bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of multidrug resistance in cancer cells by the E3 ubiquitin ligase seven‐in‐absentia homologue 1
Authors: Liu M , Aneja R , Wang H , Sun L , Dong X , Huo L , Joshi HC , Zhou J 
Published: January 2008

AbstractSeven‐in‐absentia homologue 1 (Siah1) is an E3 ubiquitin ligase that regulates the ubiquitination and proteasome‐dependent degradation of a number of proteins. Here we report that Siah1 modulates multidrug resistance 1 (MDR1)/P‐glycoprotein‐mediated drug resistance in the cancer cell lines examined. Siah1, but not its ligase‐dead mutant, down‐regulates MDR1/P‐glycoprotein and sensitizes the multidrug‐resistant cells to chemotherapeutic agents. Mechanistically, Siah1 does not promote P‐glycoprotein degradation but decreases its expression transcriptionally by promoting c‐Jun transcription factor binding to the activator protein 1 (AP1) site in the MDR1 promoter. Moreover, Siah1 triggers c‐Jun NH2‐terminal kinase (JNK) activation, leading to enhanced phosphorylation of c‐Jun, and the JNK/c‐Jun signalling axis is critical for Siah1 to down‐regulate MDR1/P‐glycoprotein expression. These findings demonstrate a previously unidentified role for Siah1 in regulating MDR1/P‐glycoprotein expression through the JNK/c‐Jun pathway. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Using prescription registries to define continuous drug use: how to fill gaps between prescriptions
Authors: Nielsen Lars Hougaard , Løkkegaard Ellen , Andreasen Anne Helms , Keiding Niels 
Published: January 2008

AbstractPharmacoepidemiological studies often use prescription registries to assess patients' drug episodes. The databases usually provide information on the date of the redemption of the prescription as well as on the dispensed amount, and this allows us to define episodes of drug use. However, when patients take less medication than prescribed, apparent gaps between prescriptions occur, and most studies handle this issue by allowing for small gaps when defining continuous drug use. This paper argues that it becomes crucial whether gaps are ‘filled’ prospectively or retrospectively. In the latter case the inferred exposure status depends on the patient's future dispensing behaviour and this can lead to severe bias in the findings of the study. In this paper we investigate this potential bias in a study of the risk of acute myocardial infarction (AMI) for women using hormone therapy (HT), and we show that the retrospective exposure definition introduces an artificially protective effect of HT. Copyright © 2008 John Wiley & Sons, Ltd.
Population‐based study of the effectiveness of bone‐specific drugs in reducing the risk of osteoporotic fracture
Authors: Perreault Sylvie , Dragomir Alice , Blais Lucie , Moride Yola , Rossignol Michel , Ste‐Marie Louis‐Georges , Fernandès Julio Cesar 
Published: January 2008

AbstractAimEvidence supports bone‐specific drugs (BSDs) efficacy in the fracture risk reduction. But treatment rates for osteoporosis among high‐risk patients are far below the recommended guidelines. A major concern about BSDs is the lack of adherence with treatment.ObjectiveTo determine if BSDs decrease fracture risk in high‐risk elderly women in real clinical setting.MethodsA nested case‐control design was used in a cohort of elderly women from the Quebec health databases. Women enter into the cohort if they are 70 years or older between 1995 and 2003. Nested case‐controls were designed for women with a diagnosis of osteoporosis (OP) and for those with a prior fracture. All cases of fractures occurring during follow‐up were matched with 10 randomly selected controls based on age, time period, bone mass density testing, and having a diagnosis of OP or a prior fracture. Use of BSDs before the index date was categorized as follows: short‐term (≤1 year), intermediate‐term (>1 and ≤ 3 years), and long‐term (>3 years). We used an adjusted conditional logistic regression model to assess BSD effect on fracture.ResultsAmong 3170 women who had a fracture, of these women, 1824 had OP and 1346 had a prior fracture. Only long‐term exposure to BSDs among women with OP reduced the fracture risk by 16% (odds ratio: 0.84; 0.73–0.97). Among women with OP, a high number of medical services or use of anticonvulsants or narcotics increased the fracture risk by 12–73%. Among women with a prior fracture, a high number of medical services or risk of fall or use of benzodiazepines, antidepressants, or narcotics increased the fracture risk by 23–77%.ConclusionThe incidence of fractures decreased by 16% among women with OP when more than 80% of BSDs was used for at least 3 years. Among women with a prior fracture, fracture risk reduction was not significant. Exposure to BSDs among women with a prior fracture is troubling, given that only approximately 12% of these individuals were being treated, and only 2% was using BSDs for the long term. Copyright © 2008 John Wiley & Sons, Ltd.
Terminal proteomics: N‐ and C‐terminal analyses for high‐fidelity identification of proteins using MS
Authors: Nakazawa Takashi , Yamaguchi Minoru , Okamura Taka‐aki , Ando Eiji , Nishimura Osamu , Tsunasawa Susumu 
Published: January 2008

AbstractIn proteomics, MS plays an essential role in identifying and quantifying proteins. To characterize mature target proteins from living cells, candidate proteins are often analyzed with PMF and MS/MS ion search methods in combination with computational search routines based on bioinformatics. In contrast to shotgun proteomics, which is widely used to identify proteins, proteomics based on the analysis of N‐ and C‐terminal amino acid sequences (terminal proteomics) should render higher fidelity results because of the high information content of terminal sequence and potentially high throughput of the method not requiring very high sequence coverage to be achieved by extensive sequencing. In line with this expectation, we review recent advances in methods for N‐ and C‐terminal amino acid sequencing of proteins. This review focuses mainly on the methods of N‐ and C‐terminal analyses based on MALDI‐TOF MS for its easy accessibility, with several complementary approaches using LC/MS/MS. We also describe problems associated with MS and possible remedies, including chemical and enzymatic procedures to enhance the fidelity of these methods.
Retracted: Mitochondria, the missing link between body and soul: Proteomic prospective evidence
Authors: Warda Mohamad , Han Jin 
Published: January 2008

AbstractRetraction: The following article from the journal PROTEOMICS, 'Mitochondria, the missing link between body and soul: Proteomic perspective evidence' by Mohamad Warda and Jin Han, published online on 23 January 2008 in Wiley InterScience (www.interscience.wiley.com), has been retracted by agreement between the authors, the journal Editor‐in‐Chief, Michael J. Dunn and the publisher Wiley‐VCH. The retraction has been agreed due a substantial overlap of the content of this article with previously published articles in other journals.PROTEOMICS apologizes to our readership.
The role of IL‐6 and IL‐11 in hyperoxic injury in developing lung
Authors: Chetty Anne , Cao Gong‐Jee , Manzo Nicholas , Nielsen Heber C , Waxman Aaron 
Published: January 2008

AbstractWe examined the cytoprotective effect of interleukin‐6 (IL‐6) and interleukin‐11 (IL‐11) during oxidant injury in neonatal lung and the regulators of cell death in vitro and in vivo after oxidant exposure. Type II cells from day 21 fetal neonatal rat lungs were treated with varying concentrations of either IL‐6 or IL‐11 for 24 hr prior to exposure to H2O2. Three‐day‐old transgenic lung‐specific IL‐11 and IL‐6 overexpressing and wild type (WT) mouse pups were exposed to hyperoxia or room air for 3 days. Type II cells exposed to either IL‐6 or IL‐11 prior to oxidant injury exhibited improved survival compared to controls, 67% ± 2.6 survivals in IL‐6 pretreated cells compared to 48% ± 1.6 in control; 63% ± 3 survivals in IL‐11 pretreated cells compared to 49% ± 2.6 in control. The number of TUNEL positive cells in hyperoxia‐exposed lungs was increased compared to room air animals (27 ± 0.9 vs. 4 ± 0.4; mean ± SEM; P < 0.05). In contrast, the number of TUNEL positive cells was reduced in hyperoxia‐exposed lungs from IL‐11 (+) mice (15.2 ± 2.2; mean ± SEM; P < 0.05). There was an enhanced accumulation of Bcl‐2 and reduction of Bax protein in hyperoxia‐exposed IL‐11 (+) compared to room air‐exposed mice. This was not seen in hyperoxia‐exposed IL‐6 (+) pups. An increase in caspase‐3 was seen in hyperoxia‐exposed lungs of WT pups compared to IL‐11 (+) pups. IL‐11 and IL‐6 provide protective effects against oxidant‐mediated injury in fetal type II cells and IL‐11 provides protection in vivo by down‐regulation of caspase‐mediated cell death. Pediatr Pulmonol. 2008; 43:297–304. © 2008 Wiley‐Liss, Inc.
Helix formation is a dynamical bottleneck in the recovery reaction of Photoactive Yellow Protein
Authors: Vreede Jocelyne , Hellingwerf Klaas J. , Bolhuis Peter G. 
Published: January 2008

AbstractThe bacterial sensor Photoactive Yellow Protein (PYP) signals the presence of blue light by undergoing a series of conformational changes. We present atomistic Parallel Tempering (Replica Exchange Molecular Dynamics) simulations of conformational changes occurring during the photo‐cycle of PYP. First, we study the signaling state formation of PYP in detail. Our previous simulations have shown that the formation of the signaling state is characterized by the solvent exposure of both the chromophore and Glu46 (Vreede J, Crielaard W, Hellingwerf KJ, Bolhuis PG. Biophys J, 2005;8:3525–3535). Subsequent NMR results agreed with this prediction, but as these experiments were performed on an N‐terminally truncated mutant, a simulation of this mutant would further substantiate our previous results. Here, we compare simulations of the truncated PYP to the NMR structures, as well as to the wild type predictions. This comparison also gives some insight into the role of the N‐terminal domain of PYP, which restricts the movement of the chromophore binding pocket (CBP) in the wild type. Second, we report simulations of the recovery of the receptor state from the signaling state. While we did not observe complete refolding of the protein, we did observe transient interactions between residues of the CBP occurring when the chromophore is in a trans configuration. Using simulations that sample anomalous exposure of the chromophore in the receptor state, we were able to sample chromophore re‐entry into its binding pocket. While the involved time scales prohibit drawing definitive conclusions even when using parallel tempering, we nevertheless propose that the formation of a helix in the CBP is essential for a successful recovery of the receptor state, and forms a kinetic barrier in this process. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Analysis and prediction of protein local structure based on structure alphabets
Authors: Dong Qiwen , Wang Xiaolong , Lin Lei , Wang Yadong 
Published: January 2008

AbstractIn recent years, protein structure prediction using local structure information has made great progress. Many fragment libraries or structure alphabets have been developed. In this study, the entropies and correlations of local structures are first calculated. The results show that neighboring local structures are strongly correlated. Then, a dual‐layer model has been designed for protein local structure prediction. The position‐specific score matrix, generated by PSI‐BLAST, is inputted to the first‐layer classifier, whose output is further enhanced by a second‐layer classifier. The neural network is selected as the classifier. Two structure alphabets are explored, which are represented in Cartesian coordinate space and in torsion angles space respectively. Testing on the nonredundant dataset shows that the dual‐layer model is an efficient method for protein local structure prediction. TheQ‐scores are 0.456 and 0.585 for the two structure alphabets, which is a significant improvement in comparison with related works. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Computational active site analysis of molecular pathways to improve functional classification of enzymes
Authors: Ozyurt A. Sinem , Selby Thomas L. 
Published: January 2008

AbstractThis study describes a method to computationally assess the function of homologous enzymes through small molecule binding interaction energy. Three experimentally determined X‐ray structures and four enzyme models from ornithine cyclo‐deaminase, alanine dehydrogenase, and mu‐crystallin were used in combination with nine small molecules to derive a function score (FS) for each enzyme‐model combination. While energy values varied for a single molecule‐enzyme combination due to differences in the active sites, we observe that the binding energies for the entire pathway were proportional for each set of small molecules investigated. This proportionality of energies for a reaction pathway appears to be dependent on the amino acids in the active site and their direct interactions with the small molecules, which allows a function score (FS) to be calculated to assess the specificity of each enzyme. Potential of mean force (PMF) calculations were used to obtain the energies, and the resulting FS values demonstrate that a measurement of function may be obtained using differences between these PMF values. Additionally, limitations of this method are discussed based on: (a) larger substrates with significant conformational flexibility; (b) low homology enzymes; and (c) open active sites. This method should be useful in accurately predicting specificity for single enzymes that have multiple steps in their reactions and in high throughput computational methods to accurately annotate uncharacterized proteins based on active site interaction analysis. Proteins 2008. © 2008 Wiley‐Liss, Inc.
The insecticidal protein hirsutellin A from the mite fungal pathogen Hirsutella thompsonii is a ribotoxin
Authors: Herrero‐Galán Elías , Lacadena Javier , Martínez del Pozo Álvaro , Boucias Drion G. , Olmo Nieves , Oñaderra Mercedes , Gavilanes José G. 
Published: January 2008

AbstractThe mite fungal pathogen Hirsutella thompsonii produces a single polypeptide chain, insecticidal protein named hirsutellin A (HtA) that is composed of 130 amino acid residues. This protein has been purified from its natural source and produced as a recombinant protein in Escherichia coli. Spectroscopic analysis has determined that the two protein forms are indistinguishable. HtA specifically inactivates ribosomes and produces the α‐fragment characteristic of ribotoxin activity on rRNA. Behaving as a cyclizing ribonuclease, HtA specifically cleaves oligonucleotides that mimick the sarcin/ricin loop of the ribosome, as well as selected polynucleotides and dinucleosides. HtA interacts with phospholipid membranes as do other ribotoxins. As a consequence of its ribonuclease activity and its ability to interact with cell membranes, HtA exhibits cytotoxic activity on human tumor cells. On the basis of these results, HtA is considered to be a member of the ribotoxin group of proteins, although it is significantly smaller (130 aa) than all known ribotoxins that are composed of 149/150 amino acids. Ribotoxins are members of a larger family of fungal ribonucleases whose members of smaller size (100/110 aa) are not cytotoxic. Thus, the characterization of the fungal ribotoxin HtA represents an important milestone in the study of the diversity and the function of fungal ribonucleases. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Unfolding and aggregation of transthyretin by the truncation of 50 N‐terminal amino acids
Authors: Mizuguchi Mineyuki , Hayashi Ayumi , Takeuchi Makoto , Dobashi Mizuki , Mori Yoshihiro , Shinoda Hiroyuki , Aizawa Tomoyasu , Demura Makoto , Kawano Keiichi 
Published: January 2008

AbstractSenile systemic amyloidosis (SSA) is caused by amyloid deposits of wild‐type transthyretin in various organs. Amyloid deposits from SSA contain large amounts of the C‐terminal fragments starting near amino acid residue 50 as well as full‐length transthyretin. Although a number of previous studies suggest the importance of the C‐terminal fragments in the pathogenesis of SSA, little is known about the structure and aggregation properties of the C‐terminal fragments of transthyretin. To understand the role of C‐terminal fragments in SSA, we examined the effects of the truncation of the N‐terminal portions on the structure and aggregation properties of wild‐type transthyretin. The deletion mutant lacking 50 N‐terminal residues was largely unfolded in terms of secondary and tertiary structure, leading to self‐assembly into spherical aggregations under nearly physiological conditions. By contrast, the deletion mutant lacking 37 N‐terminal residues did not have a strong tendency to aggregate, although it also adopted a largely unfolded conformation. These results suggest that global unfolding of transthyretin by proteolysis near amino acid residue 50 is an important step of self‐assembly into aggregations in SSA. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Acidic range titration of HEWL using a constant‐pH molecular dynamics method
Authors: Machuqueiro Miguel , Baptista António M. 
Published: January 2008

AbstractIn this work, we present the first application to a protein of the stochastic constant‐pH molecular dynamics (MD) method with the inclusion of proton tautomerism. The acidic titration of HEWL was performed under different conditions. Both generalized reaction field (GRF) and particle mesh Ewald (PME) methods were used in the treatment of the long range electrostatics and, even though the PME simulations revealed to be more stable, the better results were obtained using GRF (pKa RMSD of 0.82 for GRF and 1.13 for PME). The results using PME at different dielectric constants (2, 4, and 8) also revealed that there was no significant improvement in pKa's prediction upon increasing the dielectric constant. The secondary structure analysis of HEWL revealed a remarkably stable protein in the acidic pH range. The β‐sheet strands (unlike the α‐helices) seem to be destabilized upon pH decrease, suggesting that the β‐domain is less stable than the α‐domain. The four principal α‐helices were also ordered according to their stability in the acidic pH range and the results (4 < 1 < 2 ≈ 3) were consistent with the ones obtained in thermal denaturation studies. Proteins 2008. © 2008 Wiley‐Liss, Inc.
How to lose a kink and gain a helix: pH independent conformational changes of the fusion domains from influenza hemagglutinin in heterogeneous lipid bilayers
Authors: Jang Hyunbum , Michaud‐Agrawal Naveen , Johnston Jennifer M. , Woolf Thomas B. 
Published: January 2008

AbstractWe have simulated two conformations of the fusion domain of influenza hemagglutinin (HA) within explicit water, salt, and heterogeneous lipid bilayers composed of POPC:POPG (4:1). Each conformation has seven different starting points in which the initial peptide structure is the same for each conformation, but the location across the membrane normal and lipid arrangement around the peptide are varied, giving a combined total simulation time of 140 ns. For the HA5 conformation (primary structure from recent NMR spectroscopy at pH = 5), the peptide exhibits a stable and less kinked structure in the lipid bilayer compared to that from the NMR studies. The relative fusogenic behavior of the different conformations has been investigated by calculation of the relative free energy of insertion into the hydrophobic region of lipid bilayer as a function of the depth of immersion. For the HA7 conformations (primary structure from recent NMR spectroscopy at pH = 7.4), while the N‐terminal helix preserves its initial structure, the flexible C‐terminal chain produces a transient helical motif inside the lipid bilayer. This conformational change is pH‐independent, and is closely related to the peptide insertion into the lipid bilayer. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Prediction of protein local structures and folding fragments based on building‐block library
Authors: Dong Qiwen , Wang Xiaolong , Lin Lei 
Published: January 2008

AbstractIn recent years, protein structure prediction using local structure information has made great progress. In this study, a novel and effective method is developed to predict the local structure and the folding fragments of proteins. First, the proteins with known structures are split into fragments. Second, these fragments, represented by dihedrals, are clustered to produce the building blocks (BBs). Third, an efficient machine learning method is used to predict the local structures of proteins from sequence profiles. Finally, a bi‐gram model, trained by an iterated algorithm, is introduced to simulate the interactions of these BBs. For test proteins, the building‐block lattice is constructed, which contains all the folding fragments of the proteins. The local structures and the optimal fragments are then obtained by the dynamic programming algorithm. The experiment is performed on a subset of the PDB database with sequence identity less than 25%. The results show that the performance of the method is better than the method that uses only sequence information. When multiple paths are returned, the average classification accuracy of local structures is 72.27% and the average prediction accuracy of local structures is 67.72%, which is a significant improvement in comparison with previous studies. The method can predict not only the local structures but also the folding fragments of proteins. This work is helpful for the ab initio protein structure prediction and especially, the understanding of the folding process of proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Method for comparing the structures of protein ligand‐binding sites and application for predicting protein–drug interactions
Authors: Minai Ryoichi , Matsuo Yo , Onuki Hiroyuki , Hirota Hiroshi 
Published: January 2008

AbstractMany drugs, even ones that are designed to act selectively on a target protein, bind unintended proteins. These unintended bindings can explain side effects or indicate additional mechanisms for a drug's medicinal properties. Structural similarity between binding sites is one of the reasons for binding to multiple targets. We developed a method for the structural alignment of atoms in the solvent‐accessible surface of proteins that uses similarities in the local atomic environment, and carried out all‐against‐all structural comparisons for 48,347 potential ligand‐binding regions from a nonredundant protein structure subset (nrPDB, provided by NCBI). The relationships between the similarity of ligand‐binding regions and the similarity of the global structures of the proteins containing the binding regions were examined. We found 10,403 known ligand‐binding region pairs whose structures were similar despite having different global folds. Of these, we detected 281 region pairs that had similar ligands with similar binding modes. These proteins are good examples of convergent evolution. In addition, we found a significant correlation between Z‐score of structural similarity and true positive rate of “active” entries in the PubChem BioAssay database. Moreover, we confirmed the interaction between ibuprofen and a new target, porcine pancreatic elastase, by NMR experiment. Finally, we used this method to predict new drug–target protein interactions. We obtained 540 predictions for 105 drugs (e.g., captopril, lovastatin, flurbiprofen, metyrapone, and salicylic acid), and calculated the binding affinities using AutoDock simulation. The results of these structural comparisons are available at http://www.tsurumi.yokohama‐cu.ac.jp/fold/database.html Proteins 2008. © 2008 Wiley‐Liss, Inc.