bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved quality of life after lung transplantation in individuals with cystic fibrosis
Authors: Vermeulen Karin M. , van der Bij Wim , Erasmus Michiel E. , Duiverman Eric J. , Koëter Gerard H. , TenVergert Elisabeth M. 
Published: April 2004

AbstractThe aim of the present study was to assess the effect of lung transplantation (LgTX) on health‐related quality of life (HRQL) in a group of patients with cystic fibrosis (CF), compared to patients with other diagnoses (non‐CF). HRQL was assessed before transplantation in a group of 32 CF patients and 183 non‐CF patients. After LgTX, we conducted a prospective longitudinal study among 10 CF patients and 35 non‐CF patients who survived at least 31 months after LgTX. Measures were the Nottingham Health Profile (NHP), the State‐Trait Anxiety Inventory (STAI), the Self‐Rating Depression Scale (ZUNG), the Index of Well‐Being (IWB), and the Karnofsky Performance Index. Patients in the CF group were younger, spent more days on the waiting list, and were more likely to be working or going to school than patients with other indications. Before transplantation, CF patients and non‐CF patients experienced restrictions on almost all HRQL measures, compared to the general population. On the NHP dimensions of mobility and energy, CF patients had significantly better scores than non‐CF patients. Between 1–4 months after transplantation, scores on the NHP, ZUNG, and Karnofsky performance indices improved, and STAI and IWB scores even occurred within the reference value in both groups. Significantly better scores in the CF group compared to the non‐CF group were found on the NHP dimension of mobility 4 months after transplantation, and on the dimension of sleep 7 and 13 months after transplantation. Scores remained more or less stable over time in both groups. It may be concluded that patients in both groups experience major restrictions in HRQL before transplantation. However, pretransplant non‐CF patients experience more restrictions than CF patients. After LgTX, both groups of patients showed substantial improvement in HRQL, and this improvement was maintained until 31 months after LgTX. Pediatr Pulmonol. 2004; 37:419–426. © 2004 Wiely‐Liss, Inc.
Parent‐reported asthma in Puerto Rican children
Authors: Nazario Sylvette , Casal Jesus R. , Torres‐Palacios Alfonso , Rodriguez William , Delamater Alan M. , Applegate E. Brooks , Piedimonte Giovanni , Wanner Adam 
Published: April 2004

AbstractWe conducted a survey to determine parent‐reported asthma prevalence, morbidity, and healthcare utilization among 3,527 children attending public schools (n = 2,849) and private schools (n = 678) in San Juan, Puerto Rico. Schools were randomly selected from each of 12 geographic regions of the San Juan metropolitan area. Parents of children age 4–7 years old completed a 12‐item questionnaire on asthma diagnosis, respiratory symptoms and morbidity, and healthcare utilization. Parents of children in public schools and private schools reported similar rates of a physician having previously diagnosed asthma in their children (43.2% vs. 39.4%); however, significantly more children in public schools were reported to still have asthma at the time of the survey (32.6% vs. 23.7%). Children attending public schools vs. private schools were reported to have missed significantly more school and to have had more hospitalizations and emergency department visits. Among children reported to still have asthma, significantly more children visited an emergency department, were hospitalized, and missed more school days due to respiratory symptoms in the past year. The high prevalence of parent‐reported asthma, respiratory symptoms, and healthcare utilization among Puerto Rican children in San Juan calls for further studies using objective methods for ascertaining asthma and asthma‐related morbidity. Differences in healthcare utilization between children attending public vs. private schools suggest that socioeconomic factors play a role in asthma management in Puerto Rico. Pediatr Pulmonol. 2004; 37:453–460. © 2004 Wiely‐Liss, Inc.
Pulmonary exacerbations in cystic fibrosis
Authors: Rabin Harvey R. , Butler Steven M. , Wohl Mary Ellen B. , Geller David E. , Colin Andrew A. , Schidlow Daniel V. , Johnson Charles A. , Konstan Michael W. , Regelmann Warren E. 
Published: April 2004

AbstractThe clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12‐month baseline period, data from 11,692 patients were compared with data collected during the subsequent 6‐month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and ≥6 years of age. The outcome of interest was any antibiotic treatment in the 6‐month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients ≥6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients. Pediatr Pulmonol. 2004; 37:400–406. © 2004 Wiely‐Liss, Inc.
Mortality after pediatric lung transplantation: Autopsies vs. clinical impression
Authors: Kaditis Athanasios G. , Phadke Shruti , Dickman Paul , Webber Steven , Kurland Geoffrey , Michaels Marian G. 
Published: April 2004

AbstractAppreciable mortality accompanies pediatric lung and heart‐lung transplantation. The objective of this investigation was to compare the clinical impression of causes of death with autopsy findings in all pediatric lung or heart lung transplant recipients who had an autopsy performed between 1985–2002 at the Children's Hospital of Pittsburgh. Medical records and autopsy findings were reviewed. Thirty recipients with autopsies had 33 transplant procedures: heart‐lung (16), double lung (14), repeat lung (2), and repeat heart‐lung (1). Perioperative deaths occurred in 8 children, most often precipitated by graft dysfunction. Early deaths (2 weeks–1 year) occurred in 12 children resulting from infection. Late deaths (greater than 1 year) occurred in 10 children. Bronchiolitis obliterans complicated by infection was the major cause of death in these recipients. An autopsy confirmed the clinical impression of cause of death in 29/30 and added significant supplemental information in 16 cases. Unsuspected factors contributing to death included donor lung abnormalities, concurrent infection, and cardiovascular disease. Postmortem examination remains a critical component to augment the understanding of causes of death following pediatric thoracic transplantation. © 2004 Wiley‐Liss, Inc.
Dynamics and energetics of water permeation through the aquaporin channel
Authors: Vidossich Pietro , Cascella Michele , Carloni Paolo 
Published: April 2004

AbstractStructural properties of water inside bovine aquaporin‐1 are investigated by molecular simulation. The calculations, which are based on the recently determined X‐ray structure at 2.2 Å resolution (Sui et al., Nature 2001;414:872–878), are carried out on one monomeric subunit immersed in a water‐n‐octane‐water bilayer. Molecular dynamics (MD) simulations suggest that His182, a fully conserved residue in the channel pore, is protonated in the δ position. Furthermore, they reveal a highly ordered water structure in the channel, induced by the electrostatic properties of the protein. Multiple‐steering MD simulations are used to calculate the free‐energy of water diffusion. To the best of our knowledge, this represents the first free‐energy calculation based on the new, high‐resolution structure of the pore. The calculated barrier is 2.5 kcal/mol, and it is associated to water permeation through the Asn‐Pro‐Ala (NPA) region of the pore, where water molecules are only hydrogen‐bonded with themselves. These findings are fully consistent with those based on the previous MD studies on the human protein (de Groot and Grubmüller, Science 2001;294:2353–2357). Proteins 2004. © 2004 Wiley‐Liss, Inc.
Crystal structure of human L‐xylulose reductase holoenzyme: Probing the role of Asn107 with site‐directed mutagenesis
Authors: El‐Kabbani Ossama , Ishikura Shuhei , Darmanin Connie , Carbone Vincenzo , Chung Roland P.‐T. , Usami Noriyuki , Hara Akira 
Published: April 2004

AbstractL‐Xylulose reductase (XR), an enzyme in the uronate cycle of glucose metabolism, belongs to the short‐chain dehydrogenase/reductase (SDR) superfamily. Among the SDR enzymes, XR shows the highest sequence identity (67%) with mouse lung carbonyl reductase (MLCR), but the two enzymes show different substrate specificities. The crystal structure of human XR in complex with reduced nicotinamide adenine dinucleotide phosphate (NADPH) was determined at 1.96 Å resolution by using the molecular replacement method and the structure of MLCR as the search model. Features unique to human XR include electrostatic interactions between the N‐terminal residues of subunits related by the P‐axis, termed according to SDR convention, and an interaction between the hydroxy group of Ser185 and the pyrophosphate of NADPH. Furthermore, identification of the residues lining the active site of XR (Cys138, Val143, His146, Trp191, and Met200) together with a model structure of XR in complex with L‐xylulose, revealed structural differences with other members of the SDR family, which may account for the distinct substrate specificity of XR. The residues comprising a recently proposed catalytic tetrad in the SDR enzymes are conserved in human XR (Asn107, Ser136, Tyr149, and Lys153). To examine the role of Asn107 in the catalytic mechanism of human XR, mutant forms (N107D and N107L) were prepared. The two mutations increased Km for the substrate (>26‐fold) and Kd for NADPH (95‐fold), but only the N107L mutation significantly decreased kcat value. These results suggest that Asn107 plays a critical role in coenzyme binding rather than in the catalytic mechanism. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Atomic insight into the CD4 binding‐induced conformational changes in HIV‐1 gp120
Authors: Hsu Shang‐Te D. , Bonvin Alexandre M.J.J. 
Published: April 2004

AbstractThe entry of HIV‐1 into a target cell requires gp120 and receptor CD4 as well as coreceptor CCR5/CXCR4 recognition events associated with conformational changes of the involved proteins. The binding of CD4 to gp120 is the initiation step of the whole process involving structural rearrangements that are crucial for subsequent pathways. Despite the wealth of knowledge about the gp120/CD4 interactions, details of the conformational changes occurring at this stage remain elusive. We have performed molecular dynamics simulations in explicit solvent based on the gp120/CD4/CD4i crystal structure in conjunction with modeled V3 and V4 loops to gain insight into the dynamics of the binding process. Three differentiated interaction modes between CD4 and gp120 were found, which involve electrostatics, hydrogen bond and van der Waals networks. A “binding funnel” model is proposed based on the dynamical nature of the binding interface together with a CD4‐attraction gradient centered in gp120 at the CD4‐Phe43‐binding cavity. Distinct dynamical behaviors of free and CD4‐bound gp120 were monitored, which likely represent the ground and pre‐fusogenic states, respectively. The transition between these states revealed concerted motions in gp120 leading to: i) loop contractions around the CD4‐Phe43‐insertion cavity; ii) stabilization of the four‐stranded “bridging sheet” structure; and iii) translocation and clustering of the V3 loop and the bridging sheet leading to the formation of the coreceptor binding site. Our results provide new insight into the dynamic of the underlying molecular recognition mechanism that complements the biochemical and structural studies. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Topological thermal instability and length of proteins
Authors: Burioni Raffaella , Cassi Davide , Cecconi Fabio , Vulpiani Angelo 
Published: April 2004

AbstractWe present an analysis of the effects of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we computed the harmonic spectrum within the Gaussian Network Model (GNM) and determined their spectral dimension, a parameter describing the low frequency behavior of the density of modes. We found a surprisingly strong correlation between the spectral dimension and the number of amino acids in the protein. Considering that larger spectral dimension values relate to more topologically compact folded states, our results indicate that, for a given temperature and length of protein, the folded structure corresponds to a less compact folding, one compatible with thermodynamic stability. Proteins 2004. © 2004 Wiley‐Liss, Inc.
A new perspective on analysis of helix–helix packing preferences in globular proteins
Authors: Trovato Antonio , Seno Flavio 
Published: April 2004

AbstractFor many years, statistical analysis of protein databanks has led to the belief that the steric compatibility of helix interfaces may be the source of observed preferences for particular angles between neighboring helices. Several elegant models describing how side chains on helices can interdigitate without steric clashes were able to account quite reasonably for the observed distributions. However, it was later recognized that the ‘bare’ measured angle distribution should be corrected to avoid statistical bias.1, 2 Disappointingly, the rescaled distributions dramatically lost their similarity with theoretical predictions, casting doubts on the validity of the geometrical assumptions and models. In this article, we elucidate a few points concerning the proper choice of a random reference distribution. In particular we demonstrate the need for corrections induced by unavoidable uncertainties in determining whether two helices are in face‐to‐face contact or not and their relative orientations. By using this new rescaling, we show that ‘true’ packing angle preferences are well described by regular packing models, thus proving that preferential angles between contacting helices do exist. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Bicyclic Organo‐Peptides as Selective Carbohydrate Receptors: Design, Solid‐phase Synthesis, and on‐bead Binding Capability
Authors: Benito Juan M. , Meldal Morten 
Published: April 2004

AbstractSelective recognition of monosaccharides in polar media by conformationally restricted bicyclic peptides containing an aromatic surface to facilitate the initial interaction has been examined. Molecular modeling assisted design of these peptidic receptors has been employed to optimize guest fitting in the peptide cavity. Different solid‐phase synthetic approaches to the target structures are discussed in order to develop a flexible methodology suitable for a combinatorial approach. A series of putative receptors, differing in the aromatic spacer as well as the peptide ring size, has been synthesized and characterized by HPLC and HR‐MS. They have been subjected to FRET‐based screening for binding to mono and disaccharides. This indicates that binding properties are strongly dependent on the size and rigidity of the receptors, detecting β‐glucoside selectivity in the case of a naphthyl‐bridged cyclic dodecapeptide. In addition, an ES‐MS/MS‐based method that allows structural elucidation of single bead samples with no need of encoding techniques has been devised, which will be useful for structure elucidation in libraries of cyclic peptides.
Synthesis of 3‐Boc‐(1,3)‐oxazinane‐Protected Amino Aldehydes from Amino Acids and Their Conversion into Urea Precursors. Novel Building Blocks for Combinatorial Synthesis
Authors: Diness F. , Beyer J. , Meldal Morten 
Published: April 2004

AbstractStarting from the large pool of chiral amino acids a route to protected amino aldehyde building blocks for combinatorial chemistry has been developed. Eight α‐amino aldehydes have been synthesized from Cbz‐ or Fmoc‐protected α‐amino acids through partial reduction of Weinreb amides or partial oxidation with Dess‐Martin periodinane of amino alcohols. The α‐amino aldehydes have been protected as their acid labile 3‐Boc‐(1,3)‐oxazinanes using aminopropanol and sodium sulfate followed by treatment with Boc2O. Noteworthy, both reduction and protection proceed with minimal epimerization. 3‐Boc‐(1,3)‐oxazinane (Box) protected 2‐amino‐benzaldehyd have also been synthesized.
Molecular Connectivity: Polarity Correction to Improve Correlation with Hydrophobicity
Authors: Dearden John C. , Wong Elaine H. Y. , Walker John D. 
Published: April 2004

AbstractContrary to belief in some quarters, molecular connectivites correlate only very poorly with hydrophobicity. We have devised a simple polarity correction to the calculation of first‐order molecular connectivity (1χ), which involves subtracting, instead of adding, the bond contributions (δ values) for bonds between atoms i and j where j is a heteroatom other than halogen, to give a 1χp value. For a set of 23 diverse substituents, the correlation between 1χ and π (the hydrophobic substituent constant) yielded r2=0.123, whilst that between 1χp and π yielded r2=0.771. When the method was applied to the correlation of the protein‐binding constants for a set of 42 diverse compounds with 1χ, r2 improved from 0.078 to 0.443.
CODES/Neural Network Model: a Useful Tool for in Silico Prediction of Oral Absorption and Blood‐Brain Barrier Permeability of Structurally Diverse Drugs
Authors: Dorronsoro Isabel , Chana Antonio , Abasolo Ma Inés , Castro Ana , Gil Carmen , Stud Manfred , Martinez Ana 
Published: April 2004

AbstractTwo different neural network models able to predict both oral absorption (OA) and blood‐brain barrier (BBB) permeability of structurally diverse drugs in use clinically are presented here. Using the descriptors generated by CODES, a program which codifies molecules from a topological point of view, we avoid the uncertain choice of molecular conformation and physicochemical parameters. In this work, a method called Reduction of Dimensions, designed for compressing data, is applied for the first time in order to minimize the bias factor added to a QSAR study when the selection of descriptors are performed.
QSTR with Extended Topochemical Atom Indices. 3. Toxicity of Nitrobenzenes to Tetrahymena pyriformis
Authors: Roy Kunal , Ghosh Gopinath 
Published: April 2004

AbstractThe experimental determination of toxicological properties of commercial chemicals being costly and time consuming process, there is a need to develop mathematical predictive tool to theoretically quantify such properties. In this background, we have modeled toxicity of nitrobenzene derivatives to Tetrahymena pyriformis using extended topochemical atom (ETA) indices recently introduced by us (Roy and Ghosh, 2003). We have also modeled the toxicity data using other topological descriptors (Balaban J, kappa shape indices, connectivity indices, Wiener index) and two physicochemical variables (AlogP98, MolRef) and compared the ETA models with non‐ETA ones. Principal component factor analysis was used as the data‐preprocessing step to reduce the dimensionality of the data matrix and identify the important variables that are devoid of collinearities. Multiple linear regression analyses show that the best non‐ETA model involves 2κ and AlogP98 as predictor variables and the quality of the relation is as follows: n=42, Q2=0.70, R$ {_{{a}}^{2}}$=0.75, R2=0.76, R=0.87, F=61.0 (df 2, 39), s=0.36. On the other hand, the best ETA model has the following quality: n=42, Q2=0.88, R$ {_{{a}}^{2}}$=0.91, R2=0.92, R=0.96, F=101.4 (df 4, 37), s=0.22. The ETA relations showed positive contributions of molecular bulk (size), halogen and additional nitro substitutions in the nitrobenzene ring and negative contributions of the substituents like methyl and hydroxymethyl groups to the toxicity. An attempt to use non‐ETA descriptors along with the ETA ones slightly improves the quality in comparison to the best ETA model. Interestingly, the ETA model developed by us for the nitrobenzene toxicity is comparable to the previously reported models on the same data set (Estrada et al., 2001; Cronin et al., 1998). Thus, it appears that the ETA descriptors have significant potential in QSAR/QSPR/QSTR studies, which warrants extensive evaluation.
Screening for novel essential genes of Saccharomyces cerevisiae involved in protein secretion
Authors: Davydenko Svetlana G. , Juselius Jukka K. , Munder Thomas , Bogengruber Edith , Jäntti Jussi , Keränen Sirkka 
Published: April 2004

AbstractWe describe here a screening procedure devised for searching new genes involved in protein secretion in Saccharomyces cerevisiae. The screening procedure takes advantage of yeast strains constructed within the EUROFAN project, in which the promoters of the novel essential genes were replaced by the doxycycline‐regulated tetO7‐CYC1 promoter. This promoter is active in normal growth medium but results in downregulation of the gene in the presence of doxycycline. The yeast cells were grown in the presence or absence of doxycycline, and both the growth and secretion of the heat shock protein, Hsp150p, into the culture medium were determined. In seven strains there was a specific effect on protein secretion. In a strain in which the RPN5 gene was downregulated, the level of secreted Hsp150p was increased compared to the control culture. When RER2 was downregulated, cells secreted Hsp150p that was not of the mature size. In five strains, secretion was more severely reduced than cell growth. One of these downregulated genes, YGL098w, was recently reported to encode an ER‐located t‐SNARE, USE1. Four of the genes detected, NOG2, NOP15, RRP40 and SDA1, encode proteins involved in ribosome assembly, suggesting a possible new signalling pathway between ribosome biogenesis and production of secreted proteins. The results obtained here indicate that the present screen could be successfully used in larger scale to identify novel secretion‐related genes. Copyright © 2004 John Wiley & Sons, Ltd.