bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of a disulfide bond to the structure, stability, and dimerization of human IgG1 antibody CH3 domain
Authors: McAuley Arnold , Jacob Jaby , Kolvenbach Carl G. , Westland Kimberly , Lee Hyo Jin , Brych Stephen R. , Rehder Douglas , Kleemann Gerd R. , Brems David N. , Matsumura Masazumi 
Published: December 2007

AbstractRecombinant human monoclonal antibodies have become important protein‐based therapeutics for the treatment of various diseases. The antibody structure is complex, consisting of β‐sheet rich domains stabilized by multiple disulfide bridges. The dimerization of the CH3 domain in the constant region of the heavy chain plays a pivotal role in the assembly of an antibody. This domain contains a single buried, highly conserved disulfide bond. This disulfide bond was not required for dimerization, since a recombinant human CH3 domain, even in the reduced state, existed as a dimer. Spectroscopic analyses showed that the secondary and tertiary structures of reduced and oxidized CH3 dimer were similar, but differences were observed. The reduced CH3 dimer was less stable than the oxidized form to denaturation by guanidinium chloride (GdmCl), pH, or heat. Equilibrium sedimentation revealed that the reduced dimer dissociated at lower GdmCl concentration than the oxidized form. This implies that the disulfide bond shifts the monomer–dimer equilibrium. Interestingly, the dimer–monomer dissociation transition occurred at lower GdmCl concentration than the unfolding transition. Thus, disulfide bond formation in the human CH3 domain is important for stability and dimerization. Here we show the importance of the role played by the disulfide bond and how it affects the stability and monomer–dimer equilibrium of the human CH3 domain. Hence, these results may have implications for the stability of the intact antibody.
Folding thermodynamics and kinetics of the leucine‐rich repeat domain of the virulence factor Internalin B
Authors: Courtemanche Naomi , Barrick Doug 
Published: December 2007

AbstractAlthough the folding of α‐helical repeat proteins has been well characterized, much less is known about the folding of repeat proteins containing β‐sheets. Here we investigate the folding thermodynamics and kinetics of the leucine‐rich repeat (LRR) domain of Internalin B (InlB), an extracellular virulence factor from the bacterium Lysteria monocytogenes. This domain contains seven tandem leucine‐rich repeats, of which each contribute a single β‐strand that forms a continuous β‐sheet with neighboring repeats, and an N‐terminal α‐helical capping motif. Despite its modular structure, InlB folds in an equilibrium two‐state manner, as reflected by the identical thermodynamic parameters obtained by monitoring its sigmoidal urea‐induced unfolding transition by different spectroscopic probes. Although equilibrium two‐state folding is common in α‐helical repeat proteins, to date, InlB is the only β‐sheet‐containing repeat protein for which this behavior is observed. Surprisingly, unlike other repeat proteins exhibiting equilibrium two‐state folding, InlB also folds by a simple two‐state kinetic mechanism lacking intermediates, aside from the effects of prolyl isomerization on the denatured state. However, like other repeat proteins, InlB also folds significantly more slowly than expected from contact order. When plotted against urea, the rate constants for the fast refolding and single unfolding phases constitute a linear chevron that, when fitted with a kinetic two‐state model, yields thermodynamic parameters matching those observed for equilibrium folding. Based on these kinetic parameters, the transition state is estimated to comprise 40% of the total surface area buried upon folding, indicating that a large fraction of the native contacts are formed in the rate‐limiting step to folding.
DNA inhibits catalysis by the carboxyltransferase subunit of acetyl‐CoA carboxylase: Implications for active site communication
Authors: Benson Brian K. , Meades Glen , Grove Anne , Waldrop Grover L. 
Published: December 2007

AbstractAcetyl‐CoA carboxylase (ACC) catalyzes the first committed step in the synthesis of long‐chain fatty acids. The crystal structure of the Escherichia coli carboxyltransferase component of ACC revealed an α2β2 subunit composition with two active sites and, most importantly, a unique zinc domain in each αβ pair that is absent in the eukaryotic enzyme. We show here that carboxyltransferase binds DNA. Half‐maximal saturation of different single‐stranded or double‐stranded DNA constructs is seen at 0.5–1.0 μM, and binding is cooperative and nonspecific. The substrates (malonyl‐CoA and biocytin) inhibit DNA:carboxyltransferase complex formation. More significantly, single‐stranded DNA, double‐stranded DNA, and heparin inhibit the reaction catalyzed by carboxyltransferase, with single‐stranded DNA and heparin acting as competitive inhibitors. However, double‐inhibition experiments revealed that both DNA and heparin can bind the enzyme in the presence of a bisubstrate analog (BiSA), and the binding of BiSA has a very weak synergistic effect on the binding of the second inhibitor (DNA or heparin) and vice versa. In contrast, DNA and heparin can also bind to the enzyme simultaneously, but the binding of either molecule has a strong synergistic effect on binding of the other. An important mechanistic implication of these observations is that the dual active sites of ACC are functionally connected.
Enhanced performance in prediction of protein active sites with THEMATICS and support vector machines
Authors: Tong Wenxu , Williams Ronald J. , Wei Ying , Murga Leonel F. , Ko Jaeju , Ondrechen Mary Jo 
Published: December 2007

AbstractTheoretical microscopic titration curves (THEMATICS) is a computational method for the identification of active sites in proteins through deviations in computed titration behavior of ionizable residues. While the sensitivity to catalytic sites is high, the previously reported sensitivity to catalytic residues was not as high, about 50%. Here THEMATICS is combined with support vector machines (SVM) to improve sensitivity for catalytic residue prediction from protein 3D structure alone. For a test set of 64 proteins taken from the Catalytic Site Atlas (CSA), the average recall rate for annotated catalytic residues is 61%; good precision is maintained selecting only 4% of all residues. The average false positive rate, using the CSA annotations is only 3.2%, far lower than other 3D‐structure‐based methods. THEMATICS–SVM returns higher precision, lower false positive rate, and better overall performance, compared with other 3D‐structure‐based methods. Comparison is also made with the latest machine learning methods that are based on both sequence alignments and 3D structures. For annotated sets of well‐characterized enzymes, THEMATICS–SVM performance compares very favorably with methods that utilize sequence homology. However, since THEMATICS depends only on the 3D structure of the query protein, no decline in performance is expected when applied to novel folds, proteins with few sequence homologues, or even orphan sequences. An extension of the method to predict non‐ionizable catalytic residues is also presented. THEMATICS–SVM predicts a local network of ionizable residues with strong interactions between protonation events; this appears to be a special feature of enzyme active sites.
Use of the Ultrasonic Microprobe to Evaluate Gastric Varices –Comparison with Endoscopic Color Doppler Ultrasonography–
Authors: SATO Takahiro , YAMAZAKI Katsu , TOYOTA Jouji , KARINO Yoshiyasu , OMURA Takumi , SUGA Toshihiro 
Published: December 2007

Abstract: This study was designed to evaluate the usefulness of the ultrasonic microprobe (UMP), as compared with endoscopic color Doppler ultrasonography (ECDUS), in detecting gastric varices in 18 patients. The gastric varices detected were categorized as follows: 14 F2 type varices, four F3 type. Among the 18 cases, four had cardiac varices, nine cardiofornical varices, and five fundic varices. UMP was easily performed visually by using an endoscope with a UM‐3R (20MHz) probe, inserted via the biopsy channel, and a display unit (Olympus EU‐M20). ECDUS was performed using a PENTAX FG‐32UA and a FG‐36UX, 7.5MHz, convex type. The display monitor was a HITACHI EUB 565.We were able to clearly delineate the vessel images of gastric varices in all 18 patients using UMP. Although the overall features of the peri‐gastric collateral veins could not be discerned with UMP, the color flow images of gastric varices and peri‐gastric collateral veins were clearly visualized in all 18 patients using ECDUS. It was thus possible to determine blood flow direction using ECDUS.We found the use of UMP to be advantageous in terms of the ease of operation and the excellent view provided of gastric varices. The fact that, due to limited penetration, UMP inadequately delineates the peri‐gastric collateral veins was determined to be a major drawback. Therefore, we recommend ECDUS for evaluating overall hemodynamics. It was, however, technically difficult to scan the fundal region because of the characteristics of the ECDUS instrument.Thus, we conclude that detailed evaluation of gastric varix hemodynamics is most successfully accomplished by using UMP in conjunction with ECDUS.
Choledocholithiasis: Evaluation with MR Cholangiography
Authors: TSITOURIDIS John , KOUKLAKIS George , PAPASTERGIOU Christos , IASONIDOU Christina , XIARCHOS Panagiotis 
Published: December 2007

Abstract:This retrospective study compared imaging results with surgery findings in 26 choledocholithiasis patients who were examined with two‐dimensional fast spin‐echo (2D‐FSE) MR cholangiography and half‐Fourier acquisition single‐shot turbo spin‐echo (HASTE) MR cholangiography. Patients were examined using a 1, 5 T Philips Gyroscan ACS\11 MR scanner and a 1 T Siemens Harmony MR scanner. A total of 21 of the 26 patients with diagnosed choledocholithiasis on imaging were proven to have common bile ducts stones. Two patients had another small stone which was impacted into the Vater and which was not detected with MR cholangiography. One patient with mild dilated common bile duct and pancreatic duct also had a small impacted stone which was not detected by MR cholangiography. One patient had an irregular stone in the hepatic duct, extending partially into the left hepatic duct which was misintepretated as carcinoma. The last patient had a dilated common bile duct due to a small impacted stone which was not detected and biliary sludge which was misintepretated as a stone. The overall sensitivity of MR cholangiography in the detection of common bile duct stones was 80.8%. In conclusion MR cholangiography can rapidly evaluate the common bile duct for stones. The only problem we encountered was in the evaluation of small impacted stones at the Vater. (Dig Endosc 1999; 11: 220–224)
Gastroduodenal Vascular Ectasia in Patients with Liver Cirrhosis
Authors: YAMADA Masahiko , ICHIKAWA Masafumi , TAKAHARA Osamu , TSUCHIDA Takeshi , ISHIHARA Akira , YAMADA Masahiro , NISHIMURA Daisaku , HOSHINO Hiroshi , KATADA Naoyuki , KATO Katsumoto 
Published: December 2007

Abstract:The purpose of this study was to determine the incidence of hemorrhage due to vascular ectasia of the upper gastrointestinal tract in patients with liver cirrhosis and to assess the prevalence in cirrhotic patients without clinically overt gastrointestinal bleeding. Out of 96 cirrhotic patients with upper gastrointestinal bleeding, vascular ectasia was diagnosed in 6 patients (6.3%) as the cause of bleeding. These 6 patients had numerous spotty or confluent erythemas consisting of ectatic and tortuous capillaries throughout the antrutn and 4 patients required blood transfusion before diagnostic en‐doscopy. Several sessions of endoscopic electrocoagulation resulted in eradication of almost all the abnormal vascular lesions and marked improvement of their anemia without further transfusion. The procedure was well tolerated and no resultant complications were encountered. Among 206 cirrhotic patients without clinically overt gastrointestinal bleeding 25 patients (12.1%) were diagnosed with vascular ectasia. The hemoglobin level was significantly lower in patients with vascular ectasia than those without vascular ectasia but the other features did not differ between the two groups. Vascular ectasia is an important cause of upper gastrointestinal bleeding and anemia in patients with liver cirrhosis. Endoscopic electrocoagulation may be a safe and effective treatment for controlling blood loss from gastroduodenal vascular ectasia in this subset of patients. (Dig Endosc 1999; 11: 241–245)
Effect of social support on informed consent in older adults with Parkinson disease and their caregivers
Authors: Ford M E , Kallen M , Richardson P , Matthiesen E , Cox V , Teng E J , Cook K F , Petersen N J 
Published: December 2007

PURPOSE:To evaluate the effects of social support on comprehension and recall of consent form information in a study of Parkinson disease patients and their caregivers.DESIGN and METHODS:Comparison of comprehension and recall outcomes among participants who read and signed the consent form accompanied by a family member/friend versus those of participants who read and signed the consent form unaccompanied. Comprehension and recall of consent form information were measured at one week and one month respectively, using Part A of the Quality of Informed Consent Questionnaire (QuIC).RESULTS:The mean age of the sample of 143 participants was 71 years (SD = 8.6 years). Analysis of covariance was used to compare QuIC scores between the intervention group (n = 70) and control group (n = 73). In the 1-week model, no statistically significant intervention effect was found (p = 0.860). However, the intervention status by patient status interaction was statistically significant (p = 0.012). In the 1-month model, no statistically significant intervention effect was found (p = 0.480). Again, however, the intervention status by patient status interaction was statistically significant (p = 0.040). At both time periods, intervention group patients scored higher (better) on the QuIC than did intervention group caregivers, and control group patients scored lower (worse) on the QuIC than did control group caregivers.IMPLICATIONS:Social support played a significant role in enhancing comprehension and recall of consent form information among patients.
Informed consent in Ghana: what do participants really understand?
Authors: Hill Z , Tawiah-Agyemang C , Odei-Danso S , Kirkwood B 
Published: December 2007

Objectives:To explore how subjects in a placebo-controlled vitamin A supplementation trial among Ghanaian women aged 15–45 years perceive the trial and whether they know that not all trial capsules are the same, and to identify factors associated with this knowledge.Methods:60 semistructured interviews and 12 focus groups were conducted to explore subjects’ perceptions of the trial. Steps were taken to address areas of low comprehension, including retraining fieldworkers. 1971 trial subjects were randomly selected for a survey measuring their knowledge that not all trial capsules are the same. The subjects’ fieldworkers were also interviewed about their characteristics and trial knowledge. Factors associated with knowledge were explored using multi-level modeling.Results:Although subjects knew they were taking part in research, most thought they were receiving an active and beneficial medication. Variables associated with knowledge were education and district of residence. Radio broadcasts benefited those with some schooling. Fieldworkers’ characteristics were not associated with subjects’ knowledge.Conclusions:Research and debate on new or improved consent procedures are urgently required, particularly for subjects with little education.
Biogenicity of gold- and silver-bearing siliceous sinters forming in hot (75°C) anaerobic spring-waters of Champagne Pool, Waiotapu, North Island, New Zealand
Authors: JONES BRIAN , RENAUT ROBIN W. , ROSEN MICHAEL R. 
Published: December 2007

Champagne Pool, a large hot spring at Waiotapu in North Island, New Zealand, is rimmed by a subaerial sinter dam and a shallow subaqueous shelf that is composed of orange sinter rich in metallic sulphides. Orange siliceous flocs, also rich in sulphides, are in constant circulation in the spring pool and form loose sediment on the shelf. The orange sinters and flocs are rich in As, Sb, Tl, and Hg, and have high concentrations of Au (>100 ppm) and Ag (>330 ppm). Most metallic sulphides are amorphous and disseminated throughout the sinter, instead of forming distinct mineral phases.
The shelf sinters are domal and resemble stromatolites. The neutral chloride waters (pH 5.5; temperature 75°C), however, are virtually anaerobic. Examination of the sinters by scanning electron microscopy confirms that they are laminated and contain an abundant, low-diversity assemblage of filamentous, bacilliform, and coccoid microbes. The flocs are similarly composed of very small, silicified filaments. Silicification involved replacement of the cell walls and extensive encrustation by opal-A. Based on size and morphology, these microbes are probably anaerobic bacteria or archaea. By providing substrates for nucleation of the silica, the microbes are indirectly contributing to the formation of the gold-bearing sinters.
A combined zircon SHRIMP and Sm–Nd isotope study of high-grade paragneisses from the Mid-German Crystalline Rise: evidence for northern Gondwanan and Grenvillian provenance
Authors: ZEH A. , BRÄTZ H. , MILLAR I. L. , WILLIAMS I. S. 
Published: December 2007

SHRIMP analyses of detrital zircon cores from high-grade metasediments from the Mid-German Crystalline Rise, which is situated between Eastern Avalonia in the NW and Saxo-Thuringia in the SE, yield mostly ages of
c.
550 Ma and
c.
2.06 Ga, with minor
c.
1.0 and 2.4–2.9 Ga components. The sedimentary protoliths were deposited during the Late Proterozoic to Early Cambrian, probably prior to the break up of the northern Gondwana margin at 460–500 Ma. These data are consistent with the sediments’ high
ϵ
Nd values (0.9 to −3.0), which are comparable to those of well-documented Late Proterozoic sediments from other parts of Europe. The combined isotopic data suggest derivation of the sediments from at least three distinct crustal source regions. Dominant sources were the Avalonian–Cadomian orogenic belt (
c.
45%), situated at the northern margin of Gondwana during the Neoproterozoic, and the West African and/or eastern Amazonian cratons (
c.
45%). The Grenvillian belt was a minor source (
c.
10%).
Late Proterozoic evolution of the northern part of the Hamisana zone, northeast Sudan: constraints on Pan-African accretionary tectonics
Authors: MILLER M. M. , DIXON T. H. 
Published: December 2007

New structural data from the Red Sea Hills, northeast Sudan, add constraints to accretionary tectonic processes that acted in the Arabian-Nubian shield during the late Proterozoic. Geometric constraints provided by field data are used together with Landsat Thematic Mapper imagery to interpret the regional distribution and structural relations of spectrally and lithologically distinctive rock assemblages. In contrast to interpretations reported elsewhere, these studies indicate that the Hamisana zone, a prominent structural feature in the northern Red Sea Hills, post-dated terrane accretion. It is characterized by east-west crustal shortening and by steep folds and thrust faults. Calc-alkaline magmatism was contemporaneous with and outlasted main phase deformation, thus deformation occurred in an intra-arc setting. Thrust faults were reactivated after east-west contraction, compromising their usefulness in delineating 'sutures' or as piercing points across older faults.
Pan-African accretionary processes may have been analogous to Phanerozoic ophiolite and island arc accretion in the western North American Cordillera, where penetrative deformation occurred in response to periodic intra-plate shortening events rather than an ultimate collision of unrelated crustal fragments. Such an analogy implies a mechanism for crustal thickening by structural as well as igneous processes during evolution of an accretionary belt in a long-lived convergent margin setting, consistent with the long-standing observation that Pan-African magmatism became more evolved with time. This view emphasizes that an interplay of deformation and magmatism resulted in protracted accretion and crustal thickening, in contrast to models where crustal shortening results directly from collision of a volcanic arc, microcontinent, or other buoyant features.
Sinistral transpression and the Silurian closure of Iapetus
Authors: SOPER N. J. , STRACHAN R. A. , HOLDSWORTH R. E. , GAYER R. A. , GREILING R. O. 
Published: December 2007

In recent years conflicting models have been proposed for the late Caledonian closure of the Iapetus ocean between Laurentia, Baltica and the Avalonian terranes. Recently published structural and stratigraphic evidence from Britain, Scandinavia, East Greenland and Newfoundland is reviewed and shows that Western Avalonia, Eastern Avalonia and Baltica all docked sinistrally against Laurentia in the Silurian.
Western Avalonia collided sinistrally against the previously accreted Gander and Dunnage arc terranes on the Appalachian margin of Laurentia in mid-Silurian time and then shifted dextrally during the Acadian orogeny in the Devonian. Oblique collision of Baltica with the Greenland margin induced southeasterly crustal stacking in the Scandian orogen and sinistral transpression in the NE Greenland Caledonides, and was followed by more nearly orthogonal convergence. Eastern Avalonia underwent anticlockwise with the Scottish ‘corner’ of Laurentia, rotating into a re-entrant between Laurentia and Baltica.
Some implications of this Silurian closure model are that convergence in the Tornquist zone was modest at that time, and that the Acadian (Devonian) deformation in the northern Appalahians and Britain had a subsequent external cause, most likely the impingement of Armorica and Iberia due to the northward drift of Gondwana.