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1

Investigations into Sequence and Conformational Dependence of Backbone Entropy, Inter-basin  

E-print Network

Investigations into Sequence and Conformational Dependence of Backbone Entropy, Inter-basin The populations and transitions between Ramachandran basins are stu- died for combinations of the standard 20 and employing seven commonly used force-fields. Both the basin populations and inter-conversion rates

Berry, R. Stephen

2

Comparative experimental investigation on the actuation mechanisms of ionic polymer-metal composites with different backbones and water contents  

NASA Astrophysics Data System (ADS)

Water-based ionic polymer-metal composites (IPMCs) exhibit complex deformation properties, especially when the water content changes. To explore the general actuation mechanisms, both Nafion and Flemion membranes are used as the polymer backbones. IPMC deformation includes three stages: fast anode deformation, relaxation deformation, and slow anode deformation, which is mainly dependent on the water content and the backbone. When the water content decreases from 21 to 14 wt. %, Nafion-IPMC exhibits a large negative relaxation deformation, zero deformation, a positive relaxation deformation, and a positive steady deformation without relaxation in sequence. Despite the slow anode deformation, Flemion-IPMC also shows a slight relaxation deformation, which disappears when the water content is less than 13 wt. %. The different water states are investigated at different water contents using nuclear magnetic resonance spectroscopy. The free water, which decreases rapidly at the beginning through evaporation, is proven to be critical for relaxation deformation. For the backbone, indirect evidence from the steady current response is correlated with the slow anode deformation of Flemion-IPMC. The latter is explained by the secondary dissociation of the weak acid group -COOH. Finally, we thoroughly explain not only the three deformations by swelling but also their evolvement with decreasing water content. A fitting model is also presented based on a multi-diffusion equation to reveal the deformation processes more clearly, the results from which are in good agreement with the experimental results.

Zhu, Zicai; Chang, Longfei; Asaka, Kinji; Wang, Yanjie; Chen, Hualing; Zhao, Hongxia; Li, Dichen

2014-03-01

3

Modeling backbone flexibility to achieve sequence diversity: The design of novel alpha-helical ligands for Bcl-xL  

PubMed Central

Computational protein design can be used to select sequences that are compatible with a fixed-backbone template. This strategy has been used in numerous instances to engineer novel proteins. However, the fixed-backbone assumption severely restricts the sequence space that is accessible via design. For challenging problems, such as the design of functional proteins, this may not be acceptable. In this paper, we present a method for introducing backbone flexibility into protein design calculations and apply it to the design of diverse helical BH3 ligands that bind to the anti-apoptotic protein Bcl-xL, a member of the Bcl-2 protein family. We demonstrate how normal mode analysis can be used to sample different BH3 backbones, and show that this leads to a larger and more diverse set of low-energy solutions than can be achieved using a native high-resolution Bcl-xL complex crystal structure as a template. We tested several of the designed solutions experimentally and found that this approach worked well when normal mode calculations were used to deform a native BH3 helix structure, but less well when they were used to deform an idealized helix. A subsequent round of design and testing identified a likely source of the problem as inadequate sampling of the helix pitch. In all, we tested seventeen designed BH3 peptide sequences, including several point mutants. Of these, eight bound well to Bcl-xL and four others showed weak but detectable binding. The successful designs showed a diversity of sequences that would have been difficult or impossible to achieve using only a fixed backbone. Thus, introducing backbone flexibility via normal mode analysis effectively broadened the set of sequences identified by computational design, and provided insight into positions important for binding Bcl-xL. PMID:17597151

Fu, Xiaoran; Apgar, James R.; Keating, Amy E.

2007-01-01

4

Assessment of flexible backbone protein design methods for sequence library prediction in the therapeutic antibody Herceptin-HER2 interface  

PubMed Central

Computational protein design methods can complement experimental screening and selection techniques by predicting libraries of low-energy sequences compatible with a desired structure and function. Incorporating backbone flexibility in computational design allows conformational adjustments that should broaden the range of predicted low-energy sequences. Here, we evaluate computational predictions of sequence libraries from different protocols for modeling backbone flexibility using the complex between the therapeutic antibody Herceptin and its target human epidermal growth factor receptor 2 (HER2) as a model system. Within the program RosettaDesign, three methods are compared: The first two use ensembles of structures generated by Monte Carlo protocols for near-native conformational sampling: kinematic closure (KIC) and backrub, and the third method uses snapshots from molecular dynamics (MD) simulations. KIC or backrub methods were better able to identify the amino acid residues experimentally observed by phage display in the Herceptin–HER2 interface than MD snapshots, which generated much larger conformational and sequence diversity. KIC and backrub, as well as fixed backbone simulations, captured the key mutation Asp98Trp in Herceptin, which leads to a further threefold affinity improvement of the already subnanomolar parental Herceptin-HER2 interface. Modeling subtle backbone conformational changes may assist in the design of sequence libraries for improving the affinity of antibody–antigen interfaces and could be suitable for other protein complexes for which structural information is available. PMID:21465611

Babor, Mariana; Mandell, Daniel J; Kortemme, Tanja

2011-01-01

5

Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology  

E-print Network

to a pro- tein backbone are exquisitely sensitive to their local envi- ronment. A computer program, SPARTA of known structure. Validation shows good agreement between the SPARTA-predicted and experimental shifts

Bax, Ad

6

Transformed composite sequences for improved qubit addressing  

NASA Astrophysics Data System (ADS)

Selective laser addressing of a single atom or atomic ion qubit can be improved using narrow-band composite pulse sequences. We describe a Lie-algebraic technique to generalize known narrow-band sequences and introduce sequences related by dilation and rotation of sequence generators. Our method improves known narrow-band sequences by decreasing both the pulse time and the residual error. Finally, we experimentally demonstrate these composite sequences using 40Ca+ ions trapped in a surface-electrode ion trap.

Merrill, J. True; Doret, S. Charles; Vittorini, Grahame; Addison, J. P.; Brown, Kenneth R.

2014-10-01

7

Transformed Composite Sequences for Improved Qubit Addressing  

E-print Network

Selective laser addressing of a single atom or atomic ion qubit can be improved using narrowband composite pulse sequences. We describe a Lie-algebraic technique to generalize known narrowband sequences and introduce new sequences related by dilation and rotation of sequence generators. Our method improves known narrowband sequences by decreasing both the pulse time and the residual error. Finally, we experimentally demonstrate these composite sequences using $^{40}$Ca$^+$ ions trapped in a surface-electrode ion trap.

J. True Merrill; S. Charles Doret; Grahame D. Vittorini; J. P. Addision; Kenneth R. Brown

2014-01-06

8

Transformed Composite Sequences for Improved Qubit Addressing  

E-print Network

Selective laser addressing of a single atom or atomic ion qubit can be improved using narrowband composite pulse sequences. We describe a Lie-algebraic technique to generalize known narrowband sequences and introduce new sequences related by dilation and rotation of sequence generators. Our method improves known narrowband sequences by decreasing both the pulse time and the residual error. Finally, we experimentally demonstrate these composite sequences using $^{40}$Ca$^+$ ions trapped in a surface-electrode ion trap.

Merrill, J True; Vittorini, Grahame D; Addision, J P; Brown, Kenneth R

2014-01-01

9

Loss of Internal Backbone Carbonyls: Additional Evidence for Sequence-Scrambling in Collision-Induced Dissociation of y-Type Ions  

NASA Astrophysics Data System (ADS)

It is shown that y-type ions, after losing C-terminal H2O or NH3, can lose an internal backbone carbonyl (CO) from different peptide positions and yield structurally different product fragment ions upon collision-induced dissociation (CID). Such CO losses from internal peptide backbones of y-fragment ions are not unique to a single peptide and were observed in four of five model peptides studied herein. Experimental details on examples of CO losses from y-type fragment ions for an isotopically labeled AAAAH AA-NH2 heptapeptide and des-acetylated-?-melanocyte-stimulating hormone (d?-MSH) (SYSMEHFRWGKPV-NH2) are reported. Results from isotope labeling, tandem mass spectrometry (MSn), and ion mobility-mass spectrometry (IM-MS) confirm that CO losses from different amino acids of m/ z-isolated y-type ions yield structurally different ions. It is shown that losses of internal backbone carbonyls (as CID products of m/ z-isolated y-type ions) are among intermediate steps towards formation of rearranged or permutated product fragment ions. Possible mechanisms for generation of the observed sequence-scrambled a-"like" ions, as intermediates in sequence-scrambling pathways of y-type ions, are proposed and discussed.

Harper, Brett; Miladi, Mahsan; Solouki, Touradj

2014-10-01

10

2-Methoxy-4-methylsulfinylbenzyl: A Backbone Amide Safety-Catch Protecting Group for the Synthesis and Purification of Difficult Peptide Sequences.  

PubMed

The use of 2-methoxy-4-methylsulfinylbenzyl (Mmsb) as a new backbone amide-protecting group that acts as a safety-catch structure is proposed. Mmsb, which is stable during the elongation of the sequence and trifluoroacetic acid-mediated cleavage from the resin, improves the synthetic process as well as the properties of the quasi-unprotected peptide. Mmsb offers the possibility of purifying and characterizing complex peptide sequences, and renders the target peptide after NH4 I/TFA treatment and subsequent ether precipitation to remove the cleaved Mmsb moiety. First, the "difficult peptide" sequence H-(Ala)10 -NH2 was selected as a model to optimize the new protecting group strategy. Second, the complex, bioactive Ac-(RADA)4 -NH2 sequence was chosen to validate this methodology. The improvements in solid-phase peptide synthesis combined with the enhanced solubility of the quasi-unprotected peptides, as compared with standard sequences, made it possible to obtain purified Ac-(RADA)4 -NH2 . To extend the scope of the approach, the challenging A?(1-42) peptide was synthesized and purified in a similar manner. The proposed Mmsb strategy opens up the possibility of synthesizing other challenging small proteins. PMID:25280354

Paradís-Bas, Marta; Tulla-Puche, Judit; Albericio, Fernando

2014-11-10

11

hnCOcaNH and hncoCANH pulse sequences for rapid and unambiguous backbone assignment in (13C, 15N) labeled proteins.  

PubMed

Time-saving in data acquisition is a major thrust of NMR pulse sequence development in the context of structural proteomics research. The conventional HNCA and HN(CA)CO pulse sequences, routinely used for sequential backbone assignment, have the limitation that they cannot distinguish inter- and intra-residue correlations. In order to remove this ambiguity, one has to record HNCO and HN(CO)CA or sequential HNCA experiments which provide unambiguous information of sequential correlations. However, this almost doubles the experimental time. Besides, they require repeated scanning through the (15)N planes to search for the matching peaks along the carbon dimension. In this background, we present here two pulse sequences, termed as hncoCANH and hnCOcaNH that lead to spectra equivalent to HNCA and HN(CA)CO spectra, respectively, but with direct distinction of inter- and intra-residue peaks; these occur with opposite signs in the new experiments. The two pulse sequences have been derived by simple modification of the previously described HN(C)N pulse sequence [Panchal et al., J. Biomol. NMR 20 (2001) 135-147] to frequency-label (13)C(alpha) or (13)C' instead of (15)N during the t(1) period. Like HN(C)N, these spectra also exhibit special patterns of self and sequential peaks around glycines and prolines, which enable direct identification of certain triplets of residues and thus provide internal checks during the sequential assignment walk. The spectra enable rapid and unambiguous assignment of H(N), (15)N and (13)C(alpha) (or (13)C') in a single experiment, and thus would be of great value in high-throughput structural proteomics. PMID:20643567

Kumar, Dinesh; Reddy, Jithender G; Hosur, Ramakrishna V

2010-09-01

12

The Completely Sequenced Plasmid pEST4011 Contains a Novel IncP1 Backbone and a Catabolic Transposon Harboring tfd Genes for 2,4-Dichlorophenoxyacetic Acid Degradation  

PubMed Central

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterium Achromobacter xylosoxidans subsp. denitrificans strain EST4002 contains plasmid pEST4011. This plasmid ensures its host a stable 2,4-D+ phenotype. We determined the complete 76,958-bp nucleotide sequence of pEST4011. This plasmid is a deletion and duplication derivative of pD2M4, the 95-kb highly unstable laboratory ancestor of pEST4011, and was self-generated during different laboratory manipulations performed to increase the stability of the 2,4-D+ phenotype of the original strain, strain D2M4(pD2M4). The 47,935-bp catabolic region of pEST4011 forms a transposon-like structure with identical copies of the hybrid insertion element IS1071::IS1471 at the two ends. The catabolic regions of pEST4011 and pJP4, the best-studied 2,4-D-degradative plasmid, both contain homologous, tfd-like genes for complete 2,4-D degradation, but they have little sequence similarity other than that. The backbone genes of pEST4011 are most similar to the corresponding genes of broad-host-range self-transmissible IncP1 plasmids. The backbones of the other three IncP1 catabolic plasmids that have been sequenced (the 2,4-D-degradative plasmid pJP4, the haloacetate-catabolic plasmid pUO1, and the atrazine-catabolic plasmid pADP-1) are nearly identical to the backbone of R751, the archetype plasmid of the IncP1 ? subgroup. We show that despite the overall similarity in plasmid organization, the pEST4011 backbone is sufficiently different (51 to 86% amino acid sequence identity between individual backbone genes) from the backbones of members of the three IncP1 subgroups (the ?, ?, and ? subgroups) that it belongs to a new IncP1subgroup, the ? subgroup. This conclusion was also supported by a phylogenetic analysis of the trfA2, korA, and traG gene products of different IncP1 plasmids. PMID:15489427

Vedler, Eve; Vahter, Merle; Heinaru, Ain

2004-01-01

13

Fold homology detection using sequence fragment composition profiles of proteins.  

PubMed

The effectiveness of sequence alignment in detecting structural homology among protein sequences decreases markedly when pairwise sequence identity is low (the so-called "twilight zone" problem of sequence alignment). Alternative sequence comparison strategies able to detect structural kinship among highly divergent sequences are necessary to address this need. Among them are alignment-free methods, which use global sequence properties (such as amino acid composition) to identify structural homology in a rapid and straightforward way. We explore the viability of using tetramer sequence fragment composition profiles in finding structural relationships that lie undetected by traditional alignment. We establish a strategy to recast any given protein sequence into a tetramer sequence fragment composition profile, using a series of amino acid clustering steps that have been optimized for mutual information. Our method has the effect of compressing the set of 160,000 unique tetramers (if using the 20-letter amino acid alphabet) into a more tractable number of reduced tetramers (approximately 15-30), so that a meaningful tetramer composition profile can be constructed. We test remote homology detection at the topology and fold superfamily levels using a comprehensive set of fold homologs, culled from the CATH database that share low pairwise sequence similarity. Using the receiver-operating characteristic measure, we demonstrate potentially significant improvement in using information-optimized reduced tetramer composition, over methods relying only on the raw amino acid composition or on traditional sequence alignment, in homology detection at or below the "twilight zone". PMID:20635424

Solis, Armando D; Rackovsky, Shalom R

2010-10-01

14

Sea Lion Skeleton - Backbone  

NSDL National Science Digital Library

Sea lions are vertebrates with both backbones and ribs. The backbone is a gliding joint, allowing the animal to be flexible, while the ribs main function is to protect it's inner organs. The short tail helps to balance the animal while walking on land.

Ketan Patel (California State University, Fullerton;Student, Biological Sciences)

2007-07-27

15

Optimal arbitrarily accurate composite pulse sequences  

E-print Network

Implementing a single-qubit unitary is often hampered by imperfect control. Systematic amplitude errors ?, caused by incorrect duration or strength of a pulse, are an especially common problem. But a sequence of imperfect ...

Low, Guang Hao

16

Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences  

PubMed Central

During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life. PMID:22319215

Derr, Julien; Manapat, Michael L.; Rajamani, Sudha; Leu, Kevin; Xulvi-Brunet, Ramon; Joseph, Isaac; Nowak, Martin A.; Chen, Irene A.

2012-01-01

17

Spines, backbones and orthopedic surgery. Spines, backbones and orthopedic surgery.  

E-print Network

1/ 17 Spines, backbones and orthopedic surgery. Spines, backbones and orthopedic surgery. Simon;2/ 17 Spines, backbones and orthopedic surgery. Motivation #12;2/ 17 Spines, backbones and orthopedic and orthopedic surgery. Motivation Recent work (B-boys & Schweinsberg, Aidekon-Harris) considers branching

18

Methods and compositions for efficient nucleic acid sequencing  

DOEpatents

Disclosed are novel methods and compositions for rapid and highly efficient nucleic acid sequencing based upon hybridization with two sets of small oligonucleotide probes of known sequences. Extremely large nucleic acid molecules, including chromosomes and non-amplified RNA, may be sequenced without prior cloning or subcloning steps. The methods of the invention also solve various current problems associated with sequencing technology such as, for example, high noise to signal ratios and difficult discrimination, attaching many nucleic acid fragments to a surface, preparing many, longer or more complex probes and labelling more species.

Drmanac, Radoje (850 E. Greenwich Pl., Palo Alto, CA 94303)

2002-01-01

19

Dolphin Skeleton - Backbone  

NSDL National Science Digital Library

The dolphin is built to be sleek. Its body is made of almost entirely backbone (a gliding joint) which makes it very flexible under water. The ribs protect the inner organs of the dolphin and the tail beats from side to side, thrusting the animal forward.

Ketan Patel (California State University, Fullerton;Student, Biological Sciences)

2007-07-27

20

Soil amino acid composition across a boreal forest successional sequence  

Microsoft Academic Search

Soil amino acids are important sources of organic nitrogen for plant nutrition, yet few studies have examined which amino acids are most prevalent in the soil. In this study, we examined the composition, concentration, and seasonal patterns of soil amino acids across a primary successional sequence encompassing a natural gradient of plant productivity and soil physicochemical characteristics. Soil was collected

Nancy R. Werdin-Pfisterer; Knut Kielland; Richard D. Boone

2009-01-01

21

Integrating Information Literacy with a Sequenced English Composition Curriculum  

ERIC Educational Resources Information Center

This article details the process of implementing a sequenced information literacy program for two core English composition courses at Utah State University. An extensive needs assessment guided the project, leading to a curriculum design process with the goal of building a foundation for deeper critical thinking skills. The curriculum development…

Holliday, Wendy; Fagerheim, Britt

2006-01-01

22

Broadband CPMG sequence with short composite refocusing pulses  

NASA Astrophysics Data System (ADS)

We demonstrate that CPMG sequences with phase-modulated refocusing pulses of the same duration as the standard 180° pulses can generate echo trains with significantly increased amplitudes compared to the standard CPMG sequence in the case when there is a large range of Larmor frequencies across the sample. The best performance is achieved with symmetric phase-alternating (SPA) composite refocusing pulses of the form ?-y?+y?-y. In comparison to standard 180° pulses, we show that with SPA refocusing pulses with ? ? 27° and ? ? 126°, it is possible to double the signal-to-noise ratio without increasing the total pulse duration or power consumption of the refocusing pulses. The increased bandwidth of these pulses more than compensates for the decrease in performance in the vicinity of resonance. To achieve the full benefit of the broadband nature of the SPA pulses in a CPMG sequence, it is necessary to combine these refocusing pulses with a broadband excitation pulse. When it is not possible to use a short, high amplitude excitation pulse, we show that phase-alternating (PA) excitation pulses are suitable for this purpose. We present a detailed analysis of the underlying spin dynamics of these new pulse sequences and confirm the simulations with experiments. We show that for samples with T1/T2 > 1, the new sequences in grossly inhomogeneous fields do not only generate echoes with an increased amplitude, but also with an increased decay time. Finally, we analyze the diffusion properties and show quantitatively that the broadband sequences have a substantially higher diffusion sensitivity compared with the standard CPMG sequence.

Koroleva, Van D. M.; Mandal, Soumyajit; Song, Yi-Qiao; Hürlimann, Martin D.

2013-05-01

23

Amino Acid Composition Distribution: a Novel Sequence Representation for Prediction of Protein Subcellular Localization  

Microsoft Academic Search

A novel representation of protein sequence, amino acid composition distribution (AACD), is introduced to perform prediction of subcellular localization in this paper. First, a protein sequence is divided equally into multiple segments. Then, amino acid composition of each segment is calculated in series. After that, each protein sequence can be represented a feature vector. Finally, feature vectors of all sequences

Jianyu Shi; Shaowu Zhang; Quan Pan; Guo-Ping Zhou

2007-01-01

24

Protein-Like Tertiary Folding Behavior from Heterogeneous Backbones  

PubMed Central

Due to the vital roles proteins play in life, much effort has been invested in their mimicry by synthetic agents. One approach to this goal is to design unnatural backbone oligomers (“foldamers”) that fold like natural peptides. Despite success in secondary structure mimicry by such species, protein-like tertiary folds remain elusive. A fundamental challenge underlying this task is the design of a sequence of side chains that will specify a complex tertiary folding pattern on an unnatural backbone. We report here a sequence-based approach to convert a natural protein with a compact tertiary fold to an analogue with a backbone composed of ?20% unnatural building blocks but similar folding behavior as the parent protein. PMID:23937097

Reinert, Zachary E.; Lengyel, George A.; Horne, W. Seth

2013-01-01

25

Protein-like tertiary folding behavior from heterogeneous backbones.  

PubMed

Because proteins play vital roles in life, much effort has been invested in their mimicry by synthetic agents. One approach is to design unnatural backbone oligomers ("foldamers") that fold like natural peptides. Despite success in secondary structure mimicry by such species, protein-like tertiary folds remain elusive. A fundamental challenge underlying this task is the design of a sequence of side chains that will specify a complex tertiary folding pattern on an unnatural backbone. We report here a sequence-based approach to convert a natural protein with a compact tertiary fold to an analogue with a backbone composed of ~20% unnatural building blocks but folding behavior similar to that of the parent protein. PMID:23937097

Reinert, Zachary E; Lengyel, George A; Horne, W Seth

2013-08-28

26

Analytical expressions and lineshape simulations for Levitt-Suter-Ernst composite-pulse quadrupolar echo sequences  

NASA Astrophysics Data System (ADS)

Analytical expressions are derived for the Levitt-Suter-Emst composite quadrupolar echo sequences, allowing facile lineshape calculations for comparison with experiment. Large phase distortions in the lineshape obtained with the first-order sequence are significantly reduced with the second-order sequence. For 90° pulse lengths greater than ˜5?s, both sequences produce large phase errors for typical 2H quadrupolar coupling strengths in solids.

Barbara, Thomas M.

27

Plant development inhibitory genes in binary vector backbone improve quality event efficiency in soybean transformation.  

PubMed

Conventional Agrobacterium-mediated plant transformation often produces a significant frequency of transgenic events containing vector backbone sequence, which is generally undesirable for biotechnology applications. We tested methods to reduce the frequency of transgenic plants containing vector backbone by incorporating genes into the backbone that inhibit the development of transgenic plants. Four backbone frequency reduction genes, bacterial levansucrase (sacB), maize cytokinin oxidase (CKX), Phaseolus GA 2-oxidase (GA 2-ox), and bacterial phytoene synthase (crtB), each expressed by the enhanced CaMV 35S promoter, were placed individually in a binary vector backbone near the left border (LB) of binary vectors. In transformed soybean plants, the lowest frequency of backbone presence was observed when the constitutively expressed CKX gene was used, followed by crtB. Higher backbone frequencies were found among the plants transformed with the GA 2-oxidase and sacB vectors. In some events, transfer of short backbone fragments appeared to be caused by LB readthrough and termination within the backbone reduction gene. To determine the effect of the backbone genes on transformation frequency, the crtB and CKX vectors were then compared to a control vector in soybean transformation experiments. The results revealed that there was no significant transformation frequency difference between the crtB and control vectors, but the CKX vector showed a significant transformation frequency decrease. Molecular analysis revealed that the frequency of transgenic plants containing one or two copies of the transgene and free of backbone was significantly increased by both the CKX and crtB backbone reduction vectors, indicating that there may be a correlation between transgene copy number and backbone frequency. PMID:18253857

Ye, Xudong; Williams, Edward J; Shen, Junjiang; Esser, James A; Nichols, Amy M; Petersen, Michael W; Gilbertson, Larry A

2008-10-01

28

High-Fidelity Adiabatic Passage by Composite Sequences of Chirped Pulses  

SciTech Connect

We present a method for optimization of the technique of adiabatic passage between two quantum states by composite sequences of frequency-chirped pulses with specific relative phases: composite adiabatic passage (CAP). By choosing the composite phases appropriately the nonadiabatic losses can be canceled to any desired order with sufficiently long sequences, regardless of the nonadiabatic coupling. The values of the composite phases are universal for they do not depend on the pulse shapes and the chirp. The accuracy of the CAP technique and its robustness against parameter variations make CAP suitable for high-fidelity quantum information processing.

Torosov, Boyan T. [Department of Physics, Sofia University, 5 James Bourchier Boulevard, 1164 Sofia (Bulgaria); Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR CNRS 5209, BP 47870, F-21078 Dijon (France); Guerin, Stephane [Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR CNRS 5209, BP 47870, F-21078 Dijon (France); Vitanov, Nikolay V. [Department of Physics, Sofia University, 5 James Bourchier Boulevard, 1164 Sofia (Bulgaria)

2011-06-10

29

Diverse nucleotide compositions and sequence fluctuation in Rubisco protein genes  

NASA Astrophysics Data System (ADS)

The Rubisco protein-enzyme is arguably the most abundance protein on Earth. The biology dogma of transcription and translation necessitates the study of the Rubisco genes and Rubisco-like genes in various species. Stronger correlation of fractal dimension of the atomic number fluctuation along a DNA sequence with Shannon entropy has been observed in the studied Rubisco-like gene sequences, suggesting a more diverse evolutionary pressure and constraints in the Rubisco sequences. The strategy of using metal for structural stabilization appears to be an ancient mechanism, with data from the porphobilinogen deaminase gene in Capsaspora owczarzaki and Monosiga brevicollis. Using the chi-square distance probability, our analysis supports the conjecture that the more ancient Rubisco-like sequence in Microcystis aeruginosa would have experienced very different evolutionary pressure and bio-chemical constraint as compared to Bordetella bronchiseptica, the two microbes occupying either end of the correlation graph. Our exploratory study would indicate that high fractal dimension Rubisco sequence would support high carbon dioxide rate via the Michaelis- Menten coefficient; with implication for the control of the whooping cough pathogen Bordetella bronchiseptica, a microbe containing a high fractal dimension Rubisco-like sequence (2.07). Using the internal comparison of chi-square distance probability for 16S rRNA (~ E-22) versus radiation repair Rec-A gene (~ E-05) in high GC content Deinococcus radiodurans, our analysis supports the conjecture that high GC content microbes containing Rubisco-like sequence are likely to include an extra-terrestrial origin, relative to Deinococcus radiodurans. Similar photosynthesis process that could utilize host star radiation would not compete with radiation resistant process from the biology dogma perspective in environments such as Mars and exoplanets.

Holden, Todd; Dehipawala, S.; Cheung, E.; Bienaime, R.; Ye, J.; Tremberger, G., Jr.; Schneider, P.; Lieberman, D.; Cheung, T.

2011-10-01

30

Identical repeated backbone of the human genome  

PubMed Central

Background Identical sequences with a minimal length of about 300 base pairs (bp) have been involved in the generation of various meiotic/mitotic genomic rearrangements through non-allelic homologous recombination (NAHR) events. Genomic disorders and structural variation, together with gene remodelling processes have been associated with many of these rearrangements. Based on these observations, we identified and integrated all the 100% identical repeats of at least 300 bp in the NCBI version 36.2 human genome reference assembly into non-overlapping regions, thus defining the Identical Repeated Backbone (IRB) of the reference human genome. Results The IRB sequences are distributed all over the genome in 66,600 regions, which correspond to ~2% of the total NCBI human genome reference assembly. Important structural and functional elements such as common repeats, segmental duplications, and genes are contained in the IRB. About 80% of the IRB bp overlap with known copy-number variants (CNVs). By analyzing the genes embedded in the IRB, we were able to detect some identical genes not previously included in the Ensembl release 50 annotation of human genes. In addition, we found evidence of IRB gene copy-number polymorphisms in raw sequence reads of two diploid sequenced genomes. Conclusions In general, the IRB offers new insight into the complex organization of the identical repeated sequences of the human genome. It provides an accurate map of potential NAHR sites which could be used in targeting the study of novel CNVs, predicting DNA copy-number variation in newly sequenced genomes, and improve genome annotation. PMID:20096123

2010-01-01

31

The backbone of a city  

NASA Astrophysics Data System (ADS)

Recent studies have revealed the importance of centrality measures to analyze various spatial factors affecting human life in cities. Here we show how it is possible to extract the backbone of a city by deriving spanning trees based on edge betweenness and edge information. By using as sample cases the cities of Bologna and San Francisco, we show how the obtained trees are radically different from those based on edge lengths, and allow an extended comprehension of the “skeleton” of most important routes that so much affects pedestrian/vehicular flows, retail commerce vitality, land-use separation, urban crime and collective dynamical behaviours.

Scellato, S.; Cardillo, A.; Latora, V.; Porta, S.

2006-03-01

32

Problems with Parsimony in Sequences of Biased Base Composition Adam Eyre-Walker  

E-print Network

Problems with Parsimony in Sequences of Biased Base Composition Adam Eyre-Walker Centre- simony. Key words: Parsimony -- G + C content -- Base composition -- Substitution pattern -- Mutation. The cases are of the sort gen- erally encountered in the inference of substitution and mutation patterns (e.g

Eyre-Walker, Adam

33

The Evolution of Word Composition in Metazoan Promoter Sequence  

Microsoft Academic Search

The field of molecular evolution provides many examples of the principle that molecular differences between species contain information about evolutionary history. One surprising case can be found in the frequency of short words in DNA: more closely related species have more similar word compositions. Interest in this has often focused on its utility in deducing phylogenetic relationships. However, it is

Eliot C. Bush; Bruce T. Lahn

2006-01-01

34

Conserved thermodynamic contributions of backbone hydrogen bonds in a protein fold  

PubMed Central

Backbone–backbone hydrogen-bonding interactions are a ubiquitous and highly conserved structural feature of proteins that adopt the same fold (i.e., have the same overall backbone topology). This work addresses the question of whether or not this structural conservation is also reflected as a thermodynamic conservation. Reported here is a comparative thermodynamic analysis of backbone hydrogen bonds in two proteins that adopt the same fold but are unrelated at the primary amino acid sequence level. With amide-to-ester bond mutations introduced by total chemical synthesis methods, the thermodynamic consequences of backbone–backbone hydrogen-bond deletions at five different structurally equivalent positions throughout the ?-?-? fold of Arc repressor and CopG were assessed. The ester bond-containing analogues all folded into native-like three-dimensional structures that were destabilized from 2.5 to 6.0 kcal/(mol dimer) compared with wild-type controls. Remarkably, the five paired analogues with amide-to-ester bond mutations at structurally equivalent positions were destabilized to exactly the same degree, regardless of the degree to which the mutation site was buried in the structure. The results are interpreted as evidence that the thermodynamics of backbone–backbone hydrogen-bonding interactions in a protein fold are conserved. PMID:16473949

Wang, Min; Wales, Thomas E.; Fitzgerald, Michael C.

2006-01-01

35

Utilisation of cod backbone by biochemical fractionation  

Microsoft Academic Search

The backbone fraction obtained from industrial processing of Atlantic cod (Gadus morhua) yields about 15% of the whole fish weight. Due to a high content of muscle and bone proteins, it is a valuable raw material for further processing. In the present work minced backbones were subjected to gentle hydrolysis by proteinases to solubilize muscle proteins before the pure bone

Asbjørn Gildberg; Jan A Arnesen; Mats Carlehög

2002-01-01

36

Flexible backbone aromatic polyimide adhesives  

NASA Technical Reports Server (NTRS)

Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

Progar, Donald J.; St. Clair, Terry L.

1989-01-01

37

Flexible backbone aromatic polyimide adhesives  

NASA Technical Reports Server (NTRS)

Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

Progar, Donald J.; St.clair, Terry L.

1988-01-01

38

Enzymes/non-enzymes classification model complexity based on composition, sequence, 3D and topological indices.  

PubMed

The huge amount of new proteins that need a fast enzymatic activity characterization creates demands of protein QSAR theoretical models. The protein parameters that can be used for an enzyme/non-enzyme classification includes the simpler indices such as composition, sequence and connectivity, also called topological indices (TIs) and the computationally expensive 3D descriptors. A comparison of the 3D versus lower dimension indices has not been reported with respect to the power of discrimination of proteins according to enzyme action. A set of 966 proteins (enzymes and non-enzymes) whose structural characteristics are provided by PDB/DSSP files was analyzed with Python/Biopython scripts, STATISTICA and Weka. The list of indices includes, but it is not restricted to pure composition indices (residue fractions), DSSP secondary structure protein composition and 3D indices (surface and access). We also used mixed indices such as composition-sequence indices (Chou's pseudo-amino acid compositions or coupling numbers), 3D-composition (surface fractions) and DSSP secondary structure amino acid composition/propensities (obtained with our Prot-2S Web tool). In addition, we extend and test for the first time several classic TIs for the Randic's protein sequence Star graphs using our Sequence to Star Graph (S2SG) Python application. All the indices were processed with general discriminant analysis models (GDA), neural networks (NN) and machine learning (ML) methods and the results are presented versus complexity, average of Shannon's information entropy (Sh) and data/method type. This study compares for the first time all these classes of indices to assess the ratios between model accuracy and indices/model complexity in enzyme/non-enzyme discrimination. The use of different methods and complexity of data shows that one cannot establish a direct relation between the complexity and the accuracy of the model. PMID:18606172

Munteanu, Cristian Robert; González-Díaz, Humberto; Magalhães, Alexandre L

2008-09-21

39

Epoxy\\/Polyurethane\\/Clay Ternary Nanocomposites – Effect of Components Mixing Sequence on the Composites Properties  

Microsoft Academic Search

The present work investigates the mixing sequence of montmorillonite (MMT) and polyurethane (PUR) on epoxy resin (EP) properties. Mechanical properties were evaluated and structures analyzed by means of infrared spectroscopy (FTIR), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The measured properties of all tested compositions were improved in comparison with unmodified epoxy resin. The best mechanical properties were exhibited

M. Bakar; M. Lavorgna; J. Szyma?ska; A. D?tkowska

2012-01-01

40

Protein location prediction using atomic composition and global features of the amino acid sequence  

SciTech Connect

Subcellular location of protein is constructive information in determining its function, screening for drug candidates, vaccine design, annotation of gene products and in selecting relevant proteins for further studies. Computational prediction of subcellular localization deals with predicting the location of a protein from its amino acid sequence. For a computational localization prediction method to be more accurate, it should exploit all possible relevant biological features that contribute to the subcellular localization. In this work, we extracted the biological features from the full length protein sequence to incorporate more biological information. A new biological feature, distribution of atomic composition is effectively used with, multiple physiochemical properties, amino acid composition, three part amino acid composition, and sequence similarity for predicting the subcellular location of the protein. Support Vector Machines are designed for four modules and prediction is made by a weighted voting system. Our system makes prediction with an accuracy of 100, 82.47, 88.81 for self-consistency test, jackknife test and independent data test respectively. Our results provide evidence that the prediction based on the biological features derived from the full length amino acid sequence gives better accuracy than those derived from N-terminal alone. Considering the features as a distribution within the entire sequence will bring out underlying property distribution to a greater detail to enhance the prediction accuracy.

Cherian, Betsy Sheena, E-mail: betsy.skb@gmail.com [Centre for Bioinformatics, University of Kerala, Kariyavattom Campus, Thiruvananthapuram, Kerala (India); Nair, Achuthsankar S. [Centre for Bioinformatics, University of Kerala, Kariyavattom Campus, Thiruvananthapuram, Kerala (India)] [Centre for Bioinformatics, University of Kerala, Kariyavattom Campus, Thiruvananthapuram, Kerala (India)

2010-01-22

41

Optimum stacking sequence design of composite sandwich panel using genetic algorithms  

NASA Astrophysics Data System (ADS)

Composite sandwich structures recently gained preference for various structural components over conventional metals and simple composite laminates in the aerospace industries. For most widely used composite sandwich structures, the optimization problems only requires the determination of the best stacking sequence and the number of laminae with different fiber orientations. Genetic algorithm optimization technique based on Darwin's theory of survival of the fittest and evolution is most suitable for solving such optimization problems. The present research work focuses on the stacking sequence optimization of composite sandwich panels with laminated face-sheets for both critical buckling load maximization and thickness minimization problems, subjected to bi-axial compressive loading. In the previous studies, only balanced and even-numbered simple composite laminate panels have been investigated ignoring the effects of bending-twisting coupling terms. The current work broadens the application of genetic algorithms to more complex composite sandwich panels with balanced, unbalanced, even and odd-numbered face-sheet laminates including the effects of bending-twisting coupling terms.

Bir, Amarpreet Singh

42

External Tank - The Structure Backbone  

NASA Technical Reports Server (NTRS)

The External Tank forms the structural backbone of the Space Shuttle in the launch configuration. Because the tank flies to orbital velocity with the Space Shuttle Orbiter, minimization of weight is mandatory, to maximize payload performance. Choice of lightweight materials both for structure and thermal conditioning was necessary. The tank is large, and unique manufacturing facilities, tooling, handling, and transportation operations were required. Weld processes and tooling evolved with the design as it matured through several block changes, to reduce weight. Non Destructive Evaluation methods were used to assure integrity of welds and thermal protection system materials. The aluminum-lithium alloy was used near the end of the program and weld processes and weld repair techniques had to be refined. Development and implementation of friction stir welding was a substantial technology development incorporated during the Program. Automated thermal protection system application processes were developed for the majority of the tank surface. Material obsolescence was an issue throughout the 40 year program. The final configuration and tank weight enabled international space station assembly in a high inclination orbit allowing international cooperation with the Russian Federal Space Agency. Numerous process controls were implemented to assure product quality, and innovative proof testing was accomplished prior to delivery. Process controls were implemented to assure cleanliness in the production environment, to control contaminants, and to preclude corrosion. Each tank was accepted via rigorous inspections, including non-destructive evaluation techniques, proof testing, and all systems testing. In the post STS-107 era, the project focused on ascent debris risk reduction. This was accomplished via stringent process controls, post flight assessment using substantially improved imagery, and selective redesigns. These efforts were supported with a number of test programs to simulate combined environments. Processing improvements included development and use of low spray guns for foam application, additional human factors considerations for production, use of high fidelity mockups during hardware processing with video review, improved tank access, extensive use of non destructive evaluation, and producibility enhancements. Design improvements included redesigned bipod fittings, a bellows heater, a feedline camera active during ascent flight, removal of the protuberance airload ramps, redesigned ice frost ramps, and titanium brackets replaced aluminum brackets on the liquid oxygen feedline. Post flight assessment improved due to significant addition of imagery assets, greatly improving situational awareness. The debris risk was reduced by two orders of magnitude. During this time a major natural disaster was overcome when Katrina damaged the manufacturing facility. Numerous lessons from these efforts are documented within the paper.

Welzyn, Kenneth; Pilet, Jeffrey C.; Diecidue-Conners, Dawn; Worden, Michelle; Guillot, Michelle

2011-01-01

43

Probability distributions for the strength of composite materials II: A convergent sequence of tight bounds  

Microsoft Academic Search

A sequence of convergent upper bounds is developed for the probability distribution of strength of composite materials. The analysis is based on the well-known chain-of-bundles model, and local load sharing is assumed for the nonfailed fiber elements in each bundle. The bounds are based on the occurrence ofk or more adjacent broken fibers in a bundle, an event which is

D. G. Harlow; S. L. Phoenix

1981-01-01

44

Nucleotide composition of CO1 sequences in Chelicerata (Arthropoda): detecting new mitogenomic rearrangements.  

PubMed

Here we study the evolution of nucleotide composition in third codon-positions of CO1 sequences of Chelicerata, using a phylogenetic framework, based on 180 taxa and three markers (CO1, 18S, and 28S rRNA; 5,218 nt). The analyses of nucleotide composition were also extended to all CO1 sequences of Chelicerata found in GenBank (1,701 taxa). The results show that most species of Chelicerata have a positive strand bias in CO1, i.e., in favor of C nucleotides, including all Amblypygi, Palpigradi, Ricinulei, Solifugae, Uropygi, and Xiphosura. However, several taxa show a negative strand bias, i.e., in favor of G nucleotides: all Scorpiones, Opisthothelae spiders and several taxa within Acari, Opiliones, Pseudoscorpiones, and Pycnogonida. Several reversals of strand-specific bias can be attributed to either a rearrangement of the control region or an inversion of a fragment containing the CO1 gene. Key taxa for which sequencing of complete mitochondrial genomes will be necessary to determine the origin and nature of mtDNA rearrangements involved in the reversals are identified. Acari, Opiliones, Pseudoscorpiones, and Pycnogonida were found to show a strong variability in nucleotide composition. In addition, both mitochondrial and nuclear genomes have been affected by higher substitution rates in Acari and Pseudoscorpiones. The results therefore indicate that these two orders are more liable to fix mutations of all types, including base substitutions, indels, and genomic rearrangements. PMID:22362465

Arabi, Juliette; Judson, Mark L I; Deharveng, Louis; Lourenço, Wilson R; Cruaud, Corinne; Hassanin, Alexandre

2012-02-01

45

A new decoupling method for accurate quantification of polyethylene copolymer composition and triad sequence distribution with 13C NMR  

NASA Astrophysics Data System (ADS)

13C NMR is a powerful analytical tool for characterizing polyethylene copolymer composition and sequence distribution. Accurate characterization of the composition and sequence distribution is critical for researchers in industry and academia. Some common composite pulse decoupling (CPD) sequences used in polyethylene copolymer 13C NMR can lead to artifacts such as modulations of the decoupled 13C NMR signals (decoupling sidebands) resulting in systematic errors in quantitative analysis. A new CPD method was developed, which suppresses decoupling sidebands below the limit of detection (less than 1:40,000 compared to the intensity of the decoupled signal). This new CPD sequence consists of an improved Waltz-16 CPD, implemented as a bilevel method. Compared with other conventional CPD programs this new decoupling method produced the cleanest 13C NMR spectra for polyethylene copolymer composition and triad sequence distribution analyses.

Zhou, Zhe; Kümmerle, Rainer; Qiu, Xiaohua; Redwine, David; Cong, Rongjuan; Taha, Angela; Baugh, Dan; Winniford, Bill

2007-08-01

46

Indian Railways Backbone of Information Transport in India  

E-print Network

1 Indian Railways ­ Backbone of Information Transport in India Santosh Kumar, Ohio State University: Indian Railways is the backbone of public transport in India. With ever- increasing number of people to be the backbone of any country's economy. Indian Railways undoubtedly is the backbone of public transport in India

Kumar, Santosh

47

Human genetic-epidemiologic association analysis via allelic composition and DNA sequence similarity methods : applications to blood-based gene expression biomarkers of disease  

E-print Network

Epidemiologic Association Analysis via Allelic Composition and DNA Sequence Similarity Methods:Epidemiologic Association Analysis via Allelic Composition and DNA Sequence Similarity Methods:methods to implement these approaches. Molecular Phenotyping and Biomarker Analysis Increasing emphasis in epidemiologic

Wessel, Jennifer

2006-01-01

48

A Novel Method for Determining Microflora Composition using Dynamic Phylogenetic Analysis of 16S Ribosomal RNA Deep Sequencing Data  

PubMed Central

Deep sequencing of the 16S rRNA gene provides a comprehensive view of bacterial communities in a particular environment and has expanded our ability to study the impact of the microflora on human health and disease. Current analysis methods rely on comparisons of the sequences generated with an expanding but limited set of annotated 16S rRNA sequences or phylogenic clustering of sequences based on arbitrary similarity cutoffs. We describe a novel approach to characterize bacterial composition using deep sequencing of 16S rRNA gene. Our method defines operational taxonomic units based on phylogenetic tree reconstruction and dynamic clustering of sequences using solely sequencing data. These OTUs can be used to identify differences in bacteria abundance between environments. This approach can perform better than previous phylogenetic methods and will significantly improve our understanding of the microfloral role on human diseases by providing a comprehensive analysis of the microbial composition from various bacterial communities. PMID:21515358

Chan, Ernest R.; Hester, James; Kalady, Matthew; Xiao, Hui; Li, Xiaoxia; Serre, David

2011-01-01

49

Sequencer  

NSDL National Science Digital Library

In this activity, students enter the starting number, multiplier, and add-on for a sequence to be graphed. This activity allows students to explore arithmetic and geometric sequences as well as combinations of the two. This activity can also be used to introduce the concepts surrounding limits and infinity. This activity includes supplemental materials, including background information about the topics covered, a description of how to use the application, and exploration questions for use with the java applet.

2010-01-01

50

Evidence of Evolutionary Constraints That Influences the Sequence Composition and Diversity of Mitochondrial Matrix Targeting Signals  

PubMed Central

Mitochondrial targeting signals (MTSs) are responsible for trafficking nuclear encoded proteins to their final destination within mitochondria. These sequences are diverse, sharing little amino acid homology and vary significantly in length, and although the formation of a positively-charged amphiphilic alpha helix within the MTS is considered to be necessary and sufficient to mediate import, such a feature does not explain their diversity, nor how such diversity influences target sequence function, nor how such dissimilar signals interact with a single, evolutionarily conserved import mechanism. An in silico analysis of 296 N-terminal, matrix destined MTSs from Homo sapiens, Mus musculus, Saccharomyces cerevisiae, Arabidopsis thaliana, and Oryza sativa was undertaken to investigate relationships between MTSs, and/or, relationships between an individual targeting signal sequence and the protein that it imports. We present evidence that suggests MTS diversity is influenced in part by physiochemical and N-terminal characteristics of their mature sequences, and that some of these correlated characteristics are evolutionarily maintained across a number of taxa. Importantly, some of these associations begin to explain the variation in MTS length and composition. PMID:23825690

Doyle, Stephen R.; Kasinadhuni, Naga R. P.; Chan, Chee Kai; Grant, Warwick N.

2013-01-01

51

Simple Sequence Repeats in Escherichia coli: Abundance, Distribution, Composition, and Polymorphism  

PubMed Central

Computer-based genome-wide screening of the DNA sequence of Escherichia coli strain K12 revealed tens of thousands of tandem simple sequence repeat (SSR) tracts, with motifs ranging from 1 to 6 nucleotides. SSRs were well distributed throughout the genome. Mononucleotide SSRs were over-represented in noncoding regions and under-represented in open reading frames (ORFs). Nucleotide composition of mono- and dinucleotide SSRs, both in ORFs and in noncoding regions, differed from that of the genomic region in which they occurred, with 93% of all mononucleotide SSRs proving to be of A or T. Computer-based analysis of the fine position of every SSR locus in the noncoding portion of the genome relative to downstream ORFs showed SSRs located in areas that could affect gene regulation. DNA sequences at 14 arbitrarily chosen SSR tracts were compared among E. coli strains. Polymorphisms of SSR copy number were observed at four of seven mononucleotide SSR tracts screened, with all polymorphisms occurring in noncoding regions. SSR polymorphism could prove important as a genome-wide source of variation, both for practical applications (including rapid detection, strain identification, and detection of loci affecting key phenotypes) and for evolutionary adaptation of microbes.[The sequence data described in this paper have been submitted to the GenBank data library under accession numbers AF209020–209030 and AF209508–209518.] PMID:10645951

Gur-Arie, Riva; Cohen, Cyril J.; Eitan, Yuval; Shelef, Leora; Hallerman, Eric M.; Kashi, Yechezkel

2000-01-01

52

Infrared spectral sequence of quenched carbonaceous composite subjected to thermal annealing  

NASA Astrophysics Data System (ADS)

We investigate the spectroscopic alteration through thermal annealing on the quenched carbonaceous composite (QCC) produced from hydrocarbon plasma. The emission and absorption spectra of QCC samples annealed at various temperatures indicate that the proportion of aliphatic C-H bonds in QCC decreases relative to aromatic C-H bonds with increase of annealing temperature. By comparing the spectra of annealed QCC with observed emission spectra of proto-planetary nebulae, similarity between the spectral sequence obtained in the laboratory and that in the observational data is clearly noticed. On this basis, we discuss a simple evolutional scenario of carbon dust in circumstellar environment around cool evolved stars.

Goto, M.; Maihara, T.; Terada, H.; Kaito, C.; Kimura, S.; Wada, S.

2000-01-01

53

Postglacial climate-change record in biomarker lipid compositions of the Hani peat sequence, Northeastern China  

NASA Astrophysics Data System (ADS)

The peat sequence at Hani in northeastern China accumulated over the past 16 cal kyr in a percolation mire in which rain water and ground water seeped through the peat system. The molecular compositions of n-alkanes, n-alkanols, and n-alkanoic acids extracted from the Hani peat sequence reveal different responses to the progressive evolution of climate and changes in the nature of the peat-forming vegetation. Long chain length components that originate from the waxy coatings of subaerial vascular plants dominate the n-alkane distributions throughout the Hani peat sequence. The paleoclimate integrity of these biomarker molecules appears to be well preserved. Most of the n-alkanol distributions are similarly dominated by long chain components that indicate their origins from subaerial plants. In contrast, n-alkanoic acid distributions are dominated by secondary components that record the importance of post-depositional microbial activity in this peat sequence, which evidently can be extensive in a percolation mire. Elevated n-alkane Paq values and C 23/C 29 ratios, which are both molecular proxies for water-loving plants, record an especially moist local climate in the Bølling-Allerød (14.5 to 12.9 ka), Younger Dryas (12.9 to 11.5 ka), and Pre-Boreal (11.5 to 10.5 ka) portions of the Hani peat sequence. Depressed Paq values and C 23/C 29 ratios and larger n-alkane average chain length values indicate that the Holocene Climatic Optimum (10.5 to 6 ka) was a period of warmer climate with lower effective precipitation, which contrasts with evidence of wetter climates in most of East Asia.

Zhou, Weijian; Zheng, Yanhong; Meyers, Philip A.; Jull, A. J. Timothy; Xie, Shucheng

2010-05-01

54

Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis  

PubMed Central

Background Experimental designs that take advantage of high-throughput sequencing to generate datasets include RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), sequencing of 16S rRNA gene fragments, metagenomic analysis and selective growth experiments. In each case the underlying data are similar and are composed of counts of sequencing reads mapped to a large number of features in each sample. Despite this underlying similarity, the data analysis methods used for these experimental designs are all different, and do not translate across experiments. Alternative methods have been developed in the physical and geological sciences that treat similar data as compositions. Compositional data analysis methods transform the data to relative abundances with the result that the analyses are more robust and reproducible. Results Data from an in vitro selective growth experiment, an RNA-seq experiment and the Human Microbiome Project 16S rRNA gene abundance dataset were examined by ALDEx2, a compositional data analysis tool that uses Bayesian methods to infer technical and statistical error. The ALDEx2 approach is shown to be suitable for all three types of data: it correctly identifies both the direction and differential abundance of features in the differential growth experiment, it identifies a substantially similar set of differentially expressed genes in the RNA-seq dataset as the leading tools and it identifies as differential the taxa that distinguish the tongue dorsum and buccal mucosa in the Human Microbiome Project dataset. The design of ALDEx2 reduces the number of false positive identifications that result from datasets composed of many features in few samples. Conclusion Statistical analysis of high-throughput sequencing datasets composed of per feature counts showed that the ALDEx2 R package is a simple and robust tool, which can be applied to RNA-seq, 16S rRNA gene sequencing and differential growth datasets, and by extension to other techniques that use a similar approach. PMID:24910773

2014-01-01

55

Quantum chemical studies of peptide nucleic acid monomers and role of cyclohexyl modification on backbone flexibility  

NASA Astrophysics Data System (ADS)

Peptide nucleic acids (PNA) bind sequence specifically to DNA/RNA and are of major interest for all fields of molecular biology and could form the basis for gene-targeted drugs. Modifications are introduced in PNA to overcome problems associated with orientational selectivity in binding, to restrict conformational flexibility of backbone, and to discriminate binding for either DNA or RNA. The addition of geometrical isomers (1R,2S and 1S,2R) of cyclohexyl ring in the backbone of PNA could bring rigidification to PNA backbone and may impart specificity toward RNA. Therefore, quantum chemical studies are aimed to explore the conformational space, to find out preferred stable conformations of PNA and modified (1R,2S and 1S,2R) cyclohexyl PNA monomer. Content:text/plain; charset="UTF-8"

Sharma, Smriti; Sonavane, Uddhavesh B.; Joshi, Rajendra R.

56

Effect of annealing on phase sequence and their composition in the Pt-coated Mo system  

NASA Astrophysics Data System (ADS)

The phase formation sequence and the composition of phases induced by thermal annealing in a platinum (Pt) coated molybdenum (Mo) system were investigated by X-ray diffraction (XRD), Rutherford backscattering spectrometry (RBS) and transmission electron microscopy (TEM). The X-ray diffraction study of a 0.2 ?m thick platinum layer deposited on a Mo substrate and annealed at temperatures between 800 °C and 900 °C for different periods of time shows the formation of MoPt2 and MoPt phases. It was also found that these phases nucleate sequentially and the MoPt2 phase becomes unstable at 900 °C after a longer annealing time of 8 h. Rutherford backscattering spectroscopy and transmission electron microscopy showed that the coating thickness approximately doubled after thermal annealing, from 0.22 ?m to 0.46 ?m, due to the formation of the Pt-Mo phases.

Khumalo, Z. M.; Topi?, M.; Comrie, C. M.; Blumenthal, M.; Pineda-Vargas, C. A.; Bucher, R.; Kisslinger, K.

2014-11-01

57

Disorder Predictors Also Predict Backbone Dynamics for a Family of Disordered Proteins  

PubMed Central

Several algorithms have been developed that use amino acid sequences to predict whether or not a protein or a region of a protein is disordered. These algorithms make accurate predictions for disordered regions that are 30 amino acids or longer, but it is unclear whether the predictions can be directly related to the backbone dynamics of individual amino acid residues. The nuclear Overhauser effect between the amide nitrogen and hydrogen (NHNOE) provides an unambiguous measure of backbone dynamics at single residue resolution and is an excellent tool for characterizing the dynamic behavior of disordered proteins. In this report, we show that the NHNOE values for several members of a family of disordered proteins are highly correlated with the output from three popular algorithms used to predict disordered regions from amino acid sequence. This is the first test between an experimental measure of residue specific backbone dynamics and disorder predictions. The results suggest that some disorder predictors can accurately estimate the backbone dynamics of individual amino acids in a long disordered region. PMID:22195023

Daughdrill, Gary W.; Borcherds, Wade M.; Wu, Hongwei

2011-01-01

58

Improving the accuracy of protein stability predictions with multistate design using a variety of backbone ensembles.  

PubMed

Multistate computational protein design (MSD) with backbone ensembles approximating conformational flexibility can predict higher quality sequences than single-state design with a single fixed backbone. However, it is currently unclear what characteristics of backbone ensembles are required for the accurate prediction of protein sequence stability. In this study, we aimed to improve the accuracy of protein stability predictions made with MSD by using a variety of backbone ensembles to recapitulate the experimentally measured stability of 85 Streptococcal protein G domain ?1 sequences. Ensembles tested here include an NMR ensemble as well as those generated by molecular dynamics (MD) simulations, by Backrub motions, and by PertMin, a new method that we developed involving the perturbation of atomic coordinates followed by energy minimization. MSD with the PertMin ensembles resulted in the most accurate predictions by providing the highest number of stable sequences in the top 25, and by correctly binning sequences as stable or unstable with the highest success rate (?90%) and the lowest number of false positives. The performance of PertMin ensembles is due to the fact that their members closely resemble the input crystal structure and have low potential energy. Conversely, the NMR ensemble as well as those generated by MD simulations at 500 or 1000 K reduced prediction accuracy due to their low structural similarity to the crystal structure. The ensembles tested herein thus represent on- or off-target models of the native protein fold and could be used in future studies to design for desired properties other than stability. PMID:24174277

Davey, James A; Chica, Roberto A

2014-05-01

59

Intrinsic backbone preferences are fully present in blocked amino acids  

PubMed Central

The preferences of amino acid residues for ?,? backbone angles vary strikingly among the amino acids, as shown by the backbone angle ? found from the 3J(H?,HN) coupling constant for short peptides in water. New data for the 3J(H?,HN) values of blocked amino acids (dipeptides) are given here. Dipeptides exhibit the full range of coupling constants shown by longer peptides such as GGXGG and dipeptides present the simplest system for analyzing backbone preferences. The dipeptide coupling constants are surprisingly close to values computed from the coil library (conformations of residues not in helices and not in sheets). Published coupling constants for GGXGG peptides agree closely with dipeptide values for all nonpolar residues and for some polar residues but not for X = D, N, T, and Y, which are probably affected by polar side chain–backbone interactions in GGXGG peptides. Thus, intrinsic backbone preferences are already determined at the dipeptide level and remain almost unchanged in GGXGG peptides and are strikingly similar in the coil library of conformations from protein structures. The simplest explanation for the backbone preferences is that backbone conformations are strongly affected by electrostatic dipole–dipole interactions in the peptide backbone and by screening of these interactions with water, which depends on nearby side chains. Strong backbone electrostatic interactions occur in dipeptides. This is shown by calculations both of backbone electrostatic energy for different conformers of the alanine dipeptide in the gas phase and by electrostatic solvation free energies of amino acid dipeptides. PMID:16423894

Avbelj, Franc; Grdadolnik, Simona Golic; Grdadolnik, Joze; Baldwin, Robert L.

2006-01-01

60

Side chain chemistry mediates backbone fragmentation in hydrogen deficient peptide radicals.  

PubMed

A crown ether based, photolabile radical precursor which forms noncovalent complexes with peptides has been prepared. The peptide/precursor complexes can be electrosprayed, isolated in an ion trap, and then subjected to laser photolysis and collision induced dissociation to generate hydrogen deficient peptide radicals. It is demonstrated that these peptide radicals behave very differently from the hydrogen rich peptide radicals generated by electron capture methods. In fact, it is shown that side chain chemistry dictates both the occurrence and relative abundance of backbone fragments that are observed. Fragmentation at aromatic residues occurs preferentially over most other amino acids. The origin of this selectivity relates to the mechanism by which backbone dissociation is initiated. The first step is abstraction of a beta-hydrogen from the side chain, followed by beta-elimination to yield primarily a-type fragment ions. Calculations reveal that those side chains which can easily lose a beta-hydrogen correlate well with experimentally favored sites for backbone fragmentation. In addition, radical mediated side chain losses from the parent peptide are frequently observed. Eleven amino acids exhibit unique mass losses from side chains which positively identify that particular amino acid as part of the parent peptide. Therefore, side chain losses allow one to unambiguously narrow the possible sequences for a parent peptide, which when combined with predictable backbone fragmentation should lead to greatly increased confidence in peptide identification. PMID:19113886

Sun, Qingyu; Nelson, Hosea; Ly, Tony; Stoltz, Brian M; Julian, Ryan R

2009-02-01

61

HASH: a program to accurately predict protein H? shifts from neighboring backbone shifts.  

PubMed

Chemical shifts provide not only peak identities for analyzing nuclear magnetic resonance (NMR) data, but also an important source of conformational information for studying protein structures. Current structural studies requiring H(?) chemical shifts suffer from the following limitations. (1) For large proteins, the H(?) chemical shifts can be difficult to assign using conventional NMR triple-resonance experiments, mainly due to the fast transverse relaxation rate of C(?) that restricts the signal sensitivity. (2) Previous chemical shift prediction approaches either require homologous models with high sequence similarity or rely heavily on accurate backbone and side-chain structural coordinates. When neither sequence homologues nor structural coordinates are available, we must resort to other information to predict H(?) chemical shifts. Predicting accurate H(?) chemical shifts using other obtainable information, such as the chemical shifts of nearby backbone atoms (i.e., adjacent atoms in the sequence), can remedy the above dilemmas, and hence advance NMR-based structural studies of proteins. By specifically exploiting the dependencies on chemical shifts of nearby backbone atoms, we propose a novel machine learning algorithm, called HASH, to predict H(?) chemical shifts. HASH combines a new fragment-based chemical shift search approach with a non-parametric regression model, called the generalized additive model, to effectively solve the prediction problem. We demonstrate that the chemical shifts of nearby backbone atoms provide a reliable source of information for predicting accurate H(?) chemical shifts. Our testing results on different possible combinations of input data indicate that HASH has a wide rage of potential NMR applications in structural and biological studies of proteins. PMID:23242797

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

2013-01-01

62

Hash: a Program to Accurately Predict Protein H? Shifts from Neighboring Backbone Shifts3  

PubMed Central

Chemical shifts provide not only peak identities for analyzing NMR data, but also an important source of conformational information for studying protein structures. Current structural studies requiring H? chemical shifts suffer from the following limitations. (1) For large proteins, the H? chemical shifts can be difficult to assign using conventional NMR triple-resonance experiments, mainly due to the fast transverse relaxation rate of C? that restricts the signal sensitivity. (2) Previous chemical shift prediction approaches either require homologous models with high sequence similarity or rely heavily on accurate backbone and side-chain structural coordinates. When neither sequence homologues nor structural coordinates are available, we must resort to other information to predict H? chemical shifts. Predicting accurate H? chemical shifts using other obtainable information, such as the chemical shifts of nearby backbone atoms (i.e., adjacent atoms in the sequence), can remedy the above dilemmas, and hence advance NMR-based structural studies of proteins. By specifically exploiting the dependencies on chemical shifts of nearby backbone atoms, we propose a novel machine learning algorithm, called Hash, to predict H? chemical shifts. Hash combines a new fragment-based chemical shift search approach with a non-parametric regression model, called the generalized additive model, to effectively solve the prediction problem. We demonstrate that the chemical shifts of nearby backbone atoms provide a reliable source of information for predicting accurate H? chemical shifts. Our testing results on different possible combinations of input data indicate that Hash has a wide rage of potential NMR applications in structural and biological studies of proteins. PMID:23242797

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

2012-01-01

63

Backbone modifications in oligonucleotides and peptide nucleic acid systems  

Microsoft Academic Search

In the past year major advances have been made in the design, synthesis and characterization of two classes of modified oligonucleotides. In the first class, the phosphodiester backbone of 2'-deoxyribo-oligonucleotides has been replaced in several different ways. The second group represents a completely different type of oligonucleotide modification in which the backbone and the 2'-deoxyribose moieties are replaced by amino

Alain De Mesmaeker; Karl-Heinz Altmann; Adrian Waldner; Sebastian Wendeborn

1995-01-01

64

Backbone topology, access, and the commercial Internet, 1997 - 2000  

Microsoft Academic Search

As the Internet grows in popularity, telecommunications infrastructure in the United States continues to increase in capacity and geographic reach to meet market demand. Important components of this infrastructure include the commercial fiber-optic backbones used to transport digital information between locations. The spatial organization of commercial Internet backbones reflects an increasingly competitive privatized market for service provision, in which certain

Morton E OKelly; Tony H Grubesic

2002-01-01

65

Predicting DNA-binding proteins: approached from Chou’s pseudo amino acid composition and other specific sequence features  

Microsoft Academic Search

Summary.  DNA-binding proteins play a pivotal role in gene regulation. It is vitally important to develop an automated and efficient\\u000a method for timely identification of novel DNA-binding proteins. In this study, we proposed a method based on alone the primary\\u000a sequences of proteins to predict the DNA-binding proteins. DNA-binding proteins were encoded by autocross-covariance transform,\\u000a pseudo-amino acid composition, dipeptide composition, respectively

Y. Fang; Y. Guo; Y. Feng; M. Li

2008-01-01

66

Improved variation calling via an iterative backbone remapping and local assembly method for bacterial genomes.  

PubMed

Sequencing data analysis remains limiting and problematic, especially for low complexity repeat sequences and transposon elements due to inherent sequencing errors and short sequence read lengths. We have developed a program, ReviSeq, which uses a hybrid method composed of iterative remapping and local assembly upon a bacterial sequence backbone. Application of this method to six Brucella suis field isolates compared to the newly revised B. suis 1330 reference genome identified on average 13, 15, 19 and 9 more variants per sample than STAMPY/SAMtools, BWA/SAMtools, iCORN and BWA/PINDEL pipelines, and excluded on average 4, 2, 3 and 19 variants per sample, respectively. In total, using this iterative approach, we identified on average 87 variants including SNVs, short INDELs and long INDELs per strain when compared to the reference. Our program outperforms other methods especially for long INDEL calling. The program is available at http://reviseq.sourceforge.net. PMID:22967795

Tae, Hongseok; Settlage, Robert E; Shallom, Shamira; Bavarva, Jasmin H; Preston, Dale; Hawkins, Gregory N; Adams, L Garry; Garner, Harold R

2012-11-01

67

Toward future IP optical backbone networks  

NASA Astrophysics Data System (ADS)

The rapid and aggressive penetration of broadband access services such as fiber to the home (FTTH) has been accelerating the increase in IP traffic volume and new networking technologies are required in order to accommodate future traffic in a cost-effective manner. This paper overviews the advanced IP optical network architecture and technologies for very-large-scale IP backbone networks. These technologies are the key to accommodate the huge volumes of IP traffic expected and control network resources in an effective and dynamic manner. We describe advanced IP optical networking technologies which accommodate multiple service networks using multi-instance technologies, and enable multi-layer traffic engineering using virtual network topology technologies. The migration scenario is described from the existing networks to GMPLS networks; reference is made to the advanced Path Computation Element (PCE) which enables multi-layer traffic engineering and MPLS/GMPLS migration. New network concepts such as Layer 1 Virtual Private Network (L1VPN) and GMPLS interoperability issues, which are being discussed in IETF, are also described.

Urushidani, Shigeo

2005-11-01

68

Extracting the Information Backbone in Online System  

PubMed Central

Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such “less can be more” feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency. PMID:23690946

Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

2013-01-01

69

Extracting the information backbone in online system.  

PubMed

Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency. PMID:23690946

Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

2013-01-01

70

An Selenide-Based Approach to Photochemical Cleavage of Peptide and Protein Backbones at Engineered Backbone Esters  

PubMed Central

A strategy for photochemical cleavage of peptide and protein backbones is described, which is based on a selenide-mediated cleavage of a backbone ester moiety. Studies in model systems establish the viability of the chemistry and suggest the method could be a valuable tool for chemical biology studies of proteins. PMID:19902952

Eastwood, Amy L.; Blum, Angela P.; Zacharias, Niki M.; Dougherty, Dennis A.

2010-01-01

71

Protein backbone engineering as a strategy to advance foldamers toward the frontier of protein-like tertiary structure.  

PubMed

A variety of non-biological structural motifs have been incorporated into the backbone of natural protein sequences. In parallel work, diverse unnatural oligomers of de novo design (termed "foldamers") have been developed that fold in defined ways. In this Perspective article, we survey foundational studies on protein backbone engineering, with a focus on alterations made in the context of complex tertiary folds. We go on to summarize recent work illustrating the potential promise of these methods to provide a general framework for the construction of foldamer mimics of protein tertiary structures. PMID:25285575

Reinert, Zachary E; Horne, W Seth

2014-10-21

72

Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks  

PubMed Central

A new program, TALOS-N, is introduced for predicting protein backbone torsion angles from NMR chemical shifts. The program relies far more extensively on the use of trained artificial neural networks than its predecessor, TALOS+. Validation on an independent set of proteins indicates that backbone torsion angles can be predicted for a larger, ? 90% fraction of the residues, with an error rate smaller than ca 3.5%, using an acceptance criterion that is nearly two-fold tighter than that used previously, and a root mean square difference between predicted and crystallographically observed (?,?) torsion angles of ca 12°. TALOS-N also reports sidechain ?1 rotameric states for about 50% of the residues, and a consistency with reference structures of 89%. The program includes a neural network trained to identify secondary structure from residue sequence and chemical shifts. PMID:23728592

Shen, Yang; Bax, Ad

2013-01-01

73

Radiation safety system (RSS) backbones: Design, engineering, fabrication and installation  

SciTech Connect

The Radiation Safety System (RSS) Backbones are part of an electrical/electronic/mechanical system insuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS Backbones control the safety fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low energy beam transport. The Backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the Backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two Linac Backbone segments and experimental area segments form a continuous cable plant over 3,500 feet from beam plugs to the tip on the longest tail. The Backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

Wilmarth, J.E.; Sturrock, J.C.; Gallegos, F.R.

1998-12-01

74

RosettaBackrub--a web server for flexible backbone protein structure modeling and design  

PubMed Central

The RosettaBackrub server (http://kortemmelab.ucsf.edu/backrub) implements the Backrub method, derived from observations of alternative conformations in high-resolution protein crystal structures, for flexible backbone protein modeling. Backrub modeling is applied to three related applications using the Rosetta program for structure prediction and design: (I) modeling of structures of point mutations, (II) generating protein conformational ensembles and designing sequences consistent with these conformations and (III) predicting tolerated sequences at protein–protein interfaces. The three protocols have been validated on experimental data. Starting from a user-provided single input protein structure in PDB format, the server generates near-native conformational ensembles. The predicted conformations and sequences can be used for different applications, such as to guide mutagenesis experiments, for ensemble-docking approaches or to generate sequence libraries for protein design. PMID:20462859

Lauck, Florian; Smith, Colin A.; Friedland, Gregory F.; Humphris, Elisabeth L.; Kortemme, Tanja

2010-01-01

75

Impact of HIV-1 backbone on neutralization sensitivity: neutralization profiles of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE backbone.  

PubMed

Standardized assays to assess vaccine and antiviral drug efficacy are critical for the development of protective HIV-1 vaccines and drugs. These immune assays will be advanced by the development of standardized viral stocks, such as HIV-1 infectious molecular clones (IMC), that i) express a reporter gene, ii) are representative of globally diverse subtypes and iii) are engineered to easily exchange envelope (env) genes for expression of sequences of interest. Thus far, a subtype B IMC backbone expressing Renilla luciferase (LucR), and into which the ectodomain of heterologous env coding sequences can be expressed has been successfully developed but as execution of HIV-1 vaccine efficacy trials shifts increasingly to non-subtype B epidemics (Southern African and Southeast Asia), non-subtype B HIV-1 reagents are needed to support vaccine development. Here we describe two IMCs derived from subtypes C and CRF01_AE HIV-1 primary isolates expressing LucR (IMC.LucR) that were engineered to express heterologous gp160 Envs. 18 constructs expressing various subtypes C and CRF01_AE Envs, mostly acute, in subtype-matched and -unmatched HIV backbones were tested for functionality and neutralization sensitivity. Our results suggest a possible effect of non-env HIV-1 genes on the interaction of Env and neutralizing antibodies and highlight the need to generate a library of IMCs representative of the HIV-1 subtype spectrum to be used as standardized neutralization assay reagents for assessing HIV-1 vaccine efficacy. PMID:24312165

Chenine, Agnès-Laurence; Wieczorek, Lindsay; Sanders-Buell, Eric; Wesberry, Maggie; Towle, Teresa; Pillis, Devin M; Molnar, Sebastian; McLinden, Robert; Edmonds, Tara; Hirsch, Ivan; O'Connell, Robert; McCutchan, Francine E; Montefiori, David C; Ochsenbauer, Christina; Kappes, John C; Kim, Jerome H; Polonis, Victoria R; Tovanabutra, Sodsai

2013-01-01

76

Ethernet VPN (EVPN) & Provider Backbone Bridging Ethernet VPN  

E-print Network

. However, there exist a number of limitations. Ethernet Virtual Private Network (EVPN) and Provider Backbone Bridging Ethernet Virtual Private Network (PBBEVPN), still under standardization and a set of new requirements for Ethernet multipoint VPN service. Virtual Private LAN Services (VPLS

77

Design issues of optical IP routers for Internet backbone applications  

Microsoft Academic Search

The rapid increase of Internet traffic is pushing the deployment of WDM technology in the next-generation high-speed Internet backbone. Routers in the backbone could still be the potential bottleneck. In this article we consider some design issues of high-throughput optical routers which combine the advantages of WDM with the new optical switching technology. We first introduce a proposed Internet architecture

Franco Callegati; A. C. Cankaya; Yijun Xiong; Marc Vandenhoute

1999-01-01

78

A Cluster-Based Backbone Infrastructure for Broadcasting in MANET  

Microsoft Academic Search

Broadcasting is a fundamental service in mobile ad hoc networks (MANETs). Two categories of algorithms, based on source-independent and source-dependent connected dominating sets (CDSs), are proposed in literature to reduce the broadcast redundancy. In this paper, a cluster-based backbone infrastructure is proposed for broadcasting in MANETs. The backbone of the network takes advantage of the cluster structure and only requires

Wei Lou; Jie Wu

2003-01-01

79

The venom composition of the parasitic wasp Chelonus inanitus resolved by combined expressed sequence tags analysis and proteomic approach  

PubMed Central

Background Parasitic wasps constitute one of the largest group of venomous animals. Although some physiological effects of their venoms are well documented, relatively little is known at the molecular level on the protein composition of these secretions. To identify the majority of the venom proteins of the endoparasitoid wasp Chelonus inanitus (Hymenoptera: Braconidae), we have randomly sequenced 2111 expressed sequence tags (ESTs) from a cDNA library of venom gland. In parallel, proteins from pure venom were separated by gel electrophoresis and individually submitted to a nano-LC-MS/MS analysis allowing comparison of peptides and ESTs sequences. Results About 60% of sequenced ESTs encoded proteins whose presence in venom was attested by mass spectrometry. Most of the remaining ESTs corresponded to gene products likely involved in the transcriptional and translational machinery of venom gland cells. In addition, a small number of transcripts were found to encode proteins that share sequence similarity with well-known venom constituents of social hymenopteran species, such as hyaluronidase-like proteins and an Allergen-5 protein. An overall number of 29 venom proteins could be identified through the combination of ESTs sequencing and proteomic analyses. The most highly redundant set of ESTs encoded a protein that shared sequence similarity with a venom protein of unknown function potentially specific of the Chelonus lineage. Venom components specific to C. inanitus included a C-type lectin domain containing protein, a chemosensory protein-like protein, a protein related to yellow-e3 and ten new proteins which shared no significant sequence similarity with known sequences. In addition, several venom proteins potentially able to interact with chitin were also identified including a chitinase, an imaginal disc growth factor-like protein and two putative mucin-like peritrophins. Conclusions The use of the combined approaches has allowed to discriminate between cellular and truly venom proteins. The venom of C. inanitus appears as a mixture of conserved venom components and of potentially lineage-specific proteins. These new molecular data enrich our knowledge on parasitoid venoms and more generally, might contribute to a better understanding of the evolution and functional diversity of venom proteins within Hymenoptera. PMID:21138570

2010-01-01

80

Identical repeated backbone of the human genome  

Microsoft Academic Search

BACKGROUND: Identical sequences with a minimal length of about 300 base pairs (bp) have been involved in the generation of various meiotic\\/mitotic genomic rearrangements through non-allelic homologous recombination (NAHR) events. Genomic disorders and structural variation, together with gene remodelling processes have been associated with many of these rearrangements. Based on these observations, we identified and integrated all the 100% identical

Cinthya J Zepeda-Mendoza; Tzitziki Lemus; Omar Yáñez; Delfino García; David Valle-García; Karla F Meza-Sosa; María Gutiérrez-Arcelus; Yamile Márquez-Ortiz; Rocío Domínguez-Vidaña; Claudia Gonzaga-Jauregui; Margarita Flores; Rafael Palacios

2010-01-01

81

HIV-1 Phenotypic Reverse Transcriptase Inhibitor Drug Resistance Test Interpretation Is Not Dependent on the Subtype of the Virus Backbone  

PubMed Central

To date, the majority of HIV-1 phenotypic resistance testing has been performed with subtype B virus backbones (e.g. HXB2). However, the relevance of using this backbone to determine resistance in non-subtype B HIV-1 viruses still needs to be assessed. From 114 HIV-1 subtype C clinical samples (36 ARV-naïve, 78 ARV-exposed), pol amplicons were produced and analyzed for phenotypic resistance using both a subtype B- and C-backbone in which the pol fragment was deleted. Phenotypic resistance was assessed in resulting recombinant virus stocks (RVS) for a series of antiretroviral drugs (ARV's) and expressed as fold change (FC), yielding 1660 FC comparisons. These Antivirogram® derived FC values were categorized as having resistant or sensitive susceptibility based on biological cut-off values (BCOs). The concordance between resistance calls obtained for the same clinical sample but derived from two different backbones (i.e. B and C) accounted for 86.1% (1429/1660) of the FC comparisons. However, when taking the assay variability into account, 95.8% (1590/1660) of the phenotypic data could be considered as being concordant with respect to their resistance call. No difference in the capacity to detect resistance associated with M184V, K103N and V106M mutations was noted between the two backbones. The following was concluded: (i) A high level of concordance was shown between the two backbone phenotypic resistance profiles; (ii) Assay variability is largely responsible for discordant results (i.e. for FC values close to BCO); (iii) Confidence intervals should be given around the BCO's, when assessing resistance in HIV-1 subtype C; (iv) No systematic resistance under- or overcalling of subtype C amplicons in the B-backbone was observed; (v) Virus backbone subtype sequence variability outside the pol region does not contribute to phenotypic FC values. In conclusion the HXB2 virus backbone remains an acceptable vector for phenotyping HIV-1 subtype C pol amplicons. PMID:22496845

Bronze, Michelle; Steegen, Kim; Wallis, Carole L.; De Wolf, Hans; Papathanasopoulos, Maria A.; Van Houtte, Margriet; Stevens, Wendy S.; de Wit, Tobias Rinke; Stuyver, Lieven J.

2012-01-01

82

Polyarylether composition and membrane  

DOEpatents

A composition including a polyarylether copolymer is provided. The copolymer includes a polyarylether backbone; and a sulfonated oligomeric group bonded to the polyarylether suitable for use as a cation conducting membrane. Method of bonding a sulfonated oligomeric group to the polyarylether backbone to form a polyarylether copolymer. The membrane may be formed from the polyarylether copolymer composition. The chain length of the sulfonated oligomeric group may be controlled to affect or control the ion conductivity of the membrane.

Hung, Joyce (Auburn, AL); Brunelle, Daniel Joseph (Burnt Hills, NY); Harmon, Marianne Elisabeth (Redondo Beach, CA); Moore, David Roger (Albany, NY); Stone, Joshua James (Worcester, NY); Zhou, Hongyi (Niskayuna, NY); Suriano, Joseph Anthony (Clifton Park, NY)

2010-11-09

83

Composition-based classification of short metagenomic sequences elucidates the landscapes of taxonomic and functional enrichment of microorganisms  

PubMed Central

Compared with traditional algorithms for long metagenomic sequence classification, characterizing microorganisms’ taxonomic and functional abundance based on tens of millions of very short reads are much more challenging. We describe an efficient composition and phylogeny-based algorithm [Metagenome Composition Vector (MetaCV)] to classify very short metagenomic reads (75–100 bp) into specific taxonomic and functional groups. We applied MetaCV to the Meta-HIT data (371-Gb 75-bp reads of 109 human gut metagenomes), and this single-read-based, instead of assembly-based, classification has a high resolution to characterize the composition and structure of human gut microbiota, especially for low abundance species. Most strikingly, it only took MetaCV 10 days to do all the computation work on a server with five 24-core nodes. To our knowledge, MetaCV, benefited from the strategy of composition comparison, is the first algorithm that can classify millions of very short reads within affordable time. PMID:22941634

Liu, Jiemeng; Wang, Haifeng; Yang, Hongxing; Zhang, Yizhe; Wang, Jinfeng; Zhao, Fangqing; Qi, Ji

2013-01-01

84

Why not consider a spherical protein? Implications of backbone hydrogen bonding for protein structure and function.  

PubMed

The intrinsic ability of protein structures to exhibit the geometric features required for molecular function in the absence of evolution is examined in the context of three systems: the reference set of real, single domain protein structures, a library of computationally generated, compact homopolypeptides, artificial structures with protein-like secondary structural elements, and quasi-spherical random proteins packed at the same density as proteins but lacking backbone secondary structure and hydrogen bonding. Without any evolutionary selection, the library of artificial structures has similar backbone hydrogen bonding, global shape, surface to volume ratio and statistically significant structural matches to real protein global structures. Moreover, these artificial structures have native like ligand binding cavities, and a tiny subset has interfacial geometries consistent with native-like protein-protein interactions and DNA binding. In contrast, the quasi-spherical random proteins, being devoid of secondary structure, have a lower surface to volume ratio and lack ligand binding pockets and intermolecular interaction interfaces. Surprisingly, these quasi-spherical random proteins exhibit protein like distributions of virtual bond angles and almost all have a statistically significant structural match to real protein structures. This implies that it is local chain stiffness, even without backbone hydrogen bonding, and compactness that give rise to the likely completeness of the library solved single domain protein structures. These studies also suggest that the packing of secondary structural elements generates the requisite geometry for intermolecular binding. Thus, backbone hydrogen bonding plays an important role not only in protein structure but also in protein function. Such ability to bind biological molecules is an inherent feature of protein structure; if combined with appropriate protein sequences, it could provide the non-zero background probability for low-level function that evolution requires for selection to occur. PMID:21655593

Brylinski, Michal; Gao, Mu; Skolnick, Jeffrey

2011-10-14

85

CodonExplorer: An Interactive Online Database for the Analysis of Codon Usage and Sequence Composition  

PubMed Central

The analysis of DNA composition and codon usage reveals many factors that influence the evolution of genes and genomes. In this chapter, we show how to use CodonExplorer, a web tool and interactive database that contains millions of genes, to better understand the principles governing evolution at the single gene and whole-genome level. We present principles and practical procedures for using analyses of GC content and codon usage frequency to identify highly expressed or horizontally transferred genes and to study the relative contribution of different types of mutation to gene and genome composition. CodonExplorer’s combination of a user-friendly web interface and a comprehensive genomic database makes these diverse analyses fast and straightforward to perform. CodonExplorer is thus a powerful tool that facilitates and automates a wide range of compositional analyses. PMID:19378146

Zaneveld, Jesse; Hamady, Micah; Sueoka, Noboru; Knight, Rob

2010-01-01

86

Infrared spectral sequence of quenched carbonaceous composite subjected to thermal annealing  

Microsoft Academic Search

We investigate the spectroscopic alteration through thermal annealing on the quenched carbonaceous composite (QCC) produced from hydrocarbon plasma. The emission and absorption spectra of QCC samples annealed at various temperatures indicate that the proportion of aliphatic C-H bonds in QCC decreases relative to aromatic C-H bonds with increase of annealing temperature. By comparing the spectra of annealed QCC with observed

M. Goto; T. Maihara; H. Terada; C. Kaito; S. Kimura; S. Wada

2000-01-01

87

Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol.  

PubMed

The precise appraisal of the composition of the human gut microbiota still represents a challenging task. The advent of next generation sequencing approaches has opened new ways to dissect the microbial biodiversity of this ecosystem through the use of 16S rRNA gene-based microbiota analysis approaches. However, the detailed representation of specific groups or members of the human gut microbiota, for example Bifidobacteria, may be skewed by the PCR primers employed in the amplification step of the 16S rRNA gene-based microbial profiling pipeline and by the limited resolution of the 16S rRNA gene variable regions. Here, we define the internal transcribed spacer (ITS) sequences of all currently known Bifidobacterium taxa, providing a Bifidobacterium-specific primer pair that targets a hypervariable region within the ITS suitable for precise taxonomic identification of all 48 so far recognized members of the Bifidobacterium genus. In addition, we present an optimized protocol for ITS-based profiling utilizing qiime software, allowing accurate and subspecies-specific compositional reconstruction of the bifidobacterial community in the human gut. PMID:25117972

Milani, Christian; Lugli, Gabriele A; Turroni, Francesca; Mancabelli, Leonardo; Duranti, Sabrina; Viappiani, Alice; Mangifesta, Marta; Segata, Nicola; van Sinderen, Douwe; Ventura, Marco

2014-11-01

88

Composition and phylogenetic analysis of vitellogenin coding sequences in the Indonesian coelacanth Latimeria menadoensis.  

PubMed

The coelacanth Latimeria menadoensis, a living fossil, occupies a key phylogenetic position to explore the changes that have affected the genomes of the aquatic vertebrates that colonized dry land. This is the first study to isolate and analyze L. menadoensis mRNA. Three different vitellogenin transcripts were identified and their inferred amino acid sequences compared to those of other known vertebrates. The phylogenetic data suggest that the evolutionary history of this gene family in coelacanths was characterized by a different duplication event than those which occurred in teleosts, amniotes, and amphibia. Comparison of the three sequences highlighted differences in functional sites. Moreover, despite the presence of conserved sites compared with the other oviparous vertebrates, some sites were seen to have changed, others to be similar only to those of teleosts, and others still to resemble only to those of tetrapods. PMID:22711571

Canapa, Adriana; Olmo, Ettore; Forconi, Mariko; Pallavicini, Alberto; Makapedua, Monica Daisy; Biscotti, Maria Assunta; Barucca, Marco

2012-07-01

89

A composite map of expressed sequences and phenotypic traits of the sunflower (Helianthus annuus L.) genome  

Microsoft Academic Search

A map of the sunflower genome, based on expressed sequences and consisting of 273 loci, was constructed. The map incorporates\\u000a data from seven F2 populations, for a total of 1115 individuals. Two hundred and fourty five loci corresponding to 170 anonymous cDNA markers\\u000a and four loci for morphological markers were mapped. We also mapped 18 loci corresponding to previously described

L. Gentzbittel; E. Mestries; S. Mouzeyar; F. Mazeyrat; S. Badaoui; F. Vear; D. Tourvieille de Labrouhe; P. Nicolas

1999-01-01

90

Fragmentation Characteristics of Deprotonated N-linked Glycopeptides: Influences of Amino Acid Composition and Sequence  

NASA Astrophysics Data System (ADS)

Glycopeptide structural analysis using tandem mass spectrometry is becoming a common approach for elucidating site-specific N-glycosylation. The analysis is generally performed in positive-ion mode. Therefore, fragmentation of protonated glycopeptides has been extensively investigated; however, few studies are available on deprotonated glycopeptides, despite the usefulness of negative-ion mode analysis in detecting glycopeptide signals. Here, large sets of glycopeptides derived from well-characterized glycoproteins were investigated to understand the fragmentation behavior of deprotonated N-linked glycopeptides under low-energy collision-induced dissociation (CID) conditions. The fragment ion species were found to be significantly variable depending on their amino acid sequence and could be classified into three types: (i) glycan fragment ions, (ii) glycan-lost fragment ions and their secondary cleavage products, and (iii) fragment ions with intact glycan moiety. The CID spectra of glycopeptides having a short peptide sequence were dominated by type (i) glycan fragments (e.g., 2,4AR, 2,4AR-1, D, and E ions). These fragments define detailed structural features of the glycan moiety such as branching. For glycopeptides with medium or long peptide sequences, the major fragments were type (ii) ions (e.g., [peptide + 0,2X0-H]- and [peptide-NH3-H]-). The appearance of type (iii) ions strongly depended on the peptide sequence, and especially on the presence of Asp, Asn, and Glu. When a glycosylated Asn is located on the C-terminus, an interesting fragment having an Asn residue with intact glycan moiety, [glycan + Asn-36]-, was abundantly formed. Observed fragments are reasonably explained by a combination of existing fragmentation rules suggested for N-glycans and peptides.

Nishikaze, Takashi; Kawabata, Shin-ichirou; Tanaka, Koichi

2014-06-01

91

Complete sequence of heterogenous-composition mitochondrial genome (Brassica napus) and its exogenous source  

PubMed Central

Background Unlike maternal inheritance of mitochondria in sexual reproduction, somatic hybrids follow no obvious pattern. The introgressed segment orf138 from the mitochondrial genome of radish (Raphanus sativus) to its counterpart in rapeseed (Brassica napus) demonstrates that this inheritance mode derives from the cytoplasm of both parents. Sequencing of the complete mitochondrial genome of five species from Brassica family allowed the prediction of other extraneous sources of the cybrids from the radish parent, and the determination of their mitochondrial rearrangement. Results We obtained the complete mitochondrial genome of Ogura-cms-cybrid (oguC) rapeseed. To date, this is the first time that a heterogeneously composed mitochondrial genome was sequenced. The 258,473 bp master circle constituted of 33 protein-coding genes, 3 rRNA sequences, and 23 tRNA sequences. This mitotype noticeably holds two copies of atp9 and is devoid of cox2-2. Relative to nap mitochondrial genome, 40 point mutations were scattered in the 23 protein-coding genes. atp6 even has an abnormal start locus whereas tatC has an abnormal end locus. The rearrangement of the 22 syntenic regions that comprised 80.11% of the genome was influenced by short repeats. A pair of large repeats (9731 bp) was responsible for the multipartite structure. Nine unique regions were detected when compared with other published Brassica mitochondrial genome sequences. We also found six homologous chloroplast segments (Brassica napus). Conclusions The mitochondrial genome of oguC is quite divergent from nap and pol, which are more similar with each other. We analyzed the unique regions of every genome of the Brassica family, and found that very few segments were specific for these six mitotypes, especially cam, jun, and ole, which have no specific segments at all. Therefore, we conclude that the most specific regions of oguC possibly came from radish. Compared with the chloroplast genome, six identical regions were found in the seven mitochondrial genomes, which show that the Brassica family has a stable chloroplast-derived source. PMID:23190559

2012-01-01

92

Computational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear Epitope  

E-print Network

the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone graftingComputational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear Epitope Edited by I. Wilson Keywords: protein grafting; flexible backbone design; epitope scaffold; immunogen

Baker, David

93

Shear fracture of C\\/C composites with variable stacking sequence  

Microsoft Academic Search

Cross-ply laminated carbon–carbon composites with changing ply ratio of 0° and 90° were fractured under shear using several test methods. In these tests, special attention was placed on the understanding of the damage mechanisms. The ±45° off-axis shear test yielded the most precise shear stress–strain relation and was recommended to measure the shear modulus G12. On the other hand, for

Lars Denk; Hiroshi Hatta; Akihiro Misawa; Satoshi Somiya

2001-01-01

94

SUBMISSION TO IEEE COMMUNICATIONS MAGAZINE CASE STUDY: RESILIENT BACKBONE DESIGN FOR IPTV SERVICES 1 Case Study: Resilient Backbone Design for IPTV  

E-print Network

SUBMISSION TO IEEE COMMUNICATIONS MAGAZINE ­ CASE STUDY: RESILIENT BACKBONE DESIGN FOR IPTV SERVICES 1 Case Study: Resilient Backbone Design for IPTV Services Meeyoung Cha, Student Member, IEEE Moon, Member, IEEE Abstract-- IPTV promises personalized, intelligent, and seam- less delivery

Fisher, Kathleen

95

Sequence-based analysis of the microbial composition of water kefir from multiple sources.  

PubMed

Water kefir is a water-sucrose-based beverage, fermented by a symbiosis of bacteria and yeast to produce a final product that is lightly carbonated, acidic and that has a low alcohol percentage. The microorganisms present in water kefir are introduced via water kefir grains, which consist of a polysaccharide matrix in which the microorganisms are embedded. We aimed to provide a comprehensive sequencing-based analysis of the bacterial population of water kefir beverages and grains, while providing an initial insight into the corresponding fungal population. To facilitate this objective, four water kefirs were sourced from the UK, Canada and the United States. Culture-independent, high-throughput, sequencing-based analyses revealed that the bacterial fraction of each water kefir and grain was dominated by Zymomonas, an ethanol-producing bacterium, which has not previously been detected at such a scale. The other genera detected were representatives of the lactic acid bacteria and acetic acid bacteria. Our analysis of the fungal component established that it was comprised of the genera Dekkera, Hanseniaspora, Saccharomyces, Zygosaccharomyces, Torulaspora and Lachancea. This information will assist in the ultimate identification of the microorganisms responsible for the potentially health-promoting attributes of these beverages. PMID:24004255

Marsh, Alan J; O'Sullivan, Orla; Hill, Colin; Ross, R Paul; Cotter, Paul D

2013-11-01

96

Fast protein backbone NMR resonance assignment using the BATCH strategy.  

PubMed

Probing protein structure, dynamics, and interaction surfaces by NMR requires initial backbone resonance assignment. The protocol for this step has been progressively developed in the last 15 years to provide robust assignments. However, even in the case of favorable conditions (high field magnets and cryogenically cooled probes, small globular proteins, high sample concentration), the assignment step generally takes several days of data collection and analysis, thus precluding studies of unstable proteins and limiting high-throughput applications. Recently, we have introduced the BATCH strategy for fast protein backbone resonance assignment. BATCH benefits from the combination of several tools (BEST/ASCOM/Targeted-Sampling/COBRA/HADAMAC) for time-optimized and highly automated NMR data acquisition, processing, and analysis. In this chapter, we discuss the individual steps of the BATCH method and describe its practical implementation to obtain the backbone resonance assignment of small globular proteins in a few hours of time. PMID:22167685

Brutscher, Bernhard; Lescop, Ewen

2012-01-01

97

Azido gauche effect on the backbone conformation of ?-azidoalanine peptides.  

PubMed

To study the azido gauche effect on the backbone conformation of ?-azidoalanine (Aza) dipeptide (AAD, Ac-Aza-NHMe) and tripeptide (AAT, Ac-Aza-Aza-NH(2)), we used spectroscopic methods in combination with quantum chemistry calculations and molecular dynamics (MD) simulations. From the (1)H NMR coupling constants and (1)H,(1)H NOESY experimental data, we found that AAD in water mainly adopts a seven-membered cyclic (C(7)) rather than polyproline II (P(II)) backbone conformation and prefers the gauche- (g(-)) side-chain conformer. From the amide I IR absorption and circular dichroism (CD) spectra, the backbone conformation of AAD in water is found to deviate from P(II) but is rather close to C(7). Thus, the backbone conformation of AAD differs from that of alanine dipeptide (AD, Ac-Ala-NHMe), which is mainly P(II) in water. The underlying origin of the backbone conformational difference between AAD and AD in water was elucidated by quantum chemistry calculations with density functional theory (DFT). It was found that the C(7)/g(-) conformer is the lowest energy structure of an isolated AAD. Here, the ?-azido group forms intramolecular electrostatic interactions with two neighboring peptide bonds, which are facilitated by the azido gauche effect. Thus, the ?-azido group appears to be responsible for directing the peptide backbone conformation toward the C(7) structure. The quantum mechanical/molecular mechanical (QM/MM) MD simulations show that AAD in water adopts neither P(II) nor right-handed ?-helix (?(R)) and prefers the g(-) conformer. Thus, the intramolecular electrostatic interactions between the ?-azido group and two nearby peptide bonds are also found even in the aqueous solution structure of AAD. Consequently, the ?-azido group appears to be an effective C(7)-conformation-directing element, which may also be useful for tuning the structures of other amino acids and polypeptides. PMID:20849143

Oh, Kwang-Im; Kim, Woosung; Joo, Cheonik; Yoo, Dong-Geun; Han, Hogyu; Hwang, Geum-Sook; Cho, Minhaeng

2010-10-14

98

DNA-RNA chimera indicates the flexibility of the backbone influences the encapsulation of fluorescent AgNC emitters.  

PubMed

Many DNA scaffolds efficiently encapsulate highly emissive silver nanoclusters (AgNCs). The secondary structures and the arrangement of sequences of DNA scaffolds are important factors by which the specific features of AgNCs emitters can be determined. By introducing DNA-RNA chimera scaffolds, we here explore another factor - the flexibility of the backbone of nucleic acid-templates - in creating highly fluorescent AgNC emitters. PMID:25247813

Shah, Pratik; Thulstrup, Peter W; Cho, Seok Keun; Bjerrum, Morten Jannik; Yang, Seong Wook

2014-10-01

99

First Survey of the Wheat Chromosome 5A Composition through a Next Generation Sequencing Approach  

PubMed Central

Wheat is one of the world's most important crops and is characterized by a large polyploid genome. One way to reduce genome complexity is to isolate single chromosomes using flow cytometry. Low coverage DNA sequencing can provide a snapshot of individual chromosomes, allowing a fast characterization of their main features and comparison with other genomes. We used massively parallel 454 pyrosequencing to obtain a 2x coverage of wheat chromosome 5A. The resulting sequence assembly was used to identify TEs, genes and miRNAs, as well as to infer a virtual gene order based on the synteny with other grass genomes. Repetitive elements account for more than 75% of the genome. Gene content was estimated considering non-redundant reads showing at least one match to ESTs or proteins. The results indicate that the coding fraction represents 1.08% and 1.3% of the short and long arm respectively, projecting the number of genes of the whole chromosome to approximately 5,000. 195 candidate miRNA precursors belonging to 16 miRNA families were identified. The 5A genes were used to search for syntenic relationships between grass genomes. The short arm is closely related to Brachypodium chromosome 4, sorghum chromosome 8 and rice chromosome 12; the long arm to regions of Brachypodium chromosomes 4 and 1, sorghum chromosomes 1 and 2 and rice chromosomes 9 and 3. From these similarities it was possible to infer the virtual gene order of 392 (5AS) and 1,480 (5AL) genes of chromosome 5A, which was compared to, and found to be largely congruent with the available physical map of this chromosome. PMID:22028874

Vitulo, Nicola; Albiero, Alessandro; Forcato, Claudio; Campagna, Davide; Dal Pero, Francesca; Bagnaresi, Paolo; Colaiacovo, Moreno; Faccioli, Primetta; Lamontanara, Antonella; Simkova, Hana; Kubalakova, Marie; Perrotta, Gaetano; Facella, Paolo; Lopez, Loredana; Pietrella, Marco; Gianese, Giulio; Dolezel, Jaroslav; Giuliano, Giovanni; Cattivelli, Luigi; Valle, Giorgio; Stanca, A. Michele

2011-01-01

100

A Consistent Phylogenetic Backbone for the Fungi  

PubMed Central

The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data—a common practice in phylogenomic analyses—introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses. PMID:22114356

Ebersberger, Ingo; de Matos Simoes, Ricardo; Kupczok, Anne; Gube, Matthias; Kothe, Erika; Voigt, Kerstin; von Haeseler, Arndt

2012-01-01

101

Stretches of oligogalacturonan are present in the backbone of rhamnogalacturonan I from cotton suspension culture cell walls  

SciTech Connect

A polysaccharide fraction, solubilized from cotton suspension culture cell walls by sequential treatments by endopolygalacturonase and cellulase and purified by gel filtration chromatography, contained the sugars characteristic of rhamnogalacturonan I (RGI). A known structural feature of the backbone of RGI is the repeating disaccharide galA-rha; however, the ratio of galA to rha residues was found to be 1 {center dot} 9:1. Treatment of the RGI preparation with liquid HF (containing 1% water) at {minus}23{degree} caused cleavage of most of the rhamnosyl linkages without cleavage of galacturonosyl linkages. Neutral sugar linkages of the sidechains were also mostly cleaved. Characterization of the products from the backbone by nmr spectroscopy, compositional analysis, and liquid secondary ion mass spectrometry suggested that the backbone of the RGI is made up of short segments ({approximately} 10 units) of the galA-rha repeat interspersed with short homogalacturonan segments of {approximately} 10 galA residues of which about 40% are methyl esterified. The sequential enzyme treatments only solubilize {approximately} 40% of the RGI. The residual RGI contains a higher proportion of falA-rha repeats in its backbone.

An, Jinhua; Mort, A. (Oklahoma State Univ., Stillwater (United States))

1991-05-01

102

Cooperative UAV-Based Communications Backbone for Sensor Networks  

SciTech Connect

The objective of this project is to investigate the use of unmanned air vehicles (UAVs) as mobile, adaptive communications backbones for ground-based sensor networks. In this type of network, the UAVs provide communication connectivity to sensors that cannot communicate with each other because of terrain, distance, or other geographical constraints. In these situations, UAVs provide a vertical communication path for the sensors, thereby mitigating geographic obstacles often imposed on networks. With the proper use of UAVs, connectivity to a widely disbursed sensor network in rugged terrain is readily achieved. Our investigation has focused on networks where multiple cooperating UAVs are used to form a network backbone. The advantage of using multiple UAVs to form the network backbone is parallelization of sensor connectivity. Many widely spaced or isolated sensors can be connected to the network at once using this approach. In these networks, the UAVs logically partition the sensor network into sub-networks (subnets), with one UAV assigned per subnet. Partitioning the network into subnets allows the UAVs to service sensors in parallel thereby decreasing the sensor-to-network connectivity. A UAV services sensors in its subnet by flying a route (path) through the subnet, uplinking data collected by the sensors, and forwarding the data to a ground station. An additional advantage of using multiple UAVs in the network is that they provide redundancy in the communications backbone, so that the failure of a single UAV does not necessarily imply the loss of the network.

Roberts, R S

2001-10-07

103

Virtual Backbone Construction in MANETs Using Adjustable Transmission Ranges  

E-print Network

Virtual Backbone Construction in MANETs Using Adjustable Transmission Ranges Jie Wu, Senior Member applications in mobile ad hoc networks (MANETs) has become popular. These applications include topology management, point and area coverage, and routing protocol design. In a MANET, one challenging issue

Wu, Jie

104

Case Study: Resilient Backbone Design for IPTV Services Meeyoung Cha  

E-print Network

Case Study: Resilient Backbone Design for IPTV Services Meeyoung Cha , Gagan Choudhury , Jennifer a case study of designing resilient back- bone network for supporting IPTV services within a single network provider. We first introduce the architecture and the characteristics of IPTV traffic. We

Moon, Sue B.

105

Backbone decomposition for continuous-state branching processes with immigration  

E-print Network

Backbone decomposition for continuous-state branching processes with immigration A.E. Kyprianou and general immigration mechanism is equal in law to a continuous-time Galton Watson process with immigration from the work on consistent growth of Galton-Watson trees with immigration in Cao and Winkel [2]. Key

106

Diffusive process on a backbone structure with drift terms.  

PubMed

The effects of an external force on a diffusive process subjected to a backbone structure are investigated by considering the system governed by a Fokker-Planck equation with drift terms. Our results show an anomalous spreading which may present different diffusive regimes connected to anomalous diffusion and stationary states. PMID:23410297

Lenzi, E K; da Silva, L R; Tateishi, A A; Lenzi, M K; Ribeiro, H V

2013-01-01

107

Sequence-based analysis of the bacterial and fungal compositions of multiple kombucha (tea fungus) samples.  

PubMed

Kombucha is a sweetened tea beverage that, as a consequence of fermentation, contains ethanol, carbon dioxide, a high concentration of acid (gluconic, acetic and lactic) as well as a number of other metabolites and is thought to contain a number of health-promoting components. The sucrose-tea solution is fermented by a symbiosis of bacteria and yeast embedded within a cellulosic pellicle, which forms a floating mat in the tea, and generates a new layer with each successful fermentation. The specific identity of the microbial populations present has been the focus of attention but, to date, the majority of studies have relied on culture-based analyses. To gain a more comprehensive insight into the kombucha microbiota we have carried out the first culture-independent, high-throughput sequencing analysis of the bacterial and fungal populations of 5 distinct pellicles as well as the resultant fermented kombucha at two time points. Following the analysis it was established that the major bacterial genus present was Gluconacetobacter, present at >85% in most samples, with only trace populations of Acetobacter detected (<2%). A prominent Lactobacillus population was also identified (up to 30%), with a number of sub-dominant genera, not previously associated with kombucha, also being revealed. The yeast populations were found to be dominated by Zygosaccharomyces at >95% in the fermented beverage, with a greater fungal diversity present in the cellulosic pellicle, including numerous species not identified in kombucha previously. Ultimately, this study represents the most accurate description of the microbiology of kombucha to date. PMID:24290641

Marsh, Alan J; O'Sullivan, Orla; Hill, Colin; Ross, R Paul; Cotter, Paul D

2014-04-01

108

Sequences of Mixed Ions in Polypeptoid Surfaces  

NASA Astrophysics Data System (ADS)

Polypeptoids, a unique, sequence specific class of polymers, are used to investigate the influence of charge spacing, grouping, and chemistry on the surface properties of polymer coatings. Short peptoid oligomers composed of cationic and anionic groups, and superhydrophobic (fluorinated) functionalities were attached to a synthetic backbone to form comb-shaped molecules. These molecules display different surface chemistry as a function of side chain composition, as indicated by near edge X-ray absorption fine structure spectroscopy (NEXAFS). A 50:50 ratio of peptoid:fluorinated functionality resulted in optimal surface segregation of the comb block while preventing surface reconstruction upon immersing the polymer films in water. Antifouling experiments with the green algae Ulva showed that polymers with non-ionic peptoid functional groups resulted in superior antifouling coatings compared to polymers with charged peptoids. The effects of decreasing the peptoid charge spacing even further (zwitterionic side chains) and exploring stronger ionic moieties, such as phosphate groups, will also be discussed.

Buss, Hilda; van Zoelen, Wendy; Ellebracht, Nathan; Zuckermann, Ronald; Segalman, Rachel

2013-03-01

109

Comparative genomics of pAKD4, the prototype IncP-1?plasmid with a complete backbone  

PubMed Central

Plasmids of the incompatibility group IncP-1 are important agents of horizontal gene transfer and contribute to the spread of antibiotic resistance and xenobiotic degradation within bacterial communities. Even though some prototype plasmids have been studied in much detail, the diversity of this plasmid group was still greatly underestimated until recently, as only two of the five currently known divergent sub-groups had been described. To further improve our insight into the diversity and evolutionary history of this family of broad-host-range plasmids, we compared the complete nucleotide sequence of a new IncP-1? plasmid pAKD4 to the genomes of other IncP-1 plasmids. Plasmid pAKD4 was previously isolated by exogenous plasmid isolation from an agricultural soil in Norway. Its 56,803 bp nucleotide sequence shows high similarity in gene sequence and gene order to both plasmids pEST4011 and pIJB1, the only other IncP-1? plasmids sequenced so far. While all three plasmids have a typical IncP-1 backbone comprising replication, transfer and stable inheritance/control genes, the low sequence similarity in some regions and presence/absence of some backbone genes compared to other IncP-1 plasmids cluster them in a divergent sub-group. Therefore this study validates the presence of a real IncP-1? clade with multiple plasmids. Moreover, since both pEST4011 and pIJB1 are missing a portion of their transfer genes, pAKD4 represents the first completely sequenced self-transferable plasmid with a complete IncP-1? backbone. We therefore propose it to be the prototype IncP-1? plasmid. PMID:20018208

Sen, Diya; Yano, Hirokazu; Suzuki, Haruo; Krol, Jaroslaw E.; Rogers, Linda; Brown, Celeste J.; Top, Eva M.

2010-01-01

110

PS1-10jh: The Disruption of a Main-sequence Star of Near-solar Composition  

NASA Astrophysics Data System (ADS)

When a star comes within a critical distance to a supermassive black hole (SMBH), immense tidal forces disrupt the star, resulting in a stream of debris that falls back onto the SMBH and powers a luminous flare. In this paper, we perform hydrodynamical simulations of the disruption of a main-sequence star by an SMBH to characterize the evolution of the debris stream after a tidal disruption. We demonstrate that this debris stream is confined by self-gravity in the two directions perpendicular to the original direction of the star's travel and as a consequence has a negligible surface area and makes almost no contribution to either the continuum or line emission. We therefore propose that any observed emission lines are not the result of photoionization in this unbound debris, but are produced in the region above and below the forming elliptical accretion disk, analogous to the broad-line region (BLR) in steadily accreting active galactic nuclei. As each line within a BLR is observationally linked to a particular location in the accretion disk, we suggest that the absence of a line indicates that the accretion disk does not yet extend to the distance required to produce that line. This model can be used to understand the spectral properties of the tidal disruption event PS1-10jh, for which He II lines are observed, but the Balmer series and He I are not. Using a maximum likelihood analysis, we show that the disruption of a main-sequence star of near-solar composition can reproduce this event.

Guillochon, James; Manukian, Haik; Ramirez-Ruiz, Enrico

2014-03-01

111

Predicting Secretory Proteins of Malaria Parasite by Incorporating Sequence Evolution Information into Pseudo Amino Acid Composition via Grey System Model  

PubMed Central

The malaria disease has become a cause of poverty and a major hindrance to economic development. The culprit of the disease is the parasite, which secretes an array of proteins within the host erythrocyte to facilitate its own survival. Accordingly, the secretory proteins of malaria parasite have become a logical target for drug design against malaria. Unfortunately, with the increasing resistance to the drugs thus developed, the situation has become more complicated. To cope with the drug resistance problem, one strategy is to timely identify the secreted proteins by malaria parasite, which can serve as potential drug targets. However, it is both expensive and time-consuming to identify the secretory proteins of malaria parasite by experiments alone. To expedite the process for developing effective drugs against malaria, a computational predictor called “iSMP-Grey” was developed that can be used to identify the secretory proteins of malaria parasite based on the protein sequence information alone. During the prediction process a protein sample was formulated with a 60D (dimensional) feature vector formed by incorporating the sequence evolution information into the general form of PseAAC (pseudo amino acid composition) via a grey system model, which is particularly useful for solving complicated problems that are lack of sufficient information or need to process uncertain information. It was observed by the jackknife test that iSMP-Grey achieved an overall success rate of 94.8%, remarkably higher than those by the existing predictors in this area. As a user-friendly web-server, iSMP-Grey is freely accessible to the public at http://www.jci-bioinfo.cn/iSMP-Grey. Moreover, for the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated mathematical equations involved in this paper. PMID:23189138

Lin, Wei-Zhong; Fang, Jian-An; Xiao, Xuan; Chou, Kuo-Chen

2012-01-01

112

In Vitro Cytotoxicity, Chemotactic Effect, and Cellular Uptake of Branched Polypeptides with Poly[ l Lys] Backbone by J774 Murine Macrophage Cell Line  

Microsoft Academic Search

Branched polypeptides with polylysine backbone are promising candidates for selective delivery of drugs, epitopes. or reporter molecules. We reported earlier that polylysine-based polypeptides with polyanionic character were internalized by murine bone marrow derived macrophages via class A scavenger receptor. In the present studies, our investigations were extended to seven polypeptides with different amino acid composition and charge properties. We report

Rita Szabó; Gábor Mezö; Éva Pállinger; Péter Kovács; László Köhidai; Szilvia Bösze; Ferenc Hudecz

2008-01-01

113

Photodegradation of human growth hormone: a novel backbone cleavage between Glu-88 and Pro-89.  

PubMed

The exposure of protein pharmaceuticals to light can cause loss of potency, oxidation, structural changes and aggregation. To elucidate the chemical pathways of photodegradation, we irradiated human growth hormone (hGH) at ? = 254 nm, ? ? 265-340 nm, and ? ? 295-340 nm (using the spectral cutoff of borosilicate glass) and analyzed the products by mass spectrometry. By means of LC-MS/MS analysis, we observed an unusual peptide backbone cleavage between Glu-88 and Pro-89. The crystal structure of hGH indicates that these residues are in proximity to Trp-86, which likely mediates this backbone cleavage. The two cleavage fragments observed by MS/MS analysis indicate the loss of CO from the amide bond and replacement of the Glu-C(? O)Pro bond with a Glu-H bond, accompanied by double bond formation on proline. The reaction is oxygen-independent and likely involves hydrogen transfer to the C? of Glu-88. To probe the influence of the protein fold, we irradiated hGH in its unfolded state, in 1:1 (v/v) acetonitrile/water, and also the isolated tryptic peptide Ile-78-Arg-90, which contains the Glu-88-Pro-89 sequence. In both cases, the cleavage between Glu-88 and Pro-89 was largely suppressed, while other cleavage pathways became dominant, notably between Gln-84 and Ser-85, as well as Ser-85 and Trp-86. PMID:23721578

Steinmann, Daniel; Ji, J Andrea; Wang, Y John; Schöneich, Christian

2013-07-01

114

Native protein sequences are close to optimal for their structures  

Microsoft Academic Search

How large is the volume of sequence space that is compatible with a given protein structure? Starting from random sequences, low free energy sequences were generated for 108 protein backbone structures by using a Monte Carlo optimization procedure and a free energy function based primarily on Lennard-Jones packing interactions and the Lazaridis-Karplus implicit solvation model. Remarkably, in the designed sequences

Brian Kuhlman; David Baker

2000-01-01

115

Extracting the globally and locally adaptive backbone of complex networks.  

PubMed

A complex network is a useful tool for representing and analyzing complex systems, such as the world-wide web and transportation systems. However, the growing size of complex networks is becoming an obstacle to the understanding of the topological structure and their characteristics. In this study, a globally and locally adaptive network backbone (GLANB) extraction method is proposed. The GLANB method uses the involvement of links in shortest paths and a statistical hypothesis to evaluate the statistical importance of the links; then it extracts the backbone, based on the statistical importance, from the network by filtering the less important links and preserving the more important links; the result is an extracted subnetwork with fewer links and nodes. The GLANB determines the importance of the links by synthetically considering the topological structure, the weights of the links and the degrees of the nodes. The links that have a small weight but are important from the view of topological structure are not belittled. The GLANB method can be applied to all types of networks regardless of whether they are weighted or unweighted and regardless of whether they are directed or undirected. The experiments on four real networks show that the link importance distribution given by the GLANB method has a bimodal shape, which gives a robust classification of the links; moreover, the GLANB method tends to put the nodes that are identified as the core of the network by the k-shell algorithm into the backbone. This method can help us to understand the structure of the networks better, to determine what links are important for transferring information, and to express the network by a backbone easily. PMID:24936975

Zhang, Xiaohang; Zhang, Zecong; Zhao, Han; Wang, Qi; Zhu, Ji

2014-01-01

116

Packet-level traffic measurements from the Sprint IP backbone  

Microsoft Academic Search

Network traffic measurements provide essential data for networking research and network management. In this article we describe a passive monitoring system designed to capture GPS synchronized packet-level traffic measurements on OC-3, OC-12, and OC-48 links. Our system is deployed in four POP in the Sprint IP backbone. Measurement data is stored on a 10 Tbyte storage area network and analyzed

Chuck Fraleigh; Sue Moon; Bryan Lyles; Chase Cotton; Mujahid Khan; Deb Moll; Rob Rockell; Ted Seely; S. C. Diot

2003-01-01

117

Backbone decomposition for continuous-state branching processes with immigration  

E-print Network

In the spirit of Duqesne and Winkel (2007) and Berestycki et al. (2011) we show that supercritical continuous-state branching process with a general branching mechanism and general immigration mechanism is equal in law to a continuous-time Galton Watson process with immigration with Poissonian dressing. The result also characterises the limiting backbone decomposition which is predictable from the work on consistent growth of Galton-Watson trees with immigration in Cao and Winkel (2010).

Ren, A E Kyprianou Y-X

2011-01-01

118

Extracting the Globally and Locally Adaptive Backbone of Complex Networks  

PubMed Central

A complex network is a useful tool for representing and analyzing complex systems, such as the world-wide web and transportation systems. However, the growing size of complex networks is becoming an obstacle to the understanding of the topological structure and their characteristics. In this study, a globally and locally adaptive network backbone (GLANB) extraction method is proposed. The GLANB method uses the involvement of links in shortest paths and a statistical hypothesis to evaluate the statistical importance of the links; then it extracts the backbone, based on the statistical importance, from the network by filtering the less important links and preserving the more important links; the result is an extracted subnetwork with fewer links and nodes. The GLANB determines the importance of the links by synthetically considering the topological structure, the weights of the links and the degrees of the nodes. The links that have a small weight but are important from the view of topological structure are not belittled. The GLANB method can be applied to all types of networks regardless of whether they are weighted or unweighted and regardless of whether they are directed or undirected. The experiments on four real networks show that the link importance distribution given by the GLANB method has a bimodal shape, which gives a robust classification of the links; moreover, the GLANB method tends to put the nodes that are identified as the core of the network by the k-shell algorithm into the backbone. This method can help us to understand the structure of the networks better, to determine what links are important for transferring information, and to express the network by a backbone easily. PMID:24936975

Zhang, Xiaohang; Zhang, Zecong; Zhao, Han; Wang, Qi; Zhu, Ji

2014-01-01

119

Autonomous reconfiguration of backbones in free space optical networks  

Microsoft Academic Search

This research focuses on algorithms for autonomous reconfiguration of backbone networks utilizing the free space optical (FSO) technology. Such networks consist of high data rate and narrow beam FSO links between fixed and\\/or mobile nodes. The main challenge is to maintain the required quality and connectivity of such networks amidst changing atmospheric (obscuration\\/loss of sight\\/scintillation etc), platform (mobility\\/jitter) and traffic

Aniket Desai; Jaime Llorca; Stuart Milner

2004-01-01

120

Determination of backbone nitrogen-nitrogen J correlations in proteins.  

PubMed

Recently, a quantitative J correlation technique has been presented which makes use of homonuclear Hartmann-Hahn cross-polarization (TOCSY) to measure (3)J(C)'(C)' in proteins isotopically enriched with (13)C [Grzesiek, S. and Bax, A. (1997) J. Biomol. NMR, 9, 207-211]. Since homonuclear Hartmann-Hahn is twice as fast as conventional COSY transfer, this method is much less sensitive to transverse relaxation, which is the principal limiting factor in achieving long-range J-coupling correlations in macromolecules. Here we describe a similar experiment which is used to measure(3) J(NN) coupling constants between sequential amide(15) N nuclei in the backbone of ubiquitin. As expected from the low magnetic moment of (15)N, the (3)J(NN) coupling constants are exceedingly small, with values between 0.14 and 0.36 Hz for residues in ?-conformations and values below 0.15 Hz for residues in ?-conformations. In contrast to what is expected from a Karplus-type dependence on the backbone angle ?, large differences in the values of(3) J(NN) are observed for a number of residues with very similar backbone ? angles. A quantitative description of statistical and systematic errors, in particular of relaxation effects during the TOCSY transfer, shows that these differences are highly significant. PMID:20859784

Theis, K; Dingley, A J; Hoffmann, A; Omichinski, J G; Grzesiek, S

1997-12-01

121

Deep-UV resonance Raman analysis of the Rhodobacter capsulatus cytochrome bc?complex reveals a potential marker for the transmembrane peptide backbone.  

PubMed

Classical strategies for structure analysis of proteins interacting with a lipid phase typically correlate ensemble secondary structure content measurements with changes in the spectroscopic responses of localized aromatic residues or reporter molecules to map regional solvent environments. Deep-UV resonance Raman (DUVRR) spectroscopy probes the vibrational modes of the peptide backbone itself, is very sensitive to the ensemble secondary structures of a protein, and has been shown to be sensitive to the extent of solvent interaction with the peptide backbone [ Wang , Y. , Purrello , R. , Georgiou , S. , and Spiro , T. G. ( 1991 ) J. Am. Chem. Soc. 113 , 6368 - 6377 ]. Here we show that a large detergent solubilized membrane protein, the Rhodobacter capsulatus cytochrome bc(1) complex, has a distinct DUVRR spectrum versus that of an aqueous soluble protein with similar overall secondary structure content. Cross-section calculations of the amide vibrational modes indicate that the peptide backbone carbonyl stretching modes differ dramatically between these two proteins. Deuterium exchange experiments probing solvent accessibility confirm that the contribution of the backbone vibrational mode differences are derived from the lipid solubilized or transmembrane ?-helical portion of the protein complex. These findings indicate that DUVRR is sensitive to both the hydration status of a protein's peptide backbone, regardless of primary sequence, and its secondary structure content. Therefore, DUVRR may be capable of simultaneously measuring protein dynamics and relative water/lipid solvation of the protein. PMID:21718040

Halsey, Christopher M; Oshokoya, Olayinka O; Jiji, Renee D; Cooley, Jason W

2011-08-01

122

The role of molecular structure of sugar-phosphate backbone and nucleic acid bases in the formation of single-stranded and double-stranded DNA structures.  

PubMed

Our previous DFT computations of deoxydinucleoside monophosphate complexes with Na(+) -ions (dDMPs) have demonstrated that the main characteristics of Watson-Crick (WC) right-handed duplex families are predefined in the local energy minima of dDMPs. In this work, we study the mechanisms of contribution of chemically monotonous sugar-phosphate backbone and the bases into the double helix irregularity. Geometry optimization of sugar-phosphate backbone produces energy minima matching the WC DNA conformations. Studying the conformational variability of dDMPs in response to sequence permutation, we found that simple replacement of bases in the previously fully optimized dDMPs, e.g. by constructing Pyr-Pur from Pur-Pyr, and Pur-Pyr from Pyr-Pur sequences, while retaining the backbone geometry, automatically produces the mutual base position characteristic of the target sequence. Based on that, we infer that the directionality and the preferable regions of the sugar-phosphate torsions, combined with the difference of purines from pyrimidines in ring shape, determines the sequence dependence of the structure of WC DNA. No such sequence dependence exists in dDMPs corresponding to other DNA conformations (e.g., Z-family and Hoogsteen duplexes). Unlike other duplexes, WC helix is unique by its ability to match the local energy minima of the free single strand to the preferable conformations of the duplex. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 640-650, 2014. PMID:24170251

Poltev, Valeri; Anisimov, Victor M; Danilov, Victor I; Garcia, Dolores; Sanchez, Carolina; Deriabina, Alexandra; Gonzalez, Eduardo; Rivas, Francisco; Polteva, Nina

2014-06-01

123

Analysis of 90 Mb of the potato genome reveals conservation of gene structures and order with tomato but divergence in repetitive sequence composition  

PubMed Central

Background The Solanaceae family contains a number of important crop species including potato (Solanum tuberosum) which is grown for its underground storage organ known as a tuber. Albeit the 4th most important food crop in the world, other than a collection of ~220,000 Expressed Sequence Tags, limited genomic sequence information is currently available for potato and advances in potato yield and nutrition content would be greatly assisted through access to a complete genome sequence. While morphologically diverse, Solanaceae species such as potato, tomato, pepper, and eggplant share not only genes but also gene order thereby permitting highly informative comparative genomic analyses. Results In this study, we report on analysis 89.9 Mb of potato genomic sequence representing 10.2% of the genome generated through end sequencing of a potato bacterial artificial chromosome (BAC) clone library (87 Mb) and sequencing of 22 potato BAC clones (2.9 Mb). The GC content of potato is very similar to Solanum lycopersicon (tomato) and other dicotyledonous species yet distinct from the monocotyledonous grass species, Oryza sativa. Parallel analyses of repetitive sequences in potato and tomato revealed substantial differences in their abundance, 34.2% in potato versus 46.3% in tomato, which is consistent with the increased genome size per haploid genome of these two Solanum species. Specific classes and types of repetitive sequences were also differentially represented between these two species including a telomeric-related repetitive sequence, ribosomal DNA, and a number of unclassified repetitive sequences. Comparative analyses between tomato and potato at the gene level revealed a high level of conservation of gene content, genic feature, and gene order although discordances in synteny were observed. Conclusion Genomic level analyses of potato and tomato confirm that gene sequence and gene order are conserved between these solanaceous species and that this conservation can be leveraged in genomic applications including cross-species annotation and genome sequencing initiatives. While tomato and potato share genic features, they differ in their repetitive sequence content and composition suggesting that repetitive sequences may have a more significant role in shaping speciation than previously reported. PMID:18554403

Zhu, Wei; Ouyang, Shu; Iovene, Marina; O'Brien, Kimberly; Vuong, Hue; Jiang, Jiming; Buell, C Robin

2008-01-01

124

The Corynebacterium xerosisComposite Transposon Tn 5432Consists of Two Identical Insertion Sequences, Designated IS 1249,Flanking the Erythromycin Resistance Gene ermCX  

Microsoft Academic Search

Analysis of the 50-kb R-plasmid pTP10 from the clinical isolateCorynebacterium xerosisM82B revealed that the erythromycin resistance gene,ermCX,is located on a 4524-bp composite transposable element, Tn5432.The ends of Tn5432are identical, direct repeats of an insertion sequence, designated IS1249,encoding a putative transposase of the IS256family. IS1249consists of 1385 bp with 45\\/42 imperfect terminal inverted repeats. The nucleotide sequence of the 1754-bp Tn5432central

ANDREAS TAUCH; FRIEDRICH KASSING; JÖRN KALINOWSKI; ALFRED PÜHLER

1995-01-01

125

Sequencing-Based Analysis of the Bacterial and Fungal Composition of Kefir Grains and Milks from Multiple Sources  

PubMed Central

Kefir is a fermented milk-based beverage to which a number of health-promoting properties have been attributed. The microbes responsible for the fermentation of milk to produce kefir consist of a complex association of bacteria and yeasts, bound within a polysaccharide matrix, known as the kefir grain. The consistency of this microbial population, and that present in the resultant beverage, has been the subject of a number of previous, almost exclusively culture-based, studies which have indicated differences depending on geographical location and culture conditions. However, culture-based identification studies are limited by virtue of only detecting species with the ability to grow on the specific medium used and thus culture-independent, molecular-based techniques offer the potential for a more comprehensive analysis of such communities. Here we describe a detailed investigation of the microbial population, both bacterial and fungal, of kefir, using high-throughput sequencing to analyse 25 kefir milks and associated grains sourced from 8 geographically distinct regions. This is the first occasion that this technology has been employed to investigate the fungal component of these populations or to reveal the microbial composition of such an extensive number of kefir grains or milks. As a result several genera and species not previously identified in kefir were revealed. Our analysis shows that the bacterial populations in kefir are dominated by 2 phyla, the Firmicutes and the Proteobacteria. It was also established that the fungal populations of kefir were dominated by the genera Kazachstania, Kluyveromyces and Naumovozyma, but that a variable sub-dominant population also exists. PMID:23894461

Marsh, Alan J.; O'Sullivan, Orla; Hill, Colin; Ross, R. Paul; Cotter, Paul D.

2013-01-01

126

PS1-10jh: The Partial Disruption of a Main-Sequence Star of Near-Solar Composition  

NASA Astrophysics Data System (ADS)

When a star comes within a critical distance to a supermassive black hole, immense tidal forces can remove a significant fraction of the star's mass, resulting in a stream of debris that falls back onto the black hole and powers a luminous flare. I will be describing the results of hydrodynamical simulations to demonstrate that self-gravity, while unimportant along the direction parallel to the debris, provides significantly confinement across the debris. As a consequence, the stream has a negligible surface area and makes almost no contribution to either the continuum or line emission. We additionally find that the debris stream is strongly compressed and virialized when it returns to pericenter, resulting in a teardrop-shaped structure with a temperature profile similar to that of a Shakura-Sunyaev accretion disk, which grows at a speed somewhat less than the star's original speed at pericenter. We propose that any observed emission lines are not the result of collisional excitation, but are produced similarly to the broad-line regions commonly observed in active galactic nuclei. As each line within a broad-line region is kinematically linked to a particular location in the accretion disk, we suggest that the absence of a line indicates that the accretion disk does not yet extend to the distance required to produce that line. This model can be used to understand the spectral properties of the tidal disruption event PS1-10jh, for which HeII lines are observed, but H? is not. We show that a partial disruption of a main-sequence star of near-solar composition can reproduce this event.

Guillochon, James; Ramirez-Ruiz, E.

2013-04-01

127

Separation of small molecular peptides with the same amino acid composition but different sequences by high performance liquid chromatography-electrospray ionization-mass spectrometry  

Microsoft Academic Search

Peptidomics has emerged as a new discipline in recent years. Mass spectrometry (MS) is the most universal and efficient tool\\u000a for structure identification of proteins and peptides. However, there is a limitation for the identification of peptides with\\u000a the same amino acid composition but different sequences because these peptides have identical mass spectra of molecular ions.\\u000a This paper presents a

LiHong Liu; ZiLin Chen

2009-01-01

128

Backbone resonance assignment of Alt a 1, a unique ?-barrel protein and the major allergen of Alternaria alternata.  

PubMed

Alt a 1 is the major allergen of the fungus Alternaria alternata and can be found in the cell wall of its spores. It is a cysteine linked homodimeric protein with a unique ?-barrel fold as recently revealed by X-ray crystallography. Despite the elucidation of its structure, its biological function remains unknown. For Alternaria-sensitized patients, contact leads to respiratory allergy and in severe cases to asthma-related death. Here we report the sequence-specific Alt a 1 backbone (1)H, (15)N and (13)C chemical shift assignment. PMID:23715812

Wagner, Gabriel E; Gutfreund, Sandra; Fauland, Kerstin; Keller, Walter; Valenta, Rudolf; Zangger, Klaus

2014-10-01

129

Error tolerant NMR backbone resonance assignment and automated structure generation.  

PubMed

Error tolerant backbone resonance assignment is the cornerstone of the NMR structure determination process. Although a variety of assignment approaches have been developed, none works sufficiently well on noisy fully automatically picked peaks to enable the subsequent automatic structure determination steps. We have designed an integer linear programming (ILP) based assignment system (IPASS) that has enabled fully automatic protein structure determination for four test proteins. IPASS employs probabilistic spin system typing based on chemical shifts and secondary structure predictions. Furthermore, IPASS extracts connectivity information from the inter-residue information and the (automatically picked) (15)N-edited NOESY peaks which are then used to fix reliable fragments. When applied to automatically picked peaks for real proteins, IPASS achieves an average precision and recall of 82% and 63%, respectively. In contrast, the next best method, MARS, achieves an average precision and recall of 77% and 36%, respectively. The assignments generated by IPASS are then fed into our protein structure calculation system, FALCON-NMR, to determine the 3D structures without human intervention. The final models have backbone RMSDs of 1.25Å, 0.88Å, 1.49Å, and 0.67Å to the reference native structures for proteins TM1112, CASKIN, VRAR, and HACS1, respectively. The web server is publicly available at http://monod.uwaterloo.ca/nmr/ipass. PMID:21328705

Alipanahi, Babak; Gao, Xin; Karakoc, Emre; Li, Shuai Cheng; Balbach, Frank; Feng, Guangyu; Donaldson, Logan; Li, Ming

2011-02-01

130

?-Conjugated trinuclear group-9 metalladithiolenes with a triphenylene backbone.  

PubMed

Previously, we synthesized ?-conjugated trinuclear metalladithiolene complexes based on benzenehexathiol (J. Chem. Soc., Dalton Trans.1998, 2651; Dalton Trans.2009, 1939; Inorg. Chem.2011, 50, 6856). Here we report trinuclear complexes with a triphenylene backbone. A reaction with triphenylenehexathiol and group 9 metal precursors in the presence of triethylamine gives rise to trinuclear complexes 9-11. The planar structure of 11 is determined using single crystal X-ray diffraction analysis. The ligand-to-metal charge transfer bands of 9-11 move to longer wavelengths compared with those of mononuclear 12-14. Electrochemical measurements disclose that the one-electron and two-electron reduced mixed-valent states are stabilized thermodynamically. UV-vis-NIR spectroscopy for the reduced species of 9 identifies intervalence charge transfer bands for 9(-) and 9(2-), substantiating the existence of electronic communication among the three metal nuclei. These observations prove that the triphenylene backbone transmits ?-conjugation among the three metalladithiolene units. PMID:23758171

Sakamoto, Ryota; Kambe, Tetsuya; Tsukada, Satoru; Takada, Kenji; Hoshiko, Ken; Kitagawa, Yasutaka; Okumura, Mitsutaka; Nishihara, Hiroshi

2013-07-01

131

Analysis of BAC end sequences in oak, a keystone forest tree species, providing insight into the composition of its genome  

PubMed Central

Background One of the key goals of oak genomics research is to identify genes of adaptive significance. This information may help to improve the conservation of adaptive genetic variation and the management of forests to increase their health and productivity. Deep-coverage large-insert genomic libraries are a crucial tool for attaining this objective. We report herein the construction of a BAC library for Quercus robur, its characterization and an analysis of BAC end sequences. Results The EcoRI library generated consisted of 92,160 clones, 7% of which had no insert. Levels of chloroplast and mitochondrial contamination were below 3% and 1%, respectively. Mean clone insert size was estimated at 135 kb. The library represents 12 haploid genome equivalents and, the likelihood of finding a particular oak sequence of interest is greater than 99%. Genome coverage was confirmed by PCR screening of the library with 60 unique genetic loci sampled from the genetic linkage map. In total, about 20,000 high-quality BAC end sequences (BESs) were generated by sequencing 15,000 clones. Roughly 5.88% of the combined BAC end sequence length corresponded to known retroelements while ab initio repeat detection methods identified 41 additional repeats. Collectively, characterized and novel repeats account for roughly 8.94% of the genome. Further analysis of the BESs revealed 1,823 putative genes suggesting at least 29,340 genes in the oak genome. BESs were aligned with the genome sequences of Arabidopsis thaliana, Vitis vinifera and Populus trichocarpa. One putative collinear microsyntenic region encoding an alcohol acyl transferase protein was observed between oak and chromosome 2 of V. vinifera. Conclusions This BAC library provides a new resource for genomic studies, including SSR marker development, physical mapping, comparative genomics and genome sequencing. BES analysis provided insight into the structure of the oak genome. These sequences will be used in the assembly of a future genome sequence for oak. PMID:21645357

2011-01-01

132

Tuning the guest-binding ability of a helically folded capsule by in situ modification of the aromatic oligoamide backbone.  

PubMed

Starting from a previously described aromatic oligoamide helically folded capsule that binds tartaric acid with high affinity and diastereoselectivity, we demonstrate the feasibility of the direct in situ modification of the helix backbone, which results in a conformational change that reduces its affinity for guests by two orders of magnitude. Specifically, ring contraction of the central pyridazine unit into a pyrrole in the full helical sequence was investigated by using electrochemical and chemical processes. The sequence containing the pyrrole was synthesized independently in a convergent manner to ascertain its structure. The conformation of the pyrrolic folded capsule was elucidated in the solid state by X-ray crystallography and in solution by using (1)H and (13)C?NMR spectroscopy. Solution studies revealed an unanticipated solvent-dependent equilibrium between the anti-anti and syn-syn conformations of the pyrrole ring with respect to its two adjacent pyridine units. Titrations of the pyrrole-containing sequence monitored by (1)H?NMR spectroscopy confirmed the expected drop in affinity for tartaric acid and malic acid that arises from the conformation change in the backbone that follows the replacement of the pyridazine by a pyrrole. The reduction of the pyridazine to a pyrrole was characterized by cyclic voltammetry both on the entire sequence and on a shorter precursor. The lower cathodic potential of the precursor made its preparative-scale electroreduction possible. Direct in situ modification of the pyridazine within the entire capsule sequence was achieved chemically by using zinc in acetic acid. PMID:24402735

Lautrette, Guillaume; Aube, Christophe; Ferrand, Yann; Pipelier, Muriel; Blot, Virginie; Thobie, Christine; Kauffmann, Brice; Dubreuil, Didier; Huc, Ivan

2014-02-01

133

Water proton spin saturation affects measured protein backbone 15 N spin relaxation rates  

NASA Astrophysics Data System (ADS)

Protein backbone 15N NMR spin relaxation rates are useful in characterizing the protein dynamics and structures. To observe the protein nuclear-spin resonances a pulse sequence has to include a water suppression scheme. There are two commonly employed methods, saturating or dephasing the water spins with pulse field gradients and keeping them unperturbed with flip-back pulses. Here different water suppression methods were incorporated into pulse sequences to measure 15N longitudinal T1 and transversal rotating-frame T1? spin relaxation. Unexpectedly the 15N T1 relaxation time constants varied significantly with the choice of water suppression method. For a 25-kDa Escherichiacoli. glutamine binding protein (GlnBP) the T1 values acquired with the pulse sequence containing a water dephasing gradient are on average 20% longer than the ones obtained using a pulse sequence containing the water flip-back pulse. In contrast the two T1? data sets are correlated without an apparent offset. The average T1 difference was reduced to 12% when the experimental recycle delay was doubled, while the average T1 values from the flip-back measurements were nearly unchanged. Analysis of spectral signal to noise ratios ( s/ n) showed the apparent slower 15N relaxation obtained with the water dephasing experiment originated from the differences in 1H N recovery for each relaxation time point. This in turn offset signal reduction from 15N relaxation decay. The artifact becomes noticeable when the measured 15N relaxation time constant is comparable to recycle delay, e.g., the 15N T1 of medium to large proteins. The 15N relaxation rates measured with either water suppression schemes yield reasonable fits to the structure. However, data from the saturated scheme results in significantly lower Model-Free order parameters (< S2> = 0.81) than the non-saturated ones (< S2> = 0.88), indicating such order parameters may be previously underestimated.

Chen, Kang; Tjandra, Nico

2011-12-01

134

Stabilization of double-stranded oligonucleotides using backbone-linked disulfide bridges.  

PubMed Central

A convenient, practical route to the synthesis of disulfide-bridged oligonucleotides has been developed. Aliphatic linkers with terminal thiol groups have been attached to the phosphodiester backbones of partially or fully complementary oligonucleotide sequences and oxidized to yield covalently closed oligonucleotides with disulfide bridges. This procedure has been used to prepare a duplex with disulfide bridges at both ends and stem-loop sequences with single disulfide bridges. Oxidation of a self-complementary duplex possessing terminal thiol groups produced both hairpin and duplex structures with disulfide bridges, the relative proportions of each being dependent upon the reaction conditions. These bridged hairpin and duplex structures were shown to be interconvertible by reduction and re-oxidation. The melting profiles of disulfide-bridged oligonucleotides were compared with the same sequences without bridges and with sequences possessing triethylene glycol bridges, and in all cases the introduction of disulfide bridges resulted in a considerable increase in thermal stability. EcoRI endonuclease was capable of cleaving a disulfide-bridged duplex possessing a recognition site for this enzyme, thus supporting a lack of distortion of the recognition site. The disulfide bridges could be cleaved using a large excess of DTT to regenerate the corresponding sulfhydryl compounds. A study of the serum stabilities of disulfide-bridged oligonucleotides showed that the bridged duplexes were much more stable than their unmodified counterparts, whereas the rate of degradation of the stem-loop structures was more dependent upon the size of the loop than the presence or absence of the disulfide bridge. In summary, we have described a novel methodology, employing commercially available reagents, for the stabilization of oligonucleotide duplexes or stem-loop structures by disulfide bridge formation. Images PMID:7862534

Gao, H; Yang, M; Cook, A F

1995-01-01

135

Animal Protection and Structural Studies of a Consensus Sequence Vaccine Targeting the Receptor Binding Domain of the Type IV Pilus of Pseudomonas aeruginosa  

SciTech Connect

One of the main obstacles in the development of a vaccine against Pseudomonas aeruginosa is the requirement that it is protective against a wide range of virulent strains. We have developed a synthetic-peptide consensus-sequence vaccine (Cs1) that targets the host receptor-binding domain (RBD) of the type IV pilus of P. aeruginosa. Here, we show that this vaccine provides increased protection against challenge by the four piliated strains that we have examined (PAK, PAO, KB7 and P1) in the A.BY/SnJ mouse model of acute P. aeruginosa infection. To further characterize the consensus sequence, we engineered Cs1 into the PAK monomeric pilin protein and determined the crystal structure of the chimeric Cs1 pilin to 1.35 {angstrom} resolution. The substitutions (T130K and E135P) used to create Cs1 do not disrupt the conserved backbone conformation of the pilin RBD. In fact, based on the Cs1 pilin structure, we hypothesize that the E135P substitution bolsters the conserved backbone conformation and may partially explain the immunological activity of Cs1. Structural analysis of Cs1, PAK and K122-4 pilins reveal substitutions of non-conserved residues in the RBD are compensated for by complementary changes in the rest of the pilin monomer. Thus, the interactions between the RBD and the rest of the pilin can either be mediated by polar interactions of a hydrogen bond network in some strains or by hydrophobic interactions in others. Both configurations maintain a conserved backbone conformation of the RBD. Thus, the backbone conformation is critical in our consensus-sequence vaccine design and that cross-reactivity of the antibody response may be modulated by the composition of exposed side-chains on the surface of the RBD. This structure will guide our future vaccine design by focusing our investigation on the four variable residue positions that are exposed on the RBD surface.

Kao, Daniel J.; Churchill, Mair E.A.; Irvin, Randall T.; Hodges, Robert S. (Alberta); (Colorado)

2008-09-23

136

Subcellular location prediction of proteins using support vector machines with alignment of block sequences utilizing amino acid composition  

Microsoft Academic Search

Background: Subcellular location prediction of proteins is an important and well-studied problem in bioinformatics. This is a problem of predicting which part in a cell a given protein is transported to, where an amino acid sequence of the protein is given as an input. This problem is becoming more important since information on subcellular location is helpful for annotation of

Takeyuki Tamura; Tatsuya Akutsu

2007-01-01

137

N backbone and side-chain resonance assignments of Drosophila melanogaster Ssu72  

E-print Network

ARTICLE 1 H, 13 C and 15 N backbone and side-chain resonance assignments of Drosophila melanogaster NMR experiments to assign the backbone and side-chain resonances of the 23 kDa Ssu72 from Drosophila melanogaster in the phosphate-bound state, and use NMR titrations to examine the phosphate-binding properties

Zhou, Pei

138

A Distributed Formation of a Virtual Backbone in MANETs Using Adjustable Transmission Ranges  

Microsoft Academic Search

Recently, the use of a virtual backbone (connected dominating set) in various applications in mobile ad hoc networks (MANETs) has become popular. These applications include topology management, point and area coverage, and routing protocol design. In a mobile environment such as a MANET, one challenging issue in constructing a virtual backbone is to accomplish a distributed and localized solution that

Jie Wu; Fei Dai

2004-01-01

139

Synthesis of Triple Helix Forming Oligonucleotides with a Stretched Phosphodiester Backbone  

Microsoft Academic Search

Total synthesis of novel DMT-phosphoramidites of thymidine (11 and 15) and 2?-deoxyguanosine (8 and 20) have been accomplished. The utility of these modified building blocks in the preparation of triple helix forming oligodeoxyribonucleotides with a stretched phosphodiester backbone has been evaluated. It was found that the oligonucleotides with extended backbones were unable to enhance the binding to duplex targets containing

T. Sudhakar Rao; Krishna Jayaraman; Ross H. Durland; Ganapathi R. Revankar

1994-01-01

140

Supporting Internet Protocol TV (IPTV) in Backbone Networks: Design of Robust Routing Strategies  

E-print Network

Supporting Internet Protocol TV (IPTV) in Backbone Networks: Design of Robust Routing Strategies Paper ID: 261 (13 pages) Abstract In this paper, we consider the problem of providing IPTV services by designing routing strategies to handle catastrophic failures in a backbone network. In a typi- cal IPTV

Fisher, Kathleen

141

Laccase-assisted grafting of poly(3-hydroxybutyrate) onto the bacterial cellulose as backbone polymer: Development and characterisation.  

PubMed

Bacterial cellulose (BC) exhibits high purity, mechanical strength and an ultra-fine fibrous 3-D network structure with bio-compatible and bio-degradable characteristics, while P(3HB) are a bio-degradable matrix material derived from natural resources. Herein, we report a mild and eco-friendly fabrication of indigenously isolated P(3HB) based novel composites consisting of BC (a straight-chain polysaccharide) as a backbone polymer and laccase was used as a grafting tool. The resulting composites were characterised by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), dynamic mechanical analyser (DMA) and water contact angle analyser (WCA). The FTIR spectra of the pure P(3HB) and P(3HB) containing graft composites [P(3HB)-g-BC] showed their strong characteristic bands at 3358cm(-1), 1721cm(-1) and 1651cm(-1), respectively. A homogenous dispersion of P(3HB) in the backbone polymer of BC was achieved as evident by the SEM micrographs. XRD pattern for P(3HB) showed distinct peaks at 2? values that represent the crystalline nature of P(3HB). While, in comparison with those of neat P(3HB), the degree of crystallinity for P(3HB)-g-BC decreased and this reduction is mainly because of the new cross-linking of P(3HB) within the backbone polymer that changes the morphology and destroys the crystallites. Laccase-assisted graft composite prepared from P(3HB) and BC was fairly flexible and strong, judged by the tensile strength (64.5MPa), elongations at break (15.7%), and Young's modulus (0.98GPa) because inherently high strength of BC allowed the mechanical properties of P(3HB) to improve in the P(3HB)-g-BC composite. The hydrophilic property of the P(3HB)-g-BC was much better than that of the individual counterparts which is also a desired characteristic to enhance the biocompatibility of the materials for proper cell adhesion and proliferation. PMID:25256467

Iqbal, Hafiz M N; Kyazze, Godfrey; Tron, Thierry; Keshavarz, Tajalli

2014-11-26

142

Novel electrochemical biosensor based on functional composite nanofibers for sensitive detection of p53 tumor suppressor gene.  

PubMed

A novel electrochemical biosensor based on functional composite nanofibers for sensitive hybridization detection of p53 tumor suppressor using methylene blue (MB) as an electrochemical indicator is developed. The carboxylated multi-walled carbon nanotubes (MWNTs) doped nylon 6 (PA6) composite nanofibers (MWNTs-PA6) was prepared using electrospinning, which served as the nanosized backbone for pyrrole (Py) electropolymerization. The functional composite nanofibers (MWNTs-PA6-PPy) used as supporting scaffolds for ssDNA immobilization can dramatically increase the amount of DNA attachment and the hybridization sensitivity. The biosensor displayed good sensitivity and specificity. The target wild type p53 sequence (wtp53) can be detected as low as 50 fM and the discrimination is up to 57.5% between the wtp53 and the mutant type p53 sequence (mtp53). It holds promise for the early diagnosis of cancer development and monitoring of patient therapy. PMID:23410627

Wang, Xiaoying; Wang, Xiaobing; Wang, Xiaoning; Chen, Fentian; Zhu, Kehui; Xu, Qian; Tang, Meng

2013-02-26

143

Prediction of protein submitochondria locations by hybridizing pseudo-amino acid composition with various physicochemical features of segmented sequence  

Microsoft Academic Search

BACKGROUND: Knowing the submitochondria localization of a mitochondria protein is an important step to understand its function. We develop a method which is based on an extended version of pseudo-amino acid composition to predict the protein localization within mitochondria. This work goes one step further than predicting protein subcellular location. We also try to predict the membrane protein type for

Pufeng Du; Yanda Li

2006-01-01

144

iTIS-PseTNC: A sequence-based predictor for identifying translation initiation site in human genes using pseudo trinucleotide composition.  

PubMed

Translation is a key process for gene expression. Timely identification of the translation initiation site (TIS) is very important for conducting in-depth genome analysis. With the avalanche of genome sequences generated in the postgenomic age, it is highly desirable to develop automated methods for rapidly and effectively identifying TIS. Although some computational methods were proposed in this regard, none of them considered the global or long-range sequence-order effects of DNA, and hence their prediction quality was limited. To count this kind of effects, a new predictor, called "iTIS-PseTNC," was developed by incorporating the physicochemical properties into the pseudo trinucleotide composition, quite similar to the PseAAC (pseudo amino acid composition) approach widely used in computational proteomics. It was observed by the rigorous cross-validation test on the benchmark dataset that the overall success rate achieved by the new predictor in identifying TIS locations was over 97%. As a web server, iTIS-PseTNC is freely accessible at http://lin.uestc.edu.cn/server/iTIS-PseTNC. To maximize the convenience of the vast majority of experimental scientists, a step-by-step guide is provided on how to use the web server to obtain the desired results without the need to go through detailed mathematical equations, which are presented in this paper just for the integrity of the new prection method. PMID:25016190

Chen, Wei; Feng, Peng-Mian; Deng, En-Ze; Lin, Hao; Chou, Kuo-Chen

2014-10-01

145

Backbone of complex networks of corporations: The flow of control  

NASA Astrophysics Data System (ADS)

We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

Glattfelder, J. B.; Battiston, S.

2009-09-01

146

The dominant folding route minimizes backbone distortion in SH3.  

PubMed

Energetic frustration in protein folding is minimized by evolution to create a smooth and robust energy landscape. As a result the geometry of the native structure provides key constraints that shape protein folding mechanisms. Chain connectivity in particular has been identified as an essential component for realistic behavior of protein folding models. We study the quantitative balance of energetic and geometrical influences on the folding of SH3 in a structure-based model with minimal energetic frustration. A decomposition of the two-dimensional free energy landscape for the folding reaction into relevant energy and entropy contributions reveals that the entropy of the chain is not responsible for the folding mechanism. Instead the preferred folding route through the transition state arises from a cooperative energetic effect. Off-pathway structures are penalized by excess distortion in local backbone configurations and contact pair distances. This energy cost is a new ingredient in the malleable balance of interactions that controls the choice of routes during protein folding. PMID:23166485

Lammert, Heiko; Noel, Jeffrey K; Onuchic, José N

2012-01-01

147

Composite  

NASA Astrophysics Data System (ADS)

Particle distribution and hot workability of an in situ Al-TiCp composite were investigated. The composite was fabricated by an in situ casting method using the self-propagating high-temperature synthesis of an Al-Ti-C system. Hot-compression tests were carried out, and power dissipation maps were constructed using a dynamic material model. Small globular TiC particles were not themselves fractured, but the clustering and grain boundary segregation of the particles contributed to the cracking of the matrix by causing the debonding of matrix/particle interfaces and providing a crack propagation path. The efficiency of power dissipation increased with increasing temperature and strain rate, and the maximum efficiency was obtained at a temperature of 723 K (450 °C) and a strain rate of 1/s. The microstructural mechanism occurring in the maximum efficiency domain was dynamic recrystallization. The role of particles in the plastic flow and the microstructure evolution were discussed.

Kim, Su-Hyeon; Cho, Young-Hee; Lee, Jung-Moo

2014-06-01

148

Small RNA identification in Enterobacteriaceae using synteny and genomic backbone retention II.  

PubMed

Small RNAs are bacterial counterparts of noncoding RNAs. Increasing evidence being added in the literature indicates that these small RNAs play major roles in prokaryotes both at the transcriptome and proteome levels. Based on comparative genomic studies, we present manually curated small RNA regions in 25 recently completed genomes from Enterobacteriaceae. The study is a continuation of our earlier work that uses the presence of small RNAs sandwiched between specific conserved flanking genes retaining genomic backbone and gene synteny. Based on this study, a total of 931 identified sRNA/sRNA regions are reported. This data contains 498 small RNA homologs, 80 putative small RNA regions containing partial stretches of homologous sequences, and 353 putative nonhomologous sRNA regions. This homologs/partial homologs includes, 84 putative small RNA homologous regions retaining at least one of the conserved flanking genes pair which may possibly act as hotspots for genetic pool insertion/deletion in genomes. Nonhomologous CsrB sRNA region reported by us in Yersinia pseudotuberculosis IP32953 has been experimentally confirmed by Kulkarni's group and sraH and ryeE sRNAs from Erwinia carotovora subsp. atroseptica SCRI1043 recently added to the Rfam database are indicative proof of our positive approach. PMID:19445646

Sridhar, Jayavel; Kumar, Sivasankaran Sathesh; Rafi, Ziauddin Ahamed

2009-06-01

149

Evaluation of Diverse ?/? Backbone Patterns for Functional ?-Helix Mimicry: Analogues of the Bim BH3 Domain  

PubMed Central

Peptidic oligomers that contain both ?- and ?-amino acid residues, in regular patterns throughout the backbone, are emerging as structural mimics of ?-helix-forming conventional peptides (composed exclusively of ?-amino acid residues). Here we describe a comprehensive evaluation of diverse ?/?-peptide homologues of the Bim BH3 domain in terms of their ability to bind to the BH3-recognition sites on two partner proteins, Bcl-xL and Mcl-1. These proteins are members of the anti-apoptotic Bcl-2 family, and both bind tightly to the Bim BH3 domain itself. All ?/?-peptide homologues retain the side chain sequence of the Bim BH3 domain, but each homologue contains periodic ?-residue ? ?3-residue substitutions. Previous work has shown that the ??????? pattern, which aligns the ?3-residues in a 'stripe' along one side of the helix, can support functional ?-helix mimicry, and the results reported here support this conclusion. The present study provides the first evaluation of functional mimicry by ??? and ???? patterns, which cause the ?3-residues to spiral around the helix periphery. We find that the ???? pattern can support effective mimicry of the Bim BH3 domain, as manifested by the crystal structure of an ?/?-peptide bound to Bcl-xL, affinity for a variety of Bcl-2 family proteins, and induction of apoptotic signaling in mouse embryonic fibroblast extracts. The best ???? homologue shows substantial protection from proteolytic degradation relative to the Bim BH3 ?-peptide. PMID:22040025

Boersma, Melissa D.; Haase, Holly S.; Peterson-Kaufman, Kimberly J.; Lee, Erinna F.; Clarke, Oliver B.; Colman, Peter M.; Smith, Brian J.; Horne, W. Seth; Fairlie, W. Douglas; Gellman, Samuel H.

2012-01-01

150

4D experiments measured with APSY for automated backbone resonance assignments of large proteins.  

PubMed

Detailed structural and functional characterization of proteins by solution NMR requires sequence-specific resonance assignment. We present a set of transverse relaxation optimization (TROSY) based four-dimensional automated projection spectroscopy (APSY) experiments which are designed for resonance assignments of proteins with a size up to 40 kDa, namely HNCACO, HNCOCA, HNCACB and HN(CO)CACB. These higher-dimensional experiments include several sensitivity-optimizing features such as multiple quantum parallel evolution in a 'just-in-time' manner, aliased off-resonance evolution, evolution-time optimized APSY acquisition, selective water-handling and TROSY. The experiments were acquired within the concept of APSY, but they can also be used within the framework of sparsely sampled experiments. The multidimensional peak lists derived with APSY provided chemical shifts with an approximately 20 times higher precision than conventional methods usually do, and allowed the assignment of 90 % of the backbone resonances of the perdeuterated primase-polymerase ORF904, which contains 331 amino acid residues and has a molecular weight of 38.4 kDa. PMID:23625454

Krähenbühl, Barbara; Boudet, Julien; Wider, Gerhard

2013-06-01

151

Composites  

NASA Astrophysics Data System (ADS)

The Composites market is arguably the most challenging and profitable market for phenolic resins aside from electronics. The variety of products and processes encountered creates the challenges, and the demand for high performance in critical operations brings value. Phenolic composite materials are rendered into a wide range of components to supply a diverse and fragmented commercial base that includes customers in aerospace (Space Shuttle), aircraft (interiors and brakes), mass transit (interiors), defense (blast protection), marine, mine ducting, off-shore (ducts and grating) and infrastructure (architectural) to name a few. For example, phenolic resin is a critical adhesive in the manufacture of honeycomb sandwich panels. Various solvent and water based resins are described along with resin characteristics and the role of metal ions for enhanced thermal stability of the resin used to coat the honeycomb. Featured new developments include pultrusion of phenolic grating, success in RTM/VARTM fabricated parts, new ballistic developments for military vehicles and high char yield carbon-carbon composites along with many others. Additionally, global regional market resin volumes and sales are presented and compared with other thermosetting resin systems.

Taylor, John G.

152

The Corynebacterium xerosis composite transposon Tn5432 consists of two identical insertion sequences, designated IS1249, flanking the erythromycin resistance gene ermCX.  

PubMed

Analysis of the 50-kb R-plasmid pTP10 from the clinical isolate Corynebacterium xerosis M82B revealed that the erythromycin resistance gene, ermCX, is located on a 4524-bp composite transposable element, Tn5432. The ends of Tn5432 are identical, direct repeats of an insertion sequence, designated IS1249, encoding a putative transposase of the IS256 family. IS1249 consists of 1385 bp with 45/42 imperfect terminal inverted repeats. The nucleotide sequence of the 1754-bp Tn5432 central region is 99% identical to the previously sequenced erythromycin resistance region of the Corynebacterium diphtheriae plasmid pNG2. It encodes the erythromycin resistance gene, ermCX, and an ORF homologous to the amino-terminal end of the transposase of IS31831 from Corynebacterium glutamicum. Transposons with regions flanking the insertion sites were recovered from the C. glutamicum chromosome by a plasmid rescue technique. Insertion of Tn5432 created 8-bp target site duplications. A Tn5432-induced isoleucine/valine-auxotrophic mutant was found to carry the transposon in the 5' region of the ilvBNC cluster; in pTP10 the transposon is inserted in a region similar to replication and partitioning functions of the Enterococcus faecalis plasmid pAD1 and the Agrobacterium tumefaciens plasmid pTAR. PMID:8559800

Tauch, A; Kassing, F; Kalinowski, J; Pühler, A

1995-09-01

153

A precise reconstruction of the emergence and constrained radiations of Escherichia coli O157 portrayed by backbone concatenomic analysis  

PubMed Central

Single nucleotide polymorphisms (SNPs) in stable genome regions provide durable measurements of species evolution. We systematically identified each SNP in concatenations of all backbone ORFs in 7 newly or previously sequenced evolutionarily instructive pathogenic Escherichia coli O157:H7, O157:H?, and O55:H7. The 1,113 synonymous SNPs demonstrate emergence of the largest cluster of this pathogen only in the last millennium. Unexpectedly, shared SNPs within circumscribed clusters of organisms suggest severely restricted survival and limited effective population sizes of pathogenic O157:H7, tenuous survival of these organisms in nature, source-sink evolutionary dynamics, or, possibly, a limited number of mutations that confer selective advantage. A single large segment spanning the rfb-gnd gene cluster is the only backbone region convincingly acquired by recombination as O157 emerged from O55. This concatenomic analysis also supports using SNPs to differentiate closely related pathogens for infection control and forensic purposes. However, constrained radiations raise the possibility of making false associations between isolates. PMID:19439656

Leopold, Shana R.; Magrini, Vincent; Holt, Nicholas J.; Shaikh, Nurmohammad; Mardis, Elaine R.; Cagno, Joseph; Ogura, Yoshitoshi; Iguchi, Atsushi; Hayashi, Tetsuya; Mellmann, Alexander; Karch, Helge; Besser, Thomas E.; Sawyer, Stanley A.; Whittam, Thomas S.; Tarr, Phillip I.

2009-01-01

154

Solution structure and backbone dynamics of the defunct domain of calcium vector protein.  

PubMed

CaVP (calcium vector protein) is a Ca(2+) sensor of the EF-hand protein family which is highly abundant in the muscle of Amphioxus. Its three-dimensional structure is not known, but according to the sequence analysis, the protein is composed of two domains, each containing a pair of EF-hand motifs. We determined recently the solution structure of the C-terminal domain (Trp81-Ser161) and characterized the large conformational and dynamic changes induced by Ca(2+) binding. In contrast, the N-terminal domain (Ala1-Asp86) has lost the capacity to bind the metal ion due to critical mutations and insertions in the two calcium loops. In this paper, we report the solution structure of the N-terminal domain and its backbone dynamics based on NMR spectroscopy, nuclear relaxation, and molecular modeling. The well-resolved three-dimensional structure is typical of a pair of EF-hand motifs, joined together by a short antiparallel beta-sheet. The tertiary arrangement of the two EF-hands results in a closed-type conformation, with near-antiparallel alpha-helices, similar to other EF-hand pairs in the absence of calcium ions. To characterize the internal dynamics of the protein, we measured the (15)N nuclear relaxation rates and the heteronuclear NOE effect in (15)N-labeled N-CaVP at a magnetic field of 11.74 T and 298 K. The domain is mainly monomeric in solution and undergoes an isotropic Brownian rotational diffusion with a correlation time of 7.1 ns, in good agreement with the fluorescence anisotropy decay measurements. Data analysis using a model-free procedure showed that the amide backbone groups in the alpha-helices and beta-strands undergo highly restricted movements on a picosecond to nanosecond time scale. The amide groups in Ca(2+) binding loops and in the linker fragment also display rapid fluctuations with slightly increased amplitudes. PMID:11705378

Théret, I; Baladi, S; Cox, J A; Gallay, J; Sakamoto, H; Craescu, C T

2001-11-20

155

Pseudo 5D HN(C)N experiment to facilitate the assignment of backbone resonances in proteins exhibiting high backbone shift degeneracy  

NASA Astrophysics Data System (ADS)

Assignment of protein backbone resonances is most routinely carried out using triple resonance three-dimensional NMR experiments involving amide 1H/15N resonances. However for intrinsically unstructured proteins, alpha-helical proteins or proteins containing several disordered fragments, the assignment becomes problematic because of high-degree of backbone shift degeneracy. In this backdrop, a novel reduced-dimensionality (RD) experiment -(5, 3)D-hNCO-CANH- is presented to facilitate/validate the sequential backbone resonance assignment in such proteins. The proposed 3D NMR experiment makes use of the modulated amide 15N chemical shifts (resulting from the joint sampling along both its indirect dimensions) to resolve the ambiguity involved in connecting the neighboring amide resonances (i.e. HiNi and Hi-1Ni-1) for overlapping amide-NH peaks. The experiment -in combination with routine triple resonance 3D-NMR experiments involving backbone amide (1H/15N) and carbon (13C?/13C?) chemical shifts- will serve as a powerful complementary tool to achieve the nearly complete assignment of protein backbone resonances in a time efficient manner.

Kumar, Dinesh; Raikwal, Nisha; Shukla, Vaibhav Kumar; Pandey, Himanshu; Arora, Ashish; Guleria, Anupam

2014-09-01

156

MCBT: Multi-Hop Cluster Based Stable Backbone Trees for Data Collection and Dissemination in WSNs.  

PubMed

We propose a stable backbone tree construction algorithm using multi-hop clusters for wireless sensor networks (WSNs). The hierarchical cluster structure has advantages in data fusion and aggregation. Energy consumption can be decreased by managing nodes with cluster heads. Backbone nodes, which are responsible for performing and managing multi-hop communication, can reduce the communication overhead such as control traffic and minimize the number of active nodes. Previous backbone construction algorithms, such as Hierarchical Cluster-based Data Dissemination (HCDD) and Multicluster, Mobile, Multimedia radio network (MMM), consume energy quickly. They are designed without regard to appropriate factors such as residual energy and degree (the number of connections or edges to other nodes) of a node for WSNs. Thus, the network is quickly disconnected or has to reconstruct a backbone. We propose a distributed algorithm to create a stable backbone by selecting the nodes with higher energy or degree as the cluster heads. This increases the overall network lifetime. Moreover, the proposed method balances energy consumption by distributing the traffic load among nodes around the cluster head. In the simulation, the proposed scheme outperforms previous clustering schemes in terms of the average and the standard deviation of residual energy or degree of backbone nodes, the average residual energy of backbone nodes after disseminating the sensed data, and the network lifetime. PMID:22454570

Shin, Inyoung; Kim, Moonseong; Mutka, Matt W; Choo, Hyunseung; Lee, Tae-Jin

2009-01-01

157

Emergence of sequence type 779 methicillin-resistant Staphylococcus aureus harboring a novel pseudo staphylococcal cassette chromosome mec (SCCmec)-SCC-SCCCRISPR composite element in Irish hospitals.  

PubMed

Methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of nosocomial infection in Irish hospitals for 4 decades, and replacement of predominant MRSA clones has occurred several times. An MRSA isolate recovered in 2006 as part of a larger study of sporadic MRSA exhibited a rare spa (t878) and multilocus sequence (ST779) type and was nontypeable by PCR- and DNA microarray-based staphylococcal cassette chromosome mec (SCCmec) element typing. Whole-genome sequencing revealed the presence of a novel 51-kb composite island (CI) element with three distinct domains, each flanked by direct repeat and inverted repeat sequences, including (i) a pseudo SCCmec element (16.3 kb) carrying mecA with a novel mec class region, a fusidic acid resistance gene (fusC), and two copper resistance genes (copB and copC) but lacking ccr genes; (ii) an SCC element (17.5 kb) carrying a novel ccrAB4 allele; and (iii) an SCC element (17.4 kb) carrying a novel ccrC allele and a clustered regularly interspaced short palindromic repeat (CRISPR) region. The novel CI was subsequently identified by PCR in an additional 13 t878/ST779 MRSA isolates, six from bloodstream infections, recovered between 2006 and 2011 in 11 hospitals. Analysis of open reading frames (ORFs) carried by the CI showed amino acid sequence similarity of 44 to 100% to ORFs from S. aureus and coagulase-negative staphylococci (CoNS). These findings provide further evidence of genetic transfer between S. aureus and CoNS and show how this contributes to the emergence of novel SCCmec elements and MRSA strains. Ongoing surveillance of this MRSA strain is warranted and will require updating of currently used SCCmec typing methods. PMID:23147725

Kinnevey, Peter M; Shore, Anna C; Brennan, Grainne I; Sullivan, Derek J; Ehricht, Ralf; Monecke, Stefan; Slickers, Peter; Coleman, David C

2013-01-01

158

Emergence of Sequence Type 779 Methicillin-Resistant Staphylococcus aureus Harboring a Novel Pseudo Staphylococcal Cassette Chromosome mec (SCCmec)-SCC-SCCCRISPR Composite Element in Irish Hospitals  

PubMed Central

Methicillin-resistant Staphylococcus aureus (MRSA) has been a major cause of nosocomial infection in Irish hospitals for 4 decades, and replacement of predominant MRSA clones has occurred several times. An MRSA isolate recovered in 2006 as part of a larger study of sporadic MRSA exhibited a rare spa (t878) and multilocus sequence (ST779) type and was nontypeable by PCR- and DNA microarray-based staphylococcal cassette chromosome mec (SCCmec) element typing. Whole-genome sequencing revealed the presence of a novel 51-kb composite island (CI) element with three distinct domains, each flanked by direct repeat and inverted repeat sequences, including (i) a pseudo SCCmec element (16.3 kb) carrying mecA with a novel mec class region, a fusidic acid resistance gene (fusC), and two copper resistance genes (copB and copC) but lacking ccr genes; (ii) an SCC element (17.5 kb) carrying a novel ccrAB4 allele; and (iii) an SCC element (17.4 kb) carrying a novel ccrC allele and a clustered regularly interspaced short palindromic repeat (CRISPR) region. The novel CI was subsequently identified by PCR in an additional 13 t878/ST779 MRSA isolates, six from bloodstream infections, recovered between 2006 and 2011 in 11 hospitals. Analysis of open reading frames (ORFs) carried by the CI showed amino acid sequence similarity of 44 to 100% to ORFs from S. aureus and coagulase-negative staphylococci (CoNS). These findings provide further evidence of genetic transfer between S. aureus and CoNS and show how this contributes to the emergence of novel SCCmec elements and MRSA strains. Ongoing surveillance of this MRSA strain is warranted and will require updating of currently used SCCmec typing methods. PMID:23147725

Kinnevey, Peter M.; Shore, Anna C.; Brennan, Grainne I.; Sullivan, Derek J.; Ehricht, Ralf; Monecke, Stefan; Slickers, Peter

2013-01-01

159

Composites  

NASA Astrophysics Data System (ADS)

It is commonly known that the properties of sintered materials are strongly related to technological conditions of the densification process. This paper shows the sintering behavior of a NiAl-Al2O3 composite, and its individual components sintered separately. Each kind of material was processed via the powder metallurgy route (hot pressing). The progress of sintering at different stages of the process was tested. Changes in the microstructure were examined using scanning and transmission electron microscopy. Metal-ceramics interface was clean and no additional phases were detected. Correlation between the microstructure, density, and mechanical properties of the sintered materials was analyzed. The values of elastic constants of NiAl/Al2O3 were close to intermetallic ones due to the volume content of the NiAl phase particularly at low densities, where small alumina particles had no impact on the composite's stiffness. The influence of the external pressure of 30 MPa seemed crucial for obtaining satisfactory stiffness for three kinds of the studied materials which were characterized by a high dense microstructure with a low number of isolated spherical pores.

Chmielewski, M.; Nosewicz, S.; Pietrzak, K.; Rojek, J.; Strojny-N?dza, A.; Mackiewicz, S.; Dutkiewicz, J.

2014-11-01

160

Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold  

SciTech Connect

The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.

Azoitei, Mihai L.; Correia, Bruno E.; Ban, Yih-En Andrew; Carrico, Chris; Kalyuzhniy, Oleksandr; Chen, Lei; Schroeter, Alexandria; Huang, Po-Ssu; McLellan, Jason S.; Kwong, Peter D.; Baker, David; Strong, Roland K.; Schief, William R. (UWASH); (FHCRC); (NIAID)

2012-02-07

161

Comparison of backbone modification in protein ?-sheets by ??? residue replacement and ?-residue methylation.  

PubMed

The mimicry of protein tertiary structure by oligomers with unnatural backbones is a significant contemporary research challenge. Among common elements of secondary structure found in natural proteins, sheets have proven the most difficult to address. Here, we report the systematic comparison of different strategies for peptide backbone modification in ?-sheets with the goal of identifying the best method for replacing a multi-stranded sheet in a protein tertiary fold. The most effective sheet modifications examined led to native-like tertiary folding behavior with a thermodynamic folded stability comparable to the prototype protein on which the modified backbones are based. PMID:24909436

Lengyel, George A; Reinert, Zachary E; Griffith, Brian D; Horne, W Seth

2014-08-01

162

J. Chem. Soc., Perkin Trans. 1, 1997 1501 Building units for N-backbone cyclic peptides. Part 4.1  

E-print Network

J. Chem. Soc., Perkin Trans. 1, 1997 1501 Building units for N-backbone cyclic peptides. Part 4 for the synthesis of backbone-cyclic peptides. They are orthogonally protected at the -amino position for their incorporation into peptides by solid phase peptide synthesis. Introduction Backbone-Cyclization is a method

Kasher, Roni

163

Time between Collection and Storage Significantly Influences Bacterial Sequence Composition in Sputum Samples from Cystic Fibrosis Respiratory Infections  

PubMed Central

Spontaneously expectorated sputum is traditionally used as the sampling method for the investigation of lower airway infections. While guidelines exist for the handling of these samples for culture-based diagnostic microbiology, there is no comparable consensus on their handling prior to culture-independent analysis. The increasing incorporation of culture-independent approaches in diagnostic microbiology means that it is of critical importance to assess potential biases. The aim of this study was to assess the impact of delayed freezing on culture-independent microbiological analyses and to identify acceptable parameters for sample handling. Sputum samples from eight adult cystic fibrosis (CF) patients were collected and aliquoted into sterile Bijou bottles. Aliquots were stored at room temperature before being frozen at ?80°C for increasing intervals, up to a 72-h period. Samples were treated with propidium monoazide to distinguish live from dead cells prior to DNA extraction, and 16S rRNA gene pyrosequencing was used to characterize their bacterial compositions. Substantial variation was observed in samples with high-diversity bacterial communities over time, whereas little variation was observed in low-diversity communities dominated by recognized CF pathogens, regardless of time to freezing. Partitioning into common and rare species demonstrated that the rare species drove changes in similarity. The percentage abundance of anaerobes over the study significantly decreased after 12 h at room temperature (P = 0.008). Failure to stabilize samples at ?80°C within 12 h of collection results in significant changes in the detected community composition. PMID:24920767

Cuthbertson, Leah; Rogers, Geraint B.; Walker, Alan W.; Oliver, Anna; Hafiz, Tarana; Hoffman, Lucas R.; Carroll, Mary P.; Parkhill, Julian; Bruce, Kenneth D.

2014-01-01

164

Sequence analysis of styrenic copolymers by tandem mass spectrometry.  

PubMed

Styrene and smaller molar amounts of either m-dimethylsilylstyrene (m-DMSS) or p-dimethylsilylstyrene (p-DMSS) were copolymerized under living anionic polymerization conditions, and the compositions, architectures, and sequences of the resulting copolymers were characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry (MS(2)). MS analysis revealed that linear copolymer chains containing phenyl-Si(CH3)2H pendants were the major product for both DMSS comonomers. In addition, two-armed architectures with phenyl-Si(CH3)2-benzyl branches were detected as minor products. The comonomer sequence in the linear chains was established by MS(2) experiments on lithiated oligomers, based on the DMSS content of fragments generated by backbone C-C bond scissions and with the help of reference MS(2) spectra obtained from a polystyrene homopolymer and polystyrene end-capped with a p-DMSS block. The MS(2) data provided conclusive evidence that copolymerization of styrene/DMSS mixtures leads to chains with a rather random distribution of the silylated comonomer when m-DMSS is used, but to chains with tapered block structures, with the silylated units near the initiator, when p-DMSS is used. Hence, MS(2) fragmentation patterns permit not only differentiation of the sequences generated in the synthesis, but also the determination of specific comonomer locations along the polymer chain. PMID:25181590

Yol, Aleer M; Janoski, Jonathan; Quirk, Roderic P; Wesdemiotis, Chrys

2014-10-01

165

Multiple morphologies from amphiphilic graft copolymers based on chitooligosaccharides as backbones and polycaprolactones as branches.  

PubMed

A new route to form multiple morphologies was outlined using amphiphilic graft copolymers with interesting biological and pharmacological properties by proper adjustment of backbone and graft chain length. PMID:16010334

Wang, Caiqi; Li, Guangtao; Guo, Ruirong

2005-07-28

166

Chemorheology of phenylboronate-salicylhydroxamate crosslinked hydrogel networks with a sulfonated polymer backbone  

PubMed Central

Hydrogel networks crosslinked with polymer-bound phenylboronic acid (PBA) and salicylhydroxamic acid (SHA) demonstrate pH-reversible gel behavior due to the pH-dependent equilibrium of the crosslinking moieties that form the gel network. Furthermore, the pH at which gels behave dynamically can be controlled by use of a polyelectrolyte backbone. Here we report on the frequency-dependent chemorheological characterization of PBA-SHA crosslinked hydrogel networks with a sulfonated polymer backbone. Our results suggest that the anionic nature of the polymers allows reversible crosslinking at neutral pH that an otherwise neutral-backboned PBA-SHA crosslinked network cannot, and that these charge-induced dynamics can be effectively screened by ions in solution. Moreover, moduli-frequency data can effectively be reduced into a single master curve with a neutral-backboned PBA-SHA gel data set as the reference condition. PMID:23132956

Roberts, Meredith C.; Mahalingam, Alamelu; Hanson, Melissa C.; Kiser, Patrick F.

2012-01-01

167

Packet optical networks for high-speed TCP-IP backbones  

Microsoft Academic Search

This article presents a new proposal for TCP-IP backbone implementation based on optical packet switching technology. The proposed network architecture merges the flexibility in resource management of packet switching with the high capacity offered by full optical technology

F. Callegati; M. Casoni; C. Raffaelli

1999-01-01

168

iPro54-PseKNC: a sequence-based predictor for identifying sigma-54 promoters in prokaryote with pseudo k-tuple nucleotide composition  

PubMed Central

The ?54 promoters are unique in prokaryotic genome and responsible for transcripting carbon and nitrogen-related genes. With the avalanche of genome sequences generated in the postgenomic age, it is highly desired to develop automated methods for rapidly and effectively identifying the ?54 promoters. Here, a predictor called ‘iPro54-PseKNC’ was developed. In the predictor, the samples of DNA sequences were formulated by a novel feature vector called ‘pseudo k-tuple nucleotide composition’, which was further optimized by the incremental feature selection procedure. The performance of iPro54-PseKNC was examined by the rigorous jackknife cross-validation tests on a stringent benchmark data set. As a user-friendly web-server, iPro54-PseKNC is freely accessible at http://lin.uestc.edu.cn/server/iPro54-PseKNC. For the convenience of the vast majority of experimental scientists, a step-by-step protocol guide was provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics that were presented in this paper just for its integrity. Meanwhile, we also discovered through an in-depth statistical analysis that the distribution of distances between the transcription start sites and the translation initiation sites were governed by the gamma distribution, which may provide a fundamental physical principle for studying the ?54 promoters. PMID:25361964

Lin, Hao; Deng, En-Ze; Ding, Hui; Chen, Wei; Chou, Kuo-Chen

2014-01-01

169

Secondary-Structure Design of Proteins by a Backbone Torsion Energy  

Microsoft Academic Search

We propose a new backbone-torsion-energy term in the force field for protein systems. This torsion-energy term is represented by a double Fourier series in two variables, the backbone dihedral angles phi and \\\\psi. It gives a natural representation of the torsion energy in the Ramachandran space in the sense that any two-dimensional energy surface periodic in both phi and \\\\psi

Yoshitake Sakae; Yuko Okamoto

2006-01-01

170

On the Geometry and Electronic Structure of the As-DNA Backbone  

SciTech Connect

High-level quantum chemical calculations have been applied to investigate the geometry and electronic properties of the arsenate analogue of the DNA backbone. The optimized geometries as well as hyperconjugation effects along the C30 O30 X O50 C50 linkage (X = P,As) exhibit a remarkable similarity for both arsenates and phosphates. This suggests that arsenates, if present, might serve as a potential substitute for phosphates in the DNA backbone.

Fuentes-Cabrera, Miguel A [ORNL; Sponer, Jiri [Academy of Sciences of the Czech Republic; Sponer, Judit [Academy of Sciences of the Czech Republic; Sumpter, Bobby G [ORNL; Mladek, Arnost [Academy of Sciences of the Czech Republic

2011-01-01

171

PS1-10jh: The Disruption of a Main-Sequence Star of Near-Solar Composition  

E-print Network

When a star comes within a critical distance to a supermassive black hole (SMBH), immense tidal forces can remove a significant fraction of the star's mass, resulting in a stream of debris that falls back onto the black hole and powers a luminous flare. In this paper, we perform two hydrodynamical simulations of the disruption of a main-sequence star by a SMBH to characterize the evolution of the debris stream after a tidal disruption. We demonstrate that this debris stream is confined by self-gravity in the two directions perpendicular to the original direction of the star's travel, restricting its width and height to be only a factor of a few larger than its original size. As a consequence, the stream has a negligible surface area and makes almost no contribution to either the continuum or line emission. We propose that any observed emission lines are not the result of photoionization in the unbound debris, but are produced in the region above and below the forming elliptical accretion disk, the same region...

Guillochon, James; Ramirez-Ruiz, Enrico

2013-01-01

172

Improving the prediction accuracy of residue solvent accessibility and real-value backbone torsion angles of proteins by guided-learning through a two-layer neural network  

PubMed Central

This paper attempts to increase the prediction accuracy of residue solvent accessibility and real-value backbone torsion angles of proteins through improved learning. Most methods developed for improving the backpropagation algorithm of artificial neural networks are limited to small neural networks. Here, we introduce a guided-learning method suitable for networks of any size. The method employs a part of the weights for guiding and the other part for training and optimization. We demonstrate this technique by predicting residue solvent accessibility and real-value backbone torsion angles of proteins. In this application, the guiding factor is designed to satisfy the intuitive condition that for most residues, the contribution of a residue to the structural properties of another residue is smaller for greater separation in the protein-sequence distance between the two residues. We show that the guided-learning method makes a 2-4% reduction in ten-fold cross-validated mean absolute errors (MAE) for predicting residue solvent accessibility and backbone torsion angles, regardless of the size of database, the number of hidden layers and the size of input windows. This together with introduction of two-layer neural network with a bipolar activation function leads to a new method that has a MAE of 0.11 for residue solvent accessibility, 36° for ?, and 22° for ?. The method is available as a Real-SPINE 3.0 server in http://sparks.informatics.iupui.edu. PMID:18704931

Faraggi, Eshel; Xue, Bin; Zhou, Yaoqi

2008-01-01

173

Deriving High-Resolution Protein Backbone Structure Propensities from All Crystal Data Using the Information Maximization Device  

PubMed Central

The most informative probability distribution functions (PDFs) describing the Ramachandran phi-psi dihedral angle pair, a fundamental descriptor of backbone conformation of protein molecules, are derived from high-resolution X-ray crystal structures using an information-theoretic approach. The Information Maximization Device (IMD) is established, based on fundamental information-theoretic concepts, and then applied specifically to derive highly resolved phi-psi maps for all 20 single amino acid and all 8000 triplet sequences at an optimal resolution determined by the volume of current data. The paper shows that utilizing the latent information contained in all viable high-resolution crystal structures found in the Protein Data Bank (PDB), totaling more than 77,000 chains, permits the derivation of a large number of optimized sequence-dependent PDFs. This work demonstrates the effectiveness of the IMD and the superiority of the resulting PDFs by extensive fold recognition experiments and rigorous comparisons with previously published triplet PDFs. Because it automatically optimizes PDFs, IMD results in improved performance of knowledge-based potentials, which rely on such PDFs. Furthermore, it provides an easy computational recipe for empirically deriving other kinds of sequence-dependent structural PDFs with greater detail and precision. The high-resolution phi-psi maps derived in this work are available for download. PMID:24896099

Solis, Armando D.

2014-01-01

174

'Genome order index' should not be used for defining compositional constraints in nucleotide sequences - a case study of the Z-curve  

Microsoft Academic Search

BACKGROUND: The Z-curve is a three dimensional representation of DNA sequences proposed over a decade ago and has been extensively applied to sequence segmentation, horizontal gene transfer detection, and sequence analysis. Based on the Z-curve, a \\

Eran Elhaik; Dan Graur; Krešimir Josi?

2010-01-01

175

Acute Effects of TiO2 Nanomaterials on the Viability and Taxonomic Composition of Aquatic Bacterial Communities Assessed via High-Throughput Screening and Next Generation Sequencing  

PubMed Central

The nanotechnology industry is growing rapidly, leading to concerns about the potential ecological consequences of the release of engineered nanomaterials (ENMs) to the environment. One challenge of assessing the ecological risks of ENMs is the incredible diversity of ENMs currently available and the rapid pace at which new ENMs are being developed. High-throughput screening (HTS) is a popular approach to assessing ENM cytotoxicity that offers the opportunity to rapidly test in parallel a wide range of ENMs at multiple concentrations. However, current HTS approaches generally test one cell type at a time, which limits their ability to predict responses of complex microbial communities. In this study toxicity screening via a HTS platform was used in combination with next generation sequencing (NGS) to assess responses of bacterial communities from two aquatic habitats, Lake Michigan (LM) and the Chicago River (CR), to short-term exposure in their native waters to several commercial TiO2 nanomaterials under simulated solar irradiation. Results demonstrate that bacterial communities from LM and CR differed in their sensitivity to nano-TiO2, with the community from CR being more resistant. NGS analysis revealed that the composition of the bacterial communities from LM and CR were significantly altered by exposure to nano-TiO2, including decreases in overall bacterial diversity, decreases in the relative abundance of Actinomycetales, Sphingobacteriales, Limnohabitans, and Flavobacterium, and a significant increase in Limnobacter. These results suggest that the release of nano-TiO2 to the environment has the potential to alter the composition of aquatic bacterial communities, which could have implications for the stability and function of aquatic ecosystems. The novel combination of HTS and NGS described in this study represents a major advance over current methods for assessing ENM ecotoxicity because the relative toxicities of multiple ENMs to thousands of naturally occurring bacterial species can be assessed simultaneously under environmentally relevant conditions. PMID:25162615

Binh, Chu Thi Thanh; Tong, Tiezheng; Gaillard, Jean-Francois; Gray, Kimberly A.; Kelly, John J.

2014-01-01

176

Nonparametric Combinatorial Sequence Models  

NASA Astrophysics Data System (ADS)

This work considers biological sequences that exhibit combinatorial structures in their composition: groups of positions of the aligned sequences are "linked" and covary as one unit across sequences. If multiple such groups exist, complex interactions can emerge between them. Sequences of this kind arise frequently in biology but methodologies for analyzing them are still being developed. This paper presents a nonparametric prior on sequences which allows combinatorial structures to emerge and which induces a posterior distribution over factorized sequence representations. We carry out experiments on three sequence datasets which indicate that combinatorial structures are indeed present and that combinatorial sequence models can more succinctly describe them than simpler mixture models. We conclude with an application to MHC binding prediction which highlights the utility of the posterior distribution induced by the prior. By integrating out the posterior our method compares favorably to leading binding predictors.

Wauthier, Fabian L.; Jordan, Michael I.; Jojic, Nebojsa

177

Chiral PNAs with constrained open-chain backbones.  

PubMed

Chiral open-chain PNAs have been shown to have improved properties in terms of control of helical handedness, DNA affinity, sequence selectivity, and cellular uptake. They can be synthesized either using preformed chiral monomers or by means of a submonomeric strategy. The former is preferred when only a stereogenic center is present at C-5, whereas for PNA-bearing substituents at C-2, the submonomeric approach is preferred, since racemization, generally occurring during the solid-phase synthesis, can be minimized by this procedure. Here we describe the protocols for the synthesis of PNA oligomers containing C-2- or C-5- (or both) modified monomers and a GC method for checking the optical purity of C-2-modified PNAs. PMID:24297348

Corradini, Roberto; Tedeschi, Tullia; Sforza, Stefano; Marchelli, Rosangela

2014-01-01

178

Ebolavirus VP35 Coats the Backbone of Double-Stranded RNA for Interferon Antagonism  

PubMed Central

Recognition of viral double-stranded RNA (dsRNA) activates interferon production and immune signaling in host cells. Crystal structures of ebolavirus VP35 show that it caps dsRNA ends to prevent sensing by pattern recognition receptors such as RIG-I. In contrast, structures of marburgvirus VP35 show that it primarily coats the dsRNA backbone. Here, we demonstrate that ebolavirus VP35 also coats the dsRNA backbone in solution, although binding to the dsRNA ends probably constitutes the initial binding event. PMID:23824825

Bale, Shridhar; Julien, Jean-Philippe; Bornholdt, Zachary A.; Krois, Alexander S.; Wilson, Ian A.

2013-01-01

179

Convenient and scalable synthesis of fmoc-protected Peptide nucleic Acid backbone.  

PubMed

The peptide nucleic acid backbone Fmoc-AEG-OBn has been synthesized via a scalable and cost-effective route. Ethylenediamine is mono-Boc protected, then alkylated with benzyl bromoacetate. The Boc group is removed and replaced with an Fmoc group. The synthesis was performed starting with 50?g of Boc anhydride to give 31?g of product in 32% overall yield. The Fmoc-protected PNA backbone is a key intermediate in the synthesis of nucleobase-modified PNA monomers. Thus, improved access to this molecule is anticipated to facilitate future investigations into the chemical properties and applications of nucleobase-modified PNA. PMID:22848796

Feagin, Trevor A; Shah, Nirmal I; Heemstra, Jennifer M

2012-01-01

180

Convenient and Scalable Synthesis of Fmoc-Protected Peptide Nucleic Acid Backbone  

PubMed Central

The peptide nucleic acid backbone Fmoc-AEG-OBn has been synthesized via a scalable and cost-effective route. Ethylenediamine is mono-Boc protected, then alkylated with benzyl bromoacetate. The Boc group is removed and replaced with an Fmoc group. The synthesis was performed starting with 50?g of Boc anhydride to give 31?g of product in 32% overall yield. The Fmoc-protected PNA backbone is a key intermediate in the synthesis of nucleobase-modified PNA monomers. Thus, improved access to this molecule is anticipated to facilitate future investigations into the chemical properties and applications of nucleobase-modified PNA. PMID:22848796

Feagin, Trevor A.; Shah, Nirmal I.; Heemstra, Jennifer M.

2012-01-01

181

Backbone Ordering in Amphiphile Monolayers Jeremy Schofield and Stuart A. Rice,  

E-print Network

Backbone Ordering in Amphiphile Monolayers Jeremy Schofield and Stuart A. Rice, Department Recent X­ray diffraction 1 and infrared absorption studies 2 of liquid­supported monolayers of long chain and Rice 5 have successfully applied density functional theory to the tilting transition in long

Schofield, Jeremy

182

Accelerator Physics Accelerators form the backbone of SLAC's on-site experimental program. Research at SLAC  

E-print Network

#12;Accelerator Physics Accelerators form the backbone of SLAC's on-site experimental program. Research at SLAC is continually improving accelerators, both here and at other laboratories, and paving the way for a new generation of particle acceleration technology. SLAC's famous linear accelerator

Wechsler, Risa H.

183

Solving job shop scheduling problems utilizing the properties of backbone and “big valley”  

Microsoft Academic Search

In this paper, a new metaheuristic for the job shop scheduling problem is proposed. Our approach uses the backbone and “big\\u000a valley” properties of the job shop scheduling problem. The results of the computational experiments have demonstrated the\\u000a high efficiency of our approach. New upper bounds have been obtained for many problems.

Panos M. Pardalos; Oleg V. Shylo; Alkis Vazacopoulos

2010-01-01

184

High-cost, high-capacity backbone for global brain communication  

E-print Network

March 3, 2012) Network studies of human brain structural connectivity have identified a specific set-capacity backbone for global brain communication. connectome | graph | tractography Integrative brain function nodes), the human connectome (1�3). A large proportion of cortico-cortical axonal connections link

Pillow, Jonathan

185

Evaluating NoC communication backbones with simulation Rikard Thid, Mikael Millberg, and Axel Jantsch  

E-print Network

programmability, most NoC pro- posals recommend standardized and layered communica- tion protocolsEvaluating NoC communication backbones with simulation Rikard Thid, Mikael Millberg, and Axel. 1. Introduction In the SIA silicon roadmap[1], it is predicted that the increase in chip capacity

Jantsch, Axel

186

Graduate Education in Kinesiology: Are We Part of “America's Backbone for Competitiveness and Innovation”?  

Microsoft Academic Search

Graduate education in the United States has been identified as being the backbone of American competitiveness and innovation in a recent report by the Council of Graduate Schools. The report provides a framework for examining the role of graduate education in partnership with business and government to advance an action agenda for achieving competitiveness and innovation. The role and positioning

Karen P. DePauw

2008-01-01

187

Modeling Individual Topic-Specific Behavior and Influence Backbone Networks in Social Media  

E-print Network

Modeling Individual Topic-Specific Behavior and Influence Backbone Networks in Social Media Petko equally. Received: date / Accepted: date Abstract Information propagation in social media depends not only dynamic user behavior are needed. To this end, we propose a model for individual social media users

Varela, Carlos

188

Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity  

E-print Network

Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity Simon that the early evolution of life was dominated by RNA, which can both transfer information from generation of heterogeneous nucleic acid molecules could evolve reproducible function. For such evolution to be possible

Heller, Eric

189

Abstract--Human operation of continuum "continuous-backbone" manipulators remains difficult, because of both the  

E-print Network

Abstract--Human operation of continuum "continuous- backbone" manipulators remains difficult of freedom of the continuum manipulator, allowing an operator to perform kinematically complex grasping motivates the development of innovative user interfaces in order to simplify the task of operating robots

190

The flexibility in the proline ring couples to the protein backbone  

E-print Network

The flexibility in the proline ring couples to the protein backbone BOSCO K. HO,1 EVANGELOS A predominantly in two discrete states. However, there is also a small but significant amount of flexibility in the proline ring of high-resolution protein structures. We have found that this side-chain flexibility

Coutsias, Evangelos

191

Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing  

PubMed Central

The crystal structure of the duplex formed by oligo(2?,3?-dideoxy-?-d-glucopyranosyl)nucleotides (homo-DNA) revealed strongly inclined backbone and base-pair axes [Egli,M., Pallan,P.S., Pattanayek,R., Wilds,C.J., Lubini,P., Minasov,G., Dobler,M., Leumann,C.J. and Eschenmoser,A. (2006) Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. J. Am. Chem. Soc., 128, 10847–10856]. This inclination is easily perceived because homo-DNA exhibits only a modest helical twist. Conversely, the tight coiling of strands conceals that the backbone-base inclinations for A- (DNA and RNA) and B-form (DNA) duplexes differ considerably. We have defined a parameter ?B that corresponds to the local inclination between sugar-phosphate backbone and base plane in nucleic acid strands. Here, we show its biological significance as a predictive measure for the relative strand polarities (antiparallel, aps, or parallel, ps) in duplexes of DNA, RNA and artificial nucleic acid pairing systems. The potential of formation of ps duplexes between complementary 16-mers with eight A and U(T) residues each was investigated with DNA, RNA, 2?-O-methylated RNA, homo-DNA and p-RNA, the ribopyranosyl isomer of RNA. The thermodynamic stabilities of the corresponding aps duplexes were also measured. As shown previously, DNA is capable of forming both ps and aps duplexes. However, all other tested systems are unable to form stable ps duplexes with reverse Watson–Crick (rWC) base pairs. This observation illustrates the handicap encountered by nucleic acid systems with inclinations ?B that differ significantly from 0° to form a ps rWC paired duplex. Accordingly, RNA with a backbone-base inclination of ?30°, pairs strictly in an aps fashion. On the other hand, the more or less perpendicular orientation of backbone and bases in DNA allows it to adopt a ps rWC paired duplex. In addition to providing a rationalization of relative strand polarity with nucleic acids, the backbone-base inclination parameter is also a determinant of cross-pairing. Thus, systems with strongly deviating ?B angles will not pair with each other. Nucleic acid pairing systems with significant backbone-base inclinations can also be expected to display different stabilities depending on which terminus carries unpaired nucleotides. The negative inclination of RNA is consistent with the higher stability of duplexes with 3?- compared to those with 5?-dangling ends. PMID:17905816

Pallan, Pradeep S.; Lubini, Paolo; Bolli, Martin; Egli, Martin

2007-01-01

192

pH dependence of conformational fluctuations of the protein backbone.  

PubMed

Proton binding equilibria (pKa values) of ionizable groups in proteins are exquisitely sensitive to their microenvironments. Apparent pKa values measured for individual ionizable residues with NMR spectroscopy are actually population-weighted averages of the pKa in different conformational microstates. NMR spectroscopy experiments with staphylococcal nuclease were used to test the hypothesis that pKa values of surface Glu and Asp residues are affected by pH-sensitive fluctuations of the backbone between folded and locally unfolded conformations. (15) N spin relaxation studies showed that as the pH decreases from the neutral into the acidic range the amplitudes of backbone fluctuations in the ps-ns timescale increase near carboxylic residues. Hydrogen exchange experiments suggested that backbone conformational fluctuations promoted by decreasing pH also reflect slower local or sub-global unfolding near carboxylic groups. This study has implications for structure-based pKa calculations: (1) The timescale of the backbone's response to ionization events in proteins can range from ps to ms, and even longer; (2) pH-sensitive fluctuations of the backbone can be localized to both the segment the ionizable residue is attached to or the one that occludes the ionizable group; (3) Structural perturbations are not necessarily propagated through Coulomb interactions; instead, local fluctuations appear to be coupled through the co-operativity inherent to elements of secondary structure and to networks of hydrogen bonds. These results are consistent with the idea that local conformational fluctuations and stabilities are important determinants of apparent pKa values of ionizable residues in proteins. Proteins 2014; 82:3132-3143. © 2014 Wiley Periodicals, Inc. PMID:25137073

Richman, Daniel E; Majumdar, Ananya; García-Moreno E, Bertrand

2014-11-01

193

The IncP-1 plasmid backbone adapts to different host bacterial species and evolves through homologous recombination  

Microsoft Academic Search

Plasmids are important members of the bacterial mobile gene pool, and are among the most important contributors to horizontal gene transfer between bacteria. They typically harbour a wide spectrum of host beneficial traits, such as antibiotic resistance, inserted into their backbones. Although these inserted elements have drawn considerable interest, evolutionary information about the plasmid backbones, which encode plasmid related traits,

Peter Norberg; Maria Bergström; Vinay Jethava; Devdatt Dubhashi; Malte Hermansson

2011-01-01

194

Design of peptide standards with the same composition and minimal sequence variation (SCMSV) to monitor performance/selectivity of reversed-phase matrices  

PubMed Central

The present manuscript extends our de novo peptide design approach to the synthesis and evaluation of a new generation of reversed-phase HPLC peptide standards with the same composition and minimal sequence variation (SCMSV). Thus, we have designed and synthesized four series of peptide standards with the sequences Gly-X-Leu-Gly-Leu-Ala-Leu-Gly-Gly-Leu-Lys-Lys-amide, where the N-terminal is either N?-acetylated (Series 1) or contains a free ?-amino group (Series 3); and Gly-Gly-Leu-Gly-Gly-Ala-Leu-Gly-X-Leu-Lys-Lys-amide, where the N-terminal is either N?-acetylated (Series 2) or contains a free ?-amino group (Series 4). In this initial study, the single substitution position, X, was substituted with alkyl side-chains (Ala

Mant, Colin T.; Hodges, Robert S.

2012-01-01

195

Structural conservation, variability, and immunogenicity of the T6 backbone pilin of serotype M6 Streptococcus pyogenes.  

PubMed

Group A streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen that causes a broad range of diseases ranging from acute pharyngitis to the poststreptococcal sequelae of acute rheumatic fever. GAS pili are highly diverse, long protein polymers that extend from the cell surface. They have multiple roles in infection and are promising candidates for vaccine development. This study describes the structure of the T6 backbone pilin (BP; Lancefield T-antigen) from the important M6 serotype. The structure reveals a modular arrangement of three tandem immunoglobulin-like domains, two with internal isopeptide bonds. The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. The T6 structure also highlights a conserved pilin core whose surface is decorated with highly variable loops and extensions. Comparison to other Gram-positive BPs shows that many of the largest variable extensions are found in conserved locations. Studies with sera from patients diagnosed with GAS-associated acute rheumatic fever showed that each of the three T6 domains, and the largest of the variable extensions (V8), are targeted by IgG during infection in vivo. Although the GAS BP show large variations in size and sequence, the modular nature of the pilus proteins revealed by the T6 structure may aid the future design of a pilus-based vaccine. PMID:24778112

Young, Paul G; Moreland, Nicole J; Loh, Jacelyn M; Bell, Anita; Atatoa Carr, Polly; Proft, Thomas; Baker, Edward N

2014-07-01

196

Backbone dynamics of rusticyanin: the high hydrophobicity and rigidity of this blue copper protein is responsible for its thermodynamic properties.  

PubMed

Local dynamics and solute-solvent exchange properties of rusticyanin (Rc) from Thiobacillus ferrooxidans have been studied by applying heteronuclear ((1)H, (15)N) NMR spectroscopy. (15)N relaxation parameters have been determined for the reduced protein, and a model-free analysis has been applied. The high average value of the generalized order parameter, S(2) (0.93), indicates that Rc is very rigid. The analysis of cross correlation rates recorded in both the reduced and the oxidized forms conclusively proves that Rc possesses the same dynamic features in both oxidation states. The accessibility of backbone amide protons to the solvent at different time scales has also been studied by applying specific heteronuclear pulse sequences and by H(2)O/D(2)O exchange experiments. These experiments reveal that rusticyanin is extremely hydrophobic. The first N-35 amino acids, not present in the other BCPs, protect the beta-barrel core from its interaction with the solvent, and thus, this is one of the main factors contributing to the hydrophobicity. Both characteristics (high rigidity and hydrophobicity) are maintained in the metal ion surroundings. PMID:12950166

Jiménez, Beatriz; Piccioli, Mario; Moratal, José-María; Donaire, Antonio

2003-09-01

197

Assembly of polypeptide and protein backbone conformations from low energy ensembles of short fragments: development of strategies and construction of models for myoglobin, lysozyme, and thymosin beta 4.  

PubMed Central

Recently we developed methods for the construction of knowledge-based mean fields from a data base of known protein structures. As shown previously, this approach can be used to calculate ensembles of probable conformations for short fragments of polypeptide chains. Here we develop procedures for the assembly of short fragments to complete three-dimensional models of polypeptide chains. The amino acid sequence of a given protein is decomposed into all possible overlapping fragments of a given length, and an ensemble of probable conformations is calculated for each fragment. The fragments are assembled to a complete model by choosing appropriate conformations from the individual ensembles and by averaging over equivalent angles. Finally a consistent model is obtained by rebuilding the conformation from the average angles. From the average angles the local variability of the structure can be calculated, which is a useful criterion for the reliability of the model. The procedure is applied to the calculation of the local backbone conformations of myoglobin and lysozyme whose structures have been solved by X-ray analysis and thymosin beta 4, a polypeptide of 43 amino acid residues whose structure was recently investigated by NMR spectroscopy. We demonstrate that substantial fractions of the calculated local backbone conformations are similar to the experimentally determined structures. PMID:1304362

Sippl, M. J.; Hendlich, M.; Lackner, P.

1992-01-01

198

Protonation-deprotonation of the glycine backbone as followed by Raman scattering and multiconformational analysis  

NASA Astrophysics Data System (ADS)

Because of the absence of the side chain in its chemical structure and its well defined Raman spectra, glycine was selected here to follow its backbone protonation-deprotonation. The scan of the recorded spectra in the 1800-300 cm-1 region led us to assign those obtained at pH 1, 6 and 12 to the cationic, zwitterionic and anionic species, respectively. These data complete well those previously published by Bykov et al. (2008) [16] devoted to the high wavenumber Raman spectra (>2500 cm-1). To reinforce our discussion, DFT calculations were carried out on the clusters of glycine + 5H2O, mimicking reasonably the first hydration shell of the amino acid. Geometry optimization of 141 initial clusters, reflecting plausible combinations of the backbone torsion angles, allowed exploration of the conformational features, as well as construction of the theoretical Raman spectra by considering the most stable clusters containing each glycine species.

Hernández, Belén; Pflüger, Fernando; Kruglik, Sergei G.; Ghomi, Mahmoud

2013-11-01

199

Protein Backbone Torsion Angle-Based Structure Comparison and Secondary Structure Database Web Server  

PubMed Central

Structural information has been a major concern for biological and pharmaceutical studies for its intimate relationship to the function of a protein. Three-dimensional representation of the positions of protein atoms is utilized among many structural information repositories that have been published. The reliability of the torsional system, which represents the native processes of structural change in the structural analysis, was partially proven with previous structural alignment studies. Here, a web server providing structural information and analysis based on the backbone torsional representation of a protein structure is newly introduced. The web server offers functions of secondary structure database search, secondary structure calculation, and pair-wise protein structure comparison, based on a backbone torsion angle representation system. Application of the implementation in pair-wise structural alignment showed highly accurate results. The information derived from this web server might be further utilized in the field of ab initio protein structure modeling or protein homology-related analyses. PMID:24124412

Jung, Sunghoon; Bae, Se-Eun; Ahn, Insung

2013-01-01

200

Proposed BackBone API Preliminary Draft v1.0  

E-print Network

Smart Trek Proposed BackBone API Preliminary Draft v1.0 Table of Contents 1.0) API diagram / Introduction 2.0) Requirements 3.0) Class skeletons 4.0) Isp Examples 4.1) Domain Inbound API example 4.2) SDD Inbound API example 4.3) SDD Outbound API example 4.4) ItsFrame Inbound API example 4.5) ItsFrame Outbound

201

EMSCOPE - Electromagnetic Component of EarthScope Backbone and Transportable Array Experiments 2006-2008  

Microsoft Academic Search

USArray (http:\\/\\/www.iris.edu\\/USArray) in conjunction with EMSOC (Electromagnetic Studies of the Continents) (http:\\/\\/emsoc.ucr.edu\\/emsoc) is installing magnetotelluric (MT) stations as part of Earthscope. The MT component of Earthscope consists of permanent (Backbone) and transportable long period stations to record naturally occurring, time varying electric and magnetic fields to produce a regional lithospheric\\/asthensospheric electrical conductivity map of the United States. The recent arrival

G. Egbert; R. Evans; S. Ingate; D. Livelybrooks; K. Mickus; A. Schultz; M. Unsworth; P. Wannamaker

2007-01-01

202

Potent inhibition of HIV1 replication by backbone cyclic peptides bearing the Rev arginine rich motif  

Microsoft Academic Search

Summary  Due to its essential role in the virus life cycle, the viral regulatory protein Rev constitutes an attractive target for the\\u000a development of new antiviral molecules. In this work, a series of Backbone Cyclic Peptide (BCP) analogs that bear a conformationally\\u000a constrained arginine rich motif (ARM) of Rev were tested for in vitro inhibition of HIV-1 replication. We observed a potent

Laurent Chaloin; Fatima Smagulova; Elana Hariton-Gazal; Laurence Briant; Abraham Loyter; Christian Devaux

2007-01-01

203

Analysis of Measured Single-Hop Delay from an Operational Backbone Network  

Microsoft Academic Search

We measure and analyze the single-hop packet delay through op- erational routers in a backbone IP network. First we present our delay measurements through a single router. Then we identify step- by-step the factors contributing to single-hop delay. In addition to packet processing, transmission, and queueing delays, we iden- tify the presence of very large delays due to non-work-conserving router

Konstantina Papagiannaki; Sue B. Moon; Chuck Fraleigh; Patrick Thiran; Fouad A. Tobagi; Christophe Diot

2002-01-01

204

Tritium containing polymers having a polymer backbone substantially void of tritium  

DOEpatents

A radioluminescent light source comprises a solid mixture of a phosphorescent substance and a tritiated polymer. The solid mixture forms a solid mass having length, width, and thickness dimensions, and is capable of self-support. In one aspect of the invention, the phosphorescent substance comprises solid phosphor particles supported or surrounded within a solid matrix by a tritium containing polymer. The tritium containing polymer comprises a polymer backbone which is essentially void of tritium.

Jensen, George A. (Richland, WA); Nelson, David A. (Richland, WA); Molton, Peter M. (Richland, WA)

1992-01-01

205

Approach to detection of protein structural motifs using an encoding scheme of backbone conformations  

SciTech Connect

This paper presents an approach to detection of protein structural motifs. In our approach, first all protein backbone conformations are converted into character strings using an encoding scheme. Then we use the Smith-Waterman local alignment algorithm to detect common structural motifs. By comparing results with the PROSITE regular expression patterns, our method can detect several motifs which the PROSITE patterns fail to detect. 18 refs., 9 figs.

Matsuda, H.; Taniguchi, F.; Hashimoto, A. [Osaka Univ. (Japan)

1996-12-31

206

Assignment of Backbone Resonances in a Eukaryotic Protein Kinase – ERK2 as an Illustrative Example  

PubMed Central

Summary A first step towards the analysis of the structure, dynamics and interactions of proteins by NMR is obtaining an acceptable level of resonance assignments. This process is non-trivial in most eukaryotic kinases given their size and sub-optimal behavior in solution. Using inactive ERK2 as a representative example we describe the procedures we utilized to achieve a significant degree of completeness of backbone resonance assignment. PMID:22167683

Piserchio, Andrea; Dalby, Kevin N.; Ghose, Ranajeet

2012-01-01

207

Cryptosin induces backbone structural changes in cardiac Na+ and K+ dependent adenosinetriphosphatase.  

PubMed

Cryptosin, a new cardenolide, was found to preferentially bind to Na,K-ATPase enzyme (7), which is believed to be the ouabain binding site on cardiac sarcolemmal membrane. CD spectral studies revealed that cryptosin, in the presence of Na+ and Mg++ ions, bind to Na,K-ATPase and induce a dose-dependent change in the backbone structure of cardiac Na,K-ATPase. PMID:1965277

Venkateswara, R R; Dipak, D; Banning, J W; Vaidyanathan, C S

1990-10-01

208

Building (1 - epsilon) Dominating Sets Partition as Backbones in Wireless Sensor Networks Using Distributed Graph Coloring  

Microsoft Academic Search

\\u000a We recently proposed in [19,20] to use sequential graph coloring as a systematic algorithmic method to build (1????) dominating sets partition in Wireless Sensor Networks (WSN) modeled as Random Geometric Graphs (RGG). The resulting partition\\u000a of the network into dominating and almost dominating sets can be used as a series of rotating backbones in a WSN to prolong\\u000a the network

Dhia Mahjoub; David W. Matula

2010-01-01

209

Near-ultraviolet light-emitting diodes based on ?-conjugated linear silicon-backbone polymers  

Microsoft Academic Search

We report the basic device characteristics of light-emitting diodes (LEDs) based on linear silicon-backbone polymers, polysilanes, with a view to the possibility of employing them as an emissive material in a solid-state light source in the near-ultraviolet (NUV) or ultraviolet (UV) region. The LEDs we fabricated have a single-layer structure consisting of a thin film of polysilane polymer, together with

Hiroyuki Suzuki; Satoshi Hoshino; Chien-Hua Yuan; Michiya Fujiki; Seiji Toyoda; Nobuo Matsumoto

1998-01-01

210

Anion-conducting polymer, composition, and membrane  

DOEpatents

Anion-conducing polymers and membranes with enhanced stability to aqueous alkali include a polymer backbone with attached sulfonium, phosphazenium, phosphazene, and guanidinium residues. Compositions also with enhanced stability to aqueous alkali include a support embedded with sulfonium, phosphazenium, and guanidinium salts.

Pivovar, Bryan S. (Los Alamos, NM); Thorn, David L. (Los Alamos, NM)

2011-11-22

211

Anion-Conducting Polymer, Composition, and Membrane  

DOEpatents

Anion-conducing polymers and membranes with enhanced stability to aqueous alkali include a polymer backbone with attached sulfonium, phosphazenium, phosphazene, and guanidinium residues. Compositions also with enhanced stability to aqueous alkali include a support embedded with sulfonium, phosphazenium, and guanidinium salts.

Pivovar, Bryan S. (Los Alamos, NM); Thorn, David L. (Los Alamos, NM)

2008-10-21

212

Digital Sequences  

NASA Astrophysics Data System (ADS)

This section discusses the applications of digital sequences in acoustical system identification and characterization and describes Golay codes and binary maximum-length sequences (MLSs) in some detail. Legendre sequences and other coded signals are briefly described. Golay codes and MLS have been used for acoustic applications for years. Applications of Legendre sequences have also been reported. Digital sequences of other classes such as, e.g., binary Gold sequences and Kasami sequences have only recently found applications in acoustical system identification and characterization.

Xiang, Ning

213

Transcriptome Sequencing and Expression Analysis of Terpenoid Biosynthesis Genes in Litsea cubeba  

PubMed Central

Background Aromatic essential oils extracted from fresh fruits of Litsea cubeba (Lour.) Pers., have diverse medical and economic values. The dominant components in these essential oils are monoterpenes and sesquiterpenes. Understanding the molecular mechanisms of terpenoid biosynthesis is essential for improving the yield and quality of terpenes. However, the 40 available L. cubeba nucleotide sequences in the public databases are insufficient for studying the molecular mechanisms. Thus, high-throughput transcriptome sequencing of L. cubeba is necessary to generate large quantities of transcript sequences for the purpose of gene discovery, especially terpenoid biosynthesis related genes. Results Using Illumina paired-end sequencing, approximately 23.5 million high-quality reads were generated. De novo assembly yielded 68,648 unigenes with an average length of 834 bp. A total of 38,439 (56%) unigenes were annotated for their functions, and 35,732 and 25,806 unigenes could be aligned to the GO and COG database, respectively. By searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG), 16,130 unigenes were assigned to 297 KEGG pathways, and 61 unigenes, which contained the mevalonate and 2-C-methyl-D-erythritol 4-phosphate pathways, could be related to terpenoid backbone biosynthesis. Of the 12,963 unigenes, 285 were annotated to the terpenoid pathways using the PlantCyc database. Additionally, 14 terpene synthase genes were identified from the transcriptome. The expression patterns of the 16 genes related to terpenoid biosynthesis were analyzed by RT-qPCR to explore their putative functions. Conclusion RNA sequencing was effective in identifying a large quantity of sequence information. To our knowledge, this study is the first exploration of the L. cubeba transcriptome, and the substantial amount of transcripts obtained will accelerate the understanding of the molecular mechanisms of essential oils biosynthesis. The results may help improve future genetic and genomics studies on the molecular mechanisms behind the chemical composition of essential oils in L. cubeba fruits. PMID:24130803

Han, Xiao-Jiao; Wang, Yang-Dong; Chen, Yi-Cun; Lin, Li-Yuan; Wu, Qing-Ke

2013-01-01

214

Computational Design of the Sequence and Structure of a Protein-Binding Peptide  

SciTech Connect

The de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to G{alpha}{sub i1}. An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 {angstrom}.

Sammond, Deanne W.; Bosch, Dustin E.; Butterfoss, Glenn L.; Purbeck, Carrie; Machius, Mischa; Siderovski, David P.; Kuhlman, Brian (UNC)

2012-08-10

215

Effect of temperature and solvent composition on acid dissociation equilibria, I: Sequenced (s)(s)pKa determination of compounds commonly used as buffers in high performance liquid chromatography coupled to mass spectroscopy detection.  

PubMed

A new automated and rapid potentiometric method for determining the effect of organic-solvent composition on pK(a) has been developed. It is based on the measurements of pH values of buffer solutions of variable solvent compositions using a combined glass electrode. Additions of small volumes of one precisely thermostated solution into another, both containing exactly the same analytical concentrations of the buffer components, can produce continuous changes in the solvent composition. Two sequences of potential measurements, one of increasing and the other of decreasing solvent content, are sufficient to obtain the pK(a) values of the acidic compound within the complete solvent-composition range in about 2h. The experimental design, procedures, and calculations needed to convert the measured pH into the thermodynamic pK(a) values are thoroughly discussed. This rapid and automated method allows the systematic study of the effect of solvent compositions and temperatures on the pK(a). It has been applied to study the dissociation constants of two monoprotic acids: formic acid and triethylamine:HCl in acetonitrile/water mixtures within the range from 0 to 90% (v/v) at temperatures between 20°C and 60°C. These volatile compounds are frequently used to control the pH of the mobile phase in HPLC, especially in methods coupled to mass-spectrometry detection. The obtained pK(a) values are in excellent agreement with those previously reported. The results were fitted to empirical functions between pK(a) and temperature and composition. These equations, which can be used to estimate the pK(a) of these substances at any composition and temperature, would be highly useful in practical work during chromatographic method development. PMID:22502616

Padró, Juan M; Acquaviva, Agustín; Tascon, Marcos; Gagliardi, Leonardo G; Castells, Cecilia B

2012-05-01

216

Context and Force Field Dependence of the Loss of Protein Backbone Entropy upon Folding Using Realistic Denatured and Native State Ensembles  

PubMed Central

The loss of conformational entropy is the largest unfavorable quantity affecting a protein’s stability. We calculate the reduction in the number of backbone conformations upon folding using the distribution of backbone dihedral angles (?,?) obtained from an experimentally validated denatured state model, along with all-atom simulations for both the denatured and native states. The average loss of entropy per residue is T?SBBU-N = 0.7, 0.9, or 1.1 kcal·mol?1 at T = 298 K, depending on the force field used, with a 0.6 kcal·mol?1 dispersion across the sequence. The average equates to a decrease of a factor of 3–7 in the number of conformations available per residue (f = ?Denatured/?Native) or to a total of ftot=3n–7n for an n residue protein. Our value is smaller than most previous estimates where f = 7–20, i.e., our computed T?SBBU-N is smaller by 10–100 kcal mol?1 for n=100. The differences emerge from our use of realistic native and denatured state ensembles as well as from the inclusion of accurate local sequence preferences, neighbor effects, and correlated motions (vibrations), in contrast to some previous studies that invoke gross assumptions about the entropy in either or both states. We find that the loss of entropy primarily depends on the local environment and less on properties of the native state, with the exception of ?-helical residues in some force fields. PMID:22928488

Baxa, Michael C.; Haddadian, Esmael J.; Jha, Abhishek K.; Freed, Karl F.; Sosnick, Tobin R.

2012-01-01

217

The mouse DNA binding protein Rc for the kappa B motif of transcription and for the V(D)J recombination signal sequences contains composite DNA-protein interaction domains and belongs to a new family of large transcriptional proteins  

SciTech Connect

Rc is a DNA binding protein with dual specificities for the V(D)J recombination signal sequences and for the B motif of the immunoglobulin kappa chain gene enhancer. The largest Rc transcript present in lymphoid cells/tissues is {approximately} 9 kb. Molecular cloning and sequence determination for 8822 bp of mouse Rc cDNA revealed an open reading frame of 2282 amino acids and long 5{prime}- and 3{prime}- untranslated regions. The derived amino acid sequence contains multiple DNA and protein interaction domains. Composite ZAS structures with tandem zinc fingers, and acidic motif, and a Ser/Thr-rich segment are located near the N-terminal and the C-terminal regions. The middle region of Rc contains a lone zinc finger, an acidic motif, a Ser-rich region, a nucleus localization signal, and GTPase motifs. Cloning and characterization of a mouse Rc gene show that the Rc cDNA corresponds to seven exons located in a genomic region spanning 70 kb. Exon 2 is exceptionally large, with 5487 bp. cDNA cloning and Northern blot analyses revealed multiple Rc transcripts, probably generated by alternative splicings. Sequence comparisons show that Rc belongs to a ZAS protein family that is involved in gene transcription and/or DNA recombination. The major histocompatibility complex class I gene enhancer binding proteins MBP1 and MBP2 are other representatives of this ZAS protein family. 43 refs., 6 figs., 2 tabs.

Wu, Lai-Chu; Liu, Yiling; Li, Zhiling [Ohio State Univ., Columbus, OH (United States)] [and others] [Ohio State Univ., Columbus, OH (United States); and others

1996-08-01

218

"Splicing up" drug discovery. Cell-Based Expression and Screening of Genetically-Encoded Libraries of Backbone Cyclized Polypeptides  

PubMed Central

The present paper reviews the use of protein splicing for the biosynthesis of backbone cyclic polypeptides. This general method allows the in vivo and in vitro biosynthesis of cyclic polypeptides using recombinant DNA expression techniques. Biosynthetic access to backbone cyclic peptides opens the possibility to generate cell-based combinatorial libraries that can be screened inside living cells for their ability to attenuate or inhibit cellular processes thus providing a new way for finding therapeutic agents. PMID:19628015

Sancheti, Harshkumar; Camarero, Julio A.

2012-01-01

219

Genetic characterization by composite sequence analysis of a new pathogenic field strain of equine infectious anemia virus from the 2006 outbreak in Ireland.  

PubMed

Equine infectious anemia virus (EIAV), the causative agent of equine infectious anaemia (EIA), possesses the least-complex genomic organization of any known extant lentivirus. Despite this relative genetic simplicity, all of the complete genomic sequences published to date are derived from just two viruses, namely the North American EIAV(WYOMING) (EIAV(WY)) and Chinese EIAV(LIAONING) (EIAV(LIA)) strains. In 2006, an outbreak of EIA occurred in Ireland, apparently as a result of the importation of contaminated horse plasma from Italy and subsequent iatrogenic transmission to foals. This EIA outbreak was characterized by cases of severe, sometimes fatal, disease. To begin to understand the molecular mechanisms underlying this pathogenic phenotype, complete proviral genomic sequences in the form of 12 overlapping PCR-generated fragments were obtained from four of the EIAV-infected animals, including two of the index cases. Sequence analysis of multiple molecular clones produced from each fragment demonstrated the extent of diversity within individual viral genes and permitted construction of consensus whole-genome sequences for each of the four viral isolates. In addition, complete env gene sequences were obtained from 11 animals with differing clinical profiles, despite exposure to a common EIAV source. Although the overall genomic organization of the Irish EIAV isolates was typical of that seen in all other strains, the European viruses possessed ?80?% nucleotide sequence identity with either EIAV(WY) or EIAV(LIA). Furthermore, phylogenetic analysis suggested that the Irish EIAV isolates developed independently of the North American and Chinese viruses and that they constitute a separate monophyletic group. PMID:23175240

Quinlivan, Michelle; Cook, Frank; Kenna, Rachel; Callinan, John J; Cullinane, Ann

2013-03-01

220

Sequencing Puzzle  

NSDL National Science Digital Library

The sequencing puzzle is designed to teach high school students, and perhaps even middle school, and the general public about the basics of genome sequencing. The sequencing of the tomato genome is used as the basis for this activity. It is an interactive puzzle. In addition to the puzzle, the site also contains background information on tomatoes, DNA, and various molecular terms.

221

The role of DNA structure and dynamics in the recognition of bovine papillomavirus E2 protein target sequences.  

PubMed

The papillomavirus E2 transcription and replication factors bind to the DNA consensus ACCGN(4)CGGT sequence (E2-BS), through both direct and indirect readout mechanisms. The two symmetric half-sites ACCG.CGGT are highly conserved in the genomes and are hydrogen bound with E2. Although E2 does not contact the N4 spacer, the affinities are modulated by the base composition of this DNA part. Nevertheless, the origin of either the global recognition mechanism or the spacer effect remains unclear, particularly in the case of the bovine papillomavirus type 1 E2 (BPV-1-E2) system, used as model to study the papillomaviruses. We present, herein, studies carried out on oligomers differently recognized by the BPV-1-E2 protein and based on molecular dynamic simulations including counterions and water. The sequences contain the conserved half-sites but three different spacers (CCAT, ACGT and AAAC), resulting in very high, high and low affinity targets for BPV-1-E2. In order to estimate how much the free DNAs resemble the bound conformations, comparisons are made with two DNAs extracted from E2-BS-BPV-1 crystallographic complexes, representative of high and moderate affinity structures. The analysis of 15 ns trajectories reveals that the ACCG/CGGT half-sites, whatever the spacer, have the same behavior and adopt average stable base-pair parameters very close to those of the bound conformations. In contrast, the three different free spacers strongly differ in their BI <--> BII backbone dynamics. The low affinity AAAC spacer exhibits stable BI backbone conformations, the high affinity ACGT spacer is characterized by a dramatic instability of the CpG phosphate groups, and the CpA and GpG backbones in the very high affinity CCAT.ATGG spacer are trapped in BII conformations. All resemble more of the moderate affinity complex DNA than the high affinity one. Nevertheless, the particular behavior of the CCAT and ACGT backbones allows the emergence of BII-rich spacers, a configuration reproducing both local and global helical features of the bound DNA conformation of the high affinity complex and favoring the minor groove curvature required in the complex. In particular, the CCAT-containing site spends almost half of the time in this form that well mimics the bound one. Thus, we propose that the E2 protein could take advantage of the invariant favorable structures of the half-sites to form a pre-complex, but would require a specific spacer intrinsic malleability to lock the interaction. Finally, the backbone conformational states, by their ability to translate information coded in the sequence into structural properties, provide insight into the mechanisms that contribute to fine binding site selection and specific nucleic acid ligand recognition. PMID:15165850

Djuranovic, D; Oguey, C; Hartmann, B

2004-06-11

222

The Length and Sequence Composition of Vesicular Stomatitis Virus Intergenic Regions Affect mRNA Levels and the Site of Transcript Initiation  

Microsoft Academic Search

In this study, we used a dicistronic vesicular stomatitis virus (VSV) minigenome to investigate the effects of either single or multiple nucleotide insertions placed immediately after the nontranscribed intergenic dinu- cleotide of the M gene on VSV transcription. Both Northern blot and primer extension analysis showed that the polymerase responded to the inserted nucleotides in a sequence-specific manner such that

ELIZABETH A. STILLMAN; MICHAEL A. WHITT

1998-01-01

223

Carbon isotope composition of intermediates of the starch-malate sequence and level of the crassulacean acid metabolism in leaves of Kalanchoe blossfeldiana Tom Thumb  

Microsoft Academic Search

Isotype analyses were performed on biochemical fractions isolated from leaves of Kalanchoe blossfeldiana Tom Thumb. during aging under long days or short days. Irrespective of the age or photoperiodic conditions, the intermediates of the starch-malate sequence (starch, phosphorylated compounds and organic acids) have a level of 13C higher than that of soluble sugars, cellulose and hemicellulose. In short days, the

Eliane Deleens; Jeannine Garnier-Dardart; Orlando Queiroz

1979-01-01

224

Electrochemical DNA biosensor with chitosan-Co(3)O(4) nanorod-graphene composite for the sensitive detection of Staphylococcus aureus nuc gene sequence.  

PubMed

In this paper a novel nanocomposite material prepared by Co(3)O(4) nanorods (nano-Co(3)O(4)), graphene (GR) and chitosan (CTS) was fabricated and further modified on carbon ionic liquid electrode (CILE), which was used as the substrate electrode to construct a new electrochemical DNA biosensor. The single-stranded DNA (ssDNA) probe was immobilized on the CTS-Co(3)O(4)-GR/CILE surface by electrostatic attraction, which could hybridize with the target ssDNA sequence under the selected conditions. By using methylene blue (MB) as the electrochemical indicator, the hybridization reactions were monitored with the reduction peak current. By combining the biocompatibility of Co(3)O(4) nanorods, excellent electron transfer ability and big surface of GR, good film-forming ability of CTS and the high conductivity of CILE, the amount of ssDNA adsorbed on the electrode surface was increased and the electrochemical response of MB was accelerated. Under the optimal conditions differential pulse voltammetric responses of MB were in linear with the specific target ssDNA sequence in the concentration range from 1.0×10(-12) to 1.0×10(-6)M with the detection limit as 4.3×10(-13)M (3?). Good discrimination ability to the one-base and three-base mismatched ssDNA sequences could be achieved and the polymerase chain reaction (PCR) amplification products of Staphylococcus aureus nuc gene sequence were detected with satisfactory results. PMID:22765971

Qi, Xiaowei; Gao, Hongwei; Zhang, Yuanyuan; Wang, Xiuzhen; Chen, Ying; Sun, Wei

2012-12-01

225

A first survey of the rye (Secale cereale) genome composition through BAC end sequencing of the short arm of chromosome 1R  

PubMed Central

Background Rye (Secale cereale L.) belongs to tribe Triticeae and is an important temperate cereal. It is one of the parents of man-made species Triticale and has been used as a source of agronomically important genes for wheat improvement. The short arm of rye chromosome 1 (1RS), in particular is rich in useful genes, and as it may increase yield, protein content and resistance to biotic and abiotic stress, it has been introgressed into wheat as the 1BL.1RS translocation. A better knowledge of the rye genome could facilitate rye improvement and increase the efficiency of utilizing rye genes in wheat breeding. Results Here, we report on BAC end sequencing of 1,536 clones from two 1RS-specific BAC libraries. We obtained 2,778 (90.4%) useful sequences with a cumulative length of 2,032,538 bp and an average read length of 732 bp. These sequences represent 0.5% of 1RS arm. The GC content of the sequenced fraction of 1RS is 45.9%, and at least 84% of the 1RS arm consists of repetitive DNA. We identified transposable element junctions in BESs and developed insertion site based polymorphism markers (ISBP). Out of the 64 primer pairs tested, 17 (26.6%) were specific for 1RS. We also identified BESs carrying microsatellites suitable for development of 1RS-specific SSR markers. Conclusion This work demonstrates the utility of chromosome arm-specific BAC libraries for targeted analysis of large Triticeae genomes and provides new sequence data from the rye genome and molecular markers for the short arm of rye chromosome 1. PMID:18803819

Bartos, Jan; Paux, Etienne; Kofler, Robert; Havrankova, Miroslava; Kopecky, David; Suchankova, Pavla; Safar, Jan; Simkova, Hana; Town, Christopher D; Lelley, Tamas; Feuillet, Catherine; Dolezel, Jaroslav

2008-01-01

226

Arabidopsis family GT43 members are xylan xylosyltransferases required for the elongation of the xylan backbone.  

PubMed

Xylan is the second most abundant polysaccharide in plant biomass targeted for biofuel production. Therefore, it is imperative to understand the biochemical mechanism underlying xylan biosynthesis. Although previous genetic studies have identified several genes implicated in xylan biosynthesis, biochemical proof of any of their encoded proteins as a xylan xylosyltransferase (XylT) responsible for xylan backbone biosynthesis is still lacking. In this study, we investigated the enzymatic activities of two Arabidopsis thaliana GT43 members, IRX9 (Irregular Xylem9) and IRX14, which have been genetically shown to be non-redundantly involved in the elongation of the xylan backbone. IRX9 and IRX14, alone or simultaneously, were heterologously expressed in tobacco BY2 cells, and microsomes isolated from the transgenic BY2 cells were tested for XylT activity using xylotetraose (Xyl(4)) as an acceptor and UDP-[(14)C]xylose as a donor. It was found that although microsomes with expression of IRX9 or IRX14 alone exhibited little incorporation of radiolabeled xylose, a high level of incorporation of radiolabeled xylose onto Xyl(4) was conferred by microsomes with co-expression of IRX9 and IRX14. Further analysis using fluorescent anthranilic acid-labeled xylotetraose (Xyl(4)-AA) as an acceptor revealed that up to five ?-(1,4)-linked xylosyl residues were able to be transferred onto Xyl(4)-AA by microsomes with co-expression of IRX9 and IRX14. Furthermore, it was shown that xylooligomers ranging from Xyl(3)-AA to Xyl(6)-AA could all be used as acceptors for the xylosyl transfer by microsomes with co-expression of IRX9 and IRX14. Together, these findings provide the first biochemical evidence that IRX9 and IRX14 are xylosyltransferases that operate cooperatively in the elongation of the xylan backbone. PMID:22080591

Lee, Chanhui; Zhong, Ruiqin; Ye, Zheng-Hua

2012-01-01

227

C?-C bond cleavage of the peptide backbone in MALDI in-source decay using salicylic acid derivative matrices.  

PubMed

The use of 5-formylsalicylic acid (5-FSA) and 5-nitrosalicylic acid (5-NSA) as novel matrices for in-source decay (ISD) of peptides in matrix-assisted laser desorption/ionization (MALDI) is described. The use of 5-FSA and 5-NSA generated a- and x-series ions accompanied by oxidized peptides [M - 2 H + H](+). The preferential formation of a- and x-series ions was found to be dependent on the hydrogen-accepting ability of matrix. The hydrogen-accepting ability estimated from the ratio of signal intensity of oxidized product [M - 2 H + H](+) to that of non-oxidized protonated molecule [M + H](+) of peptide was of the order 5-NSA > 5-FSA > 5-aminosalicylic acid (5-ASA) ? 2,5-dihydroxyl benzoic acid (2,5-DHB) ? 0. The results suggest that the hydrogen transfer reaction from peptide to 5-FSA and 5-NSA occurs during the MALDI-ISD processes. The hydrogen abstraction from peptides results in the formation of oxidized peptides containing a radical site on the amide nitrogen with subsequent radical-induced cleavage at the C?-C bond, leading to the formation of a- and x-series ions. The most significant feature of MALDI-ISD with 5-FSA and 5-NSA is the specific cleavage of the C?-C bond of the peptide backbone without degradation of side-chain and post-translational modifications (PTM). The matrix provides a useful complementary method to conventional MALDI-ISD for amino acid sequencing and site localization of PTMs in peptides. PMID:21953105

Asakawa, Daiki; Takayama, Mitsuo

2011-07-01

228

Global transcriptional regulator KorC coordinates expression of three backbone modules of the broad-host-range RA3 plasmid from IncU incompatibility group.  

PubMed

The broad-host-range conjugative RA3 plasmid from IncU incompatibility group has been isolated from the fish pathogen Aeromonas hydrophila. DNA sequencing has revealed a mosaic modular structure of RA3 with the stabilization module showing some similarity to IncP-1 genes and the conjugative transfer module highly similar to that from PromA plasmids. The integrity of the mosaic plasmid genome seems to be specified by its regulatory network. In this paper the transcriptional regulator KorC was analyzed. KorCRA3 (98 amino acids) is encoded in the stabilization region and represses four strong promoters by binding to a conserved palindrome sequence, designated OC on the basis of homology to the KorC operator sequences in IncP-1 plasmids. Two of the KorCRA3-regulated promoters precede the first two cistrons in the stabilization module, one fires towards replication module, remaining one controls a tricistronic operon, whose products are involved in the conjugative transfer process. Despite the similarity between the binding sites in IncU and IncP-1 plasmids, no cross-reactivity between their KorC proteins has been detected. KorC emerges as a global regulator of RA3, coordinating all its backbone functions: replication, stable maintenance and conjugative transfer. PMID:23583562

Ludwiczak, M; Dolowy, P; Markowska, A; Szarlak, J; Kulinska, A; Jagura-Burdzy, G

2013-07-01

229

Backbone modification of retinal induces protein-like excited state dynamics in solution.  

PubMed

The drastically different reactivity of the retinal chromophore in solution compared to the protein environment is poorly understood. Here, we show that the addition of a methyl group to the C?C backbone of all-trans retinal protonated Schiff base accelerates the electronic decay in solution making it comparable to the proton pump bacteriorhodopsin. Contrary to the notion that reaction speed and efficiency are linked, we observe a concomitant 50% reduction in the isomerization yield. Our results demonstrate that minimal synthetic engineering of potential energy surfaces based on theoretical predictions can induce drastic changes in electronic dynamics toward those observed in an evolution-optimized protein pocket. PMID:22536821

Sovdat, Tina; Bassolino, Giovanni; Liebel, Matz; Schnedermann, Christoph; Fletcher, Stephen P; Kukura, Philipp

2012-05-23

230

Backbone resonance assignments of the ? sub-domain of Brevibacillus thermoruber Lon protease.  

PubMed

Lon is an ATPases associated with diverse cellular activities protease and belongs to a unique group that binds DNA. The ? sub-domain of Lon protease is responsible for DNA-binding, but the structural information for its DNA-recognition mode is still limited. Here, we report (1)H, (15)N and (13)C backbone assignment for the ? sub-domain from Brevibacillus thermoruber Lon protease as the basis for the elucidation of its structure and interactions with DNA, necessary for understanding the allosteric regulatory mechanism of the enzymatic function. PMID:23771856

Chen, Yu-Da; Wu, Shih-Hsiung; Hsu, Chun-Hua

2014-10-01

231

Backbone 1H, 15N, and 13C resonance assignments for the NOXO1? PX domain  

PubMed Central

NOXO1 (Nox Organizer 1) is a homolog of the NAPDH oxidase protein p47phox. NADPH oxidases transfer electrons from NADPH to molecular oxygen, generating the superoxide anion. NOXO1 contains an N-terminal PX (phox homology) domain and is one of several PX domain-containing proteins found in the cytosolic subunits of the NADPH oxidase complex. These PX domains bind to membrane lipids and target the protein to membranes, recruiting other cytosolic components to the membrane bound components and aiding formation of a active enzyme complex. This recruitment represents a level of regulation of these oxidases. Here we report the backbone assignments of NOXO1? PX. PMID:21188560

Davis, Nicole Y.; McPhail, Linda C.

2013-01-01

232

Synthesis and properties of carbohydrate-phosphate backbone-modified oligonucleotide analogues and nucleic acid mimetics  

NASA Astrophysics Data System (ADS)

Advances in the synthesis of oligo(deoxy)ribonucleotide analogues and nucleic acid mimetics made in the last decade are summarized. Attention is focused on new methods for the synthesis of derivatives with a modified ribose-phosphate backbone (phosphorothioate, boranophosphate, and nucleoside phosphonate derivatives) and derivatives devoid of the phosphate group. Among nucleic acid mimetics, conformationally restricted modified peptide nucleic acids, including those bearing a negative or positive charge, and morpholino oligomers are considered. Advantages and drawbacks of the main types of analogues as regards the complexity of the synthesis and the possibility of their application as antisense agents or reagents for hybridization analysis are compared.

Abramova, Tatyana V.; Silnikov, Vladimir N.

2011-05-01

233

Relative stability of major types of beta-turns as a function of amino acid composition: a study based on Ab initio energetic and natural abundance data.  

PubMed

Folding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the beta-turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence-dependent folding stability of both major types of beta-turns using simple dipeptide models (-Xxx-Yyy-). Gas-phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val-Ser, Ala-Gly, Ser-Ser) were studied. For each backbone fold most probable side-chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6-311++G(d,p)//RHF/3-21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for beta-turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly. PMID:12794897

Perczel, András; Jákli, Imre; McAllister, Michael A; Csizmadia, Imre G

2003-06-01

234

Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes  

Microsoft Academic Search

BACKGROUND: In mammals, splice-regulatory domains impose marked trends on the relative abundance of certain amino acids near exon-intron boundaries. Is this a mammalian particularity or symptomatic of exonic splicing regulation across taxa? Are such trends more common in species that a priori have a harder time identifying exon ends, that is, those with pre-mRNA rich in intronic sequence? We address

Tobias Warnecke; Joanna L Parmley; Laurence D Hurst

2008-01-01

235

Biosensors for DNA sequence detection  

NASA Technical Reports Server (NTRS)

DNA biosensors are being developed as alternatives to conventional DNA microarrays. These devices couple signal transduction directly to sequence recognition. Some of the most sensitive and functional technologies use fibre optics or electrochemical sensors in combination with DNA hybridization. In a shift from sequence recognition by hybridization, two emerging single-molecule techniques read sequence composition using zero-mode waveguides or electrical impedance in nanoscale pores.

Vercoutere, Wenonah; Akeson, Mark

2002-01-01

236

Antibacterial Studies of Cationic Polymers with Alternating, Random and Uniform Backbones  

PubMed Central

Antibacterial polymers have potential as pharmaceuticals and as coatings for implantation devices. The design of these materials will be optimized when we have a complete understanding of the structural features that impart activity toward target organisms and those that are benign with respect to the mammalian host. In this work, four series of polymers in which cationic and hydrophobic groups were distributed along the backbone were tested against six different bacterial species (both Gram positive and Gram negative) and for host cytotoxicities (red blood cell lysis). The most effective of the polymers studied are regularly spaced, featuring a 6–8 carbon stretch along the backbone between side chains that present positively charged groups. They cause potassium efflux, disorder the bacterial cytoplasmic membrane, and disrupt the membrane potential. These polymers, available from alternating ring opening metathesis polymerization (AROMP), offer proof of principle for the importance of regular spacing in antibacterial polymers and for the synthesis of additional functional materials based on regularly spaced scaffolds. PMID:21370918

Song, Airong; Walker, Stephen G.; Parker, Kathlyn A.; Sampson, Nicole S.

2011-01-01

237

Comparison of backbone dynamics of oxidized and reduced putidaredoxin by 15N NMR relaxation measurements.  

PubMed

The backbone dynamics of uniformly 15N-labeled reduced and oxidized putidaredoxin (Pdx) have been studied by 2D 15N NMR relaxation measurements. 15N T1 and T2 values and 1H-15N NOEs have been measured for the diamagnetic region of the protein. These data were analyzed by using a model-free dynamics formalism to determine the generalized order parameters (S2), the effective correlation time for internal motions (tau e), and the 15N exchange broadening contributions (Rex) for each residue, as well as the overall correlation time (tau(m)). Order parameters for the reduced Pdx are generally higher than for the oxidized Pdx, and there is increased mobility on the microsecond to millisecond time scale for the oxidized Pdx, in comparison with the reduced Pdx. These results clearly indicate that the oxidized protein exhibits higher mobility than the reduced one, which is in agreement with the recently published redox-dependent dynamics studied by amide proton exchange. In addition, we observed very high T1/T2 ratios for residues 33 and 34, giving rise to a large Rex contribution. Residue 34 is believed to be involved in the binding of Pdx to cytochrome P450cam (CYP101). The differences in the backbone dynamics are discussed in relation to the oxidation states of Pdx, and their impact on electron transfer. The entropy change occurring on oxidation of reduced Pdx has been calculated from the order parameters of the two forms. PMID:10433692

Sari, N; Holden, M J; Mayhew, M P; Vilker, V L; Coxon, B

1999-08-01

238

Supramolecular Organization of the Repetitive Backbone Unit of the Streptococcus pneumoniae Pilus  

PubMed Central

Streptococcus pneumoniae, like many other Gram-positive bacteria, assembles long filamentous pili on their surface through which they adhere to host cells. Pneumococcal pili are formed by a backbone, consisting of the repetition of the major component RrgB, and two accessory proteins (RrgA and RrgC). Here we reconstruct by transmission electron microscopy and single particle image reconstruction method the three dimensional arrangement of two neighbouring RrgB molecules, which represent the minimal repetitive structural domain of the native pilus. The crystal structure of the D2-D4 domains of RrgB was solved at 1.6 Å resolution. Rigid-body fitting of the X-ray coordinates into the electron density map enabled us to define the arrangement of the backbone subunits into the S. pneumoniae native pilus. The quantitative fitting provide evidence that the pneumococcal pilus consists uniquely of RrgB monomers assembled in a head-to-tail organization. The presence of short intra-subunit linker regions connecting neighbouring domains provides the molecular basis for the intrinsic pilus flexibility. PMID:20559564

Spraggon, Glen; Koesema, Eric; Scarselli, Maria; Malito, Enrico; Biagini, Massimiliano; Norais, Nathalie; Emolo, Carla; Barocchi, Michele Anne; Giusti, Fabiola; Hilleringmann, Markus; Rappuoli, Rino; Lesley, Scott; Covacci, Antonello; Masignani, Vega; Ferlenghi, Ilaria

2010-01-01

239

Enhancing protein backbone binding--a fruitful concept for combating drug-resistant HIV.  

PubMed

The evolution of drug resistance is one of the most fundamental problems in medicine. In HIV/AIDS, the rapid emergence of drug-resistant HIV-1 variants is a major obstacle to current treatments. HIV-1 protease inhibitors are essential components of present antiretroviral therapies. However, with these protease inhibitors, resistance occurs through viral mutations that alter inhibitor binding, resulting in a loss of efficacy. This loss of potency has raised serious questions with regard to effective long-term antiretroviral therapy for HIV/AIDS. In this context, our research has focused on designing inhibitors that form extensive hydrogen-bonding interactions with the enzyme's backbone in the active site. In doing so, we limit the protease's ability to acquire drug resistance as the geometry of the catalytic site must be conserved to maintain functionality. In this Review, we examine the underlying principles of enzyme structure that support our backbone-binding concept as an effective means to combat drug resistance and highlight their application in our recent work on antiviral HIV-1 protease inhibitors. PMID:22290878

Ghosh, Arun K; Anderson, David D; Weber, Irene T; Mitsuya, Hiroaki

2012-02-20

240

Osmolyte effects on protein stability and solubility: a balancing act between backbone and side-chains  

PubMed Central

In adaptation biology the discovery of intracellular osmolyte molecules that in some cases reach molar levels, raises questions of how they influence protein thermodynamics. We’ve addressed such questions using the premise that from atomic coordinates, the transfer free energy of a native protein (?Gtr,N) can be predicted by summing measured water-to-osmolyte transfer free energies of the protein’s solvent exposed side chain and backbone component parts. ?Gtr,D is predicted using a self avoiding random coil model for the protein, and ?Gtr,D ? ?Gtr,N, predicts the m-value, a quantity that measures the osmolyte effect on the N ? D transition. Using literature and newly measured m-values we show 1:1 correspondence between predicted and measured m-values covering a range of 12 kcal/mol/M in protein stability for 46 proteins and 9 different osmolytes. Osmolytes present a range of side chain and backbone effects on N and D solubility and protein stability key to their biological roles. PMID:21683504

Auton, Matthew; Rosgen, Jorg; Sinev, Mikhail; Holthauzen, Luis Marcelo F.; Bolen, D. Wayne

2011-01-01

241

Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement.  

PubMed

Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common use today have been designed on the assumption that each type of bond or angle has a single ideal value that is independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and, as a first step towards using such information to build more accurate models, ultra-high-resolution protein crystal structures have been used to derive a conformation-dependent library (CDL) of restraints for the protein backbone [Berkholz et al. (2009) Structure 17, 1316-1325]. Here, we report the introduction of this CDL into the phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the CDL yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In phenix, use of the CDL can be selected by simply specifying the cdl = True option. This successful implementation paves the way for further aspects of the context dependence of ideal geometry to be characterized and applied to improve experimental and predictive modeling accuracy. PMID:24890778

Moriarty, Nigel W; Tronrud, Dale E; Adams, Paul D; Karplus, P Andrew

2014-09-01

242

Aftershock Sequences  

NSDL National Science Digital Library

In this activity, learners will look at some of the characteristic properties of aftershock sequences, and relate them to variables in two equations: the modified version of Omori's Law, and the Gutenberg-Richter relation for aftershock sequences. The database provided in this link can be searched to extract the magnitude and time-after-mainshock for selected earthquakes. From this information, users can discover the real-world meanings of various properties of aftershock sequences.

243

Methylene Blue Binding to DNA with Alternating GC Base Sequence: A Modeling Study  

E-print Network

Methylene Blue Binding to DNA with Alternating GC Base Sequence: A Modeling Study Remo Rohs, HeinzVed January 18, 2000 Abstract: Photoactive methylene blue is one of the most efficient singlet oxygen-specific cleavage of the DNA backbone. Photophysical data obtained for methylene blue in complexes with DNA indicate

Rohs, Remo

244

Differential ordering of the protein backbone and side chains during protein folding revealed by site-specific recombinant infrared probes.  

PubMed

The time scale for ordering of the polypeptide backbone relative to the side chains is a critical issue in protein folding. The interplay between ordering of the backbone and ordering of the side chains is particularly important for the formation of ?-sheet structures, as the polypeptide chain searches for the native stabilizing cross-strand interactions. We have studied these issues in the N-terminal domain of protein L9 (NTL9), a model protein with mixed ?/? structure. We have developed a general approach for introducing site-specific IR probes for the side chains (azide) and backbone ((13)C?(18)O) using recombinant protein expression. Temperature-jump time-resolved IR spectroscopy combined with site-specific labeling enables independent measurement of the respective backbone and side-chain dynamics with single residue resolution. We have found that side-chain ordering in a key region of the ?-sheet structure occurs on a slower time scale than ordering of the backbone during the folding of NTL9, likely as a result of the transient formation of non-native side-chain interactions. PMID:22039909

Nagarajan, Sureshbabu; Taskent-Sezgin, Humeyra; Parul, Dzmitry; Carrico, Isaac; Raleigh, Daniel P; Dyer, R Brian

2011-12-21

245

Rational design of DNA sequence-specific zinc fingers.  

PubMed

We developed a rational scheme for designing DNA binding proteins. The scheme was applied for a zinc finger protein and the designed sequences were experimentally characterized with high DNA sequence specificity. Starting with the backbone of a known finger structure, we initially calculated amino acid sequences compatible with the expected structure and the secondary structures of the designed fingers were then experimentally confirmed. The DNA-binding function was added to the designed finger by reconsidering a section of the amino acid sequence and computationally selecting amino acids to have the lowest protein-DNA interaction energy for the target DNA sequences. Among the designed proteins, one had a gap between the lowest and second lowest protein-DNA interaction energies that was sufficient to give DNA sequence-specificity. PMID:22449981

Kono, Hidetoshi; Imanishi, Miki; Negi, Shigeru; Tatsutani, Kazuya; Sakaeda, Yui; Hashimoto, Ayaka; Nakayama, Chie; Futaki, Shiroh; Sugiura, Yukio

2012-03-23

246

1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor.  

PubMed

Nearly complete sequence-specific 1H, 13C, and 15N resonance assignments are reported for the backbone atoms of the receptor-binding domain of vascular endothelial growth factor (VEGF), a 23-kDa homodimeric protein that is a major regulator of both normal and pathological angiogenesis. The assignment strategy relied on the use of seven 3D triple-resonance experiments [HN(CO)CA, HNCA, HNCO, (HCA)CONH, HN(COCA)HA, HN(CA)HA, and CBCA-(CO)NH] and a 3D 15N-TOCSY-HSQC experiment recorded on a 0.5 mM (12 mg/mL) sample at 500 MHz, pH 7.0, 45 degrees C. Under these conditions, 15N relaxation data show that the protein has a rotational correlation time of 15.0 ns. Despite this unusually long correlation time, assignments were obtained for 94 of the 99 residues; 8 residues lack amide 1H and 15N assignments, presumably due to rapid exchange of the amide 1H with solvent under the experimental conditions used. The secondary structure of the protein was deduced from the chemical shift indices of the 1H alpha, 13C alpha, 13C beta, and 13CO nuclei, and from analysis of backbone NOEs observed in a 3D 15N-NOESY-HSQC spectrum. Two helices and a significant amount of beta-sheet structure were identified, in general agreement with the secondary structure found in a recently determined crystal structure of a similar VEGF construct [Muller YA et al., 1997, Proc Natl Acad Sci USA 94:7192-7197]. PMID:9336848

Fairbrother, W J; Champe, M A; Christinger, H W; Keyt, B A; Starovasnik, M A

1997-10-01

247

Deep sequencing on genome-wide scale reveals the unique composition and expression patterns of microRNAs in developing pollen of Oryza sativa  

Microsoft Academic Search

Background  Pollen development in flowering plants requires strict control of the gene expression program and genetic information stability\\u000a by mechanisms possibly including the miRNA pathway. However, our understanding of the miRNA pathway in pollen development\\u000a remains limited, and the dynamic profile of miRNAs in developing pollen is unknown.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Using next-generation sequencing technology, we pyrosequenced small RNA populations from rice uninucleate microspores

Li Qin Wei; Long Feng Yan; Tai Wang

2011-01-01

248

Sequence Bracelets  

NSDL National Science Digital Library

In this craft-based activity, learners make DNA sequence bracelets that carry the code of an organism such as a human, trout, chimpanzee or butterfly. This activity reinforces the principle of complementary base pairs as learners are given one strand of the sequence and they have to match up the other strand correctly.

Institute, Wellcome T.

2012-06-26

249

EMSCOPE - Electromagnetic Component of EarthScope Backbone and Transportable Array Experiments 2006-2008  

NASA Astrophysics Data System (ADS)

USArray (http://www.iris.edu/USArray) in conjunction with EMSOC (Electromagnetic Studies of the Continents) (http://emsoc.ucr.edu/emsoc) is installing magnetotelluric (MT) stations as part of Earthscope. The MT component of Earthscope consists of permanent (Backbone) and transportable long period stations to record naturally occurring, time varying electric and magnetic fields to produce a regional lithospheric/asthensospheric electrical conductivity map of the United States. The recent arrival of 28 long period MT instruments allows for the final installation of the Backbone stations throughout the US and yearly transportable array studies. The Backbone MT survey consists of 7 stations spaced throughout the continental US with preliminary installation at Soap Creek, Oregon; Parkfield, California; Braden, Missouri and Socorro, New Mexico.Siting and permitting are underway or completed at stations in eastern Montana, northern Wisconsin and Virginia. These stations will be recording for at least five years to determine electrical conductivities at depths that extend into the mantle transition zone. The first transportable array experiment was performed in the summer and fall of 2006 in central and eastern Oregon (Oregon Pilot Project) using equipment loaned from EMSOC. Thirty-one long period MT stations were recorded with 14 to 21 day occupations. Preliminary 3D inverse models indicate several lithospheric electrical conductivity anomalies including a linear zone marked by low-high conductivity transition along the Klamath-Blue Mountain Lineament associated with a linear trend of gravity minima. High electrical conductivity values occur in the upper crust under the accreted terrains in the Blue Mountains region. The second transportable array experiment was performed in the summer and fall of 2007 and completes coverage of the Oregon, Washington, and western Idaho, targeting the Cascadia subduction zone, Precambrian boundaries, and sub-basalt lithologies. The 2008 transportable MT experiment will focus on the Snake River Plain and the Yellowstone Hot Spot. The disposition of future USArray magnetotelluric geotransects will be the subject of an upcoming NSF-supported planning workshop. Time series are available now from the IRIS data center (www.iris.edu/data), and magnetotelluric transfer functions will soon be available.

Egbert, G.; Evans, R.; Ingate, S.; Livelybrooks, D.; Mickus, K.; Park, S.; Schultz, A.; Unsworth, M.; Wannamaker, P.

2007-12-01

250

Backbone dependency further improves side chain prediction efficiency in the Energy-based Conformer Library (bEBL).  

PubMed

Side chain optimization is an integral component of many protein modeling applications. In these applications, the conformational freedom of the side chains is often explored using libraries of discrete, frequently occurring conformations. Because side chain optimization can pose a computationally intensive combinatorial problem, the nature of these conformer libraries is important for ensuring efficiency and accuracy in side chain prediction. We have previously developed an innovative method to create a conformer library with enhanced performance. The Energy-based Library (EBL) was obtained by analyzing the energetic interactions between conformers and a large number of natural protein environments from crystal structures. This process guided the selection of conformers with the highest propensity to fit into spaces that should accommodate a side chain. Because the method requires a large crystallographic data-set, the EBL was created in a backbone-independent fashion. However, it is well established that side chain conformation is strongly dependent on the local backbone geometry, and that backbone-dependent libraries are more efficient in side chain optimization. Here we present the backbone-dependent EBL (bEBL), whose conformers are independently sorted for each populated region of Ramachandran space. The resulting library closely mirrors the local backbone-dependent distribution of side chain conformation. Compared to the EBL, we demonstrate that the bEBL uses fewer conformers to produce similar side chain prediction outcomes, thus further improving performance with respect to the already efficient backbone-independent version of the library. Proteins 2014; 82:3177-3187. © 2014 Wiley Periodicals, Inc. PMID:25212195

Subramaniam, Sabareesh; Senes, Alessandro

2014-11-01

251

Structural Insights into the Evolution of a Sexy Protein: Novel Topology and Restricted Backbone Flexibility in a Hypervariable Pheromone from the Red-Legged Salamander, Plethodon shermani  

PubMed Central

In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP) superfamily: a diverse class of vertebrate proteins co-opted for many biological functions – such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake “three-finger” topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF) is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s) without the immediate need for complementary mutations. Consequently, this unique adaptation may establish new paradigms for how receptor:ligand pairs co-evolve, in particular with respect to sexual conflict. PMID:24849290

Wilburn, Damien B.; Bowen, Kathleen E.; Doty, Kari A.; Arumugam, Sengodagounder; Lane, Andrew N.; Feldhoff, Pamela W.; Feldhoff, Richard C.

2014-01-01

252

Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.  

PubMed

In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP) superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF) is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s) without the immediate need for complementary mutations. Consequently, this unique adaptation may establish new paradigms for how receptor:ligand pairs co-evolve, in particular with respect to sexual conflict. PMID:24849290

Wilburn, Damien B; Bowen, Kathleen E; Doty, Kari A; Arumugam, Sengodagounder; Lane, Andrew N; Feldhoff, Pamela W; Feldhoff, Richard C

2014-01-01

253

Towards automatic protein backbone assignment using proton-detected 4D solid-state NMR data.  

PubMed

We introduce an efficient approach for sequential protein backbone assignment based on two complementary proton-detected 4D solid-state NMR experiments that correlate [Formula: see text]/Ni with CAi/COi or CAi-1/COi-1. The resulting 4D spectra exhibit excellent sensitivity and resolution and are amenable to (semi-)automatic assignment approaches. This strategy allows to obtain sequential connections with high confidence as problems related to peak overlap and multiple assignment possibilities are avoided. Non-uniform sampling schemes were implemented to allow for the acquisition of 4D spectra within a few days. Rather moderate hardware requirements enable the successful demonstration of the method on deuterated type III secretion needles using a 600 MHz spectrometer at a spinning rate of 25 kHz. PMID:25193427

Xiang, ShengQi; Chevelkov, Veniamin; Becker, Stefan; Lange, Adam

2014-11-01

254

Backbone resonance assignments of human cytosolic dNT-1 nucleotidase.  

PubMed

Cytosolic dNT-1 nucleotidase plays a key role in the homeostasis of pyrimidine deoxyribonucleotides in mammalian cells. The enzyme is responsible for the dephosphorylation of physiological substrates as well as nucleoside analogues that are used in antiviral and anticancer therapies, therefore selective inhibition of the dNT-1 nucleotidase activity may lead to an increase in efficacy of this type of therapeutic compounds. Here, we report the backbone ¹H, ¹³C and ¹?N assignments for the 47 kDa dNT-1 dimer, which will be used for structural characterisation of dNT-1 complexes with small molecule inhibitors obtained through modification of pyrimidine nucleotide scaffolds or optimisation of successful binders obtained from the screening of fragment libraries. PMID:24234349

Hnízda, Aleš; Skleni?ková, Radka; Pachl, Petr; Fábry, Milan; Tošner, Zden?k; Brynda, Ji?í; Veverka, Václav

2014-10-01

255

Transistor Properties of Novel Organic Conducting Polymers Bearing Tetrathiafulvalene Units in the Backbone  

NASA Astrophysics Data System (ADS)

The organic field-effect transistor (OFET) properties of conducting polymers bearing a tetrathiafulvalene (TTF) unit in the backbone whose termini are capped with functional groups were investigated. The OFET devices were fabricated by a solution process under various fabrication conditions. All the devices showed typical p-type semiconducting behavior as expected from the electron-donating properties of TTF derivatives. Cast films exhibited higher field-effect mobilities than spin-coated films. Surface treatment with organic silane molecules produced no noticeable effects. When using thioacetyl-capped polymer, treatment of the OFET device in an ammonia atmosphere resulted in a field-effect mobility one order of magnitude higher than that of the pristine film. By contrast, there was no such enhancement with ethyl acetate-capped polymer. Atomic force microscopy observations revealed that the ammonia treatment promoted the ordering of the polymer chain, which resulted in improved electronic conduction.

Kashimura, Yoshiaki; Goto, Touichiro; Nakashima, Hiroshi; Furukawa, Kazuaki; Wang, Erjing; Li, Hongxiang; Hu, Wenping; Torimitsu, Keiichi

2010-01-01

256

Importance of the Peptide Backbone Description in Modeling the Selectivity Filter in Potassium Channels  

PubMed Central

A dihedral energy correction (CMAP) term has been recently included in the CHARMM force field to obtain a more accurate description of the peptide backbone. Its importance in improving dynamical properties of proteins and preserving their stability in long molecular-dynamics simulations has been established for several globular proteins. Here we investigate its role in maintaining the structure and function of two potassium channels, Shaker Kv1.2 and KcsA, by performing molecular-dynamics simulations with and without the CMAP correction in otherwise identical systems. We show that without CMAP, it is not possible to maintain the experimentally observed orientations of the carbonyl groups in the selectivity filter in Shaker, and the channel loses its selectivity property. In the case of KcsA, the channel retains some selectivity even without CMAP because the carbonyl orientations are relatively better preserved compared to Shaker. PMID:19450472

Bastug, Turgut; Kuyucak, Serdar

2009-01-01

257

Side chain and backbone contributions of Phe508 to CFTR folding  

SciTech Connect

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

2010-12-07

258

Synthesis and backbone conformations of cyclic hexapeptides cyclo-(Xxx-Pro-D-Gln)2.  

PubMed

The solution syntheses of cyclo-(Xxx-Pro-D-Gln)2, where Xxx = Gly, Ala, Leu, Phe and Val are described. Several routes were examined, the most successful involving the intermediate Z-Xxx-Pro-D-Gln-O-tBu and proceeding to cyclization of H-Xxx-Pro-D-Gln-Xxx-Pro-D-Gln-OH using diphenylphosphoryl azide. The N--H regions of the proton magnetic resonance spectra of aqueous solutions of these peptides were examined, and in the Xxx = Leu and Val peptides an unsymmetrical backbone, presumably with one cis Xxx-Pro peptide bond, was found to be important. Previous reports of cyclo-(Xxx-Pro-D-Yyy)2 peptides have shown only C2-symmetric forms. PMID:6853028

Kopple, K D; Parameswaran, K N

1983-03-01

259

The Effects of NHC-Backbone Substitution on Efficiency in Ruthenium-based Olefin Metathesis  

PubMed Central

A series of ruthenium olefin metathesis catalysts bearing N-heterocyclic carbene (NHC) ligands with varying degrees of backbone and N-aryl substitution have been prepared. These complexes show greater resistance to decomposition through C–H activation of the N-aryl group, resulting in increased catalyst lifetimes. This work has utilized robotic technology to examine the activity and stability of each catalyst in metathesis, providing insights into the relationship between ligand architecture and enhanced efficiency. The development of this robotic methodology has also shown that, under optimized conditions, catalyst loadings as low as 25 ppm can lead to 100% conversion in the ring-closing metathesis of diethyl diallylmalonate. PMID:19351207

Kuhn, Kevin M.; Bourg, Jean-Baptiste; Chung, Cheol K.; Virgil, Scott C.; Grubbs, Robert H.

2009-01-01

260

Effects of NHC-backbone substitution on efficiency in ruthenium-based olefin metathesis.  

PubMed

A series of ruthenium olefin metathesis catalysts bearing N-heterocyclic carbene (NHC) ligands with varying degrees of backbone and N-aryl substitution have been prepared. These complexes show greater resistance to decomposition through C-H activation of the N-aryl group, resulting in increased catalyst lifetimes. This work has utilized robotic technology to examine the activity and stability of each catalyst in metathesis, providing insights into the relationship between ligand architecture and enhanced efficiency. The development of this robotic methodology has also shown that, under optimized conditions, catalyst loadings as low as 25 ppm can lead to 100% conversion in the ring-closing metathesis of diethyl diallylmalonate. PMID:19351207

Kuhn, Kevin M; Bourg, Jean-Baptiste; Chung, Cheol K; Virgil, Scott C; Grubbs, Robert H

2009-04-15

261

Gene families as soft cliques with backbones: Amborella contrasted with other flowering plants  

PubMed Central

Background Chaining is a major problem in constructing gene families. Results We define a new kind of cluster on graphs with strong and weak edges: soft cliques with backbones (SCWiB). This differs from other definitions in how it controls the "chaining effect", by ensuring clusters satisfy a tolerant edge density criterion that takes into account cluster size. We implement algorithms for decomposing a graph of similarities into SCWiBs. We compare examples of output from SCWiB and the Markov Cluster Algorithm (MCL), and also compare some curated Arabidopsis thaliana gene families with the results of automatic clustering. We apply our method to 44 published angiosperm genomes with annotation, and discover that Amborella trichopoda is distinct from all the others in having substantially and systematically smaller proportions of moderate- and large-size gene families. Conclusions We offer several possible evolutionary explanations for this result.

2014-01-01

262

Short sequence motifs, overrepresented in mammalian conservednon-coding sequences  

SciTech Connect

Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by patterns in mutation, suggesting thatselection which causes their conservation is not always verystrong.

Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna

2007-02-21

263

Comparison of 13C?H and 15NH backbone dynamics in protein GB1  

PubMed Central

This study presents a site-resolved experimental view of backbone C?H and NH internal motions in the 56-residue immunoglobulin-binding domain of streptococcal protein G, GB1. Using 13C?H and 15NH NMR relaxation data [T1, T2, and NOE] acquired at three resonance frequencies (1H frequencies of 500, 600, and 800 MHz), spectral density functions were calculated as F(?) = 2?J(?) to provide a model-independent way to visualize and analyze internal motional correlation time distributions for backbone groups in GB1. Line broadening in F(?) curves indicates the presence of nanosecond time scale internal motions (0.8 to 5 nsec) for all C?H and NH groups. Deconvolution of F(?) curves effectively separates overall tumbling and internal motional correlation time distributions to yield more accurate order parameters than determined by using standard model free approaches. Compared to NH groups, C?H internal motions are more broadly distributed on the nanosecond time scale, and larger C?H order parameters are related to correlated bond rotations for C?H fluctuations. Motional parameters for NH groups are more structurally correlated, with NH order parameters, for example, being larger for residues in more structured regions of ?-sheet and helix and generally smaller for residues in the loop and turns. This is most likely related to the observation that NH order parameters are correlated to hydrogen bonding. This study contributes to the general understanding of protein dynamics and exemplifies an alternative and easier way to analyze NMR relaxation data. PMID:12717014

Idiyatullin, Djaudat; Nesmelova, Irina; Daragan, Vladimir A.; Mayo, Kevin H.

2003-01-01

264

Preferential interactions between small solutes and the protein backbone: A computational analysis  

PubMed Central

To help better understand the effects of small solutes on protein stability, we carry out atomistic simulations to quantitatively characterize the interactions between two broadly used small solutes, urea and glycine betaine (GB), with a tri-glycine peptide, which is a good model for protein backbone. Multiple solute concentrations are analyzed and each solute-peptide-water ternary system is studied with ~200–300 ns of molecular dynamics simulations with the CHARMM force field. The comparison between calculated preferential interaction coefficients (?23) and experimentally measured values suggests that semi-quantitative agreement with experiments can be obtained if care is exercised to balance interactions among the solute, protein and water. On the other hand, qualitatively incorrect (i.e., wrong sign in ?23) result can be obtained if a solute model is constructed by directly taking parameters for chemically similar groups from existing force field. Such sensitivity suggests that small solute thermodynamic data can be valuable in the development of accurate force field models of biomolecules. Further decomposition of ?23 into group contributions leads to additional insights regarding the effects of small solutes on protein stability. For example, use of the CHARMM force field predicts that urea preferentially interacts with not only amide groups in the peptide backbone but also aliphatic groups, suggesting a role for these interactions in urea-induced protein denaturation; quantitatively, however, it is likely that the CHARMM force field overestimates the interaction between urea and aliphatic groups. The results on GB support a simple thermodynamic model that assumes additivity of preferential interaction between GB and various biomolecular surfaces. PMID:20121154

Ma, Liang; Pegram, Laurel; Record, M. T.; Cui, Qiang

2013-01-01

265

Dna Sequencing  

DOEpatents

A method for sequencing a strand of DNA, including the steps off: providing the strand of DNA; annealing the strand with a primer able to hybridize to the strand to give an annealed mixture; incubating the mixture with four deoxyribonucleoside triphosphates, a DNA polymerase, and at least three deoxyribonucleoside triphosphates in different amounts, under conditions in favoring primer extension to form nucleic acid fragments complementory to the DNA to be sequenced; labelling the nucleic and fragments; separating them and determining the position of the deoxyribonucleoside triphosphates by differences in the intensity of the labels, thereby to determine the DNA sequence.

Tabor, Stanley (Cambridge, MA); Richardson, Charles C. (Chestnut Hill, MA)

1995-04-25

266

The reference genetic linkage map for the multinational Brassica rapa genome sequencing project  

Microsoft Academic Search

We describe the construction of a reference genetic linkage map for the Brassica A genome, which will form the backbone for anchoring sequence contigs for the Multinational Brassica rapa Genome Sequencing Project. Seventy-eight doubled haploid lines derived from anther culture of the F1 of a cross between two diverse Chinese cabbage (B.\\u000a rapa ssp. pekinensis) inbred lines, ‘Chiifu-401-42’ (C) and

Su Ryun Choi; Graham R. Teakle; Prikshit Plaha; Jeong Hee Kim; Charlotte J. Allender; Elena Beynon; Zhong Yun Piao; Pilar Soengas; Tae Ho Han; Graham J. King; Guy C. Barker; Paul Hand; Derek J. Lydiate; Jacqueline Batley; David Edwards; Dal Hoe Koo; Jae Wook Bang; Beom-Seok Park; Yong Pyo Lim

2007-01-01

267

Proteoglycan sequence  

PubMed Central

Proteoglycans (PGs) are among the most structurally complex biomacromolecules in nature. They are present in all animal cells and frequently exert their critical biological functions through interactions with protein ligands and receptors. PGs are comprised of a core protein to which one or multiple, heterogeneous, and polydisperse glycosaminoglycan (GAG) chains are attached. Proteins, including the protein core of PGs, are now routinely sequenced either directly using proteomics or indirectly using molecular biology through their encoding DNA. The sequencing of the GAG component of PGs poses a considerably more difficult challenge because of the relatively underdeveloped state of glycomics and because the control of their biosynthesis in the endoplasmic reticulum and the Golgi is poorly understood and not believed to be template driven. Recently, the GAG chain of the simplest PG has been suggested to have a defined sequence based on its top-down Fourier transform mass spectral sequencing. This review examines the advances made over the past decade in the sequencing of GAG chains and the challenges the field face in sequencing complex PGs having critical biological functions in developmental biology and pathogenesis. PMID:22513887

Li, Lingyun; Ly, Mellisa

2012-01-01

268

Pixel-level image fusion: the case of image sequences  

Microsoft Academic Search

In pixel-level image sequence fusion, a composite image sequence has to be built of several spatially registered input image sequences. One of the primary goals in image sequence fusion is the temporal stability and consistency of the fused image sequence. To fulfill the preceding desiderata, we propose a novel approach based on a shift invariant extension of the 2D discrete

Oliver Rockinger; Thomas Fechner

1998-01-01

269

A natural fiber composite in a pelagic limestone-chert sequence. The importance of mechanical stratigraphy for fracture type development in carbonate anticlines.  

NASA Astrophysics Data System (ADS)

Thrust fault-related folds in carbonate rocks are characterized by deformation accommodated by different kinds of structures, such as joints, faults, pressure solution seams (PSSs), and deformation bands, which may form at various stages during the folding process. Defining the distribution, orientation, and the type of fold-related structures and understanding the relationships between folding and fracturing is significant both for theoretical and practical purposes. Furthermore, as the deformation related to the folding process influences fluid flow through rocks, identifying the types of structures formed during folding is as important as predicting their geometries. To unravel the relationship between mechanical stratigraphy and folding process, the well-exposed Cingoli anticline (Northern Apennines), has been studied in detail. The Upper Cretaceous-Middle Eocene stratigraphy of the Cingoli anticline is characterized by a pelagic multilayer made up of fine-grained pelagic limestones and, marly limestones, in places alternated with thin continuous chert layers. The presence of several outcrops located in different structural positions of the anticline makes the Cingoli anticline an excellent natural laboratory to investigate relationships between folding, fracturing, and mechanical stratigraphy relative to the structural setting of the fold. The field data collected show that high angle to bedding PSSs, which formed before tilting and during the first stage of folding, are not homogeneously distributed in the pelagic limestones. Generally, high angle to bedding PSSs form in the marly pelagic limestones and they have been observed in several outcrops and in different structural positions except where the marly limestones are inter-bedded with stiffer chert layers. In order to analyse theoretically what observed in the field, we compared the deformation of limestones and chert layers with the deformation acting on fiber composites. In the mechanics of materials, composites refer to a matrix reinforced with particles, fibers, or laminae. During the early stage of folding, when the compressive stress is almost bedding parallel, chert layers act as a stiff lamina embedded in a weak limestone matrix. As a result, the stress is partitioned and the chert layers bear the greatest stress. Considering the mechanical properties (Poisson and Young's modulus) of the two materials (chert and limestone), and the estimated tectonic stress acting at the onset of the folding process, the stress magnitude in the limestone beds does not reach the expected value for the onset of pressure solution. For this reason, pelagic limestones containing chert layers are mainly characterized by joints whereas PSSs form in pelagic limestones without the stiffer phase (chert). This study suggests that within the same fold, and even within the same formation, different mechanical units can be characterized by different fractures types and fluid flow behaviour as a result of mechanical stratigraphy distribution.

Petracchini, Lorenzo; Antonellini, Marco; Scrocca, Davide; Billi, Andrea

2013-04-01

270

Two-dimensional NMR spectroscopy reveals cation-triggered backbone degradation in polysulfone-based anion exchange membranes  

PubMed Central

Anion exchange membranes (AEMs) find widespread applications as an electrolyte and/or electrode binder in fuel cells, electrodialysis stacks, flow and metal-air batteries, and electrolyzers. AEMs exhibit poor stability in alkaline media; their degradation is induced by the hydroxide ion, a potent nucleophile. We have used 2D NMR techniques to investigate polymer backbone stability (as opposed to cation stability) of the AEM in alkaline media. We report the mechanism behind a peculiar, often-observed phenomenon, wherein a demonstrably stable polysulfone backbone degrades rapidly in alkaline solutions upon derivatization with alkaline stable fixed cation groups. Using COSY and heteronuclear multiple quantum correlation spectroscopy (2D NMR), we unequivocally demonstrate that the added cation group triggers degradation of the polymer backbone in alkaline via quaternary carbon hydrolysis and ether hydrolysis, leading to rapid failure. This finding challenges the existing perception that having a stable cation moiety is sufficient to yield a stable AEM and emphasizes the importance of the often ignored issue of backbone stability. PMID:23335629

Arges, Christopher G.; Ramani, Vijay

2013-01-01

271

Two-dimensional NMR spectroscopy reveals cation-triggered backbone degradation in polysulfone-based anion exchange membranes.  

PubMed

Anion exchange membranes (AEMs) find widespread applications as an electrolyte and/or electrode binder in fuel cells, electrodialysis stacks, flow and metal-air batteries, and electrolyzers. AEMs exhibit poor stability in alkaline media; their degradation is induced by the hydroxide ion, a potent nucleophile. We have used 2D NMR techniques to investigate polymer backbone stability (as opposed to cation stability) of the AEM in alkaline media. We report the mechanism behind a peculiar, often-observed phenomenon, wherein a demonstrably stable polysulfone backbone degrades rapidly in alkaline solutions upon derivatization with alkaline stable fixed cation groups. Using COSY and heteronuclear multiple quantum correlation spectroscopy (2D NMR), we unequivocally demonstrate that the added cation group triggers degradation of the polymer backbone in alkaline via quaternary carbon hydrolysis and ether hydrolysis, leading to rapid failure. This finding challenges the existing perception that having a stable cation moiety is sufficient to yield a stable AEM and emphasizes the importance of the often ignored issue of backbone stability. PMID:23335629

Arges, Christopher G; Ramani, Vijay

2013-02-12

272

Backbone Structure of the Amantadine-Blocked Trans-Membrane Domain M2 Proton Channel from Influenza A Virus  

E-print Network

Backbone Structure of the Amantadine-Blocked Trans-Membrane Domain M2 Proton Channel from Influenza proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain. INTRODUCTION Influenza is a worldwide epidemic that causes substantial morbidity and mortality. Of the three

Bertram, Richard

273

IEEE/ACM TRANSACTIONS ON NETWORKING, VOL. 18, NO. 5, OCTOBER 2010 1599 Optical Packet Buffers for Backbone Internet Routers  

E-print Network

for Backbone Internet Routers Neda Beheshti, Graduate Student Member, IEEE, Emily Burmeister, Member, IEEE McKeown, Fellow, IEEE Abstract--If optical routers are to become reality, we will need several new buffers for routers is daunting: Today's electronic routers often hold millions of packets, which is well

Ganjali, Yashar

274

Numerical modeling and Hardware-in-the-Loop simulation of undersea networks, ocean observatories and offshore communications backbones  

Microsoft Academic Search

This paper discusses the importance of taking a systems engineering approach when designing undersea networks, ocean observatories and offshore communications backbones. A design that utilizes modular components and systems, and places diligence in modeling and testing communications, power and data bandwidth requirements is essential for sustained operation and economic feasibility. An example is the modular seafloor communications network described -

Andrew M. Clark; Donna M. Kocak; Ken Martindale; Adrian Woodroffe

2009-01-01

275

On the consequences of side chain flexibility and backbone conformation on hydration and proton dissociation in perfluorosulfonic acid membranes  

E-print Network

, and also undergo proton dissociation with fewer water molecules. The calculations point to the importance dissociation in perfluorosulfonic acid membranes Stephen J. Paddison*a and James A. Elliottb Received 14th­7 explicit water molecules reveal that the perfluorocarbon backbone may adopt either an elongated geometry

Elliott, James

276

The IncP-1 plasmid backbone adapts to different host bacterial species and evolves through homologous recombination  

PubMed Central

Plasmids are important members of the bacterial mobile gene pool, and are among the most important contributors to horizontal gene transfer between bacteria. They typically harbour a wide spectrum of host beneficial traits, such as antibiotic resistance, inserted into their backbones. Although these inserted elements have drawn considerable interest, evolutionary information about the plasmid backbones, which encode plasmid related traits, is sparse. Here we analyse 25 complete backbone genomes from the broad-host-range IncP-1 plasmid family. Phylogenetic analysis reveals seven clades, in which two plasmids that we isolated from a marine biofilm represent a novel clade. We also found that homologous recombination is a prominent feature of the plasmid backbone evolution. Analysis of genomic signatures indicates that the plasmids have adapted to different host bacterial species. Globally circulating IncP-1 plasmids hence contain mosaic structures of segments derived from several parental plasmids that have evolved in, and adapted to, different, phylogenetically very distant host bacterial species. PMID:21468020

Norberg, Peter; Bergström, Maria; Jethava, Vinay; Dubhashi, Devdatt; Hermansson, Malte

2011-01-01

277

Backbone cyclic pheromone biosynthesis activating neuropeptide (PBAN) antagonists: Inhibition of melanization in the moth Spodoptera littoralis (Insecta, Lepidoptera)  

Microsoft Academic Search

Antagonistic and agonistic activities of backbone cyclic (BBC) pheromone biosynthesis activating neuropeptide (PBAN) analogues were evaluated in an attempt to identify potent melanotropic antagonists, to gain an insight into their structure–activity relationship (SAR), and to discover molecules with selective and non-selective melanotropic and pheromonotropic properties. Eight potent melanotropic BBC antagonists and seven agonists were disclosed. SAR studies revealed that the

Orna Ben-Aziz; Irina Zeltser; Kalpana Bhargava; Michael Davidovitch; Miriam Altstein

2006-01-01

278

Miniaturized proteins: the backbone cyclic proteinomimetic approach. The field of proteinomimetics utilizes peptide-based molecules to mimic  

E-print Network

Miniaturized proteins: the backbone cyclic proteinomimetic approach. Abstract: The field of proteinomimetics utilizes peptide-based molecules to mimic native protein functions. We describe a novel general method for mimicking proteins by small cyclic peptides for the purpose of drug design, and demonstrate

Kasher, Roni

279

Switching the H-bonding network of a foldamer by modulating the backbone chirality and constitutional ratio of amino acids.  

PubMed

This communication describes the folding propensity of a heterofoldamer motif featuring proline (Pro) and anthranilic acid (Ant) residues in a 1:2:1 (?:?:?) constitutional ratio. Structural investigations unequivocally suggest that the hydrogen-bonding network of this foldamer motif can be switched between 9-membered and 6-membered by modulating the backbone chirality and constitutional ratio of the amino acid residues. PMID:24057152

Ramesh, Veera V E; Vijayadas, Kuruppanthara N; Dhokale, Snehal; Gonnade, Rajesh G; Rajamohanan, Pattuparambil R; Sanjayan, Gangadhar J

2013-11-01

280

Influence of the backbone structure on the release of bioactive volatiles from maleic acid-based polymer conjugates.  

PubMed

Poly(maleic acid monoester)-based ?-mercapto ketones were synthesized and investigated as potential delivery systems for the controlled release of bioactive, volatile, ?,?-unsaturated enones (such as damascones and damascenones) by retro 1,4-addition. The bioconjugates were prepared in a one-pot synthesis using 2-mercaptoethanol as a linker. The thiol group of 2-mercaptoethanol adds to the double bond of the enone to form a ?-mercapto ketone, which was then grafted via nucleophilic ring-opening of the remaining alcohol function onto a series of alternating copolymers of maleic anhydride and 1-octadecene, ethylene, isobutylene, and methyl vinyl ether. The influence of copolymer backbones on the release of ?-damascone was investigated in buffered aqueous solution as a function of pH and time. In the presence of a cationic surfactant, the polymer conjugates were transferred from an aqueous medium to a cotton surface. The deposition and the release of ?-damascone from the cotton surface as a function of the polymer backbone structure were measured by fluorescence spectroscopy and dynamic headspace analysis, respectively. All polymer conjugates were found to deliver higher amounts of the volatile into the headspace than the reference consisting of unmodified ?-damascone. Polymers with a hydrophobic backbone were generally efficiently deposited on the cotton surface, but released ?-damascone only moderately in solution. Conjugates with a more hydrophilic backbone release the active compound more efficiently in water, but are deposited to a lower extent onto the target surface. A good balance of the hydrophobicity and hydrophilicity of the polymer backbone is the key factor to maximize the deposition of the conjugates on the target surface and to optimize the release of the bioactive volatiles. PMID:20936844

Berthier, Damien L; Paret, Nicolas; Trachsel, Alain; Herrmann, Andreas

2010-11-17

281

Dual-functional ROMP-based betaines: effect of hydrophilicity and backbone structure on nonfouling properties.  

PubMed

Foundational materials for nonfouling coatings were designed and synthesized from a series of novel dual-functional zwitterionic polymers, Poly[NRZI], which were easily obtained via ring-opening metathesis polymerization (ROMP) followed by a single step transformation of the cationic precursor, Poly[NR(+)], to the zwitterion, Poly[NRZI]. The resulting unique dual-functional structure contained the anion and the cation within the same repeat unit but on separate side chains, enabling the hydrophilicity of the system to be tuned at the repeat unit level. These dual-functional zwitterionic polymers were specifically designed to investigate the impact of structural changes, including the backbone, hydrophilicity, and charge, on the overall nonfouling properties. To evaluate the importance of backbone structure, and as a direct comparison to previously studied methacrylate-based betaines, norbornene-based carbo- and sulfobetaines (Poly[NCarboZI] and Poly[NSulfoZI]) as well as a methacrylate-based sulfobetaine (Poly[MASulfoZI]) were synthesized. These structures contain the anion-cation pairs on the same side chain. Nonfouling coatings were prepared from copolymers, composed of the zwitterionic/cationic precursor monomer and an ethoxysilane-containing monomer. The coatings were evaluated by using protein adsorption studies, which clearly indicated that the overall hydrophilicity has a major influence on the nonfouling character of the materials. The most hydrophilic coating, from the oligoethylene glycol (OEG)-containing dual-functional betaine, Poly[NOEGZI-co-NSi], showed the best resistance to nonspecific protein adsorption (?(FIB) = 0.039 ng/mm(2)). Both norbornene-based polymers systems, Poly[NSulfoZI] and Poly[NCarboZI], were more hydrophilic and thus more resistant to protein adsorption than the methacrylate-based Poly[MASulfoZI]. Comparing the protein resistance of the dual-functional zwitterionic coatings, Poly[NRZI-co-NSi], to that of their cationic counterparts, Poly[NR(+)-co-NSi], revealed the importance of screening electrostatic interactions. The adsorption of negatively charged proteins on zwitterionic coatings was significantly less, despite the fact that both coatings had similar wetting properties. These results demonstrate that the unique, tunable dual-functional zwitterionic polymers reported here can be used to make coatings that are highly efficient at resisting protein adsorption. PMID:22126398

Colak, Semra; Tew, Gregory N

2012-01-10

282

Automatic Sequence Design of Major Histocompatibility Complex Class I Binding Peptides Impairing CD8 T Cell Recognition*S  

E-print Network

Automatic Sequence Design of Major Histocompatibility Complex Class I Binding Peptides Impairing CD of peptides likely to bind the HLA-A2 major histocompatibility complex (MHC) class I allele. The only-ray structures of HLA-A0201-peptide complexes. Each template consists of the bound peptide backbone and the full

Fernández de Córdoba, Pedro

283

OLIGOMERIZATION OF A RETROVIRAL MATRIX PROTEIN IS FACILITATED BY BACKBONE FLEXIBILITY ON NS TIMESCALE  

PubMed Central

Oligomerization capacity of the retroviral matrix protein is an important feature that affects assembly of immature virions and their interaction with cellular membrane. A combination of NMR relaxation measurements and advanced analysis of molecular dynamics simulation trajectory provided an unprecedentedly detailed insight into internal mobility of matrix proteins of the Mason-Pfizer monkey virus. Strong evidences have been obtained that the oligomerization capacity of the wild type matrix protein is closely related to the enhanced dynamics of several parts of its backbone on ns timescale. Increased flexibility has been observed for two regions: the loop between ?-helices ?2 and ?3 and the C-terminal half of ?-helix ?3 which accommodate amino acid residues that form the oligomerization interface. On the other hand, matrix mutant R55F that has changed structure and does not exhibit any specific oligomerization in solution was found considerably more rigid. Our results document that conformational selection mechanism together with induced fit and favorable structural pre-organization play an important role in the control of the oligomerization process. PMID:21366213

Srb, Pavel; Vlach, Jiri; Prchal, Jan; Grocky, Marian; Ruml, Tomas; Lang, Jan; Hrabal, Richard

2011-01-01

284

Rapid chain tracing of polypeptide backbones in electron-density maps.  

PubMed

A method for the rapid tracing of polypeptide backbones has been developed. The method creates an approximate chain tracing that is useful for visual evaluation of whether a structure has been solved and for use in scoring the quality of electron-density maps. The essence of the method is to (i) sample candidate C(alpha) positions at spacings of approximately 0.6 A along ridgelines of high electron density, (ii) list all possible nonapeptides that satisfy simple geometric and density criteria using these candidate C(alpha) positions, (iii) score the nonapeptides and choose the highest scoring ones, and (iv) find the longest chains that can be made by connecting nonamers. An indexing and storage scheme that allows a single calculation of most distances and density values is used to speed up the process. The method was applied to 42 density-modified electron-density maps at resolutions from 1.5 to 3.8 A. A total of 21 428 residues in these maps were traced in 24 CPU min with an overall r.m.s.d. of 1.61 A for C(alpha) atoms compared with the known refined structures. The method appears to be suitable for rapid evaluation of electron-density map quality. PMID:20179340

Terwilliger, Thomas C

2010-03-01

285

Ionization Cross Sections and Dissociation Channels of the DNA Sugar-Phosphate Backbone by Electron Collisions  

NASA Technical Reports Server (NTRS)

It has been suggested that the genotoxic effects of ionizing radiation in living cells are not caused by the highly energetic incident radiation, but rather are induced by less energetic secondary species generated, the most abundant of which are free electrons.' The secondary electrons will further react to cause DNA damage via indirect and direct mechanisms. Detailed knowledge of these mechanisms is ultimately important for the development of global models of cellular radiation damage. We are studying one possible mechanism for the formation cf DNA strand breaks involving dissociative ionization of the DNA sugar-phosphate backbone induced by secondary electron co!lisions. We will present ionization cross sections at electron collision energies between threshold and 10 KeV using the improved binary encounter dipole (iBED) formulation' Preliminary results of the possible dissociative ionization pathways will be presented. It is speculated that radical fragments produced from the dissociative ionization can further react, providing a possible mechanism for double strand breaks and base damage.

Dateo, Christopher; Huo, Winifred M.; Fletcher, Graham D.

2004-01-01

286

Backbone exponents of the two-dimensional q-state Potts model: A Monte Carlo investigation  

NASA Astrophysics Data System (ADS)

We determine the backbone exponent Xb of several critical and tricritical q-state Potts models in two dimensions. The critical systems include the bond percolation, the Ising, the q=2-?(3), 3, and 4 state Potts, and the Baxter-Wu model, and the tricritical ones include the q=1 Potts model and the Blume-Capel model. For this purpose, we formulate several efficient Monte Carlo methods and sample the probability P2 of a pair of points connected via at least two independent paths. Finite-size-scaling analysis of P2 yields Xb as 0.3566(2), 0.2696(3), 0.2105(3), and 0.127(4) for the critical q=2-?(3), 1,2, 3, and 4 state Potts model, respectively. At tricriticality, we obtain Xb=0.0520(3) and 0.0753(6) for the q=1 and 2 Potts model, respectively. For the critical q?0 Potts model it is derived that Xb=3/4. From a scaling argument, we find that, at tricriticality, Xb reduces to the magnetic exponent, as confirmed by the numerical results.

Deng, Youjin; Blöte, Henk W.; Nienhuis, Bernard

2004-02-01

287

Dependence of Crystallite Formation and Preferential Backbone Orientations on the Side Chain Pattern in PBDTTPD Polymers.  

PubMed

Alkyl substituents appended to the ?-conjugated main chain account for the solution-processability and film-forming properties of most ?-conjugated polymers for organic electronic device applications, including field-effect transistors (FETs) and bulk-heterojunction (BHJ) solar cells. Beyond film-forming properties, recent work has emphasized the determining role that side-chain substituents play on polymer self-assembly and thin-film nanostructural order, and, in turn, on device performance. However, the factors that determine polymer crystallite orientation in thin-films, implying preferential backbone orientation relative to the device substrate, are a matter of some debate, and these structural changes remain difficult to anticipate. In this report, we show how systematic changes in the side-chain pattern of poly(benzo[1,2-b:4,5-b']dithiophene-alt-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers can (i) influence the propensity of the polymer to order in the ?-stacking direction, and (ii) direct the preferential orientation of the polymer crystallites in thin films (e.g., "face-on" vs "edge-on"). Oriented crystallites, specifically crystallites that are well-ordered in the ?-stacking direction, are believed to be a key contributor to improved thin-film device performance in both FETs and BHJ solar cells. PMID:25347287

El Labban, Abdulrahman; Warnan, Julien; Cabanetos, Clément; Ratel, Olivier; Tassone, Christopher; Toney, Michael F; Beaujuge, Pierre M

2014-11-26

288

Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR  

PubMed Central

We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with 1H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of 15N and 13C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu+ (diamagnetic) or Cu2+ (paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to 1H-1H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a Gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable. PMID:22723345

Knight, Michael J.; Pell, Andrew J.; Bertini, Ivano; Felli, Isabella C.; Gonnelli, Leonardo; Pierattelli, Roberta; Herrmann, Torsten; Emsley, Lyndon; Pintacuda, Guido

2012-01-01

289

Soluble fluorinated polyimides that contain curable acetylene units in the backbone  

SciTech Connect

Soluble polyimides that contain internal acetylene groups in the backbone were prepared by reacting 2,2-bis(3,4-dicarboxyphenyl)hexafluoropropane dianhydride with various ratio of bis(3-aminophenyl)acetylene and 4,4`-diaminodiphenyl ether. The polyimides were soluble in organic solvents such as N-methylpyrrolidone (NMP) and N,N-dimethylacetamide, and exhibited reduced viscosities in the range of 0.76-1.44 (in NMP at 30{degrees}C). The crosslinking behavior was examined by DSC. The onset of exotherm appeared at 321-345{degrees}C depending on the acetylene content. After thermal treatment at 350{degrees}C, the polyimides became insoluble in any organic solvents examined and in conc. sulfuric acid. The viscoelastic analyses showed the effect of crosslinking clearly. For example, Tg increased with thermal treatment, and was finally above 400{degrees}C. The drop of modulus at higher temperature also became very small. The TGA analyses also showed excellent thermal stability.

Takeichi, T.; Ogura, S. [Toyohashi Univ. of Technology, Aichi (Japan)

1993-12-31

290

Oligomerization of a retroviral matrix protein is facilitated by backbone flexibility on nanosecond time scale.  

PubMed

The oligomerization capacity of the retroviral matrix protein is an important feature that affects assembly of immature virions and their interaction with cellular membrane. A combination of NMR relaxation measurements and advanced analysis of molecular dynamics simulation trajectory provided an unprecedentedly detailed insight into internal mobility of matrix proteins of the Mason-Pfizer monkey virus. Strong evidence have been obtained that the oligomerization capacity of the wild-type matrix protein is closely related to the enhanced dynamics of several parts of its backbone on a nanosecond time scale. Increased flexibility has been observed for two regions: the loop between ?-helices ?2 and ?3 and the C-terminal half of ?-helix ?3 which accommodate amino acid residues that form the oligomerization interface. On the other hand, matrix mutant R55F that has changed structure and does not exhibit any specific oligomerization in solution was found considerably more rigid. Our results document that conformational selection mechanism together with induced fit and favorable structural preorganization play an important role in the control of the oligomerization process. PMID:21366213

Srb, Pavel; Vlach, Ji?í; Prchal, Jan; Grocký, Marián; Ruml, Tomáš; Lang, Jan; Hrabal, Richard

2011-03-24

291

An Enhanced Backbone-Assisted Reliable Framework for Wireless Sensor Networks  

PubMed Central

An extremely reliable source to sink communication is required for most of the contemporary WSN applications especially pertaining to military, healthcare and disaster-recovery. However, due to their intrinsic energy, bandwidth and computational constraints, Wireless Sensor Networks (WSNs) encounter several challenges in reliable source to sink communication. In this paper, we present a novel reliable topology that uses reliable hotlines between sensor gateways to boost the reliability of end-to-end transmissions. This reliable and efficient routing alternative reduces the number of average hops from source to the sink. We prove, with the help of analytical evaluation, that communication using hotlines is considerably more reliable than traditional WSN routing. We use reliability theory to analyze the cost and benefit of adding gateway nodes to a backbone-assisted WSN. However, in hotline assisted routing some scenarios where source and the sink are just a couple of hops away might bring more latency, therefore, we present a Signature Based Routing (SBR) scheme. SBR enables the gateways to make intelligent routing decisions, based upon the derived signature, hence providing lesser end-to-end delay between source to the sink communication. Finally, we evaluate our proposed hotline based topology with the help of a simulation tool and show that the proposed topology provides manifold increase in end-to-end reliability. PMID:22294890

Tufail, Ali; Khayam, Syed Ali; Raza, Muhammad Taqi; Ali, Amna; Kim, Ki-Hyung

2010-01-01

292

Sequential backbone assignment of uniformly 13C-labeled RNAs by a two-dimensional P(CC)H-TOCSY triple resonance NMR experiment.  

PubMed

A new 1H-13C-31P triple resonance experiment is described which allows unambiguous sequential backbone assignment in 13C-labeled oligonucleotides via through-bond coherence transfer from 31P via 13C to 1H. The approach employs INEPT to transfer coherence from 31P to 13C and homonuclear TOCSY to transfer the 13C coherence through the ribose ring, followed by 13C to 1H J-cross-polarisation. The efficiencies of the various possible transfer pathways are discussed. The most efficient route involves transfer of 31Pi coherence via C4'i and C4'i-1, because of the relatively large JPC4' couplings involved. Via the homonuclear and heteronuclear mixing periods, the C4'i and C4'i-1 coherences are subsequently transferred to, amongst others, H1'i and H1'i-1, respectively, leading to a 2D 1H-31P spectrum which allows a sequential assignment in the 31P-1H1' region of the spectrum, i.e. in the region where the proton resonances overlap least. The experiment is demonstrated on a 13C-labeled RNA hairpin with the sequence 5'(GGGC-CAAA-GCCU)3'. PMID:7533569

Wijmenga, S S; Heus, H A; Leeuw, H A; Hoppe, H; van der Graaf, M; Hilbers, C W

1995-01-01

293

MSLICE Sequencing  

NASA Technical Reports Server (NTRS)

MSLICE Sequencing is a graphical tool for writing sequences and integrating them into RML files, as well as for producing SCMF files for uplink. When operated in a testbed environment, it also supports uplinking these SCMF files to the testbed via Chill. This software features a free-form textural sequence editor featuring syntax coloring, automatic content assistance (including command and argument completion proposals), complete with types, value ranges, unites, and descriptions from the command dictionary that appear as they are typed. The sequence editor also has a "field mode" that allows tabbing between arguments and displays type/range/units/description for each argument as it is edited. Color-coded error and warning annotations on problematic tokens are included, as well as indications of problems that are not visible in the current scroll range. "Quick Fix" suggestions are made for resolving problems, and all the features afforded by modern source editors are also included such as copy/cut/paste, undo/redo, and a sophisticated find-and-replace system optionally using regular expressions. The software offers a full XML editor for RML files, which features syntax coloring, content assistance and problem annotations as above. There is a form-based, "detail view" that allows structured editing of command arguments and sequence parameters when preferred. The "project view" shows the user s "workspace" as a tree of "resources" (projects, folders, and files) that can subsequently be opened in editors by double-clicking. Files can be added, deleted, dragged-dropped/copied-pasted between folders or projects, and these operations are undoable and redoable. A "problems view" contains a tabular list of all problems in the current workspace. Double-clicking on any row in the table opens an editor for the appropriate sequence, scrolling to the specific line with the problem, and highlighting the problematic characters. From there, one can invoke "quick fix" as described above to resolve the issue. Once resolved, saving the file causes the problem to be removed from the problem view.

Crockett, Thomas M.; Joswig, Joseph C.; Shams, Khawaja S.; Norris, Jeffrey S.; Morris, John R.

2011-01-01

294

Insertion Sequences  

PubMed Central

Insertion sequences (ISs) constitute an important component of most bacterial genomes. Over 500 individual ISs have been described in the literature to date, and many more are being discovered in the ongoing prokaryotic and eukaryotic genome-sequencing projects. The last 10 years have also seen some striking advances in our understanding of the transposition process itself. Not least of these has been the development of various in vitro transposition systems for both prokaryotic and eukaryotic elements and, for several of these, a detailed understanding of the transposition process at the chemical level. This review presents a general overview of the organization and function of insertion sequences of eubacterial, archaebacterial, and eukaryotic origins with particular emphasis on bacterial elements and on different aspects of the transposition mechanism. It also attempts to provide a framework for classification of these elements by assigning them to various families or groups. A total of 443 members of the collection have been grouped in 17 families based on combinations of the following criteria: (i) similarities in genetic organization (arrangement of open reading frames); (ii) marked identities or similarities in the enzymes which mediate the transposition reactions, the recombinases/transposases (Tpases); (iii) similar features of their ends (terminal IRs); and (iv) fate of the nucleotide sequence of their target sites (generation of a direct target duplication of determined length). A brief description of the mechanism(s) involved in the mobility of individual ISs in each family and of the structure-function relationships of the individual Tpases is included where available. PMID:9729608

Mahillon, Jacques; Chandler, Michael

1998-01-01

295

Solution studies of staphylococcal nuclease H124L. 1. Backbone sup 1 H and sup 15 N resonances and secondary structure of the unligated enzyme as identified by three-dimensional NMR spectroscopy  

SciTech Connect

The backbone {sup 1}H and {sup 15}N resonances of unligated staphylococcal nuclease H124L (recombinant protein produced in Escherichia coli whose sequence is identical to the nuclease produced by the V8 strain of Staphylococcus aureus) have been assigned by three-dimensional (3D) {sup 1}H-{sup 15}N NOESY-HMQC NMR spectroscopy at 14.1 tesla. The protein sample used in this study was labeled uniformly with {sup 15}N to a level greater than 95% by growing the E. coli host on a medium containing (99% {sup 15}N)ammonium sulfate as the sole nitrogen source. The assignments include 82% of the backbone {sup 1}H{sup N} and {sup 1}H{sup {alpha}} resonances as well as the {sup 15}N resonances of non-proline residues. Secondary structural elements ({alpha}-helices, {beta}-sheets, reverse turns, and loops) were determined by analysis of patterns of NOE connectivities present in the 3D spectrum.

Wang, Jinfeng; Mooberry, E.S.; Walkenhorst, W.F.; Markley, J.L. (Univ. of Wisconsin, Madison (United States))

1992-01-28

296

Contribution of the Mannan Backbone of Cryptococcal Glucuronoxylomannan and a Glycolytic Enzyme of Staphylococcus aureus to Contact-Mediated Killing of Cryptococcus neoformans?  

PubMed Central

The fungal pathogen Cryptococcus neoformans is killed by the bacterium Staphylococcus aureus, and the killing is inhibited by soluble capsular polysaccharides. To investigate the mechanism of killing, cells in coculture were examined by scanning and transmission electron microscopy. S. aureus attached to the capsule of C. neoformans, and the ultrastructure of the attached C. neoformans cells was characteristic of dead cells. To identify the molecules that contributed to the fungal-bacterial interaction, we treated each with NaIO4 or protease. Treatment of C. neoformans with NaIO4 promoted adherence. It was inferred that cleavage of xylose and glucuronic acid side chains of glucuronoxylomannan (GXM) allowed S. aureus to recognize mannose residues in the backbone, which resisted periodate oxidation. On the other hand, treatment of S. aureus with protease decreased adherence, suggesting that protein contributed to attachment in S. aureus. In confirmation, side chain-cleaved polysaccharide or defined ?-(1?3)-mannan inhibited the killing at lower concentrations than native GXM did. Also, these polysaccharides reduced the adherence of the two species and induced clumping of pure S. aureus cells. ?-(1?3)-Mannooligosaccharides with a degree of polymerization (DP) of ?3 induced cluster formation of S. aureus in a dose-dependent manner. Surface plasmon resonance analyses showed interaction of GXM and surface protein from S. aureus; the interaction was inhibited by oligosaccharides with a DP of ?3. Conformations of ?-(1?3) oligosaccharides were predicted. The three-dimensional structures of mannooligosaccharides larger than triose appeared curved and could be imagined to be recognized by a hypothetical staphylococcal lectin. Native polyacrylamide gel electrophoresis of staphylococcal protein followed by electroblotting, enzyme-linked immunolectin assay, protein staining, and N-terminal amino acid sequencing suggested that the candidate protein was triosephosphate isomerase (TPI). The enzymatic activities were confirmed by using whole cells of S. aureus. TPI point mutants of S. aureus decreased the ability to interact with C. neoformans. Thus, TPI on S. aureus adheres to the capsule of C. neoformans by recognizing the structure of mannotriose units in the backbone of GXM; we suggest that this contact is required for killing of C. neoformans. PMID:17483230

Ikeda, Reiko; Saito, Fumito; Matsuo, Miki; Kurokawa, Kenji; Sekimizu, Kazuhisa; Yamaguchi, Masashi; Kawamoto, Susumu

2007-01-01

297

The Construction of Metal-Organic Framework with Active Backbones by the Utilization of Reticular Chemistry  

NASA Astrophysics Data System (ADS)

With the principles of reticular chemistry, metal-organic frameworks with ultra-high porosity, chiral-recognition unit as a chiral stationary phase, metalloporhyrins for enhanced hydrogen adsorption and an intrinsic conductivity to form porous conductors, have been prepared. This dissertation presents how the principles of reticular chemistry were utilized to achieve in the preparations of metal-organic frameworks with a large surface area and active backbones. Through the simple isoreticular (having the same framework topology) expansion from MOF-177 composed with 1,3,5-tris(4'-carboxyphenyl-)benzene (BTB3-) as the strut; MOF-200 was prepared with 4,4',4"-(benzene-1,3,5-triyl-tris(benzene-4,1-diy1))tribenzoic acid an extension from BTB3- by a phenylene unit to yield one of the most porous MOFs with a Langmuir surface area of 10,400 m2. and the lowest density of 0.22 cm3.g-1. A successful thermal polymerization reaction at 325 °C inside of the pores of highly porous MOF, MOF-177, was performed and verified the integrity of the MOF structure even after the thermal reaction. 1,4-Diphenylbutadiyne that is known to polymerize upon heating to form a conjugated backbone was impregnated via solution-diffusion into MOF-177 and then subsequently polymerized by heat to form polymer impregnated MOF-177. Characterization was carried out using powder X-ray diffraction and volumetric sorption analyzer. MOF-1020 with a linear quaterphenyl dicarboxylate-based strut was designed to contain a chiral bisbinaphthyl crown-ether moiety for alkyl ammonium resolution was precisely placed into a Zn4O(CO2)6-based cubic MOF structure. Unfortunately, the chiral resolution was not achieved due to the sensitivity and the pore environment of MOF-1020. However, an interesting phenomenon was observed, where the loss of crystallinity occurs upon solvent removal while the crystallites remain shiny and crystalline, but it readily is restored upon re-solvation of the crystallites. This rare phenomenon was studied by powder X-ray diffraction and supported by gas adsorption and thermogravimetric analysis. Layered MOFs with metalloporphyrins with Zn, Cu, Co and Fe at their +2 oxidation states as struts were prepared to facilitate non-structural metal sites and tested for hydrogen adsorption and the binding enthalpies. Steep uptakes are indeed observed, but rather due to the optimal interlayer distance of 9 A for dihydrogen, and the binding enthalpies are 6.7 -- 7.6 kJ . mo1-1 which are not ·extraordinary. Although the metals did not seem to play a large role, a trend was observed where the binding enthalpies increase as the metals in the metalloporphyrins go from late to early transition metals. With the concept of conductive metal oxides, a journey of constructing conductive MOFs was taken by attempting the formation of metal-carbon bonds by linking transition metal ions with conjugated organic struts which are 1,4-benzenediisonitrile, 1,4-benzenediethynylide and p-cyanophenylethynylide. Among the attempted systems, a reaction of Cr(III) and 1,4-benzenediethynylide yielded an amorphous material with a BET (Brunauer-Emmett-Teller) surface area of 80 m2.g-1, hydrogen uptake of 47 cm 3. g-1 and a resistance of 20 MO. Also a crystalline compound was prepared by mimicking Prussian blue by using p-cyanophenylethynylide where one end can bind metal with ethynylic carbon and the other end with the cyano nitrogen by following the similar synthesis of Prussian blue analogues. The principles of reticular chemistry are demonstrated through each chapter and show how powerful and beneficial reticular chemistry is by allowing the predetermination of the structure and function. The details of the ways to approach an ideal compound and the synthetic aspects are also described in this dissertation.

Choi, Eunwoo

298

Composition of the summer photosynthetic pico and nanoplankton communities in the Beaufort Sea assessed by T-RFLP and sequences of the 18S rRNA gene from flow cytometry sorted samples.  

PubMed

The composition of photosynthetic pico and nanoeukaryotes was investigated in the North East Pacific and the Arctic Ocean with special emphasis on the Beaufort Sea during the MALINA cruise in summer 2009. Photosynthetic populations were sorted using flow cytometry based on their size and pigment fluorescence. Diversity of the sorted photosynthetic eukaryotes was determined using terminal-restriction fragment length polymorphism analysis and cloning/sequencing of the 18S ribosomal RNA gene. Picoplankton was dominated by Mamiellophyceae, a class of small green algae previously included in the prasinophytes: in the North East Pacific, the contribution of an Arctic Micromonas ecotype increased steadily northward becoming the only taxon occurring at most stations throughout the Beaufort Sea. In contrast, nanoplankton was more diverse: North Pacific stations were dominated by Pseudo-nitzschia sp. whereas those in the Beaufort Sea were dominated by two distinct Chaetoceros species as well as by Chrysophyceae, Pelagophyceae and Chrysochromulina spp.. This study confirms the importance of Arctic Micromonas within picoplankton throughout the Beaufort Sea and demonstrates that the photosynthetic picoeukaryote community in the Arctic is much less diverse than at lower latitudes. Moreover, in contrast to what occurs in warmer waters, most of the key pico- and nanoplankton species found in the Beaufort Sea could be successfully established in culture. PMID:22278671

Balzano, Sergio; Marie, Dominique; Gourvil, Priscillia; Vaulot, Daniel

2012-08-01

299

Phosphine-catalyzed alpha-P-addition on activated alkynes: A new route to P-C-P backbones.  

PubMed

n-Tributylphosphine was found to efficiently catalyze the alpha-P addition of H-phosphonates, H-phosphinates, and H-phosphine oxide pronucleophiles on alkynes bearing phosphane oxide activating moieties. The reaction leads to 2-aryl-1-vinyl-1,1-diphosphane dioxide derivatives in good yields affording a new route to P-C-P backbones. The products of this reaction are easily converted to biologically important 1,1-bis-phosphonates analogues. PMID:16956207

Lecerclé, Delphine; Sawicki, Marcin; Taran, Frédéric

2006-09-14

300

Soluble semi-conductive chelate polymers containing Cr(III) in the backbone: Synthesis, characterization, optical, electrochemical, and electrical properties  

Microsoft Academic Search

Soluble kinds of coordination polymers containing Cr(III) ion in the backbone were synthesized. Structures of the polymers were characterized by FT-IR, UV–vis, 1H and 13C NMR, and size exclusion chromatography (SEC). Thermal degradation data were obtained by TG–DTA and DSC techniques. Cyclic voltammetry (CV) measurements were carried out and the HOMO–LUMO energy levels and electrochemical band gaps (Eg?) were calculated.

Mehmet Y?ld?r?m; ?smet Kaya

2009-01-01

301

Direct formation of the C5'-radical in the sugar-phosphate backbone of DNA by high-energy radiation.  

PubMed

Neutral sugar radicals formed in DNA sugar-phosphate backbone are well-established as precursors of biologically important damage such as DNA strand scission and cross-linking. In this work, we present electron spin resonance (ESR) evidence showing that the sugar radical at C5' (C5'(•)) is one of the most abundant (ca. 30%) sugar radicals formed by ?- and Ar ion-beam irradiated hydrated DNA samples. Taking dimethyl phosphate as a model of sugar-phosphate backbone, ESR and theoretical (DFT) studies of ?-irradiated dimethyl phosphate were carried out. CH(3)OP(O(2)(-))OCH(2)(•) is formed via deprotonation from the methyl group of directly ionized dimethyl phosphate at 77 K. The formation of CH(3)OP(O(2)(-))OCH(2)(•) is independent of dimethyl phosphate concentration (neat or in aqueous solution) or pH. ESR spectra of C5'(•) found in DNA and of CH(3)OP(O(2)(-))OCH(2)(•) do not show an observable ?-phosphorus hyperfine coupling (HFC). Furthermore, C5'(•) found in DNA does not show a significant C4'-H ?-proton HFC. Applying the DFT/B3LYP/6-31G(d) method, a study of conformational dependence of the phosphorus HFC in CH(3)OP(O(2)(-))OCH(2)(•) shows that in its minimum energy conformation, CH(3)OP(O(2)(-))OCH(2)(•), has a negligible ?-phosphorus HFC. On the basis of these results, the formation of radiation-induced C5'(•) is proposed to occur via a very rapid deprotonation from the directly ionized sugar-phosphate backbone, and the rate of this deprotonation must be faster than that of energetically downhill transfer of the unpaired spin (hole) from ionized sugar-phosphate backbone to the DNA bases. Moreover, C5'(•) in irradiated DNA is found to be in a conformation that does not exhibit ?-proton or ?-phosphorus HFCs. PMID:22553971

Adhikary, Amitava; Becker, David; Palmer, Brian J; Heizer, Alicia N; Sevilla, Michael D

2012-05-24

302

Direct Formation of the C5?-Radical in the Sugar-Phosphate Backbone of DNA by High Energy Radiation  

PubMed Central

Neutral sugar radicals formed in DNA sugar-phosphate backbone are well-established as precursors of biologically important damage such as DNA-strand scission and crosslinking. In this work, we present electron spin resonance (ESR) evidence showing that the sugar radical at C5? (C5?•) is one of the most abundant (ca. 30%) sugar radicals formed by ?- and Ar ion-beam irradiated hydrated DNA samples. Taking dimethyl phosphate as a model of sugar-phosphate backbone, ESR and theoretical (DFT) studies of ?-irradiated dimethyl phosphate were carried out. CH3OP(O2?)OCH2• is formed via deprotonation from the methyl group of directly ionized dimethyl phosphate at 77 K. Formation of CH3OP(O2?)OCH2• is independent of dimethyl phosphate concentration (neat or in aqueous solution) or pH. ESR spectra of C5?• found in DNA and of CH3OP(O2?)OCH2• do not show an observable ?-phosphorous hyperfine coupling (HFC). Further, C5?• found in DNA does not show a significant C4?-H ?–proton HFC. Applying the DFT/B3LYP/6-31G(d) method, a study of conformational dependence of the phosphorous HFC in CH3OP(O2?)OCH2• shows that in its minimum energy conformation, CH3OP(O2?)OCH2• has a negligible ?-phosphorous HFC. Based on these results, formation of radiation-induced C5?• is proposed to occur via a very rapid deprotonation from the directly ionized sugar-phosphate backbone and rate of this deprotonation must be faster than that of energetically downhill transfer of the unpaired spin (hole) from ionized sugar-phosphate backbone to the DNA bases. Moreover, C5?• in irradiated DNA is found to be in a conformation that does not exhibit ? proton or ? phosphorous HFCs. PMID:22553971

Adhikary, Amitava; Becker, David; Palmer, Brian J.; Heizer, Alicia N.; Sevilla, Michael D.

2012-01-01

303

Deuterium spin probes of backbone order in proteins: 2H NMR relaxation study of deuterated carbon alpha sites.  

PubMed

(2)H spin relaxation NMR experiments to study the dynamics of deuterated backbone alpha-positions, D(alpha), are developed. To date, solution-state (2)H relaxation measurements in proteins have been confined to side-chain deuterons-primarily (13)CH(2)D or (13)CHD(2) methyl groups. It is shown that quantification of (2)H relaxation rates at D(alpha) backbone positions and the derivation of associated order parameters of C(alpha)-D(alpha) bond vector motions in small [U-(15)N,(13)C,(2)H]-labeled proteins is feasible with reasonable accuracy. The utility of the developed methodology is demonstrated on a pair of proteins-ubiquitin (8.5 kDa) at 10, 27, and 40 degrees C, and a variant of GB1 (6.5 kDa) at 22 degrees C. In both proteins, the D(alpha)-derived parameters of the global rotational diffusion tensor are in good agreement with those obtained from (15)N relaxation rates. Semiquantitative solution-state NMR measurements yield an average value of the quadrupolar coupling constant, QCC, for D(alpha) sites in proteins equal to 174 kHz. Using a uniform value of QCC for all D(alpha) sites, we show that C(alpha)-D(alpha) bond vectors are motionally distinct from the backbone amide N-H bond vectors, with (2)H-derived squared order parameters of C(alpha)-D(alpha) bond vector motions, S(2)(CalphaDalpha), on average slightly higher than their N-H amides counterparts, S(2)(NH). For ubiquitin, the (2)H-derived backbone mobility compares well with that found in a 1-mus molecular dynamics simulation. PMID:19821582

Sheppard, Devon; Li, Da-Wei; Brüschweiler, Rafael; Tugarinov, Vitali

2009-11-01

304

Photoinduced bending behavior of cross-linked azobenzene liquid-crystalline polymer films with a poly(oxyethylene) backbone.  

PubMed

Cross-linked azobenzene liquid-crystalline polymer films with a poly(oxyethylene) backbone are synthesized by photoinitiated cationic copolymerization. Azobenzene moieties in the film surface toward the light source are simultaneously photoaligned during photopolymerization with unpolarized 436 nm light and thus form a splayed alignment in the whole film. The prepared films show reversible photoinduced bending behavior with opposite bending directions when different surfaces of one film face to ultraviolet light irradiation. PMID:24771514

Lv, Jiu-an; Wang, Weiru; Xu, Jixiang; Ikeda, Tomiki; Yu, Yanlei

2014-07-01

305

Effect of a modified isoindole backbone on the electrical optical and physical properties of the isoindole organis semiconductor system  

Microsoft Academic Search

Primarily it was endeavoured to synthesise conducting polymers bearing a modified isoindole backbone with potentially enhanced electrical, optical and physical properties. The addition of electron donating methoxy groups on to the N-methylisoindole system results in alternations to the resultant polymer’s optical and physical properties. The synthesis of the new compounds 5-methoxy-N-methylisoindole and 5, 6-dimethoxy-N-methylisoindole was carried out via a devised

Matthew Boylan

2001-01-01

306

Fluoride anion binding by cyclic boronic esters: influence of backbone chelate on receptor integrity.  

PubMed

A systematic investigation of fluoride anion binding properties as a function of chelate backbone has been carried out for ferrocene functionalised boronic esters of the types FcB(OR)2 and fc[B(OR)2]2 [Fc = ferrocenyl = (eta5-C5H5)Fe(eta5-C5H4); fc = ferrocendiyl = Fe(eta5-C5H4)2]. Cyclic boronic esters containing a saturated five- or six-membered chelate ring are readily synthesized from ferrocene, and selectively bind fluoride via Lewis acid/base chemistry in chloroform solution. The resulting complexes are characterized by relatively weak fluoride binding (e.g.K = 35.8 +/- 9.8 M(-1) for FcBO2C2H2Ph2-S,S), and by cathodic shifts in the ferrocene oxidation potential that form the basis for electrochemical or colorimetric fluoride detection. The fluoride selectivity of these systems is attributed to relatively weak Lewis acidity, resulting in weak F- binding, and essentially no binding of potentially competitive anions. By contrast, more elaborate Lewis acid frameworks based on calix[4]arene (calixH4), such as (FcB)2calix or fcB2calix, do not survive intact exposure to standard fluoride sources (e.g. [nBu4N]F.xH2O solutions in chloroform or acetonitrile). Instead B-O bond cleavage occurs yielding the parent calixarene; the differences between alkoxo- and aryloxo-functionalised derivatives can be rationalised, at least in part, by consideration of the differences in electron donating capabilities of RO- (R = alkyl, aryl). PMID:16865177

Bresner, Christopher; Day, Joanna K; Coombs, Natalie D; Fallis, Ian A; Aldridge, Simon; Coles, Simon J; Hursthouse, Michael B

2006-08-14

307

Catalytic mechanism of RNA backbone cleavage by ribonuclease H from quantum mechanics/molecular mechanics simulations.  

PubMed

We use quantum mechanics/molecular mechanics simulations to study the cleavage of the ribonucleic acid (RNA) backbone catalyzed by ribonuclease H. This protein is a prototypical member of a large family of enzymes that use two-metal catalysis to process nucleic acids. By combining Hamiltonian replica exchange with a finite-temperature string method, we calculate the free energy surface underlying the RNA-cleavage reaction and characterize its mechanism. We find that the reaction proceeds in two steps. In a first step, catalyzed primarily by magnesium ion A and its ligands, a water molecule attacks the scissile phosphate. Consistent with thiol-substitution experiments, a water proton is transferred to the downstream phosphate group. The transient phosphorane formed as a result of this nucleophilic attack decays by breaking the bond between the phosphate and the ribose oxygen. In the resulting intermediate, the dissociated but unprotonated leaving group forms an alkoxide coordinated to magnesium ion B. In a second step, the reaction is completed by protonation of the leaving group, with a neutral Asp132 as a likely proton donor. The overall reaction barrier of ?15 kcal mol(-1), encountered in the first step, together with the cost of protonating Asp132, is consistent with the slow measured rate of ?1-100/min. The two-step mechanism is also consistent with the bell-shaped pH dependence of the reaction rate. The nonmonotonic relative motion of the magnesium ions along the reaction pathway agrees with X-ray crystal structures. Proton-transfer reactions and changes in the metal ion coordination emerge as central factors in the RNA-cleavage reaction. PMID:21539371

Rosta, Edina; Nowotny, Marcin; Yang, Wei; Hummer, Gerhard

2011-06-15

308

The multiscale backbone of the human phenotype network based on biological pathways  

PubMed Central

Background Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes. Results The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. We extract the multi-scale information backbone of the PHPN based on the local densities of the network and discarding weak connection. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present examples of expected clinical connections identified by PHPN as proof of principle. Conclusions We unveil a previously uncharacterized connection between phenotype modules and discuss potential mechanistic connections that are obvious only in retrospect. The PHPN shows tremendous potential to become a useful tool both in the unveiling of the diseases’ common biology, and in the elaboration of diagnosis and treatments. PMID:24460644

2014-01-01

309

Extensive backbone dynamics in the GCAA RNA tetraloop analyzed using 13C NMR spin relaxation and specific isotope labeling  

PubMed Central

Conformational dynamics play a key role in the properties and functions of proteins and nucleic acids. Heteronuclear NMR spin relaxation is a uniquely powerful site-specific probe of dynamics in proteins and has found increasing applications to nucleotide base side chains and anomeric sites in RNA. Applications to the nucleic acid ribose backbone, however, have been hampered by strong magnetic coupling among ring carbons in uniformly 13C-labeled samples. In this work, we apply a recently-developed, metabolically-directed isotope labeling scheme that places 13C with high efficiency and specificity at the nucleotide ribose C2’ and C4’ sites. We take advantage of this scheme to explore backbone dynamics in the well-studied GCAA RNA tetraloop. Using a combination of CPMG (Carr-Purcell-Meiboom-Gill) and R1? relaxation dispersion spectroscopy to explore exchange processes on the microsecond to millisecond timescale, we find an extensive pattern of dynamic transitions connecting a set of relatively well-defined conformations. In many cases, the observed transitions appear to be linked to C3’-endo/C2’-endo sugar pucker transitions of the corresponding nucleotides, and may also be correlated across multiple nucleotides within the tetraloop. These results demonstrate the power of NMR spin relaxation based on alternate-site isotope labeling to open a new window into the dynamic properties of ribose backbone groups in RNA. PMID:19049467

Johnson, James E.; Hoogstraten, Charles G.

2009-01-01

310

A maximum entropy approach to the study of residue-specific backbone angle distributions in ?-synuclein, an intrinsically disordered protein.  

PubMed

?-Synuclein is an intrinsically disordered protein of 140 residues that switches to an ?-helical conformation upon binding phospholipid membranes. We characterize its residue-specific backbone structure in free solution with a novel maximum entropy procedure that integrates an extensive set of NMR data. These data include intraresidue and sequential H(N) ? H(?) and H(N) ? H(N) NOEs, values for (3) JHNH?, (1) JH?C?, (2) JC?N, and (1) JC?N, as well as chemical shifts of (15)N, (13)C(?), and (13)C' nuclei, which are sensitive to backbone torsion angles. Distributions of these torsion angles were identified that yield best agreement to the experimental data, while using an entropy term to minimize the deviation from statistical distributions seen in a large protein coil library. Results indicate that although at the individual residue level considerable deviations from the coil library distribution are seen, on average the fitted distributions agree fairly well with this library, yielding a moderate population (20-30%) of the PPII region and a somewhat higher population of the potentially aggregation-prone ? region (20-40%) than seen in the database. A generally lower population of the ?R region (10-20%) is found. Analysis of (1)H ? (1)H NOE data required consideration of the considerable backbone diffusion anisotropy of a disordered protein. PMID:24976112

Mantsyzov, Alexey B; Maltsev, Alexander S; Ying, Jinfa; Shen, Yang; Hummer, Gerhard; Bax, Ad

2014-09-01

311

Altered Backbone and Side-Chain Interactions Result in Route Heterogeneity during the Folding of Interleukin-1? (IL-1?)  

PubMed Central

Deletion of the ?-bulge trigger-loop results in both a switch in the preferred folding route, from the functional loop packing folding route to barrel closure, as well as conversion of the agonist activity of IL-1? into antagonist activity. Conversely, circular permutations of IL-1? conserve the functional folding route as well as the agonist activity. These two extremes in the folding-functional interplay beg the question of whether mutations in IL-1? would result in changes in the populations of heterogeneous folding routes and the signaling activity. A series of topologically equivalent water-mediated ?-strand bridging interactions within the pseudosymmetric ?-trefoil fold of IL-1? highlight the backbone water interactions that stabilize the secondary and tertiary structure of the protein. Additionally, conserved aromatic residues lining the central cavity appear to be essential for both stability and folding. Here, we probe these protein backbone-water molecule and side chain-side chain interactions and the role they play in the folding mechanism of this geometrically stressed molecule. We used folding simulations with structure-based models, as well as a series of folding kinetic experiments to examine the effects of the F42W core mutation on the folding landscape of IL-1?. This mutation alters water-mediated backbone interactions essential for maintaining the trefoil fold. Our results clearly indicate that this perturbation in the primary structure alters a structural water interaction and consequently modulates the population of folding routes accessed during folding and signaling activity. PMID:23972849

Capraro, Dominique T.; Lammert, Heiko; Heidary, David K.; Roy, Melinda; Gross, Larry A.; Onuchic, Jose N.; Jennings, Patricia A.

2013-01-01

312

Short-distance probes for protein backbone structure based on energy transfer between bimane and transition metal ions  

PubMed Central

The structure and dynamics of proteins underlies the workings of virtually every biological process. Existing biophysical methods are inadequate to measure protein structure at atomic resolution, on a rapid time scale, with limited amounts of protein, and in the context of a cell or membrane. FRET can measure distances between two probes, but depends on the orientation of the probes and typically works only over long distances comparable with the size of many proteins. Also, common probes used for FRET can be large and have long, flexible attachment linkers that position dyes far from the protein backbone. Here, we improve and extend a fluorescence method called transition metal ion FRET that uses energy transfer to transition metal ions as a reporter of short-range distances in proteins with little orientation dependence. This method uses a very small cysteine-reactive dye monobromobimane, with virtually no linker, and various transition metal ions bound close to the peptide backbone as the acceptor. We show that, unlike larger fluorophores and longer linkers, this donor–acceptor pair accurately reports short-range distances and changes in backbone distances. We further extend the method by using cysteine-reactive metal chelators, which allow the technique to be used in protein regions of unknown secondary structure or when native metal ion binding sites are present. This improved method overcomes several of the key limitations of classical FRET for intramolecular distance measurements. PMID:19805285

Taraska, Justin W.; Puljung, Michael C.; Zagotta, William N.

2009-01-01

313

Electron-impact total ionization cross sections of DNA sugar-phosphate backbone and an additivity principle  

NASA Technical Reports Server (NTRS)

The improved binary-encounter dipole (iBED) model [W.M. Huo, Phys. Rev. A64, 042719-1 (2001)l is used to study the total ionization cross sections of the DNA sugar-phosphate backbone by electron impact. Calculations using neutral fragments found that the total ionization cross sections of C3' - and C5', -deoxyribose-phospate, two conformers of the sugar-phosphate backbone, are close to each other. Furthermore, the sum of the ionization cross sections of the separate deoxyribose and phosphate fragments is in close agreement with the C3' - and C5" -deoxyribose-phospate cross sections, differing by less than 10%. The result implies that certain properties of the-DNA, like the total singly ionization cross section, are localized properties and a building-up or additivity principle may apply. This allows us to obtain accurate properties of larger molecular systems built up from the results of smaller subsystem fragments. Calculations are underway using a negatively charged sugar-phosphate backbone with a metal counter-ion.

Huo, Winifred M.; Dateo, Christopher E.

2005-01-01

314

The Role of Backbone Hydrogen Bonds in the Transition State for Protein Folding of a PDZ Domain  

PubMed Central

Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a ?-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding. PMID:24748272

Pedersen, S?ren W.; Hultqvist, Greta; Str?mgaard, Kristian; Jemth, Per

2014-01-01

315

Direct measurement of the correlated dynamics of the protein-backbone and proximal waters of hydration in mechanically strained elastin  

E-print Network

We report on the direct measurement of the correlation times of the protein backbone carbons and proximal waters of hydration in mechanically strained elastin by nuclear magnetic resonance methods. The experimental data indicate a decrease in the correlation times of the carbonyl carbons as the strain on the biopolymer is increased. These observations are in good agreement with short 4ns molecular dynamics simulations of (VPGVG)3, a well studied mimetic peptide of elastin. The experimental results also indicate a reduction in the correlation time of proximal waters of hydration with increasing strain applied to the elastomer. A simple model is suggested that correlates the increase in the motion of proximal waters of hydration to the increase in frequency of libration of the protein backbone that develops with increasing strain. Together, the reduction in the protein entropy accompanied with the increase in entropy of the proximal waters of hydration with increasing strain, support the notion that the source of elasticity is driven by an entropic mechanism arising from the change in entropy of the protein backbone.

Cheng Sun; Odingo Mitchell; Jiaxin Huang; Gregory S. Boutis

2011-04-05

316

Controlled actuation of Nafion-based Ionic Polymer-metal Composites (IPMCs) with Ethylene Glycol as Solvent  

E-print Network

Controlled actuation of Nafion-based Ionic Polymer-metal Composites (IPMCs) with Ethylene Glycol for Advanced Materials 9500 Gilman Drive La Jolla, CA 92093-0416 Abstract Ionic polymer-metal composites (IPMCs of counterions that balance the electrical charge of anions covalently fixed to the backbone membrane. IPMCs

Nemat-Nasser, Sia

317

Polyproline II structure in a sequence of seven alanine residues.  

PubMed

A sequence of seven alanine residues-too short to form an alpha-helix and whose side chains do not interact with each other-is a particularly simple model for testing the common description of denatured proteins as structureless random coils. The (3)J(HN alpha) coupling constants of individual alanine residues have been measured from 2 to 56 degrees C by using isotopically labeled samples. The results display a thermal transition between different backbone conformations, which is confirmed by CD spectra. The NMR results suggest that polyproline II is the dominant conformation at 2 degrees C and the content of beta strand is increased by approximately 10% at 55 degrees C relative to that at 2 degrees C. The polyproline II conformation is consistent with recent studies of short alanine peptides, including structure prediction by ab initio quantum mechanics and solution structures for both a blocked alanine dipeptide and an alanine tripeptide. CD and other optical spectroscopies have found structure in longer "random coil" peptides and have implicated polyproline II, which is a major backbone conformation in residues within loop regions of protein structures. Our result suggests that the backbone conformational entropy in alanine peptides is considerably smaller than estimated by the random coil model. New thermodynamic data confirm this suggestion: the entropy loss on alanine helix formation is only 2.2 entropy units per residue. PMID:12091708

Shi, Zhengshuang; Olson, C Anders; Rose, George D; Baldwin, Robert L; Kallenbach, Neville R

2002-07-01

318

Polyproline II structure in a sequence of seven alanine residues  

NASA Astrophysics Data System (ADS)

A sequence of seven alanine residuestoo short to form an -helix and whose side chains do not interact with each otheris a particularly simple model for testing the common description of denatured proteins as structureless random coils. The 3JHN coupling constants of individual alanine residues have been measured from 2 to 56°C by using isotopically labeled samples. The results display a thermal transition between different backbone conformations, which is confirmed by CD spectra. The NMR results suggest that polyproline II is the dominant conformation at 2°C and the content of strand is increased by approximately 10% at 55°C relative to that at 2°C. The polyproline II conformation is consistent with recent studies of short alanine peptides, including structure prediction by ab initio quantum mechanics and solution structures for both a blocked alanine dipeptide and an alanine tripeptide. CD and other optical spectroscopies have found structure in longer "random coil" peptides and have implicated polyproline II, which is a major backbone conformation in residues within loop regions of protein structures. Our result suggests that the backbone conformational entropy in alanine peptides is considerably smaller than estimated by the random coil model. New thermodynamic data confirm this suggestion: the entropy loss on alanine helix formation is only 2.2 entropy units per residue.

Shi, Zhengshuang; Olson, C. Anders; Rose, George D.; Baldwin, Robert L.; Kallenbach, Neville R.

2002-07-01

319

Bioinformatic sequence identification from sequence family databases  

Microsoft Academic Search

We have developed a tool in order to identify sequences in relation to a sequence family database. This tool combines several algorithms: BLAST, multiple sequence alignment and phylogenetic tree building. After identification of the most similar gene family to the query sequence, this query sequence is added to the whole family alignment and the phylogenetic tree of the family is

Anne-Muriel Arigon; Guy Perrière; Manolo Gouy

320

Holoprosencephaly sequence.  

PubMed

Holoprosencephaly (HPE) sequence is a rare spectrum of cerebral and facial malformations resulting from incomplete division of the embryonic forebrain into distinct lateral cerebral hemisphere. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. A subtype of HPE called middle inter-hemispheric variant (MIHF) has been also reported. The etiology is heterogeneous: teratogens, chromosomal abnormalities and single gene mutations can be involved. Holoprosencephaly results in early morbidity and mortality with a reduced survival beyond neonatal period. The disorder is estimated to occur in 1/16,000 live births. This case report presents a male new born diagnosed with holoprosencephaly, accompanied by median cleft palate, absent nasal bones and chromosomal abnormalities. PMID:21655669

Colet?, Elena; Siminel, Mirela; Gheonea, Mihaela

2011-01-01

321

Alkynyl phosphonate DNA: a versatile "click"able backbone for DNA-based biological applications.  

PubMed

Major hurdles associated with DNA-based biological applications include, among others, targeted cell delivery, undesirable nonspecific effects, toxicity associated with various analogues or the reagents used to deliver oligonucleotides to cells, and stability toward intracellular enzymes. Although a plethora of diverse analogues have been investigated, a versatile methodology that can systematically address these challenges has not been developed. In this contribution, we present a new, Clickable, and versatile chemistry that can be used to rapidly introduce diverse functionality for studying these various problems. As a demonstration of the approach, we synthesized the core analogue, which is useful for introducing additional functionality, the triazolylphosphonate, and present preliminary data on its biological properties. We have developed a new phosphoramidite synthon--the alkynyl phosphinoamidite, which is compatible with conventional solid-phase oligonucleotide synthesis. Postsynthesis, the alkynylphosphonate can be functionalized via "Click" chemistry to generate the 1,2,3-triazolyl or substituted 1,2,3-triazolyl phosphonate-2'-deoxyribonucleotide internucleotide linkage. This manuscript describes the automated, solid-phase synthesis of mixed backbone oligodeoxyribonucleotides (ODNs) having 1,2,3-triazolylphosphonate (TP) as well as phosphate or thiophosphate internucleotide linkages and also 2'-OMe ribonucleotides and locked nucleic acids (LNAs) at selected sites. Nuclease stability assays demonstrate that the TP linkage is highly resistant toward 5'- and 3'-exonucleases, whereas melting studies indicate a slight destabilization when a TP-modified ODN is hybridized to its complementary RNA. A fluorescently labeled 16-mer ODN modified with two TP linkages shows efficient cellular uptake during passive transfection. Of particular interest, the subcellular distribution of TP-modified ODNs is highly dependent on cell type; a significant nuclear uptake is observed in HeLa cells, whereas diffuse cytoplasmic fluorescence is found in the WM-239A cell line. Cytoplasmic distribution is also present in human neuroblastoma cells (SK-N-F1), but Jurkat cells show both diffuse and punctate cytoplasmic uptake. Our results demonstrate that triazolylphosphonate ODNs are versatile additions to the oligonucleotide chemist's toolbox relative to designing new biological research reagents. PMID:22612466

Krishna, Heera; Caruthers, Marvin H

2012-07-18

322

Development of novel bifunctional chelating agents containing rigid cyclic hydrocarbon backbones  

SciTech Connect

We are developing a new class of ligands in which the metal-binding polyaminocarboxylate groups are incorporated onto rigid cyclic hydrocarbon backbones. These ligands, with increased preorganization, should produce radiometal-bioconjugates with higher in-vivo stability. The synthesis of the first in this series of ligands (2,3-diaminobicyclo[2.2.2] octanetetraacetic acid, BODTA) began with a Diels-Alder reaction of 1,3-diacetylimidazolin-2-one and 1,3-cyclohexadiene. Base hydrolysis, alkylation with ethyl iodoacetate, hydrolysis of the esters, and catalytic hydrogenation gave BODTA. For conjugation to MAbs, an average of one COOH group of unsaturated BODTA was converted into an NHS ester using 0.8 equivalent of DCC. The second ligand under development is the decadentate tethered bis-cyclohexyl-EDTA (bis-CDTA) in which 2 cyclohexyl rings are tied together with an ethylene tether. Acylation of monotrityl-1,2-diaminocyclohexane with the di-NHS ester of oxalic acid, reduction of the amide moieties, and removal of the trityl groups followed by cyanomethylation has afforded a hexanitrile whose hydrolysis will produce tethered bis-CDTA. An anti-CEA F(ab{prime}){sub 2} MAb was conjugated with an average of 0.6 BODTA per MAb molecule, labeled with Co-57, and purified by size-exclusion HPLC. Stability of this radioconjugate in mouse serum at 48 h was somewhat better (2% loss) than that of the conventional DTPA-dianhydride (DTPA-DA) conjugate (8% loss). In human tumor-xenografted nude mice (LS-174T cells), tumor (T), blood (B), liver (L), and kidney (K) uptakes (% ID/g) at 24h were: TODTA, 21.6, 4.4, 4.8, 6.0; DTPA-DA, 13.6, 2.5, 5.0, 2.9. The tumor to normal tissue ratios at 48 h for BODTA and DTPA-DA respectively were: T/B, 18.0, 13.9; T/L 4.9, 2.3; T/K, 5.4, 3.9. These preliminary results show promise for using the basic BODTA structure to produce improved bioconjugates with small radiometal ions.

Sweet, M.P.; Joshi, V.; Mease, R.C. [Brookhaven National Laboratory, Upton, NY (United States)] [and others

1995-05-01

323

New Helical Foldamers: Heterogeneous Backbones with 1:2 and 2:1 [alpha]:[superscript beta]-Amino Acid Residue Patterns  

SciTech Connect

Foldamers, oligomers with strong folding propensities, are subjects of growing interest because such compounds offer unique scaffolds for the development of molecular function. We report two new foldamer classes, oligopeptides with regular 1:2 or 2:1 patterns of {alpha}- and {beta}-amino acid residues. Two distinct helical conformations are detected via 2D NMR in methanol for each backbone. One of the helices for each backbone is characterized via X-ray crystallography.

Schmitt, Margaret A.; Choi, SooHyuk; Guzei, Ilia A.; Gellman, Samuel H. (UW)

2008-10-03

324

Prediction of Mutational Tolerance in HIV-1 Protease and Reverse Transcriptase Using Flexible Backbone Protein Design  

PubMed Central

Predicting which mutations proteins tolerate while maintaining their structure and function has important applications for modeling fundamental properties of proteins and their evolution; it also drives progress in protein design. Here we develop a computational model to predict the tolerated sequence space of HIV-1 protease reachable by single mutations. We assess the model by comparison to the observed variability in more than 50,000 HIV-1 protease sequences, one of the most comprehensive datasets on tolerated sequence space. We then extend the model to a second protein, reverse transcriptase. The model integrates multiple structural and functional constraints acting on a protein and uses ensembles of protein conformations. We find the model correctly captures a considerable fraction of protease and reverse-transcriptase mutational tolerance and shows comparable accuracy using either experimentally determined or computationally generated structural ensembles. Predictions of tolerated sequence space afforded by the model provide insights into stability-function tradeoffs in the emergence of resistance mutations and into strengths and limitations of the computational model. PMID:22927804

Varela, Rocco; O Conchuir, Shane; Kortemme, Tanja

2012-01-01

325

Molecular basis for nanoscopic membrane curvature generation from quantum mechanical models and synthetic transporter sequences  

PubMed Central

We investigate the physical origin of peptide-induced membrane curvature by contrasting differences between H-bonding interactions of prototypical cationic amino acids, arginine (Arg) and lysine (Lys), with phosphate groups of phospholipid heads using quantum mechanical (QM) calculations of a minimum model, and test the results via synthetic oxaorbornene-based transporter sequences without the geometric constraints of polypeptide backbones. QM calculations suggest that although individual Lys can in principle coordinate two phosphates, they are not able to do so at small inter-Lys distances without drastic energetic penalties. In contrast, Arg can coordinate two phosphates down to less than 5 Å, where guanidinium groups can stack ‘face to face’. In agreement with these observations, poly-Lys cannot generate the nanoscale positive curvature necessary for inducing negative Gaussian membrane curvature, in contrast to poly-Arg. Also consistent with QM calculations, polyguanidine-oxanorbornene homopolymers (PGONs) showed that curvature generation is exquisitely sensitive to the guanidinium group spacing when the phosphate groups are near close packing. Addition of phenyl or butyl hydrophobic groups into guanidine-oxanorbornene polymers increased the amount of induced saddle-splay membrane curvature, and broadened the range of lipid compositions where saddle-splay curvature was induced. The enhancement of saddle-splay curvature generation and relaxation of lipid composition requirements via addition of hydrophobicity is consistent with activity profiles. While PGON polymers displayed selective antimicrobial activity against prototypical (Gram positive and negative) bacteria, polymers with phenyl and butyl groups were also active against red blood cells. Our results suggest that it is possible to achieve deterministic molecular design of pore forming peptides. PMID:23061419

Schmidt, Nathan W.; Lis, Michael; Zhao, Kun; Lai, Ghee Hwee; Alexandrova, Anastassia; Tew, Gregory N.; Wong, Gerard C. L.

2013-01-01

326

Complete DNA sequence of yeast chromosome XI  

Microsoft Academic Search

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome XI has been determined. In addition to a compact arrangement of potential protein coding sequences, the 666,448-base-pair sequence has revealed general chromosome patterns; in particular, alternating regional variations in average base composition correlate with variations in local gene density along the chromosome. Significant discrepancies with the previously published genetic map

B. Dujon; D. Alexandraki; B. André; W. Ansorge; V. Baladron; J. P. G. Ballesta; A. Banrevi; P. A. Bolle; M. Bolotin-Fukuhara; P. Bossier; G. Bou; J. Boyer; M. J. Buitrago; G. Cherét; L. Colleaux; B. Dalgnan-Fornier; F. Del Rey; C. Dion; H. Domdey; A. Düsterhöft; S. Düsterhus; K.-D. Entian; H. Erfle; P. F. Esteban; H. Feldmann; L. Fernandes; G. M. Fobo; C. Fritz; H. Fukuhara; C. Gabel; L. Gaillon; J. M. Carcia-Cantalejo; J. J. Garcia-Ramirez; M. E. Gent; M. Ghazvini; A. Goffeau; A. Gonzaléz; D. Grothues; P. Guerreiro; J. Hegemann; N. Hewitt; F. Hilger; C. P. Hollenberg; O. Horaitis; K. J. Indge; A. Jacquier; C. M. James; J. C. Jauniaux; A. Jimenez; H. Keuchel; L. Kirchrath; K. Kleine; P. Kötter; P. Legrain; S. Liebl; E. J. Louis; A. Maia E Silva; C. Marck; A.-L. Monnier; D. Möstl; S. Müller; B. Obermaier; S. G. Oliver; C. Pallier; S. Pascolo; F. Pfeiffer; P. Philippsen; R. J. Planta; F. M. Pohl; T. M. Pohl; R. Pöhlmann; D. Portetelle; B. Purnelle; V. Puzos; M. Ramezani Rad; S. W. Rasmussen; M. Remacha; J. L. Revuelta; G.-F. Richard; M. Rieger; C. Rodrigues-Pousada; M. Rose; T. Rupp; M. A. Santos; C. Schwager; C. Sensen; J. Skala; H. Soares; F. Sor; J. Stegemann; H. Tettelin; A. Thierry; M. Tzermia; L. A. Urrestarazu; L. van Dyck; J. C. van Vliet-Reedijk; M. Valens; M. Vandenbo; C. Vilela; S. Vissers; D. von Wettstein; H. Voss; S. Wiemann; G. Xu; J. Zimmermann; M. Haasemann; I. Becker; H. W. Mewes

1994-01-01

327

Notched Strength of Composite Materials  

Microsoft Academic Search

A macroscopic model for predicting the strength of a composite laminate containing a circular notch is introduced. A property, which quantifies the reduction in strength of a given composite material or laminate due to a circular notch, is proposed. The superposition of notched strength data for several important composite material systems and laminate stacking sequences is achieved through development of

R. Byron Pipes; Robert C. Wetherhold; John W. Gillespie

1979-01-01

328

Complete Genome Sequence and Comparative Genomics of Shigella flexneri Serotype 2a Strain 2457T  

Microsoft Academic Search

We determined the complete genome sequence of Shigella flexneri serotype 2a strain 2457T (4,599,354 bp). Shigella species cause >1 million deaths per year from dysentery and diarrhea and have a lifestyle that is markedly different from those of closely related bacteria, including Escherichia coli. The genome exhibits the backbone and island mosaic structure of E. coli pathogens, albeit with much

J. Wei; M. B. Goldberg; V. Burland; M. M. Venkatesan; W. Deng; G. Fournier; G. F. Mayhew; G. Plunkett; D. J. Rose; A. Darling; B. Mau; N. T. Perna; S. M. Payne; L. J. Runyen-Janecky; S. Zhou; D. C. Schwartz; F. R. Blattner

2003-01-01

329

Fold versus Sequence Effects on the Driving Force for Protein Mediated Electron Transfer  

PubMed Central

Electron transport chains composed of electron transfer reactions mainly between proteins provide fast, efficient flow of energy in a variety of metabolic pathways. Reduction potentials are essential characteristics of the proteins because they determine the driving forces for the electron transfers. Since both polar and charged groups from the backbone and side chains define the electrostatic environment, both the fold and the sequence will contribute. However, while the role of a specific sequence may be determined by experimental mutagenesis studies of reduction potentials, understanding the role of the fold by experiment is much more difficult. Here, continuum electrostatics and density functional theory calculations are used to analyze reduction potentials in [4Fe-4S] proteins. A key feature is that multiple homologous proteins in three different folds are compared: six high potential iron-sulfur proteins, four bacterial ferredoxins, and four nitrogenase iron proteins. Calculated absolute reduction potentials are shown to be in quantitative agreement with electrochemical reduction potentials. Calculations further demonstrate that the contribution of the backbone is larger than that of the side chains and is consistent for homologous proteins but differs for non-homologous proteins, indicating that the fold is the major protein factor determining the reduction potential while the specific amino acid sequence tunes the reduction potential for a given fold. Moreover, the fold contribution is determined mainly by the proximity of the redox site to the protein surface and the orientation of the dipoles of backbone near the redox site. PMID:20635418

Perrin, Bradley Scott; Ichiye, Toshiko

2010-01-01

330

SCORM Sequencing Testing for Sequencing Control Mode  

Microsoft Academic Search

In SCORM 2004 defines the sequencing information that describes how SCORM-conformant content may be sequenced to the learner through a set of learner or system-initiated navigation events. It provides users the ability to prescribe the intend learning sequencing strategy by themselves, but quit many completed definitions and lacking the testing mechanism for these authored sequencing information results in usual developers

Hsuan-pu Chang; Kuen Han Jan; Timothy K. Shih; Chun-chia Wang

2006-01-01

331

Backbone Dynamics of the 18.5 kDa Isoform of Myelin Basic Protein Reveals Transient ?-Helices and a Calmodulin-Binding Site  

PubMed Central

The 18.5 kDa isoform of myelin basic protein (MBP) is the predominant form in adult human central nervous system myelin. It is an intrinsically disordered protein that functions both in membrane adhesion, and as a linker connecting the oligodendrocyte membrane to the underlying cytoskeleton; its specific interactions with calmodulin and SH3-domain containing proteins suggest further multifunctionality in signaling. Here, we have used multidimensional heteronuclear nuclear magnetic resonance spectroscopy to study the conformational dependence on environment of the protein in aqueous solution (100 mM KCl) and in a membrane-mimetic solvent (30% TFE-d2), particularly to analyze its secondary structure using chemical shift indexing, and to investigate its backbone dynamics using 15N spin relaxation measurements. Collectively, the data revealed three major segments of the protein with a propensity toward ?-helicity that was stabilized by membrane-mimetic conditions: T33-D46, V83-T92, and T142-L154 (murine 18.5 kDa sequence numbering). All of these regions corresponded with bioinformatics predictions of ordered secondary structure. The V83-T92 region comprises a primary immunodominant epitope that had previously been shown by site-directed spin labeling and electron paramagnetic resonance spectroscopy to be ?-helical in membrane-reconstituted systems. The T142-L154 segment overlapped with a predicted calmodulin-binding site. Chemical shift perturbation experiments using labeled MBP and unlabeled calmodulin demonstrated a dramatic conformational change in MBP upon association of the two proteins, and were consistent with the C-terminal segment of MBP being the primary binding site for calmodulin. PMID:18326633

Libich, David S.; Harauz, George

2008-01-01

332

Incorporation of Heterocycles into the Backbone of Peptoids to Generate Diverse Peptoid-Inspired One Bead One Compound Libraries  

PubMed Central

Combinatorial libraries of peptoids (oligo-N-substituted glycines) have proven to be useful sources of protein ligands. Each unit of the peptoid oligomer is derived from 2-haloacetic acid and a primary amine. In order to increase the chemical diversity available in peptoid libraries, we demonstrate here that heterocyclic halomethyl carboxylic acids can be employed as backbone building blocks in the synthesis of peptoid-based oligomers. Optimized conditions are reported that allow the creation of large, high quality combinatorial libraries containing these units. PMID:22320121

Aditya, Animesh; Kodadek, Thomas

2012-01-01

333

Incorporation of heterocycles into the backbone of peptoids to generate diverse peptoid-inspired one bead one compound libraries.  

PubMed

Combinatorial libraries of peptoids (oligo-N-substituted glycines) have proven to be useful sources of protein ligands. Each unit of the peptoid oligomer is derived from 2-haloacetic acid and a primary amine. To increase the chemical diversity available in peptoid libraries, we demonstrate here that heterocyclic halomethyl carboxylic acids can be employed as backbone building blocks in the synthesis of peptoid-based oligomers. Optimized conditions are reported that allow the creation of large, high quality combinatorial libraries containing these units. PMID:22320121

Aditya, Animesh; Kodadek, Thomas

2012-03-12

334

CURVES+ web server for analyzing and visualizing the helical, backbone and groove parameters of nucleic acid structures  

PubMed Central

Curves+, a revised version of the Curves software for analyzing the conformation of nucleic acid structures, is now available as a web server. This version, which can be freely accessed at http://gbio-pbil.ibcp.fr/cgi/Curves_plus/, allows the user to upload a nucleic acid structure file, choose the nucleotides to be analyzed and after optionally setting a number of input variables, view the numerical and graphic results online or download files containing a set of helical, backbone and groove parameters that fully describe the structure. PDB format files are also provided for offline visualization of the helical axis and groove geometry. PMID:21558323

Blanchet, Christophe; Pasi, Marco; Zakrzewska, Krystyna; Lavery, Richard

2011-01-01

335

Modeling of electrochemomechanical response of ionic polymer-metal composites with various solvents  

E-print Network

Ionic polymer-metal composites IPMCs consist of a perfluorinated ionomer membrane usually Nafion to the backbone ionomer. IPMCs are electroactive materials with potential applications as soft actuators profound effects on the nature of the IPMCs' actuation. For example, we have discovered experimentally

Nemat-Nasser, Sia

336

Effect of solvents on the chemical and physical properties of ionic polymer-metal composites  

E-print Network

online 25 May 2006 Ionic polymer-metal composites IPMCs consist of a perfluorinated ionomer membrane to the backbone ionomer. IPMCs are electroactive materials with potential applications as actuators and sensors additional problems. These and related factors limit the application of IPMCs with water as the solvent. We

Nemat-Nasser, Sia

337

Inferring phylogenies of evolving sequences without multiple sequence alignment  

PubMed Central

Alignment-free methods, in which shared properties of sub-sequences (e.g. identity or match length) are extracted and used to compute a distance matrix, have recently been explored for phylogenetic inference. However, the scalability and robustness of these methods to key evolutionary processes remain to be investigated. Here, using simulated sequence sets of various sizes in both nucleotides and amino acids, we systematically assess the accuracy of phylogenetic inference using an alignment-free approach, based on D2 statistics, under different evolutionary scenarios. We find that compared to a multiple sequence alignment approach, D2 methods are more robust against among-site rate heterogeneity, compositional biases, genetic rearrangements and insertions/deletions, but are more sensitive to recent sequence divergence and sequence truncation. Across diverse empirical datasets, the alignment-free methods perform well for sequences sharing low divergence, at greater computation speed. Our findings provide strong evidence for the scalability and the potential use of alignment-free methods in large-scale phylogenomics. PMID:25266120

Chan, Cheong Xin; Bernard, Guillaume; Poirion, Olivier; Hogan, James M.; Ragan, Mark A.

2014-01-01

338

Solution structure and backbone dynamics of the DNA-binding domain of mouse Sox-5  

PubMed Central

The fold of the murine Sox-5 (mSox-5) HMG box in free solution has been determined by multidimensional NMR using 15N-labeled protein and has been found to adopt the characteristic twisted L-shape made up of two wings: the major wing comprising helix 1 (F10–F25) and helix 2 (N32–A43), the minor wing comprising helix 3 (P51–Y67) in weak antiparallel association with the N-terminal extended segment. 15N relaxation measurements show considerable mobility (reduced order parameter, S2) in the minor wing that increases toward the amino and carboxy termini of the chain. The mobility of residues C-terminal to Q62 is significantly greater than the equivalent residues of non-sequence-specific boxes, and these residues show a weaker association with the extended N-terminal segment than in non-sequence boxes. Comparison with previously determined structures of HMG boxes both in free solution and complexed with DNA shows close similarity in the packing of the hydrophobic cores and the relative disposition of the three helices. Only in hSRY/DNA does the arrangement of aromatic sidechains differ significantly from that of mSox-5, and only in rHMG1 box 1 bound to cisplatinated DNA does helix 1 have no kink. Helix 3 in mSox-5 is terminated by P68, a conserved residue in DNA sequence-specific HMG boxes, which results in the chain turning through ?90°. PMID:11266597

Cary, Peter D.; Read, Christopher M.; Davis, Ben; Driscoll, Paul C.; Crane-Robinson, Colyn

2001-01-01

339

Synthesis of graft polyrotaxane by simultaneous capping of backbone and grafting from rings of pseudo-polyrotaxane  

PubMed Central

Summary Graft polyrotaxanes, with poly(?-caprolactone) (PCL) graft chains on the ring components were synthesized by the simultaneous ring-opening polymerization of ?-caprolactone from both ends of the backbone polymer, an end-functionalized polyethylene glycol (PEG) and the formation of inclusion complexes with ?-cyclodextrin (?-CD). PEG with multiple functional groups at each end was prepared by the condensation of PEG-amine and D-gluconic acid; the PEG derivative formed an inclusion complex with ?-CD. The polymerization of multiple hydroxy groups at the backbone ends resulted in a star-shaped end group, which served as a bulky capping group to prevent dethreading. In contrast, PEG with only one hydroxy group at each end did not produce polyrotaxanes, indicating that single PCL chains were too thin to confine ?-CDs to the complex. In addition, the grafting polymerization proceeded properly only when robust hydrogen bonds formed between ?-CDs were dissociated using a basic catalyst. Since the dissociation also induced dethreading, kinetic control of the polymerization and dissociation were crucial for producing graft polyrotaxanes. Consequently, this three-step reaction yielded graft polyrotaxanes in a good yield, demonstrating a significant simplification of the synthesis of graft polyrotaxanes. PMID:25383129

Inoue, Katsunari; Kudo, Masabumi

2014-01-01

340

Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid  

PubMed Central

While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (?GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an ‘accessory’ during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. PMID:25200075

Babbitt, Gregory A.; Alawad, Mohammed A.; Schulze, Katharina V.; Hudson, André O.

2014-01-01

341

Metal coordination architectures of triazole-based ligands: Effect of the backbone of bridging ligands on the construction of polymers  

NASA Astrophysics Data System (ADS)

In our efforts to investigate the influence of the backbone of different triazole-based bridging ligands on the structure of their metal complexes, four new coordination polymers, {[Cu(L1)2(H2O)2]Cl2}n (1), [Cu(L2)2Cl2]n (2), [Co(L2)2(SCN)2]n (3), and [Cu(L3)2(NO3)2]n (4), (L1 = 1,2-bis(triazol-1-ylmethyl)benzene, L2 = 1,3-bis(triazol-1-ylmethyl)benzene, L3 = 1,4-bis(triazol-1-ylmethyl)benzene), have been synthesized. All the complexes have been structurally characterized by IR, elemental analysis and single-crystal X-ray diffraction. Structural analyses show that 1 and 4 possess 2D coordination networks with (4,4) topology, and 1 shows a diagonal-diagonal inclined interpenetration. 2 and 3 are isostructural and feature 1D double chain, which further connected by C-H···Cl or ?···? weak interactions to form 2D supramolecular frameworks. The results show that the structures of ligands (with different non-coordination backbone spacers) play important roles in the formation of such coordination architectures. Furthermore, EPR (Electron Paramagnetic Resonance) spectra of CuII complexes (1, 2, and 4) have been investigated in the solid state at room temperature.

Du, Jian-Long; Hu, Tong-Liang; Bu, Xian-He

2012-04-01

342

Localization of electrons in the sugar/phosphate backbone in DNA investigated via resonant Auger decay spectra  

SciTech Connect

In order to elucidate the localized nature of electrons in sugar/phosphate backbone in DNA molecules, resonant Auger decay spectra excited by soft x-rays around the inner-shell ionization thresholds have been measured for single-strand DNA. The systems investigated are thin films of DNA as well as related phosphorus compounds such as nucleotide (adenosine triphosphate, ATP), sodium phosphate, and indium phosphide. For ATP and DNA, it was observed that the resonant excitations from P 1s to valence unoccupied {pi}* orbitals are followed by spectator-type Auger decays where the excited electrons remain in valence orbitals during the core-hole decays. It was also found that the energy of the P KL{sub 2,3}L{sub 2,3} (2p{sup -1}{center_dot}{pi}*) spectator Auger peak shifts linearly with the photon energy due to the resonant Auger Raman scattering. Most of the decay channel at the core-to-valence resonant excitation is spectator-type Auger decay in DNA, which is quite different from the Auger decay processes in metallic and semiconducting materials. We conclude that the excited electrons in valence unoccupied states around the phosphates in DNA molecules are strongly localized, resulting in the insulating properties in a one-dimensional direction along sugar/phosphate backbone.

Baba, Yuji; Sekiguchi, Tetsuhiro; Shimoyama, Iwao; Hirao, Norie [Japan Atomic Energy Agency, Tokai-mura, Naka-gun, Ibaraki-ken, 319-1195 (Japan); Nath, Krishna G. [INRS-EMT, University of Quebec, 1650 Boul. Lionel Boulet, Varennes, QC, J3X 1S2 (Canada)

2006-11-15

343

Resolution of deep nodes yields an improved backbone phylogeny and a new basal lineage to study early evolution of Asteraceae.  

PubMed

A backbone phylogeny that fully resolves all subfamily and deeper nodes of Asteraceae was constructed using 14 chloroplast DNA loci. The recently named genus Famatinanthus was found to be sister to the Mutisioideae-Asteroideae clade that represents more than 99% of Asteraceae and was found to have the two chloroplast inversions present in all Asteraceae except the nine genera of Barnadesioideae. A monotypic subfamily Famatinanthoideae and tribe Famatinantheae are named herein as new. Relationships among the basal lineages of the family were resolved with strong support in the Bayesian analysis as (Barnadesioideae (Famatinanthoideae (Mutisioideae (Stifftioideae (Wunderlichioideae-Asteroideae))))). Ancestral state reconstruction of ten morphological characters at the root node of the Asteraceae showed that the ancestral sunflower would have had a woody habit, alternate leaves, solitary capitulescences, epaleate receptacles, smooth styles, smooth to microechinate pollen surface sculpturing, white to yellow corollas, and insect-mediated pollination. Herbaceous habit, echinate pollen surface, pubescent styles, and cymose capitulescences were reconstructed for backbone nodes of the phylogeny corresponding to clades that evolved shortly after Asteraceae dispersed out of South America. No support was found for discoid capitula, multiseriate involucres or bird pollination as the ancestral character condition for any node. Using this more resolved phylogenetic tree, the recently described Raiguenrayun cura+Mutisiapollis telleriae fossil should be associated to a more derived node than previously suggested when time calibrating phylogenies of Asteraceae. PMID:25083940

Panero, Jose L; Freire, Susana E; Ariza Espinar, Luis; Crozier, Bonnie S; Barboza, Gloria E; Cantero, Juan J

2014-11-01

344

Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells.  

PubMed

PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology. PMID:24577484

Yu, Yuan; Tong, Qi; Li, Zhongxia; Tian, Jinhai; Wang, Yizhi; Su, Feng; Wang, Yongsheng; Liu, Jun; Zhang, Yong

2014-01-01

345

Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells  

NASA Astrophysics Data System (ADS)

PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.

Yu, Yuan; Tong, Qi; Li, Zhongxia; Tian, Jinhai; Wang, Yizhi; Su, Feng; Wang, Yongsheng; Liu, Jun; Zhang, Yong

2014-02-01

346

Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid.  

PubMed

While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (?GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. PMID:25200075

Babbitt, Gregory A; Alawad, Mohammed A; Schulze, Katharina V; Hudson, André O

2015-01-01

347

Backbone resonance assignment of the HEAT1-domain of the human eukaryotic translation initiation factor 4GI.  

PubMed

Controlling translation during protein synthesis is crucial for cell proliferation and differentiation. Protein translation is orchestrated by an assembly of various protein components at the ribosomal subunits. The eukaryotic translation initiation factor 4G (eIF4G) plays an important role in the formation of the translation initiation complex eIF4F consisting of eIF4G, the ATP dependent RNA helicase eIF4A and the cap binding protein eIF4E. One of the functions of eIF4G is the enhancement of the activity of eIF4A facilitated mainly through binding to the HEAT1 domain of eIF4G. In order to understand the interaction of HEAT1 with eIF4A and other components during translation initiation backbone assignment is essential. Here we report the (1)H, (13)C and (15)N backbone assignment for the HEAT1 domain of human eIF4G isoform I (eIF4GI-HEAT1), the first of three HEAT domains of eIF4G (29 kDa) as a basis for the elucidation of its structure and interactions with its binding partners, necessary for understanding the mechanism of its biological function. PMID:23325513

Akabayov, Sabine R; Wagner, Gerhard

2014-04-01

348

Photovoltaic Characteristics of Phthalocyanine-Polysilane Composite Films  

Microsoft Academic Search

Poly[p-(methylphenylsilanylene)anthrylene] (PMPSA) which introduced anthracene into the Si-Si backbone structure of poly(methylphenylsilanylene) (PMPS) was synthesized. Schottky barrier photovoltaic cells consisting of semitransparent aluminum and phthalocyanine (H2Pc) dispersed in PMPSA were fabricated (H2Pc-PMPSA). The effects of a binder polymer and annealing of PMPSA on the photovoltaic characteristics were investigated. Since the conductivity of H2Pc-PMPSA composite films increases by the introduction of

Yutaka Haga; Yuto Harada

2001-01-01

349

Solid state nuclear magnetic resonance investigation of polymer backbone dynamics in poly(ethylene oxide) based lithium and sodium polyether-ester-sulfonate ionomers  

NASA Astrophysics Data System (ADS)

Polymer backbone dynamics of single ion conducting poly(ethylene oxide) (PEO)-based ionomer samples with low glass transition temperatures (Tg) have been investigated using solid-state nuclear magnetic resonance. Experiments detecting 13C with 1H decoupling under magic angle spinning (MAS) conditions identified the different components of the polymer backbone (PEO spacer and isophthalate groups) and their relative mobilities for a suite of lithium- and sodium-containing ionomer samples with varying cation contents. Variable temperature (203-373 K) 1H-13C cross-polarization MAS (CP-MAS) experiments also provided qualitative assessment of the differences in the motions of the polymer backbone components as a function of cation content and identity. Each of the main backbone components exhibit distinct motions, following the trends expected for motional characteristics based on earlier Quasi Elastic Neutron Scattering and 1H spin-lattice relaxation rate measurements. Previous 1H and 7Li spin-lattice relaxation measurements focused on both the polymer backbone and cation motion on the nanosecond timescale. The studies presented here assess the slower timescale motion of the polymer backbone allowing for a more comprehensive understanding of the polymer dynamics. The temperature dependences of 13C linewidths were used to both qualitatively and quantitatively examine the effects of cation content and identity on PEO spacer mobility. Variable contact time 1H-13C CP-MAS experiments were used to further assess the motions of the polymer backbone on the microsecond timescale. The motion of the PEO spacer, reported via the rate of magnetization transfer from 1H to 13C nuclei, becomes similar for T ˜x 1{.1} Tg in all ionic samples, indicating that at similar elevated reduced temperatures the motions of the polymer backbones on the microsecond timescale become insensitive to ion interactions. These results present an improved picture, beyond those of previous findings, for the dependence of backbone dynamics on cation density (and here, cation identity as well) in these amorphous PEO-based ionomer systems.

Roach, David J.; Dou, Shichen; Colby, Ralph H.; Mueller, Karl T.

2013-05-01

350

Backbone-only restraints for fast determination of the protein fold: The role of paramagnetism-based restraints. Cytochrome b562 as an example  

NASA Astrophysics Data System (ADS)

CH ? residual dipolar couplings (? rdc's) were measured for the oxidized cytochrome b562 from Escherichia coli as a result of its partial self-orientation in high magnetic fields due to the anisotropy of the overall magnetic susceptibility tensor. Both the low spin iron (III) heme and the four-helix bundle fold contribute to the magnetic anisotropy tensor. CH ? ? rdc's, which span a larger range than the analogous NH values (already available in the literature) sample large space variations at variance with NH ? rdc's, which are largely isooriented within ? helices. The whole structure is now significantly refined with the chemical shift index and CH ? ? rdc's. The latter are particularly useful also in defining the molecular magnetic anisotropy parameters. It is shown here that the backbone folding can be conveniently and accurately determined using backbone restraints only, which include NOEs, hydrogen bonds, residual dipolar couplings, pseudocontact shifts, and chemical shift index. All these restraints are easily and quickly determined from the backbone assignment. The calculated backbone structure is comparable to that obtained by using also side chain restraint. Furthermore, the structure obtained with backbone only restraints is, in its whole, very similar to that obtained with the complete set of restraints. The paramagnetism based restraints are shown to be absolutely relevant, especially for ? rdc's.

Banci, Lucia; Bertini, Ivano; Felli, Isabella C.; Sarrou, Josephine

2005-02-01

351

?ABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA  

PubMed Central

We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters. PMID:25260586

Pasi, Marco; Maddocks, John H.; Beveridge, David; Bishop, Thomas C.; Case, David A.; Cheatham, Thomas; Dans, Pablo D.; Jayaram, B.; Lankas, Filip; Laughton, Charles; Mitchell, Jonathan; Osman, Roman; Orozco, Modesto; Pérez, Alberto; Petkevi?i?t?, Daiva; Spackova, Nada; Sponer, Jiri; Zakrzewska, Krystyna; Lavery, Richard

2014-01-01

352

?ABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA.  

PubMed

We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters. PMID:25260586

Pasi, Marco; Maddocks, John H; Beveridge, David; Bishop, Thomas C; Case, David A; Cheatham, Thomas; Dans, Pablo D; Jayaram, B; Lankas, Filip; Laughton, Charles; Mitchell, Jonathan; Osman, Roman; Orozco, Modesto; Pérez, Alberto; Petkevi?i?t?, Daiva; Spackova, Nada; Sponer, Jiri; Zakrzewska, Krystyna; Lavery, Richard

2014-10-29

353

Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism.  

PubMed

Filoviruses, including Marburg virus (MARV) and Ebola virus (EBOV), cause fatal hemorrhagic fever in humans and non-human primates. All filoviruses encode a unique multi-functional protein termed VP35. The C-terminal double-stranded (ds)RNA-binding domain (RBD) of VP35 has been implicated in interferon antagonism and immune evasion. Crystal structures of the VP35 RBD from two ebolaviruses have previously demonstrated that the viral protein caps the ends of dsRNA. However, it is not yet understood how the expanses of dsRNA backbone, between the ends, are masked from immune surveillance during filovirus infection. Here, we report the crystal structure of MARV VP35 RBD bound to dsRNA. In the crystal structure, molecules of dsRNA stack end-to-end to form a pseudo-continuous oligonucleotide. This oligonucleotide is continuously and completely coated along its sugar-phosphate backbone by the MARV VP35 RBD. Analysis of dsRNA binding by dot-blot and isothermal titration calorimetry reveals that multiple copies of MARV VP35 RBD can indeed bind the dsRNA sugar-phosphate backbone in a cooperative manner in solution. Further, MARV VP35 RBD can also cap the ends of the dsRNA in solution, although this arrangement was not captured in crystals. Together, these studies suggest that MARV VP35 can both coat the backbone and cap the ends, and that for MARV, coating of the dsRNA backbone may be an essential mechanism by which dsRNA is masked from backbone-sensing immune surveillance molecules. PMID:23028316

Bale, Shridhar; Julien, Jean-Philippe; Bornholdt, Zachary A; Kimberlin, Christopher R; Halfmann, Peter; Zandonatti, Michelle A; Kunert, John; Kroon, Gerard J A; Kawaoka, Yoshihiro; MacRae, Ian J; Wilson, Ian A; Saphire, Erica Ollmann

2012-09-01

354

Investigating the role of a backbone to substrate hydrogen bond in OMP decarboxylase using a site-specific amide to ester substitution.  

PubMed

Hydrogen bonds between backbone amide groups of enzymes and their substrates are often observed, but their importance in substrate binding and/or catalysis is not easy to investigate experimentally. We describe the generation and kinetic characterization of a backbone amide to ester substitution in the orotidine 5'-monophosphate (OMP) decarboxylase from Methanobacter thermoautotrophicum (MtOMPDC) to determine the importance of a backbone amide-substrate hydrogen bond. The MtOMPDC-catalyzed reaction is characterized by a rate enhancement (?10(17)) that is among the largest for enzyme-catalyzed reactions. The reaction proceeds through a vinyl anion intermediate that may be stabilized by hydrogen bonding interaction between the backbone amide of a conserved active site serine residue (Ser-127) and oxygen (O4) of the pyrimidine moiety and/or electrostatic interactions with the conserved general acidic lysine (Lys-72). In vitro translation in conjunction with amber suppression using an orthogonal amber tRNA charged with l-glycerate ((HO)S) was used to generate the ester backbone substitution (S127(HO)S). With 5-fluoro OMP (FOMP) as substrate, the amide to ester substitution increased the value of Km by ?1.5-fold and decreased the value of kcat by ?50-fold. We conclude that (i) the hydrogen bond between the backbone amide of Ser-127 and O4 of the pyrimidine moiety contributes a modest factor (?10(2)) to the 10(17) rate enhancement and (ii) the stabilization of the anionic intermediate is accomplished by electrostatic interactions, including its proximity of Lys-72. These conclusions are in good agreement with predictions obtained from hybrid quantum mechanical/molecular mechanical calculations. PMID:25275007

Desai, Bijoy J; Goto, Yuki; Cembran, Alessandro; Fedorov, Alexander A; Almo, Steven C; Gao, Jiali; Suga, Hiroaki; Gerlt, John A

2014-10-21

355

Marburg Virus VP35 Can Both Fully Coat the Backbone and Cap the Ends of dsRNA for Interferon Antagonism  

PubMed Central

Filoviruses, including Marburg virus (MARV) and Ebola virus (EBOV), cause fatal hemorrhagic fever in humans and non-human primates. All filoviruses encode a unique multi-functional protein termed VP35. The C-terminal double-stranded (ds)RNA-binding domain (RBD) of VP35 has been implicated in interferon antagonism and immune evasion. Crystal structures of the VP35 RBD from two ebolaviruses have previously demonstrated that the viral protein caps the ends of dsRNA. However, it is not yet understood how the expanses of dsRNA backbone, between the ends, are masked from immune surveillance during filovirus infection. Here, we report the crystal structure of MARV VP35 RBD bound to dsRNA. In the crystal structure, molecules of dsRNA stack end-to-end to form a pseudo-continuous oligonucleotide. This oligonucleotide is continuously and completely coated along its sugar-phosphate backbone by the MARV VP35 RBD. Analysis of dsRNA binding by dot-blot and isothermal titration calorimetry reveals that multiple copies of MARV VP35 RBD can indeed bind the dsRNA sugar-phosphate backbone in a cooperative manner in solution. Further, MARV VP35 RBD can also cap the ends of the dsRNA in solution, although this arrangement was not captured in crystals. Together, these studies suggest that MARV VP35 can both coat the backbone and cap the ends, and that for MARV, coating of the dsRNA backbone may be an essential mechanism by which dsRNA is masked from backbone-sensing immune surveillance molecules. PMID:23028316

Bale, Shridhar; Halfmann, Peter; Zandonatti, Michelle A.; Kunert, John; Kroon, Gerard J. A.; Kawaoka, Yoshihiro; MacRae, Ian J.; Wilson, Ian A.; Saphire, Erica Ollmann

2012-01-01

356

TACN-based cationic lipids with amino acid backbone and double tails: materials for non-viral gene delivery.  

PubMed

Cationic lipids have become an efficient type of non-viral vectors for gene delivery. In this Letter, four cationic lipids containing 1,4,7-triazacyclononane (TACN) headgroup, glutamic/aspartic acid backbone and dioleyl tails were designed and synthesized. The TACN headgroup gives these lipids excellent pH buffering capacities, which were higher than branched 25 kDa PEI. Cationic liposomes prepared from these lipids and DOPE showed good DNA affinity, and full DNA condensation was found at N/P ratio of 3 via agarose gel electrophoresis. The lipoplexes were characterized by dynamic light scattering (DLS) assay, which gave proper particle sizes and zeta-potentials for transfection. In vitro gene transfection results in two cell lines reveal that TAN (with aspartic acid and amide bond in the structure) shows the best transfection efficiency, which is close to commercially available transfection agent Lipofectamine 2000. PMID:24618298

Wang, Bing; Yi, Wen-Jing; Zhang, Ji; Zhang, Qin-Fang; Xun, Miao-Miao; Yu, Xiao-Qi

2014-04-01

357

Conformationally Restricted GABA with Bicyclo[3.1.0]hexane Backbone as the First Highly Selective BGT-1 Inhibitor.  

PubMed

On the basis of the three-dimensional diversity-oriented conformational restriction strategy using key chiral cyclopropane units, we previously identified 3 ((2S,3R)-4-amino-3,4-methanobutyric acid) with a chiral trans-cyclopropane structure as a ?-aminobutyric acid (GABA) transporter inhibitor selective for GABA transporter (GAT) subtypes GAT-3 and BGT-1 (betaine/GABA transporter-1). Further conformational restriction of 3 with the rigid bicyclo[3.1.0]hexane backbone led to the successful development of the first highly potent and selective BGT-1 inhibitor 4 (IC50 = 0.59 ?M). The bioactive conformation of 3 for BGT-1 was also identified. PMID:25147609

Kobayashi, Takaaki; Suemasa, Akihiro; Igawa, Arisa; Ide, Soichiro; Fukuda, Hayato; Abe, Hiroshi; Arisawa, Mitsuhiro; Minami, Masabumi; Shuto, Satoshi

2014-08-14

358

The backbone structure of the thermophilic Thermoanaerobacter tengcongensis ribose binding protein is essentially identical to its mesophilic E. coli homolog  

SciTech Connect

We report the X-ray crystal structure of a Thermoanaerobacter tengcongensis ribose binding protein (tteRBP) determined to 1.9 {angstrom} resolution. We find that tteRBP is significantly more stable ({sup app}T{sub m} value {approx} 102 C) than the mesophilic Escherichia coli ribose binding protein (ecRBP) ({sup app}T{sub m} value {approx} 56 C). The tteRBP has essentially the identical backbone conformation (0.41 {angstrom} RMSD of 235/271 C{sub {alpha}} positions and 0.65 {angstrom} RMSD of 270/271 C{sub {alpha}} positions) as ecRBP. Classification of the amino acid substitutions as a function of structure therefore allows the identification of amino acids which potentially contribute to the observed thermal stability of tteRBP in the absence of large structural heterogeneities.

Cuneo, Matthew J.; Tian, Yaji; Allert, Malin; Hellinga, Homme W. (Duke)

2008-10-27

359

Structural elucidation of a novel core oligosaccharide backbone of the lipopolysaccharide from the new bacterial species Agrobacterium larrymoorei.  

PubMed

Agrobacterium larrymoorei is a Gram-negative phytopathogenic bacterium, which produces tumours on Ficus benjamina plants and differs from other Agrobacteria both genetically and biochemically. The lipopolysaccharide (LPS) plays an important role in the pathogenesis of Agrobacteria. The present paper is the first report on the molecular primary structure of the core region of an Agrobacterium LPS. The following structure of the core and lipid A carbohydrate backbone of an R-form LPS of A. larrymoorei was determined by chemical degradations and 1D and 2D NMR spectroscopy: [carbohydrate structure: see text] All sugars are alpha-D-pyranoses if not stated otherwise, Kdo is 3-deoxy-D-manno-oct-2-ulosonic acid, Qui3NAcyl is 3,6-dideoxy-3-(3-hydroxy-2,3-dimethyl-5-oxoprolylamino)glucose, GlcAN and GalAN are amides of GlcA and GalA. PMID:14670730

Molinaro, Antonio; De Castro, Cristina; Lanzetta, Rosa; Parrilli, Michelangelo; Raio, Aida; Zoina, Astolfo

2003-11-14

360

NMR microscopy of pore-space backbones in rock, sponge, and sand in comparison with random percolation model objects  

NASA Astrophysics Data System (ADS)

Two- and three-dimensional ``random swiss-cheese percolation'' and ``random-site percolation'' pore networks were simulated on a computer. The results were used as templates for the fabrication of model objects. The flow of water through the pore spaces of these objects was studied with the aid of NMR microscopy in the velocity-mapping variant. Up to three spatial dimensions and three dimensions for the three velocity components were examined. The results for the model objects were juxtaposed to those for lacunar materials such as pumice, sponge, sand, and glass bead agglomerates. Parameters characterizing the structure were evaluated from conventional NMR images of the water-filled pore spaces. The percolation backbone was determined by eliminating all voxels with velocities below the noise level.

Klemm, A.; Müautller, H.-P.; Kimmich, R.

1997-04-01

361

Backbone dynamics of an oncogenic mutant of Cdc42Hs shows increased flexibility at the nucleotide-binding site.  

PubMed

Cdc42Hs, a member of the Ras superfamily of GTP-binding signal transduction proteins, binds guanine nucleotides, and acts as a molecular-timing switch in multiple signal transduction pathways. The structure of the wild-type protein has been solved (Feltham et al. (1997) Biochemistry 36, 8755-8766), and the backbone dynamics have been characterized by NMR spectroscopy (Loh et al. (1999) Biochemistry 38, 12547-12557). The F28L mutation of Cdc42Hs is characterized by an increased rate of cycling between the GTP and GDP-bound forms leading to cell transformation (Lin et al. (1997) Curr. Biol. 7, 794-797). Here, we describe the backbone dynamics of Cdc42Hs(F28L)-GDP using 1H-15N NMR measurements of T1, T1rho, and steady-state NOE at two magnetic field strengths. Residue-specific values of the generalized order parameters (Ss2 and Sf2), local correlation time (tau(e)), and exchange rate (R(ex)) were obtained using the Lipari-Szabo formalism. Chemical-shift perturbation analysis suggested that very little structural change was evident outside of the nucleotide-binding site. However, residues comprising the nucleotide-binding site, as well as the nucleotide itself, exhibit increased dynamics over a wide range of time scales in Cdc42Hs(F28L) relative to the wild type. In addition to changes in dynamics measured by relaxation methods, hydrogen-deuterium exchange indicated a substantial disruption of the hydrogen-bonding network within the nucleotide-binding site. Thus, local dynamic changes introduced by a single-point mutation can affect important aspects of signaling processes without disrupting the conformation of the whole protein. PMID:15287724

Adams, Paul D; Loh, Adrienne P; Oswald, Robert E

2004-08-10

362

Backbone motions in a crystalline protein from field-dependent 2H-NMR relaxation and line-shape analysis.  

PubMed

We have used 2H-nmr to study backbone dynamics of the 2H-labeled, slowly exchanging amide sites of fully hydrated, crystalline hen egg white lysozyme. Order parameters are determined from the residual quadrupole coupling and values increase from S2 = 0.85 at 290 K to S2 = 0.94 at 200 K. Dynamical rates are determined from spin-lattice relaxation at three nmr frequencies (38.8, 61.5, and 76.7 MHz). The approach used here is thus distinct from solution nmr studies where dynamical amplitudes and rates are both determined from relaxation measurements. At temperatures below 250 K, relaxation is independent of the nmr frequency indicating that backbone motions are fast compared to the nmr frequencies. However, as the temperature is increased above 250 K, relaxation is significantly more efficient at the lowest frequency, which shows, in addition, the presence of motions that are slow compared to the nmr frequencies. Using the values of S2 determined from the residual quadrupole coupling and a model-free relaxation formalism that allows for fast and slow internal motions, we conclude that these slow motions have correlation times in the range of 0.1 to 1.0 microsecond and are effectively frozen out at 250 K where fast motions of the amide planes with approximately 15 ps effective correlation times and 9 degrees rms amplitudes dominate relaxation. The fast internal motions increase slightly in amplitude as the temperature rises toward 290 K, but the correlation time, as is also observed in solution nmr studies of RNase H, is approximately constant. These findings are consistent with hypotheses of dynamic glass transitions in hydrated proteins arising from temperature-dependent damping of harmonic modes of motion above the transition point. PMID:10644947

Mack, J W; Usha, M G; Long, J; Griffin, R G; Wittebort, R J

2000-01-01

363

The Backbone Dynamics of the Amyloid Precursor Protein Transmembrane Helix Provides a Rationale for the Sequential Cleavage Mechanism of ?-Secretase  

PubMed Central

The etiology of Alzheimer’s disease depends on the relative abundance of different amyloid-? (A?) peptide species. These peptides are produced by sequential proteolytic cleavage within the transmembrane helix of the 99 residue C-terminal fragment of the amyloid precursor protein (C99) by the intramembrane protease ?-secretase. Intramembrane proteolysis is thought to require local unfolding of the substrate helix, which has been proposed to be cleaved as a homodimer. Here, we investigated the backbone dynamics of the substrate helix. Amide exchange experiments of monomeric recombinant C99 and of synthetic transmembrane domain peptides reveal that the N-terminal Gly-rich homodimerization domain exchanges much faster than the C-terminal cleavage region. MD simulations corroborate the differential backbone dynamics, indicate a bending motion at a di-glycine motif connecting dimerization and cleavage regions, and detect significantly different H-bond stabilities at the initial cleavage sites. Our results are consistent with the following hypotheses about cleavage of the substrate. First, the GlyGly hinge may precisely position the substrate within ?-secretase such that its catalytic center must start proteolysis at the known initial cleavage sites. Second, the ratio of cleavage products formed by subsequent sequential proteolysis could be influenced by differential extents of solvation and by the stabilities of H-bonds at alternate initial sites. Third, the flexibility of the Gly-rich domain may facilitate substrate movement within the enzyme during sequential proteolysis. Fourth, dimerization may affect substrate processing by decreasing the dynamics of the dimerization region and by increasing that of the C-terminal part of the cleavage region. PMID:23265086

Pester, Oxana; Barrett, Paul J.; Hornburg, Daniel; Hornburg, Philipp; Probstle, Rasmus; Widmaier, Simon; Kutzner, Christoph; Durrbaum, Milena; Kapurniotu, Aphrodite; Sanders, Charles R.; Scharnagl, Christina; Langosch, Dieter

2013-01-01

364

Anatomy as the Backbone of an Integrated First Year Medical Curriculum: Design and Implementation  

PubMed Central

Morehouse School of Medicine chose to restructure its first year medical curriculum in 2005. The anatomy faculty had prior experience in integrating courses, stemming from the successful integration of individual anatomical sciences courses into a single course called Human Morphology. The integration process was expanded to include the other first year basic science courses (Biochemistry, Physiology, and Neurobiology) as we progressed toward an integrated curriculum. A team, consisting of the course directors, a curriculum coordinator and the Associate Dean for Educational and Faculty Affairs, was assembled to build the new curriculum. For the initial phase, the original course titles were retained but the lecture order was reorganized around the Human Morphology topic sequence. The material from all four courses was organized into four sequential units. Other curricular changes included placing laboratories and lectures more consistently in the daily routine, reducing lecture time from 120 to 90 minute blocks, eliminating unnecessary duplication of content, and increasing the amount of independent study time. Examinations were constructed to include questions from all courses on a single test, reducing the number of examination days in each block from three to one. The entire restructuring process took two years to complete, and the revised curriculum was implemented for the students entering in 2007. The outcomes of the restructured curriculum include a reduction in the number of contact hours by 28%, higher or equivalent subject examination average scores, enhanced student satisfaction, and a first year curriculum team better prepared to move forward with future integration. PMID:21538939

Klement, Brenda J.; Paulsen, Douglas F.; Wineski, Lawrence E

2011-01-01

365

Adaptive seeds tame genomic sequence comparison  

PubMed Central

The main way of analyzing biological sequences is by comparing and aligning them to each other. It remains difficult, however, to compare modern multi-billionbase DNA data sets. The difficulty is caused by the nonuniform (oligo)nucleotide composition of these sequences, rather than their size per se. To solve this problem, we modified the standard seed-and-extend approach (e.g., BLAST) to use adaptive seeds. Adaptive seeds are matches that are chosen based on their rareness, instead of using fixed-length matches. This method guarantees that the number of matches, and thus the running time, increases linearly, instead of quadratically, with sequence length. LAST, our open source implementation of adaptive seeds, enables fast and sensitive comparison of large sequences with arbitrarily nonuniform composition. PMID:21209072

Kielbasa, Szymon M.; Wan, Raymond; Sato, Kengo; Horton, Paul; Frith, Martin C.

2011-01-01

366

Experimental study of Nafion- and Flemion-based ionic polymer metal composites (IPMCs) with ethylene glycol as solvent  

Microsoft Academic Search

Ionic polymer-metal composites (IPMCs) consist of a perfluorinated ionomer membrane (usually Nafion® or Flemion®) plated on both faces with a noble metal such as gold or platinum and neutralized with a certain amount of counterions that balance the electrical charge of anions covalently fixed to the membrane backbone. IPMCs are electroactive materials that can be used as actuators and sensors.

Siavouche Nemat-Nasser; Shahram Zamani

2003-01-01

367

Optimization of gene sequences under constant mutational pressure and selection  

NASA Astrophysics Data System (ADS)

We have analyzed the influence of constant mutational pressure and selection on the nucleotide composition of DNA sequences of various size, which were represented by the genes of the Borrelia burgdorferi genome. With the help of MC simulations we have found that longer DNA sequences accumulate much less base substitutions per sequence length than short sequences. This leads us to the conclusion that the accuracy of replication may determine the size of genome.

Kowalczuk, M.; Gierlik, A.; Mackiewicz, P.; Cebrat, S.; Dudek, M. R.

1999-12-01

368

The DNA Sequence of Equine Herpesvirus 2  

Microsoft Academic Search

The complete DNA sequence of equine herpesvirus 2 (EHV-2) strain 86\\/67 was determined, The genome is 184,427 bp in size and has a base composition of 57.5% G + C. Unusually for a herpesvirus, about a third of the sequence distributed in several large blocks appears not to encode proteins. The 79 open reading frames that were identified as probably

Elizabeth A. R. Telford; Moira S. Watson; Heather C. Aird; Jacqueline Perry; Andrew J. Davison

1995-01-01

369

Some biological sequence metrics  

Microsoft Academic Search

Some new metria are introduced to measure the distance between biological sequences, such as amino acid sequences or nucleotide sequences. These metrics generalize a metric of Sellers, who considered only single deletions, mutations, and insertions. The present metria allow, for example, multiple deletions and insertions and single mutations. They also allow computation of the distance among more than two sequences.

M. S. WATERMAN; T. F. SMITH; W. A. BEYER

1976-01-01

370

Role of the backbone conformation at position 7 in the structure and activity of marinostatin, an ester-linked serine protease inhibitor.  

PubMed

Rational design of inhibitors: The cis-amide backbone at position 7 in the serine protease inhibitor marinostatin was replaced with an E or Z olefin. The E olefin analogue was not active, but the Z analogue was. The cis conformation might play a critical role in organizing a canonical structure for binding to proteases. PMID:22851252

Taichi, Misako; Yamazaki, Toshimasa; Nishiuchi, Yuji

2012-09-01

371

High-Resolution NMR Structure and Backbone Dynamics of the Bacillus subtilis Response Regulator, Spo0F: Implications for Phosphorylation and Molecular  

E-print Network

High-Resolution NMR Structure and Backbone Dynamics of the Bacillus subtilis Response Regulator in Bacillus subtilis. Three-dimensional 1H, 15N, and 13C experiments have been used to obtain full side chain-protein interactions and for determining the lifetimes of the phosphorylated state. Bacillus subtilis responds

McIntosh, Lawrence P.

372

K U R S A R A h D H O L Z W A R T H Backbone Conformational Change in the A -B Transition of  

E-print Network

K U R S A R A h D H O L Z W A R T H Backbone Conformational Change in the A -B Transition of Deoxyribonucleic Acidt Tom Kursar and G. Holzwarth*,t ABSTRACT: Infrared linear dichroism studies of A- and B (Fraser and Fraser, 1951;Sutherland and Tsuboi, 1957; Bradbury et al., 1961; Falk et al., 1963;Tsuboi

Coley, Phyllis

373

Backbone assignments of the 26 kDa neuron-specific ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1)  

E-print Network

of Parkinson's disease. Herein, we present the NMR backbone assignments of human UCH-L1, thus enabling future De-ubiquitination Á Ubiquitin C-terminal hydrolase Á Knotted proteins Á Parkinson's disease with Parkinson's disease (PD) (the UCH-L1 gene is also referred to as PARK5). The I93 M mutation has been

Jackson, Sophie

374

Genome Sequencing Centers  

Cancer.gov

The Cancer Genome Atlas (TCGA) Genome Sequencing Centers (GSCs) perform large-scale DNA sequencing using the latest sequencing technologies. Supported by the National Human Genome Research Institute (NHGRI) large-scale sequencing program, the GSCs generate the enormous volume of data required by TCGA, while continually improving existing technologies and methods to expand the frontier of what can be achieved in cancer genome sequencing.

375

Sequence control in polymer chemistry through the Passerini three-component reaction.  

PubMed

A new strategy to achieve sequence control in polymer chemistry based on the iterative application of the versatile Passerini three-component reaction (P-3CR) in combination with efficient thiol-ene addition reactions is introduced. First, stearic acid was used as a starting substrate to build up a sequence-defined tetramer with a molecular weight of 1.6 kDa. Using an acid-functionalized PEG allowed for an easier isolation of the sequence-defined macromolecules by simple precipitation and led to a sequence-defined pentamer in a block-copolymer architecture. Importantly, this new strategy completely avoids protecting group chemistry. By following this strategy, a different side chain can be introduced to the polymer/oligomer backbone in a simple way and at a defined position within the macromolecule. PMID:24307280

Solleder, Susanne C; Meier, Michael A R

2014-01-13

376

their sequenc-es. Nature is  

E-print Network

remote evolutionary relationships." This idea of using protein structure rather than amino-acid sequences) and his co-workers found a gene that controls the size of the tomato fruit, but the evolu- tionary. Proteins are linear polymers of amino acids. Since the amino-acid sequence determines all protein

Keinan, Alon

377

A protein block based fold recognition method for the annotation of twilight zone sequences.  

PubMed

The description of protein backbone was recently improved with a group of structural fragments called Structural Alphabets instead of the regular three states (Helix, Sheet and Coil) secondary structure description. Protein Blocks is one of the Structural Alphabets used to describe each and every region of protein backbone including the coil. According to de Brevern (2000) the Protein Blocks has 16 structural fragments and each one has 5 residues in length. Protein Blocks fragments are highly informative among the available Structural Alphabets and it has been used for many applications. Here, we present a protein fold recognition method based on Protein Blocks for the annotation of twilight zone sequences. In our method, we align the predicted Protein Blocks of a query amino acid sequence with a library of assigned Protein Blocks of 953 known folds using the local pair-wise alignment. The alignment results with z-value ? 2.5 and P-value ? 0.08 are predicted as possible folds. Our method is able to recognize the possible folds for nearly 35.5% of the twilight zone sequences with their predicted Protein Block sequence obtained by pb_prediction, which is available at Protein Block Export server. PMID:22591480

Suresh, V; Ganesan, K; Parthasarathy, S

2013-03-01

378

RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures  

SciTech Connect

Among the hundreds of nucleic acid analogues that have been studied over the last two decades only very few exhibit backbones with linkers between residues that are either shorter or longer than the four-atom linker O3{prime}-P-O5{prime}-C5{prime} connecting sugar ring moieties in DNA and RNA. 2{prime}-Deoxyribonucleoside dimers connected by a five-atom linker O3{prime}-CH*(CH{sub 3})-CO-NH-CH{sub 2} (* designates a chiral center) were reported to lead to only a slight destabilization of RNA-DNA hybrids in which the DNA strand contained one or several of these amide-linked dimers (De Napoli, L., Iadonisi, A., Montesarchio, D., Varra, M., and Piccialli, G. (1995) Synthesis of thymidine dimers containing a new internucleosidic amide linkage and their incorporation into oligodeoxyribonucleotides, Bioorg. Med. Chem. Lett. 5, 1647-1652). To analyze the influence of various chemistries of such five-atom amide linkers on the RNA-binding affinity of modified DNA strands, we have synthesized five different amide-linked dimers, including structures with homochiral linkers of the type X3{prime}-C*H(CH{sub 3})-CO-NH-CH{sub 2} (X = O, CH{sub 2}) as well as the corresponding analogues carrying methoxy groups at the 2{prime}-position of the 3{prime}-nucleosides. We have conducted a detailed thermodynamic analysis of duplex formation between the modified DNA and RNA, with the DNA strands containing between one and seven consecutive modified dimers. Some of the five-atom-linked dimers lead to significantly higher RNA-binding affinities compared with that of native DNA. Interestingly, the linkers with opposite stereochemistry at the chiral center stabilize duplexes between the modified DNA and RNA to different degrees. CD spectroscopy in solution and a crystal structure of an RNA-DNA duplex with a single amide-linked dimer demonstrate that the longer amide backbones do not disrupt the duplex geometry. These observations provide further evidence that stable cross-pairing between two different types of nucleic acids does not require the numbers of atoms linking their individual residues to match.

Pallan, Pradeep S.; von Matt, Peter; Wilds, Christopher J.; Altmann, Karl-Heinz; Egli, Martin (SFIT); (Novartis); (Vanderbilt)

2010-03-08

379

Genome Sequence Databases (Overview): Sequencing and Assembly  

SciTech Connect

From the date its role in heredity was discovered, DNA has been generating interest among scientists from different fields of knowledge: physicists have studied the three dimensional structure of the DNA molecule, biologists tried to decode the secrets of life hidden within these long molecules, and technologists invent and improve methods of DNA analysis. The analysis of the nucleotide sequence of DNA occupies a special place among the methods developed. Thanks to the variety of sequencing technologies available, the process of decoding the sequence of genomic DNA (or whole genome sequencing) has become robust and inexpensive. Meanwhile the assembly of whole genome sequences remains a challenging task. In addition to the need to assemble millions of DNA fragments of different length (from 35 bp (Solexa) to 800 bp (Sanger)), great interest in analysis of microbial communities (metagenomes) of different complexities raises new problems and pushes some new requirements for sequence assembly tools to the forefront. The genome assembly process can be divided into two steps: draft assembly and assembly improvement (finishing). Despite the fact that automatically performed assembly (or draft assembly) is capable of covering up to 98% of the genome, in most cases, it still contains incorrectly assembled reads. The error rate of the consensus sequence produced at this stage is about 1/2000 bp. A finished genome represents the genome assembly of much higher accuracy (with no gaps or incorrectly assembled areas) and quality ({approx}1 error/10,000 bp), validated through a number of computer and laboratory experiments.

Lapidus, Alla L.

2009-01-01

380

Sequence Bundles: a novel method for visualising, discovering and exploring sequence motifs  

PubMed Central

Background We introduce Sequence Bundles--a novel data visualisation method for representing multiple sequence alignments (MSAs). We identify and address key limitations of the existing bioinformatics data visualisation methods (i.e. the Sequence Logo) by enabling Sequence Bundles to give salient visual expression to sequence motifs and other data features, which would otherwise remain hidden. Methods For the development of Sequence Bundles we employed research-led information design methodologies. Sequences are encoded as uninterrupted, semi-opaque lines plotted on a 2-dimensional reconfigurable grid. Each line represents a single sequence. The thickness and opacity of the stack at each residue in each position indicates the level of conservation and the lines' curved paths expose patterns in correlation and functionality. Several MSAs can be visualised in a composite image. The Sequence Bundles method is designed to favour a tangible, continuous and intuitive display of information. Results We have developed a software demonstration application for generating a Sequence Bundles visualisation of MSAs provided for the BioVis 2013 redesign contest. A subsequent exploration of the visualised line patterns allowed for the discovery of a number of interesting features in the dataset. Reported features include the extreme conservation of sequences displaying a specific residue and bifurcations of the consensus sequence. Conclusions Sequence Bundles is a novel method for visualisation of MSAs and the discovery of sequence motifs. It can aid in generating new insight and hypothesis making. Sequence Bundles is well disposed for future implementation as an interactive visual analytics software, which can complement existing visualisation tools. PMID:25237395

2014-01-01

381

Automated DNA Sequencing System  

SciTech Connect

Oak Ridge National Laboratory (ORNL) is developing a core DNA sequencing facility to support biological research endeavors at ORNL and to conduct basic sequencing automation research. This facility is novel because its development is based on existing standard biology laboratory equipment; thus, the development process is of interest to the many small laboratories trying to use automation to control costs and increase throughput. Before automation, biology Laboratory personnel purified DNA, completed cycle sequencing, and prepared 96-well sample plates with commercially available hardware designed specifically for each step in the process. Following purification and thermal cycling, an automated sequencing machine was used for the sequencing. A technician handled all movement of the 96-well sample plates between machines. To automate the process, ORNL is adding a CRS Robotics A- 465 arm, ABI 377 sequencing machine, automated centrifuge, automated refrigerator, and possibly an automated SpeedVac. The entire system will be integrated with one central controller that will direct each machine and the robot. The goal of this system is to completely automate the sequencing procedure from bacterial cell samples through ready-to-be-sequenced DNA and ultimately to completed sequence. The system will be flexible and will accommodate different chemistries than existing automated sequencing lines. The system will be expanded in the future to include colony picking and/or actual sequencing. This discrete event, DNA sequencing system will demonstrate that smaller sequencing labs can achieve cost-effective the laboratory grow.

Armstrong, G.A.; Ekkebus, C.P.; Hauser, L.J.; Kress, R.L.; Mural, R.J.

1999-04-25

382

Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins.  

PubMed

A molecular-level understanding of the function of a protein requires knowledge of both its structural and dynamic properties. NMR spectroscopy allows the measurement of generalized order parameters that provide an atomistic description of picosecond and nanosecond fluctuations in protein structure. Molecular dynamics (MD) simulation provides a complementary approach to the study of protein dynamics on similar time scales. Comparisons between NMR spectroscopy and MD simulations can be used to interpret experimental results and to improve the quality of simulation-related force fields and integration methods. However, apparent systematic discrepancies between order parameters extracted from simulations and experiments are common, particularly for elements of noncanonical secondary structure. In this paper, results from a 1.2 micros explicit solvent MD simulation of the protein ubiquitin are compared with previously determined backbone order parameters derived from NMR relaxation experiments [Tjandra, N.; Feller, S. E.; Pastor, R. W.; Bax, A. J. Am. Chem. Soc. 1995, 117, 12562-12566]. The simulation reveals fluctuations in three loop regions that occur on time scales comparable to or longer than that of the overall rotational diffusion of ubiquitin and whose effects would not be apparent in experimentally derived order parameters. A coupled analysis of internal and overall motion yields simulated order parameters substantially closer to the experimentally determined values than is the case for a conventional analysis of internal motion alone. Improved agreement between simulation and experiment also is encouraging from the viewpoint of assessing the accuracy of long MD simulations. PMID:18311962

Maragakis, Paul; Lindorff-Larsen, Kresten; Eastwood, Michael P; Dror, Ron O; Klepeis, John L; Arkin, Isaiah T; Jensen, Morten Ø; Xu, Huafeng; Trbovic, Nikola; Friesner, Richard A; Iii, Arthur G Palmer; Shaw, David E

2008-05-15

383

Solvent- and thermoresponsive polyrotaxanes with beta-cyclodextrin dispersed/aggregated structures on a pluronic F127 backbone.  

PubMed

A series of polyrotaxane-based triblock copolymers comprising beta-cyclodextrins (beta-CDs) threaded onto a distal 2-bromopropionyl end-capped Pluronic F127 as a central block and poly(N-isopropylacrylamide) outer blocks as end-stoppers were prepared via ATRP of N-isopropylacrylamide in aqueous solution. The structure of the resulting copolymers was characterized in detail by (1)H NMR, (13)C NMR, GPC, and WXRD techniques. Unlike those CD-based polyrotaxanes exhibiting the characteristic tunnel-type crystal structure, these copolymers precipitated from DMF with anhydrous ether preserve a dispersed-state structure in which the beta-CDs are loosely distributed along the Pluronic F127 chain, while they present an aggregated structure in which the beta-CDs are densely stacked one by one along the polymer backbone, holding the typical tunnel-like crystal structure after incubation in water and freeze-drying. The beta-CD dispersed and aggregated states are convertible by the incubation or precipitation treatments. Furthermore, annealing at various temperatures manifests them having the thermoresponsibility in the solid state. These copolymers containing the beta-CD dispersed structure possess an imperfect crystal PEO domain, while those with the beta-CD aggregated structure hold both a microcrystal and an imperfect crystal PEO domain. Hence, the as-prepared polyrotaxane-based triblock copolymers are not only solvent-sensitive but also thermoresponsible supramolecular materials. PMID:20373770

Wang, Jin; Gao, Peng; Ye, Lin; Zhang, Ai-ying; Feng, Zeng-guo

2010-04-29

384

Synthesis and in vitro antioxidant functions of protein hydrolysate from backbones of Rastrelliger kanagurta by proteolytic enzymes  

PubMed Central

Every year, a huge quantity of fishery wastes and by-products are generated by fish processing industries. These wastes are either underutilized to produce low market value products or dumped leading to environmental issues. Complete utilization of fishery wastes for recovering value added products would be beneficial to the society and individual. The fish protein hydrolysates and derived peptides of fishery resources are widely used as nutritional supplements, functional ingredients, and flavor enhancers in food, beverage and pharmaceutical industries. Antioxidants from fishery resources have attracted the attention of researchers as they are cheaper in cost, easy to derive, and do not have side effects. Thus the present investigation was designed to produce protein hydrolysate by pepsin and papain digestion from the backbones of Rastrelliger kanagurta (Indian mackerel) and evaluate its antioxidant properties through various in vitro assays. The results reveal that both hydrolysates are potent antioxidants, capable of scavenging 46% and 36% of DPPH (1,1-diphenyl-2 picrylhydrazyl) and 58.5% and 37.54% of superoxide radicals respectively. The hydrolysates exhibit significant (p < 0.05) reducing power and lipid peroxidation inhibition. Among the two hydrolysates produced, pepsin derived fraction is superior than papain derived fraction in terms of yield, DH (Degree of hydrolysis), and antioxidant activity. PMID:24596496

Sheriff, Sheik Abdulazeez; Sundaram, Balasubramanian; Ramamoorthy, Baranitharan; Ponnusamy, Ponmurugan

2013-01-01

385

Backbone and ILV methyl resonance assignments of E. coli thymidylate synthase bound to cofactor and a nucleotide analogue  

PubMed Central

Thymidylate synthase (TSase) is a 62 kDa homodimeric enzyme required for de novo synthesis of thymidine monophosphate (dTMP) in most organisms. This makes the enzyme an excellent target for anticancer and microbial antibiotic drugs. In addition, TSase has been shown to exhibit negative cooperativity and half-the-sites reactivity. For these collective reasons, TSase is widely studied, and much is known about its kinetics and structure as it progresses through a multi-step catalytic cycle. Recently, nuclear magnetic resonance (NMR) spin relaxation has been instrumental in demonstrating the critical role of dynamics in enzyme function in small model systems. These studies raise questions about how dynamics affect function in larger enzymes with more complex reaction coordinates. TSase is an ideal candidate given its size, oligomeric state, cooperativity, and status as a drug target. Here, as a pre-requisite to spin relaxation studies, we present the backbone and ILV methyl resonance assignments of TSase from Escherichia coli bound to a substrate analogue and cofactor. PMID:23653343

Sapienza, Paul J.; Lee, Andrew L.

2013-01-01

386

A new photoactive building block for investigation of DNA backbone interactions: photoaffinity labeling of human DNA polymerase beta.  

PubMed

The cross-linking of target proteins or nucleic acids to light-activatable ligands is an important tool for elucidating molecular interactions. Through the use of photoaffinity-labeling reagents, several new insights into nucleic acid interactions have been obtained, for example in DNA replication and repair. In most known photoprobes, the applied light-sensitive functionalities are placed directly at the nucleobase or are attached via linkers to either the nucleobase or the phosphate backbone. Here we describe the first photoprobe that bears a light-sensitive aryl(trifluoromethyl)diazirine at the sugar moiety of a DNA oligonucleotide. We devised a route for the synthesis of the modified nucleoside and its incorporation into an oligonucleotide. The photoactive species was proven to be stable under the conditions employed in routine automated DNA synthesis. The modified oligonucleotide was shown by subsequent photolabeling studies of human DNA polymerase beta to form a covalent complex to the enzyme upon irradiation with near-UV light. PMID:17106908

Liebmann, Meike; Di Pasquale, Francesca; Marx, Andreas

2006-12-01

387

Backbone amide linker (BAL) strategy for Nalpha-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of peptide aldehydes.  

PubMed

A rapid and efficient strategy has been developed for the general synthesis of complex peptide aldehydes. N(alpha)-Benzyloxycarbonylamino acids were converted to protected aldehyde building blocks for solid-phase synthesis in four steps and moderate overall yields. The aldehydes were protected as 1,3-dioxolanes except for one case where a dimethyl acetal was used. These protected amino aldehyde monomers were then incorporated onto 5-[(2 or 4)-formyl-3,5-dimethoxyphenoxy]butyryl-resin (BAL-PEG-PS) by reductive amination, following which the penultimate residue was introduced by HATU-mediated acylation. The resultant resin-bound dipeptide unit, anchored by a backbone amide linkage (BAL), was extended further by routine Fmoc chemistry procedures. Several model peptide aldehydes were prepared in good yields and purities. Some epimerization of the C-terminal residue occurred (10% to 25%), due to the intrinsic stereolability conferred by the aldehyde functional group, rather than any drawbacks to the synthesis procedure. PMID:16001455

Kappel, Joseph C; Barany, George

2005-09-01

388

Novel Enterokinase Cleavage Sequences.  

National Technical Information Service (NTIS)

Novel enterokinase cleavage sequences are provided. Also disclosed are methods for the rapid isolation of a protein of interest present in a fusion protein construct including a novel enterokinase cleavage sequence of the present invention and a ligand re...

A. C. Ley, C. J. Luneau, R. C. Ladner

2005-01-01

389

Sequencing General Chemistry  

NSDL National Science Digital Library

The material in the authors' general chemistry curriculum has been rearranged into a sequence thought to be more logical to students than the traditional sequence. This fresh approach does not radically change course content but rather produces a systemat

Yoblinski, B. J.

2003-03-01

390

Sequence information signal processor  

NASA Technical Reports Server (NTRS)

An electronic circuit is used to compare two sequences, such as genetic sequences, to determine which alignment of the sequences produces the greatest similarity. The circuit includes a linear array of series-connected processors, each of which stores a single element from one of the sequences and compares that element with each successive element in the other sequence. For each comparison, the processor generates a scoring parameter that indicates which segment ending at those two elements produces the greatest degree of similarity between the sequences. The processor uses the scoring parameter to generate a similar scoring parameter for a comparison between the stored element and the next successive element from the other sequence. The processor also delivers the scoring parameter to the next processor in the array for use in generating a similar scoring parameter for another pair of elements. The electronic circuit determines which processor and alignment of the sequences produce the scoring parameter with the highest value.

Peterson, John C. (Inventor); Chow, Edward T. (Inventor); Waterman, Michael S. (Inventor); Hunkapillar, Timothy J. (Inventor)

1999-01-01

391

Cellulases and coding sequences  

DOEpatents

The present invention provides three fungal cellulases, their coding sequences, recombinant DNA molecules comprising the cellulase coding sequences, recombinant host cells and methods for producing same. The present cellulases are from Orpinomyces PC-2.

Li, Xin-Liang (Athens, GA); Ljungdahl, Lars G. (Athens, GA); Chen, Huizhong (Lawrenceville, GA)

2001-01-01

392

Cellulases and coding sequences  

DOEpatents

The present invention provides three fungal cellulases, their coding sequences, recombinant DNA molecules comprising the cellulase coding sequences, recombinant host cells and methods for producing same. The present cellulases are from Orpinomyces PC-2.

Li, Xin-Liang (Athens, GA); Ljungdahl, Lars G. (Athens, GA); Chen, Huizhong (Lawrenceville, GA)

2001-02-20

393

Sequencing with graphene pores  

NASA Astrophysics Data System (ADS)

Solid-state nanopores are often used for biomolecular analysis, but have so far been unable to sequence DNA. Marija Drndi? asks whether nanopores made in graphene could fulfil all of the requirements needed for sequencing.

Drndi?, Marija

2014-10-01

394

Pest-resistant plants comprising a construct encoding a vacuole targeting sequence and avidin or streptavidin  

US Patent & Trademark Office Database

This invention relates to nucleic acids encoding chimeric polypeptides comprising vacuole targeting sequences and sequences encoding avidin or streptavidin. The nucleic acids are useful for conferring pest resistance on plants and in the production of compositions useful as pesticides.

2005-12-06

395

Spooky Sequences- Square Numbers  

NSDL National Science Digital Library

This interactive Flash game helps students recognize and generate the sequence of square numbers, and also to discover the pattern of differences between them. The applet displays a sequence of six consecutive square numbers with one number missing. The player provides the missing number to "send the ghosts back to the haunted house." Each game consists of five sequences to complete.

Cogan, Mark

2002-01-01

396

The DynaMine webserver: predicting protein dynamics from sequence  

PubMed Central

Protein dynamics are important for understanding protein function. Unfortunately, accurate protein dynamics information is difficult to obtain: here we present the DynaMine webserver, which provides predictions for the fast backbone movements of proteins directly from their amino-acid sequence. DynaMine rapidly produces a profile describing the statistical potential for such movements at residue-level resolution. The predicted values have meaning on an absolute scale and go beyond the traditional binary classification of residues as ordered or disordered, thus allowing for direct dynamics comparisons between protein regions. Through this webserver, we provide molecular biologists with an efficient and easy to use tool for predicting the dynamical characteristics of any protein of interest, even in the absence of experimental observations. The prediction results are visualized and can be directly downloaded. The DynaMine webserver, including instructive examples describing the meaning of the profiles, is available at http://dynamine.ibsquare.be. PMID:24728994

Cilia, Elisa; Pancsa, Rita; Tompa, Peter; Lenaerts, Tom; Vranken, Wim F.

2014-01-01

397

Effects of sequence distribution and specific interactions on the ordering and interfacial behavior of copolymers  

NASA Astrophysics Data System (ADS)

Copolymers provide a route to novel polymeric materials by combining two or more existing monomers and arranging them in new ways. Self-consistent mean field theory (SCFT) is a powerful tool for exploring the many possible sequence distributions for copolymers and predicting their equilibrium behavior. In this thesis, SCFT calculations are used in combination with experiments to learn more about the ordering and interfacial behavior of block, random, and gradient copolymers. A symmetric diblock copolymer melt undergoes separation into lamellar microphases above a critical order-disorder transition. A symmetric gradient copolymer with a controlled composition gradient along its backbone also forms lamellae, but at a higher degree of incompatibility with broader interfaces and wider periodic spacing. Upon renormalization to their respective critical points, it is seen that the scaling behavior of symmetric diblock and gradient copolymers is universal across a wide range in incompatibility, regardless of the sequence distribution. The interfacial segregation of diblock, random, and gradient copolymers synthesized by ring-opening metathesis polymerization was measured with forward recoil spectrometry and analyzed using SOFT. The diblock copolymers form an interfacial monolayer with low interfacial tension, and the random copolymers form a wetting layer at the interface. The gradient copolymers exhibit intermediate behavior by forming a low interfacial energy layer that is slightly broader than a monolayer. The nature of the gradient can be altered to create a tailored interfacial copolymer monolayer that has a desired interfacial width. SCFT studies on a system of asymmetric AB copolymer and A and C homopolymers where B and C have favorable interactions show that the copolymer modifies the interfacial curvature so that swollen micelles, inverse swollen micelles, or bicontinuous microemulsions can form. The calculations also show that nanoparticles can be encapsulated in the center of the swollen micelles. A copolymer synthesis method combining anionic and nitroxide mediated controlled radical polymerizations was developed as a corresponding experimental system. In this system, the A homopolymer is polystyrene, the C homopolymer is poly(2-vinylpyridine), and the AB copolymer is a block-random copolymer where the first block is deuterated polystyrene and the second block is a random copolymer of polystyrene and poly(4-hydroxystyrene).

Lefebvre, Michelle Denise

398

Sequence for yourself  

NSDL National Science Digital Library

Appropriate for high school students, this animation shows how scientists can determine the sequence of bases in human DNA. The animation provides an overview of the many steps involved in a sequencing method called the map-based shotgun approach. As the animation points out, there are other methods for sequencing and other variations on the approach shown here. There are five parts to the animation, and students use control buttons to navigate through it. The animation emphasizes that scientists currently cannot sequence an entire chromosome at once. Instead, they deal with overlapping, short lengths of DNA and work backwards to determine the sequence of a chromosome. Copyright 2005 Eisenhower National Clearinghouse

Unit, Wgbh S.

2001-01-01

399

Computational methods in sequence and structure prediction  

NASA Astrophysics Data System (ADS)

This dissertation is organized into two parts. In the first part, we will discuss three computational methods for cis-regulatory element recognition in three different gene regulatory networks as the following: (a) Using a comprehensive "Phylogenetic Footprinting Comparison" method, we will investigate the promoter sequence structures of three enzymes (PAL, CHS and DFR) that catalyze sequential steps in the pathway from phenylalanine to anthocyanins in plants. Our result shows there exists a putative cis-regulatory element "AC(C/G)TAC(C)" in the upstream of these enzyme genes. We propose this cis-regulatory element to be responsible for the genetic regulation of these three enzymes and this element, might also be the binding site for MYB class transcription factor PAP1. (b) We will investigate the role of the Arabidopsis gene glutamate receptor 1.1 (AtGLR1.1) in C and N metabolism by utilizing the microarray data we obtained from AtGLR1.1 deficient lines (antiAtGLR1.1). We focus our investigation on the putatively co-regulated transcript profile of 876 genes we have collected in antiAtGLR1.1 lines. By (a) scanning the occurrence of several groups of known abscisic acid (ABA) related cisregulatory elements in the upstream regions of 876 Arabidopsis genes; and (b) exhaustive scanning of all possible 6-10 bps motif occurrence in the upstream regions of the same set of genes, we are able to make a quantative estimation on the enrichment level of each of the cis-regulatory element candidates. We finally conclude that one specific cis-regulatory element group, called "ABRE" elements, are statistically highly enriched within the 876-gene group as compared to their occurrence within the genome. (c) We will introduce a new general purpose algorithm, called "fuzzy REDUCE1", which we have developed recently for automated cis-regulatory element identification. In the second part, we will discuss our newly devised protein design framework. With this framework we have developed a software package which is capable of designing novel protein structures at the atomic resolution. This software package allows us to perform protein structure design with a flexible backbone. The backbone flexibility includes loop region relaxation as well as a secondary structure collective mode relaxation scheme. (Abstract shortened by UMI.)

Lang, Caiyi

400

DNA microarray profiling of a diverse collection of nosocomial methicillin-resistant staphylococcus aureus isolates assigns the majority to the correct sequence type and staphylococcal cassette chromosome mec (SCCmec) type and results in the subsequent identification and characterization of novel SCCmec-SCCM1 composite islands.  

PubMed

One hundred seventy-five isolates representative of methicillin-resistant Staphylococcus aureus (MRSA) clones that predominated in Irish hospitals between 1971 and 2004 and that previously underwent multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing were characterized by spa typing (175 isolates) and DNA microarray profiling (107 isolates). The isolates belonged to 26 sequence type (ST)-SCCmec types and subtypes and 35 spa types. The array assigned all isolates to the correct MLST clonal complex (CC), and 94% (100/107) were assigned an ST, with 98% (98/100) correlating with MLST. The array assigned all isolates to the correct SCCmec type, but subtyping of only some SCCmec elements was possible. Additional SCCmec/SCC genes or DNA sequence variation not detected by SCCmec typing was detected by array profiling, including the SCC-fusidic acid resistance determinant Q6GD50/fusC. Novel SCCmec/SCC composite islands (CIs) were detected among CC8 isolates and comprised SCCmec IIA-IIE, IVE, IVF, or IVg and a ccrAB4-SCC element with 99% DNA sequence identity to SCC(M1) from ST8/t024-MRSA, SCCmec VIII, and SCC-CI in Staphylococcus epidermidis. The array showed that the majority of isolates harbored one or more superantigen (94%; 100/107) and immune evasion cluster (91%; 97/107) genes. Apart from fusidic acid and trimethoprim resistance, the correlation between isolate antimicrobial resistance phenotype and the presence of specific resistance genes was ?97%. Array profiling allowed high-throughput, accurate assignment of MRSA to CCs/STs and SCCmec types and provided further evidence of the diversity of SCCmec/SCC. In most cases, array profiling can accurately predict the resistance phenotype of an isolate. PMID:22869569

Shore, Anna C; Brennan, Orla M; Deasy, Emily C; Rossney, Angela S; Kinnevey, Peter M; Ehricht, Ralf; Monecke, Stefan; Coleman, David C

2012-10-01

401

DNA Microarray Profiling of a Diverse Collection of Nosocomial Methicillin-Resistant Staphylococcus aureus Isolates Assigns the Majority to the Correct Sequence Type and Staphylococcal Cassette Chromosome mec (SCCmec) Type and Results in the Subsequent Identification and Characterization of Novel SCCmec-SCCM1 Composite Islands  

PubMed Central

One hundred seventy-five isolates representative of methicillin-resistant Staphylococcus aureus (MRSA) clones that predominated in Irish hospitals between 1971 and 2004 and that previously underwent multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing were characterized by spa typing (175 isolates) and DNA microarray profiling (107 isolates). The isolates belonged to 26 sequence type (ST)-SCCmec types and subtypes and 35 spa types. The array assigned all isolates to the correct MLST clonal complex (CC), and 94% (100/107) were assigned an ST, with 98% (98/100) correlating with MLST. The array assigned all isolates to the correct SCCmec type, but subtyping of only some SCCmec elements was possible. Additional SCCmec/SCC genes or DNA sequence variation not detected by SCCmec typing was detected by array profiling, including the SCC-fusidic acid resistance determinant Q6GD50/fusC. Novel SCCmec/SCC composite islands (CIs) were detected among CC8 isolates and comprised SCCmec IIA-IIE, IVE, IVF, or IVg and a ccrAB4-SCC element with 99% DNA sequence identity to SCCM1 from ST8/t024-MRSA, SCCmec VIII, and SCC-CI in Staphylococcus epidermidis. The array showed that the majority of isolates harbored one or more superantigen (94%; 100/107) and immune evasion cluster (91%; 97/107) genes. Apart from fusidic acid and trimethoprim resistance, the correlation between isolate antimicrobial resistance phenotype and the presence of specific resistance genes was ?97%. Array profiling allowed high-throughput, accurate assignment of MRSA to CCs/STs and SCCmec types and provided further evidence of the diversity of SCCmec/SCC. In most cases, array profiling can accurately predict the resistance phenotype of an isolate. PMID:22869569

Brennan, Orla M.; Deasy, Emily C.; Rossney, Angela S.; Kinnevey, Peter M.; Ehricht, Ralf; Monecke, Stefan; Coleman, David C.

2012-01-01

402

Biological sequence compression algorithms.  

PubMed

Today, more and more DNA sequences are becoming available. The information about DNA sequences are stored in molecular biology databases. The size and importance of these databases will be bigger and bigger in the future, therefore this information must be stored or communicated efficiently. Furthermore, sequence compression can be used to define similarities between biological sequences. The standard compression algorithms such as gzip or compress cannot compress DNA sequences, but only expand them in size. On the other hand, CTW (Context Tree Weighting Method) can compress DNA sequences less than two bits per symbol. These algorithms do not use special structures of biological sequences. Two characteristic structures of DNA sequences are known. One is called palindromes or reverse complements and the other structure is approximate repeats. Several specific algorithms for DNA sequences that use these structures can compress them less than two bits per symbol. In this paper, we improve the CTW so that characteristic structures of DNA sequences are available. Before encoding the next symbol, the algorithm searches an approximate repeat and palindrome using hash and dynamic programming. If there is a palindrome or an approximate repeat with enough length then our algorithm represents it with length and distance. By using this preprocessing, a new program achieves a little higher compression ratio than that of existing DNA-oriented compression algorithms. We also describe new compression algorithm for protein sequences. PMID:11700586

Matsumoto, T; Sadakane, K; Imai, H

2000-01-01

403

Multiple N-methylation of MT-II backbone amide bonds leads to melanocortin receptor subtype hMC1R selectivity; pharmacological and conformational studies  

PubMed Central

Multiple N-methylation is a novel technology to improve bioavailability of peptides and increase receptor subtype selectivity. This technique has been applied here to the superpotent but non-selective cyclic peptide MT-II. A library of all possible 31 backbone N-methylated derivatives has been synthesized and tested for binding and activation at melanocortin receptor subtypes 1, 3, 4 and 5. It turned out that selectivity is improved with every introduced N-methyl group, resulting in several N-methylated selective and potent agonists for the hMC1R. The most potent of these derivatives is N-methylated on four out of five amide bonds in the cyclic structure. Its solution structure indicates a strongly preferred backbone conformation which resembles other a-MSH analogs but possesses much less flexibility and in addition distinct differences in the spatial arrangement of individual amino acid side chains. PMID:20496895

Doedens, Lucas; Opperer, Florian; Cai, Minying; Beck, Johannes G.; Dedek, Matt; Palmer, Erin; Hruby, Victor J.; Kessler, Horst

2010-01-01

404

¹H, ¹³C and ¹?N backbone resonance assignments of the monomeric human M-ficolin fibrinogen-like domain secreted by Brevibacillus choshinensis.  

PubMed

M-ficolin, which forms trimer-based multimers, is a pathogen-recognition protein in the innate immune system, and it binds to ligands through its fibrinogen-like (FBG) domain. As the first step toward the elucidation of the molecular basis for pathogen-recognition by the M-ficolin multimers, we assigned the backbone resonances of the monomeric mutant of the M-ficolin FBG domain, recombinantly expressed by Brevibacillus choshinensis. Like the wild-type trimeric FBG domain, the monomeric FBG domain also requires His251, His284 and His297 for the ligand-binding activity, as judged by mutational analyses using zonal affinity chromatography. The secondary structure predicted by the backbone resonance assignments is similar to that of the trimeric FBG domain in the crystal, indicating that the monomeric FBG domain is folded correctly to perform its function. PMID:23708873

Tanio, Michikazu; Kusunoki, Hideki; Kohno, Toshiyuki

2014-04-01

405

Effect of a neutralized phosphate backbone on the minor groove of B-DNA: molecular dynamics simulation studies  

Microsoft Academic Search

Alternative models have been presented to provide explanations for the sequence-dependent variation of the DNA minor groove width. In a structural model groove narrowing in A-tracts results from direct, short-range interactions among DNA bases. In an electrostatic model, the narrow minor groove of A-tracts is proposed to respond to sequence- dependent localization of water and cations. Molecular dynamics simulations on

Donald Hamelberg; Loren Dean Williams; W. David Wilson

2002-01-01

406

Small Angle Neutron Scattering Study of Conformation of Oligo(ethylene glycol) Grafted Polystyrene in Dilute Solutions: Effect of the Backbone Length  

SciTech Connect

The conformation and clusterization of comb like polymers of polystyrene densely grafted with oligo(ethylene glycol) (OEG) side chains in 1.0 wt% solutions of D2O, toluene-d8 and methanol-d4 was investigated as a function of the degree of polymerization (DP) of the backbone by small angle neutron scattering (SANS). Each side chain had four EG repeat units and the DP of the polystyrene backbone was varied from 8 to 85. The global conformation of the polymers in toluene and methanol was shown to assume ellipsoidal, cylindrical or worm-like chain morphologies with increasing DP of the polystyrene backbone. At the same time, in D2O, the polymer conformation was described by the form factor of rigid cylinders. The second viral coefficient was measured for the polymer with a DP of 85 in all three solvents and the solvent quality of toluene, methanol and D2O was identified as good, marginal and poor for this polymer. Due to a poor solvent quality, the PS backbone (DP = 85) is partially collapsed in D2O whereas it is moderately expanded in toluene and methanol. Polymers with the DP of 8 were found to aggregate into clusters in all three solvents, with the characteristic size between 100 and 200 ?and a fractal dimension of 2. With increase of the DP, the clusters diminished in D2O and completely disappeared in toluene and methanol. This observation suggests that the clusterization of these short side-chain polymers is caused by end group and hydrogen bonding interactions between different chains.

Cheng, Gang [ORNL; Hong, Kunlun [ORNL; Hua, Fengjun [ORNL; Melnichenko, Yuri B [ORNL; Wignall, George D [ORNL; Mays, Jimmy [ORNL

2008-01-01

407

The role of backbone conformational heat capacity in protein stability: Temperature dependent dynamics of the B1 domain of Streptococcal protein G  

Microsoft Academic Search

The contributions of backbone NH group dynamics to the conformational heat capacity of the B1 domain of Strepto- coccal protein G have been estimated from the temperature dependence of 15N NMR-derived order parameters. Longitudinal ~R1! and transverse ~R2! relaxation rates, transverse cross-relaxation rates ~hxy!, and steady state $1H% -15N nuclear Overhauser effects were measured at temperatures of 0, 10, 20,

Michael J. Seewald; Kumar Pichumani; Cheri Stowell; Benjamin V. Tibbals; Lynne Regan; Martin J. Stone

2000-01-01

408

Synthesis and characterization of a novel kind soluble, conjugated, and fluorescent chelate polymer containing fluorene ring in the backbone: Optical, electrical, and electrochemical properties  

Microsoft Academic Search

A novel highly soluble coordination polymer, poly(3,4-HBA-Cr-FDA), containing Cr(III) ion in the backbone was synthesized. Monomeric model compounds (MC-1 and MC-2) were also synthesized as the comparison materials. The structures were characterized by FT-IR, UV–vis, 1H and 13C NMR, and size exclusion chromatography (SEC). SEC results showed that the novel polymer had 65–68 repeated units. ICP-AES was used to determine

Mehmet Y?ld?r?m; ?smet Kaya

2011-01-01

409

Bismuth-catalyzed synthesis of polycyclic aromatic hydrocarbons (PAHs) with a phenanthrene backbone via cyclization and aromatization of 2-(2-arylphenyl)vinyl ethers.  

PubMed

The reaction of 2-(2-arylphenyl)vinyl ethers in the presence of a catalytic amount of bismuth(III) triflate gave substituted phenanthrenes in excellent yields under mild reaction conditions. The reaction was also applied to the construction of other polycyclic aromatic hydrocarbons (PAHs), such as chrysene, helicene, and pyrene having a phenanthrene backbone, via regioselective cyclization. This method has the advantages of easy availability of the cyclization precursors, operational simplicity, and high reaction efficiency. PMID:25076204

Murai, Masahito; Hosokawa, Naoki; Roy, David; Takai, Kazuhiko

2014-08-15

410

Assignment of the backbone sup 1 H and sup 15 N NMR resonances of bacteriophage T4 lysozyme  

SciTech Connect

The proton and nitrogen ({sup 15}NH-H{sup {alpha}}-H{sup {beta}}) resonances of bacteriophage T4 lysozyme were assigned by {sup 15}N-aided {sup 1}H NMR. The assignments were directed from the backbone amide {sup 1}H-{sup 15}N nuclei, with the heteronuclear single-multiple-quantum coherence (HSMQC) spectrum of uniformly {sup 15}N enriched pro