectrometric detection of the extent and position of covalent modifications is a rapid, sensitive method for the study of protein structure and flexibility. By altering the pH of the solution, we have induced non-denaturing changes in the structure of bacterial ribosomal proteins and detected these conformational changes by covalent labeling. Changes in ribosomal protein modification across a pH range from 6.6 to 8.3 are unique to each protein, and correlate with their structural environment in the ribosome. Lysine residues whose extent of modification increases as a function of increasing pH are on the surface of proteins, but in close proximity either to glutamate and aspartate residues, or to rRNA backbone phosphates. Increasing pH disrupts tertiary and quaternary interactions mediated by hydrogen bonding or ionic interactions, and regions of protein structure whose conformations are sensitive to these changes are of potential importance in modulating the flexibility of the ribosome or its interaction with other cellular complexes.
The contribution of sound intensity in vocal emotion perception: behavioral and electrophysiological evidence.

PubMed

Chen, Xuhai; Yang, Jianfeng; Gan, Shuzhen; Yang, Yufang

2012-01-01

Although its role is frequently stressed in acoustic profile for vocal emotion, sound intensity is frequently regarded as a control parameter in neurocognitive studies of vocal emotion, leaving its role and neural underpinnings unclear. To investigate these issues, we asked participants to rate the angry level of neutral and angry prosodies before and after sound intensity modification in Experiment 1, and recorded electroencephalogram (EEG) for mismatching emotional prosodies with and without sound intensity modification and for matching emotional prosodies while participants performed emotional feature or sound intensity congruity judgment in Experiment 2. It was found that sound intensity modification had significant effect on the rating of angry level for angry prosodies, but not for neutral ones. Moreover, mismatching emotional prosodies, relative to matching ones, induced enhanced N2/P3 complex and theta band synchronization irrespective of sound intensity modification and task demands. However, mismatching emotional prosodies with reduced sound intensity showed prolonged peak latency and decreased amplitude in N2/P3 complex and smaller theta band synchronization. These findings suggest that though it cannot categorically affect emotionality conveyed in emotional prosodies, sound intensity contributes to emotional significance quantitatively, implying that sound intensity should not simply be taken as a control parameter and its unique role needs to be specified in vocal emotion studies.
The Contribution of Sound Intensity in Vocal Emotion Perception: Behavioral and Electrophysiological Evidence

PubMed Central

Chen, Xuhai; Yang, Jianfeng; Gan, Shuzhen; Yang, Yufang

2012-01-01

Although its role is frequently stressed in acoustic profile for vocal emotion, sound intensity is frequently regarded as a control parameter in neurocognitive studies of vocal emotion, leaving its role and neural underpinnings unclear. To investigate these issues, we asked participants to rate the angry level of neutral and angry prosodies before and after sound intensity modification in Experiment 1, and recorded electroencephalogram (EEG) for mismatching emotional prosodies with and without sound intensity modification and for matching emotional prosodies while participants performed emotional feature or sound intensity congruity judgment in Experiment 2. It was found that sound intensity modification had significant effect on the rating of angry level for angry prosodies, but not for neutral ones. Moreover, mismatching emotional prosodies, relative to matching ones, induced enhanced N2/P3 complex and theta band synchronization irrespective of sound intensity modification and task demands. However, mismatching emotional prosodies with reduced sound intensity showed prolonged peak latency and decreased amplitude in N2/P3 complex and smaller theta band synchronization. These findings suggest that though it cannot categorically affect emotionality conveyed in emotional prosodies, sound intensity contributes to emotional significance quantitatively, implying that sound intensity should not simply be taken as a control parameter and its unique role needs to be specified in vocal emotion studies. PMID:22291928
siRNAmod: A database of experimentally validated chemically modified siRNAs.

PubMed

Dar, Showkat Ahmad; Thakur, Anamika; Qureshi, Abid; Kumar, Manoj

2016-01-28

Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod.
Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations.

PubMed

Jiang, Jun; Aduri, Raviprasad; Chow, Christine S; SantaLucia, John

2014-04-01

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson-Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity.
Non-coding RNA networks in cancer.

PubMed

Anastasiadou, Eleni; Jacob, Leni S; Slack, Frank J

2018-01-01

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.
Structure, chaperone-like activity and allergenicity profile of bovine caseins upon peroxynitrite modification: New evidences underlying mastitis pathomechanisms.

PubMed

Sadeghian, Tanaz; Tavaf, Zohreh; Oryan, Ahmad; Shokouhi, Raheleh; Pourpak, Zahra; Moosavi-Movahedi, Ali Akbar; Yousefi, Reza

2018-01-01

Mastitis, an inflammatory reaction frequently develops in response to intra-mammary bacterial infection‌‌, may induce the generation of peroxynitrite (PON)‌ which is a highly potent reactive oxygen and nitrogen species. Caseins as the intrinsically unfolded proteins seem feasible substrates to react with PON. Therefore, in the current study, structural and functional aspects of both β-casein (β-CN) and whole casein fraction (WCF) were evaluated after PON modification, using a variety of techniques. Modification of the bovine caseins with PON results in an important enhancement in the carbonyl, nitrotryptophan, nitrotyrosine and dityrosine content of these proteins‌. The results of fluorescence and far UV-CD assessments suggested significant structural alteration of caseins upon PON-modification. The chaperone-like activity of β-casein was significantly altered after PON modification. The results of scanning electron microscopy suggest that bovine caseins display unique morphological features after treatment with PON. Also, the PON-modified caseins preserved their allergenicity profile and displayed partial resistance against digestion by the pancreatic proteases. Ascorbic acid, an important antioxidant component of milk, was also capable to significantly prevent the PON-induced structural damages in bovine milk caseins. In conclusion, our results suggest that PON may have significant role in the structural and functional alteration of milk caseins. Also, the PON-induced structural damaging effects of caseins might be effectively prevented by a sufficient level of milk antioxidant components particularly by ascorbic acid. Copyright © 2017 Elsevier B.V. All rights reserved.
Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-only, ADHD and conduct problems, and controls.

PubMed

Helseth, Sarah A; Waschbusch, Daniel A; Gnagy, Elizabeth M; Onyango, Adia N; Burrows-MacLean, Lisa; Fabiano, Gregory A; Coles, Erika K; Chacko, Anil; Wymbs, Brian T; Walker, Kathryn S; Wymbs, Frances A; Garefino, Allison; Massetti, Greta M; Robb Mazzant, Jessica; Hoffman, Martin T; Waxmonsky, James G; Nichols-Lopez, Kristin; Pelham, William E

2015-04-01

This study compared the unique and combined effects of evidence-based treatments for ADHD-stimulant medication and behavior modification-on children's rates of reinforcement for deviant peer behavior (RDPB). Using a within-subjects design, 222 elementary school-age children attending a summer treatment program, including 151 children with ADHD (127 male), with and without comorbid conduct problems, and 71 control children (57 male), received varying combinations of behavior modification (no, low-intensity, and high-intensity) and methylphenidate (placebo, 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg). RDPB was measured through direct observation and compared across all behavior modification and medication conditions. Children with ADHD reinforced the deviant behavior of their peers at a significantly higher rate than control children in the absence of either intervention. However, that difference largely disappeared in the presence of both behavior modification and medication. Both low and high-intensity behavior modification, as well as medium (0.30 mg/kg) and high (0.60 mg/kg) doses of methylphenidate, significantly reduced the rate of ADHD children's RDPB to levels similar to the control group. Results indicate that although untreated children with ADHD do engage in RDPB at a greater rate than their non-ADHD peers, existing evidence-based interventions can substantially decrease the presence of RDPB, thereby limiting potential iatrogenic effects in group-based treatment settings. (c) 2015 APA, all rights reserved).
Spatial and temporal plasticity of chromatin during programmed DNA-reorganization in Stylonychia macronuclear development

PubMed Central

Postberg, Jan; Heyse, Katharina; Cremer, Marion; Cremer, Thomas; Lipps, Hans J

2008-01-01

Background: In this study we exploit the unique genome organization of ciliates to characterize the biological function of histone modification patterns and chromatin plasticity for the processing of specific DNA sequences during a nuclear differentiation process. Ciliates are single-cell eukaryotes containing two morphologically and functionally specialized types of nuclei, the somatic macronucleus and the germline micronucleus. In the course of sexual reproduction a new macronucleus develops from a micronuclear derivative. During this process specific DNA sequences are eliminated from the genome, while sequences that will be transcribed in the mature macronucleus are retained. Results: We show by immunofluorescence microscopy, Western analyses and chromatin immunoprecipitation (ChIP) experiments that each nuclear type establishes its specific histone modification signature. Our analyses reveal that the early macronuclear anlage adopts a permissive chromatin state immediately after the fusion of two heterochromatic germline micronuclei. As macronuclear development progresses, repressive histone modifications that specify sequences to be eliminated are introduced de novo. ChIP analyses demonstrate that permissive histone modifications are associated with sequences that will be retained in the new macronucleus. Furthermore, our data support the hypothesis that a PIWI-family protein is involved in a transnuclear cross-talk and in the RNAi-dependent control of developmental chromatin reorganization. Conclusion: Based on these data we present a comprehensive analysis of the spatial and temporal pattern of histone modifications during this nuclear differentiation process. Results obtained in this study may also be relevant for our understanding of chromatin plasticity during metazoan embryogenesis. PMID:19014664
Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

PubMed

Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

2005-06-01

Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

Analysis of the Yukawa gravitational potential in f (R ) gravity. II. Relativistic periastron advance

NASA Astrophysics Data System (ADS)

De Laurentis, Mariafelicia; De Martino, Ivan; Lazkoz, Ruth

2018-05-01

Alternative theories of gravity may serve to overcome several shortcomings of the standard cosmological model but, in their weak field limit, general relativity must be recovered so as to match the tight constraints at the Solar System scale. Therefore, testing such alternative models at scales of stellar systems could give a unique opportunity to confirm or rule them out. One of the most straightforward modifications is represented by analytical f (R )-gravity models that introduce a Yukawa-like modification to the Newtonian potential thus modifying the dynamics of particles. Using the geodesics equations, we have illustrated the amplitude of these modifications. First, we have integrated numerically the equations of motion showing the orbital precession of a particle around a massive object. Second, we have computed an analytic expression for the periastron advance of systems having their semimajor axis much shorter than the Yukawa-scale length. Finally, we have extended our results to the case of a binary system composed of two massive objects. Our analysis provides a powerful tool to obtain constraints on the underlying theory of gravity using current and forthcoming data sets.
Cytidine Diphosphoramidate Kinase: An Enzyme Required for the Biosynthesis of the O-Methyl Phosphoramidate Modification in the Capsular Polysaccharides of Campylobacter jejuni.

PubMed

Taylor, Zane W; Raushel, Frank M

2018-04-17

Campylobacter jejuni, a leading cause of gastroenteritis, produces a capsular polysaccharide that is derivatized with a unique O-methyl phosphoramidate (MeOPN) modification. This modification contributes to serum resistance and invasion of epithelial cells. Previously, the first three biosynthetic steps for the formation of MeOPN were elucidated. The first step is catalyzed by a novel glutamine kinase (Cj1418), which catalyzes the adenosine triphosphate (ATP)-dependent phosphorylation of the amide nitrogen of l-glutamine. l-Glutamine phosphate is used by cytidine triphosphate (CTP):phosphoglutamine cytidylyltransferase (Cj1416) to displace pyrophosphate from CTP to generate cytidine diphosphate (CDP)-l-glutamine, which is then hydrolyzed by γ-glutamyl-CDP-amidate hydrolase (Cj1417) to form cytidine diphosphoramidate (CDP-NH 2 ). Here, we show that Cj1415 catalyzes the ATP-dependent phosphorylation of CDP-NH 2 to form 3'-phospho-cytidine-5'-diphosphoramidate. Cj1415 will also catalyze the phosphorylation of adenosine diphosphoramidate (ADP-NH 2 ) and uridine diphosphoramidate (UDP-NH 2 ) but at significantly reduced rates. It is proposed that Cj1415 be named cytidine diphosphoramidate kinase.
RNA Framework: an all-in-one toolkit for the analysis of RNA structures and post-transcriptional modifications.

PubMed

Incarnato, Danny; Morandi, Edoardo; Simon, Lisa Marie; Oliviero, Salvatore

2018-06-09

RNA is emerging as a key regulator of a plethora of biological processes. While its study has remained elusive for decades, the recent advent of high-throughput sequencing technologies provided the unique opportunity to develop novel techniques for the study of RNA structure and post-transcriptional modifications. Nonetheless, most of the required downstream bioinformatics analyses steps are not easily reproducible, thus making the application of these techniques a prerogative of few laboratories. Here we introduce RNA Framework, an all-in-one toolkit for the analysis of most NGS-based RNA structure probing and post-transcriptional modification mapping experiments. To prove the extreme versatility of RNA Framework, we applied it to both an in-house generated DMS-MaPseq dataset, and to a series of literature available experiments. Notably, when starting from publicly available datasets, our software easily allows replicating authors' findings. Collectively, RNA Framework provides the most complete and versatile toolkit to date for a rapid and streamlined analysis of the RNA epistructurome. RNA Framework is available for download at: http://www.rnaframework.com.
A Class of Reactive Acyl-CoA Species Reveals the Non-Enzymatic Origins of Protein Acylation

PubMed Central

Wagner, Gregory R.; Bhatt, Dhaval P.; O’Connell, Thomas M.; Thompson, J. Will; Dubois, Laura G.; Backos, Donald S.; Yang, Hao; Mitchell, Grant A.; Ilkayeva, Olga R.; Stevens, Robert D.; Grimsrud, Paul A.; Hirschey, Matthew D.

2017-01-01

SUMMARY The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergoes intramolecular catalysis to form reactive intermediates which non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized a protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the ‘acylomes’ of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation, and validated malate dehydrogenase as a key target. These data uncover a fundamental relationship between reactive acyl-CoA species and proteins, and define a new regulatory paradigm in metabolism. PMID:28380375
Sulfenic acid chemistry, detection and cellular lifetime☆

PubMed Central

Gupta, Vinayak; Carroll, Kate S.

2014-01-01

Background Reactive oxygen species-mediated cysteine sulfenic acid modification has emerged as an important regulatory mechanism in cell signaling. The stability of sulfenic acid in proteins is dictated by the local microenvironment and ability of antioxidants to reduce this modification. Several techniques for detecting this cysteine modification have been developed, including direct and in situ methods. Scope of review This review presents a historical discussion of sulfenic acid chemistry and highlights key examples of this modification in proteins. A comprehensive survey of available detection techniques with advantages and limitations is discussed. Finally, issues pertaining to rates of sulfenic acid formation, reduction, and chemical trapping methods are also covered. Major conclusions Early chemical models of sulfenic acid yielded important insights into the unique reactivity of this species. Subsequent pioneering studies led to the characterization of sulfenic acid formation in proteins. In parallel, the discovery of oxidant-mediated cell signaling pathways and pathological oxidative stress has led to significant interest in methods to detect these modifications. Advanced methods allow for direct chemical trapping of protein sulfenic acids directly in cells and tissues. At the same time, many sulfenic acids are short-lived and the reactivity of current probes must be improved to sample these species, while at the same time, preserving their chemical selectivity. Inhibitors with binding scaffolds can be rationally designed to target sulfenic acid modifications in specific proteins. General significance Ever increasing roles for protein sulfenic acids have been uncovered in physiology and pathology. A more complete understanding of sulfenic acid-mediated regulatory mechanisms will continue to require rigorous and new chemical insights. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. PMID:23748139
Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary (STROBE-Vet) Statement.

PubMed

Sargeant, J M; O'Connor, A M; Dohoo, I R; Erb, H N; Cevallos, M; Egger, M; Ersbøll, A K; Martin, S W; Nielsen, L R; Pearl, D L; Pfeiffer, D U; Sanchez, J; Torrence, M E; Vigre, H; Waldner, C; Ward, M P

2016-11-01

Reporting of observational studies in veterinary research presents challenges that often are not addressed in published reporting guidelines. To develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. Consensus meeting of experts. Mississauga, Canada. Seventeen experts from North America, Europe, and Australia. Experts completed a pre-meeting survey about whether items in the STROBE statement should be modified or added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. During the meeting, each STROBE item was discussed to determine whether or not rewording was recommended and whether additions were warranted. Anonymous voting was used to determine consensus. Six items required no modifications or additions. Modifications or additions were made to the STROBE items 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). The methods and processes used were similar to those used for other extensions of the STROBE statement. The use of this STROBE statement extension should improve reporting of observational studies in veterinary research by recognizing unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Dietary fat and fiber interact to uniquely modify global histone post-translational epigenetic programming in a rat colon cancer progression model.

PubMed

Triff, Karen; McLean, Mathew W; Callaway, Evelyn; Goldsby, Jennifer; Ivanov, Ivan; Chapkin, Robert S

2018-04-16

Dietary fermentable fiber generates short-chain fatty acids (SCFA), e.g., butyrate, in the colonic lumen which serves as a chemoprotective histone deacetylase inhibitor and/or as an acetylation substrate for histone acetylases. In addition, n-3 polyunsaturated fatty acids (n-3 PUFA) in fish oil can affect the chromatin landscape by acting as ligands for tumor suppressive nuclear receptors. In an effort to gain insight into the global dimension of post-translational modification of histones (including H3K4me3 and H3K9ac) and clarify the chemoprotective impact of dietary bioactive compounds on transcriptional control in a preclinical model of colon cancer, we generated high-resolution genome-wide RNA (RNA-Seq) and "chromatin-state" (H3K4me3-seq and H3K9ac-seq) maps for intestinal (epithelial colonocytes) crypts in rats treated with a colon carcinogen and fed diets containing bioactive (i) fish oil, (ii) fermentable fiber (a rich source of SCFA), (iii) a combination of fish oil plus pectin or (iv) control, devoid of fish oil or pectin. In general, poor correlation was observed between differentially transcribed (DE) and enriched genes (DERs) at multiple epigenetic levels. The combinatorial diet (fish oil + pectin) uniquely affected transcriptional profiles in the intestinal epithelium, e.g., upregulating lipid catabolism and beta-oxidation associated genes. These genes were linked to activated ligand-dependent nuclear receptors associated with n-3 PUFA and were also correlated with the mitochondrial L-carnitine shuttle and the inhibition of lipogenesis. These findings demonstrate that the chemoprotective fish oil + pectin combination diet uniquely induces global histone state modifications linked to the expression of chemoprotective genes. This article is protected by copyright. All rights reserved. © 2018 UICC.
Structural Analysis of PTM Hotspots (SAPH-ire) – A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families*

PubMed Central

Dewhurst, Henry M.; Choudhury, Shilpa; Torres, Matthew P.

2015-01-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)—a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits—conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit–N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. PMID:26070665
Ratcheting up the ratchet: on the evolution of cumulative culture

PubMed Central

Tennie, Claudio; Call, Josep; Tomasello, Michael

2009-01-01

Some researchers have claimed that chimpanzee and human culture rest on homologous cognitive and learning mechanisms. While clearly there are some homologous mechanisms, we argue here that there are some different mechanisms at work as well. Chimpanzee cultural traditions represent behavioural biases of different populations, all within the species’ existing cognitive repertoire (what we call the ‘zone of latent solutions’) that are generated by founder effects, individual learning and mostly product-oriented (rather than process-oriented) copying. Human culture, in contrast, has the distinctive characteristic that it accumulates modifications over time (what we call the ‘ratchet effect’). This difference results from the facts that (i) human social learning is more oriented towards process than product and (ii) unique forms of human cooperation lead to active teaching, social motivations for conformity and normative sanctions against non-conformity. Together, these unique processes of social learning and cooperation lead to humans’ unique form of cumulative cultural evolution. PMID:19620111
Supramolecular Assembly of a Biomineralizing Antimicrobial Peptide in Coarse-Grained Monte Carlo Simulations (Postprint)

DTIC Science & Technology

2010-07-05

aqueous solutions at a wide pH range.7 Silica forms rapidly at room temperature in the absence of other ionic catalysts or cofactors (buffers, salts...and other ionic species) that are normally required with in vitro biosilica synthesis. The silaffins are uniquely functionalized; serine residues are...alkaline conditions mimic the properties of the poly- ionic modifications on native silaffins.13,14 The zwitterionic properties facilitate intermolecular
Contamination Control Assessment of the World's Largest Space Environment Simulation Chamber

NASA Technical Reports Server (NTRS)

Snyder, Aaron; Henry, Michael W.; Grisnik, Stanley P.; Sinclair, Stephen M.

2012-01-01

The Space Power Facility s thermal vacuum test chamber is the largest chamber in the world capable of providing an environment for space simulation. To improve performance and meet stringent requirements of a wide customer base, significant modifications were made to the vacuum chamber. These include major changes to the vacuum system and numerous enhancements to the chamber s unique polar crane, with a goal of providing high cleanliness levels. The significance of these changes and modifications are discussed in this paper. In addition, the composition and arrangement of the pumping system and its impact on molecular back-streaming are discussed in detail. Molecular contamination measurements obtained with a TQCM and witness wafers during two recent integrated system tests of the chamber are presented and discussed. Finally, a concluding remarks section is presented.
Histone modifications controlling native and induced neural stem cell identity.

PubMed

Broccoli, Vania; Colasante, Gaia; Sessa, Alessandro; Rubio, Alicia

2015-10-01

During development, neural progenitor cells (NPCs) that are capable of self-renewing maintain a proliferative cellular pool while generating all differentiated neural cell components. Although the genetic network of transcription factors (TFs) required for neural specification has been well characterized, the unique set of histone modifications that accompanies this process has only recently started to be investigated. In vitro neural differentiation of pluripotent stem cells is emerging as a powerful system to examine epigenetic programs. Deciphering the histone code and how it shapes the chromatin environment will reveal the intimate link between epigenetic changes and mechanisms for neural fate determination in the developing nervous system. Furthermore, it will offer a molecular framework for a stringent comparison between native and induced neural stem cells (iNSCs) generated by direct neural cell conversion. Copyright © 2015 Elsevier Ltd. All rights reserved.
Recording electrocardiograms using 3-limb lead cables instead of the standard 4: a modification to minimize incorrect electrode placements.

PubMed

Soliman, Elsayed Z

2008-01-01

The similarity between and the number of limb lead cables play an important role in the frequency of incorrect connection of limb electrodes. Hence, a modified electrocardiogram (ECG) acquisition procedure is proposed in this brief communication, whereby the left-leg (LL) and right-leg (RL) electrode cables are combined into 1 cable, referred to as combined LL/RL cable. The electrode wires in the combined LL/RL cable are connected to 2 electrodes placed on both sides of the LL. The combined LL/RL cable is unique enough (being thicker) not to be mistaken with the upper limb electrode cables. The proposed modification will not in any way influence the ECG waveforms or amplitudes, and it can be expected to substantially reduce incorrect limb electrode placements.
The new MSFC Solar vector magnetograph. Center director's discretionary fund

NASA Technical Reports Server (NTRS)

Hagyard, M. J.; West, E. A.; Cumings, N. P.

1984-01-01

The unique MSFC solar vector magnetograph allows measurements of all three components of the Sun's photospheric magnetic field over a wide field-of-view with spatial resolution determined by a 2.7 x 2.7 arc second pixel size. This system underwent extensive modifications to improve its sensitivity and temporal response. The modifications included replacing an SEC vidicon detector with a solid-state CCD camera; replacing the original digital logic circuitry with an electronic controller and a computer to provide complete, programmable control over the entire operation of the magnetograph; and installing a new polarimeter which consists of a single electro-optical modulator coupled with interchangeable waveplates mounted on a rotating assembly. The system is described and results of calibrations and tests are presented. Initial observations of solar magnetic fields with the new magnetograph are presented.
Rhabdom evolution in butterflies: insights from the uniquely tiered and heterogeneous ommatidia of the Glacial Apollo butterfly, Parnassius glacialis.

PubMed

Matsushita, Atsuko; Awata, Hiroko; Wakakuwa, Motohiro; Takemura, Shin-ya; Arikawa, Kentaro

2012-09-07

The eye of the Glacial Apollo butterfly, Parnassius glacialis, a 'living fossil' species of the family Papilionidae, contains three types of spectrally heterogeneous ommatidia. Electron microscopy reveals that the Apollo rhabdom is tiered. The distal tier is composed exclusively of photoreceptors expressing opsins of ultraviolet or blue-absorbing visual pigments, and the proximal tier consists of photoreceptors expressing opsins of green or red-absorbing visual pigments. This organization is unique because the distal tier of other known butterflies contains two green-sensitive photoreceptors, which probably function in improving spatial and/or motion vision. Interspecific comparison suggests that the Apollo rhabdom retains an ancestral tiered pattern with some modification to enhance its colour vision towards the long-wavelength region of the spectrum.
The partial retro-inverso modification: a road traveled together.

PubMed

Chorev, Michael

2005-01-01

In the mid-1970s, Dr. Murray Goodman was interested in a reversed peptide bond as a surrogate to understand the functional role of the amide bond in aspartame, a dipeptide sweetener. Very soon, realizing the breath and potential of this modification, Murray expanded this activity into a full program and I was fortunate to be part of it. Together we formulated new concepts such as the partially modified retro-inverso and end-group modified retro-inverso transformations, tested hypotheses, generated novel nomenclature, developed synthetic routes, characterized the preferred conformations of the unique building blocks employed in this modification, the gem-diaminoalkyl and the C2-substituted malonyl residues, and studied the biological activity of retro-inverso isomers of bioactive peptides. In the early 1980s several laboratories initiated extensive research targeted at the retro-inverso modification. The revival of this field led to new applications, new methods of synthesis, and new insights on the conformational and topological properties of the retro-inverso modification. Among the fields that embraced the retro-inverso concept were immunology as pertains to subjects such as synthetic vaccines, immunomodulators, and diagnostic tools, and drug delivery field as pertains to targeted and nontargeted cell permeation vectors loaded with bioactive cargo. Doctor Murray Goodman's sudden death leaves behind not only family, friends, and colleagues, but also an impressive record of scientific achievements among which is the revival of the modern era of the retro-inverso transformation. Murray's numerous contributions, excellent leadership, enthusiastic promotion, and outstanding teachings in this field will carry and illuminate his memory far into the future. Copyright 2005 Wiley Periodicals, Inc
Profiling of integral membrane proteins and their post translational modifications using high-resolution mass spectrometry

PubMed Central

Souda, Puneet; Ryan, Christopher M.; Cramer, William A.; Whitelegge, Julian

2011-01-01

Integral membrane proteins pose challenges to traditional proteomics approaches due to unique physicochemical properties including hydrophobic transmembrane domains that limit solubility in aqueous solvents. A well resolved intact protein molecular mass profile defines a protein’s native covalent state including post-translational modifications, and is thus a vital measurement toward full structure determination. Both soluble loop regions and transmembrane regions potentially contain post-translational modifications that must be characterized if the covalent primary structure of a membrane protein is to be defined. This goal has been achieved using electrospray-ionization mass spectrometry (ESI-MS) with low-resolution mass analyzers for intact protein profiling, and high-resolution instruments for top-down experiments, toward complete covalent primary structure information. In top-down, the intact protein profile is supplemented by gas-phase fragmentation of the intact protein, including its transmembrane regions, using collisionally activated and/or electroncapture dissociation (CAD/ECD) to yield sequence-dependent high-resolution MS information. Dedicated liquid chromatography systems with aqueous/organic solvent mixtures were developed allowing us to demonstrate that polytopic integral membrane proteins are amenable to ESI-MS analysis, including top-down measurements. Covalent post-translational modifications are localized regardless of their position in transmembrane domains. Top-down measurements provide a more detail oriented high-resolution description of post-transcriptional and post-translational diversity for enhanced understanding beyond genomic translation. PMID:21982782
Profiling of integral membrane proteins and their post translational modifications using high-resolution mass spectrometry.

PubMed

Souda, Puneet; Ryan, Christopher M; Cramer, William A; Whitelegge, Julian

2011-12-01

Integral membrane proteins pose challenges to traditional proteomics approaches due to unique physicochemical properties including hydrophobic transmembrane domains that limit solubility in aqueous solvents. A well resolved intact protein molecular mass profile defines a protein's native covalent state including post-translational modifications, and is thus a vital measurement toward full structure determination. Both soluble loop regions and transmembrane regions potentially contain post-translational modifications that must be characterized if the covalent primary structure of a membrane protein is to be defined. This goal has been achieved using electrospray-ionization mass spectrometry (ESI-MS) with low-resolution mass analyzers for intact protein profiling, and high-resolution instruments for top-down experiments, toward complete covalent primary structure information. In top-down, the intact protein profile is supplemented by gas-phase fragmentation of the intact protein, including its transmembrane regions, using collisionally activated and/or electron-capture dissociation (CAD/ECD) to yield sequence-dependent high-resolution MS information. Dedicated liquid chromatography systems with aqueous/organic solvent mixtures were developed allowing us to demonstrate that polytopic integral membrane proteins are amenable to ESI-MS analysis, including top-down measurements. Covalent post-translational modifications are localized regardless of their position in transmembrane domains. Top-down measurements provide a more detail oriented high-resolution description of post-transcriptional and post-translational diversity for enhanced understanding beyond genomic translation. Copyright © 2011 Elsevier Inc. All rights reserved.
Global regulation of post-translational modifications on core histones.

PubMed

Galasinski, Scott C; Louie, Donna F; Gloor, Kristen K; Resing, Katheryn A; Ahn, Natalie G

2002-01-25

Full-length masses of histones were analyzed by mass spectrometry to characterize post-translational modifications of bulk histones and their changes induced by cell stimulation. By matching masses of unique peptides with full-length masses, H4 and the variants H2A.1, H2B.1, and H3.1 were identified as the main histone forms in K562 cells. Mass changes caused by covalent modifications were measured in a dose- and time-dependent manner following inhibition of phosphatases by okadaic acid. Histones H2A, H3, and H4 underwent changes in mass consistent with altered acetylation and phosphorylation, whereas H2B mass was largely unchanged. Unexpectedly, histone H4 became almost completely deacetylated in a dose-dependent manner that occurred independently of phosphorylation. Okadaic acid also partially blocked H4 hyperacetylation induced by trichostatin-A, suggesting that the mechanism of deacetylation involves inhibition of H4 acetyltransferase activity, following perturbation of cellular phosphatases. In addition, mass changes in H3 in response to okadaic acid were consistent with phosphorylation of methylated, acetylated, and phosphorylated forms. Finally, kinetic differences were observed with respect to the rate of phosphorylation of H2A versus H4, suggesting differential regulation of phosphorylation at sites on these proteins, which are highly related by sequence. These results provide novel evidence that global covalent modifications of chromatin-bound histones are regulated through phosphorylation-dependent mechanisms.
Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations

PubMed Central

Jiang, Jun; Aduri, Raviprasad; Chow, Christine S.; SantaLucia, John

2014-01-01

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson–Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity. PMID:24371282

An Application of Discriminant Analysis to the Selection of Software Cost Estimating Models.

DTIC Science & Technology

1984-09-01

the PRICE S Users Manual (29:111-25) was used with a slight modification. Based on the experience and advice of Captain Joe Dean, Electronic System...this study, and EXP is the expansion factor listed in the PRICE S User’s Manual . Another important factor needing explanation is development cost...coefficients and a unique constant. According to the SPSS manual (26:445) "Under the assumption of a multivariate normal distribution, the
An anionic Na(i)-organic framework platform: separation of organic dyes and post-modification for highly sensitive detection of picric acid.

PubMed

Chen, Di-Ming; Tian, Jia-Yue; Wang, Zhuo-Wei; Liu, Chun-Sen; Chen, Min; Du, Miao

2017-09-26

A cage-based anionic Na(i)-organic framework with a unique Na 9 cluster-based secondary building unit and a cage-in-cage structure was constructed. The selective separation of dyes with different charges and sizes was investigated. Furthermore, the Rh6G@MOF composite could be applied as a recyclable fluorescent sensor for detecting picric acid (PA) with high sensitivity and selectivity.
Hybrid membrane-microfluidic components using a novel ceramic MEMS technology

NASA Astrophysics Data System (ADS)

Lutz, Brent J.; Polyakov, Oleg; Rinaldo, Chris

2012-03-01

A novel hybrid nano/microfabrication technology has been employed to produce unique MEMS and microfluidic components that integrate nanoporous membranes. The components are made by micromachining a self-organized nanostructured ceramic material that is biocompatible and amenable to surface chemistry modification. Microfluidic structures, such as channels and wells, can be made with a precision of <2 microns. Thin-film membranes can be integrated into the bottom of these structures, featuring a wide range of possible thicknesses, from 100 micron to <50 nm. Additionally, these membranes may be non-porous or porous (with controllable pore sizes from 200 nm to <5 nm), for sophisticated size-based separations. With previous and current support from the NIH SBIR program, we have built several unique devices, and demonstrated improved separations, cell culturing, and imaging (optical and electron microscopy) versus standard products. Being ceramic, the material is much more robust to demanding environments (e.g. high and low temperatures and organic solvents), compared to polymer-based devices. Additionally, we have applied multiple surface modification techniques, including atomic layer deposition, to manipulate properties such as electrical conductivity. This microfabrication technology is highly scaleable, and thus can yield low-cost, reliable, disposable microcomponents and devices. Specific applications that can benefit from this technology includes cell culturing and assays, imaging by cryo-electron tomography, environmental sample processing, as well as many others.
Metal dust deposition in a shotgun wound associated with barrel modification.

PubMed

Williams, Andrew S; Bowes, Matthew J

2016-03-01

Contact-range gunshot wounds commonly demonstrate deposition of black soot in and around the wound. Deposition of other visible pigments originating from the firearm has not been specifically described. In the current case, an adult male was found dead adjacent to a shotgun fixed in a vice grip with a modified, shortened barrel. A handheld, powered, metal grinding wheel was nearby. Autopsy revealed an intraoral gunshot wound, including soot deposition in and around the mouth and within the wound track. In addition, there was a peculiar, gray, lustrous film on the lips, gingiva, and anterior teeth. The material was concentrated around the most severe areas of injury in the anterior mouth and easily rubbed off with a cotton swab. It was not visualized in the rest of the mouth and not present in the larynx, or the esophagus. Overall, our opinion is that this unique, gray, lustrous film represents deposition of fine metallic dust that accumulated in the barrel of the shotgun during its modification with the grinding wheel. This type of unique pigment deposition should be recognized by forensic pathologists as possibly being related to the discharge of a firearm with a recently modified barrel or other cause for fine metallic dust accumulation within the barrel. Depending on the circumstances of the case, collection of samples of such metal dust deposits could be indicated for subsequent analysis.
Strategies for the acquisition of transcriptional and epigenetic information in single cells.

PubMed

Li, Guang; Dzilic, Elda; Flores, Nick; Shieh, Alice; Wu, Sean M

2017-03-01

As the basic unit of living organisms, each single cell has unique molecular signatures and functions. Our ability to uncover the transcriptional and epigenetic signature of single cells has been hampered by the lack of tools to explore this area of research. The advent of microfluidic single cell technology along with single cell genome-wide DNA amplification methods had greatly improved our understanding of the expression variation in single cells. Transcriptional expression profile by multiplex qPCR or genome-wide RNA sequencing has enabled us to examine genes expression in single cells in different tissues. With the new tools, the identification of new cellular heterogeneity, novel marker genes, unique subpopulations, and spatial locations of each single cell can be acquired successfully. Epigenetic modifications for each single cell can also be obtained via similar methods. Based on single cell genome sequencing, single cell epigenetic information including histone modifications, DNA methylation, and chromatin accessibility have been explored and provided valuable insights regarding gene regulation and disease prognosis. In this article, we review the development of strategies to obtain single cell transcriptional and epigenetic data. Furthermore, we discuss ways in which single cell studies may help to provide greater understanding of the mechanisms of basic cardiovascular biology that will eventually lead to improvement in our ability to diagnose disease and develop new therapies.
The effect of ultrasonic nanocrystalline surface modification on the high-frequency fretting wear behavior of AISI304 steel.

PubMed

Cho, In-Shik; Lee, Chang-Soon; Amanov, Auezhan; Pyoun, Young-Shik; Park, In-Gyu

2011-01-01

The fact that one of fundamental characteristics of fretting is the very small sliding amplitude dictates the unique feature of wear mechanism. Ultrasonic Nanocrystalline Surface Modification (UNSM) technology was applied in order to investigate its effect on the high-frequency fretting wear behavior of AISI304 steel. Its influence on the fretting wear is also reported in this paper with these treated and untreated samples. UNSM delivers force onto the workpiece surface 20,000 times per second with 1,000 to 4,000 contact counts per square millimeter. UNSM creates homogenous nanocrystalline structures as well on the surface. UNSM process is expected to eliminate or significantly retard the formation of fretting wear. Nanocrystalline structure generation after UNSM has been reported to produce its unique structure and to offer a variety of beneficial properties compared to conventionally treated materials. A deformed layer of 220 microm exhibits high dislocation density, where top layer transformed to a nanostructure of the grain size in 23 nm and mechanical twins were observed. Deformation-induced martensite was observed to form at the intersections of mechanical twins, whose volume fraction has increased up to 38.4% and wear loss rate at 800,000 cycles has decreased by 40%. In this paper, experimental results are discussed to elucidate potential mechanism of high-frequency fretting wear.
Toward a rigorous network of protein-protein interactions of the model sulfate reducer Desulfovibrio vulgaris Hildenborough

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chhabra, S.R.; Joachimiak, M.P.; Petzold, C.J.

Protein–protein interactions offer an insight into cellular processes beyond what may be obtained by the quantitative functional genomics tools of proteomics and transcriptomics. The aforementioned tools have been extensively applied to study E. coli and other aerobes and more recently to study the stress response behavior of Desulfovibrio 5 vulgaris Hildenborough, a model anaerobe and sulfate reducer. In this paper we present the first attempt to identify protein-protein interactions in an obligate anaerobic bacterium. We used suicide vector-assisted chromosomal modification of 12 open reading frames encoded by this sulfate reducer to append an eight amino acid affinity tag to themore » carboxy-terminus of the chosen proteins. Three biological replicates of the 10 ‘pulled-down’ proteins were separated and analyzed using liquid chromatography-mass spectrometry. Replicate agreement ranged between 35% and 69%. An interaction network among 12 bait and 90 prey proteins was reconstructed based on 134 bait-prey interactions computationally identified to be of high confidence. We discuss the biological significance of several unique metabolic features of D. vulgaris revealed by this protein-protein interaction data 15 and protein modifications that were observed. These include the distinct role of the putative carbon monoxide-induced hydrogenase, unique electron transfer routes associated with different oxidoreductases, and the possible role of methylation in regulating sulfate reduction.« less
Transmission fidelity is the key to the build-up of cumulative culture

PubMed Central

Lewis, Hannah M.; Laland, Kevin N.

2012-01-01

Many animals have socially transmitted behavioural traditions, but human culture appears unique in that it is cumulative, i.e. human cultural traits increase in diversity and complexity over time. It is often suggested that high-fidelity cultural transmission is necessary for cumulative culture to occur through refinement, a process known as ‘ratcheting’, but this hypothesis has never been formally evaluated. We discuss processes of information transmission and loss of traits from a cognitive viewpoint alongside other cultural processes of novel invention (generation of entirely new traits), modification (refinement of existing traits) and combination (bringing together two established traits to generate a new trait). We develop a simple cultural transmission model that does not assume major evolutionary changes (e.g. in brain architecture) and show that small changes in the fidelity with which information is passed between individuals can lead to cumulative culture. In comparison, modification and combination have a lesser influence on, and novel invention appears unimportant to, the ratcheting process. Our findings support the idea that high-fidelity transmission is the key driver of human cumulative culture, and that progress in cumulative culture depends more on trait combination than novel invention or trait modification. PMID:22734060
Transmission fidelity is the key to the build-up of cumulative culture.

PubMed

Lewis, Hannah M; Laland, Kevin N

2012-08-05

Many animals have socially transmitted behavioural traditions, but human culture appears unique in that it is cumulative, i.e. human cultural traits increase in diversity and complexity over time. It is often suggested that high-fidelity cultural transmission is necessary for cumulative culture to occur through refinement, a process known as 'ratcheting', but this hypothesis has never been formally evaluated. We discuss processes of information transmission and loss of traits from a cognitive viewpoint alongside other cultural processes of novel invention (generation of entirely new traits), modification (refinement of existing traits) and combination (bringing together two established traits to generate a new trait). We develop a simple cultural transmission model that does not assume major evolutionary changes (e.g. in brain architecture) and show that small changes in the fidelity with which information is passed between individuals can lead to cumulative culture. In comparison, modification and combination have a lesser influence on, and novel invention appears unimportant to, the ratcheting process. Our findings support the idea that high-fidelity transmission is the key driver of human cumulative culture, and that progress in cumulative culture depends more on trait combination than novel invention or trait modification.
Modification of anti-bacterial surface properties of textile polymers by vacuum arc ion source implantation

NASA Astrophysics Data System (ADS)

Nikolaev, A. G.; Yushkov, G. Yu.; Oks, E. M.; Oztarhan, A.; Akpek, A.; Hames-Kocabas, E.; Urkac, E. S.; Brown, I. G.

2014-08-01

Ion implantation provides an important technology for the modification of material surface properties. The vacuum arc ion source is a unique instrument for the generation of intense beams of metal ions as well as gaseous ions, including mixed metal-gas beams with controllable metal:gas ion ratio. Here we describe our exploratory work on the application of vacuum arc ion source-generated ion beams for ion implantation into polymer textile materials for modification of their biological cell compatibility surface properties. We have investigated two specific aspects of cell compatibility: (i) enhancement of the antibacterial characteristics (we chose to use Staphylococcus aureus bacteria) of ion implanted polymer textile fabric, and (ii) the "inverse" concern of enhancement of neural cell growth rate (we chose Rat B-35 neuroblastoma cells) on ion implanted polymer textile. The results of both investigations were positive, with implantation-generated antibacterial efficiency factor up to about 90%, fully comparable to alternative conventional (non-implantation) approaches and with some potentially important advantages over the conventional approach; and with enhancement of neural cell growth rate of up to a factor of 3.5 when grown on suitably implanted polymer textile material.
Hot gas ingestion testing of an advanced STOVL concept in the NASA Lewis 9- by 15-foot low speed wind tunnel with flow visualization

NASA Technical Reports Server (NTRS)

Johns, Albert L.; Flood, Joseph D.; Strock, Thomas W.; Amuedo, Kurt C.

1988-01-01

Advanced Short Takeoff/Vertical Landing (STOVL) aircraft capable of operating from remote sites, damaged runways, and small air capable ships are being pursued for deployment around the turn of the century. To achieve this goal, it is important that the technologies critical to this unique class of aircraft be developed. Recognizing this need, NASA Lewis Research Center, McDonnell Douglas Aircraft, and DARPA defined a cooperative program for testing in the NASA Lewis 9- by 15-Foot Low Speed Wind Tunnel (LSWT) to establish a database for hot gas ingestion, one of the technologies critical to STOVL. Results from a test program are presented along with a discussion of the facility modifications allowing this type of testing at model scale. These modifications to the tunnel include a novel ground plane, an elaborate model support which included 4 degrees of freedom, heated high pressure air for nozzle flow, a suction system exhaust for inlet flow, and tunnel sidewall modifications. Several flow visualization techniques were employed including water mist in the nozzle flows and tufts on the ground plane. Headwind (free-stream) velocity was varied from 8 to 23 knots.
Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function.

PubMed

Väre, Ville Y P; Eruysal, Emily R; Narendran, Amithi; Sarachan, Kathryn L; Agris, Paul F

2017-03-16

RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA's cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.
Emotion recognition training using composite faces generalises across identities but not all emotions.

PubMed

Dalili, Michael N; Schofield-Toloza, Lawrence; Munafò, Marcus R; Penton-Voak, Ian S

2017-08-01

Many cognitive bias modification (CBM) tasks use facial expressions of emotion as stimuli. Some tasks use unique facial stimuli, while others use composite stimuli, given evidence that emotion is encoded prototypically. However, CBM using composite stimuli may be identity- or emotion-specific, and may not generalise to other stimuli. We investigated the generalisability of effects using composite faces in two experiments. Healthy adults in each study were randomised to one of four training conditions: two stimulus-congruent conditions, where same faces were used during all phases of the task, and two stimulus-incongruent conditions, where faces of the opposite sex (Experiment 1) or faces depicting another emotion (Experiment 2) were used after the modification phase. Our results suggested that training effects generalised across identities. However, our results indicated only partial generalisation across emotions. These findings suggest effects obtained using composite stimuli may extend beyond the stimuli used in the task but remain emotion-specific.
Ionic liquid-modified materials for solid-phase extraction and separation: a review.

PubMed

Vidal, Lorena; Riekkola, Marja-Liisa; Canals, Antonio

2012-02-17

In recent years, materials science has propelled to the research forefront. Ionic liquids with unique and fascinating properties have also left their footprints to the developments of materials science during the last years. In this review we highlight some of their recent advances and provide an overview at the current status of ionic liquid-modified materials applied in solid-phase extraction, liquid and gas chromatography and capillary electrochromatography with reference to recent applications. In addition, the potential of ionic liquids in the modification of capillary inner wall in capillary electrophoresis is demonstrated. The main target material modified with ionic liquids is silica, but polymers and monoliths have recently joined the studies. Although imidazolium is still clearly the most commonly used ionic liquid for the covalently modification of materials, the exploitation of pyridinium and phosphonium will most probably increase in the future. Copyright © 2011 Elsevier B.V. All rights reserved.
Rembrandt's late self-portraits: psychological and medical aspects.

PubMed

Marcus, Esther-Lee; Clarfield, A Mark

2002-01-01

The Dutch painter Rembrandt (1606-1669) left behind the largest series of self-portraits in the history of art. These paintings were produced over a period of time from age 22 years until just a few months before Rembrandt's death at age 63. This series gives us a unique opportunity to explore the development, maturity, and aging of the artist. The changes in Rembrandt's face and expression from one self-portrait to the next may be attributable to any combination of the following factors: normal aging changes, modifications and developments of his artistic style, alterations in the way he viewed himself, and changes in the way Rembrandt wanted us to see him. In addition, the modifications may be attributed in part to some illnesses from which the artist may have suffered and/or to a decline in his eyesight that may have influenced both his ability to detect details and his ability to paint.
An algorithm to count the number of repeated patient data entries with B tree.

PubMed

Okada, M; Okada, M

1985-04-01

An algorithm to obtain the number of different values that appear a specified number of times in a given data field of a given data file is presented. Basically, a well-known B-tree structure is employed in this study. Some modifications were made to the basic B-tree algorithm. The first step of the modifications is to allow a data item whose values are not necessary distinct from one record to another to be used as a primary key. When a key value is inserted, the number of previous appearances is counted. At the end of all the insertions, the number of key values which are unique in the tree, the number of key values which appear twice, three times, and so forth are obtained. This algorithm is especially powerful for a large size file in disk storage.
The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making

PubMed Central

2016-01-01

This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis. PMID:27617777
The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making.

PubMed

Long, Marcus J C; Aye, Yimon

2016-10-02

This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis.
Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

PubMed Central

Burska, Agata N.; Hunt, Laura; Strollo, Rocky; Ryan, Brent J.; Vital, Ed; Nissim, Ahuva; Winyard, Paul G.; Emery, Paul; Ponchel, Frederique

2014-01-01

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential. PMID:24782594
The NASA Langley Laminar-Flow-Control (LFC) experiment on a swept, supercritical airfoil: Design overview

NASA Technical Reports Server (NTRS)

Harris, Charles D.; Harvey, William D.; Brooks, Cuyler W., Jr.

1988-01-01

A large-chord, swept, supercritical, laminar-flow-control (LFC) airfoil was designed and constructed and is currently undergoing tests in the Langley 8 ft Transonic Pressure Tunnel. The experiment was directed toward evaluating the compatibility of LFC and supercritical airfoils, validating prediction techniques, and generating a data base for future transport airfoil design as part of NASA's ongoing research program to significantly reduce drag and increase aircraft efficiency. Unique features of the airfoil included a high design Mach number with shock free flow and boundary layer control by suction. Special requirements for the experiment included modifications to the wind tunnel to achieve the necessary flow quality and contouring of the test section walls to simulate free air flow about a swept model at transonic speeds. Design of the airfoil with a slotted suction surface, the suction system, and modifications to the tunnel to meet test requirements are discussed.

The Amplatzer Vascular Plug: Review of Evolution and Current Applications

PubMed Central

Lopera, Jorge E.

2015-01-01

The Amplatzer Vascular Plug (AVP) was created for peripheral embolization as a modification of the family of Amplatz septal occluders used in the treatment of congenital heart malformations. The device has evolved over the years and multiple versions have been launched into the market. Each of the versions of the device has some important modifications in terms of the size of the introducer's system, number of layers, and resultant thrombogenicity. It is very important for the operator to become familiar with the unique features of the AVP, and to understand the advantages and limitations of each model in the AVP family to achieve an optimal embolic result. The purpose of this article is to review the evolution and current clinical applications of the AVP in the field of interventional radiology, with emphasis on the advantages and limitations of this device in comparison with other embolization agents. PMID:26622098
Progressing From Initially Ambiguous Functional Analyses: Three Case Examples

PubMed Central

Tiger, Jeffrey H.; Fisher, Wayne W.; Toussaint, Karen A.; Kodak, Tiffany

2009-01-01

Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments. PMID:19233611
Patterned Colloidal Photonic Crystals.

PubMed

Hou, Jue; Li, Mingzhu; Song, Yanlin

2018-03-01

Colloidal photonic crystals (PCs) have been well developed because they are easy to prepare, cost-effective, and versatile with regards to modification and functionalization. Patterned colloidal PCs contribute a novel approach to constructing high-performance PC devices with unique structures and specific functions. In this review, an overview of the strategies for fabricating patterned colloidal PCs, including patterned substrate-induced assembly, inkjet printing, and selective immobilization and modification, is presented. The advantages of patterned PC devices are also discussed in detail, for example, improved detection sensitivity and response speed of the sensors, control over the flow direction and wicking rate of microfluidic channels, recognition of cross-reactive molecules through an array-patterned microchip, fabrication of display devices with tunable patterns, well-arranged RGB units, and wide viewing-angles, and the ability to construct anti-counterfeiting devices with different security strategies. Finally, the perspective of future developments and challenges is presented. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Endowing carbon nanotubes with biological and biomedical properties by chemical modifications.

PubMed

Battigelli, Alessia; Ménard-Moyon, Cécilia; Da Ros, Tatiana; Prato, Maurizio; Bianco, Alberto

2013-12-01

The scope of nanotechnology is gaining importance in biology and medicine. Carbon nanotubes (CNTs) have emerged as a promising tool due to their unique properties, high specific surface area, and capacity to cross biological barriers. These properties offer a variety of opportunities for applications in nanomedicine, such as diagnosis, disease treatment, imaging, and tissue engineering. Nevertheless, pristine CNTs are insoluble in water and in most organic solvents; thereby functionalization of their surface is necessary to increase biocompatibility. Derivatization of CNTs also gives the possibility to conjugate different biological and bioactive molecules including drugs, proteins, and targeting ligands. This review focuses on the chemical modifications of CNTs that have been developed to impart specific properties for biological and medical purposes. Biomolecules can be covalently grafted or non-covalently adsorbed on the nanotube surface. In addition, the inner core of CNTs can be exploited to encapsulate drugs, nanoparticles, or radioactive elements. © 2013.
Physical Property Investigation of Contemporary Glass lonomer and Resin Modified Glass lonomer Restorative Materials

DTIC Science & Technology

2016-05-24

racteristics. 7•13•14 These modifications have included the use of alternative polyacids, 7•15•16 water- activated dehydrated polyacid powders, 7•15•17...cermets, 18 metal additions, 19’ 21 smaller glass particle size, 22 antibacterial agent s, n.24 different glass compositions, 15•25 and most recently...methacrylate (HEMA) or is uniquely grafted on the polyalkenoate acid chain. These monomers polymerize either by external photo activation or by an
Measuring medium-induced gluons via jet grooming

NASA Astrophysics Data System (ADS)

Tywoniuk, Konrad; Mehtar-Tani, Yacine

2017-11-01

Jet substructure observables and applications of jet grooming techniques in heavy-ion collisions are still in its infancy and provide new alleys for studying medium modifications of perturbative degrees of freedom. We note that these measurements, given the right transverse momentum range, can be uniquely sensitive to rare medium-induced emissions inside of the jet cone. This corresponds to an infrared enhancement that would, for instance, affect the distribution of the groomed momentum-sharing variable zg measured using the SoftDrop procedure.
5-Hydroxymethylcytosine Profiling in Human DNA.

PubMed

Thomson, John P; Nestor, Colm E; Meehan, Richard R

2017-01-01

Since its "re-discovery" in 2009, there has been significant interest in defining the genome-wide distribution of DNA marked by 5-hydroxymethylation at cytosine bases (5hmC). In recent years, technological advances have resulted in a multitude of unique strategies to map 5hmC across the human genome. Here we discuss the wide range of approaches available to map this modification and describe in detail the affinity based methods which result in the enrichment of 5hmC marked DNA for downstream analysis.
Interfacing Neural Network Components and Nucleic Acids

PubMed Central

Lissek, Thomas

2017-01-01

Translating neural activity into nucleic acid modifications in a controlled manner harbors unique advantages for basic neurobiology and bioengineering. It would allow for a new generation of biological computers that store output in ultra-compact and long-lived DNA and enable the investigation of animal nervous systems at unprecedented scales. Furthermore, by exploiting the ability of DNA to precisely influence neuronal activity and structure, it could be possible to more effectively create cellular therapy approaches for psychiatric diseases that are currently difficult to treat. PMID:29255707
Composite casting/bonding construction of an air-cooled, high temperature radial turbine wheel

NASA Technical Reports Server (NTRS)

Hammer, A. N.; Aigret, G.; Rodgers, C.; Metcalfe, A. G.

1983-01-01

A composite casting/bonding technique has been developed for the fabrication of a unique air-cooled, high temperature radial inflow turbine wheel design applicable to auxilliary power units with small rotor diameters and blade entry heights. The 'split blade' manufacturing procedure employed is an alternative to complex internal ceramic coring. Attention is given to both aerothermodynamic and structural design, of which the latter made advantageous use of the exploration of alternative cooling passage configurations through CAD/CAM system software modification.
Are rare-earth nanoparticles suitable for in vivo applications?

PubMed

Liu, Chunyan; Hou, Yi; Gao, Mingyuan

2014-10-29

Rare earth (RE) nanoparticles have attracted considerable attention due to their unique optical and magnetic properties associated with f-electrons. The recent accomplishments in RE nanoparticle synthesis have aroused great interest of scientists to further explore their biomedical applications. This Research News summarizes recent achievements in controlled synthesis of magnetic and luminescent RE nanoparticles, surface modification, and toxicity studies of RE nanomaterials, and highlights state-of-the-art in in vivo applications of RE nanoparticles. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Dreamtime astronomy: development of a new indigenous program at Sydney Observatory

NASA Astrophysics Data System (ADS)

Wyatt, Geoffrey; Stephenson, Toner; Hamacher, Duane W.

2014-07-01

The Australian National Curriculum promotes Indigenous culture in school education programs. To foster a broader appreciation of cultural astronomy, to utilise the unique astronomical heritage of the site, and to develop an educational program within the framework of the National Curriculum, Sydney Observatory launched Dreamtime Astronomy - a program incorporating Australian Indigenous culture, astronomy, and Sydney's astronomical history and heritage. This paper reviews the development and implementation of this program and discusses modifications following an evaluation that was conducted by schools.
Study for incorporating time-synchronized approach control into the CH-47/VALT digital navigation system

NASA Technical Reports Server (NTRS)

Mcconnell, W. J., Jr.

1979-01-01

Techniques for obtaining time synchronized (4D) approach control in the VALT research helicopter is described. Various 4D concepts and their compatibility with the existing VALT digital computer navigation and guidance system hardware and software are examined. Modifications to various techniques were investigated in order to take advantage of the unique operating characteristics of the helicopter in the terminal area. A 4D system is proposed, combining the direct to maneuver with the existing VALT curved path generation capability.
Anodic Oxidative Modification of Egg White for Heat Treatment.

PubMed

Takahashi, Masahito; Handa, Akihiro; Yamaguchi, Yusuke; Kodama, Risa; Chiba, Kazuhiro

2016-08-31

A new functionalization of egg white was achieved by an electrochemical reaction. The method involves electron transfer from thiol groups of egg white protein to form disulfide bonds. The oxidized egg white produced less hydrogen sulfide during heat treatment; with sufficient application of electricity, almost no hydrogen sulfide was produced. In addition, gels formed by heating electrochemically oxidized egg white exhibited unique properties, such as a lower gelation temperature and a softened texture, presumably due to protein aggregation and electrochemically mediated intramolecular disulfide bond formation.
Recent advances in gossypol derivatives and analogs: a chemistry and biology view.

PubMed

Lu, Yuzhi; Li, Jun; Dong, Chun-E; Huang, Jian; Zhou, Hai-Bing; Wang, Wei

2017-07-01

Gossypol as a natural occurring polyphenol has been studied in a wide range of therapeutic contexts for a long time. The chemical modifications on gossypol were limited due to the unique chemical properties of polyphenols. The design and synthesis of gossypol derivatives and the exploration of their biological activities are the interest of the synthetic chemists, medicinal chemists and pharmacologists. Thus, the progress of diverse gossypol derivatives and analogs' synthesis, biological activities, mechanism elucidation and drug discovery based on gossypol scaffold is summarized.
White Dwarf Critical Tests for Modified Gravity.

PubMed

Jain, Rajeev Kumar; Kouvaris, Chris; Nielsen, Niklas Grønlund

2016-04-15

Scalar-tensor theories of gravity can lead to modifications of the gravitational force inside astrophysical objects. We exhibit that compact stars such as white dwarfs provide a unique setup to test beyond Horndeski theories of G^{3} type. We obtain stringent and independent constraints on the parameter ϒ characterizing the deviations from Newtonian gravity using the mass-radius relation, the Chandrasekhar mass limit, and the maximal rotational frequency of white dwarfs. We find that white dwarfs impose stronger constraints on ϒ than red and brown dwarfs.
Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras

PubMed Central

Warren, Jeremy G.; Lincoln, James E.; Kirkpatrick, Bruce C.

2015-01-01

Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or, alternatively, it has a different mechanism of substrate binding than other polygalacturonases characterized to date. PMID:26571265
Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

PubMed

Warren, Jeremy G; Lincoln, James E; Kirkpatrick, Bruce C

2015-01-01

Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or, alternatively, it has a different mechanism of substrate binding than other polygalacturonases characterized to date.
On the Development of a Unique Arc Jet Test Apparatus for Control Surface Seal Evaluations

NASA Technical Reports Server (NTRS)

Finkbeiner, Joshua R.; Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; Robbie, Malcolm; Baker, Gus; Erker, Arthur

2004-01-01

NASA Glenn has developed a unique test apparatus capable of evaluating control surface seal and flap designs under simulated reentry heating conditions in NASA Johnson's arc jet test facility. The test apparatus is capable of testing a variety of seal designs with a variety of control surface materials and designs using modular components. The flap angle can be varied during testing, allowing modification of the seal environment while testing is in progress. The flap angle is varied using an innovative transmission system which limits heat transfer from the hot flap structure to the motor, all while keeping the components properly aligned regardless of thermal expansion. A combination of active and passive cooling is employed to prevent thermal damage to the test fixture while still obtaining the target seal temperature.
Quantum-Sequencing: Fast electronic single DNA molecule sequencing

NASA Astrophysics Data System (ADS)

Casamada Ribot, Josep; Chatterjee, Anushree; Nagpal, Prashant

2014-03-01

A major goal of third-generation sequencing technologies is to develop a fast, reliable, enzyme-free, high-throughput and cost-effective, single-molecule sequencing method. Here, we present the first demonstration of unique ``electronic fingerprint'' of all nucleotides (A, G, T, C), with single-molecule DNA sequencing, using Quantum-tunneling Sequencing (Q-Seq) at room temperature. We show that the electronic state of the nucleobases shift depending on the pH, with most distinct states identified at acidic pH. We also demonstrate identification of single nucleotide modifications (methylation here). Using these unique electronic fingerprints (or tunneling data), we report a partial sequence of beta lactamase (bla) gene, which encodes resistance to beta-lactam antibiotics, with over 95% success rate. These results highlight the potential of Q-Seq as a robust technique for next-generation sequencing.
A new numerical approach for uniquely solvable exterior Riemann-Hilbert problem on region with corners

NASA Astrophysics Data System (ADS)

Zamzamir, Zamzana; Murid, Ali H. M.; Ismail, Munira

2014-06-01

Numerical solution for uniquely solvable exterior Riemann-Hilbert problem on region with corners at offcorner points has been explored by discretizing the related integral equation using Picard iteration method without any modifications to the left-hand side (LHS) and right-hand side (RHS) of the integral equation. Numerical errors for all iterations are converge to the required solution. However, for certain problems, it gives lower accuracy. Hence, this paper presents a new numerical approach for the problem by treating the generalized Neumann kernel at LHS and the function at RHS of the integral equation. Due to the existence of the corner points, Gaussian quadrature is employed which avoids the corner points during numerical integration. Numerical example on a test region is presented to demonstrate the effectiveness of this formulation.

Mandibular second molar exhibiting a unique "Y-" and "J-" "shaped" root canal anatomy diagnosed using cone-beam computed tomographic scanning: A case report.

PubMed

Parashar, Saumya-Rajesh; Kowsky, R Dinesh; Natanasabapathy, Velmurugan

2017-01-01

This article aims to report a unique case with aberrant root canal anatomy exhibiting "Y-" and "J"-shaped canal pattern in a mandibular second molar. Anatomic complexities may pose challenges for endodontic treatment. Before performing endodontic treatment, the clinician should be aware of the internal anatomy of the tooth being treated and should recognize anatomic aberrations if present. Presence of unusual anatomy may call for modifications in treatment planning. This report describes in detail about a mandibular second molar tooth associated with two paramolar tubercles having a peculiar "Y-" and "J-"shaped canal anatomy detected with the aid of cone beam computed tomography, which has never been reported in the dental literature. The proposed treatment protocol for the endodontic management of the same has also been discussed.
Effects of behavioral and pharmacological therapies on peer reinforcement of deviancy in children with ADHD-only, ADHD and conduct problems, and controls

PubMed Central

Helseth, Sarah A.; Waschbusch, Daniel A.; Gnagy, Elizabeth M.; Onyango, Adia N.; Burrows-MacLean, Lisa; Fabiano, Gregory A.; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Wymbs, Frances A.; Garefino, Allison; Massetti, Greta M.; Mazzant, Jessica Robb; Hoffman, Martin T.; Waxmonsky, James G.; Nichols-Lopez, Kristin; Pelham, William E.

2015-01-01

Objective This study compared the unique and combined effects of evidence-based treatments for ADHD —stimulant medication and behavior modification—on children’s rates of reinforcement for deviant peer behavior (RDPB). Method Using a within-subjects design, 222 elementary school-age children attending a summer treatment program, including 151 children with ADHD (127 male), with and without comorbid conduct problems, and 71 control children (57 male), received varying combinations of behavior modification (no, low-intensity, and high-intensity) and methylphenidate (placebo, 0.15 mg/kg, 0.30 mg/kg, and 0.60 mg/kg). RDPB was measured through direct observation and compared across all behavior modification and medication conditions. Results Children with ADHD reinforced the deviant behavior of their peers at a significantly higher rate than control children in the absence of either intervention. However, that difference largely disappeared in the presence of both behavior modification and medication. Both low and high-intensity behavior modification, as well as medium (0.30 mg/kg) and high (0.60 mg/kg) doses of methylphenidate, significantly reduced the rate of ADHD children’s RDPB to levels similar to the control group. Conclusions Results indicate that although untreated children with ADHD do engage in RDPB at a greater rate than their non-ADHD peers, existing evidence-based interventions can substantially decrease the presence of RDPB, thereby limiting potential iatrogenic effects in group-based treatment settings. Public Health Significance Statement This study found that children with behavior disorders reinforced their peers' deviant behaviors much more than typically developing children. However, behavior modification and medication treatments both reduced reinforcement rates, indicating that peer contagion can easily be managed in group-based treatments for children PMID:25495357
Dynamically and epigenetically coordinated GATA/ETS/SOX transcription factor expression is indispensable for endothelial cell differentiation

PubMed Central

Nakaki, Ryo; Shimamura, Teppei; Matsunaga, Taichi; Yamamizu, Kohei; Katayama, Shiori; Suehiro, Jun-ichi; Osawa, Tsuyoshi; Aburatani, Hiroyuki; Kodama, Tatsuhiko; Wada, Youichiro; Yamashita, Jun K.

2017-01-01

Abstract Although studies of the differentiation from mouse embryonic stem (ES) cells to vascular endothelial cells (ECs) provide an excellent model for investigating the molecular mechanisms underlying vascular development, temporal dynamics of gene expression and chromatin modifications have not been well studied. Herein, using transcriptomic and epigenomic analyses based on H3K4me3 and H3K27me3 modifications at a genome-wide scale, we analysed the EC differentiation steps from ES cells and crucial epigenetic modifications unique to ECs. We determined that Gata2, Fli1, Sox7 and Sox18 are master regulators of EC that are induced following expression of the haemangioblast commitment pioneer factor, Etv2. These master regulator gene loci were repressed by H3K27me3 throughout the mesoderm period but rapidly transitioned to histone modification switching from H3K27me3 to H3K4me3 after treatment with vascular endothelial growth factor. SiRNA knockdown experiments indicated that these regulators are indispensable not only for proper EC differentiation but also for blocking the commitment to other closely aligned lineages. Collectively, our detailed epigenetic analysis may provide an advanced model for understanding temporal regulation of chromatin signatures and resulting gene expression profiles during EC commitment. These studies may inform the future development of methods to stimulate the vascular endothelium for regenerative medicine. PMID:28334937
DOE Office of Scientific and Technical Information (OSTI.GOV)

Stella, Stefano; University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen; Molina, Rafael

Crystal structures of BurrH and the BurrH–DNA complex are reported. DNA editing offers new possibilities in synthetic biology and biomedicine for modulation or modification of cellular functions to organisms. However, inaccuracy in this process may lead to genome damage. To address this important problem, a strategy allowing specific gene modification has been achieved through the addition, removal or exchange of DNA sequences using customized proteins and the endogenous DNA-repair machinery. Therefore, the engineering of specific protein–DNA interactions in protein scaffolds is key to providing ‘toolkits’ for precise genome modification or regulation of gene expression. In a search for putative DNA-bindingmore » domains, BurrH, a protein that recognizes a 19 bp DNA target, was identified. Here, its apo and DNA-bound crystal structures are reported, revealing a central region containing 19 repeats of a helix–loop–helix modular domain (BurrH domain; BuD), which identifies the DNA target by a single residue-to-nucleotide code, thus facilitating its redesign for gene targeting. New DNA-binding specificities have been engineered in this template, showing that BuD-derived nucleases (BuDNs) induce high levels of gene targeting in a locus of the human haemoglobin β (HBB) gene close to mutations responsible for sickle-cell anaemia. Hence, the unique combination of high efficiency and specificity of the BuD arrays can push forward diverse genome-modification approaches for cell or organism redesign, opening new avenues for gene editing.« less
Tailored HIV-1 vectors for genetic modification of primary human dendritic cells and monocytes.

PubMed

Durand, Stéphanie; Nguyen, Xuan-Nhi; Turpin, Jocelyn; Cordeil, Stephanie; Nazaret, Nicolas; Croze, Séverine; Mahieux, Renaud; Lachuer, Joël; Legras-Lachuer, Catherine; Cimarelli, Andrea

2013-01-01

Monocyte-derived dendritic cells (MDDCs) play a key role in the regulation of the immune system and are the target of numerous gene therapy applications. The genetic modification of MDDCs is possible with human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LVs) but requires high viral doses to bypass their natural resistance to viral infection, and this in turn affects their physiological properties. To date, a single viral protein is able to counter this restrictive phenotype, Vpx, a protein derived from members of the HIV-2/simian immunodeficiency virus SM lineage that counters at least two restriction factors present in myeloid cells. By tagging Vpx with a short heterologous membrane-targeting domain, we have obtained HIV-1 LVs incorporating high levels of this protein (HIV-1-Src-Vpx). These vectors efficiently transduce differentiated MDDCs and monocytes either as previously purified populations or as populations within unsorted peripheral blood mononuclear cells (PBMCs). In addition, these vectors can be efficiently pseudotyped with receptor-specific envelopes, further restricting their cellular tropism almost uniquely to MDDCs. Compared to conventional HIV-1 LVs, these novel vectors allow for an efficient genetic modification of MDDCs and, more importantly, do not cause their maturation or affect their survival, which are unwanted side effects of the transduction process. This study describes HIV-1-Src-Vpx LVs as a novel potent tool for the genetic modification of differentiated MDDCs and of circulating monocyte precursors with strong potential for a wide range of gene therapy applications.
Modification of Different Zirconium Propoxide Precursors by Diethanolamine. Is There a Shelf Stability Issue for Sol-Gel Applications?

PubMed Central

Spijksma, Gerald I.; Blank, Dave H. A.; Bouwmeester, Henny J. M.; Kessler, Vadim G.

2009-01-01

Modification of different zirconium propoxide precursors with H2dea was investigated by characterization of the isolated modified species. Upon modification of zirconium n-propoxide and [Zr(OnPr)(OiPr)3(iPrOH)]2 with ½ a mol equivalent of H2dea the complexes [Zr2(OnPr)6(OCH2CH2)2NH]2 (1) and [Zr2(OnPr)2(OiPr)4(OCH2CH2)2NH]2 (2) were obtained. However, 1H-NMR studies of these tetranuclear compounds showed that these are not time-stable either in solution or solid form. The effect of this time instability on material properties is demonstrated by light scattering and TEM experiments. Modification of zirconium isopropoxide with either ½ or 1 equivalent mol of H2dea results in formation of the trinuclear complex, Zr{η3μ2-NH(C2H4O)2}3[Zr(OiPr)3]2(iPrOH)2 (3) countering a unique nona-coordinated central zirconium atom. This complex 3 is one of the first modified zirconium propoxide precursors shown to be stable in solution for long periods of time. The particle size and morphology of the products of sol-gel synthesis are strongly dependent on the time factor and eventual heat treatment of the precursor solution. Reproducible sol-gel synthesis requires the use of solution stable precursors. PMID:20087472
Stand-Alone Pulmonary Vein Isolation Versus Pulmonary Vein Isolation With Additional Substrate Modification as Index Ablation Procedures in Patients With Persistent and Long-Standing Persistent Atrial Fibrillation: The Randomized Alster-Lost-AF Trial (Ablation at St. Georg Hospital for Long-Standing Persistent Atrial Fibrillation).

PubMed

Fink, Thomas; Schlüter, Michael; Heeger, Christian-Hendrik; Lemes, Christine; Maurer, Tilman; Reissmann, Bruno; Riedl, Johannes; Rottner, Laura; Santoro, Francesco; Schmidt, Boris; Wohlmuth, Peter; Mathew, Shibu; Sohns, Christian; Ouyang, Feifan; Metzner, Andreas; Kuck, Karl-Heinz

2017-07-01

Pulmonary vein isolation (PVI) for persistent atrial fibrillation is associated with limited success rates and often requires multiple procedures to maintain stable sinus rhythm. In the prospective and randomized Alster-Lost-AF trial (Ablation at St. Georg Hospital for Long-Standing Persistent Atrial Fibrillation), we sought to assess, in patients with symptomatic persistent or long-standing persistent atrial fibrillation, the outcomes of initial ablative strategies comprising either stand-alone PVI (PVI-only approach) or a stepwise approach of PVI followed by complex fractionated atrial electrogram ablation and linear ablation (Substrate-modification approach). Patients were randomized 1:1 to stand-alone PVI or PVI plus substrate modification. The primary study end point was freedom from recurrence of any atrial tachyarrhythmia, outside a 90-day blanking period, at 12 months. A total of 124 patients were enrolled, with 118 patients included in the analysis (61 in the PVI-only group, 57 in the Substrate-modification group). Atrial tachyarrhythmias recurred in 28 PVI-only group patients and 24 Substrate-modification group patients, for 1-year freedom from tachyarrhythmia recurrence after a single ablation procedure of 54% (95% confidence interval, 43%-68%) in the PVI-only and 57% (95% confidence interval, 46%-72%) in the Substrate-modification group ( P =0.86). Twenty-four patients in the PVI-only group (39%) and 18 in the Substrate-modification group (32%) were without arrhythmia recurrence and off antiarrhythmic drug therapy at the end of the 12-month follow-up. In patients with persistent and long-standing persistent atrial fibrillation, no significant difference was observed in 12-month freedom from atrial tachyarrhythmias between an index ablative approach of stand-alone PVI and a stepwise approach of PVI plus complex fractionated atrial electrogram and linear ablation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00820625. © 2017 American Heart Association, Inc.
H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome

PubMed Central

Pauler, Florian M.; Sloane, Mathew A.; Huang, Ru; Regha, Kakkad; Koerner, Martha V.; Tamir, Ido; Sommer, Andreas; Aszodi, Andras; Jenuwein, Thomas; Barlow, Denise P.

2009-01-01

In mammals, genome-wide chromatin maps and immunofluorescence studies show that broad domains of repressive histone modifications are present on pericentromeric and telomeric repeats and on the inactive X chromosome. However, only a few autosomal loci such as silent Hox gene clusters have been shown to lie in broad domains of repressive histone modifications. Here we present a ChIP-chip analysis of the repressive H3K27me3 histone modification along chr 17 in mouse embryonic fibroblast cells using an algorithm named broad local enrichments (BLOCs), which allows the identification of broad regions of histone modifications. Our results, confirmed by BLOC analysis of a whole genome ChIP-seq data set, show that the majority of H3K27me3 modifications form BLOCs rather than focal peaks. H3K27me3 BLOCs modify silent genes of all types, plus flanking intergenic regions and their distribution indicates a negative correlation between H3K27me3 and transcription. However, we also found that some nontranscribed gene-poor regions lack H3K27me3. We therefore performed a low-resolution analysis of whole mouse chr 17, which revealed that H3K27me3 is enriched in mega-base-pair-sized domains that are also enriched for genes, short interspersed elements (SINEs) and active histone modifications. These genic H3K27me3 domains alternate with similar-sized gene-poor domains. These are deficient in active histone modifications, as well as H3K27me3, but are enriched for long interspersed elements (LINEs) and long-terminal repeat (LTR) transposons and H3K9me3 and H4K20me3. Thus, an autosome can be seen to contain alternating chromatin bands that predominantly separate genes from one retrotransposon class, which could offer unique domains for the specific regulation of genes or the silencing of autonomous retrotransposons. PMID:19047520
The Crystal Structure of Giardia duodenalis 14-3-3 in the Apo Form: When Protein Post-Translational Modifications Make the Difference

PubMed Central

Fiorillo, Annarita; di Marino, Daniele; Bertuccini, Lucia; Via, Allegra; Pozio, Edoardo; Camerini, Serena; Ilari, Andrea; Lalle, Marco

2014-01-01

The 14-3-3s are a family of dimeric evolutionary conserved pSer/pThr binding proteins that play a key role in multiple biological processes by interacting with a plethora of client proteins. Giardia duodenalis is a flagellated protozoan that affects millions of people worldwide causing an acute and chronic diarrheal disease. The single giardial 14-3-3 isoform (g14-3-3), unique in the 14-3-3 family, needs the constitutive phosphorylation of Thr214 and the polyglycylation of its C-terminus to be fully functional in vivo. Alteration of the phosphorylation and polyglycylation status affects the parasite differentiation into the cyst stage. To further investigate the role of these post-translational modifications, the crystal structure of the g14-3-3 was solved in the unmodified apo form. Oligomers of g14-3-3 were observed due to domain swapping events at the protein C-terminus. The formation of filaments was supported by TEM. Mutational analysis, in combination with native PAGE and chemical cross-linking, proved that polyglycylation prevents oligomerization. In silico phosphorylation and molecular dynamics simulations supported a structural role for the phosphorylation of Thr214 in promoting target binding. Our findings highlight unique structural features of g14-3-3 opening novel perspectives on the evolutionary history of this protein family and envisaging the possibility to develop anti-giardial drugs targeting g14-3-3. PMID:24658679
Blind identification of the kinetic parameters in three-compartment models

NASA Astrophysics Data System (ADS)

Riabkov, Dmitri Y.; Di Bella, Edward V. R.

2004-03-01

Quantified knowledge of tissue kinetic parameters in the regions of the brain and other organs can offer information useful in clinical and research applications. Dynamic medical imaging with injection of radioactive or paramagnetic tracer can be used for this measurement. The kinetics of some widely used tracers such as [18F]2-fluoro-2-deoxy-D-glucose can be described by a three-compartment physiological model. The kinetic parameters of the tissue can be estimated from dynamically acquired images. Feasibility of estimation by blind identification, which does not require knowledge of the blood input, is considered analytically and numerically in this work for the three-compartment type of tissue response. The non-uniqueness of the two-region case for blind identification of kinetic parameters in three-compartment model is shown; at least three regions are needed for the blind identification to be unique. Numerical results for the accuracy of these blind identification methods in different conditions were considered. Both a separable variables least-squares (SLS) approach and an eigenvector-based algorithm for multichannel blind deconvolution approach were used. The latter showed poor accuracy. Modifications for non-uniform time sampling were also developed. Also, another method which uses a model for the blood input was compared. Results for the macroparameter K, which reflects the metabolic rate of glucose usage, using three regions with noise showed comparable accuracy for the separable variables least squares method and for the input model-based method, and slightly worse accuracy for SLS with the non-uniform sampling modification.
Simple algorithm for improved security in the FDDI protocol

NASA Astrophysics Data System (ADS)

Lundy, G. M.; Jones, Benjamin

1993-02-01

We propose a modification to the Fiber Distributed Data Interface (FDDI) protocol based on a simple algorithm which will improve confidential communication capability. This proposed modification provides a simple and reliable system which exploits some of the inherent security properties in a fiber optic ring network. This method differs from conventional methods in that end to end encryption can be facilitated at the media access control sublayer of the data link layer in the OSI network model. Our method is based on a variation of the bit stream cipher method. The transmitting station takes the intended confidential message and uses a simple modulo two addition operation against an initialization vector. The encrypted message is virtually unbreakable without the initialization vector. None of the stations on the ring will have access to both the encrypted message and the initialization vector except the transmitting and receiving stations. The generation of the initialization vector is unique for each confidential transmission and thus provides a unique approach to the key distribution problem. The FDDI protocol is of particular interest to the military in terms of LAN/MAN implementations. Both the Army and the Navy are considering the standard as the basis for future network systems. A simple and reliable security mechanism with the potential to support realtime communications is a necessary consideration in the implementation of these systems. The proposed method offers several advantages over traditional methods in terms of speed, reliability, and standardization.
Characterization of the Mouse Pancreatic Islet Proteome and Comparative Analysis with Other Mouse Tissues

PubMed Central

Petyuk, Vladislav A.; Qian, Wei-Jun; Hinault, Charlotte; Gritsenko, Marina A.; Singhal, Mudita; Monroe, Matthew E.; Camp, David G.; Kulkarni, Rohit N.; Smith, Richard D.

2009-01-01

The pancreatic islets of Langerhans, and especially the insulin-producing beta cells, play a central role in the maintenance of glucose homeostasis. Alterations in the expression of multiple proteins in the islets that contribute to the maintenance of islet function are likely to underlie the pathogenesis of type 2 diabetes. To identify proteins that constitute the islet proteome, we provide the first comprehensive proteomic characterization of pancreatic islets for mouse, the most commonly used animal model in diabetes research. Using strong cation exchange fractionation coupled with reversed phase LC-MS/MS we report the confident identification of 17,350 different tryptic peptides covering 2,612 proteins having at least two unique peptides per protein. The dataset also identified ~60 post-translationally modified peptides including oxidative modifications and phosphorylation. While many of the identified phosphorylation sites corroborate those previously known, the oxidative modifications observed on cysteinyl residues reveal potentially novel information suggesting a role for oxidative stress in islet function. Comparative analysis with 15 available proteomic datasets from other mouse tissues and cells revealed a set of 133 proteins predominantly expressed in pancreatic islets. This unique set of proteins, in addition to those with known functions such as peptide hormones secreted from the islets, contains several proteins with as yet unknown functions. The mouse islet protein and peptide database accessible at http://ncrr.pnl.gov, provides an important reference resource for the research community to facilitate research in the diabetes and metabolism fields. PMID:18570455
Microsensors for border patrol applications

NASA Astrophysics Data System (ADS)

Falkofske, Dwight; Krantz, Brian; Shimazu, Ron; Berglund, Victor

2005-05-01

A top concern in homeland security efforts is the lack of ability to monitor the thousands of miles of open border with our neighbors. It is not currently feasible to continually monitor the borders for illegal intrusions. The MicroSensor System (MSS) seeks to achieve a low-cost monitoring solution that can be efficiently deployed for border patrol applications. The modifications and issues regarding the unique requirements of this application will be discussed and presented. The MicroSensor System was developed by the Defense Microelectronics Activity (DMEA) for military applications, but border patrol applications, with their unique sensor requirements, demand careful adaptation and modification from the military application. Adaptation of the existing sensor design for border applications has been initiated. Coverage issues, communications needs, and other requirements need to be explored for the border patrol application. Currently, border patrol has a number of deficiencies that can be addressed with a microsensor network. First, a distributed networked sensor field could mitigate the porous border intruder detection problem. Second, a unified database needs to be available to identify aliens attempting to cross into the United States. This database needs to take unique characteristics (e.g. biometrics, fingerprints) recovered from a specialized field unit to reliably identify intruders. Finally, this sensor network needs to provide a communication ability to allow border patrol officers to have quick access to intrusion information as well as equipment tracking and voice communication. MSS already addresses the sensing portion of the solution, including detection of acoustic, infrared, magnetic, and seismic events. MSS also includes a low-power networking protocol to lengthen the battery life. In addition to current military requirements, MSS needs a solar panel solution to extend its battery life to 5 years, and an additional backbone communication link. Expanding the capabilities of MSS will go a long way to improving the security of the nation's porous borders.
Earth Science Keyword Stewardship: Access and Management through NASA's Global Change Master Directory (GCMD) Keyword Management System (KMS)

NASA Astrophysics Data System (ADS)

Stevens, T.; Olsen, L. M.; Ritz, S.; Morahan, M.; Aleman, A.; Cepero, L.; Gokey, C.; Holland, M.; Cordova, R.; Areu, S.; Cherry, T.; Tran-Ho, H.

2012-12-01

Discovering Earth science data can be complex if the catalog holding the data lacks structure. Controlled keyword vocabularies within metadata catalogues can improve data discovery. NASA's Global Change Master Directory's (GCMD) Keyword Management System (KMS) is a recently released a RESTful web service for managing and providing access to controlled keywords (science keywords, service keywords, platforms, instruments, providers, locations, projects, data resolution, etc.). The KMS introduces a completely new paradigm for the use and management of the keywords and allows access to these keywords as SKOS Concepts (RDF), OWL, standard XML, and CSV. A universally unique identifier (UUID) is automatically assigned to each keyword, which uniquely identifies each concept and its associated information. A component of the KMS is the keyword manager, an internal tool that allows GCMD science coordinators to manage concepts. This includes adding, modifying, and deleting broader, narrower, or related concepts and associated definitions. The controlled keyword vocabulary represents over 20 years of effort and collaboration with the Earth science community. The maintenance, stability, and ongoing vigilance in maintaining mutually exclusive and parallel keyword lists is important for a "normalized" search and discovery, and provides a unique advantage for the science community. Modifications and additions are made based on community suggestions and internal review. To help maintain keyword integrity, science keyword rules and procedures for modification of keywords were developed. This poster will highlight the use of the KMS as a beneficial service for the stewardship and access of the GCMD keywords. Users will learn how to access the KMS and utilize the keywords. Best practices for managing an extensive keyword hierarchy will also be discussed. Participants will learn the process for making keyword suggestions, which subsequently help in building a controlled keyword vocabulary to improve earth science data discovery and access.
Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families.

PubMed

Dewhurst, Henry M; Choudhury, Shilpa; Torres, Matthew P

2015-08-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)--a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits--conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit-N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Surface modification of medical implant materials with hydrophilic polymers for enhanced biocompatibility and delivery of therapeutic agents

NASA Astrophysics Data System (ADS)

Urbaniak, Daniel J.

2004-11-01

In the research reported here, the surface modification of medical grade poly(dimethyl siloxane), polyetherurethane, and stainless steel through gamma-radiation grafting of hydrophilic polymers was investigated. Emphasis was placed on developing improved and simplified surface modification methods that produce more stable and more bioacceptible hydrophilic graft surfaces. As a result of this research, new surface modification techniques were developed that yield significantly improved surface stability unachievable using previous surface modification techniques. The surface modification of poly(dimethyl siloxane) with hydrophilic polymers was carried out using gamma radiation initiated graft polymerization. The addition of alkali metal hydroxides afforded a unique way to enhance the grafting of N-vinyl-2 pyrrolidone, dimethylacryamide, 2-methacryloyloxyethyl phosphoryl choline, N,N-dimethyl-N-(methacryloyloxyethyl)-N-(3-sulfopropyl)-ammonium-betaine, N,N-dimethyl-N-(methacrylamidopropyl)-N-(3-sulfopropyl)-ammonium-betaine, and copolymers thereof to silicones. Ethanolamine was found to further enhance the grafting of some hydrophilic polymers to silicone. The resulting hydrophilic surface grafts were resistant to hydrophobic surface rearrangement. This process overcomes previous problems inherent in silicone surface modification. The technique was also found to moderately enhance the grafting of hydrophilic monomers to polyetherurethane and to 316-L stainless steel. The surface modification of 316-L stainless steel was further enhanced by treating the substrates with a chromium III methacrylate bonding agent prior to irradiation. The coatings were evaluated for their potential use as depots for delivering therapeutic agents. The release of ofloxacin from surface-modified poly(dimethyl siloxane) and dexamethasone from surface-modified 316-L stainless steel was evaluated by in-vitro experiments. Therapeutic levels of drugs were released from surface-modified specimens via a burst effect. Improved surface characterization methods were another aspect of this research. New nanomechanical testing techniques were developed and used to evaluate the viscoelastic surface mechanical properties of low modulus surface-modified specimens. Dynamic nanoindentation characterization techniques were designed to measure the storage modulus and loss modulus of compliant viscoelastic substrate surfaces. The results of these experiments were compared with modulus data obtained by conventional dynamic mechanical spectroscopy. Nanoscratch testing methods were also developed that qualitatively compared the abrasion resistance of surface-modified substrates. (Abstract shortened by UMI.)
Methods and processes of developing the strengthening the reporting of observational studies in epidemiology - veterinary (STROBE-Vet) statement.

PubMed

Sargeant, J M; O'Connor, A M; Dohoo, I R; Erb, H N; Cevallos, M; Egger, M; Ersbøll, A K; Martin, S W; Nielsen, L R; Pearl, D L; Pfeiffer, D U; Sanchez, J; Torrence, M E; Vigre, H; Waldner, C; Ward, M P

2016-11-01

The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. To develop an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety. A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare, and food safety outcomes. Consensus meeting May 11-13, 2014 in Mississauga, Ontario, Canada. Seventeen experts from North America, Europe, and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals. Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and if items should be added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re-wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition. The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered: 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding). Published literature was not always available to support modification to, or inclusion of, an item. The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare, or food safety outcomes by recognizing the unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Transition Services for DHH Adolescents and Young Adults With Disabilities: Challenges and Theoretical Frameworks.

PubMed

Luft, Pamela

2015-01-01

Deaf and hard of hearing (DHH) adolescents and young adults with disabilities (DWD) are a highly diverse group who may also demonstrate a range of functional limitations. These present unique challenges to professional efforts to provide high-quality transition services. Despite these issues, a majority of this population has cognitive abilities within the typical range, and therefore, their transition expectations should be commensurately high in comparison to those of their DHH peers. Research-based transition practices offer a range of interventions, and although none have been validated with DHH or DWD students, several provide important foundational learning opportunities. Yet their implementation will require modifications with programming and expertise beyond what is available in most school districts. Use of a multilevel, ecological framework and person-centered planning offers systematic strategies for increasing access to transition resources and supports to address these unique needs and lead to successful adulthood.
State of the art: dual-energy CT of the abdomen.

PubMed

Marin, Daniele; Boll, Daniel T; Mileto, Achille; Nelson, Rendon C

2014-05-01

Recent technologic advances in computed tomography (CT)--enabling the nearly simultaneous acquisition of clinical images using two different x-ray energy spectra--have sparked renewed interest in dual-energy CT. By interrogating the unique characteristics of different materials at different x-ray energies, dual-energy CT can be used to provide quantitative information about tissue composition, overcoming the limitations of attenuation-based conventional single-energy CT imaging. In the past few years, intensive research efforts have been devoted to exploiting the unique and powerful opportunities of dual-energy CT for a variety of clinical applications. This has led to CT protocol modifications for radiation dose reduction, improved diagnostic performance for detection and characterization of diseases, as well as image quality optimization. In this review, the authors discuss the basic principles, instrumentation and design, examples of current clinical applications in the abdomen and pelvis, and future opportunities of dual-energy CT.
Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents.

PubMed

Debele, Tilahun Ayane; Mekuria, Shewaye Lakew; Tsai, Hsieh-Chih

2016-11-01

Polysaccharide-based nanoparticles have fascinated attention as a vesicle of different pharmaceutical agents due to their unique multi-functional groups in addition to their physicochemical properties, including biocompatibility and biodegradability. The existence of multi-functional groups on the polysaccharide backbone permits facile chemical or biochemical modification to synthesize polysaccharide based nanoparticles with miscellaneous structures. Polysaccharide-based nanogels have high water content, large surface area for multivalent bioconjugation, tunable size, and interior network for the incorporation of different pharmaceutical agents. These unique properties offer great potential for the utilization of polysaccharide-based nanogels in the drug delivery systems. Hence, this review describes chemistry of certain common polysaccharides, several methodologies used to synthesize polysaccharide nanoparticles and primarily focused on the polysaccharide (or polysaccharide derivative) based nanogels as the carrier of pharmaceutical agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Advancing epilepsy treatment through personalized genetic zebrafish models.

PubMed

Griffin, A; Krasniak, C; Baraban, S C

2016-01-01

With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts. © 2016 Elsevier B.V. All rights reserved.
Catalysis by metal-organic frameworks: fundamentals and opportunities.

PubMed

Ranocchiari, Marco; van Bokhoven, Jeroen Anton

2011-04-14

Crystalline porous materials are extremely important for developing catalytic systems with high scientific and industrial impact. Metal-organic frameworks (MOFs) show unique potential that still has to be fully exploited. This perspective summarizes the properties of MOFs with the aim to understand what are possible approaches to catalysis with these materials. We categorize three classes of MOF catalysts: (1) those with active site on the framework, (2) those with encapsulated active species, and (3) those with active sites attached through post-synthetic modification. We identify the tunable porosity, the ability to fine tune the structure of the active site and its environment, the presence of multiple active sites, and the opportunity to synthesize structures in which key-lock bonding of substrates occurs as the characteristics that distinguish MOFs from other materials. We experience a unique opportunity to imagine and design heterogeneous catalysts, which might catalyze reactions previously thought impossible.
Preservation and Modification of Culture in Family Socialization: Development of Parenting Measures for Korean Immigrant Families

PubMed Central

Choi, Yoonsun; Kim, You Seung; Drankus, Dina; Kim, Hyun Jee

2012-01-01

This study aims to describe the family socialization beliefs and practices of Korean immigrant parents through testing psychometric properties of several newly developed items and scales to assess the major components of the Korean traditional concept of family socialization, ga-jung-kyo-yuk. These new measures were examined for validity and reliability. The findings show that Korean immigrant parents largely preserve their traditional and core parenting values, while also showing meaningful, yet not very dramatic, signs of adopting new cultural traits. The results also suggest that the acculturative process may not be simply bilinear but may generate a new, unique and blended value and behavior set from the two (or more) cultures involved. Culturally appropriate practice requires not only further validation of existing knowledge with minority groups, but the development of a theoretical framework of family socialization that recognizes the cultural uniqueness of immigrant families. PMID:24765236
High-power direct-diode laser successes

NASA Astrophysics Data System (ADS)

Haake, John M.; Zediker, Mark S.

2004-06-01

Direct diode laser will become much more prevalent in the solar system of manufacturing due to their high efficiency, small portable size, unique beam profiles, and low ownership costs. There has been many novel applications described for high power direct diode laser [HPDDL] systems but few have been implemented in extreme production environments due to diode and diode system reliability. We discuss several novel applications in which the HPDDL have been implemented and proven reliable and cost-effective in production environments. These applications are laser hardening/surface modification, laser wire feed welding and laser paint stripping. Each of these applications uniquely tests the direct diode laser systems capabilities and confirms their reliability in production environments. A comparison of the advantages direct diode laser versus traditional industrial lasers such as CO2 and Nd:YAG and non-laser technologies such a RF induction, and MIG welders for each of these production applications is presented.
Recent advances in the discovery of potent and selective HDAC6 inhibitors.

PubMed

Wang, Xiu-Xiu; Wan, Ren-Zhong; Liu, Zhao-Peng

2018-01-01

Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein trafficking and degradation, cell shape and migration. Selective HDAC6 inhibitors are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Therefore, extensive investigations have been made in the discovery of selective HDAC6 inhibitors. Based on their different zinc binding groups (ZBGs), in this review, HDAC6 inhibitors are grouped as hydroxamic acids, a sulfur containing ZBG based derivatives and other ZBG-derived compounds, and their enzymatic inhibitory activity, selectivity and other biological activities are introduced and summarized. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Linear Proof Mass Actuator

NASA Technical Reports Server (NTRS)

Holloway, Sidney E., III

1994-01-01

This paper describes the mechanical design, analysis, fabrication, testing, and lessons learned by developing a uniquely designed spaceflight-like actuator. The linear proof mass actuator (LPMA) was designed to attach to both a large space structure and a ground test model without modification. Previous designs lacked the power to perform in a terrestrial environment while other designs failed to produce the desired accelerations or frequency range for spaceflight applications. Thus, the design for a unique actuator was conceived and developed at NASA Langley Research Center. The basic design consists of four large mechanical parts (mass, upper housing, lower housing, and center support) and numerous smaller supporting components including an accelerometer, encoder, and four drive motors. Fabrication personnel were included early in the design phase of the LPMA as part of an integrated manufacturing process to alleviate potential difficulties in machining an already challenging design. Operating testing of the LPMA demonstrated that the actuator is capable of various types of load functions.
Linear Proof Mass Actuator

NASA Technical Reports Server (NTRS)

Holloway, S. E., III

1995-01-01

This paper describes the mechanical design, analysis, fabrication, testing, and lessons learned by developing a uniquely designed spaceflight-like actuator. The Linear Proof Mass Actuator (LPMA) was designed to attach to both a large space structure and a ground test model without modification. Previous designs lacked the power to perform in a terrestrial environment while other designs failed to produce the desired accelerations or frequency range for spaceflight applications. Thus, the design for a unique actuator was conceived and developed at NASA Langley Research Center. The basic design consists of four large mechanical parts (Mass, Upper Housing, Lower Housing, and Center Support) and numerous smaller supporting components including an accelerometer, encoder, and four drive motors. Fabrication personnel were included early in the design phase of the LPMA as part of an integrated manufacturing process to alleviate potential difficulties in machining an already challenging design. Operational testing of the LPMA demonstrated that the actuator is capable of various types of load functions.
Resin-assisted Enrichment of N-terminal Peptides for Characterizing Proteolytic Processing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jong Seo; Dai, Ziyu; Aryal, Uma K.

2013-06-17

Proteolytic processing is a ubiquitous, irreversible posttranslational modification that plays an important role in cellular regulation in all living organisms. Herein we report a resin-assisted positive selection method for specifically enriching protein N-terminal peptides to facilitate the characterization of proteolytic processing events by liquid chromatography-tandem mass spectrometry. In this approach, proteins are initially reduced and alkylated and their lysine residues are converted to homoarginines. Then, protein N-termini are selectively converted to reactive thiol groups. We demonstrate that these sequential reactions were achieved with nearly quantitative efficiencies. Thiol-containing N-terminal peptides are then captured (>98% efficiency) by a thiol-affinity resin, a significantmore » improvement over the traditional avidin/biotin enrichment. Application to cell lysates of Aspergillus niger, a filamentous fungus of interest for biomass degradation, enabled the identification of 1672 unique protein N-termini and proteolytic cleavage sites from 690 unique proteins.« less
Tissue Regeneration: A Silk Road.

PubMed

Jao, Dave; Mou, Xiaoyang; Hu, Xiao

2016-08-05

Silk proteins are natural biopolymers that have extensive structural possibilities for chemical and mechanical modifications to facilitate novel properties, functions, and applications in the biomedical field. The versatile processability of silk fibroins (SF) into different forms such as gels, films, foams, membranes, scaffolds, and nanofibers makes it appealing in a variety of applications that require mechanically superior, biocompatible, biodegradable, and functionalizable biomaterials. There is no doubt that nature is the world's best biological engineer, with simple, exquisite but powerful designs that have inspired novel technologies. By understanding the surface interaction of silk materials with living cells, unique characteristics can be implemented through structural modifications, such as controllable wettability, high-strength adhesiveness, and reflectivity properties, suggesting its potential suitability for surgical, optical, and other biomedical applications. All of the interesting features of SF, such as tunable biodegradation, anti-bacterial properties, and mechanical properties combined with potential self-healing modifications, make it ideal for future tissue engineering applications. In this review, we first demonstrate the current understanding of the structures and mechanical properties of SF and the various functionalizations of SF matrices through chemical and physical manipulations. Then the diverse applications of SF architectures and scaffolds for different regenerative medicine will be discussed in detail, including their current applications in bone, eye, nerve, skin, tendon, ligament, and cartilage regeneration.
New insights into metabolic signaling and cell survival: the role of beta-O-linkage of N-acetylglucosamine.

PubMed

Ngoh, Gladys A; Jones, Steven P

2008-12-01

The involvement of glucose in fundamental metabolic pathways represents a core element of biology. Late in the 20th century, a unique glucose-derived signal was discovered, which appeared to be involved in a variety of cellular processes, including mitosis, transcription, insulin signaling, stress responses, and potentially, Alzheimer's disease, and diabetes. By definition, this glucose-fed signaling system was a post-translational modification to proteins. However, unlike classical cotranslational N-glycosylation occurring in the endoplasmic reticulum and Golgi apparatus, this process occurs elsewhere throughout the cell in a highly dynamic fashion, similar to the quintessential post-translational modification, phosphorylation. This more recently described post-translational modification, the beta-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to nucleocytoplasmic proteins, represents an under-investigated area of biology. This signaling system operates in all of the tissues examined and seems to have persisted throughout all multicellular eukaryotes. Thus, it comes with little surprise that O-GlcNAc signaling is an integral system and viable target for biomedical investigation. This system may be a boundless source for insight into a variety of diseases and yield numerous opportunities for drug design. This Perspective will address recent insights into O-GlcNAc signaling in the cardiovascular system as a paradigm for its involvement in other biological systems.
Oxidative precipitation of ruthenium oxide for supercapacitors: Enhanced capacitive performances by adding cetyltrimethylammonium bromide

NASA Astrophysics Data System (ADS)

Chen, I.-Li; Wei, Yu-Chen; Chen, Tsan-Yao; Hu, Chi-Chang; Lin, Tsang-Lang

2014-12-01

Thermally stable and porous RuO2·xH2O with superior rate-retention capability is prepared by the H2O2-oxidative precipitation method modified with the cetyltrimethylammonium bromide (CTAB) template. The specific capacitance and rate-retention of RuO2·xH2O are considerably enhanced by the CTAB modification and annealing at 200 °C because of extremely localized crystallization and pore opening of slightly sintered RuO2·xH2O nanoparticles trapped with CTAB. This unique structure, confirmed by the X-ray absorption spectroscopic (XAS), Raman spectroscopic, and transmission electron microscopic (TEM) analyses, favors the utilization of RuO2·xH2O nanocrystals and increases the electrolyte accessibility in comparing with RuO2·xH2O without CTAB modification. The preferential orientation growth along the {101} facet of RuO2 nanocrystals in some local regions is acquired by the CTAB modification and annealing in air at temperatures ≥350 °C. Such preferential orientation growth of RuO2 crystallites is attributable to the oxidation of trapped surfactants during the thermal annealing process, which adsorb on the high surface energy planes of RuO2.
PEPlife: A Repository of the Half-life of Peptides

NASA Astrophysics Data System (ADS)

Mathur, Deepika; Prakash, Satya; Anand, Priya; Kaur, Harpreet; Agrawal, Piyush; Mehta, Ayesha; Kumar, Rajesh; Singh, Sandeep; Raghava, Gajendra P. S.

2016-11-01

Short half-life is one of the key challenges in the field of therapeutic peptides. Various studies have reported enhancement in the stability of peptides using methods like chemical modifications, D-amino acid substitution, cyclization, replacement of labile aminos acids, etc. In order to study this scattered data, there is a pressing need for a repository dedicated to the half-life of peptides. To fill this lacuna, we have developed PEPlife (http://crdd.osdd.net/raghava/peplife), a manually curated resource of experimentally determined half-life of peptides. PEPlife contains 2229 entries covering 1193 unique peptides. Each entry provides detailed information of the peptide, like its name, sequence, half-life, modifications, the experimental assay for determining half-life, biological nature and activity of the peptide. We also maintain SMILES and structures of peptides. We have incorporated web-based modules to offer user-friendly data searching and browsing in the database. PEPlife integrates numerous tools to perform various types of analysis such as BLAST, Smith-Waterman algorithm, GGSEARCH, Jalview and MUSTANG. PEPlife would augment the understanding of different factors that affect the half-life of peptides like modifications, sequence, length, route of delivery of the peptide, etc. We anticipate that PEPlife will be useful for the researchers working in the area of peptide-based therapeutics.
Research at NASA's NFAC wind tunnels

NASA Technical Reports Server (NTRS)

Edenborough, H. Kipling

1990-01-01

The National Full-Scale Aerodynamics Complex (NFAC) is a unique combination of wind tunnels that allow the testing of aerodynamic and dynamic models at full or large scale. It can even accommodate actual aircraft with their engines running. Maintaining full-scale Reynolds numbers and testing with surface irregularities, protuberances, and control surface gaps that either closely match the full-scale or indeed are those of the full-scale aircraft help produce test data that accurately predict what can be expected from future flight investigations. This complex has grown from the venerable 40- by 80-ft wind tunnel that has served for over 40 years helping researchers obtain data to better understand the aerodynamics of a wide range of aircraft from helicopters to the space shuttle. A recent modification to the tunnel expanded its maximum speed capabilities, added a new 80- by 120-ft test section and provided extensive acoustic treatment. The modification is certain to make the NFAC an even more useful facility for NASA's ongoing research activities. A brief background is presented on the original facility and the kind of testing that has been accomplished using it through the years. A summary of the modification project and the measured capabilities of the two test sections is followed by a review of recent testing activities and of research projected for the future.
Mixed ion/electron-conductive protective soft nanomatter-based conformal surface modification of lithium-ion battery cathode materials

NASA Astrophysics Data System (ADS)

Park, Jang-Hoon; Kim, Ju-Myung; Lee, Chang Kee; Lee, Sang-Young

2014-10-01

Understanding and control of interfacial phenomena between electrode material and liquid electrolytes are of major scientific importance for boosting development of high-performance lithium ion batteries with reliable electrochemical/safety attributes. Here, as an innovative surface engineering approach to address the interfacial issues, a new concept of mixed ion/electron-conductive soft nanomatter-based conformal surface modification of the cathode material is presented. The soft nanomatter is comprised of an electron conductive carbonaceous (C) substance embedded in an ion conductive polyimide (PI) nanothin compliant film. In addition to its structural uniqueness, the newly proposed surface modification benefits from a simple fabrication process. The PI/carbon soft nanomatter is directly synthesized on LiCoO2 surface via one-pot thermal treatment of polyamic acid (=PI precursor) and sucrose (=carbon source) mixture, where the LiCoO2 powders are chosen as a model system to explore the feasibility of this surface engineering strategy. The resulting PI/carbon coating layer facilitates electronic conduction and also suppresses unwanted side reactions arising from the cathode material-liquid electrolyte interface. These synergistic coating effects of the multifunctional PI/carbon soft nanomatter significantly improve high-voltage cell performance and also mitigate interfacial exothermic reaction between cathode material and liquid electrolyte.
Improving efficacy of cancer immunotherapy by genetic modification of natural killer cells.

PubMed

Burga, Rachel A; Nguyen, Tuongvan; Zulovich, Jane; Madonna, Sarah; Ylisastigui, Loyda; Fernandes, Rohan; Yvon, Eric

2016-11-01

Natural killer (NK) cells are members of the innate immune system that recognize target cells via activating and inhibitory signals received through cell receptors. Derived from the lymphoid lineage, NK cells are able to produce cytokines and exert a cytotoxic effect on viral infected and malignant cells. It is their unique ability to lyse target cells rapidly and without prior education that renders NK cells a promising effector cell for adoptive cell therapy. However, both viruses and tumors employ evasion strategies to avoid attack by NK cells, which represent biological challenges that need to be harnessed to fully exploit the cytolytic potential of NK cells. Using genetic modification, the function of NK cells can be enhanced to improve their homing, cytolytic activity, in vivo persistence and safety. Examples include gene modification to express chemokine, high-affinity Fc receptor and chimeric antigen receptors, suicide genes and the forced expression of cytokines such as interleukin (IL)-2 and IL-15. Preclinical studies have clearly demonstrated that such approaches are effective in improving NK-cell function, homing and safety. In this review, we summarize the recent advances in the genetic manipulations of NK cells and their application for cellular immunotherapeutic strategies. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Combinatorial modification of human histone H4 quantitated by two-dimensional liquid chromatography coupled with top down mass spectrometry.

PubMed

Pesavento, James J; Bullock, Courtney R; LeDuc, Richard D; Mizzen, Craig A; Kelleher, Neil L

2008-05-30

Quantitative proteomics has focused heavily on correlating protein abundances, ratios, and dynamics by developing methods that are protein expression-centric (e.g. isotope coded affinity tag, isobaric tag for relative and absolute quantification, etc.). These methods effectively detect changes in protein abundance but fail to provide a comprehensive perspective of the diversity of proteins such as histones, which are regulated by post-translational modifications. Here, we report the characterization of modified forms of HeLa cell histone H4 with a dynamic range >10(4) using a strictly Top Down mass spectrometric approach coupled with two dimensions of liquid chromatography. This enhanced dynamic range enabled the precise characterization and quantitation of 42 forms uniquely modified by combinations of methylation and acetylation, including those with trimethylated Lys-20, monomethylated Arg-3, and the novel dimethylated Arg-3 (each <1% of all H4 forms). Quantitative analyses revealed distinct trends in acetylation site occupancy depending on Lys-20 methylation state. Because both modifications are dynamically regulated through the cell cycle, we simultaneously investigated acetylation and methylation kinetics through three cell cycle phases and used these data to statistically assess the robustness of our quantitative analysis. This work represents the most comprehensive analysis of histone H4 forms present in human cells reported to date.
Metastable Atom-Activated Dissociation Mass Spectrometry of Phosphorylated and Sulfonated Peptides in Negative Ion Mode

NASA Astrophysics Data System (ADS)

Cook, Shannon L.; Jackson, Glen P.

2011-06-01

The dissociation behavior of phosphorylated and sulfonated peptide anions was explored using metastable atom-activated dissociation mass spectrometry (MAD-MS) and collision-induced dissociation (CID). A beam of high kinetic energy helium (He) metastable atoms was exposed to isolated phosphorylated and sulfonated peptides in the 3- and 2- charge states. Unlike CID, where phosphate losses are dominant, the major dissociation channels observed using MAD were Cα - C peptide backbone cleavages and neutral losses of CO2, H2O, and [CO2 + H2O] from the charge reduced (oxidized) product ion, consistent with an electron detachment dissociation (EDD) mechanism such as Penning ionization. Regardless of charge state or modification, MAD provides ample backbone cleavages with little modification loss, which allows for unambiguous PTM site determination. The relative abundance of certain fragment ions in MAD is also demonstrated to be somewhat sensitive to the number and location of deprotonation sites, with backbone cleavage somewhat favored adjacent to deprotonated sites like aspartic acid residues. MAD provides a complementary dissociation technique to CID, ECD, ETD, and EDD for peptide sequencing and modification identification. MAD offers the unique ability to analyze highly acidic peptides that contain few to no basic amino acids in either negative or positive ion mode.
Focused ion beam source method and apparatus

DOEpatents

Pellin, Michael J.; Lykke, Keith R.; Lill, Thorsten B.

2000-01-01

A focused ion beam having a cross section of submicron diameter, a high ion current, and a narrow energy range is generated from a target comprised of particle source material by laser ablation. The method involves directing a laser beam having a cross section of critical diameter onto the target, producing a cloud of laser ablated particles having unique characteristics, and extracting and focusing a charged particle beam from the laser ablated cloud. The method is especially suited for producing focused ion beams for semiconductor device analysis and modification.
Modelling of the mechanical behavior of a polyurethane finger interphalangeal joint endoprosthesis after surface modification by ion implantation

NASA Astrophysics Data System (ADS)

Beliaev, A.; Svistkov, A.; Iziumov, R.; Osorgina, I.; Kondyurin, A.; Bilek, M.; McKenzie, D.

2016-04-01

Production of biocompatible implants made of polyurethane treated with plasma is very perspective. During plasma treatment the surface of polyurethane acquires unique physic-chemical properties. However such treatment may change the mechanical properties of polyurethane which may adversely affect the deformation behaviour of the real implant. Therefore careful study of the mechanical properties of the plasma-modified polyurethane is needed. In this paper, experimental observations of the elastic characteristics of plasma treated polyurethane and modelling of the deformation behaviour of polyurethane bio-implants are reported.
Emissions control for ground power gas turbines

NASA Technical Reports Server (NTRS)

Rudney, R. A.; Priem, R. J.; Juhasz, A. J.; Anderson, D. N.; Mroz, T. S.; Mularz, E. J.

1977-01-01

The similarities and differences of emissions reduction technology for aircraft and ground power gas turbines is described. The capability of this technology to reduce ground power emissions to meet existing and proposed emissions standards is presented and discussed. Those areas where the developing aircraft gas turbine technology may have direct application to ground power and those areas where the needed technology may be unique to the ground power mission are pointed out. Emissions reduction technology varying from simple combustor modifications to the use of advanced combustor concepts, such as catalysis, is described and discussed.

Design, building and test of one prototype and four final position sensor assemblies: Hall effect position sensors

NASA Technical Reports Server (NTRS)

1976-01-01

This report covers the development of a three channel Hall effect position sensing system for the commutation of a three phase dc torquer motor. The effort consisted of the evaluation, modification and re-packaging of a commercial position sensor and the design of a target configuration unique to this application. The resulting design meets the contract requirements and, furthermore, the test results indicate not only the practicality and versatility of the design, but also that there may be higher limits of resolution and accuracy achievable.
A Programmable DNA Double-Write Material: Synergy of Photolithography and Self-Assembly Nanofabrication.

PubMed

Song, Youngjun; Takahashi, Tsukasa; Kim, Sejung; Heaney, Yvonne C; Warner, John; Chen, Shaochen; Heller, Michael J

2017-01-11

We demonstrate a DNA double-write process that uses UV to pattern a uniquely designed DNA write material, which produces two distinct binding identities for hybridizing two different complementary DNA sequences. The process requires no modification to the DNA by chemical reagents and allows programmed DNA self-assembly and further UV patterning in the UV exposed and nonexposed areas. Multilayered DNA patterning with hybridization of fluorescently labeled complementary DNA sequences, biotin probe/fluorescent streptavidin complexes, and DNA patterns with 500 nm line widths were all demonstrated.
Unique Structural Modifications Are Present in the Lipopolysaccharide from Colistin-Resistant Strains of Acinetobacter baumannii

DTIC Science & Technology

2013-10-01

13). Freeze-dried bacteria were resuspended in endotoxin -free water at a concentration of 10 mg/ml. A 12.5-ml volume of 90% phenol was added, and the...temperature for 30 min. The aqueous phase was collected, and an equal volume of endotoxin -free water was added to the organic phase. The sample was...The resultant pel- let was resuspended at a concentration of 10 mg/ml in endotoxin -free water, treated with DNase (Sigma, St. Louis, MO) at 100 g/ml
Television observations of Mercury by Mariner 10

NASA Technical Reports Server (NTRS)

Murray, B. C.; Belton, M. J. S.; Danielson, E. G.; Davies, M. E.; Gault, D. E.; Hapke, B.; Oleary, B.; Strom, R. G.; Suomi, V.; Trask, N.

1977-01-01

The morphology and optical properties of the surface of Mercury resemble those of the Moon in remarkable detail, recording a very similar sequence of events; chemical and mineralogical similarity of the outer layers is implied. Mercury is probably a differentiated planet with an iron-rich core. Differentiation is inferred to have occurred very early. No evidence of atmospheric modification of any landform is found. Large-scale scarps and ridges unlike lunar or Martian features may reflect a unique period of planetary compression near the end of heavy bombardment, perhaps related to contraction of the core.
Television observations of Mercury by Mariner 10

NASA Technical Reports Server (NTRS)

Murray, B. C.; Belton, M. J. S.; Danielson, G. E.; Davies, M. E.; Gault, D. E.; Hapke, B.; Oleary, B.; Strom, R. G.; Suomi, V.; Trask, N.

1974-01-01

The morphology and optical properties of the surface of Mercury resemble that of the moon in remarkable detail, recording a very similar sequence of events; chemical and mineralogical similarity of the outer layers is implied. Mercury is probably a differentiated planet with an iron-rich core. Differentiation is inferred to have occurred very early. No evidence of atmospheric modification of any landform is found. Large-scale scarps and ridges unlike lunar or Martian features may reflect a unique period of planetary compression near the end of heavy bombardment, perhaps related to contraction of the core.
Plasma surface modification of rigid contact lenses decreases bacterial adhesion.

PubMed

Wang, Yingming; Qian, Xuefeng; Zhang, Xiaofeng; Xia, Wei; Zhong, Lei; Sun, Zhengtai; Xia, Jing

2013-11-01

Contact lens safety is an important topic in clinical studies. Corneal infections usually occur because of the use of bacteria-carrying contact lenses. The current study investigated the impact of plasma surface modification on bacterial adherence to rigid contact lenses made of fluorosilicone acrylate materials. Boston XO and XO2 contact lenses were modified using plasma technology (XO-P and XO2-P groups). Untreated lenses were used as controls. Plasma-treated and control lenses were incubated in solutions containing Staphylococcus aureus or Pseudomonas aeruginosa. MTT colorimetry, colony-forming unit counting method, and scanning electron microscopy were used to measure bacterial adhesion. MTT colorimetry measurements showed that the optical density (OD) values of XO-P and XO2-P were significantly lower than those of XO and XO2, respectively, after incubation with S. aureus (P < 0.01). The OD value of XO-P was also much lower than that of XO after incubation with P. aeruginosa (P < 0.01). Colony-forming unit counting revealed that a significantly lower number of bacterial colonies attached to the XO-P versus XO lenses and to the XO2-P versus XO2 lenses incubated with S. aureus (P < 0.01). Fewer bacterial colonies attached to the XO-P versus XO lenses incubated with P. aeruginosa (P < 0.01). Further, scanning electron microscopy suggested different bacterial adhesion morphology on plasma-treated versus control lenses. Plasma surface modification can significantly decrease bacterial adhesion to fluorosilicone acrylate contact lenses. This study provides important evidence of a unique benefit of plasma technology in contact lens surface modification.
Porous NiTi for bone implants: a review.

PubMed

Bansiddhi, A; Sargeant, T D; Stupp, S I; Dunand, D C

2008-07-01

NiTi foams are unique among biocompatible porous metals because of their high recovery strain (due to the shape-memory or superelastic effects) and their low stiffness facilitating integration with bone structures. To optimize NiTi foams for bone implant applications, two key areas are under active study: synthesis of foams with optimal architectures, microstructure and mechanical properties; and tailoring of biological interactions through modifications of pore surfaces. This article reviews recent research on NiTi foams for bone replacement, focusing on three specific topics: (i) surface modifications designed to create bio-inert porous NiTi surfaces with low Ni release and corrosion, as well as bioactive surfaces to enhance and accelerate biological activity; (ii) in vitro and in vivo biocompatibility studies to confirm the long-term safety of porous NiTi implants; and (iii) biological evaluations for specific applications, such as in intervertebral fusion devices and bone tissue scaffolds. Possible future directions for bio-performance and processing studies are discussed that could lead to optimized porous NiTi implants.
Porous NiTi for bone implants: A review

PubMed Central

Bansiddhi, A.; Sargeant, T.D.; Stupp, S.I.; Dunand, D.C.

2011-01-01

NiTi foams are unique among biocompatible porous metals because of their high recovery strain (due to the shape-memory or superelastic effects) and their low stiffness facilitating integration with bone structures. To optimize NiTi foams for bone implant applications, two key areas are under active study: synthesis of foams with optimal architectures, microstructure and mechanical properties; and tailoring of biological interactions through modifications of pore surfaces. This article reviews recent research on NiTi foams for bone replacement, focusing on three specific topics: (i) surface modifications designed to create bio-inert porous NiTi surfaces with low Ni release and corrosion, as well as bioactive surfaces to enhance and accelerate biological activity; (ii) In vitro and in vivo biocompatibility studies to confirm the long-term safety of porous NiTi implants; and (iii) biological evaluations for specific applications, such as in intervertebral fusion devices and bone tissue scaffolds. Possible future directions for bio-performance and processing studies are discussed that could lead to optimized porous NiTi implants. PMID:18348912
Design and Fabrication of the Lithium Tokamak Experiment

NASA Astrophysics Data System (ADS)

Kozub, Thomas; Majeski, Richard; Kaita, Robert; Priniski, Craig; Zakharov, Leonid

2006-10-01

The design objective of the lithium tokamak experiment (LTX) is to investigate the equilibrium and stability of tokamak discharges with near-zero recycling. The construction of LTX incorporates the conversion of the existing current drive experiment (CDX) vessel into one with a nearly complete plasma facing surface of liquid lithium This paper will describe the design, fabrication, and installation activities required to convert CDX into LTX. The most significant new feature is the addition of a plasma facing liner on a shell that will be operated at 300 C to 400 C and covered with an evaporated layer of liquid lithium. The shell has been fabricated in-house from explosively bonded stainless steel on copper to a rather unique geometry to match the outer flux surface. Other significant device modifications include the construction of a new ohmic heating power system, rebuilding of the vacuum vessel, new lithium evaporators, additional diagnostics, modifications to the poloidal field coil geometry and their associated power supplies. Details on the progress of this conversion will be reported.
SH2 Domain Histochemistry.

PubMed

Buhs, Sophia; Nollau, Peter

2017-01-01

Among posttranslational modifications, the phosphorylation of tyrosine residues is a key modification in cell signaling. Because of its biological importance, characterization of the cellular state of tyrosine phosphorylation is of great interest. Based on the unique properties of endogenously expressed SH2 domains recognizing tyrosine phosphorylated signaling proteins with high specificity we have developed an alternative approach, coined SH2 profiling, enabling us to decipher complex patterns of tyrosine phosphorylation in various normal and cancerous tissues. So far, SH2 profiling has largely been applied for the analysis of protein extracts with the limitation that information on spatial distribution and intensity of tyrosine phosphorylation within a tissue is lost. Here, we describe a novel SH2 domain based strategy for differential characterization of the state of tyrosine phosphorylation in formaldehyde-fixed and paraffin-embedded tissues. This approach demonstrates that SH2 domains may serve as very valuable tools for the analysis of the differential state of tyrosine phosphorylation in primary tissues fixed and processed under conditions frequently applied by routine pathology laboratories.
tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

NASA Astrophysics Data System (ADS)

Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

2016-11-01

Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria--which models tuberculous granulomas--are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria.
Modification of the internal surface of photonic crystal fibers with Ag and Au nanoparticles for application as sensor elements

NASA Astrophysics Data System (ADS)

Pidenko, Pavel S.; Borzov, Victor M.; Savenko, Olga A.; Skaptsov, Alexander A.; Skibina, Yulia S.; Goryacheva, Irina Yu.; Rusanova, Tatiana Yu.

2017-03-01

Photonic crystal fibers (PCFs) are one of the most promising materials for biosensors construction due to their unique optical properties. The modification of PCF by noble metal nanoparticles (NPs) provides the SPR and SERS signal detection where as the application amino group-containing compounds allows efficient binding of biomolecules. In this work the internal surface of glass hollow core photonic crystal fibers (HC-PCFs) has been modified Ag and Au nanoparticles using three different approaches. PCFs were treated by: 1) mixture of NPs and precursors for silanization (tetraethoxysilane (TEOS) and (3-aminopropyl)triethoxysilane (APTES)); 2) alternately deposition of polyelectrolytes and NPs, 3) mixture of chitosan with NPs. The shift of local maxima in the HC-PCF transmission spectrum has been selected as a signal for estimating the amount of NPs on the HC-PCF inner surface. The most efficient techniques were the chitosan application for Ag NPs and silanization for Au NPs. The obtaining PCFs could be useful for creating biosensitive elements.
Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design

NASA Astrophysics Data System (ADS)

Shiraki, Tomohiro; Shiraishi, Tomonari; Juhász, Gergely; Nakashima, Naotoshi

2016-06-01

Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E112*) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering-based applications including photonic devices and (bio)imaging/sensing.
Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids.

PubMed

Morales, Jorge; Hashimoto, Muneaki; Williams, Tom A; Hirawake-Mogi, Hiroko; Makiuchi, Takashi; Tsubouchi, Akiko; Kaga, Naoko; Taka, Hikari; Fujimura, Tsutomu; Koike, Masato; Mita, Toshihiro; Bringaud, Frédéric; Concepción, Juan L; Hashimoto, Tetsuo; Embley, T Martin; Nara, Takeshi

2016-05-11

The remodelling of organelle function is increasingly appreciated as a central driver of eukaryotic biodiversity and evolution. Kinetoplastids including Trypanosoma and Leishmania have evolved specialized peroxisomes, called glycosomes. Glycosomes uniquely contain a glycolytic pathway as well as other enzymes, which underpin the physiological flexibility of these major human pathogens. The sister group of kinetoplastids are the diplonemids, which are among the most abundant eukaryotes in marine plankton. Here we demonstrate the compartmentalization of gluconeogenesis, or glycolysis in reverse, in the peroxisomes of the free-living marine diplonemid, Diplonema papillatum Our results suggest that peroxisome modification was already under way in the common ancestor of kinetoplastids and diplonemids, and raise the possibility that the central importance of gluconeogenesis to carbon metabolism in the heterotrophic free-living ancestor may have been an important selective driver. Our data indicate that peroxisome modification is not confined to the kinetoplastid lineage, but has also been a factor in the success of their free-living euglenozoan relatives. © 2016 The Author(s).
A Balanced Protocol for Return to School for Children and Youth Following Concussive Injury.

PubMed

DeMatteo, Carol; Stazyk, Kathy; Giglia, Lucy; Mahoney, William; Singh, Sheila K; Hollenberg, Robert; Harper, Jessica A; Missiuna, Cheryl; Law, Mary; McCauley, Dayle; Randall, Sarah

2015-07-01

Few protocols exist for returning children/youth to school after concussion. Childhood concussion can significantly affect school performance, which is vital to social development, academic learning, and preparation for future roles. The goal of this knowledge translation research was to develop evidence based materials to inform physicians about pediatric concussion. The Return to School (RTS) concussion protocol was developed following the National Institute for Health and Care Excellence procedures. Based on a scoping review, and stakeholder opinions, an RTS protocol was developed for children/youth. This unique protocol focuses on school adaptation in 4 main areas: (a) timetable/attendance, (b) curriculum, (c) environmental modifications, and (d) activity modifications. A balance of cognitive rest and timely return to school need to be considered for returning any student to school after a concussion. Implementation of these new recommendations may be an important tool in prevention of prolonged absence from school and academic failure while supporting brain recovery. © The Author(s) 2015.
Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

NASA Astrophysics Data System (ADS)

Lovell, Kimberly M.; Prevatt-Smith, Katherine M.; Lozama, Anthony; Prisinzano, Thomas E.

Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a basic nitrogen. There have been several total synthesis approaches to salvinorin A, and these will be detailed within this chapter. Additionally, research efforts have concentrated on structure modification of the salvinorin A scaffold through semi-synthetic methods. Most modifications have focused on the manipulation of the acetate at C-2 and the furan ring. However, chemistry has also been developed to generate analogs at the C-1 ketone, the C-4 methyl ester, and the C-17 lactone. The synthetic methodologies developed for the salvinorin A scaffold will be described, as well as specific analogs with interesting biological activities.
Modification of the semitransparent Prunus serrula bark film: Making rubber out of bark

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, X.; Zaremba, C.; Stucky, G.D.

1998-11-01

The authors report an extensive structural and mechanical characterization of the semitransparent bark of Prunus serrula. Variations in the properties were observed. Mechanical properties along the fiber axis of these films are strongly related to the cell dimensions. Several trends can be seen with increasing cell length: tensile strength and Young`s modulus increase; ductility decreases. Perpendicular to the fiber axis, similar radial dimensions of the bark cells contributes to similar mechanical properties. Plasticization not only shrinks the dimension of the bulk films along the tangential axis, which is unique, but also dramatically changes the mechanical properties. The authors have shown,more » for the first time, that the mechanical properties of the Prunus serrula bark can be effectively tailored with different plasticization and modification agents. The plastic bark can be successfully converted to rubberlike material either temporally or permanently, or it can be strengthened by tensile deformation of the plasticized bark.« less
Heavy flavour production in proton-lead and lead-lead collisions with LHCb

NASA Astrophysics Data System (ADS)

Winn, Michael

2017-11-01

The LHCb experiment offers the unique opportunity to study heavy-ion interactions in the forward region (2 < η < 5), in a kinematic domain complementary to the other 3 large experiments at the LHC. The detector has excellent capabilities for reconstructing quarkonia and open charm states, including baryons, down to zero pT. It can separate the prompt and displaced charm components. In pPb collisions, both forward and backward rapidities are covered thanks to the possibility of beam reversal. Results include measurements of the nuclear modification factor and forward-backward ratio for charmonium, open charm and bottomonium states. These quantities are sensitive probes for nuclear effects in heavy flavour production. Perspectives are given with the large accumulated luminosity during the 2016 pPb run at the LHC. In 2015, LHCb participated successfully for the first time in the PbPb data-taking. The status of the forward prompt J/ψ nuclear modification factor measurement in lead-lead collisions is discussed.
The unique experience of home for parents and carers of children with disabilities.

PubMed

Aplin, Tammy; Thornton, Heloise; Gustafsson, Louise

2017-01-24

The aim of this paper was to investigate the experience of home for parents and carers of children with disabilities in Australia. Data for this qualitative study were gathered using semi-structured interviews with four families living in their own homes. An inductive thematic analysis revealed two main themes. The first was titled 'Aspects making everyday life easier' explored the aspects of the home environment that facilitated home life for the child, including access to transport, services, family and home modifications. The second theme 'Decisions and efforts to create opportunities for the child' emphasized the efforts made by parents and carers to promote their child's independence and participation including a strong consideration for their children's future needs. The study indicated that the location of home, appropriate home modifications and planning for the future defined the experience of home for parents and carers. These findings identify some important considerations for occupational therapists when providing services in the homes of families with children who have a disability.
tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence

PubMed Central

Chionh, Yok Hian; McBee, Megan; Babu, I. Ramesh; Hia, Fabian; Lin, Wenwei; Zhao, Wei; Cao, Jianshu; Dziergowska, Agnieszka; Malkiewicz, Andrzej; Begley, Thomas J.; Alonso, Sylvie; Dedon, Peter C.

2016-01-01

Microbial pathogens adapt to the stress of infection by regulating transcription, translation and protein modification. We report that changes in gene expression in hypoxia-induced non-replicating persistence in mycobacteria—which models tuberculous granulomas—are partly determined by a mechanism of tRNA reprogramming and codon-biased translation. Mycobacterium bovis BCG responded to each stage of hypoxia and aerobic resuscitation by uniquely reprogramming 40 modified ribonucleosides in tRNA, which correlate with selective translation of mRNAs from families of codon-biased persistence genes. For example, early hypoxia increases wobble cmo5U in tRNAThr(UGU), which parallels translation of transcripts enriched in its cognate codon, ACG, including the DosR master regulator of hypoxic bacteriostasis. Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria. PMID:27834374

Micro-masonry for 3D additive micromanufacturing.

PubMed

Keum, Hohyun; Kim, Seok

2014-08-01

Transfer printing is a method to transfer solid micro/nanoscale materials (herein called 'inks') from a substrate where they are generated to a different substrate by utilizing elastomeric stamps. Transfer printing enables the integration of heterogeneous materials to fabricate unexampled structures or functional systems that are found in recent advanced devices such as flexible and stretchable solar cells and LED arrays. While transfer printing exhibits unique features in material assembly capability, the use of adhesive layers or the surface modification such as deposition of self-assembled monolayer (SAM) on substrates for enhancing printing processes hinders its wide adaptation in microassembly of microelectromechanical system (MEMS) structures and devices. To overcome this shortcoming, we developed an advanced mode of transfer printing which deterministically assembles individual microscale objects solely through controlling surface contact area without any surface alteration. The absence of an adhesive layer or other modification and the subsequent material bonding processes ensure not only mechanical bonding, but also thermal and electrical connection between assembled materials, which further opens various applications in adaptation in building unusual MEMS devices.
ARIES: NASA Langley's Airborne Research Facility

NASA Technical Reports Server (NTRS)

Wusk, Michael S.

2002-01-01

In 1994, the NASA Langley Research Center (LaRC) acquired a B-757-200 aircraft to replace the aging B-737 Transport Systems Research Vehicle (TSRV). The TSRV was a modified B-737-100, which served as a trailblazer in the development of glass cockpit technologies and other innovative aeronautical concepts. The mission for the B-757 is to continue the three-decade tradition of civil transport technology research begun by the TSRV. Since its arrival at Langley, this standard 757 aircraft has undergone extensive modifications to transform it into an aeronautical research "flying laboratory". With this transformation, the aircraft, which has been designated Airborne Research Integrated Experiments System (ARIES), has become a unique national asset which will continue to benefit the U.S. aviation industry and commercial airline customers for many generations to come. This paper will discuss the evolution of the modifications, detail the current capabilities of the research systems, and provide an overview of the research contributions already achieved.
Genomic analysis of organismal complexity in the multicellular green alga Volvox carteri

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prochnik, Simon E.; Umen, James; Nedelcu, Aurora

2010-07-01

Analysis of the Volvox carteri genome reveals that this green alga's increased organismal complexity and multicellularity are associated with modifications in protein families shared with its unicellular ancestor, and not with large-scale innovations in protein coding capacity. The multicellular green alga Volvox carteri and its morphologically diverse close relatives (the volvocine algae) are uniquely suited for investigating the evolution of multicellularity and development. We sequenced the 138 Mb genome of V. carteri and compared its {approx}14,500 predicted proteins to those of its unicellular relative, Chlamydomonas reinhardtii. Despite fundamental differences in organismal complexity and life history, the two species have similarmore » protein-coding potentials, and few species-specific protein-coding gene predictions. Interestingly, volvocine algal-specific proteins are enriched in Volvox, including those associated with an expanded and highly compartmentalized extracellular matrix. Our analysis shows that increases in organismal complexity can be associated with modifications of lineage-specific proteins rather than large-scale invention of protein-coding capacity.« less
Java web tools for PCR, in silico PCR, and oligonucleotide assembly and analysis.

PubMed

Kalendar, Ruslan; Lee, David; Schulman, Alan H

2011-08-01

The polymerase chain reaction is fundamental to molecular biology and is the most important practical molecular technique for the research laboratory. We have developed and tested efficient tools for PCR primer and probe design, which also predict oligonucleotide properties based on experimental studies of PCR efficiency. The tools provide comprehensive facilities for designing primers for most PCR applications and their combinations, including standard, multiplex, long-distance, inverse, real-time, unique, group-specific, bisulphite modification assays, Overlap-Extension PCR Multi-Fragment Assembly, as well as a programme to design oligonucleotide sets for long sequence assembly by ligase chain reaction. The in silico PCR primer or probe search includes comprehensive analyses of individual primers and primer pairs. It calculates the melting temperature for standard and degenerate oligonucleotides including LNA and other modifications, provides analyses for a set of primers with prediction of oligonucleotide properties, dimer and G-quadruplex detection, linguistic complexity, and provides a dilution and resuspension calculator. Copyright © 2011 Elsevier Inc. All rights reserved.
Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

PubMed Central

Doolittle-Hall, Janet M.; Cunningham Glasspoole, Danielle L.; Seaman, William T.; Webster-Cyriaque, Jennifer

2015-01-01

Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures. PMID:26569308
Supercritical fluid technology: a promising approach in pharmaceutical research.

PubMed

Girotra, Priti; Singh, Shailendra Kumar; Nagpal, Kalpana

2013-02-01

Supercritical fluids possess the unique properties of behaving like liquids and gases, above their critical point. Supercritical fluid technology has recently emerged as a green and novel technique for various processes such as solubility enhancement of poorly soluble drugs, plasticization of polymers, surface modification, nanosizing and nanocrystal modification, and chromatographic extraction. Research interest in this area has been fuelled because of the numerous advantages that the technology offers over the conventional methods. This work aims to review the merits, demerits, and various processes such as rapid expansion of supercritical solutions (RESS), particles from gas saturated solutions (PGSS), gas antisolvent process (GAS), supercritical antisolvent process (SAS) and polymerization induced phase separation (PIPS), that have enabled this technology to considerably raise the interest of researchers over the past two decades. An insight has been given into the numerous applications of this technology in pharmaceutical industry and the future challenges which must be appropriately dealt with to make it effective on a commercial scale.
Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development.

PubMed

Ikegami, Kohta; Ohgane, Jun; Tanaka, Satoshi; Yagi, Shintaro; Shiota, Kunio

2009-01-01

Genes constitute only a small proportion of the mammalian genome, the majority of which is composed of non-genic repetitive elements including interspersed repeats and satellites. A unique feature of the mammalian genome is that there are numerous tissue-dependent, differentially methylated regions (T-DMRs) in the non-repetitive sequences, which include genes and their regulatory elements. The epigenetic status of T-DMRs varies from that of repetitive elements and constitutes the DNA methylation profile genome-wide. Since the DNA methylation profile is specific to each cell and tissue type, much like a fingerprint, it can be used as a means of identification. The formation of DNA methylation profiles is the basis for cell differentiation and development in mammals. The epigenetic status of each T-DMR is regulated by the interplay between DNA methyltransferases, histone modification enzymes, histone subtypes, non-histone nuclear proteins and non-coding RNAs. In this review, we will discuss how these epigenetic factors cooperate to establish cell- and tissue-specific DNA methylation profiles.
Yeast synthetic biology for the production of recombinant therapeutic proteins.

PubMed

Kim, Hyunah; Yoo, Su Jin; Kang, Hyun Ah

2015-02-01

The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases. Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins. Yeasts are capable of robust growth on simple media, readily accommodate genetic modifications, and incorporate typical eukaryotic post-translational modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has been used as a major host for the production of biopharmaceuticals; however, several nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica have gained increasing attention as alternative hosts for the industrial production of recombinant proteins. In this review, we address the established and emerging genetic tools and host strains suitable for recombinant protein production in various yeast expression systems, particularly focusing on current efforts toward synthetic biology approaches in developing yeast cell factories for the production of therapeutic recombinant proteins. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.
Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes

NASA Astrophysics Data System (ADS)

Qie, Yaqing; Yuan, Hengfeng; von Roemeling, Christina A.; Chen, Yuanxin; Liu, Xiujie; Shih, Kevin D.; Knight, Joshua A.; Tun, Han W.; Wharen, Robert E.; Jiang, Wen; Kim, Betty Y. S.

2016-05-01

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.
PEG-stabilized core-shell surface-imprinted nanoparticles.

PubMed

Moczko, Ewa; Guerreiro, Antonio; Piletska, Elena; Piletsky, Sergey

2013-08-06

Here we present a simple technique to produce target-specific molecularly imprinted polymeric nanoparticles (MIP NPs) and their surface modification in order to prevent the aggregation process that is ever-present in most nanomaterial suspensions/dispersions. Specifically, we studied the influence of surface modification of MIP NPs with polymerizable poly(ethylene glycol) on their degree of stability in water, in phosphate buffer, and in the presence of serum proteins. Grafting a polymer shell on the surface of nanoparticles decreases the surface energy, enhances the polarity, and as a result improves the dispersibility, storage, and colloidal stability as compared to those of core (unmodified) particles. Because of the unique solid-phase approach used for synthesis, the binding sites of MIP NPs are protected during grafting, and the recognition properties of nanoparticles are not affected. These results are significant for developing nanomaterials with selective molecular recognition, increased biocompatibility, and stability in solution. Materials synthesized this way have the potential to be used in a variety of technological fields, including in vivo applications such as drug delivery and imaging.
Ecological health in the Nation's streams

USGS Publications Warehouse

Carlisle, Daren M.; Woodside, Michael D.

2013-01-01

Aquatic biological communities, which are collections of organisms, are a direct measure of stream health because they indicate the ability of a stream to support life. This fact sheet highlights selected findings of a national assessment of stream health by the National Water-Quality Assessment (NAWQA) Program of the U.S. Geological Survey (USGS). The assessment was unique in that it integrated the condition of three biological communities—algae, macroinvertebrates, and fish—as well as measures of streamflow modification, pesticides, nutrients, and other factors. At least one biological community was altered at 83 percent of assessed streams, and the occurrence of altered communities was highest in urban streams. Streamflows were modified at 86 percent of assessed streams, and increasing severity of streamflow modification was associated with increased occurrence of altered biological communities. Agricultural and urban land use in watersheds may contribute pesticides and nutrients to stream waters, and increasing concentrations of these chemicals were associated with increased occurrence of altered biological communities.
Pull-down Assay to Characterize Ca2+/Calmodulin Binding to Plant Receptor Kinases.

PubMed

Kaufmann, Christine; Sauter, Margret

2017-01-01

Plant receptor-like kinases (RLKs) are regulated by posttranscriptional modification and by interaction with regulatory proteins. A common modification of RLKs is (auto)phosphorylation, and a common regulatory protein is the calcium sensor calmodulin (CaM). We have developed protocols to detect the interaction of an RLK with CaM. The interaction with CaM was shown by bimolecular fluorescence complementation (BiFC) (see Chapter 14) and pull-down assay (this chapter). Both methods offer unique advantages. BiFC is useful in showing interaction of soluble as well as of membrane-bound proteins in planta. Pull-down assays are restricted to soluble proteins and provide in vitro data. The pull-down assay provides the advantage that proteins can be modified prior to binding and that experimental conditions such as the concentration of Ca 2+ or other divalent cations can be controlled. This chapter provides a pull-down protocol to study RLK-CaM interaction with optional steps to investigate the impact of RLK phosphorylation or of Ca 2+ .
Seaweed Hydrocolloid Production: An Update on Enzyme Assisted Extraction and Modification Technologies

PubMed Central

Rhein-Knudsen, Nanna; Ale, Marcel Tutor; Meyer, Anne S.

2015-01-01

Agar, alginate, and carrageenans are high-value seaweed hydrocolloids, which are used as gelation and thickening agents in different food, pharmaceutical, and biotechnological applications. The annual global production of these hydrocolloids has recently reached 100,000 tons with a gross market value just above US$ 1.1 billion. The techno-functional properties of the seaweed polysaccharides depend strictly on their unique structural make-up, notably degree and position of sulfation and presence of anhydro-bridges. Classical extraction techniques include hot alkali treatments, but recent research has shown promising results with enzymes. Current methods mainly involve use of commercially available enzyme mixtures developed for terrestrial plant material processing. Application of seaweed polysaccharide targeted enzymes allows for selective extraction at mild conditions as well as tailor-made modifications of the hydrocolloids to obtain specific functionalities. This review provides an update of the detailed structural features of κ-, ι-, λ-carrageenans, agars, and alginate, and a thorough discussion of enzyme assisted extraction and processing techniques for these hydrocolloids. PMID:26023840
Impact of Site-Directed Mutant Luciferase on Quantitative Green and Orange/Red Emission Intensities in Firefly Bioluminescence

NASA Astrophysics Data System (ADS)

Wang, Yu; Akiyama, Hidefumi; Terakado, Kanako; Nakatsu, Toru

2013-08-01

Firefly bioluminescence has attracted great interest because of its high quantum yield and intriguing modifiable colours. Modifications to the structure of the enzyme luciferase can change the emission colour of firefly bioluminescence, and the mechanism of the colour change has been intensively studied by biochemists, structural biologists, optical physicists, and quantum-chemistry theorists. Here, we report on the quantitative spectra of firefly bioluminescence catalysed by wild-type and four site-directed mutant luciferases. While the mutation caused different emission spectra, the spectra differed only in the intensity of the green component (λmax ~ 560 nm). In contrast, the orange (λmax ~ 610 nm) and red (λmax ~ 650 nm) components present in all the spectra were almost unaffected by the modifications to the luciferases and changes in pH. Our results reveal that the intensity of the green component is the unique factor that is influenced by the luciferase structure and other reaction conditions.
Seaweed hydrocolloid production: an update on enzyme assisted extraction and modification technologies.

PubMed

Rhein-Knudsen, Nanna; Ale, Marcel Tutor; Meyer, Anne S

2015-05-27

Agar, alginate, and carrageenans are high-value seaweed hydrocolloids, which are used as gelation and thickening agents in different food, pharmaceutical, and biotechnological applications. The annual global production of these hydrocolloids has recently reached 100,000 tons with a gross market value just above US$ 1.1 billion. The techno-functional properties of the seaweed polysaccharides depend strictly on their unique structural make-up, notably degree and position of sulfation and presence of anhydro-bridges. Classical extraction techniques include hot alkali treatments, but recent research has shown promising results with enzymes. Current methods mainly involve use of commercially available enzyme mixtures developed for terrestrial plant material processing. Application of seaweed polysaccharide targeted enzymes allows for selective extraction at mild conditions as well as tailor-made modifications of the hydrocolloids to obtain specific functionalities. This review provides an update of the detailed structural features of κ-, ι-, λ-carrageenans, agars, and alginate, and a thorough discussion of enzyme assisted extraction and processing techniques for these hydrocolloids.
Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design

PubMed Central

Shiraki, Tomohiro; Shiraishi, Tomonari; Juhász, Gergely; Nakashima, Naotoshi

2016-01-01

Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E112*) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering–based applications including photonic devices and (bio)imaging/sensing. PMID:27345862
FEL for the polymer processing industries

NASA Astrophysics Data System (ADS)

Kelley, Michael J.

1997-05-01

Polymers are everywhere in modern life because of their unique combination of end-use functionalities, ease of processing, recycling potential and modest cost. The physical and economic scope of the infrastructure committed to present polymers makes the introduction of entirely new chemistry unlikely. Rather, the breadth of commercial offerings more likely to shrink in the face of the widening mandate for recycling, especially of packaging. Improved performance and new functionality must therefore come by routes such as surface modification. However they must come with little environmental impact and at painfully low cost. Processing with strongly absorbed light offers unique advantages. The journal and patent literatures disclose a number of examples of benefits that can be achieved, principally by use of excimer lasers or special UV lamps. Examples of commercialization are few, however, because of the unit cost and maximum scale of existing light sources. A FEL, however, offers unique advantages: tunability to the optimum wavelength, potential for scale up to high average power, and a path to attractively low unit cost of light. A business analysis of prospective applications defines the technical and economic requirements a FEL for polymer surface processing must meet. These are compared to FEL technology as it now stands and as it is envisioned.
YopJ Family Effectors Promote Bacterial Infection through a Unique Acetyltransferase Activity

PubMed Central

2016-01-01

SUMMARY Gram-negative bacterial pathogens rely on the type III secretion system to inject virulence proteins into host cells. These type III secreted “effector” proteins directly manipulate cellular processes to cause disease. Although the effector repertoires in different bacterial species are highly variable, the Yersinia outer protein J (YopJ) effector family is unique in that its members are produced by diverse animal and plant pathogens as well as a nonpathogenic microsymbiont. All YopJ family effectors share a conserved catalytic triad that is identical to that of the C55 family of cysteine proteases. However, an accumulating body of evidence demonstrates that many YopJ effectors modify their target proteins in hosts by acetylating specific serine, threonine, and/or lysine residues. This unique acetyltransferase activity allows the YopJ family effectors to affect the function and/or stability of their targets, thereby dampening innate immunity. Here, we summarize the current understanding of this prevalent and evolutionarily conserved type III effector family by describing their enzymatic activities and virulence functions in animals and plants. In particular, the molecular mechanisms by which representative YopJ family effectors subvert host immunity through posttranslational modification of their target proteins are discussed. PMID:27784797
Ultrafast adsorption and selective desorption of aqueous aromatic dyes by graphene sheets modified by graphene quantum dots

NASA Astrophysics Data System (ADS)

Ying, Yulong; He, Peng; Ding, Guqiao; Peng, Xinsheng

2016-06-01

Graphene modified by graphene quantum dots (GQDs) has been employed to remove toxic organic dyes. An excellent removal capacity (497 mg g-1) and record-breaking adsorption rate (475 mg g-1 min-1 at 20 °C) were demonstrated for Rhodamine B. The enhancement in performance by nearly a factor of three compared to that of graphene was ascribed to the greatly increased accessible surface area of graphene in aqueous solution as well as the increase in surface charges with the modification with GQDs. Besides, this unique adsorption behavior of the modified graphene was expanded to other typical toxic aqueous aromatic dyes such as Evans Blue, Methyl Orange, Malachite Green and Rose Bengal. What is more, a unique desorption behavior of dyes was first observed when employing different solvents, which enabled the GQD-modified graphene to be exploited for selective extraction of dyes and recycling of the adsorbent. The adsorption and desorption mechanism were further investigated. Combining high removal capacity, rapid adsorption kinetics, good recyclability and unique selective desorption, GQD-modified graphene has potential applications in both water purification and separation of aromatic dyes.
D-amino acid-containing supramolecular nanofibers for potential cancer therapeutics.

PubMed

Wang, Huaimin; Feng, Zhaoqianqi; Xu, Bing

2017-02-01

Nanostructures formed by peptides that self-assemble in water through non-covalent interactions have attracted considerable attention because peptides possess several unique advantages, such as modular design and easiness of synthesis, convenient modification with known functional motifs, good biocompatibility, low immunogenicity and toxicity, inherent biodegradability, and fast responses to a wide range of external stimuli. After about two decades of development, peptide-based supramolecular nanostructures have already shown great potentials in the fields of biomedicine. Among a range of biomedical applications, using such nanostructures for cancer therapy has attracted increased interests since cancer remains the major threat for human health. Comparing with L-peptides, nanostructures containing peptides made of D-amino acid (i.e., D-peptides) bear a unique advantage, biostability (i.e., resistance towards most of endogenous enzymes). The exploration of nanostructures containing D-amino acids, especially their biomedical applications, is still in its infancy. Herein we review the recent progress of D-amino acid-containing supramolecular nanofibers as an emerging class of biomaterials that exhibit unique features for the development of cancer therapeutics. In addition, we give a brief perspective about the challenges and promises in this research direction. Copyright © 2016 Elsevier B.V. All rights reserved.

Manatee lays groundwork for commercial use of Orimulsion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makansi, J.

1994-09-01

This article describes the conversion of an oil fired plant to Orimulsion described as a fourth fossil fuel, Orimulsion will replace oil at FP and L's Manatee station. The project involves unique business arrangements as well as important combustion, emissions control, and fuel handling system modifications. Florida Power and Light Co (FP and L) spent several years investigating the use of Orimulsion, including a full-scale five-months demonstration at its Sanford Station Unit 4. Now, the utility has taken the next giant leap; it has committed to convert the Manatee station for full-scale use of this unique fuel. The resulting projectmore » breaks new ground in the electric-generating business in several ways, including these: It represents the first long-term commercial contract for use of Orimulsion in the US, and the largest commitment world-wide. It involves unique business arrangements--not the least of which is the second major contract at an electric-utility station for a third-party-owned and operated flue-gas desulfurization (FGD) system. It indicates risk-taking on the part of utilities--with two 800-MW units, Manatee embodies a substantial amount of FP and L's total and incremental capacity base.« less
Salivary gland proteome analysis reveals modulation of anopheline unique proteins in insensitive acetylcholinesterase resistant Anopheles gambiae mosquitoes.

PubMed

Cornelie, Sylvie; Rossignol, Marie; Seveno, Martial; Demettre, Edith; Mouchet, François; Djègbè, Innocent; Marin, Philippe; Chandre, Fabrice; Corbel, Vincent; Remoué, Franck; Mathieu-Daudé, Françoise

2014-01-01

Insensitive acetylcholinesterase resistance due to a mutation in the acetylcholinesterase (ace) encoding ace-1 gene confers cross-resistance to organophosphate and carbamate insecticides in Anopheles gambiae populations from Central and West Africa. This mutation is associated with a strong genetic cost revealed through alterations of some life history traits but little is known about the physiological and behavioural changes in insects bearing the ace-1(R) allele. Comparative analysis of the salivary gland contents between An. gambiae susceptible and ace-1(R) resistant strains was carried out to charaterize factors that could be involved in modifications of blood meal process, trophic behaviour or pathogen interaction in the insecticide-resistant mosquitoes. Differential analysis of the salivary gland protein profiles revealed differences in abundance for several proteins, two of them showing major differences between the two strains. These two proteins identified as saglin and TRIO are salivary gland-1 related proteins, a family unique to anopheline mosquitoes, one of them playing a crucial role in salivary gland invasion by Plasmodium falciparum sporozoites. Differential expression of two other proteins previously identified in the Anopheles sialome was also observed. The differentially regulated proteins are involved in pathogen invasion, blood feeding process, and protection against oxidation, relevant steps in the outcome of malaria infection. Further functional studies and insect behaviour experiments would confirm the impact of the modification of the sialome composition on blood feeding and pathogen transmission abilities of the resistant mosquitoes. The data supports the hypothesis of alterations linked to insecticide resistance in the biology of the primary vector of human malaria in Africa.
Rehabilitation and education are underutilized for mild stroke and TIA sufferers.

PubMed

Faux, Steven G; Arora, Pooja; Shiner, Christine T; Thompson-Butel, Angelica G; Klein, Linda A

2018-06-01

Transient ischemic attack (TIA) and mild stroke represent a large proportion of cerebrovascular events, at high risk of being followed by recurrent, serious events. The importance of early education addressing risk management, secondary prevention and lifestyle modifications is the centerpiece of further stroke prevention. However, delivering education and rehabilitation to this population can be complex and challenging. Via synthesis of a narrative review and clinical experience, we explore the unique and inherent complexities of rehabilitation management and education provision for patients following mild stroke and TIA. A considerable proportion of TIA/mild stroke survivors have ongoing rehabilitation needs that are poorly addressed. The need for rehabilitation in these patients is often overlooked, and available assessment tools lack the sensitivity to identify common subtle impairments in cognition, mood, language and fatigue. Active and accessible education interventions need to be initiated early after the event, and integrated with ongoing rehabilitation management. Priority areas in need of future development in this field are highlighted and discussed. Implications for rehabilitation Survivors of mild stroke and TIA have ongoing unmet rehabilitation needs and require a unique approach to rehabilitation and education. Rehabilitation needs are difficult to assess and poorly addressed in this cohort, where available assessment tools lack the sensitivity required to identify subtle impairments. Education needs to be initiated early after the event and involve active engagement of the patient in order to improve stroke knowledge, mood and motivate adherence to lifestyle modifications and secondary prevention. Rehabilitation physicians are currently an underutilized resource, who should be more involved in the management of all patients following TIA or mild stroke.
Least-Squares Data Adjustment with Rank-Deficient Data Covariance Matrices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, J.G.

2011-07-01

A derivation of the linear least-squares adjustment formulae is required that avoids the assumption that the covariance matrix of prior parameters can be inverted. Possible proofs are of several kinds, including: (i) extension of standard results for the linear regression formulae, and (ii) minimization by differentiation of a quadratic form of the deviations in parameters and responses. In this paper, the least-squares adjustment equations are derived in both these ways, while explicitly assuming that the covariance matrix of prior parameters is singular. It will be proved that the solutions are unique and that, contrary to statements that have appeared inmore » the literature, the least-squares adjustment problem is not ill-posed. No modification is required to the adjustment formulae that have been used in the past in the case of a singular covariance matrix for the priors. In conclusion: The linear least-squares adjustment formula that has been used in the past is valid in the case of a singular covariance matrix for the covariance matrix of prior parameters. Furthermore, it provides a unique solution. Statements in the literature, to the effect that the problem is ill-posed are wrong. No regularization of the problem is required. This has been proved in the present paper by two methods, while explicitly assuming that the covariance matrix of prior parameters is singular: i) extension of standard results for the linear regression formulae, and (ii) minimization by differentiation of a quadratic form of the deviations in parameters and responses. No modification is needed to the adjustment formulae that have been used in the past. (author)« less
The CEMHaVi program: control, evaluation, and modification of lifestyles in obese youth.

PubMed

Vanhelst, Jérémy; Marchand, Frédéric; Fardy, Paul; Zunquin, Gautier; Loeuille, Guy-André; Renaut, Hervé; Mikulovic, Jacques; Hurdiel, Rémy; Béghin, Laurent; Theunynck, Denis

2010-01-01

Obesity in children has increased in recent years. Many studies with differing methodologies have been undertaken to treat obesity. The Control, Evaluation, and Modification of Lifestyles in Obese Youth (CEMHaVi) program is a unique 2-year health-wellness program of physical activity and health education for obese youth. Findings of this study represent results at 1-year follow-up. The purpose of this study was to evaluate the effects of the CEMHaVi program. Physician-referred subjects (N = 26) participated in the study, 14 girls (13.4 +/- 2.9 years) and 12 boys (12.3 +/- 2.8 years). Measurements included height, weight, body mass index (BMI), academic performance, sleep habits, and health knowledge. The intervention consisted of a unique program of physical activity, including a variety of games specifically selected to be enjoyable, maintain interest, and motivate subjects to adhere. Activity sessions were offered once per week, 2 hours each session, for 12 months. A health education program was offered once every 3 months for 2 hours per session. Health knowledge, academic performance, self-esteem, and sleep were assessed before and after the intervention. Means were calculated at baseline and following intervention and were compared by paired t tests. Findings suggest significant improvements in academic performance (P < .001), quality and quantity of sleep (P < .05), and obesity (P < .05). The program reduced BMI and improved health knowledge, sleep, and academic performance in obese children. The feasibility of a beneficial lifestyle intervention program is encouraging in addressing obesity and related issues in young boys and girls.
Characterization and application of a surface modification designed for QCM-D studies of biotinylated biomolecules.

PubMed

Nilebäck, Erik; Feuz, Laurent; Uddenberg, Hans; Valiokas, Ramūnas; Svedhem, Sofia

2011-10-15

The rapid development of surface sensitive biosensor technologies, especially towards nanoscale devices, requires increasing control of surface chemistry to provide reliable and reproducible results, but also to take full advantage of the sensing opportunities. Here, we present a surface modification strategy to allow biotinylated biomolecules to be immobilized to gold coated sensor crystals for quartz crystal microbalance with dissipation monitoring (QCM-D) sensing. The unique feature of QCM-D is its sensitivity to nanomechanical (viscoelastic) properties at the sensing interface. The surface modification was based on mixed monolayers of oligo(ethylene glycol) (OEG) disulfides, with terminal -OH or biotin groups, on gold. Mixtures containing 1% of the biotin disulfide were concluded to be the most appropriate based on the performance when streptavidin was immobilized to biotinylated sensors and the subsequent biotinylated bovine serum albumin (BSA) interaction was studied. The OEG background kept the unspecific protein binding to a minimum, even when subjected to serum solutions with a high protein concentration. Based on characterization by contact angle goniometry, ellipsometry, and infrared spectroscopy, the monolayers were shown to be well-ordered, with the OEG chains predominantly adopting a helical conformation but also partly an amorphous structure. Storage stability was concluded to depend mainly on light exposure while almost all streptavidin binding activity was retained when storing the sensors cold and dark for 8 weeks. The surface modification was also tested for repeated antibody-antigen interactions between BSA and anti-BSA (immobilized to biotinylated protein A) in QCM-D measurements lasting for >10h with intermediate basic regeneration. This proved an excellent stability of the coating and good reproducibility was obtained for 5 interaction cycles. With this kind of generic surface modification QCM-D can be used in a variety of biosensing applications to provide not only mass but also relevant information of the structural properties of adlayers. Copyright © 2011 Elsevier B.V. All rights reserved.
The molecular biology of environmental aromatic hydrocarbons: Progress report for the period September 1, 1986 through July 31, 1987

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, S.B.

Our laboratory has explored the use of short DNA oligomers as targets for activated polycyclic aromatic hydrocarbons, such as benzo(a)pyrene diol epoxide (BPDE), in order to detect alterations in DNA sequence arrangement. In this model system, oligomers alkylated with (+)-BPDE are ligated into M13 viral DNA and used to transfect Escherichia coli. These cells are plated on agar, incubated at 37/sup 0/C, progeny viral clones are selected, amplified, and the viral DNAs isolated are sequenced at the site of oligomer insertion. We have devised a procedure for the preparation of unique duplex DNA oligomers such that the site of oligomermore » alkylation is specific for a single deoxynucleotide species in the two DNA strands. The procedure for oligomer assembly also allows us to vary the position of the alkylated residue in each of the two strands. Using our model system, the results obtained over the past year can be summarized as follows. When nonalkylated oligomer constructs are ligated into M13 viral DNA and used to transfect E. coli, no modifications in DNA sequence arrangement are detected in progeny viral DNAs. On the other hand, with oligomer constructs containing BP-adducts two major types of modifications in DNA sequence arrangement were observed: (1) large deletions, and (2) nonhomologous (illegitimate) recombinants. Both of these DNA modifications result in the complete removal of the oligomer insert. Transfection of E. coli that are recA/sup -/ does not alter these DNA modifications, therefore, it appears that the deletions and recombinants induced by the alkylated inserts are not under control of the RecA gene. As the distance between the alkylated residues in the duplex strands is increased, the number of recombinant events detected is reduced. In addition to the above types of DNA modifications, restoration of the original nucleotide sequence in the alkylated construct was also observed in progeny viral DNAs. 7 refs., 6 figs., 2 tabs.« less
In-Medium Parton Branching Beyond Eikonal Approximation

NASA Astrophysics Data System (ADS)

Apolinário, Liliana

2017-03-01

The description of the in-medium modifications of partonic showers has been at the forefront of current theoretical and experimental efforts in heavy-ion collisions. It provides a unique laboratory to extend our knowledge frontier of the theory of the strong interactions, and to assess the properties of the hot and dense medium (QGP) that is produced in ultra-relativistic heavy-ion collisions at RHIC and the LHC. The theory of jet quenching, a commonly used alias for the modifications of the parton branching resulting from the interactions with the QGP, has been significantly developed over the last years. Within a weak coupling approach, several elementary processes that build up the parton shower evolution, such as single gluon emissions, interference effects between successive emissions and corrections to radiative energy loss of massive quarks, have been addressed both at eikonal accuracy and beyond by taking into account the Brownian motion that high-energy particles experience when traversing a hot and dense medium. In this work, by using the setup of single gluon emission from a color correlated quark-antiquark pair in a singlet state (qbar{q} antenna), we calculate the in-medium gluon radiation spectrum beyond the eikonal approximation. The results show that we are able to factorize broadening effects from the modifications of the radiation process itself. This constitutes the final proof that a probabilistic picture of the parton shower evolution holds even in the presence of a QGP.
Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis

PubMed Central

Carroll, James A.; Olano, L. Rennee; Sturdevant, Daniel E.; Rosa, Patricia A.

2015-01-01

The saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies. Therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of L. biflexa during exponential growth and in stationary phase. Using these data, we identified abundantly produced proteins in each cellular fraction and quantified the transcript levels from a subset of these genes using quantitative reverse transcription-PCR (RT-PCR). These proteins should prove useful as cellular markers and as controls for gene expression studies. We also observed a significant number of L. biflexa membrane-associated proteins with multiple isoforms, each having unique isoelectric focusing points. L. biflexa cell lysates were examined for several posttranslational modifications suggested by the protein patterns. Methylation and acetylation of lysine residues were predominately observed in the proteins of the membrane-associated fraction, while phosphorylation was detected mainly among soluble proteins. These three posttranslational modification systems appear to be conserved between the free-living species L. biflexa and the pathogenic species Leptospira interrogans, suggesting an important physiological advantage despite the varied life cycles of the different species. PMID:26655756
Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis.

PubMed

Stewart, Philip E; Carroll, James A; Olano, L Rennee; Sturdevant, Daniel E; Rosa, Patricia A

2016-02-15

The saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies. Therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of L. biflexa during exponential growth and in stationary phase. Using these data, we identified abundantly produced proteins in each cellular fraction and quantified the transcript levels from a subset of these genes using quantitative reverse transcription-PCR (RT-PCR). These proteins should prove useful as cellular markers and as controls for gene expression studies. We also observed a significant number of L. biflexa membrane-associated proteins with multiple isoforms, each having unique isoelectric focusing points. L. biflexa cell lysates were examined for several posttranslational modifications suggested by the protein patterns. Methylation and acetylation of lysine residues were predominately observed in the proteins of the membrane-associated fraction, while phosphorylation was detected mainly among soluble proteins. These three posttranslational modification systems appear to be conserved between the free-living species L. biflexa and the pathogenic species Leptospira interrogans, suggesting an important physiological advantage despite the varied life cycles of the different species. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Wolffian duct derivative anomalies: technical considerations when encountered during robot-assisted radical prostatectomy.

PubMed

Acharya, Sujeet S; Gundeti, Mohan S; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2009-04-01

Although malformations of the genitourinary tract are typically identified during childhood, they can remain silent until incidental detection in evaluation and treatment of other pathologies during adulthood. The advent of the minimally invasive era in urologic surgery has given rise to unique challenges in the surgical management of anomalies of the genitourinary tract. This article reviews the embryology of anomalies of Wolffian duct (WD) derivatives with specific attention to the seminal vesicles, vas deferens, ureter, and kidneys. This is followed by a discussion of the history of the laparoscopic approach to WD derivative anomalies. Finally, we present two cases to describe technical considerations when managing these anomalies when encountered during robotic-assisted radical prostatectomy. The University of Chicago Robotic Laparoscopic Radical Prostatectomy (RLRP) database was reviewed for cases where anomalies of WD derivatives were encountered. We describe how modifications in technique allowed for completion of the procedure without difficulty. None Of the 1230 RLRP procedures performed at our institution by three surgeons, only two cases (0.16%) have been noted to have a WD anomaly. These cases were able to be completed without difficulty by making simple modifications in technique. Although uncommon, it is important for the urologist to be familiar with the origin and surgical management of WD anomalies, particularly when detected incidentally during surgery. Simple modifications in technique allow for completion of RLRP without difficulty.
Creation of hydrophilic nitric oxide releasing polymers via plasma surface modification.

PubMed

Pegalajar-Jurado, A; Joslin, J M; Hawker, M J; Reynolds, M M; Fisher, E R

2014-08-13

Herein, we describe the surface modification of an S-nitrosated polymer derivative via H2O plasma treatment, resulting in polymer coatings that maintained their nitric oxide (NO) releasing capabilities, but exhibited dramatic changes in surface wettability. The poly(lactic-co-glycolic acid)-based hydrophobic polymer was nitrosated to achieve a material capable of releasing the therapeutic agent NO. The NO-loaded films were subjected to low-temperature H2O plasma treatments, where the treatment power (20-50 W) and time (1-5 min) were varied. The plasma treated polymer films were superhydrophilic (water droplet spread completely in <100 ms), yet retained 90% of their initial S-nitrosothiol content. Under thermal conditions, NO release profiles were identical to controls. Under buffer soak conditions, the NO release profile was slightly lowered for the plasma-treated materials; however, they still result in physiologically relevant NO fluxes. XPS, SEM-EDS, and ATR-IR characterization suggests the plasma treatment resulted in polymer rearrangement and implantation of hydroxyl and carbonyl functional groups. Plasma treated samples maintained both hydrophilic surface properties and NO release profiles after storage at -18 °C for at least 10 days, demonstrating the surface modification and NO release capabilities are stable over time. The ability to tune polymer surface properties while maintaining bulk properties and NO release properties, and the stability of those properties under refrigerated conditions, represents a unique approach toward creating enhanced therapeutic biopolymers.
Modification of surface properties of cellulosic substrates by quaternized silicone emulsions.

PubMed

Purohit, Parag S; Somasundaran, P

2014-07-15

The present work describes the effect of quaternization of silicones as well as the relevant treatment parameter pH on the frictional, morphological and relaxation properties of fabric substrates. Due to their unique surface properties, silicone polymers are extensively used to modify surface properties of various materials, although the effects of functionalization of silicones and relevant process conditions on modification of substrates are not well understood. Specifically we show a considerable reduction in fabric friction, roughness and waviness upon treatment with quaternized silicones. The treatment at acidic pH results in better deposition of silicone polymers onto the fabric as confirmed through streaming potential measurements which show charge reversal of the fabric. Interestingly, Raman spectroscopy studies show the band of C-O ring stretching mode at ∼1095 cm(-1) shift towards higher wavenumber indicating lowering of stress in fibers upon appropriate silicone treatment. Thus along with the morphological and frictional properties being altered, silicone treatment can lead to a reduction in fabric strain. It is concluded that the electrostatic interactions play an initial role in modification of the fiber substrate followed by multilayer deposition of polymer. This multi-technique approach to study fiber properties upon treatment by combining macro to molecular level methods has helped in understanding of new functional coating materials. Copyright © 2014 Elsevier Inc. All rights reserved.
Molecular Toolkit for Gene Expression Control and Genome Modification in Rhodococcus opacus PD630

DOE PAGES

DeLorenzo, Drew M.; Rottinghaus, Austin G.; Henson, William R.; ...

2018-01-24

Rhodococcus opacus PD630 is a non-model, gram-positive bacterium that possesses desirable traits for lignocellulosic biomass conversion. In particular, it has a relatively rapid growth rate, exhibits genetic tractability, produces high quantities of lipids, and can tolerate and consume toxic, lignin-derived aromatic compounds. Despite these unique, industrially relevant characteristics, R. opacus has been underutilized due to a lack of reliable genetic parts and engineering tools. In this work, we developed a molecular toolbox for reliable gene expression control and genome modification in R. opacus. To facilitate predictable gene expression, a constitutive promoter library spanning ~45-fold in output was constructed. To improvemore » the characterization of available plasmids, the copy numbers of four heterologous and nine endogenous plasmids were determined using quantitative PCR. The molecular toolbox was further expanded by screening a previously unreported antibiotic resistance marker (HygR) and constructing a curable plasmid backbone for temporary gene expression (pB264). Furthermore, a system for genome modification was devised, and three neutral integration sites were identified using a novel combination of transcriptomic data, genomic architecture, and growth rate analysis. Finally, the first reported system for targeted, tunable gene repression in Rhodococcus was developed by utilizing CRISPR interference (CRISPRi). Overall, this work greatly expands the ability to manipulate and engineer R. opacus, making it a viable new chassis for bioproduction from renewable feedstocks.« less
Molecular Toolkit for Gene Expression Control and Genome Modification in Rhodococcus opacus PD630

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeLorenzo, Drew M.; Rottinghaus, Austin G.; Henson, William R.

Rhodococcus opacus PD630 is a non-model, gram-positive bacterium that possesses desirable traits for lignocellulosic biomass conversion. In particular, it has a relatively rapid growth rate, exhibits genetic tractability, produces high quantities of lipids, and can tolerate and consume toxic, lignin-derived aromatic compounds. Despite these unique, industrially relevant characteristics, R. opacus has been underutilized due to a lack of reliable genetic parts and engineering tools. In this work, we developed a molecular toolbox for reliable gene expression control and genome modification in R. opacus. To facilitate predictable gene expression, a constitutive promoter library spanning ~45-fold in output was constructed. To improvemore » the characterization of available plasmids, the copy numbers of four heterologous and nine endogenous plasmids were determined using quantitative PCR. The molecular toolbox was further expanded by screening a previously unreported antibiotic resistance marker (HygR) and constructing a curable plasmid backbone for temporary gene expression (pB264). Furthermore, a system for genome modification was devised, and three neutral integration sites were identified using a novel combination of transcriptomic data, genomic architecture, and growth rate analysis. Finally, the first reported system for targeted, tunable gene repression in Rhodococcus was developed by utilizing CRISPR interference (CRISPRi). Overall, this work greatly expands the ability to manipulate and engineer R. opacus, making it a viable new chassis for bioproduction from renewable feedstocks.« less
Using Chromatin Immunoprecipitation in Toxicology: A Step-by-Step Guide to Increasing Efficiency, Reducing Variability, and Expanding Applications.

PubMed

McCullough, Shaun D; On, Doan M; Bowers, Emma C

2017-05-02

Histone modifications work in concert with DNA methylation to regulate cellular structure, function, and response to environmental stimuli. More than 130 unique histone modifications have been described to date, and chromatin immunoprecipitation (ChIP) allows for the exploration of their associations with the regulatory regions of target genes and other DNA/chromatin-associated proteins across the genome. Many variations of ChIP have been developed in the 30 years since its earliest version came into use, which makes it challenging for users to integrate the procedure into their research programs. Furthermore, the differences in ChIP protocols can confound efforts to increase reproducibility across studies. The streamlined ChIP procedure presented here can be readily applied to samples from a wide range of in vitro studies (cell lines and primary cells) and clinical samples (peripheral leukocytes) in toxicology. We also provide detailed guidance on the optimization of critical protocol parameters, such as chromatin fixation, fragmentation, and immunoprecipitation, to increase efficiency and improve reproducibility. Expanding toxicoepigenetic studies to more readily include histone modifications will facilitate a more comprehensive understanding of the role of the epigenome in environmental exposure effects and the integration of epigenetic data in mechanistic toxicology, adverse outcome pathways, and risk assessment. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.
A Novel Proteomics Approach to Identify SUMOylated Proteins and Their Modification Sites in Human Cells*

PubMed Central

Galisson, Frederic; Mahrouche, Louiza; Courcelles, Mathieu; Bonneil, Eric; Meloche, Sylvain; Chelbi-Alix, Mounira K.; Thibault, Pierre

2011-01-01

The small ubiquitin-related modifier (SUMO) is a small group of proteins that are reversibly attached to protein substrates to modify their functions. The large scale identification of protein SUMOylation and their modification sites in mammalian cells represents a significant challenge because of the relatively small number of in vivo substrates and the dynamic nature of this modification. We report here a novel proteomics approach to selectively enrich and identify SUMO conjugates from human cells. We stably expressed different SUMO paralogs in HEK293 cells, each containing a His6 tag and a strategically located tryptic cleavage site at the C terminus to facilitate the recovery and identification of SUMOylated peptides by affinity enrichment and mass spectrometry. Tryptic peptides with short SUMO remnants offer significant advantages in large scale SUMOylome experiments including the generation of paralog-specific fragment ions following CID and ETD activation, and the identification of modified peptides using conventional database search engines such as Mascot. We identified 205 unique protein substrates together with 17 precise SUMOylation sites present in 12 SUMO protein conjugates including three new sites (Lys-380, Lys-400, and Lys-497) on the protein promyelocytic leukemia. Label-free quantitative proteomics analyses on purified nuclear extracts from untreated and arsenic trioxide-treated cells revealed that all identified SUMOylated sites of promyelocytic leukemia were differentially SUMOylated upon stimulation. PMID:21098080
Solid-state mAbs and ADCs subjected to heat-stress stability conditions can be covalently modified with buffer and excipient molecules.

PubMed

Valliere-Douglass, John F; Lewis, Patsy; Salas-Solano, Oscar; Jiang, Shan

2015-02-01

We report that a unique type of chemical modification occurs on lyophilized proteins. Freeze-dried mAbs and antibody-drug conjugates (ADCs) can be covalently modified with buffer and excipient molecules on the side chains of Glu, Asp, Thr, and Ser amino acids when subjected to temperature stress. The reaction occurs primarily via condensation of common buffers and excipients such as histidine, tris, trehalose and sucrose, with Glu and Asp carboxylates in the primary sequence of proteins. The reaction was also found to proceed through condensation of carboxylate containing buffers such as citrate, with Thr and Ser hydroxyls in the primary sequence of proteins. Based on the mass of the covalent adducts observed on mAbs and ADCs, it is apparent that the reaction produces water as a product and is thus favored in a low moisture environments such as a lyophilized protein cake. Herein, we present the evidence for the covalent modification of proteins drawn from case studies of in-depth characterization of heat-stressed mAbs and ADCs in the solid state. We also demonstrate how common charge variant assays such as imaged capillary isoelectric focusing and mass spectrometry can be used to monitor this specific class of protein modification. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Thermoacoustic tomography for an integro-differential wave equation modeling attenuation

NASA Astrophysics Data System (ADS)

Acosta, Sebastián; Palacios, Benjamín

2018-02-01

In this article we study the inverse problem of thermoacoustic tomography (TAT) on a medium with attenuation represented by a time-convolution (or memory) term, and whose consideration is motivated by the modeling of ultrasound waves in heterogeneous tissue via fractional derivatives with spatially dependent parameters. Under the assumption of being able to measure data on the whole boundary, we prove uniqueness and stability, and propose a convergent reconstruction method for a class of smooth variable sound speeds. By a suitable modification of the time reversal technique, we obtain a Neumann series reconstruction formula.
Nanomedicine applications in orthopedic medicine: state of the art

PubMed Central

Mazaheri, Mozhdeh; Eslahi, Niloofar; Ordikhani, Farideh; Tamjid, Elnaz; Simchi, Abdolreza

2015-01-01

The technological and clinical need for orthopedic replacement materials has led to significant advances in the field of nanomedicine, which embraces the breadth of nanotechnology from pharmacological agents and surface modification through to regulation and toxicology. A variety of nanostructures with unique chemical, physical, and biological properties have been engineered to improve the functionality and reliability of implantable medical devices. However, mimicking living bone tissue is still a challenge. The scope of this review is to highlight the most recent accomplishments and trends in designing nanomaterials and their applications in orthopedics with an outline on future directions and challenges. PMID:26451110

Synthesis of boron nitride nanotubes and their applications

PubMed Central

Kalay, Saban; Yilmaz, Zehra; Sen, Ozlem; Emanet, Melis; Kazanc, Emine

2015-01-01

Summary Boron nitride nanotubes (BNNTs) have been increasingly investigated for use in a wide range of applications due to their unique physicochemical properties including high hydrophobicity, heat and electrical insulation, resistance to oxidation, and hydrogen storage capacity. They are also valued for their possible medical and biomedical applications including drug delivery, use in biomaterials, and neutron capture therapy. In this review, BNNT synthesis methods and the surface modification strategies are first discussed, and then their toxicity and application studies are summarized. Finally, a perspective for the future use of these novel materials is discussed. PMID:25671154
Nanomedicine applications in orthopedic medicine: state of the art.

PubMed

Mazaheri, Mozhdeh; Eslahi, Niloofar; Ordikhani, Farideh; Tamjid, Elnaz; Simchi, Abdolreza

2015-01-01

The technological and clinical need for orthopedic replacement materials has led to significant advances in the field of nanomedicine, which embraces the breadth of nanotechnology from pharmacological agents and surface modification through to regulation and toxicology. A variety of nanostructures with unique chemical, physical, and biological properties have been engineered to improve the functionality and reliability of implantable medical devices. However, mimicking living bone tissue is still a challenge. The scope of this review is to highlight the most recent accomplishments and trends in designing nanomaterials and their applications in orthopedics with an outline on future directions and challenges.
Tailoring lumazine synthase assemblies for bionanotechnology.

PubMed

Azuma, Yusuke; Edwardson, Thomas G W; Hilvert, Donald

2018-05-21

Nanoscale compartments formed by hierarchical protein self-assembly are valuable platforms for nanotechnology development. The well-defined structure and broad chemical functionality of protein cages, as well as their amenability to genetic and chemical modification, have enabled their repurposing for diverse applications. In this review, we summarize progress in the engineering of the cage-forming enzyme lumazine synthase. This bacterial nanocompartment has proven to be a malleable scaffold. The natural protein has been diversified to afford a family of unique proteinaceous capsules that have been modified, evolved and assembled with other components to produce nanoreactors, artificial organelles, delivery vehicles and virus mimics.
Kerosene-base fuels in small gasoline engines. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Failla, C.C.; Pouring, A.A.

1991-01-01

This document presents the results of an engineering study to demonstrate the technology for converting small gasoline spark-ignited engines, to burn kerosene type fuels to power small generators (0.5 to 3.0 kw). Commercially available (plus those in the developmental stage), reciprocating, two-stroke, four stroke and rotary engines were evaluated for their conversion potential. Unique combustion systems were identified and trade-off studies conducted on engine type, combustion systems, and modification required to burn kerosene type fuels, with special emphasis given to minimizing life cycle cost. Recommendations for the most feasible system are given.
A taxonomy for user-healthcare robot interaction.

PubMed

Bzura, Conrad; Im, Hosung; Liu, Tammy; Malehorn, Kevin; Padir, Taskin; Tulu, Bengisu

2012-01-01

This paper evaluates existing taxonomies aimed at characterizing the interaction between robots and their users and modifies them for health care applications. The modifications are based on existing robot technologies and user acceptance of robotics. Characterization of the user, or in this case the patient, is a primary focus of the paper, as they present a unique new role as robot users. While therapeutic and monitoring-related applications for robots are still relatively uncommon, we believe they will begin to grow and thus it is important that the spurring relationship between robot and patient is well understood.
Upper extremity weightlifting injuries: Diagnosis and management.

PubMed

Golshani, Kayvon; Cinque, Mark E; O'Halloran, Peter; Softness, Kenneth; Keeling, Laura; Macdonell, J Ryan

2018-03-01

Common upper extremity injuries in resistance training athletes include muscle strains, ligament sprains, pectoralis major tendon ruptures, distal biceps tendon ruptures, and chronic shoulder pain and capsulolabral injuries. While each injury is unique in its specific anatomic location and mechanism, each is preventable with proper exercise technique, safety and maintenance of muscle balance. Conservative treatment is the therapeutic modality of choice and these injuries generally resolve with workout modification, appropriate recovery, anti-inflammatory medication, and physical therapy. If conservative treatment fails, surgical intervention is often successful and can return the weightlifter to a level of performance near their pre-injury level.
Carbon Nanotube-Reinforced Thermotropic Liquid Crystal Polymer Nanocomposites

PubMed Central

Kim, Jun Young

2009-01-01

This paper focuses on the fabrication via simple melt blending of thermotropic liquid crystal polyester (TLCP) nanocomposites reinforced with a very small quantity of modified carbon nanotube (CNT) and the unique effects of the modified CNT on the physical properties of the nanocomposites. The thermal, mechanical, and rheological properties of modified CNT-reinforced TLCP nanocomposites are highly dependent on the uniform dispersion of CNT and the interactions between the CNT and TLCP, which can be enhanced by chemical modification of the CNT, providing a design guide of CNT-reinforced TLCP nanocomposites with great potential for industrial uses.
Resonance Production in Heavy-Ion Collisions

NASA Astrophysics Data System (ADS)

Knospe, Anders G.

2018-02-01

Hadronic resonances are unique probes that allow the properties of heavyion collisions to be studied. Topics that can be studied include modification of spectral shapes, in-medium energy loss of parsons, vector-meson spin alignment, hydrodynamic flow, recombination, strangeness production, and the properties of the hadronic phase. Measurements of resonances in p+p, p+A, and d+A collisions serve as baselines for heavy-ion studies and also permit searches for possible collective effects in these smaller systems. These proceedings present a selection of results related to these topics from experiments at RHIC, LHC, and other facilities, as well as comparisons to theoretical models.
Inventory of native vegetation and related resources from space photography

NASA Technical Reports Server (NTRS)

Poulton, C. E.; Johnson, J. R.; Mouat, D. A.

1970-01-01

The application of space and high flight photography to vegetational resources in Arizona is discussed. Ecologically based vegetation-landform and land use maps are prepared. The use of material from the Apollo 9 flight and high flight aerial photography are discussed. Land uses that result in a conversion or strong modification of the natural vegetation are presented. The vegetation-landform units have an ecological basis and are meaningful from a land use point of view because they identify areas with unique potentials or limitations for use or development under various land uses. Examples of these relationships are given.
High Power Helicon Plasma Source for Plasma Processing

NASA Astrophysics Data System (ADS)

Prager, James; Ziemba, Timothy; Miller, Kenneth E.

2015-09-01

Eagle Harbor Technologies (EHT), Inc. is developing a high power helicon plasma source. The high power nature and pulsed neutral gas make this source unique compared to traditional helicon source. These properties produce a plasma flow along the magnetic field lines, and therefore allow the source to be decoupled from the reaction chamber. Neutral gas can be injected downstream, which allows for precision control of the ion-neutral ratio at the surface of the sample. Although operated at high power, the source has demonstrated very low impurity production. This source has applications to nanoparticle productions, surface modification, and ionized physical vapor deposition.
Water/alcohol soluble conjugated polymers as highly efficient electron transporting/injection layer in optoelectronic devices.

PubMed

Huang, Fei; Wu, Hongbin; Cao, Yong

2010-07-01

Water/alcohol soluble conjugated polymers (WSCPs) can be processed from water or other polar solvents, which offer good opportunities to avoid interfacial mixing upon fabrication of multilayer polymer optoelectronic devices by solution processing, and can dramatically improve charge injection from high work-function metal cathode resulting in greatly enhancement of the device performance. In this critical review, the authors provide a brief review of recent developments in this field, including the materials design, functional principles, and their unique applications as interface modification layer in solution-processable multilayer optoelectronic devices (135 references).
Modular solar food dryers for farm use

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, C.J. Jr.; Coleman, R.L.; Berry, R.E.

1981-01-01

Several solar food dryer modules have been constructed. Their design has been based on a low-cost, small-scale solar dryer using a unique parabolic reflector construction to increase radiation on the drying surface. Each module has a drying surface of 1.1 M/sup 2/ and a parabolic reflector area of 3.3 M/sup 2/. Some modules are being used to dry mango slices (a potential new food product) for market testing, while others are used for experiments to improve drying efficiency. A description is given of the operating conditions of the modules drying mango slices and the most effective modifications.
Successful Solutions to SSME/AT Development Turbine Blade Distress

NASA Technical Reports Server (NTRS)

Montgomery, Stuart K.

1999-01-01

As part of the High-Pressure Fuel Turbopump/Alternate Turbopump (HPFTP/AT) turbine blade development program, unique turbine blade design features were implemented to address 2nd stage turbine blade high cycle fatigue distress and improve turbine robustness. Features included the addition of platform featherseal dampers, asymmetric blade tip seal segments, gold plating of the blade attachments, and airfoil tip trailing edge modifications. Development testing shows these features have eliminated turbine blade high cycle fatigue distress and consequently these features are currently planned for incorporation to the flight configuration. Certification testing will begin in 1999. This presentation summarizes these features.
Mercury's surface: Preliminary description and interpretation from Mariner 10 pictures

USGS Publications Warehouse

Murray, B.C.; Belton, M.J.S.; Danielson, G. Edward; Davies, M.E.; Gault, D.E.; Hapke, B.; O'Leary, B.; Strom, R.G.; Suomi, V.; Trask, N.

1974-01-01

The surface morphology and optical properties of Mercury resemble those of the moon in remarkable detail and record a very similar sequence of events. Chemical and mineralogical similarity of the outer layers of Mercury and the moon is implied; Mercury is probably a differentiated planet with a large iron-rich core. Differentiation is inferred to have occurred very early. No evidence of atmospheric modification of landforms has been found. Large-scale scarps and ridges unlike lunar or martian features may reflect a unique period of planetary compression near the end of heavy bombardment by small planetesimals.
Stable isotope dimethyl labelling for quantitative proteomics and beyond

PubMed Central

Hsu, Jue-Liang; Chen, Shu-Hui

2016-01-01

Stable-isotope reductive dimethylation, a cost-effective, simple, robust, reliable and easy-to- multiplex labelling method, is widely applied to quantitative proteomics using liquid chromatography-mass spectrometry. This review focuses on biological applications of stable-isotope dimethyl labelling for a large-scale comparative analysis of protein expression and post-translational modifications based on its unique properties of the labelling chemistry. Some other applications of the labelling method for sample preparation and mass spectrometry-based protein identification and characterization are also summarized. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644970
Making sense of nonbusiness accounting.

PubMed

Anthony, R N

1980-01-01

The nonbusiness world of municipalities, colleges and universities, hospitals, and other nonprofit organizations follows its own rules when it comes to financial statements, and these are often confusing to anyone who is accustomed to business accounting. According to this author, it was the concept of fund accounting that divided the two worlds of business and nonbusiness accounting and led to a situation where it is almost impossible to judge the financial performance of nonbusiness entities. He shows how financial statements of the business and nonbusiness worlds can use the same standards, with a few modifications for the unique features of nonbusiness organizations.
Cost effectiveness as applied to the Viking Lander systems-level thermal development test program

NASA Technical Reports Server (NTRS)

Buna, T.; Shupert, T. C.

1974-01-01

The economic aspects of thermal testing at the systems-level as applied to the Viking Lander Capsule thermal development program are reviewed. The unique mission profile and pioneering scientific goals of Viking imposed novel requirements on testing, including the development of a simulation technique for the Martian thermal environment. The selected approach included modifications of an existing conventional thermal vacuum facility, and improved test-operational techniques that are applicable to the simulation of the other mission phases as well, thereby contributing significantly to the cost effectiveness of the overall thermal test program.
Human Germline CRISPR-Cas Modification: Toward a Regulatory Framework

PubMed Central

Evitt, Niklaus H.; Mascharak, Shamik; Altman, Russ B.

2015-01-01

CRISPR germline editing therapies (CGETs) hold unprecedented potential to eradicate hereditary disorders. However, the prospect of altering the human germline has sparked a debate over the safety, efficacy, and morality of CGETs, triggering a funding moratorium by the NIH. There is an urgent need for practical paths for the evaluation of these capabilities. We propose a model regulatory framework for CGET research, clinical development, and distribution. Our model takes advantage of existing legal and regulatory institutions but adds elevated scrutiny at each stage of CGET development to accommodate the unique technical and ethical challenges posed by germline editing. PMID:26632357
SAE Mil-1394 For Military and Aerospace Vehicle Applications

NASA Technical Reports Server (NTRS)

Dunga, Larry; Wroble, Mike; Kreska, Jack

2004-01-01

Unique opportunity to utilize new technology while increasing vehicle and crew member safety. Demonstration of new technology that can be utilized for Crew Exploration Vehicle and other future manned vehicles. Future work for other cameras in the vehicle that can be IEEE1394 based without major vehicle modifications. Demonstrates that LM can share information and knowledge between internal groups and NASA to assist in providing a product in support of the NASA Return to Flight Activities. This upgrade will provide a flight active data bus that is 100 times faster than any similar bus on the vehicle.
Carbon nanotubes: a potential concept for drug delivery applications.

PubMed

Kumar, Rakesh; Dhanawat, Meenakshi; Kumar, Sudhir; Singh, Brahma N; Pandit, Jayant K; Sinha, Vivek R

2014-04-01

The unique properties of carbon nanotubes (CNTs) make them a highly interesting and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and lot more. Even though highly beneficial, the biocompatibility of CNTs is a major issue in their questioning their potential application in targeting drug delivery. Studies confirmed subdued toxicity of CNTs following slight modifications like functionalization, controlled dimensions, purification etc. A well-established mechanism for cellular internalization is an insistent need to attain a more efficient and targeted delivery. Recent patents have been thoroughly discussed in the text below.

Running Injuries During Adolescence and Childhood.

PubMed

Krabak, Brian J; Snitily, Brian; Milani, Carlo J E

2016-02-01

The popularity of running among young athletes has significantly increased over the past few decades. As the number of children who participate in running increases, so do the potential number of injuries to this group. Proper care of these athletes includes a thorough understanding of the unique physiology of the skeletally immature athlete and common injuries in this age group. Treatment should focus on athlete education, modification of training schedule, and correction of biomechanical deficits contributing to injury. Early identification and correction of these factors will allow a safe return to running sports. Copyright © 2016 Elsevier Inc. All rights reserved.
An Unorthodox Sensory Adaptation Site in the Escherichia coli Serine Chemoreceptor

PubMed Central

Han, Xue-Sheng

2014-01-01

The serine chemoreceptor of Escherichia coli contains four canonical methylation sites for sensory adaptation that lie near intersubunit helix interfaces of the Tsr homodimer. An unexplored fifth methylation site, E502, lies at an intrasubunit helix interface closest to the HAMP domain that controls input-output signaling in methyl-accepting chemotaxis proteins. We analyzed, with in vivo Förster resonance energy transfer (FRET) kinase assays, the serine thresholds and response cooperativities of Tsr receptors with different mutationally imposed modifications at sites 1 to 4 and/or at site 5. Tsr variants carrying E or Q at residue 502, in combination with unmodifiable D and N replacements at adaptation sites 1 to 4, underwent both methylation and demethylation/deamidation, although detection of the latter modifications required elevated intracellular levels of CheB. These Tsr variants could not mediate a chemotactic response to serine spatial gradients, demonstrating that adaptational modifications at E502 alone are not sufficient for Tsr function. Moreover, E502 is not critical for Tsr function, because only two amino acid replacements at this residue abrogated serine chemotaxis: Tsr-E502P had extreme kinase-off output and Tsr-E502I had extreme kinase-on output. These large threshold shifts are probably due to the unique HAMP-proximal location of methylation site 5. However, a methylation-mimicking glutamine at any Tsr modification site raised the serine response threshold, suggesting that all sites influence signaling by the same general mechanism, presumably through changes in packing stability of the methylation helix bundle. These findings are consistent with control of input-output signaling in Tsr through dynamic interplay of the structural stabilities of the HAMP and methylation bundles. PMID:24272777
Unexpected expansion of tRNA substrate recognition by the yeast m1G9 methyltransferase Trm10.

PubMed

Swinehart, William E; Henderson, Jeremy C; Jackman, Jane E

2013-08-01

N-1 Methylation of the nearly invariant purine residue found at position 9 of tRNA is a nucleotide modification found in multiple tRNA species throughout Eukarya and Archaea. First discovered in Saccharomyces cerevisiae, the tRNA methyltransferase Trm10 is a highly conserved protein both necessary and sufficient to catalyze all known instances of m1G9 modification in yeast. Although there are 19 unique tRNA species that contain a G at position 9 in yeast, and whose fully modified sequence is known, only 9 of these tRNA species are modified with m1G9 in wild-type cells. The elements that allow Trm10 to distinguish between structurally similar tRNA species are not known, and sequences that are shared between all substrate or all nonsubstrate tRNAs have not been identified. Here, we demonstrate that the in vitro methylation activity of yeast Trm10 is not sufficient to explain the observed pattern of modification in vivo, as additional tRNA species are substrates for Trm10 m1G9 methyltransferase activity. Similarly, overexpression of Trm10 in yeast yields m1G9 containing tRNA species that are ordinarily unmodified in vivo. Thus, yeast Trm10 has a significantly broader tRNA substrate specificity than is suggested by the observed pattern of modification in wild-type yeast. These results may shed light onto the suggested involvement of Trm10 in other pathways in other organisms, particularly in higher eukaryotes that contain up to three different genes with sequence similarity to the single TRM10 gene in yeast, and where these other enzymes have been implicated in pathways beyond tRNA processing.
Use of a Scale Model in the Design of Modifications to the NASA Glenn Icing Research Tunnel

NASA Technical Reports Server (NTRS)

Canacci, Victor A.; Gonsalez, Jose C.; Spera, David A.; Burke, Thomas (Technical Monitor)

2001-01-01

Major modifications were made in 1999 to the 6- by 9-Foot (1.8- by 2.7-m) Icing Research tunnel (IRT) at the NASA Glenn Research Center, including replacement of its heat exchanger and associated ducts and turning vanes, and the addition of fan outlet guide vanes (OGV's). A one-tenth scale model of the IRT (designated as the SMIRT) was constructed with and without these modifications and tested to increase confidence in obtaining expected improvements in flow quality around the tunnel loop. The SMIRT is itself an aerodynamic test facility whose flow patterns without modifications have been shown to be accurate, scaled representations of those measured in the IRT prior to the 1999 upgrade program. In addition, tests in the SMIRT equipped with simulated OGV's indicated that these devices in the IRT might reduce flow distortions immediately downstream of the fan by two thirds. Flow quality parameters measured in the SMIRT were projected to the full-size modified IRT, and quantitative estimates of improvements in flow quality were given prior to construction. In this paper, the results of extensive flow quality studies conducted in the SMIRT are documented. Samples of these are then compared with equivalent measurements made in the full-scale IRT, both before and after its configuration was upgraded. Airspeed, turbulence intensity, and flow angularity distributions are presented for cross sections downstream of the drive fan, both upstream and downstream of the replacement flat heat exchanger, in the stilling chamber, in the test section, and in the wakes of the new comer turning vanes with their unique expanding and contracting designs. Lessons learned from these scale-model studies are discussed.
Comprehensive genome-wide proteomic analysis of human placental tissue for the Chromosome-Centric Human Proteome Project.

PubMed

Lee, Hyoung-Joo; Jeong, Seul-Ki; Na, Keun; Lee, Min Jung; Lee, Sun Hee; Lim, Jong-Sun; Cha, Hyun-Jeong; Cho, Jin-Young; Kwon, Ja-Young; Kim, Hoguen; Song, Si Young; Yoo, Jong Shin; Park, Young Mok; Kim, Hail; Hancock, William S; Paik, Young-Ki

2013-06-07

As a starting point of the Chromosome-Centric Human Proteome Project (C-HPP), we established strategies of genome-wide proteomic analysis, including protein identification, quantitation of disease-specific proteins, and assessment of post-translational modifications, using paired human placental tissues from healthy and preeclampsia patients. This analysis resulted in identification of 4239 unique proteins with high confidence (two or more unique peptides with a false discovery rate less than 1%), covering 21% of approximately 20, 059 (Ensembl v69, Oct 2012) human proteins, among which 28 proteins exhibited differentially expressed preeclampsia-specific proteins. When these proteins are assigned to all human chromosomes, the pattern of the newly identified placental protein population is proportional to that of the gene count distribution of each chromosome. We also identified 219 unique N-linked glycopeptides, 592 unique phosphopeptides, and 66 chromosome 13-specific proteins. In particular, protein evidence of 14 genes previously known to be specifically up-regulated in human placenta was verified by mass spectrometry. With respect to the functional implication of these proteins, 38 proteins were found to be involved in regulatory factor biosynthesis or the immune system in the placenta, but the molecular mechanism of these proteins during pregnancy warrants further investigation. As far as we know, this work produced the highest number of proteins identified in the placenta and will be useful for annotating and mapping all proteins encoded in the human genome.
Analysis of strain-specific genes in glutamic acid-producing Corynebacterium glutamicum ssp. lactofermentum AJ 1511.

PubMed

Nishio, Yousuke; Koseki, Chie; Tonouchi, Naoto; Matsui, Kazuhiko; Sugimoto, Shinichi; Usuda, Yoshihiro

2017-07-11

Strains of the bacterium, Corynebacterium glutamicum, are widely used for the industrial production of L-glutamic acid and various other substances. C. glutamicum ssp. lactofermentum AJ 1511, formerly classified as Brevibacterium lactofermentum, and the closely related C. glutamicum ATCC 13032 have been used as industrial strains for more than 50 years. We determined the whole genome sequence of C. glutamicum AJ 1511 and performed genome-wide comparative analysis with C. glutamicum ATCC 13032 to determine strain-specific genetic differences. This analysis revealed that the genomes of the two industrial strains are highly similar despite the phenotypic differences between the two strains. Both strains harbored unique genes but gene transpositions or inversions were not observed. The largest unique region, a 220-kb AT-rich region located between 1.78 and 2.00 Mb position in C. glutamicum ATCC 13032 genome, was missing in the genome of C. glutamicum AJ 1511. The next two largest unique regions were present in C. glutamicum AJ 1511. The first region (413-484 kb position) contains several predicted transport proteins, enzymes involved in sugar metabolism, and transposases. The second region (1.47-1.50 Mb position) encodes restriction modification systems. A gene predicted to encode NADH-dependent glutamate dehydrogenase, which is involved in L-glutamate biosynthesis, is present in C. glutamicum AJ 1511. Strain-specific genes identified in this study are likely to govern phenotypes unique to each strain.
The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that might not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on November 18-19, 2008 in Chicago, IL, to achieve the objective. Before the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Before the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items would need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional subitem was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.
When biomolecules meet graphene: from molecular level interactions to material design and applications.

PubMed

Li, Dapeng; Zhang, Wensi; Yu, Xiaoqing; Wang, Zhenping; Su, Zhiqiang; Wei, Gang

2016-12-01

Graphene-based materials have attracted increasing attention due to their atomically-thick two-dimensional structures, high conductivity, excellent mechanical properties, and large specific surface areas. The combination of biomolecules with graphene-based materials offers a promising method to fabricate novel graphene-biomolecule hybrid nanomaterials with unique functions in biology, medicine, nanotechnology, and materials science. In this review, we focus on a summarization of the recent studies in functionalizing graphene-based materials using different biomolecules, such as DNA, peptides, proteins, enzymes, carbohydrates, and viruses. The different interactions between graphene and biomolecules at the molecular level are demonstrated and discussed in detail. In addition, the potential applications of the created graphene-biomolecule nanohybrids in drug delivery, cancer treatment, tissue engineering, biosensors, bioimaging, energy materials, and other nanotechnological applications are presented. This review will be helpful to know the modification of graphene with biomolecules, understand the interactions between graphene and biomolecules at the molecular level, and design functional graphene-based nanomaterials with unique properties for various applications.
Basic Mechanics of DNA Methylation and the Unique Landscape of the DNA Methylome in Metal-Induced Carcinogenesis

PubMed Central

Brocato, Jason; Costa, Max

2013-01-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypomethylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance. PMID:23844698
Pharmaceutical Additive Manufacturing: a Novel Tool for Complex and Personalized Drug Delivery Systems.

PubMed

Zhang, Jiaxiang; Vo, Anh Q; Feng, Xin; Bandari, Suresh; Repka, Michael A

2018-06-25

Inter-individual variability is always an issue when treating patients of different races, genders, ages, pharmacogenetics, and pharmacokinetic characteristics. However, the development of novel dosage forms is limited by the huge investments required for production line modifications and dosages diversity. Additive manufacturing (AM) or 3D printing can be a novel alternative solution for the development of controlled release dosages because it can produce personalized or unique dosage forms and more complex drug-release profiles. The primary objective of this manuscript is to review the 3D printing processes that have been used in the pharmaceutical area, including their general aspects, materials, and the operation of each AM technique. Advantages and shortcomings of the technologies are discussed with respect to practice and practical applications. Thus, this review will provide an overview and discussion on advanced pharmaceutical AM technologies, which can be used to produce unique controlled drug delivery systems and personalized dosages for the future of personalized medicine.
Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis.

PubMed

Brocato, Jason; Costa, Max

2013-07-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypo-methylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance.
Advanced nanocarriers based on heparin and its derivatives for cancer management.

PubMed

Yang, Xiaoye; Du, Hongliang; Liu, Jiyong; Zhai, Guangxi

2015-02-09

To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin-drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.
Synthesis of Gold Nanoparticles with Buffer-Dependent Variations of Size and Morphology in Biological Buffers.

PubMed

Ahmed, Syed Rahin; Oh, Sangjin; Baba, Rina; Zhou, Hongjian; Hwang, Sungu; Lee, Jaebeom; Park, Enoch Y

2016-12-01

The demand for biologically compatible and stable noble metal nanoparticles (NPs) has increased in recent years due to their inert nature and unique optical properties. In this article, we present 11 different synthetic methods for obtaining gold nanoparticles (Au NPs) through the use of common biological buffers. The results demonstrate that the sizes, shapes, and monodispersity of the NPs could be varied depending on the type of buffer used, as these buffers acted as both a reducing agent and a stabilizer in each synthesis. Theoretical simulations and electrochemical experiments were performed to understand the buffer-dependent variations of size and morphology exhibited by these Au NPs, which revealed that surface interactions and the electrostatic energy on the (111) surface of Au were the determining factors. The long-term stability of the synthesized NPs in buffer solution was also investigated. Most NPs synthesized using buffers showed a uniquely wide range of pH stability and excellent cell viability without the need for further modifications.
Evolution of thorax architecture in ant castes highlights trade-off between flight and ground behaviors

PubMed Central

Keller, Roberto A; Peeters, Christian; Beldade, Patrícia

2014-01-01

The concerted evolution of morphological and behavioral specializations has compelling examples in ant castes. Unique to ants is a marked divergence between winged queens and wingless workers, but morphological specializations for behaviors on the ground have been overlooked. We analyzed thorax morphology of queens and workers in species from 21 of the 25 ant subfamilies. We uncovered unique skeletomuscular modifications in workers that presumably increase power and flexibility of head–thorax articulation, emphasizing that workers are not simply wingless versions of queens. We also identified two distinct types of queens and showed repeated evolutionary associations with strategies of colony foundation. Solitary founding queens that hunt have a more worker-like thorax. Our results reveal that ants invest in the relative size of thorax segments according to their tasks. Versatility of head movements allows for better manipulation of food and objects, which arguably contributed to the ants’ ecological and evolutionary success. DOI: http://dx.doi.org/10.7554/eLife.01539.001 PMID:24399458
Structural basis for catalysis at the membrane-water interface.

PubMed

Dufrisne, Meagan Belcher; Petrou, Vasileios I; Clarke, Oliver B; Mancia, Filippo

2017-11-01

The membrane-water interface forms a uniquely heterogeneous and geometrically constrained environment for enzymatic catalysis. Integral membrane enzymes sample three environments - the uniformly hydrophobic interior of the membrane, the aqueous extramembrane region, and the fuzzy, amphipathic interfacial region formed by the tightly packed headgroups of the components of the lipid bilayer. Depending on the nature of the substrates and the location of the site of chemical modification, catalysis may occur in each of these environments. The availability of structural information for alpha-helical enzyme families from each of these classes, as well as several beta-barrel enzymes from the bacterial outer membrane, has allowed us to review here the different ways in which each enzyme fold has adapted to the nature of the substrates, products, and the unique environment of the membrane. Our focus here is on enzymes that process lipidic substrates. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.
Evolution of thorax architecture in ant castes highlights trade-off between flight and ground behaviors.

PubMed

Keller, Roberto A; Peeters, Christian; Beldade, Patrícia

2014-01-01

The concerted evolution of morphological and behavioral specializations has compelling examples in ant castes. Unique to ants is a marked divergence between winged queens and wingless workers, but morphological specializations for behaviors on the ground have been overlooked. We analyzed thorax morphology of queens and workers in species from 21 of the 25 ant subfamilies. We uncovered unique skeletomuscular modifications in workers that presumably increase power and flexibility of head-thorax articulation, emphasizing that workers are not simply wingless versions of queens. We also identified two distinct types of queens and showed repeated evolutionary associations with strategies of colony foundation. Solitary founding queens that hunt have a more worker-like thorax. Our results reveal that ants invest in the relative size of thorax segments according to their tasks. Versatility of head movements allows for better manipulation of food and objects, which arguably contributed to the ants' ecological and evolutionary success. DOI: http://dx.doi.org/10.7554/eLife.01539.001.
Protein synthesis in geostimulated root caps

NASA Technical Reports Server (NTRS)

Feldman, L. J.

1982-01-01

A study is presented of the processes occurring in the root cap of corn which are requisite for the formation of root cap inhibitor and which can be triggered or modulated by both light and gravity. The results of this study indicate the importance of protein synthesis for light-induced gravitropic bending in roots. Root caps in which protein synthesis is prevented are unable to induce downward bending. This suggests that light acts by stimulating proteins which are necessary for the translation of the gravitropic stimulus into a growth response (downward bending). The turnover of protein with time was also examined in order to determine whether light acts by stimulating the synthesis of unique proteins required for downward growth. It is found that auxin in combination with light allows for the translation of the gravitropic stimulus into a growth response at least in part through the modification of protein synthesis. It is concluded that unique proteins are stimulated by light and are involved in promoting the downward growth in roots which are responding to gravity.
A neuronal morphologic type unique to humans and great apes

PubMed Central

Nimchinsky, Esther A.; Gilissen, Emmanuel; Allman, John M.; Perl, Daniel P.; Erwin, Joseph M.; Hof, Patrick R.

1999-01-01

We report the existence and distribution of an unusual type of projection neuron, a large, spindle-shaped cell, in layer Vb of the anterior cingulate cortex of pongids and hominids. These spindle cells were not observed in any other primate species or any other mammalian taxa, and their volume was correlated with brain volume residuals, a measure of encephalization in higher primates. These observations are of particular interest when considering primate neocortical evolution, as they reveal possible adaptive changes and functional modifications over the last 15–20 million years in the anterior cingulate cortex, a region that plays a major role in the regulation of many aspects of autonomic function and of certain cognitive processes. That in humans these unique neurons have been shown previously to be severely affected in the degenerative process of Alzheimer’s disease suggests that some of the differential neuronal susceptibility that occurs in the human brain in the course of age-related dementing illnesses may have appeared only recently during primate evolution. PMID:10220455
CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.

PubMed

Zhang, Zijun; Xing, Yi

2017-09-19

Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation. CLAM recovered a large number of novel RNA regulatory sites inaccessible by uniquely mapped reads. The functional significance of these sites was demonstrated by consensus motif patterns and association with alternative splicing (splicing factors), transcript abundance (AGO2) and mRNA half-life (m6A). CLAM provides a useful tool to discover novel protein-RNA interactions and RNA modification sites from CLIP-seq and RIP-seq data, and reveals the significant contribution of repetitive elements to the RNA regulatory landscape of the human transcriptome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
What Indigenous Australian clients value about primary health care: a systematic review of qualitative evidence.

PubMed

Gomersall, Judith Streak; Gibson, Odette; Dwyer, Judith; O'Donnell, Kim; Stephenson, Matthew; Carter, Drew; Canuto, Kootsy; Munn, Zachary; Aromataris, Edoardo; Brown, Alex

2017-08-01

To synthesise client perceptions of the unique characteristics and value of care provided in Aboriginal Community Controlled Health Organisations (ACCHOs) compared to mainstream/general practitioner services, and implications for improving access to quality, appropriate primary health care for Indigenous Australians. Standardised systematic review methods with modification informed by ethical and methodological considerations in research involving Indigenous Australians. Perceived unique valued characteristics of ACCHOs were: 1) accessibility, facilitated by ACCHOs welcoming social spaces and additional services; 2) culturally safe care; and 3) appropriate care, responsive to holistic needs. Provider-client relationships characterised by shared understanding of clients' needs, Indigenous staff, and relationships between clients who share the same culture, are central to ACCHO clients' perceptions of ACCHOs' unique value. The client perceptions provide insights about how ACCHOs address socio-economic factors that contribute to high levels of chronic disease in Indigenous communities, why mainstream PHC provider care cannot substitute for ACCHO care, and how to improve accessibility and quality of care in mainstream providers. Implications for public health: To increase utilisation of PHC services in Indigenous Australian communities, and help close the gaps between the health status of Indigenous and non-Indigenous Australians, Indigenous community leaders and Australian governments should prioritise implementing effective initiatives to support quality health care provision by ACCHOs. © 2017 The Authors.

YopJ Family Effectors Promote Bacterial Infection through a Unique Acetyltransferase Activity.

PubMed

Ma, Ka-Wai; Ma, Wenbo

2016-12-01

Gram-negative bacterial pathogens rely on the type III secretion system to inject virulence proteins into host cells. These type III secreted "effector" proteins directly manipulate cellular processes to cause disease. Although the effector repertoires in different bacterial species are highly variable, the Yersinia outer protein J (YopJ) effector family is unique in that its members are produced by diverse animal and plant pathogens as well as a nonpathogenic microsymbiont. All YopJ family effectors share a conserved catalytic triad that is identical to that of the C55 family of cysteine proteases. However, an accumulating body of evidence demonstrates that many YopJ effectors modify their target proteins in hosts by acetylating specific serine, threonine, and/or lysine residues. This unique acetyltransferase activity allows the YopJ family effectors to affect the function and/or stability of their targets, thereby dampening innate immunity. Here, we summarize the current understanding of this prevalent and evolutionarily conserved type III effector family by describing their enzymatic activities and virulence functions in animals and plants. In particular, the molecular mechanisms by which representative YopJ family effectors subvert host immunity through posttranslational modification of their target proteins are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Structure-Function, Stability, and Chemical Modification of the Cyanobacterial Cytochrome b6f Complex from Nostoc sp. PCC 7120*

PubMed Central

Baniulis, Danas; Yamashita, Eiki; Whitelegge, Julian P.; Zatsman, Anna I.; Hendrich, Michael P.; Hasan, S. Saif; Ryan, Christopher M.; Cramer, William A.

2009-01-01

The crystal structure of the cyanobacterial cytochrome b6f complex has previously been solved to 3.0-Å resolution using the thermophilic Mastigocladus laminosus whose genome has not been sequenced. Several unicellular cyanobacteria, whose genomes have been sequenced and are tractable for mutagenesis, do not yield b6f complex in an intact dimeric state with significant electron transport activity. The genome of Nostoc sp. PCC 7120 has been sequenced and is closer phylogenetically to M. laminosus than are unicellular cyanobacteria. The amino acid sequences of the large core subunits and four small peripheral subunits of Nostoc are 88 and 80% identical to those in the M. laminosus b6f complex. Purified b6f complex from Nostoc has a stable dimeric structure, eight subunits with masses similar to those of M. laminosus, and comparable electron transport activity. The crystal structure of the native b6f complex, determined to a resolution of 3.0Å (PDB id: 2ZT9), is almost identical to that of M. laminosus. Two unique aspects of the Nostoc complex are: (i) a dominant conformation of heme bp that is rotated 180° about the α- and γ-meso carbon axis relative to the orientation in the M. laminosus complex and (ii) acetylation of the Rieske iron-sulfur protein (PetC) at the N terminus, a post-translational modification unprecedented in cyanobacterial membrane and electron transport proteins, and in polypeptides of cytochrome bc complexes from any source. The high spin electronic character of the unique heme cn is similar to that previously found in the b6f complex from other sources. PMID:19189962
Structure of aryl O -demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohler, Amanda C.; Mills, Matthew J. L.; Adams, Paul D.

Some strains of soil and marine bacteria have evolved intricate metabolic pathways for using environmentally derived aromatics as a carbon source. Many of these metabolic pathways go through intermediates such as vanillate, 3-O-methylgallate, and syringate. Demethylation of these compounds is essential for downstream aryl modification, ring opening, and subsequent assimilation of these compounds into the tricarboxylic acid (TCA) cycle, and, correspondingly, there are a variety of associated aryl demethylase systems that vary in complexity. Intriguingly, only a basic understanding of the least complex system, the tetrahydrofolate-dependent aryl demethylase LigM from Sphingomonas paucimobilis, a bacterial strain that metabolizes lignin-derived aromatics, wasmore » previously available. LigM-catalyzed demethylation enables further modification and rin g opening of the single-ring aromatics vanillate and 3-Omethylgallate, which are common byproducts of biofuel production. We characterize aryl O-demethylation by LigM and report its 1.81-Å crystal structure, revealing a unique demethylase fold and a canonical folate-binding domain. Structural homology and geometry optimization calculations enabled the identification of LigM's tetrahydrofolate-binding site and protein-folate interactions. Computationally guided mutagenesis and kinetic analyses allowed the identification of the enzyme's aryl-binding site location and determination of its unique, catalytic tyrosine-dependent reaction mechanism. This work defines LigM as a distinct demethylase, both structurally and functionally, and provides insight into demethylation and its reaction requirements. Our results afford the mechanistic details required for efficient utilization of LigM as a tool for aryl O-demethylation and as a component of synthetic biology efforts to valorize previously underused aromatic compounds.« less
Structure of aryl O -demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism

DOE PAGES

Kohler, Amanda C.; Mills, Matthew J. L.; Adams, Paul D.; ...

2017-04-03

Some strains of soil and marine bacteria have evolved intricate metabolic pathways for using environmentally derived aromatics as a carbon source. Many of these metabolic pathways go through intermediates such as vanillate, 3-O-methylgallate, and syringate. Demethylation of these compounds is essential for downstream aryl modification, ring opening, and subsequent assimilation of these compounds into the tricarboxylic acid (TCA) cycle, and, correspondingly, there are a variety of associated aryl demethylase systems that vary in complexity. Intriguingly, only a basic understanding of the least complex system, the tetrahydrofolate-dependent aryl demethylase LigM from Sphingomonas paucimobilis, a bacterial strain that metabolizes lignin-derived aromatics, wasmore » previously available. LigM-catalyzed demethylation enables further modification and rin g opening of the single-ring aromatics vanillate and 3-Omethylgallate, which are common byproducts of biofuel production. We characterize aryl O-demethylation by LigM and report its 1.81-Å crystal structure, revealing a unique demethylase fold and a canonical folate-binding domain. Structural homology and geometry optimization calculations enabled the identification of LigM's tetrahydrofolate-binding site and protein-folate interactions. Computationally guided mutagenesis and kinetic analyses allowed the identification of the enzyme's aryl-binding site location and determination of its unique, catalytic tyrosine-dependent reaction mechanism. This work defines LigM as a distinct demethylase, both structurally and functionally, and provides insight into demethylation and its reaction requirements. Our results afford the mechanistic details required for efficient utilization of LigM as a tool for aryl O-demethylation and as a component of synthetic biology efforts to valorize previously underused aromatic compounds.« less
Extracellular Matrix Remodeling: The Common Denominator in Connective Tissue DiseasesPossibilities for Evaluation and Current Understanding of the Matrix as More Than a Passive Architecture, but a Key Player in Tissue Failure

PubMed Central

Nielsen, Mette J.; Sand, Jannie M.; Henriksen, Kim; Genovese, Federica; Bay-Jensen, Anne-Christine; Smith, Victoria; Adamkewicz, Joanne I.; Christiansen, Claus; Leeming, Diana J.

2013-01-01

Abstract Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive tissue remodeling leading to tissue stiffness, as well as by changes in the signaling potential of both intact matrix and fragments thereof. Although tissue structure until recently was viewed as a simple architecture anchoring cells and proteins, this complex grid may contain essential information enabling the maintenance of the structure and normal functioning of tissue. The aims of this review are to (1) discuss the structural components of the matrix and the relevance of their mutations to the pathology of diseases such as fibrosis and cancer, (2) introduce the possibility that post-translational modifications (PTMs), such as protease cleavage, citrullination, cross-linking, nitrosylation, glycosylation, and isomerization, generated during pathology, may be unique, disease-specific biochemical markers, (3) list and review the range of simple enzyme-linked immunosorbent assays (ELISAs) that have been developed for assessing the extracellular matrix (ECM) and detecting abnormal ECM remodeling, and (4) discuss whether some PTMs are the cause or consequence of disease. New evidence clearly suggests that the ECM at some point in the pathogenesis becomes a driver of disease. These pathological modified ECM proteins may allow insights into complicated pathologies in which the end stage is excessive tissue remodeling, and provide unique and more pathology-specific biochemical markers. PMID:23046407
Genomic characterization of a Helicobacter pylori isolate from a patient with gastric cancer in China

PubMed Central

2014-01-01

Background Helicobacter pylori is well known for its relationship with the occurrence of several severe gastric diseases. The mechanisms of pathogenesis triggered by H. pylori are less well known. In this study, we report the genome sequence and genomic characterizations of H. pylori strain HLJ039 that was isolated from a patient with gastric cancer in the Chinese province of Heilongjiang, where there is a high incidence of gastric cancer. To investigate potential genomic features that may be involved in pathogenesis of carcinoma, the genome was compared to three previously sequenced genomes in this area. Result We obtained 42 contigs with a total length of 1,611,192 bp and predicted 1,687 coding sequences. Compared to strains isolated from gastritis and ulcers in this area, 10 different regions were identified as being unique for HLJ039; they mainly encoded type II restriction-modification enzyme, type II m6A methylase, DNA-cytosine methyltransferase, DNA methylase, and hypothetical proteins. A unique 547-bp fragment sharing 93% identity with a hypothetical protein of Helicobacter cinaedi ATCC BAA-847 was not present in any other previous H. pylori strains. Phylogenetic analysis based on core genome single nucleotide polymorphisms shows that HLJ039 is defined as hspEAsia subgroup, which belongs to the hpEastAsia group. Conclusion DNA methylations, variations of the genomic regions involved in restriction and modification systems, are the “hot” regions that may be related to the mechanism of H. pylori-induced gastric cancer. The genome sequence will provide useful information for the deep mining of potential mechanisms related to East Asian gastric cancer. PMID:24565107
Structure-Function, Stability, and Chemical Modification of the Cyanobacterial Cytochrome b[subscript 6]f Complex from Nostoc sp. PCC 7120

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baniulis, Danas; Yamashita, Eiki; Whitelegge, Julian P.

2009-06-08

The crystal structure of the cyanobacterial cytochrome b{sub 6}f complex has previously been solved to 3.0-{angstrom} resolution using the thermophilic Mastigocladus laminosus whose genome has not been sequenced. Several unicellular cyanobacteria, whose genomes have been sequenced and are tractable for mutagenesis, do not yield b{sub 6}f complex in an intact dimeric state with significant electron transport activity. The genome of Nostoc sp. PCC 7120 has been sequenced and is closer phylogenetically to M. laminosus than are unicellular cyanobacteria. The amino acid sequences of the large core subunits and four small peripheral subunits of Nostoc are 88 and 80% identical tomore » those in the M. laminosus b{sub 6}f complex. Purified b{sub 6}f complex from Nostoc has a stable dimeric structure, eight subunits with masses similar to those of M. laminosus, and comparable electron transport activity. The crystal structure of the native b{sub 6}f complex, determined to a resolution of 3.0{angstrom} (PDB id: 2ZT9), is almost identical to that of M. laminosus. Two unique aspects of the Nostoc complex are: (i) a dominant conformation of heme b{sub p} that is rotated 180 deg. about the {alpha}- and {gamma}-meso carbon axis relative to the orientation in the M. laminosus complex and (ii) acetylation of the Rieske iron-sulfur protein (PetC) at the N terminus, a post-translational modification unprecedented in cyanobacterial membrane and electron transport proteins, and in polypeptides of cytochrome bc complexes from any source. The high spin electronic character of the unique heme cn is similar to that previously found in the b{sub 6}f complex from other sources.« less
Chromatin configuration and epigenetic landscape at the sex chromosome bivalent during equine spermatogenesis

PubMed Central

Baumann, Claudia; Daly, Christopher M.; McDonnell, Sue M.; Viveiros, Maria M.; De La Fuente, Rabindranath

2011-01-01

Pairing of the sex chromosomes during mammalian meiosis is characterized by the formation of a unique heterochromatin structure at the XY body. The mechanisms underlying the formation of this nuclear domain are reportedly highly conserved from marsupials to mammals. In this study, we demonstrate that in contrast to all eutherian species studied to date, partial synapsis of the heterologous sex chromosomes during pachytene stage in the horse is not associated with the formation of a typical macrochromatin domain at the XY body. While phosphorylated histone H2AX (γH2AX) and macroH2A1.2 are present as a diffuse signal over the entire macrochromatin domain in mouse pachytene spermatocytes, γH2AX, macroH2A1.2, and the cohesin subunit SMC3 are preferentially enriched at meiotic sex chromosome cores in equine spermatocytes. Moreover, although several histone modifications associated with this nuclear domain in the mouse such as H3K4me2 and ubH2A are conspicuously absent in the equine XY body, prominent RNA polymerase II foci persist at the sex chromosomes. Thus, the localization of key marker proteins and histone modifications associated with the XY body in the horse differs significantly from all other mammalian systems described. These results demonstrate that the epigenetic landscape and heterochromatinization of the equine XY body might be regulated by alternative mechanisms and that some features of XY body formation may be evolutionary divergent in the domestic horse. We propose equine spermatogenesis as a unique model system for the study of the regulatory networks leading to the epigenetic control of gene expression during XY body formation. PMID:21274552
redox Signaling by 8-nitro-cyclic guanosine monophosphate: nitric oxide- and reactive oxygen species-derived electrophilic messenger.

PubMed

Fujii, Shigemoto; Akaike, Takaaki

2013-10-10

Emerging evidence has revealed that nitric oxide (NO)- and reactive oxygen species (ROS)-derived electrophiles formed in cells mediate signal transduction for responses to oxidative stress. The cyclic nucleotide with a nitrated guanine moiety-8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)-first identified in 2007 as a second messenger for NO and ROS-has certain unique properties that its parental cGMP lacks. For example, it can react with particular protein Cys thiols because of its electrophilicity and can cause unique post-translational modifications of redox-sensor proteins such as Keap1 and H-Ras. Site-specific S-guanylation of Keap1 at Cys434 induced NO- and ROS-mediated adaptive responses to oxidative stress. H-Ras Cys184 S-guanylation was recently found to be involved in activation of mitogen-activated protein kinase cascades as manifested by cellular senescence and heart failure in mouse cardiac hypertrophy models. The latest finding related to the concept of electrophile-based redox signaling is a potent regulatory function of endogenously produced hydrogen sulfide for redox signaling via 8-nitro-cGMP. Electrophile modification of 8-nitro-cGMP, as a second messenger for NO and ROS, by hydrogen sulfide (i.e., electrophile sulfhydration) can most likely effect physiological regulation of cellular redox signaling. Continued investigation of the precise function of cellular hydrogen sulfide that may control electrophile-dependent redox cellular signaling, most typically via 8-nitro-cGMP formation, may provide novel insights into the molecular mechanisms of oxidative stress responses, oxidative stress-related pathology and disease control, and development of therapeutics for various diseases.
Journal article reporting standards for quantitative research in psychology: The APA Publications and Communications Board task force report.

PubMed

Appelbaum, Mark; Cooper, Harris; Kline, Rex B; Mayo-Wilson, Evan; Nezu, Arthur M; Rao, Stephen M

2018-01-01

Following a review of extant reporting standards for scientific publication, and reviewing 10 years of experience since publication of the first set of reporting standards by the American Psychological Association (APA; APA Publications and Communications Board Working Group on Journal Article Reporting Standards, 2008), the APA Working Group on Quantitative Research Reporting Standards recommended some modifications to the original standards. Examples of modifications include division of hypotheses, analyses, and conclusions into 3 groupings (primary, secondary, and exploratory) and some changes to the section on meta-analysis. Several new modules are included that report standards for observational studies, clinical trials, longitudinal studies, replication studies, and N-of-1 studies. In addition, standards for analytic methods with unique characteristics and output (structural equation modeling and Bayesian analysis) are included. These proposals were accepted by the Publications and Communications Board of APA and supersede the standards included in the 6th edition of the Publication Manual of the American Psychological Association (APA, 2010). (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Ultrafast surface modification of Ni3S2 nanosheet arrays with Ni-Mn bimetallic hydroxides for high-performance supercapacitors.

PubMed

Zou, Xu; Sun, Qing; Zhang, Yuxin; Li, Guo-Dong; Liu, Yipu; Wu, Yuanyuan; Yang, Lan; Zou, Xiaoxin

2018-03-14

Amorphous Ni-Mn bimetallic hydroxide film on the three-dimensional nickle foam (NF)-supported conductive Ni 3 S 2 nanosheets (denoted as Ni-Mn-OH@Ni 3 S 2 /NF) is successfully synthesized by an ultrafast process (5 s). The fascinating structural characteristic endows Ni-Mn-OH@Ni 3 S 2 /NF electrodes better electrochemical performance. The specific capacitance of 2233.3 F g -1 at a current density of 15 A g -1 can achieve high current density charge and discharge at 20/30 A g -1 that the corresponding capacitance is 1529.16 and 1350 F g -1 , respectively. As well as good cycling performance after 1000 cycles can maintain 72% at 15 A g -1 . The excellent performance can be attributed to unique surface modification nanostructures and the synergistic effect of the bimetallic hydroxide film. The impressive results provide new opportunity to produce advanced electrode materials by simple and green route and this material is expected to apply in high energy density storage systems.
Highly Modified Cellulose Nanocrystals and Formation of Epoxy-CNC Nanocomposites.

PubMed

Abraham, Eldho; Kam, Doron; Nevo, Yuval; Slattegard, Rikard; Rivkin, Amit; Lapidot, Shaul; Shoseyov, Oded

2016-10-05

This work presents an environmentally friendly, iodine-catalysed chemical modification method to generate highly hydrophobic, optically active cellulose nanocrystals (CNC). The high degree of ester substitution (DS=2.18), hydrophobicity, crystalline behaviour and optical activity of the generated acetylated CNC (Ac-CNC) were quantified by TEM, FTIR, solid 13C NMR, contact angle, XRD and POM analyses. Ac-CNC possessing substantial enhancement in thermal stability (16.8%) and forms thin films with interlayer distance of 50-150 nm, presenting cavities suitable for entrapping nano and micro particles. Generated Ac-CNC proved as an effective reinforcing agent in hydrophobic polymer matrices for fabricating high performance nanocomposites. When integrated at a very low weight percentage (0.5%) in an epoxy matrix, Ac-CNC provided for a 73% increase in tensile strength and a 98% increase in modulus, demonstrating its remarkable reinforcing potential and effective stress transfer behaviour. The method of modification and the unique properties of the modified CNC (hydrophobicity, crystallinity, reinforcing ability and optical activity) render them a novel bionanomaterial for a range of multipurpose applications.
Synthesis and Modification of Holey Graphene for Energy Storage

NASA Technical Reports Server (NTRS)

Lin, Yi; Kim, Jae-Woo; Connell, John W.

2015-01-01

Porous graphene materials have recently drawn significant interest for energy storage applications due to the effective use of the graphitic surface area provided by the pores. Holey graphene is a type of porous graphene with pores in the form of physical through thickness holes. This type of porous graphene provides a unique morphology that allows for effective transport of molecular species through the graphene plane. Therefore, as we recently demonstrated, holey graphene could be advantageous in the preparation of electrodes in supercapacitors with high volumetric performance.1 We have developed methodologies to scalably prepare holey graphene materials with or without the use of catalysts (Figure 1).1,2 In this presentation, we will discuss the choice of synthetic strategies and experimental conditions on the morphology and physical properties of holey graphene (Figure 2) and the effect on their electrochemical properties. We will also present the results on the further modification of holey graphene to study their physical and chemical properties, especially with regard to the stability and chemical reactivity of carbons located around the edges of the holes.
Statistically qualified neuro-analytic failure detection method and system

DOEpatents

Vilim, Richard B.; Garcia, Humberto E.; Chen, Frederick W.

2002-03-02

An apparatus and method for monitoring a process involve development and application of a statistically qualified neuro-analytic (SQNA) model to accurately and reliably identify process change. The development of the SQNA model is accomplished in two stages: deterministic model adaption and stochastic model modification of the deterministic model adaptation. Deterministic model adaption involves formulating an analytic model of the process representing known process characteristics, augmenting the analytic model with a neural network that captures unknown process characteristics, and training the resulting neuro-analytic model by adjusting the neural network weights according to a unique scaled equation error minimization technique. Stochastic model modification involves qualifying any remaining uncertainty in the trained neuro-analytic model by formulating a likelihood function, given an error propagation equation, for computing the probability that the neuro-analytic model generates measured process output. Preferably, the developed SQNA model is validated using known sequential probability ratio tests and applied to the process as an on-line monitoring system. Illustrative of the method and apparatus, the method is applied to a peristaltic pump system.
Human-specific features of spatial gene expression and regulation in eight brain regions.

PubMed

Xu, Chuan; Li, Qian; Efimova, Olga; He, Liu; Tatsumoto, Shoji; Stepanova, Vita; Oishi, Takao; Udono, Toshifumi; Yamaguchi, Katsushi; Shigenobu, Shuji; Kakita, Akiyoshi; Nawa, Hiroyuki; Khaitovich, Philipp; Go, Yasuhiro

2018-06-13

Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1,851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, while the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species. Published by Cold Spring Harbor Laboratory Press.
Oxidized Base Damage and Single-Strand Break Repair in Mammalian Genomes: Role of Disordered Regions and Posttranslational Modifications in Early Enzymes

PubMed Central

Hegde, Muralidhar L.; Izumi, Tadahide; Mitra, Sankar

2012-01-01

Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/ SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed. PMID:22749145
The SR-71 Test Bed Aircraft: A Facility for High-Speed Flight Research

NASA Technical Reports Server (NTRS)

Corda, Stephen; Moes, Timothy R.; Mizukami, Masashi; Hass, Neal E.; Jones, Daniel; Monaghan, Richard C.; Ray, Ronald J.; Jarvis, Michele L.; Palumbo, Nathan

2000-01-01

The SR-71 test bed aircraft is shown to be a unique platform to flight-test large experiments to supersonic Mach numbers. The test bed hardware mounted on the SR-71 upper fuselage is described. This test bed hardware is composed of a fairing structure called the "canoe" and a large "reflection plane" flat plate for mounting experiments. Total experiment weights, including the canoe and reflection plane, as heavy as 14,500 lb can be mounted on the aircraft and flight-tested to speeds as fast as Mach 3.2 and altitudes as high as 80,000 ft. A brief description of the SR-71 aircraft is given, including details of the structural modifications to the fuselage, modifications to the J58 engines to provide increased thrust, and the addition of a research instrumentation system. Information is presented based on flight data that describes the SR-71 test bed aerodynamics, stability and control, structural and thermal loads, the canoe internal environment, and reflection plane flow quality. Guidelines for designing SR-71 test bed experiments are also provided.
Low-rate image coding using vector quantization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makur, A.

1990-01-01

This thesis deals with the development and analysis of a computationally simple vector quantization image compression system for coding monochrome images at low bit rate. Vector quantization has been known to be an effective compression scheme when a low bit rate is desirable, but the intensive computation required in a vector quantization encoder has been a handicap in using it for low rate image coding. The present work shows that, without substantially increasing the coder complexity, it is indeed possible to achieve acceptable picture quality while attaining a high compression ratio. Several modifications to the conventional vector quantization coder aremore » proposed in the thesis. These modifications are shown to offer better subjective quality when compared to the basic coder. Distributed blocks are used instead of spatial blocks to construct the input vectors. A class of input-dependent weighted distortion functions is used to incorporate psychovisual characteristics in the distortion measure. Computationally simple filtering techniques are applied to further improve the decoded image quality. Finally, unique designs of the vector quantization coder using electronic neural networks are described, so that the coding delay is reduced considerably.« less
Micro-masonry for 3D Additive Micromanufacturing

PubMed Central

Keum, Hohyun; Kim, Seok

2014-01-01

Transfer printing is a method to transfer solid micro/nanoscale materials (herein called ‘inks’) from a substrate where they are generated to a different substrate by utilizing elastomeric stamps. Transfer printing enables the integration of heterogeneous materials to fabricate unexampled structures or functional systems that are found in recent advanced devices such as flexible and stretchable solar cells and LED arrays. While transfer printing exhibits unique features in material assembly capability, the use of adhesive layers or the surface modification such as deposition of self-assembled monolayer (SAM) on substrates for enhancing printing processes hinders its wide adaptation in microassembly of microelectromechanical system (MEMS) structures and devices. To overcome this shortcoming, we developed an advanced mode of transfer printing which deterministically assembles individual microscale objects solely through controlling surface contact area without any surface alteration. The absence of an adhesive layer or other modification and the subsequent material bonding processes ensure not only mechanical bonding, but also thermal and electrical connection between assembled materials, which further opens various applications in adaptation in building unusual MEMS devices. PMID:25146178
A direct, ratiometric, and quantitative MALDI–MS assay for protein methyltransferases and acetyltransferases

PubMed Central

Richardson, Stacie L.; Hanjra, Pahul; Zhang, Gang; Mackie, Brianna D.; Peterson, Darrell L.; Huang, Rong

2016-01-01

Protein methylation and acetylation play important roles in biological processes, and misregulation of these modifications is involved in various diseases. Therefore, it is critical to understand the activities of the enzymes responsible for these modifications. Herein we describe a sensitive method for ratiometric quantification of methylated and acetylated peptides via MALDI-MS by direct spotting of enzymatic methylation and acetylation reaction mixtures without tedious purification procedures. The quantifiable detection limit for peptides with our method is approximately 10 fmol. This is achieved by increasing the signal-to-noise ratio through the addition of NH4H2PO4 to the matrix solution and reduction of the matrix α-cyanohydroxycinnamic acid concentration to 2 mg/ml. We have demonstrated the application of this method in enzyme kinetic analysis and inhibition studies. The unique feature of this method is the simultaneous quantification of multiple peptide species for investigation of processivity mechanisms. Its wide buffer compatibility makes it possible to be adapted to investigate the activity of any protein methyltransferase or acetyltransferase. PMID:25778392

A novel intranuclear RNA vector system for long-term stem cell modification

PubMed Central

Ikeda, Yasuhiro; Makino, Akiko; Matchett, William E.; Holditch, Sara J.; Lu, Brian; Dietz, Allan B.; Tomonaga, Keizo

2015-01-01

Genetically modified stem and progenitor cells have emerged as a promising regenerative platform in the treatment of genetic and degenerative disorders, highlighted by their successful therapeutic use in inherent immunodeficiencies. However, biosafety concerns over insertional mutagenesis resulting from integrating recombinant viral vectors have overshadowed the widespread clinical applications of genetically modified stem cells. Here, we report an RNA-based episomal vector system, amenable for long-term transgene expression in stem cells. Specifically, we used a unique intranuclear RNA virus, Borna disease virus (BDV), as the gene transfer vehicle, capable of persistent infections in various cell types. BDV-based vectors allowed for long-term transgene expression in mesenchymal stem cells (MSCs) without affecting cellular morphology, cell surface CD105 expression, or the adipogenicity of MSCs. Similarly, replication-defective BDV vectors achieved long-term transduction of human induced pluripotent stem cells (iPSCs), while maintaining the ability to differentiate into three embryonic germ layers. Thus, the BDV-based vectors offer a genomic modification-free, episomal RNA delivery system for sustained stem cell transduction. PMID:26632671
Epigenetic legacy of parental experiences: Dynamic and interactive pathways to inheritance.

PubMed

Champagne, Frances A

2016-11-01

The quality of the environment experienced by an individual across his or her lifespan can result in a unique developmental trajectory with consequences for adult phenotype and reproductive success. However, it is also evident that these experiences can impact the development of offspring with continued effect on subsequent generations. Epigenetic mechanisms have been proposed as a mediator of both these within- and across-generation effects, and there is increasing evidence to support the role of environmentally induced changes in DNA methylation, posttranslational histone modifications, and noncoding RNAs in predicting these outcomes. Advances in our understanding of these molecular modifications contribute to increasingly nuanced perspectives on plasticity and transmission of phenotypes across generations. A challenge that emerges from this research is in how we integrate these "new" perspectives with traditional views of development, reproduction, and inheritance. This paper will highlight evidence suggestive of an epigenetic impact of the environment on mothers, fathers, and their offspring, and illustrate the importance of considering the dynamic nature of reproduction and development and inclusive views of inheritance within the evolving field of behavioral and environmental epigenetics.
Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori.

PubMed

Lehours, Philippe; Dupouy, Sandrine; Chaineux, Julien; Ruskoné-Fourmestraux, Agnès; Delchier, Jean-Charles; Morgner, Andrea; Mégraud, Francis; Ménard, Armelle

2007-04-01

Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.
Disulfide bonds in ER protein folding and homeostasis

PubMed Central

Feige, Matthias J.; Hendershot, Linda M.

2010-01-01

Proteins that are expressed outside the cell must be synthesized, folded and assembled in a way that ensures they can function in their designate location. Accordingly these proteins are primarily synthesized in the endoplasmic reticulum (ER), which has developed a chemical environment more similar to that outside the cell. This organelle is equipped with a variety of molecular chaperones and folding enzymes that both assist the folding process, while at the same time exerting tight quality control measures that are largely absent outside the cell. A major post-translational modification of ER-synthesized proteins is disulfide bridge formation, which is catalyzed by the family of protein disulfide isomerases. As this covalent modification provides unique structural advantages to extracellular proteins, multiple pathways to their formation have evolved. However, the advantages that disulfide bonds impart to these proteins come at a high cost to the cell. Very recent reports have shed light on how the cell can deal with or even exploit the side reactions of disulfide bond formation to maintain homeostasis of the ER and its folding machinery. PMID:21144725
Progressing from initially ambiguous functional analyses: three case examples.

PubMed

Tiger, Jeffrey H; Fisher, Wayne W; Toussaint, Karen A; Kodak, Tiffany

2009-01-01

Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman [Iwata, B. A., Dorsey, M. F., Slifer, K. J., Bauman, K. E., & Richman, G. S. (1994). Toward a functional analysis of self-injury. Journal of Applied Behavior Analysis, 27, 197-209 (Reprinted from Analysis and Intervention in Developmental Disabilities, 2, 3-20, 1982)]. These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments.
O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling.

PubMed

Shi, Jianhua; Gu, Jin-hua; Dai, Chun-ling; Gu, Jianlan; Jin, Xiaoxia; Sun, Jianming; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

2015-09-28

Apoptosis plays an important role in neural development and neurological disorders. In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. O-GlcNAcylation-induced apoptosis was attenuated by over-expression of AKT. We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. The elevation of O-GlcNAcylation coincided with activation of cell apoptosis. Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling.
Biosynthesis of Nucleoside Diphosphoramidates in Campylobacter jejuni.

PubMed

Taylor, Zane W; Brown, Haley A; Holden, Hazel M; Raushel, Frank M

2017-11-21

Campylobacter jejuni is a pathogenic Gram-negative bacterium and a leading cause of food-borne gastroenteritis. C. jejuni produces a capsular polysaccharide (CPS) that contains a unique O-methyl phosphoramidate modification (MeOPN). Recently, the first step in the biosynthetic pathway for the assembly of the MeOPN modification to the CPS was elucidated. It was shown that the enzyme Cj1418 catalyzes the phosphorylation of the amide nitrogen of l-glutamine to form l-glutamine phosphate. In this investigation, the metabolic fate of l-glutamine phosphate was determined. The enzyme Cj1416 catalyzes the displacement of pyrophosphate from MgCTP by l-glutamine phosphate to form CDP-l-glutamine. The enzyme Cj1417 subsequently catalyzes the hydrolysis of CDP-l-glutamine to generate cytidine diphosphoramidate and l-glutamate. The structures of the two novel intermediates, CDP-l-glutamine and cytidine diphosphoramidate, were confirmed by 31 P nuclear magnetic resonance spectroscopy and mass spectrometry. It is proposed that the enzyme Cj1416 be named CTP:phosphoglutamine cytidylyltransferase and that the enzyme Cj1417 be named γ-glutamyl-CDP-amidate hydrolase.
Glycation & Insulin Resistance: Novel Mechanisms and Unique Targets?

PubMed Central

Song, Fei; Schmidt, Ann Marie

2012-01-01

Objectives Multiple biochemical, metabolic and signal transduction pathways contribute to insulin resistance. In this review, we present the evidence that the post-translational process of protein glycation may play role in insulin resistance. The post-translational modifications, the advanced glycation endproducts (AGEs), are formed and accumulate by endogenous and exogenous mechanisms. Methods and Results AGEs may contribute to insulin resistance by a variety of mechanisms, including generation of tumor necrosis factor-alpha, direct modification of the insulin molecule thereby leading to its impaired action, generation of oxidative stress, and impairment of mitochondrial function, as examples. AGEs may stimulate signal transduction via engagement of cellular receptors, such as RAGE, or receptor for AGE. AGE-RAGE interaction perpetuates AGE formation and cellular stress via induction of inflammation, oxidative stress and reduction in the expression and activity of the enzyme, glyoxalase I that detoxifies the AGE precursor, methylglyoxal, or MG. Conclusions Once set in motion, glycation-promoting mechanisms may stimulate ongoing AGE production and target tissue stresses that reduce insulin responsiveness. Strategies to limit AGE accumulation and action may contribute to prevention of insulin resistance and its consequences. PMID:22815341
PEG-Stabilized Core–Shell Surface-Imprinted Nanoparticles

PubMed Central

Moczko, Ewa; Guerreiro, Antonio; Piletska, Elena; Piletsky, Sergey

2016-01-01

Here we present a simple technique to produce target-specific molecularly imprinted polymeric nanoparticles (MIP NPs) and their surface modification in order to prevent the aggregation process that is ever-present in most nanomaterial suspensions/dispersions. Specifically, we studied the influence of surface modification of MIP NPs with polymerizable poly(ethylene glycol) on their degree of stability in water, in phosphate buffer, and in the presence of serum proteins. Grafting a polymer shell on the surface of nanoparticles decreases the surface energy, enhances the polarity, and as a result improves the dispersibility, storage, and colloidal stability as compared to those of core (unmodified) particles. Because of the unique solid-phase approach used for synthesis, the binding sites of MIP NPs are protected during grafting, and the recognition properties of nanoparticles are not affected. These results are significant for developing nanomaterials with selective molecular recognition, increased biocompatibility, and stability in solution. Materials synthesized this way have the potential to be used in a variety of technological fields, including in vivo applications such as drug delivery and imaging. PMID:23855734
Formation of a Crack-Free, Hybrid Skin Layer with Tunable Surface Topography and Improved Gas Permeation Selectivity on Elastomers Using Gel–Liquid Infiltration Polymerization

DOE PAGES

Wang, Mengyuan; Gorham, Justin M.; Killgore, Jason P.; ...

2017-07-31

Surface modifications of elastomers and gels are crucial for emerging applications such as soft robotics and flexible electronics, in large part because they provide a platform to control wettability, adhesion, and permeability. Current surface modification methods via ultraviolet-ozone (UVO) and/or O2 plasma, atomic layer deposition (ALD), plasmas deposition, and chemical treatment impart a dense polymer or inorganic layer on the surface that is brittle and easy to fracture at low strain levels. This paper presents a new method, based on gel–liquid infiltration polymerization, to form hybrid skin layers atop elastomers. The method is unique in that it allows for controlmore » of the skin layer topography, with tunable feature sizes and aspect ratios as high as 1.8 without fracture. Unlike previous techniques, the skin layer formed here dramatically improves the barrier properties of the elastomer, while preserving skin layer flexibility. Furthermore, the method is versatile and likely applicable to most interfacial polymerization systems and network polymers on flat and patterned surfaces.« less
Formation of a Crack-Free, Hybrid Skin Layer with Tunable Surface Topography and Improved Gas Permeation Selectivity on Elastomers Using Gel–Liquid Infiltration Polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Mengyuan; Gorham, Justin M.; Killgore, Jason P.

Surface modifications of elastomers and gels are crucial for emerging applications such as soft robotics and flexible electronics, in large part because they provide a platform to control wettability, adhesion, and permeability. Current surface modification methods via ultraviolet-ozone (UVO) and/or O2 plasma, atomic layer deposition (ALD), plasmas deposition, and chemical treatment impart a dense polymer or inorganic layer on the surface that is brittle and easy to fracture at low strain levels. This paper presents a new method, based on gel–liquid infiltration polymerization, to form hybrid skin layers atop elastomers. The method is unique in that it allows for controlmore » of the skin layer topography, with tunable feature sizes and aspect ratios as high as 1.8 without fracture. Unlike previous techniques, the skin layer formed here dramatically improves the barrier properties of the elastomer, while preserving skin layer flexibility. Furthermore, the method is versatile and likely applicable to most interfacial polymerization systems and network polymers on flat and patterned surfaces.« less
Differentiating Positional Isomers of Nucleoside Modifications by Higher-Energy Collisional Dissociation Mass Spectrometry (HCD MS)

NASA Astrophysics Data System (ADS)

Jora, Manasses; Burns, Andrew P.; Ross, Robert L.; Lobue, Peter A.; Zhao, Ruoxia; Palumbo, Cody M.; Beal, Peter A.; Addepalli, Balasubrahmanyam; Limbach, Patrick A.

2018-06-01

The analytical identification of positional isomers (e.g., 3-, N 4-, 5-methylcytidine) within the > 160 different post-transcriptional modifications found in RNA can be challenging. Conventional liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) approaches rely on chromatographic separation for accurate identification because the collision-induced dissociation (CID) mass spectra of these isomers nearly exclusively yield identical nucleobase ions (BH2 +) from the same molecular ion (MH+). Here, we have explored higher-energy collisional dissociation (HCD) as an alternative fragmentation technique to generate more informative product ions that can be used to differentiate positional isomers. LC-MS/MS of modified nucleosides characterized using HCD led to the creation of structure- and HCD energy-specific fragmentation patterns that generated unique fingerprints, which can be used to identify individual positional isomers even when they cannot be separated chromatographically. While particularly useful for identifying positional isomers, the fingerprinting capabilities enabled by HCD also offer the potential to generate HPLC-independent spectral libraries for the rapid analysis of modified ribonucleosides. [Figure not available: see fulltext.
Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids.

PubMed

Iyer, Lakshminarayan M; Tahiliani, Mamta; Rao, Anjana; Aravind, L

2009-06-01

Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity of the conventional bases. While a large number of modified bases have been identified, many of the enzymes generating them still remain to be discovered. Recently, members of the 2-oxoglutarate- and iron(II)-dependent dioxygenase super-family, which modify diverse substrates from small molecules to biopolymers, were predicted and subsequently confirmed to catalyze oxidative modification of bases in nucleic acids. Of these, two distinct families, namely the AlkB and the kinetoplastid base J binding proteins (JBP) catalyze in situ hydroxylation of bases in nucleic acids. Using sensitive computational analysis of sequences, structures and contextual information from genomic structure and protein domain architectures, we report five distinct families of 2-oxoglutarate- and iron(II)-dependent dioxygenase that we predict to be involved in nucleic acid modifications. Among the DNA-modifying families, we show that the dioxygenase domains of the kinetoplastid base J-binding proteins belong to a larger family that includes the Tet proteins, prototyped by the human oncogene Tet1, and proteins from basidiomycete fungi, chlorophyte algae, heterolobosean amoeboflagellates and bacteriophages. We present evidence that some of these proteins are likely to be involved in oxidative modification of the 5-methyl group of cytosine leading to the formation of 5-hydroxymethylcytosine. The Tet/JBP homologs from basidiomycete fungi such as Laccaria and Coprinopsis show large lineage-specific expansions and a tight linkage with genes encoding a novel and distinct family of predicted transposases, and a member of the Maelstrom-like HMG family. We propose that these fungal members are part of a mobile transposon. To the best of our knowledge, this is the first report of a eukaryotic transposable element that encodes its own DNA-modification enzyme with a potential regulatory role. Through a wider analysis of other poorly characterized DNA-modifying enzymes we also show that the phage Mu Mom-like proteins, which catalyze the N6-carbamoylmethylation of adenines, are also linked to diverse families of bacterial transposases, suggesting that DNA modification by transposable elements might have a more general presence than previously appreciated. Among the other families of 2-oxoglutarate- and iron(II)-dependent dioxygenases identified in this study, one which is found in algae, is predicted to mainly comprise of RNA-modifying enzymes and shows a striking diversity in protein domain architectures suggesting the presence of RNA modifications with possibly unique adaptive roles. The results presented here are likely to provide the means for future investigation of unexpected epigenetic modifications, such as hydroxymethyl cytosine, that could profoundly impact our understanding of gene regulation and processes such as DNA demethylation.
Scavenging iron: a novel mechanism of plant immunity activation by microbial siderophores.

PubMed

Aznar, Aude; Chen, Nicolas W G; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

2014-04-01

Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H₂O₂ staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity.
Development of high-productivity, strong cation-exchange adsorbers for protein capture by graft polymerization from membranes with different pore sizes

PubMed Central

Chenette, Heather C.S.; Robinson, Julie R.; Hobley, Eboni; Husson, Scott M.

2012-01-01

This paper describes the surface modification of macroporous membranes using ATRP (atom transfer radical polymerization) to create cation-exchange adsorbers with high protein binding capacity at high product throughput. The work is motivated by the need for a more economical and rapid capture step in downstream processing of protein therapeutics. Membranes with three reported nominal pore sizes (0.2, 0.45, 1.0 μm) were modified with poly(3-sulfopropyl methacrylate, potassium salt) tentacles, to create a high density of protein binding sites. A special formulation was used in which the monomer was protected by a crown ether to enable surface-initiated ATRP of this cationic polyelectrolyte. Success with modification was supported by chemical analysis using Fourier-transform infrared spectroscopy and indirectly by measurement of pure water flux as a function of polymerization time. Uniformity of modification within the membranes was visualized with confocal laser scanning microscopy. Static and dynamic binding capacities were measured using lysozyme protein to allow comparisons with reported performance data for commercial cation-exchange materials. Dynamic binding capacities were measured for flow rates ranging from 13 to 109 column volumes (CV)/min. Results show that this unique ATRP formulation can be used to fabricate cation-exchange membrane adsorbers with dynamic binding capacities as high as 70 mg/mL at a throughput of 100 CV/min and unprecedented productivity of 300 mg/mL/min. PMID:23175597
Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

PubMed Central

Aznar, Aude; Chen, Nicolas W.G.; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

2014-01-01

Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H2O2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001
Cancer Chemoprevention by Dietary Polyphenols: Promising Role for Epigenetics

PubMed Central

Link, Alexander; Balaguer, Francesc; Goel, Ajay

2010-01-01

Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans. In this article, we first discuss the contribution of diet and environmental factors on epigenetic alterations; subsequently, we provide a comprehensive review of literature on the role of various dietary polyphenols. In particular, we summarize the current knowledge on a large number of dietary agents and their effects on DNA methylation, histone modifications and regulation of expression of non-coding miRNAs in various in vitro and in vivo models. We emphasize how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopreventive strategies for reducing the health burden of cancer and other diseases in humans. PMID:20599773
Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer's disease.

PubMed

Vu, Hang Thi; Akatsu, Hiroyasu; Hashizume, Yoshio; Setou, Mitsutoshi; Ikegami, Koji

2017-01-09

Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer's disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.
The chemical modification and characterization of polypropylene membrane with environment response by in-situ chlorinating graft copolymerization

NASA Astrophysics Data System (ADS)

Zhang, Yue; Liu, Jiankai; Hu, Wenjie; Feng, Ying; Zhao, Jiruo

2017-08-01

In this study, a novel chemical surface modification method of polyolefin membranes is applied following the in-situ chlorinating graft copolymerization (ISCGC). Polypropylene (PP)/methyl methacrylate (MMA) system was used as an example. A unique structure was formed by the modification process on the original membrane surface and the product exhibited an environmental response. Chlorine free radicals were generated using ultraviolet and heat and were used to capture the hydrogen in the polymer chains on the substrate surface. The formed macromolecular radicals could react with MMA over 2 h to achieve a high coverage ratio polymer on the PP membrane surface. The graft copolymers were characterized using FTIR, 1H-NMR, DSC, and XPS, which all proved the feasibility of chemically modifying the PP membrane surface by ISCGC. The surface morphology of the grafted PP membrane was characterized using SEM and AFM. The results showed that the grafted product presents a uniform, neat, and dense mastoid structure with an average thickness of 4.44 μm, which was expected to be similar to the brush-like surface structure. The contact angle and AFM tests indicated that the product surface is responsive to solvent and pH. The experimental results showed that the PP membrane surface structure can be reconstructed using ISCGC, a method that can be used for environment-responsive polymer materials. Moreover, the product has the characteristics of polymer interfacial brush.
Providing Public Space Continuities in Post-Industrial Areas through Remodelling Land/Water Connections

NASA Astrophysics Data System (ADS)

Burda, Izabela M.; Nyka, Lucyna

2017-10-01

This article examines the problem of urban transformation strategies applied in recent years which are based on the creation of new water areas and modification of existing ones. The research is an attempt to prove that modifications of plans of water areas and forms of their borders may play an important role in achieving the best quality public spaces in post-industrial territories. The basis for demonstrating the importance of modifying water borders, and introducing new forms of water-based structures in cities, are theoretical surveys, comparative studies and in-field analyses. It can be seen that post-industrial areas, which used to create voids in the urban fabric, can be perceived as unique but isolated places that should be integrated into the layout of cities. Thus, creating continuity of public spaces that will relate converted areas to their surroundings is a well-known objective of many transformation strategies. This research proves that an effective strategy toward achieving this goal can be based on the modification of relationships between land and water. Namely, the introduction of new water areas, designing new pieces of land that protrude into the water, softening the boundaries of water lines or the opposite, like structuring smaller water flows into well-defined canals, may significantly contribute to the quality of public spaces. As such, all of this fosters the development of sustainable cities and contributes significantly to the emergence of high-quality urban landscapes.

Science requirements and optimization of the silicon pore optics design for the Athena mirror

NASA Astrophysics Data System (ADS)

Willingale, R.; Pareschi, G.; Christensen, F.; den Herder, J.-W.; Ferreira, D.; Jakobsen, A.; Ackermann, M.; Collon, M.; Bavdaz, M.

2014-07-01

The science requirements for the Athena X-ray mirror are to provide a collecting area of 2 m2 at 1 keV, an angular resolution of ~5 arc seconds half energy eidth (HEW) and a field of view of diameter 40-50 arc minutes. This combination of area and angular resolution over a wide field are possible because of unique features of the Silicon pore optics (SPO) technology used. Here we describe the optimization and modifications of the SPO technology required to achieve the Athena mirror specification and demonstrate how the optical design of the mirror system impacts on the scientific performance of Athena.
Concrescence of permanent maxillary second and third molars: case report of non-surgical root canal treatment.

PubMed

Foran, Denise; Komabayashi, Takashi; Lin, Louis M

2012-03-01

Concrescence is a rare developmental anomaly with an overall incidence of 0.8% in the permanent dentition. While many case reports describe the treatment of concrescence with extraction, there are few reports of non-surgical root canal treatment (NSRCT), due to the atypical root form, canal morphology, and technical difficulties involved in concrescence. This unique case report describes a technical modification of NSRCT that can retain joined posterior maxillary teeth to maintain natural posterior occlusion without surgical intervention or dental implants, thereby avoiding the risk of damage to a large portion of the alveolar bone near the maxillary sinus.
Small is beautiful: features of the smallest insects and limits to miniaturization.

PubMed

Polilov, Alexey A

2015-01-07

Miniaturization leads to considerable reorganization of structures in insects, affecting almost all organs and tissues. In the smallest insects, comparable in size to unicellular organisms, modifications arise not only at the level of organs, but also at the cellular level. Miniaturization is accompanied by allometric changes in many organ systems. The consequences of miniaturization displayed by different insect taxa include both common and unique changes. Because the smallest insects are among the smallest metazoans and have the most complex organization among organisms of the same size, their peculiar structural features and the factors that limit their miniaturization are of considerable theoretical interest to general biology.
Is It Possible To Fabricate a Nanocomposite with Excellent Mechanical Property Using Unmodified Inorganic Nanoparticles Directly?

PubMed

Zhang, Chunhua; Xia, Liangjun; Lyu, Pei; Wang, Yun; Li, Chen; Xiao, Xingfang; Dai, Fangyin; Xu, Weilin; Liu, Xin; Deng, Bo

2018-05-09

Unmodified ZrO 2 nanoparticles (ZDNPs) are used for the enhancement of polyurethane (PU) films. Optimized strain and toughness of PU/ZDNP nanocomposite at 9.09 wt % ZDNPs are up to 2714.6%, and 280.8 MJ m -3 , respectively. The unique bimodal ZDNP aggregate size distribution which exploits both interfacial positively and negatively toughening mechanisms accounts mainly for the excellent mechanical property of PU/ZDNP nanocomposite. The dependence of different toughening mechanisms on three sizes of ZDNP aggregates is summarized. These findings provide a new avenue for the industrial production of nanocomposites at low cost without surface modification of inorganic nanoparticles.
Apollo food technology

NASA Technical Reports Server (NTRS)

Smith, M. C., Jr.; Heidelbaugh, N. D.; Rambaut, P. C.; Rapp, R. M.; Wheeler, H. O.; Huber, C. S.; Bourland, C. T.

1975-01-01

Large improvements and advances in space food systems achieved during the Apollo food program are discussed. Modifications of the Apollo food system were directed primarily toward improving delivery of adequate nutrition to the astronaut. Individual food items and flight menus were modified as nutritional countermeasures to the effects of weightlessness. Unique food items were developed, including some that provided nutritional completeness, high acceptability, and ready-to-eat, shelf-stable convenience. Specialized food packages were also developed. The Apollo program experience clearly showed that future space food systems will require well-directed efforts to achieve the optimum potential of food systems in support of the physiological and psychological well-being of astronauts and crews.
Is Hymenoplasty Anti-Feminist?

PubMed

Heinrichs, Gretchen

2015-01-01

Hymenoplasty is a practice that must be judged from within its cultural confines and not only from outside. It offers women who have grown up within the sexual norms of a Western society the chance to return to their parental culture, with its female-specific virginity expectations. Hymenoplasty allows women to be sexually active prior to marriage, which equalizes the discrepancy between gender norms on premarital sexual experience. Caution is needed when comparing hymenoplasty to female genital mutilation. However, comparing hymenoplasty to other cosmetic genital modification procedures raises unique ethical, social, and medical quandaries that highlight the importance of patient's autonomy. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.
Evaluation of the Cloud Fields in the UK Met Office HadGEM3-UKCA Model Using the CCCM Satellite Data Product to Advance Our Understanding of the Influence of Clouds on Tropospheric Composition and Chemistry

NASA Technical Reports Server (NTRS)

Varma, Sunil; Voulgarakis, Apostolos; Liu, Hongyu; Crawford, James H.; White, James

2016-01-01

To determine the role of clouds in driving inter-annual and inter-seasonal variability of trace gases in the troposphere and lower stratosphere with a particular focus on the importance of cloud modification of photolysis. To evaluate the cloud fields and their vertical distribution in the HadGEM3 model utilizing CCCM, a unique 3-D cloud data product merged from multiple A-Train satellites (CERES, CloudSat, CALIPSO, and MODIS) developed at the NASA Langley Research Center.
A phototactic micromotor based on platinum nanoparticle decorated carbon nitride.

PubMed

Ye, Zhenrong; Sun, Yunyu; Zhang, Hui; Song, Bo; Dong, Bin

2017-11-30

In this paper, we report a unique phototactic (both positive and negative) micromotor based on platinum nanoparticle decorated carbon nitride. The phototaxis relies on the self-diffusiophoretic mechanism and different surface modifications. The micromotor reported in the current study does not require the addition of any external fuels and shows versatile motion behaviour, i.e. start, stop, directional and programmable motion, which is controlled by light. In addition, since the actuation of the precipitated micromotors at the bottom of a solution using light results in the opacity changes from transparent to translucent, we anticipate that the current micromotor may have potential application in the field of smart windows.
Current Radiation Issues for Programmable Elements and Devices

NASA Technical Reports Server (NTRS)

Katz, R.; Wang, J. J.; Koga, R.; LaBel, A.; McCollum, J.; Brown, R.; Reed, R. A.; Cronquist, B.; Crain, S.; Scott, T.;

1998-01-01

State of the an programmable devices are utilizing advanced processing technologies, non-standard circuit structures, and unique electrical elements in commercial-off-the-shelf (COTS)-based, high-performance devices. This paper will discuss that the above factors, coupled with the systems application environment, have a strong interplay that affect the radiation hardness of programmable devices and have resultant system impacts in (1) reliability of the unprogrammed, biased antifuse for heavy ions (rupture), (2) logic upset manifesting itself as clock upset, and (3) configuration upset. General radiation characteristics of advanced technologies are examined and manufacturers' modifications to their COTS-based and their impact on future programmable devices will be analyzed.

Recent Progress in Aptamer-Based Functional Probes for Bioanalysis and Biomedicine.

PubMed

Zhang, Huimin; Zhou, Leiji; Zhu, Zhi; Yang, Chaoyong

2016-07-11

Nucleic acid aptamers are short synthetic DNA or RNA sequences that can bind to a wide range of targets with high affinity and specificity. In recent years, aptamers have attracted increasing research interest due to their unique features of high binding affinity and specificity, small size, excellent chemical stability, easy chemical synthesis, facile modification, and minimal immunogenicity. These properties make aptamers ideal recognition ligands for bioanalysis, disease diagnosis, and cancer therapy. This review highlights the recent progress in aptamer selection and the latest applications of aptamer-based functional probes in the fields of bioanalysis and biomedicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Induced Pluripotent Stem Cells from Nonhuman Primates.

PubMed

Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

2016-01-01

Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.
Synthetic Developments of Nontoxic Quantum Dots.

PubMed

Das, Adita; Snee, Preston T

2016-03-03

Semiconductor nanocrystals, or quantum dots (QDs), are candidates for biological sensing, photovoltaics, and catalysis due to their unique photophysical properties. The most studied QDs are composed of heavy metals like cadmium and lead. However, this engenders concerns over heavy metal toxicity. To address this issue, numerous studies have explored the development of nontoxic (or more accurately less toxic) quantum dots. In this Review, we select three major classes of nontoxic quantum dots composed of carbon, silicon and Group I-III-VI elements and discuss the myriad of synthetic strategies and surface modification methods to synthesize quantum dots composed of these material systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Strangulation by Feeding Tube in a 23-Month-Old With Down Syndrome: Case Report and Review of Literature.

PubMed

Woodham, Paige C; Fulcher, James W; Ward, Michael E

2016-12-01

Ligature strangulation, although typically homicidal in nature, has been reported as accidental in both the pediatric and adult populations. The unique mode of accidental strangulation with a gastric feeding tube in a 23-month-old with Down syndrome is currently unreported in the literature and has prompted us to report this case and look into safety modifications that can be made to these common medical devices. Given the number of children with gastric feeding tubes and concern over this exact scenario brought up by parents, it is unusual that a similar case has not been reported.
The ilmenite liquidus and depths of segregation for high-Ti picrite glasses

NASA Technical Reports Server (NTRS)

Hess, P. C.

1993-01-01

Lunar picrite glasses represent primitive and perhaps near primary liquids which have suffered only minor degrees of crystallization or near crustal modification. These glasses are multisaturated with olivine and orthopyroxene at pressures from 20-25 kb. I argue below that high TiO2 mare glasses were indeed equilibrated with orthopyroxene and were segregated from the lunar mantle at mean depths of 400-500 km. The glasses are typically modelled as products of relatively low degrees of melting of an hybridized source resulting from the overturn and mixing of the gravitationally unstable cumulate pile. But the models are neither unique nor, in some cases, correct.
Genetic Control of Wayward Pluripotent Stem Cells and Their Progeny after Transplantation

PubMed Central

Kiuru, Maija; Boyer, Julie L.; O’Connor, Timothy P.; Crystal, Ronald G.

2011-01-01

The proliferative capacity of pluripotent stem cells and their progeny brings a unique aspect to therapeutics, in that once a transplant is initiated the therapist no longer has control of the therapy. In the context of the recent FDA approval of a human ESC trial and report of a neuronal-stem-cell-derived tumor in a human trial, strategies need to be developed to control wayward pluripotent stem cells. Here, we focus on one approach: direct genetic modification of the cells prior to transplantation with genes that can prevent the adverse events and/or eliminate the transplanted cells and their progeny. PMID:19341619
Comparison of flank modification on Ascraeus and Arsia Montes volcanoes, Mars

NASA Technical Reports Server (NTRS)

Zimbelman, James R.

1993-01-01

Geologic mapping of the Tharsis Montes on Mars is in progress as part of the Mars Geologic Mapping Program of NASA. Mapping of the southern flanks of Ascraeus Mons at 1:500,000 scale was undertaken first followed by detailed mapping of Arsia Mons; mapping of Pavonis Mons will begin later this year. Results indicate that each of the Tharsis volcanoes displays unique variations on the general 'theme' of a martian shield volcano. Here we concentrate on the flank characteristics on Ascraeus Mons and Arsia Mons, the northernmost and southernmost of the Tharsis Montes, as illustrative of the most prominent trends.
Total synthesis of (+/-)-taiwaniaquinol B via a domino intramolecular friedel-crafts acylation/carbonyl alpha-tert-alkylation reaction.

PubMed

Fillion, Eric; Fishlock, Dan

2005-09-28

The first synthesis of taiwaniaquinol B, a 6-nor-5(6-->7)abeoabietane-type diterpenoid exhibiting the uncommon fused 6-5-6 tricyclic carbon skeleton, was accomplished in 15 steps. A Lewis acid-promoted tandem intramolecular Friedel-Crafts/carbonyl alpha-tert-alkylation reaction was exploited as the core strategy for the synthesis of the sterically congested 1-indanone-containing tricyclic structure. This multiple carbon-carbon bond forming reaction exploits the unique reactivity of Meldrum's acid. The facile precursor synthesis makes this a useful methodology for the expedient modification and assembly of sterically congested 1-indanone-containing ring systems.
Evolution of phage display technology: from discovery to application.

PubMed

Rahbarnia, Leila; Farajnia, Safar; Babaei, Hossein; Majidi, Jafar; Veisi, Kamal; Ahmadzadeh, Vahideh; Akbari, Bahman

2017-03-01

Phage display technology as a selection-based system is an attractive method for evolution of new biological drugs. Unique ability of phage libraries for displaying proteins on bacteriophage surfaces enable them to make a major contribution in diverse fields of researches related to the diagnosis and therapy of diseases. One of the great challenges facing researchers is the modification of phage display technology and the development of new applications. This article reviews the molecular basis of phage display library, and summarizes the novel and specific applications of this technique in the field of biological drugs development including therapeutic antibodies, peptides, vaccines, and catalytic antibodies.
The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A two-day consensus meeting was held on November 18-19, 2008 in Chicago, IL, United States of America, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors, and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines For Randomized Control Trials) statement for livestock and food safety (LFS) and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.
The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety by modifying the CONSORT statement.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J; Ward, M P; Wills, R

2010-03-01

The conduct of randomized controlled trials in livestock with production, health and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on 18-19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food-safety outcomes.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

PubMed

O'Connor, A M; Sargeant, J M; Gardner, I A; Dickson, J S; Torrence, M E; Dewey, C E; Dohoo, I R; Evans, R B; Gray, J T; Greiner, M; Keefe, G; Lefebvre, S L; Morley, P S; Ramirez, A; Sischo, W; Smith, D R; Snedeker, K; Sofos, J N; Ward, M P; Wills, R

2010-01-01

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A two-day consensus meeting was held on November 18-19, 2008 in Chicago, Ill, United States of America, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety (LFS) and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.
Understanding the Role of O-GlcNAc Modifications in Plant Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olszewski, Neil, E.

2011-06-16

This project has contributed towards understanding the role of O-GlcNAc (O-linked N-acetylglucosamine) transferases (OGTs) in plants. Through analyses of single and double mutants, we have investigated the unique and overlapping functions of SECRET AGENT (SEC) and SPINDLY (SPY), the arabidopsis OGTs. This work showed that SEC functions as negative regulators of the long-day flowering pathway. SEC also has a positive role in regulation of rosette. An E. coli co-expression system that allows potential substrates to be co-expressed with and O-GlcNAc modified by SEC was developed. We showed that SEC is a bona fide OGT that modifies itself with single O-linkedmore » GlcNAc(s). Using this system, we tested a number of proteins that were hypothesized to be substrates of SEC and identified a number of substrates include GIGANTEA (GI), a component of the long day flowering pathway. The hypothesis that O-GlcNAc modification controls GI activity was tested by first mapping where E. coli-expressed SEC modifies GI and then assessing the activity of a non-modifiable mutant form of GI. The activity of the mutant form of GI was indistinguishable from that of wild type suggesting that either O-GlcNAc does not regulate GI activity or that additional modification sites exist on GI. In collaboration with Dr. Juan Antonio Garcia at Universidad Autónoma de Madrid the role of O-GlcNAc modification of the plum pox virus coat protein (PPV-CP) was investigated. SEC was shown to O-GlcNAc modify PPV-CP and the modification was shown to facilitate the infection process. E. coli-expressed SEC was shown to modify the same PPV-CP sites that are modified in plants. SEC has a large protein interaction domain called the TPR domain that has been hypothesized to have a role in determining the substrate specificity of the enzyme and/or to regulate its activity. A mutational analysis of the TPR domain did not find evidence for a role in substrate specificity but did obtain evidence that the domain regulates enzyme activity.« less
Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

PubMed

Nally, Jarlath E; Grassmann, Andre A; Planchon, Sébastien; Sergeant, Kjell; Renaut, Jenny; Seshu, Janakiram; McBride, Alan J; Caimano, Melissa J

2017-01-01

Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC) peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE). Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed ( p < 0.05, fold change >1.25 or < -1.25) across all three conditions. Differentially expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs) are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30 leptospires by 2-D immunoblotting confirmed that modification of proteins with trimethyllysine and acetyllysine occurs to a different degree in response to mammalian host signals encountered during persistent renal colonization. These results provide novel insights into differential protein and PTMs present in response to mammalian host signals which can be used to further define the unique equilibrium that exists between pathogenic leptospires and their reservoir host of infection.
Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary (STROBE-Vet) Statement.

PubMed

Sargeant, J M; O'Connor, A M; Dohoo, I R; Erb, H N; Cevallos, M; Egger, M; Ersbøll, A K; Martin, S W; Nielsen, L R; Pearl, D L; Pfeiffer, D U; Sanchez, J; Torrence, M E; Vigre, H; Waldner, C; Ward, M P

2016-12-01

The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare and food safety outcomes. The consensus meeting was held 11-13 May 2014 in Mississauga, Ontario, Canada. Seventeen experts from North America, Europe and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals. Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and whether items should be added to address unique issues related to observational studies in animal species with health, production, welfare or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re-wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition. The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered as follows: 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations) and 22 (funding). Published literature was not always available to support modification to, or inclusion of, an item. The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare or food safety outcomes by recognizing the unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture and wildlife. © 2016 The Authors. Zoonoses and Public Health published by Blackwell Verlag GmbH.
Assessing the Priority Area of Mountainous Tourism Using Geospatial Approach in Kendal Regency, Central Java

NASA Astrophysics Data System (ADS)

Riwayatiningsih; Purnaweni, Hartuti

2018-02-01

Kendal is one of 35 regencies in Central Java which has diverse topographies, from low land, hilly, to mountainous areas. Mountainous area of Kendal with numerous unique and distinct natural environments, supported by various unique and distinct culture of its community can be used for tourism activities. Kendal has natural and sociocultural resources for developing tourism that must be considered by the local government. Therefore, nature based tourism resources assessment is important in order to determine the appropriate area in the planning of sustainable tourism destination. The objectives of this study are to assess and prioritize the potential area of mountainous tourism object in Kendal using geospatial approach based on criteria attractiveness, accessibility and amenity of the tourism object. Those criteria are modification of ADO-ODTWA guidelines and condition of the study location. There are 16 locations of tourism object that will be assessed. The result will be processed using ArcMap 10.3. The result will show the most potential tourism object that could become priority for mountainous tourism development in Kendal.
Transcultural Diabetes Nutrition Algorithm: A Malaysian Application

PubMed Central

Hamdy, Osama; Chin Chia, Yook; Lin Lim, Shueh; Kumari Natkunam, Santha; Yeong Tan, Ming; Sulaiman, Ridzoni; Nisak, Barakatun; Chee, Winnie Siew Swee; Marchetti, Albert; Hegazi, Refaat A.; Mechanick, Jeffrey I.

2013-01-01

Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations. PMID:24385984
Transcultural diabetes nutrition algorithm: a malaysian application.

PubMed

Hussein, Zanariah; Hamdy, Osama; Chin Chia, Yook; Lin Lim, Shueh; Kumari Natkunam, Santha; Hussain, Husni; Yeong Tan, Ming; Sulaiman, Ridzoni; Nisak, Barakatun; Chee, Winnie Siew Swee; Marchetti, Albert; Hegazi, Refaat A; Mechanick, Jeffrey I

2013-01-01

Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations.
Quinovosamycins: new tunicamycin-type antibiotics in which the α, β-1″,11'-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine.

PubMed

Price, Neil Pj; Labeda, David P; Naumann, Todd A; Vermillion, Karl E; Bowman, Michael J; Berhow, Mark A; Metcalf, William W; Bischoff, Kenneth M

2016-08-01

Tunicamycins (TUN) are potent inhibitors of polyprenyl phosphate N-acetylhexosamine 1-phosphate transferases (PPHP), including essential eukaryotic GPT enzymes and bacterial HexNAc 1-P translocases. Hence, TUN blocks the formation of eukaryotic N-glycoproteins and the assembly of bacterial call wall polysaccharides. The genetic requirement for TUN production is well-established. Using two genes unique to the TUN pathway (tunB and tunD) as probes we identified four new prospective TUN-producing strains. Chemical analysis showed that one strain, Streptomyces niger NRRL B-3857, produces TUN plus new compounds, named quinovosamycins (QVMs). QVMs are structurally akin to TUN, but uniquely in the 1″,11'-HexNAc sugar head group, which is invariably d-GlcNAc for the known TUN, but is d-QuiNAc for the QVM. Surprisingly, this modification has only a minor effect on either the inhibitory or antimicrobial properties of QVM and TUN. These findings have unexpected consequences for TUN/QVM biosynthesis, and for the specificity of the PPHP enzyme family.
Information Needs Assessment for a Medicine Ward-Focused Rounding Dashboard.

PubMed

Aakre, Christopher A; Chaudhry, Rajeev; Pickering, Brian W; Herasevich, Vitaly

2016-08-01

To identify the routine information needs of inpatient clinicians on the general wards for the development of an electronic dashboard. Survey of internal medicine and subspecialty clinicians from March 2014-July 2014 at Saint Marys Hospital in Rochester, Minnesota. An information needs assessment was generated from all unique data elements extracted from all handoff and rounding tools used by clinicians in our ICUs and general wards. An electronic survey was distributed to 104 inpatient medical providers. 89 unique data elements were identified from currently utilized handoff and rounding instruments. All data elements were present in our multipurpose ICU-based dashboard. 42 of 104 (40 %) surveys were returned. Data elements important (50/89, 56 %) and unimportant (24/89, 27 %) for routine use were identified. No significant differences in data element ranking were observed between supervisory and nonsupervisory roles. The routine information needs of general ward clinicians are a subset of data elements used routinely by ICU clinicians. Our findings suggest an electronic dashboard could be adapted from the critical care setting to the general wards with minimal modification.
Under the Skin of a Lion: Unique Evidence of Upper Paleolithic Exploitation and Use of Cave Lion (Panthera spelaea) from the Lower Gallery of La Garma (Spain).

PubMed

Cueto, Marián; Camarós, Edgard; Castaños, Pedro; Ontañón, Roberto; Arias, Pablo

2016-01-01

Pleistocene skinning and exploitation of carnivore furs have been previously inferred from archaeological evidence. Nevertheless, the evidence of skinning and fur processing tends to be weak and the interpretations are not strongly sustained by the archaeological record. In the present paper, we analyze unique evidence of patterned anthropic modification and skeletal representation of fossil remains of cave lion (Panthera spelaea) from the Lower Gallery of La Garma (Cantabria, Spain). This site is one of the few that provides Pleistocene examples of lion exploitation by humans. Our archaeozoological study suggests that lion-specialized pelt exploitation and use might have been related to ritual activities during the Middle Magdalenian period (ca. 14800 cal BC). Moreover, the specimens also represent the southernmost European and the latest evidence of cave lion exploitation in Iberia. Therefore, the study seeks to provide alternative explanations for lion extinction in Eurasia and argues for a role of hunting as a factor to take into account.
Under the Skin of a Lion: Unique Evidence of Upper Paleolithic Exploitation and Use of Cave Lion (Panthera spelaea) from the Lower Gallery of La Garma (Spain)

PubMed Central

Camarós, Edgard; Castaños, Pedro; Ontañón, Roberto; Arias, Pablo

2016-01-01

Pleistocene skinning and exploitation of carnivore furs have been previously inferred from archaeological evidence. Nevertheless, the evidence of skinning and fur processing tends to be weak and the interpretations are not strongly sustained by the archaeological record. In the present paper, we analyze unique evidence of patterned anthropic modification and skeletal representation of fossil remains of cave lion (Panthera spelaea) from the Lower Gallery of La Garma (Cantabria, Spain). This site is one of the few that provides Pleistocene examples of lion exploitation by humans. Our archaeozoological study suggests that lion-specialized pelt exploitation and use might have been related to ritual activities during the Middle Magdalenian period (ca. 14800 cal BC). Moreover, the specimens also represent the southernmost European and the latest evidence of cave lion exploitation in Iberia. Therefore, the study seeks to provide alternative explanations for lion extinction in Eurasia and argues for a role of hunting as a factor to take into account. PMID:27783697
A unique iron-sulfur cluster is crucial for oxygen tolerance of a [NiFe]-hydrogenase.

PubMed

Goris, Tobias; Wait, Annemarie F; Saggu, Miguel; Fritsch, Johannes; Heidary, Nina; Stein, Matthias; Zebger, Ingo; Lendzian, Friedhelm; Armstrong, Fraser A; Friedrich, Bärbel; Lenz, Oliver

2011-05-01

Hydrogenases are essential for H(2) cycling in microbial metabolism and serve as valuable blueprints for H(2)-based biotechnological applications. However, most hydrogenases are extremely oxygen sensitive and prone to inactivation by even traces of O(2). The O(2)-tolerant membrane-bound [NiFe]-hydrogenase of Ralstonia eutropha H16 is one of the few examples that can perform H(2) uptake in the presence of ambient O(2). Here we show that O(2) tolerance is crucially related to a modification of the internal electron-transfer chain. The iron-sulfur cluster proximal to the active site is surrounded by six instead of four conserved coordinating cysteines. Removal of the two additional cysteines alters the electronic structure of the proximal iron-sulfur cluster and renders the catalytic activity sensitive to O(2) as shown by physiological, biochemical, spectroscopic and electrochemical studies. The data indicate that the mechanism of O(2) tolerance relies on the reductive removal of oxygenic species guided by the unique architecture of the electron relay rather than a restricted access of O(2) to the active site.
Capacity improvement of the carbon-based electrochemical capacitor by zigzag-edge introduced graphene

NASA Astrophysics Data System (ADS)

Tamura, Naoki; Tomai, Takaaki; Oka, Nobuto; Honma, Itaru

2018-01-01

The electrochemical properties of graphene edge has been attracted much attention. Especially, zigzag edge has high electrochemical activity because neutral radical exits on edge. However, due to a lack of efficient production method for zigzag graphene, the electrochemical properties of zigzag edge have not been experimentally demonstrated and the capacitance enhancement of carbonaceous materials in energy storage devices by the control in their edge states is still challenge. In this study, we fabricated zigzag-edge-rich graphene by a one-step method combining graphene exfoliation in supercritical fluid and anisotropic etching by catalytic nanoparticles. This efficient production of zigzag-edge-rich graphene allows us to investigate the electrochemical activity of zigzag edge. By cyclic voltammetry, we revealed the zigzag edge-introduced graphene exhibited unique redox reaction in aqueous acid solution. Moreover, by the calculation on the density function theory (DFT), this unique redox potential for zigzag edge-introduced graphene can be attributed to the proton-insertion/-extraction reactions at the zigzag edge. This finding indicates that the graphene edge modification can contribute to the further increase in the capacitance of the carbon-based electrochemical capacitor.
Persistent electrochemical performance in epitaxial VO 2(B)

DOE PAGES

Lee, Shinbuhm; Sun, Xiao -Guang; Lubimtsev, Andrew A.; ...

2017-03-07

Discovering high-performance energy storage materials is indispensable for renewable energy, electric vehicle performance, and mobile computing. Owing to the open atomic framework and good room temperature conductivity, bronze-phase vanadium dioxide [VO 2(B)] has been regarded as a highly promising electrode material for Li ion batteries. However, previous attempts were unsuccessful to show the desired cycling performance and capacity without chemical modification. Here, we show with epitaxial VO 2(B) films that one can accomplish the theoretical limit for capacity with persistent charging–discharging cyclability owing to the high structural stability and unique open pathways for Li ion conduction. Atomic-scale characterization by scanningmore » transmission electron microscopy and density functional theory calculations also reveal that the unique open pathways in VO 2(B) provide the most stable sites for Li adsorption and diffusion. Furthermore, this work ultimately demonstrates that VO 2(B) is a highly promising energy storage material and has no intrinsic hindrance in achieving superior cyclability with a very high power and capacity in a Li-ion conductor.« less
Integrative analysis with ChIP-seq advances the limits of transcript quantification from RNA-seq

PubMed Central

Liu, Peng; Sanalkumar, Rajendran; Bresnick, Emery H.; Keleş, Sündüz; Dewey, Colin N.

2016-01-01

RNA-seq is currently the technology of choice for global measurement of transcript abundances in cells. Despite its successes, isoform-level quantification remains difficult because short RNA-seq reads are often compatible with multiple alternatively spliced isoforms. Existing methods rely heavily on uniquely mapping reads, which are not available for numerous isoforms that lack regions of unique sequence. To improve quantification accuracy in such difficult cases, we developed a novel computational method, prior-enhanced RSEM (pRSEM), which uses a complementary data type in addition to RNA-seq data. We found that ChIP-seq data of RNA polymerase II and histone modifications were particularly informative in this approach. In qRT-PCR validations, pRSEM was shown to be superior than competing methods in estimating relative isoform abundances within or across conditions. Data-driven simulations suggested that pRSEM has a greatly decreased false-positive rate at the expense of a small increase in false-negative rate. In aggregate, our study demonstrates that pRSEM transforms existing capacity to precisely estimate transcript abundances, especially at the isoform level. PMID:27405803
77 FR 54663 - Administrative Simplification: Adoption of a Standard for a Unique Health Plan Identifier...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

...This final rule adopts the standard for a national unique health plan identifier (HPID) and establishes requirements for the implementation of the HPID. In addition, it adopts a data element that will serve as an other entity identifier (OEID), or an identifier for entities that are not health plans, health care providers, or individuals, but that need to be identified in standard transactions. This final rule also specifies the circumstances under which an organization covered health care provider must require certain noncovered individual health care providers who are prescribers to obtain and disclose a National Provider Identifier (NPI). Lastly, this final rule changes the compliance date for the International Classification of Diseases, 10th Revision, Clinical Modification (ICD- 10-CM) for diagnosis coding, including the Official ICD-10-CM Guidelines for Coding and Reporting, and the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) for inpatient hospital procedure coding, including the Official ICD-10-PCS Guidelines for Coding and Reporting, from October 1, 2013 to October 1, 2014.
First Direct Dating for the Construction and Modification of the Baphuon Temple Mountain in Angkor, Cambodia.

PubMed

Leroy, Stéphanie; Hendrickson, Mitch; Delqué-Kolic, Emmanuelle; Vega, Enrique; Dillmann, Philippe

2015-01-01

Architecture represents key evidence of dynastic practice and change in the archaeological world. Chronologies for many important buildings and sequences, including the iconic temples of medieval Angkor in Cambodia, are based solely on indirect associations from inscriptions and architectural styles. The Baphuon temple, one of the last major buildings in Angkor without textual or scientifically-derived chronological evidence, is crucial both for the context and date of its construction and the period when its western façade was modified into a unique, gigantic Reclining Buddha. Its construction was part of a major dynastic change and florescence of the Hindu-Mahayana Buddhist state and the modification is the key evidence of Theravada Buddhist power after Angkor's decline in the 15th century. Using a newly-developed approach based on AMS radiocarbon dating to directly date four iron crampons integrated into the structure we present the first direct evidence for the history of the Baphuon. Comprehensive study of ferrous elements shows that both construction and modification were critically earlier than expected. The Baphuon can now be considered as the major temple associated with the imperial reformations and territorial consolidation of Suryavarman I (1010-1050 AD) for whom no previous building to legitimize his reign could be identified. The Theravada Buddhist modification is a hundred years prior to the conventional 16th century estimation and is not associated with renewed use of Angkor. Instead it relates to the enigmatic Ayutthayan occupation of Angkor in the 1430s and 40s during a major period of climatic instability. Accurately dating iron with relatively low carbon content is a decisive step to test long-standing assumptions about architectural histories and political processes for states that incorporated iron into buildings (e.g., Ancient Greece, medieval India). Furthermore, this new approach has the potential to revise chronologies related to iron consumption practices since the origins of ferrous metallurgy three millennia ago.
First Direct Dating for the Construction and Modification of the Baphuon Temple Mountain in Angkor, Cambodia

PubMed Central

Leroy, Stéphanie; Hendrickson, Mitch; Delqué-Kolic, Emmanuelle; Vega, Enrique; Dillmann, Philippe

2015-01-01

Architecture represents key evidence of dynastic practice and change in the archaeological world. Chronologies for many important buildings and sequences, including the iconic temples of medieval Angkor in Cambodia, are based solely on indirect associations from inscriptions and architectural styles. The Baphuon temple, one of the last major buildings in Angkor without textual or scientifically-derived chronological evidence, is crucial both for the context and date of its construction and the period when its western façade was modified into a unique, gigantic Reclining Buddha. Its construction was part of a major dynastic change and florescence of the Hindu-Mahayana Buddhist state and the modification is the key evidence of Theravada Buddhist power after Angkor's decline in the 15th century. Using a newly-developed approach based on AMS radiocarbon dating to directly date four iron crampons integrated into the structure we present the first direct evidence for the history of the Baphuon. Comprehensive study of ferrous elements shows that both construction and modification were critically earlier than expected. The Baphuon can now be considered as the major temple associated with the imperial reformations and territorial consolidation of Suryavarman I (1010–1050 AD) for whom no previous building to legitimize his reign could be identified. The Theravada Buddhist modification is a hundred years prior to the conventional 16th century estimation and is not associated with renewed use of Angkor. Instead it relates to the enigmatic Ayutthayan occupation of Angkor in the 1430s and 40s during a major period of climatic instability. Accurately dating iron with relatively low carbon content is a decisive step to test long-standing assumptions about architectural histories and political processes for states that incorporated iron into buildings (e.g., Ancient Greece, medieval India). Furthermore, this new approach has the potential to revise chronologies related to iron consumption practices since the origins of ferrous metallurgy three millennia ago. PMID:26535895
Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth

PubMed Central

Carabetta, Valerie J.; Greco, Todd M.; Tanner, Andrew W.

2016-01-01

ABSTRACT Nε-Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. IMPORTANCE The past decade highlighted Nε-lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis. To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth. PMID:27376153
Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth.

PubMed

Carabetta, Valerie J; Greco, Todd M; Tanner, Andrew W; Cristea, Ileana M; Dubnau, David

2016-05-01

N ε -Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. The past decade highlighted N ε -lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis . To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth.

Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post-synthetic Modification with Hydrophilic Side Chains.

PubMed

Pansuwan, Haruthai; Ditmangklo, Boonsong; Vilaivan, Chotima; Jiangchareon, Banphot; Pan-In, Porntip; Wanichwecharungruang, Supason; Palaga, Tanapat; Nuanyai, Thanesuan; Suparpprom, Chaturong; Vilaivan, Tirayut

2017-09-20

Peptide nucleic acid (PNA) is a nucleic acid mimic in which the deoxyribose-phosphate was replaced by a peptide-like backbone. The absence of negative charge in the PNA backbone leads to several unique behaviors including a stronger binding and salt independency of the PNA-DNA duplex stability. However, PNA possesses poor aqueous solubility and cannot directly penetrate cell membranes. These are major obstacles that limit in vivo applications of PNA. In previous strategies, the PNA can be conjugated to macromolecular carriers or modified with positively charged side chains such as guanidinium groups to improve the aqueous solubility and cell permeability. In general, a preformed modified PNA monomer was required. In this study, a new approach for post-synthetic modification of PNA backbone with one or more hydrophilic groups was proposed. The PNA used in this study was the conformationally constrained pyrrolidinyl PNA with prolyl-2-aminocyclopentanecarboxylic acid dipeptide backbone (acpcPNA) that shows several advantages over the conventional PNA. The aldehyde modifiers carrying different linkers (alkylene and oligo(ethylene glycol)) and end groups (-OH, -NH 2 , and guanidinium) were synthesized and attached to the backbone of modified acpcPNA by reductive alkylation. The hybrids between the modified acpcPNAs and DNA exhibited comparable or superior thermal stability with base-pairing specificity similar to those of unmodified acpcPNA. Moreover, the modified apcPNAs also showed the improvement of aqueous solubility (10-20 folds compared to unmodified PNA) and readily penetrate cell membranes without requiring any special delivery agents. This study not only demonstrates the practicality of the proposed post-synthetic modification approach for PNA modification, which could be readily applied to other systems, but also opens up opportunities for using pyrrolidinyl PNA in various applications such as intracellular RNA sensing, specific gene detection, and antisense and antigene therapy.
O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakaidani, Yuta; Ichiyanagi, Naoki; Saito, Chika

2012-03-02

Highlights: Black-Right-Pointing-Pointer We characterized A130022J15Rik (Eogt1)-a mouse gene homologous to Drosophila Eogt. Black-Right-Pointing-Pointer Eogt1 encodes EGF domain O-GlcNAc transferase. Black-Right-Pointing-Pointer Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. Black-Right-Pointing-Pointer O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-{beta}-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shownmore » whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.« less
Deaggregation, Modification, and Developing Applications for Detonation Nanodiamond

NASA Astrophysics Data System (ADS)

Mochalin, Vadym

2017-06-01

Nanodiamond powder (ND) is one of the most promising materials for advanced composites and biomedical applications. It is also a commercial precursor for carbon nanoonions - material for high power micrometer size supercapacitors and potentially, Li-ion batteries. ND is produced by detonation of explosives with negative oxygen balance in a closed chamber, where extremely high pressures and temperatures develop during detonation. ND consists of diamond particles of 5 nm diameter, combining fully accessible large surface and rich and tailorable surface chemistry. ND has unique properties including optical, electrical, thermal, and mechanical, and is biocompatible and non-toxic. Due to numerous surface functional groups, ND has catalytic and electrochemical activity. Several techniques have been proposed for ND deaggregation based on milling with costly ceramic microbeads, leaving difficult to remove contaminations in the resulting ND suspension. We have recently discovered a novel, green technique for ND deaggregation using sonication in aqueous sodium chloride slurry. Upon completion of the process sodium chloride can be easily washed out with water leaving behind no contaminants and yielding stable single-digit ND colloids. Modification and development of applications for ND in composites, drug delivery, biomedical imaging, etc., will be also discussed.
The evaluation of shear deformation for contact analysis with large displacement

NASA Astrophysics Data System (ADS)

Nizam, Z. M.; Obiya, H.; Ijima, K.; Azhar, A. T. S.; Hazreek, Z. A. M.; Shaylinda, M. Z. N.

2018-04-01

A common problem encountered in the study of contact problem is the failure to obtain stable and accurate convergence result when the contact node is close to the element edge, which is referred as “critical area”. In previous studies, the modification of the element force equation to apply it to a node-element contact problem using the Euler-Bernoulli beam theory [1]. A simple single-element consists two edges and a contact point was used to simulate contact phenomenon of a plane frame. The modification was proven to be effective by the converge-ability of the unbalanced force at the tip of element edge, which enabled the contact node to “pass-through”, resulting in precise results. However, in another recent study, we discover that, if shear deformation based on Timoshenko beam theory is taken into consideration, a basic simply supported beam coordinate afforded a much simpler and more efficient technique for avoiding the divergence of the unbalanced force in the “critical area”. Using our unique and robust Tangent Stiffness Method, the improved equation can be used to overcome any geometrically nonlinear analyses, including those involving extremely large displacements.
Nucleolar Reorganization Upon Site-Specific Double-Strand Break Induction.

PubMed

Franek, Michal; Kovaříková, Alena; Bártová, Eva; Kozubek, Stanislav

2016-11-01

DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment. Here, we directed formation of double-strand breaks in rRNA genes with I- PpoI endonuclease, and we studied nucleolar morphology, DDR, and chromatin modifications. We observed a pronounced formation of I- PpoI-induced nucleolar caps, positive on BRCA1, NBS1, MDC1, γH2AX, and UBF1 proteins. We showed interaction of nucleolar protein TCOF1 with HDAC1 and TCOF1 with CARM1 after DNA injury. Moreover, H3R17me2a modification mediated by CARM1 was found in I- PpoI-induced nucleolar caps. Finally, we report that heterochromatin protein 1 is not involved in DNA repair of nucleolar caps.
Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

PubMed

Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

2017-02-22

Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.
Mudskippers and Their Genetic Adaptations to an Amphibious Lifestyle

PubMed Central

You, Xinxin; Sun, Min; Li, Jia; Bian, Chao; Chen, Jieming; Yu, Hui; Shi, Qiong

2018-01-01

Simple Summary Mudskippers are an interesting group of goggle-eyed amphibious fish that can live both in water and on land. They are a useful model for obtaining insights into the genetic mechanisms underlying the terrestrial adaptations of amphibious fish. This review summarizes the morphological and physiological modifications of representative mudskippers, and focuses on the recent advancement of genomic studies on their genetic adaptations to the amphibious lifestyle. Abstract Mudskippers are the largest group of amphibious teleost fish that are uniquely adapted to live on mudflats. During their successful transition from aqueous life to terrestrial living, these fish have evolved morphological and physiological modifications of aerial vision and olfaction, higher ammonia tolerance, aerial respiration, improved immunological defense against terrestrial pathogens, and terrestrial locomotion using protruded pectoral fins. Comparative genomic and transcriptomic data have been accumulated and analyzed for understanding molecular mechanisms of the terrestrial adaptations. Our current review provides a general introduction to mudskippers and recent research advances of their genetic adaptations to the amphibious lifestyle, which will be helpful for understanding the evolutionary transition of vertebrates from water to land. Our insights into the genomes and transcriptomes will also support molecular breeding, functional identification, and natural compound screening. PMID:29414871
Characterizing the surface charge of synthetic nanomembranes by the streaming potential method

PubMed Central

Datta, Subhra; Conlisk, A. T.; Kanani, Dharmesh M.; Zydney, Andrew L.; Fissell, William H.; Roy, Shuvo

2010-01-01

The inference of the surface charge of polyethylene glycol (PEG)-coated and uncoated silicon membranes with nanoscale pore sizes from streaming potential measurements in the presence of finite electric double layer (EDL) effects is studied theoretically and experimentally. The developed theoretical model for inferring the pore wall surface charge density from streaming potential measurements is applicable to arbitrary pore cross-sectional shapes and accounts for the effect of finite salt concentration on the ionic mobilities and the thickness of the deposited layer of PEG. Theoretical interpretation of the streaming potential data collected from silicon membranes having nanoscale pore sizes, with/without pore wall surface modification with PEG, indicates that finite electric double layer (EDL) effects in the pore-confined electrolyte significantly affect the interpretation of the membrane charge and that surface modification with PEG leads to a reduction in the pore wall surface charge density. The theoretical model is also used to study the relative significance of the following uniquely nanoscale factors affecting the interpretation of streaming potential in moderate to strongly charged pores: altered net charge convection by applied pressure differentials, surface-charge effects on ionic conduction, and electroosmotic convection of charges. PMID:20462592
Lipid A structural modifications in extreme conditions and identification of unique modifying enzymes to define the Toll-like receptor 4 structure-activity relationship.

PubMed

Scott, Alison J; Oyler, Benjamin L; Goodlett, David R; Ernst, Robert K

2017-11-01

Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant. A limited 'toolbox' of lipid A-modifying enzymes has been defined and is largely composed of enzymes from mesophile human and zoonotic pathogens. Expansion of this 'toolbox' will result from extending the search into lipid A biosynthesis and modification by bacteria living at the extremes. Here, we review the fundamentals of lipid A structure, advances in lipid A uses in TLR4 modulation, and the search for novel lipid A-modifying systems in extremophile bacteria. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2017 Elsevier B.V. All rights reserved.
Crystal structure of chiral gammaPNA with complementary DNA strand: insights into the stability and specificity of recognition and conformational preorganization.

PubMed

Yeh, Joanne I; Shivachev, Boris; Rapireddy, Srinivas; Crawford, Matthew J; Gil, Roberto R; Du, Shoucheng; Madrid, Marcela; Ly, Danith H

2010-08-11

We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by multiple-wavelength anomalous diffraction phasing method on a zinc derivative. This structure represents the first high-resolution 3D view of a hybrid duplex containing a contiguous chiral PNA strand with complete gamma-backbone modification ("gammaPNA"). Unlike the achiral counterpart, which adopts a random-fold, this particular gammaPNA is already preorganized into a right-handed helix as a single strand. The new structure illustrates the unique characteristics of this modified PNA, possessing conformational flexibility while maintaining sufficient structural integrity to ultimately adopt the preferred P-helical conformation upon hybridization with DNA. The unusual structural adaptability found in the gammaPNA strand is crucial for enabling the accommodation of backbone modifications while constraining conformational states. In conjunction with NMR analysis characterizing the structures and substructures of the individual building blocks, these results provide unprecedented insights into how this new class of chiral gammaPNA is preorganized and stabilized, before and after hybridization with a cDNA strand. Such knowledge is crucial for the future design and development of PNA for applications in biology, biotechnology, and medicine.
Graphene-based two-dimensional Janus materials

NASA Astrophysics Data System (ADS)

Ng, Sze-Wing; Noor, Nuruzzaman; Zheng, Zijian

2018-04-01

Two-dimensional (2D) Janus materials with opposing components and properties on two sides have recently attracted fevered attention from various research fields for use as, for example, oil/water separating membranes, interfacial layers for mass transfer, 2D sensors and actuators. The Janus structure allows for a unidirectional transportation system and programmed response to certain stimuli to be achieved. Graphene, the 2D honeycomb network formed from one atomic layer of carbon atoms, has also received substantial research interest because of its intriguing structure and fascinating properties. The high mechanical strength, flexibility and optical transparency make graphene a unique candidate as a building block of 2D Janus materials through asymmetric modification with different functional groups on the graphene surfaces. This article reviews graphene-based 2D Janus materials, starting with a theoretical understanding of the behavior of Janus graphene. Then, different strategies for fabricating Janus graphene and its derivatives are reviewed in detail according to the chemical strategies of the modification methods. The applications of graphene-based Janus materials are discussed with a specific focus on the Janus structures that lead to bandgap engineering, as well as the construction of a responsive system on graphene.
Coordination-Assisted Bioorthogonal Chemistry: Orthogonal Tetrazine Ligation with Vinylboronic Acid and a Strained Alkene.

PubMed

Eising, Selma; Xin, Bo-Tao; Kleinpenning, Fleur; Heming, Juriaan; Florea, Bogdan; Overkleeft, Herman; Bonger, Kimberly Michelle

2018-05-28

Bioorthogonal chemistry can be used for the selective modification of biomolecules without interfering with any other functionality present. Recent developments in the field provided orthogonal bioorthogonal reactions for modification of multiple biomolecules simultaneously. During our research, we have observed exceptional high reaction rates in the bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction between non-strained vinylboronic acids (VBAs) and dipyridyl-s-tetrazines relative to that of tetrazines bearing a methyl or phenyl substituent. As VBAs are mild Lewis acids, we hypothesize that coordination of the pyridyl nitrogen to the boronic acid promotes the tetrazine ligation. Here, we explore the molecular basis and scope of the VBA-tetrazine ligation in more detail and benefit from its unique reactivity in the simultaneous orthogonal tetrazine labelling of two proteins modified with VBA and norbornene, a widely used strained alkene. We further show that the two orthogonal iEDDA reactions can be carried out in living cells by labelling of the proteasome using a non-selective probe equipped with a VBA and a subunit-selective one bearing a norbornene. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Post-SELEX optimization of aptamers.

PubMed

Gao, Shunxiang; Zheng, Xin; Jiao, Binghua; Wang, Lianghua

2016-07-01

Aptamers are functional single-stranded DNA or RNA oligonucleotides, selected in vitro by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), which can fold into stable unique three-dimensional structures that bind their target ligands with high affinity and specificity. Although aptamers show a number of favorable advantages such as better stability and easier modification when compared with the properties of antibodies, only a handful of aptamers have entered clinical trials and only one, pegaptanib, has received US Food and Drug Administration approval for clinical use. The main reasons that limit the practical application of aptamers are insufficient nuclease stability, bioavailability, thermal stability, or even affinity. Some aptamers obtained from modified libraries show better properties; however, polymerase amplification of nucleic acids containing non-natural bases is currently a primary drawback of the SELEX process. This review focuses on several post-SELEX optimization strategies of aptamers identified in recent years. We describe four common methods in detail: truncation, chemical modification, bivalent or multivalent aptamer construction, and mutagenesis. We believe that these optimization strategies should improve one or more specific properties of aptamers, and the type of feature(s) selected for improvement will be dependent on the application purpose.
CrisprGE: a central hub of CRISPR/Cas-based genome editing.

PubMed

Kaur, Karambir; Tandon, Himani; Gupta, Amit Kumar; Kumar, Manoj

2015-01-01

CRISPR system is a powerful defense mechanism in bacteria and archaea to provide immunity against viruses. Recently, this process found a new application in intended targeting of the genomes. CRISPR-mediated genome editing is performed by two main components namely single guide RNA and Cas9 protein. Despite the enormous data generated in this area, there is a dearth of high throughput resource. Therefore, we have developed CrisprGE, a central hub of CRISPR/Cas-based genome editing. Presently, this database holds a total of 4680 entries of 223 unique genes from 32 model and other organisms. It encompasses information about the organism, gene, target gene sequences, genetic modification, modifications length, genome editing efficiency, cell line, assay, etc. This depository is developed using the open source LAMP (Linux Apache MYSQL PHP) server. User-friendly browsing, searching facility is integrated for easy data retrieval. It also includes useful tools like BLAST CrisprGE, BLAST NTdb and CRISPR Mapper. Considering potential utilities of CRISPR in the vast area of biology and therapeutics, we foresee this platform as an assistance to accelerate research in the burgeoning field of genome engineering. © The Author(s) 2015. Published by Oxford University Press.
Modulating supramolecular binding of carbon dioxide in a redox-active porous metal-organic framework

PubMed Central

Lu, Zhenzhong; Godfrey, Harry G. W.; da Silva, Ivan; Cheng, Yongqiang; Savage, Mathew; Tuna, Floriana; McInnes, Eric J. L.; Teat, Simon J.; Gagnon, Kevin J.; Frogley, Mark D.; Manuel, Pascal; Rudić, Svemir; Ramirez-Cuesta, Anibal J.; Easun, Timothy L.; Yang, Sihai; Schröder, Martin

2017-01-01

Hydrogen bonds dominate many chemical and biological processes, and chemical modification enables control and modulation of host–guest systems. Here we report a targeted modification of hydrogen bonding and its effect on guest binding in redox-active materials. MFM-300(VIII) {[VIII2(OH)2(L)], LH4=biphenyl-3,3′,5,5′-tetracarboxylic acid} can be oxidized to isostructural MFM-300(VIV), [VIV2O2(L)], in which deprotonation of the bridging hydroxyl groups occurs. MFM-300(VIII) shows the second highest CO2 uptake capacity in metal-organic framework materials at 298 K and 1 bar (6.0 mmol g−1) and involves hydrogen bonding between the OH group of the host and the O-donor of CO2, which binds in an end-on manner, =1.863(1) Å. In contrast, CO2-loaded MFM-300(VIV) shows CO2 bound side-on to the oxy group and sandwiched between two phenyl groups involving a unique ···c.g.phenyl interaction [3.069(2), 3.146(3) Å]. The macroscopic packing of CO2 in the pores is directly influenced by these primary binding sites. PMID:28194014
Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses

PubMed Central

Menachery, Vineet D.; Eisfeld, Amie J.; Schäfer, Alexandra; Josset, Laurence; Sims, Amy C.; Proll, Sean; Fan, Shufang; Li, Chengjun; Neumann, Gabriele; Tilton, Susan C.; Chang, Jean; Gralinski, Lisa E.; Long, Casey; Green, Richard; Williams, Christopher M.; Weiss, Jeffrey; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Katze, Michael G.; Kawaoka, Yoshihiro

2014-01-01

ABSTRACT The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications. PMID:24846384
Avian Biotechnology.

PubMed

Nakamura, Yoshiaki

2017-01-01

Primordial germ cells (PGCs) generate new individuals through differentiation, maturation and fertilization. This means that the manipulation of PGCs is directly linked to the manipulation of individuals, making PGCs attractive target cells in the animal biotechnology field. A unique biological property of avian PGCs is that they circulate temporarily in the vasculature during early development, and this allows us to access and manipulate avian germ lines. Following the development of a technique for transplantation, PGCs have become central to avian biotechnology, in contrast to the use of embryo manipulation and subsequent transfer to foster mothers, as in mammalian biotechnology. Today, avian PGC transplantation combined with recent advanced manipulation techniques, including cell purification, cryopreservation, depletion, and long-term culture in vitro, have enabled the establishment of genetically modified poultry lines and ex-situ conservation of poultry genetic resources. This chapter introduces the principles, history, and procedures of producing avian germline chimeras by transplantation of PGCs, and the current status of avian germline modification as well as germplasm cryopreservation. Other fundamental avian reproductive technologies are described, including artificial insemination and embryo culture, and perspectives of industrial applications in agriculture and pharmacy are considered, including poultry productivity improvement, egg modification, disease resistance impairment and poultry gene "pharming" as well as gene banking.
Influence of sexual selection and feeding functional morphology on diversification rate of parrotfishes (Scaridae).

PubMed

Kazancioglu, Erem; Near, Thomas J; Hanel, Reinhold; Wainwright, Peter C

2009-10-07

Scaridae (parrotfishes) is a prominent clade of 96 species that shape coral reef communities worldwide through their actions as grazing herbivores. Phylogenetically nested within Labridae, the profound ecological impact and high species richness of parrotfishes suggest that their diversification and ecological success may be linked. Here, we ask whether parrotfish evolution is characterized by a significant burst of lineage diversification and whether parrotfish diversity is shaped more strongly by sexual selection or modifications of the feeding mechanism. We first examined scarid diversification within the greater context of labrid diversity. We used a supermatrix approach for 252 species to propose the most extensive phylogenetic hypothesis of Labridae to date, and time-calibrated the phylogeny with fossil and biogeographical data. Using divergence date estimates, we find that several parrotfish clades exhibit the highest diversification rates among all labrid lineages. Furthermore, we pinpoint a rate shift at the shared ancestor of Scarus and Chlorurus, a scarid subclade characterized by territorial behaviour and strong sexual dichromatism, suggesting that sexual selection was a major factor in parrotfish diversification. Modifications of the pharyngeal and oral jaws that happened earlier in parrotfish evolution may have contributed to this diversity by establishing parrotfishes as uniquely capable reef herbivores.
A Giant Chelonioid Turtle from the Late Cretaceous of Morocco with a Suction Feeding Apparatus Unique among Tetrapods

PubMed Central

Bardet, Nathalie; Jalil, Nour-Eddine; de Lapparent de Broin, France; Germain, Damien; Lambert, Olivier; Amaghzaz, Mbarek

2013-01-01

Background Secondary adaptation to aquatic life occurred independently in several amniote lineages, including reptiles during the Mesozoic and mammals during the Cenozoic. These evolutionary shifts to aquatic environments imply major morphological modifications, especially of the feeding apparatus. Mesozoic (250–65 Myr) marine reptiles, such as ichthyosaurs, plesiosaurs, mosasaurid squamates, crocodiles, and turtles, exhibit a wide range of adaptations to aquatic feeding and a broad overlap of their tooth morphospaces with those of Cenozoic marine mammals. However, despite these multiple feeding behavior convergences, suction feeding, though being a common feeding strategy in aquatic vertebrates and in marine mammals in particular, has been extremely rarely reported for Mesozoic marine reptiles. Principal Findings A relative of fossil protostegid and dermochelyoid sea turtles, Ocepechelon bouyai gen. et sp. nov. is a new giant chelonioid from the Late Maastrichtian (67 Myr) of Morocco exhibiting remarkable adaptations to marine life (among others, very dorsally and posteriorly located nostrils). The 70-cm-long skull of Ocepechelon not only makes it one of the largest marine turtles ever described, but also deviates significantly from typical turtle cranial morphology. It shares unique convergences with both syngnathid fishes (unique long tubular bony snout ending in a rounded and anteriorly directed mouth) and beaked whales (large size and elongated edentulous jaws). This striking anatomy suggests extreme adaptation for suction feeding unmatched among known turtles. Conclusion/Significance The feeding apparatus of Ocepechelon, a bony pipette-like snout, is unique among tetrapods. This new taxon exemplifies the successful systematic and ecological diversification of chelonioid turtles during the Late Cretaceous. This new evidence for a unique trophic specialization in turtles, along with the abundant marine vertebrate faunas associated to Ocepechelon in the Late Maastrichtian phosphatic beds of Morocco, further supports the hypothesis that marine life was, at least locally, very diversified just prior to the Cretaceous/Palaeogene (K/Pg) biotic crisis. PMID:23874378
Eusocial insects as emerging models for behavioural epigenetics.

PubMed

Yan, Hua; Simola, Daniel F; Bonasio, Roberto; Liebig, Jürgen; Berger, Shelley L; Reinberg, Danny

2014-10-01

Understanding the molecular basis of how behavioural states are established, maintained and altered by environmental cues is an area of considerable and growing interest. Epigenetic processes, including methylation of DNA and post-translational modification of histones, dynamically modulate activity-dependent gene expression in neurons and can therefore have important regulatory roles in shaping behavioural responses to environmental cues. Several eusocial insect species - with their unique displays of behavioural plasticity due to age, morphology and social context - have emerged as models to investigate the genetic and epigenetic underpinnings of animal social behaviour. This Review summarizes recent studies in the epigenetics of social behaviour and offers perspectives on emerging trends and prospects for establishing genetic tools in eusocial insects.

Decomposition of Rotor Hopfield Neural Networks Using Complex Numbers.

PubMed

Kobayashi, Masaki

2018-04-01

A complex-valued Hopfield neural network (CHNN) is a multistate model of a Hopfield neural network. It has the disadvantage of low noise tolerance. Meanwhile, a symmetric CHNN (SCHNN) is a modification of a CHNN that improves noise tolerance. Furthermore, a rotor Hopfield neural network (RHNN) is an extension of a CHNN. It has twice the storage capacity of CHNNs and SCHNNs, and much better noise tolerance than CHNNs, although it requires twice many connection parameters. In this brief, we investigate the relations between CHNN, SCHNN, and RHNN; an RHNN is uniquely decomposed into a CHNN and SCHNN. In addition, the Hebbian learning rule for RHNNs is decomposed into those for CHNNs and SCHNNs.
Cryogenic On-Orbit Liquid Depot-Storage, Acquisition and Transfer (COLD-SAT) Experiment Conceptual Design and Feasibility Study

NASA Technical Reports Server (NTRS)

Kramer, Edward (Editor)

1998-01-01

The cryogenic fluid management technologies required for the exploration of the solar system can only be fully developed via space-based experiments. A dedicated spacecraft is the most efficient way to perform these experiments. This report documents the extended conceptual design of the COLD-SAT spacecraft, capable of meeting these experimental requirements. All elements, including the spacecraft, ground segment, launch site modifications and launch vehicle operations, and flight operations are included. Greatly expanded coverage is provided for those areas unique to this cryogenic spacecraft, such as the experiment system, attitude control system, and spacecraft operations. Supporting analyses are included as are testing requirements, facilities surveys, and proposed project timelines.
Congenital zygomatico-mandibular fusion (pseudo-syngnathia?) in conjunction with unilateral anophthalmia: review of terminology and classification.

PubMed

Tauro, David P; Kallappanavar, N K; Kiran, H Y; Girhe, Vijaykumar J

2012-09-01

Syngnathia per se is a rare congenital disorder. A literature survey reveals a total of 26 cases of syngnathia in the English literature since 1936, of which only seven cases involved fusion of the ascending ramus of the mandible to the posterior portion of the maxilla and zygomatic complex. The remaining 19 involved fusion of the alveolar ridges of the maxilla and mandible. This is a unique case of fusion of the mandible to the zygomatic complex presenting with a unilateral anophthalmic orbit in an 18-day-old neonate. The use of the term syngnathia has been reviewed and a modification in classification has been suggested.
Organic compounds used in animal husbandry: Chapter 13

USGS Publications Warehouse

Wershaw, Robert L.; Shore, Laurence S.; Pruden, Amy; Shore, Laurence S.

2009-01-01

Although in general, the same drugs are used by humans as for animal husbandry, some compounds are unique to CAFOs. In raising and fattening steers, anabolic steroids are widely used in the US. In the cattle industry, large use is made of the acaricides, avermectins, and the cypermethrins as well as juvenile growth hormone inhibitor for fly and tick control that could affect soil fauna in very small quantities as they reach the environment without any modification. In poultry, the organic arsenides have been widely used for decades to control coccidiosis and increase growth. The environmental fate of the arsenic excreted in the poultry feces is therefore been an area of concern.
Phase retrieval based wavefront sensing experimental implementation and wavefront sensing accuracy calibration

NASA Astrophysics Data System (ADS)

Mao, Heng; Wang, Xiao; Zhao, Dazun

2009-05-01

As a wavefront sensing (WFS) tool, Baseline algorithm, which is classified as the iterative-transform algorithm of phase retrieval, estimates the phase distribution at pupil from some known PSFs at defocus planes. By using multiple phase diversities and appropriate phase unwrapping methods, this algorithm can accomplish reliable unique solution and high dynamic phase measurement. In the paper, a Baseline algorithm based wavefront sensing experiment with modification of phase unwrapping has been implemented, and corresponding Graphical User Interfaces (GUI) software has also been given. The adaptability and repeatability of Baseline algorithm have been validated in experiments. Moreover, referring to the ZYGO interferometric results, the WFS accuracy of this algorithm has been exactly calibrated.
Zinc finger nuclease technology: advances and obstacles in modelling and treating genetic disorders.

PubMed

Jabalameli, Hamid Reza; Zahednasab, Hamid; Karimi-Moghaddam, Amin; Jabalameli, Mohammad Reza

2015-03-01

Zinc finger nucleases (ZFNs) are engineered restriction enzymes designed to target specific DNA sequences within the genome. Assembly of zinc finger DNA-binding domain to a DNA-cleavage domain enables the enzyme machinery to target unique locus in the genome and invoke endogenous DNA repair mechanisms. This machinery offers a versatile approach in allele editing and gene therapy. Here we discuss the architecture of ZFNs and strategies for generating targeted modifications within the genome. We review advances in gene therapy and modelling of the disease using these enzymes and finally, discuss the practical obstacles in using this technology. Copyright © 2014 Elsevier B.V. All rights reserved.
Cycle life machine for AX-5 space suit

NASA Technical Reports Server (NTRS)

Schenberger, Deborah S.

1990-01-01

In order to accurately test the AX-5 space suit, a complex series of motions needed to be performed which provided a unique opportunity for mechanism design. The cycle life machine design showed how 3-D computer images can enhance mechanical design as well as help in visualizing mechanisms before manufacturing them. In the early stages of the design, potential problems in the motion of the joint and in the four bar linkage system were resolved using CAD. Since these problems would have been very difficult and tedious to solve on a drawing board, they would probably not have been addressed prior to fabrication, thus limiting the final design or requiring design modification after fabrication.
Selected Topics on the Synthesis, Properties and Applications of Multiwalled Carbon Nanotubes

PubMed Central

Stoner, B.R.; Brown, B.; Glass, J.T.

2014-01-01

Summary In summary, MWCNTs have been examined for a variety of electronic applications due to their unique structure and chemistry. Electrodes for field emission, energy and sensor applications hold particular interest. MWCNTs provide a very high surface area, relatively easy methods of surface modification, controllable and high concentration of reactive surface sites, and high specific capacitance. Combining MWCNTs with graphene structures, oxide and metal nanoparticles and certain polymers extends their performance and functionality. Such hybrid structures have been produced in situ during CNT growth and in two-step processes. Excellent progress on understanding the mechanisms of CNT growth has enabled numerous growth methods to all yield MWCNT structures in a variety of morphologies. PMID:24910503
Direct Human Contact with Siloxanes (Silicones) – Safety or Risk Part 1. Characteristics of Siloxanes (Silicones)

PubMed Central

Mojsiewicz-Pieńkowska, Krystyna; Jamrógiewicz, Marzena; Szymkowska, Katarzyna; Krenczkowska, Dominika

2016-01-01

Siloxanes are commonly known as silicones. They belong to the organosilicon compounds and are exclusively obtained by synthesis. Their chemical structure determines a range of physicochemical properties which were recognized as unique. Due to the susceptibility to chemical modifications, ability to create short, long or complex polymer particles, siloxanes found an application in many areas of human life. Siloxanes differ in particle size, molecular weight, shape and chemical groups. As a result, this determines the different physico-chemical properties, that directly affect the safety or the risk of their use. The areas that can be a source of danger to human health will be commented in this paper. PMID:27303296
A modified PATH algorithm rapidly generates transition states comparable to those found by other well established algorithms

PubMed Central

Chandrasekaran, Srinivas Niranj; Das, Jhuma; Dokholyan, Nikolay V.; Carter, Charles W.

2016-01-01

PATH rapidly computes a path and a transition state between crystal structures by minimizing the Onsager-Machlup action. It requires input parameters whose range of values can generate different transition-state structures that cannot be uniquely compared with those generated by other methods. We outline modifications to estimate these input parameters to circumvent these difficulties and validate the PATH transition states by showing consistency between transition-states derived by different algorithms for unrelated protein systems. Although functional protein conformational change trajectories are to a degree stochastic, they nonetheless pass through a well-defined transition state whose detailed structural properties can rapidly be identified using PATH. PMID:26958584
Synopsis and Review of the American College of Cardiology Foundation/American Heart Association 2013 ST-Elevation Myocardial Infarction Guideline.

PubMed

Brown, Helen F

2014-01-01

The "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines" is a major revision of the 2004 guideline. This article provides a synopsis and review of the guideline focusing on changes in patient care and implementing processes to ensure quality care. The implementation of this guideline provides nursing with a unique opportunity to affect patients and families primarily by recognition of the event and education about lifestyle modification and disease management. Regionalization of emergency systems provides a novel situation for nursing to develop interdepartmental and system protocols.
Osmotic Homeostasis

PubMed Central

Zeidel, Mark L.

2015-01-01

Alterations in water homeostasis can disturb cell size and function. Although most cells can internally regulate cell volume in response to osmolar stress, neurons are particularly at risk given a combination of complex cell function and space restriction within the calvarium. Thus, regulating water balance is fundamental to survival. Through specialized neuronal “osmoreceptors” that sense changes in plasma osmolality, vasopressin release and thirst are titrated in order to achieve water balance. Fine-tuning of water absorption occurs along the collecting duct, and depends on unique structural modifications of renal tubular epithelium that confer a wide range of water permeability. In this article, we review the mechanisms that ensure water homeostasis as well as the fundamentals of disorders of water balance. PMID:25078421
Zero-Gravity Atmospheric Cloud Physics Experiment Laboratory engineering concepts/design tradeoffs. Volume 1: Study results

NASA Technical Reports Server (NTRS)

Greco, R. V.; Eaton, L. R.; Wilkinson, H. C.

1974-01-01

The work is summarized which was accomplished from January 1974 to October 1974 for the Zero-Gravity Atmospheric Cloud Physics Laboratory. The definition and development of an atmospheric cloud physics laboratory and the selection and delineation of candidate experiments that require the unique environment of zero gravity or near zero gravity are reported. The experiment program and the laboratory concept for a Spacelab payload to perform cloud microphysics research are defined. This multimission laboratory is planned to be available to the entire scientific community to utilize in furthering the basic understanding of cloud microphysical processes and phenomenon, thereby contributing to improved weather prediction and ultimately to provide beneficial weather control and modification.
Poly(ADP-ribosyl)ation is recognized by ECT2 during mitosis.

PubMed

Li, Mo; Bian, Chunjing; Yu, Xiaochun

2014-01-01

Poly(ADP-ribosyl)ation is an unique posttranslational modification and required for spindle assembly and function during mitosis. However, the molecular mechanism of poly(ADP-ribose) (PAR) in mitosis remains elusive. Here, we show the evidence that PAR is recognized by ECT2, a key guanine nucleotide exchange factor in mitosis. The BRCT domain of ECT2 directly binds to PAR both in vitro and in vivo. We further found that α-tubulin is PARylated during mitosis. PARylation of α-tubulin is recognized by ECT2 and recruits ECT2 to mitotic spindle for completing mitosis. Taken together, our study reveals a novel mechanism by which PAR regulates mitosis.
Prolactin-secreting pituitary adenoma in a man with gigantism: a case report.

PubMed

Peillon, F; Philippon, J; Brandi, A M; Fohanno, D; Laplane, D; Dubois, M P; Decourt, J

1979-12-01

A prolactin-secreting pituitary adenoma was removed trans-sphenoidally from a 37 years old man with gigantism (218 cm). Serum levels of prolactin (PRL) were elevated pre-operatively and decreased after administration of L-Dopa with no increase after TRH as is usually observed in PRL-secreting adenomas. Growth hormone (GH) and somatomedin serum levels were normal with no modification of GH after insulin hypoglycemia, oral glucose loading or L-Dopa. Morphological examination of the tumour demonstrated the presence of lactotrophs by light and electron microscopy and by immunofluorescense staining. No somatotrophs were found. In this unique case, the relationship between a PRL-secreting adenoma and gigantism is discussed.
Laser-induced transitions between triply excited hollow states

NASA Astrophysics Data System (ADS)

Madsen, L. B.; Schlagheck, P.; Lambropoulos, P.

2000-12-01

Using complex scaling and a correlated basis constructed in terms of B splines, we calculate the Li+ photoion yield in the presence of a laser-induced coupling between the triply excited 2s22p(2Po) and 2s2p2(2De) resonances in lithium, the first of which is assumed to be excited by synchrotron radiation from the ground state. The laser coupling between the triply excited states is shown to lead to a significant and readily measurable modification of the line profile which provides a unique probe of the dipole strength between highly correlated triply excited states. We also present results for some higher-lying triply excited states of 2Po symmetry.
Energy consumption program: A computer model simulating energy loads in buildings

NASA Technical Reports Server (NTRS)

Stoller, F. W.; Lansing, F. L.; Chai, V. W.; Higgins, S.

1978-01-01

The JPL energy consumption computer program developed as a useful tool in the on-going building modification studies in the DSN energy conservation project is described. The program simulates building heating and cooling loads and computes thermal and electric energy consumption and cost. The accuracy of computations are not sacrificed, however, since the results lie within + or - 10 percent margin compared to those read from energy meters. The program is carefully structured to reduce both user's time and running cost by asking minimum information from the user and reducing many internal time-consuming computational loops. Many unique features were added to handle two-level electronics control rooms not found in any other program.
Studying Cold Nuclear Matter with the MPC-EX of PHENIX

NASA Astrophysics Data System (ADS)

Grau, Nathan; Phenix Collaboration

2017-09-01

Highly asymmetric collision systems, such as d+Au, provide a unique environment to study cold nuclear matter. Potential measurements range from pinning down the modification of the nuclear wave function, i.e. saturation, to studying final state interactions, i.e. energy loss. The PHENIX experiment has enhanced the muon piston calorimeter (MPC) with a silicon-tungsten preshower, the MPC-EX. With its fine segmentation the MPC-EX extends the photon detection capability at 3 < | η | < 3.8. In this talk we review the current status of the detector, its calibration, and its identification capabilities using the 2016 d+Au dataset. We also discuss the specific physics observables the MPC-EX can measure.
Identification of unique food handling practices that could represent food safety risks for minority consumers.

PubMed

Henley, Shauna C; Stein, Susan E; Quinlan, Jennifer J

2012-11-01

Foodborne illness caused by Salmonella and Campylobacter is a concern for consumers, and there is evidence that minority racial-ethnic populations experience greater rates of illness because of these pathogens. The limited body of research concerning food safety knowledge and practices among minority consumers has focused more on general food safety knowledge than on culturally specific food handling practices. The purpose of the research reported here was to explore food handling behaviors of minority racial-ethnic consumers through in-depth discussions in focus group settings. In this way, we hoped to identify potential unique, previously unidentified food handling practices among these consumers. Nine focus groups were held in Philadelphia, PA. Three focus groups were conducted with African American consumers, three with Hispanic consumers, and three with Asian consumers. In all, 56 consumers participated. Data were recorded, transcribed, and analyzed for unique and potentially unsafe food handling behaviors. Potentially unsafe food handling practices identified among all three groups included extended time to transport food from retail to home and washing of raw poultry. Culturally unique behaviors within groups included (i) using hot water (Asian, Hispanic) or acidic solutions (African American, Hispanic) to clean raw poultry, (ii) purchasing live poultry (Asian, Hispanic), (iii) cooking poultry overnight (African American), and (iv) preparing bite-size pieces of meat prior to cooking (Asian, Hispanic). To have focus groups include a limited number of participants and nonrandom sampling means that these themes and trends cannot be extrapolated to represent food mishandling among these populations in general. Results presented here allow modification of an existing food safety survey to identify the prevalence of these food handling practices among consumers of different demographics.
Improved electrochemical properties of morphology-controlled titania/titanate nanostructures prepared by in-situ hydrothermal surface modification of self-source Ti substrate for high-performance supercapacitors.

PubMed

Banerjee, Arghya Narayan; Anitha, V C; Joo, Sang W

2017-10-16

Ti substrate surface is modified into two-dimensional (2D) TiO 2 nanoplatelet or one-dimensional (1D) nanorod/nanofiber (or a mixture of both) structure in a controlled manner via a simple KOH-based hydrothermal technique. Depending on the KOH concentration, different types of TiO 2 nanostructures (2D platelets, 1D nanorods/nanofibers and a 2D+1D mixed sample) are fabricated directly onto the Ti substrate surface. The novelty of this technique is the in-situ modification of the self-source Ti surface into titania nanostructures, and its direct use as the electrochemical microelectrode without any modifications. This leads to considerable improvement in the interfacial properties between metallic Ti and semiconducting TiO 2 . Since interfacial states/defects have profound effect on charge transport properties of electronic/electrochemical devices, therefore this near-defect-free interfacial property of Ti-TiO 2 microelectrode has shown high supercapacitive performances for superior charge-storage devices. Additionally, by hydrothermally tuning the morphology of titania nanostructures, the electrochemical properties of the electrodes are also tuned. A Ti-TiO 2 electrode comprising of a mixture of 2D-platelet+1D-nanorod structure reveals very high specific capacitance values (~7.4 mF.cm -2 ) due to the unique mixed morphology which manifests higher active sites (hence, higher utilization of the active materials) in terms of greater roughness at the 2D-platelet structures and higher surface-to-volume-ratio in the 1D-nanorod structures.

Locomotor Dysfunction after Long-Duration Space Flight and Development of Countermeasures to Facilitate Faster Recovery

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Wood, S. J.; Cohen, H. S.; Bloomberg, J. J.

2012-01-01

Exposure to the microgravity conditions of space flight induces adaptive modification in sensorimotor function allowing astronauts to operate in this unique environment. This adaptive state, however, is inappropriate for a 1-g environment. Consequently astronauts must spend time readapting to Earth s gravity following their return to Earth. During this readaptation period, alterations in sensorimotor function cause various disturbances in astronaut gait during postflight walking. They often rely more on vision for postural and gait stability and many report the need for greater cognitive supervision of motor actions that previous to space flight were fully automated. Over the last several years our laboratory has investigated postflight astronaut locomotion with the aim of better understanding how adaptive changes in underlying sensorimotor mechanisms contribute to postflight gait dysfunction. Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibularly-mediated reflexive head movement during locomotion after space flight. Furthermore, during motor learning, adaptive transitions are composed of two main mechanisms: strategic and plastic. Strategic mechanisms represent immediate and transitory modifications in control to deal with changes in the prevailing environment that, if prolonged, induce plastic mechanisms designed to automate new behavioral responses. The goal of the present study was to examine the contributions of sensorimotor subsystems such as the vestibular and body load sensing (BLS) somatosensory influences on head movement control during locomotion after long-duration space flight. Further we present data on the two motor learning processes during readaptation of locomotor function after long-duration space flight.
Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation

PubMed Central

Esser, Dominik; Rauch, Bernadette

2014-01-01

SUMMARY The metabolism of Archaea, the third domain of life, resembles in its complexity those of Bacteria and lower Eukarya. However, this metabolic complexity in Archaea is accompanied by the absence of many “classical” pathways, particularly in central carbohydrate metabolism. Instead, Archaea are characterized by the presence of unique, modified variants of classical pathways such as the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway. The pentose phosphate pathway is only partly present (if at all), and pentose degradation also significantly differs from that known for bacterial model organisms. These modifications are accompanied by the invention of “new,” unusual enzymes which cause fundamental consequences for the underlying regulatory principles, and classical allosteric regulation sites well established in Bacteria and Eukarya are lost. The aim of this review is to present the current understanding of central carbohydrate metabolic pathways and their regulation in Archaea. In order to give an overview of their complexity, pathway modifications are discussed with respect to unusual archaeal biocatalysts, their structural and mechanistic characteristics, and their regulatory properties in comparison to their classic counterparts from Bacteria and Eukarya. Furthermore, an overview focusing on hexose metabolic, i.e., glycolytic as well as gluconeogenic, pathways identified in archaeal model organisms is given. Their energy gain is discussed, and new insights into different levels of regulation that have been observed so far, including the transcript and protein levels (e.g., gene regulation, known transcription regulators, and posttranslational modification via reversible protein phosphorylation), are presented. PMID:24600042
POTAMOS mass spectrometry calculator: computer aided mass spectrometry to the post-translational modifications of proteins. A focus on histones.

PubMed

Vlachopanos, A; Soupsana, E; Politou, A S; Papamokos, G V

2014-12-01

Mass spectrometry is a widely used technique for protein identification and it has also become the method of choice in order to detect and characterize the post-translational modifications (PTMs) of proteins. Many software tools have been developed to deal with this complication. In this paper we introduce a new, free and user friendly online software tool, named POTAMOS Mass Spectrometry Calculator, which was developed in the open source application framework Ruby on Rails. It can provide calculated mass spectrometry data in a time saving manner, independently of instrumentation. In this web application we have focused on a well known protein family of histones whose PTMs are believed to play a crucial role in gene regulation, as suggested by the so called "histone code" hypothesis. The PTMs implemented in this software are: methylations of arginines and lysines, acetylations of lysines and phosphorylations of serines and threonines. The application is able to calculate the kind, the number and the combinations of the possible PTMs corresponding to a given peptide sequence and a given mass along with the full set of the unique primary structures produced by the possible distributions along the amino acid sequence. It can also calculate the masses and charges of a fragmented histone variant, which carries predefined modifications already implemented. Additional functionality is provided by the calculation of the masses of fragments produced upon protein cleavage by the proteolytic enzymes that are most widely used in proteomics studies. Copyright © 2014 Elsevier Ltd. All rights reserved.
Impact of Xist RNA on chromatin modifications and transcriptional silencing maintenance at different stages of imprinted X chromosome inactivation in vole Microtus levis.

PubMed

Shevchenko, Alexander I; Grigor'eva, Elena V; Medvedev, Sergey P; Zakharova, Irina S; Dementyeva, Elena V; Elisaphenko, Eugeny A; Malakhova, Anastasia A; Pavlova, Sophia V; Zakian, Suren M

2018-03-01

In vole Microtus levis, cells of preimplantation embryo and extraembryonic tissues undergo imprinted X chromosome inactivation (iXCI) which is triggered by a long non-coding nuclear RNA, Xist. At early stages of iXCI, chromatin of vole inactive X chromosome is enriched with the HP1 heterochromatin-specific protein, trimethylated H3K9 and H4K20 attributable to constitutive heterochromatin. In the study, using vole trophoblast stem (TS) cells as a model of iXCI, we further investigated chromatin of the inactive X chromosome of M. levis and tried to find out the role of Xist RNA. We demonstrated that chromatin of the inactive X chromosome in vole TS cells also contained the SETDB1 histone methyltransferase and KAP1 protein. In addition, we observed that Xist RNA did not contribute significantly to maintenance of X chromosome inactive state during iXCI in vole TS cells. Xist repression affected neither transcriptional silencing caused by iXCI nor maintenance of trimethylated H3K9 and H4K20 as well as HP1, KAP1, and SETDB1 on the inactive X chromosome. Moreover, the unique repertoire of chromatin modifications on the inactive X chromosome in vole TS cells could be disrupted by a chemical compound, DZNep, and then restored even in the absence of Xist RNA. However, Xist transcript was necessary for recruitment of an additional repressive histone modification, trimethylated H3K27, to the inactive X chromosome during vole TS cell differentiation.
EpiProfile Quantifies Histone Peptides With Modifications by Extracting Retention Time and Intensity in High-resolution Mass Spectra*

PubMed Central

Yuan, Zuo-Fei; Lin, Shu; Molden, Rosalynn C.; Cao, Xing-Jun; Bhanu, Natarajan V.; Wang, Xiaoshi; Sidoli, Simone; Liu, Shichong; Garcia, Benjamin A.

2015-01-01

Histone post-translational modifications contribute to chromatin function through their chemical properties which influence chromatin structure and their ability to recruit chromatin interacting proteins. Nanoflow liquid chromatography coupled with high resolution tandem mass spectrometry (nanoLC-MS/MS) has emerged as the most suitable technology for global histone modification analysis because of the high sensitivity and the high mass accuracy of this approach that provides confident identification. However, analysis of histones with this method is even more challenging because of the large number and variety of isobaric histone peptides and the high dynamic range of histone peptide abundances. Here, we introduce EpiProfile, a software tool that discriminates isobaric histone peptides using the distinguishing fragment ions in their tandem mass spectra and extracts the chromatographic area under the curve using previous knowledge about peptide retention time. The accuracy of EpiProfile was evaluated by analysis of mixtures containing different ratios of synthetic histone peptides. In addition to label-free quantification of histone peptides, EpiProfile is flexible and can quantify different types of isotopically labeled histone peptides. EpiProfile is unique in generating layouts (i.e. relative retention time) of histone peptides when compared with manual quantification of the data and other programs (such as Skyline), filling the need of an automatic and freely available tool to quantify labeled and non-labeled modified histone peptides. In summary, EpiProfile is a valuable nanoflow liquid chromatography coupled with high resolution tandem mass spectrometry-based quantification tool for histone peptides, which can also be adapted to analyze nonhistone protein samples. PMID:25805797
Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster

PubMed Central

Rosenbaum, Erica E.; Vasiljevic, Eva; Brehm, Kimberley S.; Colley, Nansi Jo

2014-01-01

As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan) undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II), α-mannosidase-IIb (α-Man-IIb), a β-N-acetylglucosaminidase called fused lobes (Fdl), and hexosaminidase 1 (Hexo1). We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights into the functions of glycosyl hydrolases in the secretory pathway. PMID:24785692
OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.

PubMed

Simon, Dan N; Wriston, Amanda; Fan, Qiong; Shabanowitz, Jeffrey; Florwick, Alyssa; Dharmaraj, Tejas; Peterson, Sherket B; Gruenbaum, Yosef; Carlson, Cathrine R; Grønning-Wang, Line M; Hunt, Donald F; Wilson, Katherine L

2018-05-17

The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails. Using mass spectrometry, we identified 11 O -GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O -GlcNAc-modified at seven sites. By contrast, O -GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35. We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro. Interestingly, deletion Δ35, which does not remove the majority of identified O -GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1. These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function. The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
Decoupling the Arrhenius equation via mechanochemistry.

PubMed

Andersen, Joel M; Mack, James

2017-08-01

Mechanochemistry continues to reveal new possibilities in chemistry including the opportunity for "greening" reactions. Nevertheless, a clear understanding of the energetic transformations within mechanochemical systems remains elusive. We employed a uniquely modified ball mill and strategically chosen Diels-Alder reactions to evaluate the role of several ball-milling variables. This revealed three different energetic regions that we believe are defining characteristics of most, if not all, mechanochemical reactors. Relative to the locations of a given ball mill's regions, activation energy determines whether a reaction is energetically easy (Region I), challenging (Region II), or unreasonable (Region III) in a given timeframe. It is in Region II, that great sensitivity to mechanochemical conditions such as vial material and oscillation frequency emerge. Our unique modifications granted control of reaction vessel temperature, which in turn allowed control of the locations of Regions I, II, and III for our mill. Taken together, these results suggest envisioning vibratory mills (and likely other mechanochemical methodologies) as molecular-collision facilitating devices that act upon molecules occupying a thermally-derived energy distribution. This unifies ball-milling energetics with solution-reaction energetics via a common tie to the Arrhenius equation, but gives mechanochemistry the unique opportunity to influence either half of the equation. In light of this, we discuss a strategy for translating solvent-based reaction conditions to ball milling conditions. Lastly, we posit that the extra control via frequency factor grants mechanochemistry the potential for greater selectivity than conventional solution reactions.
Enzymes from solvent-tolerant microbes: useful biocatalysts for non-aqueous enzymology.

PubMed

Gupta, Anshu; Khare, S K

2009-01-01

Solvent-tolerant microbes are a newly emerging class that possesses the unique ability to thrive in the presence of organic solvents. Their enzymes adapted to mediate cellular and metabolic processes in a solvent-rich environment and are logically stable in the presence of organic solvents. Enzyme catalysis in non-aqueous/low-water media is finding increasing applications for the synthesis of industrially important products, namely peptides, esters, and other trans-esterification products. Solvent stability, however, remains a prerequisite for employing enzymes in non-aqueous systems. Enzymes, in general, get inactivated or give very low rates of reaction in non-aqueous media. Thus, early efforts, and even some recent ones, have aimed at stabilization of enzymes in organic media by immobilization, surface modifications, mutagenesis, and protein engineering. Enzymes from solvent-tolerant microbes appear to be the choicest source for studying solvent-stable enzymes because of their unique ability to survive in the presence of a range of organic solvents. These bacteria circumvent the solvent's toxic effects by virtue of various adaptations, e.g. at the level of the cytoplasmic membrane, by degradation and transformation of solvents, and by active excretion of solvents. The recent screening of these exotic microbes has generated some naturally solvent-stable proteases, lipases, cholesterol oxidase, cholesterol esterase, cyclodextrin glucanotransferase, and other important enzymes. The unique properties of these novel biocatalysts have great potential for applications in non-aqueous enzymology for a range of industrial processes.
ECM turnover-stimulated gene delivery through collagen-mimetic peptide-plasmid integration in collagen.

PubMed

Urello, Morgan A; Kiick, Kristi L; Sullivan, Millicent O

2017-10-15

Gene therapies have great potential in regenerative medicine; however, clinical translation has been inhibited by low stability and limited transfection efficiencies. Herein, we incorporate collagen-mimetic peptide (CMP)-linked polyplexes in collagen scaffolds to increase DNA stability by up to 400% and enable tailorable in vivo transgene expression at 100-fold higher levels and 10-fold longer time periods. These improvements were directly linked to a sustained interaction between collagen and polyplexes that persisted during cellular remodeling, polyplex uptake, and intracellular trafficking. Specifically, incorporation of CMPs into polyethylenimine (PEI) polyplexes preserved serum-exposed polyplex-collagen activity over a period of 14days, with 4 orders-of-magnitude more intact DNA present in CMP-modified polyplex-collagen relative to unmodified polyplex-collagen after a 10day incubation under cell culture conditions. CMP-modification also altered endocytic uptake, as indicated by gene silencing studies showing a nearly 50% decrease in transgene expression in response to caveolin-1 silencing in modified samples versus only 30% in unmodified samples. Furthermore, cellular internalization studies demonstrated that polyplex-collagen association persisted within cells in CMP polyplexes, but not in unmodified polyplexes, suggesting that CMP linkage to collagen regulates intracellular transport. Moreover, experiments in an in vivo repair model showed that CMP modification enabled tailoring of transgene expression from 4 to 25days over a range of concentrations. Overall, these findings demonstrate that CMP decoration provides substantial improvements in gene retention, altered release kinetics, improved serum-stability, and improved gene activity in vivo. This versatile technique has great potential for multiple applications in regenerative medicine. In this work, we demonstrate a novel approach for stably integrating DNA into collagen scaffolds to exploit the natural process of collagen remodelling for high efficiency non-viral gene delivery. The incorporation of CMPs into DNA polyplexes, coupled with the innate affinity between CMPs and collagen, not only permitted improved control over polyplex retention and release, but also provided a series of substantial and highly unique benefits via the stable and persistent linkage between CMP-polyplexes and collagen fragments. Specifically, CMP-modification of polyplexes was demonstrated to (i) control release for nearly a month, (ii) improve vector stability under physiological-like conditions, and (iii) provide ligands able to efficiently transfer genes via endocytic collagen pathways. These unique properties overcome key barriers inhibiting non-viral gene therapy. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Surface modification techniques for increased corrosion tolerance of zirconium fuel cladding

NASA Astrophysics Data System (ADS)

Carr, James Patrick, IV

Corrosion is a major issue in applications involving materials in normal and severe environments, especially when it involves corrosive fluids, high temperatures, and radiation. Left unaddressed, corrosion can lead to catastrophic failures, resulting in economic and environmental liabilities. In nuclear applications, where metals and alloys, such as steel and zirconium, are extensively employed inside and outside of the nuclear reactor, corrosion accelerated by high temperatures, neutron radiation, and corrosive atmospheres, corrosion becomes even more concerning. The objectives of this research are to study and develop surface modification techniques to protect zirconium cladding by the incorporation of a specific barrier coating, and to understand the issues related to the compatibility of the coatings examined in this work. The final goal of this study is to recommend a coating and process that can be scaled-up for the consideration of manufacturing and economic limits. This dissertation study builds on previous accident tolerant fuel cladding research, but is unique in that advanced corrosion methods are tested and considerations for implementation by industry are practiced and discussed. This work will introduce unique studies involving the materials and methods for accident tolerant fuel cladding research by developing, demonstrating, and considering materials and processes for modifying the surface of zircaloy fuel cladding. This innovative research suggests that improvements in the technique to modify the surface of zirconium fuel cladding are likely. Three elements selected for the investigation of their compatibility on zircaloy fuel cladding are aluminum, silicon, and chromium. These materials are also currently being investigated at other labs as alternate alloys and coatings for accident tolerant fuel cladding. This dissertation also investigates the compatibility of these three elements as surface modifiers, by comparing their microstructural and mechanical properties. To test their application for use in corrosive atmospheres, the corrosion behaviors are also compared in steam, water, and boric-acid environments. Various methods of surface modification were attempted in this investigation, including dip coating, diffusion bonding, casting, sputtering, and evaporation. The benefits and drawbacks of each method are discussed with respect to manufacturing and economic limits. Characterization techniques utilized in this work include optical microscopy, scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, nanoindentation, adhesion testing, and atomic force microscopy. The composition, microstructure, hardness, modulus, and coating adhesion were studied to provide encompassing properties to determine suitable comparisons and to choose an ideal method to scale to industrial applications. The experiments, results, and detailed discussions are presented in the following chapters of this dissertation research.
Integrative analysis with ChIP-seq advances the limits of transcript quantification from RNA-seq.

PubMed

Liu, Peng; Sanalkumar, Rajendran; Bresnick, Emery H; Keleş, Sündüz; Dewey, Colin N

2016-08-01

RNA-seq is currently the technology of choice for global measurement of transcript abundances in cells. Despite its successes, isoform-level quantification remains difficult because short RNA-seq reads are often compatible with multiple alternatively spliced isoforms. Existing methods rely heavily on uniquely mapping reads, which are not available for numerous isoforms that lack regions of unique sequence. To improve quantification accuracy in such difficult cases, we developed a novel computational method, prior-enhanced RSEM (pRSEM), which uses a complementary data type in addition to RNA-seq data. We found that ChIP-seq data of RNA polymerase II and histone modifications were particularly informative in this approach. In qRT-PCR validations, pRSEM was shown to be superior than competing methods in estimating relative isoform abundances within or across conditions. Data-driven simulations suggested that pRSEM has a greatly decreased false-positive rate at the expense of a small increase in false-negative rate. In aggregate, our study demonstrates that pRSEM transforms existing capacity to precisely estimate transcript abundances, especially at the isoform level. © 2016 Liu et al.; Published by Cold Spring Harbor Laboratory Press.
Elucidation of terpenoid metabolism in Scoparia dulcis by RNA-seq analysis.

PubMed

Yamamura, Yoshimi; Kurosaki, Fumiya; Lee, Jung-Bum

2017-03-07

Scoparia dulcis biosynthesize bioactive diterpenes, such as scopadulcic acid B (SDB), which are known for their unique molecular skeleton. Although the biosynthesis of bioactive diterpenes is catalyzed by a sequence of class II and class I diterpene synthases (diTPSs), the mechanisms underlying this process are yet to be fully identified. To elucidate these biosynthetic machinery, we performed a high-throughput RNA-seq analysis, and de novo assembly of clean reads revealed 46,332 unique transcripts and 40,503 two unigenes. We found diTPSs genes including a putative syn-copalyl diphosphate synthase (SdCPS2) and two kaurene synthase-like (SdKSLs) genes. Besides them, total 79 full-length of cytochrome P450 (CYP450) genes were also discovered. The expression analyses showed selected CYP450s associated with their expression pattern of SdCPS2 and SdKSL1, suggesting that CYP450 candidates involved diterpene modification. SdCPS2 represents the first predicted gene to produce syn-copalyl diphosphate in dicots. In addition, SdKSL1 potentially contributes to the SDB biosynthetic pathway. Therefore, these identified genes associated with diterpene biosynthesis lead to the development of genetic engineering focus on diterpene metabolism in S. dulcis.
Elucidation of terpenoid metabolism in Scoparia dulcis by RNA-seq analysis

PubMed Central

Yamamura, Yoshimi; Kurosaki, Fumiya; Lee, Jung-Bum

2017-01-01

Scoparia dulcis biosynthesize bioactive diterpenes, such as scopadulcic acid B (SDB), which are known for their unique molecular skeleton. Although the biosynthesis of bioactive diterpenes is catalyzed by a sequence of class II and class I diterpene synthases (diTPSs), the mechanisms underlying this process are yet to be fully identified. To elucidate these biosynthetic machinery, we performed a high-throughput RNA-seq analysis, and de novo assembly of clean reads revealed 46,332 unique transcripts and 40,503 two unigenes. We found diTPSs genes including a putative syn-copalyl diphosphate synthase (SdCPS2) and two kaurene synthase-like (SdKSLs) genes. Besides them, total 79 full-length of cytochrome P450 (CYP450) genes were also discovered. The expression analyses showed selected CYP450s associated with their expression pattern of SdCPS2 and SdKSL1, suggesting that CYP450 candidates involved diterpene modification. SdCPS2 represents the first predicted gene to produce syn-copalyl diphosphate in dicots. In addition, SdKSL1 potentially contributes to the SDB biosynthetic pathway. Therefore, these identified genes associated with diterpene biosynthesis lead to the development of genetic engineering focus on diterpene metabolism in S. dulcis. PMID:28266568
Toward Perovskite Solar Cell Commercialization: A Perspective and Research Roadmap Based on Interfacial Engineering.

PubMed

Rajagopal, Adharsh; Yao, Kai; Jen, Alex K-Y

2018-06-08

High-efficiency and low-cost perovskite solar cells (PVKSCs) are an ideal candidate for addressing the scalability challenge of solar-based renewable energy. The dynamically evolving research field of PVKSCs has made immense progress in solving inherent challenges and capitalizing on their unique structure-property-processing-performance traits. This review offers a unique outlook on the paths toward commercialization of PVKSCs from the interfacial engineering perspective, relevant to both specialists and nonspecialists in the field through a brief introduction of the background of the field, current state-of-the-art evolution, and future research prospects. The multifaceted role of interfaces in facilitating PVKSC development is explained. Beneficial impacts of diverse charge-transporting materials and interfacial modifications are summarized. In addition, the role of interfaces in improving efficiency and stability for all emerging areas of PVKSC design are also evaluated. The authors' integral contributions in this area are highlighted on all fronts. Finally, future research opportunities for interfacial material development and applications along with scalability-durability-sustainability considerations pivotal for facilitating laboratory to industry translation are presented. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Lithographically Encrypted Inverse Opals for Anti-Counterfeiting Applications.

PubMed

Heo, Yongjoon; Kang, Hyelim; Lee, Joon-Seok; Oh, You-Kwan; Kim, Shin-Hyun

2016-07-01

Colloidal photonic crystals possess inimitable optical properties of iridescent structural colors and unique spectral shape, which render them useful for security materials. This work reports a novel method to encrypt graphical and spectral codes in polymeric inverse opals to provide advanced security. To accomplish this, this study prepares lithographically featured micropatterns on the top surface of hydrophobic inverse opals, which serve as shadow masks against the surface modification of air cavities to achieve hydrophilicity. The resultant inverse opals allow rapid infiltration of aqueous solution into the hydrophilic cavities while retaining air in the hydrophobic cavities. Therefore, the structural color of inverse opals is regioselectively red-shifted, disclosing the encrypted graphical codes. The decoded inverse opals also deliver unique reflectance spectral codes originated from two distinct regions. The combinatorial code composed of graphical and optical codes is revealed only when the aqueous solution agreed in advance is used for decoding. In addition, the encrypted inverse opals are chemically stable, providing invariant codes with high reproducibility. In addition, high mechanical stability enables the transfer of the films onto any surfaces. This novel encryption technology will provide a new opportunity in a wide range of security applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The elastase-PK101 structure: Mechanism of an ultrasensitive activity-based probe revealed

DOE PAGES

Lechtenberg, Bernhard C.; Robinson, Howard R.; Kasperkiewicz, Paulina; ...

2015-01-22

Human neutrophil elastase (HNE) plays a central role in neutrophil host defense, but its broad specificity makes HNE a difficult target for both inhibitor and probe development. Recently, we identified the unnatural amino acid containing activity-based probe PK101, which exhibits astounding sensitivity and selectivity for HNE, yet completely lacks mechanistic explanation for its unique characteristics. Here, we present the crystal structure of the HNE-PK101 complex which not only reveals the basis for PK101 ultrasensitivity but also uncovers so far unrecognized HNE features. Strikingly, the Nle( O-Bzl) function in the P4 position of PK101 reveals and leverages an “exo-pocket” on HNEmore » as a critical factor for selectivity. Furthermore, the PK101 P3 position harbors a methionine dioxide function, which mimics a post-translationally oxidized methionine residue and forms a critical hydrogen bond to the backbone amide of Gly219 of HNE. Gly219 resides in a Gly–Gly motif that is unique to HNE, yet compulsory for this interaction. Consequently, this feature enables HNE to accommodate substrates that have undergone methionine oxidation, which constitutes a hallmark post-translational modification of neutrophil signaling.« less
Biocompatibility assessment of synthetic sling materials for female stress urinary incontinence.

PubMed

Gomelsky, Alex; Dmochowski, Roger R

2007-10-01

We evaluated the performance and complications of currently available synthetic sling materials with a focus on in vitro and in vivo biocompatibility, and acceptance in the human body. We reviewed the MEDLINE database for relevant literature pertaining to various synthetic sling materials. The Food and Drug Administration regulations regarding the regulation and biocompatibility testing of synthetic meshes were also reviewed. Many synthetic meshes used for sling construction were introduced before rigorous Food and Drug Administration regulations were passed and, thus, some became associated with unique complications. Most meshes used in pubovaginal and mid urethral sling surgery are associated with high short-term success rates and relatively few intraoperative complications. Despite modifications and additives, slings constructed from polytetrafluoroethylene and polyethylene are poorly accepted by the human body. Flexible, macroporous, polypropylene meshes appear to integrate more completely with human tissue than other synthetic materials. However, multifilament and nonknitted polypropylene slings may integrate poorly. The composition, weave and pore size of each material are unique. These properties are responsible for the strength and durability of the material, as well as the ultimate acceptance and incorporation in the human body. Each material should be individually evaluated and patients should be counseled appropriately before implantation.
Biomechanics and functional morphology of a climbing monocot

PubMed Central

Hesse, Linnea; Wagner, Sarah T.; Neinhuis, Christoph

2016-01-01

Plants with a climbing growth habit possess unique biomechanical properties arising from adaptations to changing loading conditions connected with close attachment to mechanical supports. In monocot climbers, mechanical adaptation is restricted by the absence of a bifacial vascular cambium. Flagellaria indica was used to investigate the mechanical properties and adaptations of a monocot climber that, uniquely, attaches to the surrounding vegetation via leaf tendrils. Biomechanical methods such as three-point bending and torsion tests were used together with anatomical studies on tissue development, modification and distribution. In general, the torsional modulus was lower than the bending modulus; hence, torsional stiffness was less than flexural stiffness. Basal parts of mature stems showed the greatest stiffness while that of more apical stem segments levelled off. Mechanical properties were modulated via tissue maturation processes mainly affecting the peripheral region of the stem. Peripheral vascular bundles showed a reduction in the amount of conducting tissue while the proportion and density of the bundle sheath increased. Furthermore, adjacent bundle sheaths merged resulting in a dense ring of fibrous tissue. Although F. indica lacks secondary cambial growth, the climbing habit is facilitated by a complex interaction of tissue maturation and attachment. PMID:26819259
RNA-Seq analyses reveal the order of tRNA processing events and the maturation of C/D box and CRISPR RNAs in the hyperthermophile Methanopyrus kandleri

PubMed Central

Su, Andreas A. H.; Tripp, Vanessa; Randau, Lennart

2013-01-01

The methanogenic archaeon Methanopyrus kandleri grows near the upper temperature limit for life. Genome analyses revealed strategies to adapt to these harsh conditions and elucidated a unique transfer RNA (tRNA) C-to-U editing mechanism at base 8 for 30 different tRNA species. Here, RNA-Seq deep sequencing methodology was combined with computational analyses to characterize the small RNome of this hyperthermophilic organism and to obtain insights into the RNA metabolism at extreme temperatures. A large number of 132 small RNAs were identified that guide RNA modifications, which are expected to stabilize structured RNA molecules. The C/D box guide RNAs were shown to exist as circular RNA molecules. In addition, clustered regularly interspaced short palindromic repeats RNA processing and potential regulatory RNAs were identified. Finally, the identification of tRNA precursors before and after the unique C8-to-U8 editing activity enabled the determination of the order of tRNA processing events with termini truncation preceding intron removal. This order of tRNA maturation follows the compartmentalized tRNA processing order found in Eukaryotes and suggests its conservation during evolution. PMID:23620296

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