bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Substrate-Binding Variants of the cAMP-Dependent Protein Kinase to Identify Novel Targets and a Kinase Domain Important for Substrate Interactions in Saccharomyces cerevisiae
Authors: Deminoff Stephen J , Howard Susie C , Hester Arelis , Warner Sarah , Herman Paul K 
Published: June 2006

Abstract
Protein kinases mediate much of the signal transduction in eukaryotic cells and defects in kinase function are associated with a variety of human diseases. To understand and correct these defects, we will need to identify the physiologically relevant substrates of these enzymes. The work presented here describes a novel approach to this identification process for the cAMP-dependent protein kinase (PKA) in Saccharomyces cerevisiae. This approach takes advantage of two catalytically inactive PKA variants, Tpk1K336A/H338A and Tpk1R324A, that exhibit a stable binding to their substrates. Most protein kinases, including the wild-type PKA, associate with substrates with a relatively low affinity. The binding observed here was specific to substrates and was dependent upon PKA residues known to be important for interactions with peptide substrates. The general utility of this approach was demonstrated by the ability to identify both previously described and novel PKA substrates in S. cerevisiae. Interestingly, the positions of the residues altered in these variants implicated a particular region within the PKA kinase domain, corresponding to subdomain XI, in the binding and/or release of protein substrates. Moreover, the high conservation of the residues altered and, in particular, the invariant nature of the R324 position suggest that this approach might be generally applicable to other protein kinases.
Deletion Polymorphism ofDisc1Is Common to All 129 Mouse Substrains: Implications for Gene-Targeting Studies of Brain Function
Authors: Clapcote Steven J , Roder John C 
Published: June 2006

AbstractWe report that the Disc1 gene in all extant 129 mouse inbred substrains has a deletion, previously considered specific to the 129S6/SvEv substrain, which is predicted to abolish production of the full-length protein. This finding has implications for the study of knockout mice generated from 129-derived embryonic stem cells.
Overexpression and Characterization of the Rhodobacter sphaeroides PufX Membrane Protein in Escherichia coli †
Authors: Onodera Shiho , Suzuki Hiroaki , Shimada Yuichiro , Kobayashi Masayuki , Nozawa Tsunenori , Wang Zheng‐Yu 
Published: June 2006

AbstractHeterologous expression of the PufX membrane protein from purple photosynthetic bacterium Rhodobacter sphaeroides was attempted by using Escherichia (E.) coli cells. The PufX was overexpressed as a recombinant protein with a histidine tag added to the carboxyl terminus, and can be extracted from the cell membrane by various detergents. Circular dichroism measurements showed that the expressed PufX protein had α‐helix contents of 29% in organic solvents and 22–26% in 0.8–2.0% (w/v) n‐octyl β‐d‐glucopyranoside solutions, suggesting that the PufX contains a substantial α‐helical region composed of 18–22 amino acids. The PufX expressed in E. coli was examined by reconstitution experiments with LH1 α‐ and β‐polypeptides and bacteriochlorophyll a. It was shown that the PufX inhibited not only the reconstitution of the LH1 complex, but also the formation of the B820 subunit type complex at high concentrations, indicating that the expressed PufX is biologically active. Large‐scale expression of the functional PufX membrane protein provides sufficient quantity for further biophysical and structural analyses of its biological function, and adds another example for producing highly hydrophobic integral membrane proteins using the E. coli expression system.
Mechanistic Studies on the Photochemical Deprotection of 3′,5′‐Dimethoxybenzoin Esters
Authors: Pirrung Michael C. , Ye Tong , Zhou Zheng , Simon John D. 
Published: June 2006

ABSTRACTSeveral mechanistic alternatives proposed for the photochemical deprotection of dimethoxybenzoin esters are presented. Both experimental and theoretical evidence suggest the mechanism is heterolysis of the singlet excited state to form a carbox‐ylate and the α‐ketocation. The α‐ketocation has been observed by transient spectroscopy. We propose the α‐ketocation undergoes electrocyclization to an intermediate with extended conjugation, whose deprotonation gives the observed benzofuran product. A Brønsted study of the rates of benzofuran formation with dimethoxybenzoin esters derived from acids of varying pKa shows the rate is independent of the basicity of the leaving group. In this multistep reaction, benzofuran formation by a final deprotonation is slower than α‐ketocation generation.
Geographic Variation in Somatic Growth of Redside Shiner
Authors: Houston Derek D. , Belk Mark C. 
Published: June 2006

AbstractThe geographic variation in growth rate and resulting body size is poorly known for most fish species. In this paper, we used data derived from otoliths to describe patterns of growth in redside shiners Richardsonius balteatus from seven native populations across the southern portion of its range, and we compare growth with latitude, elevation, and growing season to determine which of these environmental factors best predicts the growth patterns among these populations. To determine whether observed differences in growth resulted from environmental or genetic variation, we conducted a common‐environment experiment on fish from three of the seven populations that showed contrasting patterns between latitude and length of growing season. Redside shiners exhibited about a 60% difference in size at age among populations in their natural environments. Growing season length was the best predictor of body size among these populations (Akaike weight = 0.78). In a common environment, temperature‐specific growth rates differed among populations, indicating that some of the observed differences in size at age among populations are genetically based. Although populations of redside shiners with shorter growing seasons exhibited higher field growth rates than expected, the pattern of variation in individual growth rates among populations in a common environment was not consistent with either a countergradient variation model or a local adaptation model of growth.
Thermal Habitat Use by Lake Trout in Two Contrasting Yukon Territory Lakes
Authors: Mackenzie‐Grieve Jody L. , Post John R. 
Published: June 2006

AbstractThermal habitat use by lake trout Salvelinus namaycush in two northern lakes in the southern portion of the Yukon Territory that differ in morphometry and thermal regime was monitored using temperature‐sensitive acoustics and radiotelemetry. We then contrasted in situ temperature selection by lake trout in these lakes with previously published estimates of the species' optimal thermal range of 8–12°C. We found that thermal habitat use by lake trout in the two northern lakes is not consistent with these literature‐derived expectations. In Dezadeash Lake, which is isothermal in summer, temperatures typically exceeded the literature‐derived upper limit of 12°C. Throughout the summer lake trout sought the coldest water in the lake, which was in the form of shallow coldwater plumes derived from alpine ice‐pack meltwater streams. Once lake temperatures declined in the fall, lake trout were distributed throughout the lake. In Kathleen Lake, where water temperatures ranged from approximately 2°C to 12°C in the summer, the majority of lake trout selected habitats throughout the summer and fall that were colder than the 8°C lower limit of their literature‐derived optimal thermal range. Our results highlight the importance of summer thermal refugia for lake trout inhabiting marginal systems and the variation in thermal habitat use among populations inhabiting different thermal environments. Given the established importance of thermal habitat availability to lake trout production, our results suggest the need to better understand optimal thermal habitat characteristics in nature, particularly in light of factors such as climate warming.
Mass Customisation and the Manufactured Module
Authors: Woudhuysen James 
Published: June 2006

AbstractJames Woudhuysen, Professor of Forecasting and Innovation at De Montfort University, and co‐author of Why is Construction So Backwards? (Wiley‐Academy, 2004), talks to Stephen Kieran and James Timberlake of KieranTimberlake Architects about how they are setting out to refabricate architecture.
Think Big for the Developing World
Authors: Dingle Ceri , Regan Viv 
Published: June 2006

Abstract2005 was tagged the ‘year of Africa’. In fact, it should go down in history as the year Africa's development was firmly reined in by Western policy‐makers, say Ceri Dingle and Viv Regan, director and assistant director of the education charity, NGO and NVYO WORLD. Africa needs development, but not the small‐minded sustainable variety. Could it be that a lack of confidence and ambition in development among the industrialised nations is holding back the developing world?
Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non‐syndromic split‐hand/foot malformation
Authors: Everman David B. , Morgan Chad T. , Lyle Robert , Laughridge Mary E. , Bamshad Michael J. , Clarkson Katie B. , Colby Randall , Gurrieri Fiorella , Innes A. Micheil , Roberson Jacquelyn , Schrander‐Stumpel Connie , van Bokhoven Hans , Antonarakis Stylianos E. , Schwartz Charles E. 
Published: June 2006

AbstractSplit‐hand/foot malformation (SHFM), or ectrodactyly, is characterized by underdeveloped or absent central digital rays, clefts of the hands and feet, and variable syndactyly of the remaining digits. SHFM occurs as both an isolated finding and a component of many syndromes. SHFM is a heterogeneous condition caused by multiple loci, including SHFM1 (chromosome region 7q21‐q22), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27), and SHFM5 (2q31). Mutations in TP63 at the SHFM4 locus are known to underlie both syndromic and non‐syndromic forms SHFM, but the causes of most non‐syndromic SHFM cases remain unknown. The recent identification of submicroscopic tandem chromosome duplications affecting the SHFM3 locus in seven families with non‐syndromic SHFM has helped to further unravel the molecular basis of this malformation. In our ongoing studies of the SHFM3 locus in 44 additional cases of syndromic and non‐syndromic SHFM, we have identified similar chromosome rearrangements in eight additional cases (18%), using pulsed‐field gel electrophoresis (PFGE). We have also utilized real‐time quantitative PCR (qPCR) to test for the duplications. Seven of the cases with rearrangements were non‐syndromic. The current findings bring the total of SHFM3‐associated cases with chromosome rearrangements to 15, which constitute 29% (15 of 51) of the cases screened to date. This includes 9 of 9 cases (100%) with known linkage to the SHFM3 locus, all of whom have non‐syndromic SHFM, and 6 of 42 additional cases (14%), four of whom have non‐syndromic SHFM. Thus, SHFM3 abnormalities underlie a substantial proportion of SHFM cases and appear to be a more frequent cause of non‐syndromic SHFM than mutations in TP63. © 2006 Wiley‐Liss, Inc.
Mosaicism for a full mutation, premutation, and deletion of the CGG repeats results in 22% FMRP and elevated FMR1 mRNA levels in a high‐functioning fragile X male
Authors: Han Xiao‐Dong , Powell Berkley R. , Phalin Judith L. , Chehab Farid F. 
Published: June 2006

AbstractThe molecular basis in the majority of fragile X patients results from expansion of the CGG repeats in the FMR1 gene causing its transcriptional silencing and deficiency of its encoded protein FMRP. In this communication, we report on a male patient who lacks the characteristic physical features of fragile X and carries a fully methylated mutation, a premutation, a non‐methylated full mutation, and a microdeletion encompassing the entire CGG repeat region and 42 bp of upstream flanking sequence. Southern blot analysis revealed that the methylated full mutation accounted for only 10% of his genotype while the premutation/non‐methylated full mutation and the microdeletion constituted 37% and 53%, respectively. Immunofluorescent staining of FMRP demonstrated the presence of 22% FMRP in his peripheral blood leukocytes and quantitative RT‐PCR revealed a 3.6‐fold elevation of FMR1 mRNA levels. Developmental assessments indicated that while he has a learning disability, he does not have mental retardation. Because previous reports had noted that 28% FMRP expression is associated with a characteristic fragile X phenotype, we propose that in our patient the association of 22% FMRP levels with normal physical features and a high‐functioning status may have resulted from increased FMRP stability by a mechanism that takes into account the CGG microdeletion and elevated mRNA levels. © 2006 Wiley‐Liss, Inc.
The near universal presence of autism spectrum disorders in children with Smith–Lemli–Opitz syndrome
Authors: Sikora Darryn M. , Pettit‐Kekel Kersti , Penfield Jennifer , Merkens Louise S. , Steiner Robert D. 
Published: June 2006

AbstractSmith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive condition caused by a defect in cholesterol synthesis. Affected children often have malformations and mental retardation. Autistic behaviors also are evident. The purpose of the present study was to determine the prevalence of autism spectrum disorders (ASDs) in children with SLOS. Fourteen children, 3–16 years old, were evaluated using three different methods to document autistic symptoms: (a) parent interview, (b) direct observation, and (c) a behavior checklist. Blood sterols were also measured at regular intervals. Each subject was determined to have Autistic Disorder, Pervasive Developmental Disorder, not otherwise specified (PDD NOS), or no diagnosis on the autism spectrum, based on DSM‐IV criteria. Correlations among variables were calculated, and blood sterol levels were compared between diagnostic groups. Approximately three‐fourths of the children with SLOS (71–86% depending on the evaluation method) had an ASD, about 50% diagnosed with Autistic Disorder and the rest with PDD NOS. The children's baseline cholesterol, 7‐dehydrocholesterol (7‐DHC), and 8‐dehydrocholesterol (8‐DHC) levels, and cholesterol levels following supplementation did not correlate with the presence or severity of autistic symptoms. These results suggest that most children with SLOS have some variant of autism. SLOS appears to have the most consistent relationship with autism of any single gene disorder. Therefore, a link between cholesterol metabolism and autism is suggested. With further study, these findings, together with knowledge of the genetic and biochemical defects in SLOS, will likely provide valuable insights into the causes of autism in general. © 2006 Wiley‐Liss, Inc.
Stabilization of bzip Peptides through Incorporation of Fluorinated Aliphatic Residues
Authors: Son Soojin , Tanrikulu I. Caglar , Tirrell David A. 
Published: June 2006

AbstractTwo fluorinated amino acids, 5,5,5‐trifluoroisoleucine (5TFI) and (2S,3R)‐4,4,4‐trifluorovaline (4TFV), which have been shown to serve as isoleucine surrogates in protein synthesis in Escherichia coli, have been incorporated in vivo into basic leucine zipper (bzip) peptides derived from GCN4. The extents of residue‐specific incorporation of 5TFI and 4TFV were 90 and 88 %, respectively, of the encoded isoleucine residues, as evidenced by MALDI mass spectrometry and amino acid analysis. Both circular dichroism and equilibrium sedimentation studies of the fluorinated bzip peptides indicated preservation of secondary and higher‐order protein structure. Thermal‐denaturation experiments showed an increase of 27 °C in melting temperature when isoleucine was replaced by 5TFI. However, the Tm of the peptide containing 4TFV was increased by only 4 °C over that of the peptide containing valine. Similar trends were observed in chemical denaturation studies in which ΔΔGunfold in water was determined to be 2.1 or 0.3 kcal mol−1 upon incorporation of 5TFI or 4TFV, respectively. When the fluorinated peptides were tested for DNA binding, both their affinity and specificity were similar to those of the respective hydrogenated peptides. These results suggest that fluorinated amino acids, even when introduced into the same positions, can have markedly different effects on the physical properties of proteins, while having little impact on secondary and higher‐order structure.
Impact of 16‐slice computed tomography in percutaneous coronary intervention of chronic total occlusions
Authors: Yokoyama Naoyuki , Yamamoto Yoshito , Suzuki Shigeru , Suzuki Masatoshi , Konno Kumiko , Kozuma Ken , Kaminaga Tatsuro , Isshiki Takaaki 
Published: June 2006

AbstractThe main reason for failure of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is because the calcified plaque prevents the guide wire crossing the occlusion. We aimed to identify the route, and characterize plaque components within CTO, using 16‐slice computed tomography (MSCT). Twenty three angiographic CTO in 22 patients (mean age 69 ±± 5 years, 17 males) were included. All patients had undergone MSCT prior to PCI. Images were analyzed for lesion visibility and plaque characteristics of CTO. The presence and location of calcified plaque within the CTO were systematically assessed. Each lesion was classified as a noncalcified, moderately calcified, or exclusively calcified plaque. Procedural failure was defined as the inability to cross a guide wire through the occlusion. All coronary routes of CTO segment were visualized. MSCT revealed three markedly bent CTO segments (13.0%), which could not be identified by coronary angiography only. Calcified plaques were detected in 30 lesions of 19 CTO segments (82.6%), but were not detected in the other four. The majority of calcified plaque was located in the proximal lesion, or both proximal and distal lesions. Fifteen out of 30 calcified lesions (50.0%) were exclusively calcified plaques. Overall procedural success was obtained in 21 CTOs (91.3%). MSCT can accurately identify the route of the CTO segment and evaluate both distribution and amount of the calcified plaque within it. Even with the complicated and/or calcified lesions, PCI success rate was excellent under MSCT guidance. MSCT should become a useful tool in PCI of CTO. © 2006 Wiley‐Liss, Inc.
Impact of three or more sirolimus‐eluting stents versus paclitaxel‐eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention
Authors: Chu William W. , Kuchulakanti Pramod K. , Torguson Rebecca , Wang Betty , Clavijo Leonardo C. , Suddath William O. , Pichard Augusto D. , Satler Lowell F. , Kent Kenneth M. , Waksman Ron 
Published: June 2006

AbstractObjectives:The purpose of this study was to examine the clinical outcomes of patients who underwent stenting with ≥3 sirolimus‐eluting stents (SES) when compared with those treated with ≥3 paclitaxel‐eluting stents (PES).Background:Drug‐eluting stent (DES) implantation for single coronary lesions is proven to be effective and durable.Methods:A total of 126 patients who received DES were identified, of which 66 patients received ≥3 SES (SES group) and 60 patients received ≥3 PES (PES group).Results:The baseline clinical and angiographic characteristics were compatible between the two study groups. During the index hospitalization, all clinical outcomes were similar between the two groups. There were no deaths or Q‐wave myocardial infarctions (MIs) in either group. At 30 days' and 6 months' follow‐up, all clinical outcomes, including death, Q‐wave MI, non–Q‐wave MI, target lesion revascularization, target vascular revascularization, and major adverse cardiac events, were compatible between both groups. There were 2 patients (3.0%) with subacute thrombosis in the SES group and 1 patient (1.7%) in the PES group, but there was no statistical significance. There was no late thrombosis from either group. In addition, patients in the SES group had similar event‐free survival rates as compared with those in the PES group (P = 0.56).Conclusions:Patients who require ≥3 DES implantations experienced increased adverse clinical events as compared with historical single stent implantation. However, there were no differences in safety and efficacy among the patients treated with SES as compared with those treated with PES. © 2006 Wiley‐Liss., Inc.
Discrete Organic Nanotubes Based on a Combination of Covalent and Non‐Covalent Approaches
Authors: Block Marco A. Balbo , Kaiser Christian , Khan Anzar , Hecht Stefan 
Published: June 2006

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Genetic determinants for activated fluoropyrimidine chemotherapy
Authors: Gmeiner William H. 
Published: June 2006

AbstractFluoropyrimidines (FPs) remain widely used for the treatment of diverse malignancies more than four decades following the initial report of 5‐fluorouracil (5FU), the archetypal FP, as a novel compound with potential anti‐neoplastic activity. Subsequent decades of research have enriched our understanding of the biochemical mechanisms that are important for FP activation as well as the genetic determinants that are predictive of the likely success, or failure, of FP chemotherapy for a particular individual. The concept that chemotherapy should be customized to complement the genetic profiles of cancer patients has become increasingly important as genotyping of tumor samples has become possible and as the number of available anticancer drugs has increased. Significant progress has been made in identifying the gene expression profiles for cancer patients who are likely to benefit from treatment with FPs. In this review, we will summarize the results of retrospective clinical studies correlating response to FP chemotherapy with the expression of specific genes, such as TS and DPD. We will also present a summary of FPs in current clinical use, including orally bioavailable FPs such as capecitabine, as well as FPs that are in pre‐clinical development, such as FdUMP[10]. Refinement of a target population through pharmacogenetic analysis and development of novel FPs that evoke very high response rates in this target population will likely result in the use of FP regimens in the coming era when cancer becomes a largely manageable disease. Drug Dev. Res. 67:119–129, 2006. © 2006 Wiley‐Liss, Inc.