bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution structure of hypothetical nudix hydrolase DR0079 from extremely radiation‐resistant Deinococcus radiodurans bacterium
Authors: Buchko Garry W. , Ni Shuisong , Holbrook Stephen R. , Kennedy Michael A. 
Published: April 2004

AbstractUsing nuclear magnetic resonance (NMR) based methods, including residual dipolar coupling restraints, we have determined the solution structure of the hypothetical Deinococcus radiodurans Nudix protein DR0079 (171 residues, MW = 19.3 kDa). The protein contains eight β‐strands and three α‐helices organized into three subdomains: an N‐terminal β‐sheet (1–34), a central Nudix core (35–140), and a C‐terminal helix‐turn‐helix (141–171). The Nudix core and the C‐terminal helix‐turn‐helix form the fundamental fold common to the Nudix family, a large mixed β‐sheet sandwiched between α‐helices. The residues that compose the signature Nudix sequence, GX5EX7REUXEEXGU (where U = I, L, or V and X = any amino acid), are contained in a turn‐helix‐turn motif on the face of the mixed β‐sheet. Chemical shift mapping experiments suggest that DR0079 binds Mg2+. Experiments designed to determine the biological function of the protein indicate that it is not a type I isopentenyl‐diphosphate δ‐isomerase and that it does not bind α,β‐methyleneadenosine 5′‐triphosphate (AMPCPP) or guanosine 5′‐[β,γ‐imido]triphosphate (GMPPNP). In this article, the structure of DR0079 is compared to other known Nudix protein structures, a potential substrate‐binding surface is proposed, and its possible biological function is discussed. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Modeling effects of mutations in coiled‐coil structures: Case study using epidermolysis bullosa simplex mutations in segment 1a of k5/k14 intermediate filaments
Authors: Smith Thomasin A. , Steinert Peter M. , Parry David A.D. 
Published: April 2004

AbstractThe sequence of a protein chain determines both its conformation and its function in vivo. An attempt is made to gain an understanding of the classes of deformations that can arise in an important structural motif, the α‐helical coiled coil, as a consequence of mutations occurring in its underlying heptad substructure. In order to do so we consider the model structure of segment 1A in intermediate filaments and then investigate the structures arising from each of the 22 mutations observed in cytokeratin K5/K14 molecules that lead to variants of epidermolysis bullosa simplex. These are refined separately using a molecular dynamics protocol. The mutations often result in a significant distortion of the backbone over a turn or so of the α helix in either the chain itself or its constituent partner, leading to the likelihood of impaired chain aggregation and hence molecular assembly. One mutant (K14‐L143P; 1A‐28) gave rise to structural distortion along almost the entire length of segment 1A. The remaining structures showed less deformation, and normal‐looking intermediate filaments are likely in vivo. In addition, an identical mutation in the same position in each of the chains in the heterodimer did not necessarily give equivalent structural distortions. Although proline mutations frequently lead to the most severe structural deformations, a non‐proline substitution (K14‐R125S; 1A‐10) gave rise to the largest local structural disruption that was observed. Unexpectedly, mutations in positions a and d were not always of the greatest structural significance, although three in position a were shown by AGADIR to result in a significant increase in α‐helix stability. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Importance of hydrophobic cluster formation through long‐range contacts in the folding transition state of two‐state proteins
Authors: Selvaraj S. , Gromiha M. Michael 
Published: April 2004

AbstractUnderstanding the folding pathways of proteins is a challenging task. The Φ value approach provides a detailed understanding of transition‐state structures of folded proteins. In this work, we have computed the hydrophobicity associated with each residue in the folded state of 16 two‐state proteins and compared the Φ values of each mutant residue. We found that most of the residues with high Φ value coincide with local maximum in surrounding hydrophobicity, or have nearby residues that show such maximum in hydrophobicity, indicating the importance of hydrophobic interactions in the transition state. We have tested our approach to different structural classes of proteins, such as α‐helical, SH3 domains of all‐β proteins, β‐sandwich, and α/β proteins, and we observed a good agreement with experimental results. Further, we have proposed a hydrophobic contact network pattern to relate the Φ values with long‐range contacts, which will be helpful to understand the transition‐state structures of folded proteins. The present approach could be used to identify potential hydrophobic clusters that may form through long‐range contacts during the transition state. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Pex5p binding affinities for canonical and noncanonical PTS1 peptides
Authors: Maynard Ernest L. , Gatto Gregory J. , Berg Jeremy M. 
Published: April 2004

AbstractThe majority of proteins targeted to the peroxisomal lumen contain a C‐terminal peroxisomal targeting signal‐1 (PTS1) that is bound by the peroxin Pex5p. The PTS1 is generally regarded as a C‐terminal tripeptide that adheres to the consensus (S/A/C)(K/R/H)(L/M). Previously, we studied the binding affinity of peptides of the form YQX(‐3)X(‐2)X(‐1) to the peptide‐binding domain of human Pex5p (referred to as Pex5p‐C). Optimal affinity was found for YQSKL, which bound with an affinity of 200 ± 40 nM. To extend this work, we investigated the properties of a peptide containing the last 9 residues of acyl‐CoA oxidase (RHYLKPLQSKL) and discovered that it binds to Pex5p‐C with a dissociation constant of 1.4 ± 0.4 nM, 180 times tighter than YQSKL. Further analysis revealed that the enhanced affinity is primarily due to the presence of leucine in the (‐5) position. In addition, a peptide corresponding to the luciferase C‐terminus (YKGGKSKL) was found to bind Pex5p‐C about 20 times tighter than YQSKL. The majority of this effect results from having lysine in position (‐4). Catalase contains a noncanonical PTS1 (‐AREKANL). The affinity of YQANL was found to be 3600 ± 400 nM. This relatively weak binding is consistent with previous unsuccessful attempts to direct chloramphenicol acetyltransferase to the peroxisome by fusing ‐ANL to its C‐terminus (‐GGA‐ANL). The peptides YKANL, YEKANL, YREKANL, and YAREKANL all bound Pex5p‐C with higher affinities than did YQANL, but the affinities are still lower than peptides that correspond to functional targeting signals in other contexts. Because both catalase and Pex5p are tetramers (as opposed to the monomeric Pex5p‐C and the peptides used in our studies), multidentate effects on binding affinity between Pex5p and other oligomeric proteins should be considered. Our study provides direct thermodynamic data revealing that peptide binding to Pex5p‐C binding is favored by lysine in the (‐4) position and leucine in the (‐5) position. Our results suggest that peptides or proteins with optimized residues in the (‐4) and/or (‐5) positions can bind to Pex5p with affinities that are at least two orders of magnitude greater than that of YQSKL, and that this stabilization can compensates for otherwise weakly binding PTS1s. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Solution structure of BmKK2, a new potassium channel blocker from the venom of chinese scorpion Buthus martensi Karsch
Authors: Zhang Naixia , Li Minghua , Chen Xiang , Wang Yuefeng , Wu Gong , Hu Guoyuan , Wu Houming 
Published: April 2004

AbstractA natural K+ channel blocker, BmKK2 (a member of scorpion toxin subfamily α‐KTx 14), which is composed of 31 amino acid residues and purified from the venom of the Chinese scorpion Buthus martensi Karsch, was characterized using whole‐cell patch‐clamp recording in rat hippocampal neurons. The three dimensional structure of BmKK2 was determined with two‐dimensional NMR spectroscopy and molecular modelling techniques. In solution this toxin adopted a common α/β‐motif, but showed distinct local conformation in the loop between α‐helix and β‐sheet in comparison with typical short‐chain scorpion toxins (e.g., CTX and NTX). Also, the α helix is shorter and the β‐sheet element is smaller (each strand consisted only two residues). The unusual structural feature of BmKK2 was attributed to the shorter loop between the α‐helix and β‐sheet and the presence of two consecutive Pro residues at position 21 and 22 in the loop. Moreover, two models of BmKK2/hKv1.3 channel and BmKK2/rSK2 channel complexes were simulated with docking calculations. The results demonstrated the existence of a α‐mode binding between the toxin and the channels. The model of BmKK2/rSK2 channel complex exhibited favorable contacts both in electrostatic and hydrophobic, including a network of five hydrogen bonds and bigger interface containing seven pairs of inter‐residue interactions. In contrast, the model of BmKK2/hKv1.3 channel complex, containing only three pairs of inter‐residue interactions, exhibited poor contacts and smaller interface. The results well explained its lower activity towards Kv channel, and predicted that it may prefer a type of SK channel with a narrower entryway as its specific receptor. Proteins 2004. © 2004 Wiley‐Liss, Inc.
A 4.2 kDa synthetic peptide as a potential probe to evaluate the antibacterial activity of coumarin drugs
Authors: Scatigno Andreza C. , Garrido Saulo S. , Marchetto Reinaldo 
Published: April 2004

AbstractThe coumarin antibiotics are potent inhibitors of DNA replication whose target is the enzyme DNA gyrase, an ATP‐dependent bacterial type II topoisomerase. The coumarin drugs inhibit gyrase action by competitive binding to the ATP‐binding site of DNA gyrase B protein. The production of new biologically active products has stimulated additional studies on coumarin–gyrase interactions. In this regard, a 4.2 kDa peptide mimic of DNA gyrase B protein from Escherichia coli has been designed and synthesized. The peptide sequence includes the natural fragment 131–146 (coumarin resistance‐determining region) and a segment containing the gyrase–DNA interaction region (positions 753–770). The peptide mimic binds to novobiocin (Ka = 1.4 ± 0.3 × 105 M−1), plasmid (Ka = 1.6 ± 0.5 × 106 M−1) and ATP (Ka = 1.9 ± 0.4 × 103 M−1), results previously found with the intact B protein. On the other hand, the binding to novobiocin was reduced when a mutation of Arg‐136 to Leu‐136 was introduced, a change previously found in the DNA gyrase B protein from several coumarin‐resistant clinical isolates of Escherichia coli. In contrast, the binding to plasmid and to ATP was not altered. These results suggest that synthetic peptides designed in a similar way to that described here could be used as mimics of DNA gyrase in studies which seek a better understanding of the ATP, as well as coumarin, binding to the gyrase and also the mechanism of action of this class of antibacterial drugs. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
[D‐Ala2]‐deltorphin I peptoid and retropeptoid analogues: synthesis, biological activity and conformational investigations
Authors: Biondi Laura , Giannini Elisa , Filira Fernando , Gobbo Marina , Negri Lucia , Rocchi Raniero 
Published: April 2004

AbstractThe synthesis is described of a [D‐Ala2]‐deltorphin I peptoid analogue in which all amino acid residues have been substituted by the corresponding N‐alkylglycine residues. The [D‐Ala2]‐deltorphin I retropeptoid was also prepared as well as [Ala1,D‐Ala2]‐deltorphin 1 and the corresponding peptoid. Structural investigations by FT‐IR and fluorescence measurements were carried out on the synthetic analogues and on some [D‐Ala2]‐deltorphin 1 peptide–peptoid hybrids previously prepared. According to the fluorescence measurements the distance between the aromatic residues in the deltorphin I peptoid and retropeptoid is similar to that suggested for the δ‐ and µ‐opioids, respectively. Measurements of CD in the presence of β‐cyclodextrin, and some preliminary pharmacological experiments were also performed. No dichroic bands are present in the spectrum of the [Ntyr1,D‐Ala2]‐deltorphin I, but an increasing dichroic effect appears in the spectra of both the deltorphin I peptoid and retropeptoid. Activity tests on isolated organ preparations showed that the modifications made produced a dramatic decrease in the agonistic activity of the synthetic derivatives. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Development of a liquid extraction method and comparison with dynamic thermal stripping–thermal desorption (DTS–TD) method: sorption of D‐limonene by flexible packaging films
Authors: Caner Cengiz 
Published: March 2004

AbstractThe sorption of D‐limonene into polymeric structures in contact with food simulant liquids (ethanol and acetic acid solutions) was determined using two methods, liquid extraction (LE) and dynamic thermal stripping–thermal desorption (DTS–TD). The polymeric films studied were PP (polypropylene), PE/nylon/EVOH/PE (polyethylene/nylon/ethylene vinyl alcohol/polyethylene) and metPET/VA EVA/LLDPE (metallized polyethylene terephthalate/ethylenevinyl acetate/linear low density polyethylene). Our assessment showed that both LE and DTS–TD techniques are valuable procedures. LE was evaluated as an alternative method with the advantage of being a simplified process. It was possible to measure the amount of D‐limonene in the polymers using both methods. Correlation between methods was >82% and for the single layer polymers >92%. The respective sorption values obtained by the two methods were also found to be in good agreement. LE is simple and rapid to perform and, in general, gives slightly lower results compared to DTS–TS sorption tests conducted with adequate food simulants. The results indicate that the liquid extraction method is an excellent technique for the determination of sorbate concentration in polymeric structures. Copyright © 2004 John Wiley & Sons, Ltd.
Operating Characteristic Curves for the Exponential Bayes‐Truncated Test
Authors: Wang Fu‐Kwun , Keats J. Bert 
Published: April 2004

AbstractOperating characteristic (OC) curves are often useful in determining how large a sample is required to detect a specified difference for a particular consumer and producer risk. In this paper, OC curves with Bayes stopping rules for the exponential distribution are developed. Example curves are provided for the sequential and batch testing situations. The power of the test is greater under batch testing. A table illustrates the performance of the plans for stopping at each opportunity in a sample of size 20. Some examples are used to demonstrate the application of the proposed methodology. Copyright © 2004 John Wiley & Sons, Ltd.
Libra: a computational economy‐based job scheduling system for clusters
Authors: Sherwani Jahanzeb , Ali Nosheen , Lotia Nausheen , Hayat Zahra , Buyya Rajkumar 
Published: April 2004

AbstractClusters of computers have emerged as mainstream parallel and distributed platforms for high‐performance, high‐throughput and high‐availability computing. To enable effective resource management on clusters, numerous cluster management systems and schedulers have been designed. However, their focus has essentially been on maximizing CPU performance, but not on improving the value of utility delivered to the user and quality of services. This paper presents a new computational economy driven scheduling system called Libra, which has been designed to support allocation of resources based on the users' quality of service requirements. It is intended to work as an add‐on to the existing queuing and resource management system. The first version has been implemented as a plugin scheduler to the Portable Batch System. The scheduler offers market‐based economy driven service for managing batch jobs on clusters by scheduling CPU time according to user‐perceived value (utility), determined by their budget and deadline rather than system performance considerations. The Libra scheduler has been simulated using the GridSim toolkit to carry out a detailed performance analysis. Results show that the deadline and budget based proportional resource allocation strategy improves the utility of the system and user satisfaction as compared with system‐centric scheduling strategies. Copyright © 2004 John Wiley & Sons, Ltd.
Common subgraph isomorphism detection by backtracking search
Authors: Krissinel Evgeny B. , Henrick Kim 
Published: April 2004

AbstractGraph theory offers a convenient and highly attractive approach to various tasks of pattern recognition. Provided there is a graph representation of the object in question (e.g. a chemical structure or protein fold), the recognition procedure is reduced to the problem of common subgraph isomorphism (CSI). Complexity of this problem shows combinatorial dependence on the size of input graphs, which in many practical cases makes the approach computationally intractable. Among the optimal algorithms for CSI, the leading place in practice belongs to algorithms based on maximal clique detection in the association graph. Backtracking algorithms for CSI, first developed two decades ago, are rarely used. We propose an improved backtracking algorithm for CSI, which differs from its predecessors by better search strategy and is therefore more efficient. We found that the new algorithm outperforms the traditional maximal clique approach by orders of magnitude in computational time. Copyright © 2004 John Wiley & Sons, Ltd.
Developmental regulation of connexins 26, 32, 36, and 43 in trigeminal neurons
Authors: Honma Shiho , De Shampa , Li Daniel , Shuler Charles F. , Turman Jack E. 
Published: April 2004

AbstractThe transition from sucking to chewing during postnatal development is accompanied by changes in masticatory muscle activity patterns. We previously demonstrated that changes in numerous parameters of chemical synapses among neurons, and intrinsic membrane properties of neurons, comprising brainstem oral‐motor circuits are coincident with changes in masticatory muscle activity patterns. Considering recent findings that implicate a role for gap junctions in early locomotor and respiratory behaviors, our present study focuses on the developmental regulation of connexin proteins in trigeminal neurons as a first step in understanding a role for gap junctions in developing oral‐motor circuits used for ingestive behaviors. We conducted immunohistochemistry studies to examine connexin (Cx) 26, 32, 36, and 43 expression in trigeminal motor and mesencephalic trigeminal nuclei during postnatal development at the light and electron microscopic levels. Postnatal days (P) 1, 6, 14, 21, and adult mice were used. Cx32, 36, and 43 expression was developmentally regulated in the trigeminal motor nucleus, while Cx26 expression remained high throughout postnatal development. In the mesencephalic trigeminal nucleus, Cx26, 32, and 43 expression was intense throughout development, with only Cx36 showing a developmental regulation. Ultrastructural examination of neonatal trigeminal motoneurons and mesencephalic trigeminal neurons revealed connexin expression in cell membranes, cytoplasm, and cell nuclei (Cx43, Cx32). Our results show that connexin proteins are differentially regulated between trigeminal motoneurons and mesencephalic trigeminal neurons during development, and suggest a possible role for gap junctions in the development of trigeminal neurons and the function and maturation of oral‐motor circuits. Synapse 52:258–271, 2004. © 2004 Wiley‐Liss, Inc.
Ultrastructural interactions between terminals expressing the norepinephrine transporter and dopamine neurons in the rat and monkey ventral tegmental area
Authors: Liprando Lindsay A. , Miner Leeann H. , Blakely Randy D. , Lewis David A. , Sesack Susan R. 
Published: April 2004

AbstractThe norepinephrine (NE) system is implicated in the etiology and treatment of depression and drugs blocking the NE transporter (NET) are effective antidepressants. It is possible that dopamine (DA) also plays a role in depression and the action of antidepressant drugs, although the mechanisms whereby NE and DA interact have not been fully elaborated. We examined whether NE neurons might alter DA transmission via synaptic projections to cells in the ventral tegmental area (VTA) by using electron microscopic dual labeling immunocytochemistry in the rat and monkey. NET was used as a marker for NE axons, whereas the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), served as a label for DA neurons. We observed three types of spatial relationships between these profiles that were similar in type but varied in frequency between rodent and primate. The most common arrangement involved nonsynaptic appositions between NET‐immunoreactive (‐ir) axons and TH‐ir dendrites. Such relationships may facilitate extrasynaptic actions of NE on DA cell activity. The other commonly observed arrangement involved adjacent profiles that were otherwise separated by glia. These relationships may represent regions where NE is prevented from reaching DA cells. In only a few cases were synapses observed between NET‐ir axons and TH‐ir dendrites. This finding suggests that NE can synaptically regulate DA neurons, although functional interactions are more likely to involve extrasynaptic mechanisms. Finally, in the VTA of both species the majority of NET‐ir axons exhibited no detectable TH immunoreactivity. The latter finding agrees with observations in cortical regions and represents the first report of its type in a subcortical structure. Synapse 52:233–244, 2004. © 2004 Wiley‐Liss, Inc.
Comparison of unreamed nailing and external fixation of tibial diastases—mechanical conditions during healing and biological outcome
Authors: Klein P. , Opitz M. , Schell H. , Taylor W. R. , Heller M. O. , Kassi J.‐P. , Kandziora F. , Duda G. N. 
Published: April 2004

AbstractLocked intramedullary nailing and external fixation are alternatives for the stabilization of tibial shaft fractures. The goal of this study was to determine to what extent the mechanical conditions at the fracture site influence the healing process after unreamed tibial nailing compared to external fixation. A standardized tibial diastasis was stabilized with either a locked unreamed tibial nail or a monolateral fixator in a sheep model. Interfragmentary movements and ground reaction parameters were monitored in vivo throughout the healing period. After sacrifice, the tibiae were examined mechanically and histologically. Bending angles and axial torsion at the fracture site were larger in the nail group within the first five weeks post‐operatively. Unlike the fixator group, the operated limb in the nail group did not return to full weight bearing during the treatment period. Mechanical and histomorphometrical observations showed significantly inferior bone healing in the nail group compared to the fixator group. In this study, unreamed nailing of a tibial diastasis did not provide rotational stability of the osteosynthesis and resulted in a significant delay in bone healing. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
THEORIZING AMERICA
Authors: RODGERS DANIEL T. 
Published: April 2004

James E. Block, A Nation of Agents: The American Path to a Modern Self and Society (Cambridge, MA: Belknap Press of Harvard University Press, 2002)Sheldon S. Wolin, Tocqueville Between Two Worlds: The Making of a Political and Theoretical Life (Princeton, NJ: Princeton University Press, 2001)