bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin αIIbβ3:ligand interactions are linked to binding‐site remodeling
Authors: Hantgan Roy R. , Stahle Mary C. , Connor John H. , Horita David A. , Rocco Mattia , McLane Mary A. , Yakovlev Sergiy , Medved Leonid 
Published: July 2006

AbstractThis study tested the hypothesis that high‐affinity binding of macromolecular ligands to the αIIbβ3 integrin is tightly coupled to binding‐site remodeling, an induced‐fit process that shifts a conformational equilibrium from a resting toward an open receptor. Interactions between αIIbβ3 and two model ligands—echistatin, a 6‐kDa recombinant protein with an RGD integrin‐targeting sequence, and fibrinogen's γ‐module, a 30‐kDa recombinant protein with a KQAGDV integrin binding site—were measured by sedimentation velocity, fluorescence anisotropy, and a solid‐phase binding assay, and modeled by molecular graphics. Studying echistatin variants (R24A, R24K, D26A, D26E, D27W, D27F), we found that electrostatic contacts with charged residues at the αIIb/β3 interface, rather than nonpolar contacts, perturb the conformation of the resting integrin. Aspartate 26, which interacts with the nearby MIDAS cation, was essential for binding, as D26A and D26E were inactive. In contrast, R24K was fully and R24A partly active, indicating that the positively charged arginine 24 contributes to, but is not required for, integrin recognition. Moreover, we demonstrated that priming—i.e., ectodomain conformational changes and oligomerization induced by incubation at 35°C with the ligand‐mimetic peptide cHarGD—promotes complex formation with fibrinogen's γ‐module. We also observed that the γ‐module's flexible carboxy terminus was not required for αIIbβ3 integrin binding. Our studies differentiate priming ligands, which bind to the resting receptor and perturb its conformation, from regulated ligands, where binding‐site remodeling must first occur. Echistatin's binding energy is sufficient to rearrange the subunit interface, but regulated ligands like fibrinogen must rely on priming to overcome conformational barriers.
A structural rationale for SV40 Vp1 temperature‐sensitive mutants and their complementation
Authors: Kasamatsu Harumi , Woo Jennifer , Nakamura Akiko , Müller Peter , Tevethia M. Judith , Liddington Robert C. 
Published: August 2006

AbstractTwo groups of temperature‐sensitive (ts) mutants, termed ts B and ts C, have mutations in the major capsid protein of SV40, Vp1. These mutants have virion assembly defects at the nonpermissive temperature, but can complement one another when two mutants, one from each group, coinfect a cell. A third group of mutants, termed ts BC, have related phenotypes, but do not complement other mutants. We found that the mutations fall into two structural and functional classes. All ts C and one ts BC mutations map to the region close to the Ca2+ binding sites, and are predicted to disrupt the insertion of the distal part of the C‐terminal invading arm (C‐arm) into the receiving clamp. They share a severe defect in assembly at the nonpermissive temperature, with few capsid proteins attached to the viral minichromosome. By contrast, all ts B and most ts BC mutations map to a contiguous region including acceptor sites for the proximal part of the C‐arm and intrapentamer contacts. These mutants form assembly intermediates that carry substantial capsid proteins on the minichromosome. Thus, accurate virion assembly is prevented by mutations that disrupt interactions between the receiving pentamer and both the proximal and distal parts of the C‐arms, with the latter having a greater effect. The distinct spatial localization and assembly defects of the two classes of mutants provide a rationale for their intracistronic complementation and suggest models of capsid assembly.
Energetics of aliphatic deletions in protein cores
Authors: Bueno Marta , Campos Luis A. , Estrada Jorge , Sancho Javier 
Published: July 2006

AbstractAlthough core residues can sometimes be replaced by shorter ones without introducing significant changes in protein structure, the energetic consequences are typically large and destabilizing. Many efforts have been devoted to understand and predict changes in stability from analysis of the environment of mutated residues, but the relationships proposed for individual proteins have often failed to describe additional data. We report here 17 apoflavodoxin large‐to‐small mutations that cause overall protein destabilizations of 0.6–3.9 kcal.mol−1. By comparing two‐state urea and three‐state thermal unfolding data, the overall destabilizations observed are partitioned into effects on the N‐to‐I and on the I‐to‐U equilibria. In all cases, the equilibrium intermediate exerts a “buffering” effect that reduces the impact of the overall destabilization on the N‐to‐I equilibrium. The performance of several structure‐energetics relationships, proposed to explain the energetics of hydrophobic shortening mutations, has been evaluated by using an apoflavodoxin data set consisting of 14 mutations involving branching‐conservative aliphatic side‐chain shortenings and a larger data set, including similar mutations implemented in seven model proteins. Our analysis shows that the stability changes observed for any of the different types of mutations (LA, IA, IV, and VA) in either data set are best explained by a combination of differential hydrophobicity and of the calculated volume of the modeled cavity (as previously observed for LA and IA mutations in lysozyme T4). In contrast, sequence conservation within the flavodoxin family, which is a good predictor for charge‐reversal stabilizing mutations, does not perform so well for aliphatic shortening ones.
A model for the coupling of α‐helix and tertiary contact formation
Authors: Hausrath Andrew C. 
Published: August 2006

AbstractPeptides corresponding to excised α‐helical segments of natural proteins can spontaneously form helices in solution. However, peptide helices are usually substantially less stable in solution than in the structural context of a folded protein, because of the additional interactions possible between helices in a protein. Such interactions can be thought of as coupling helix formation and tertiary contact formation. The relative energetic contributions of the two processes to the total energy of the folded state of a protein is a matter of current debate. To investigate this balance, an extended helix‐coil model (XHC) that incorporates both effects has been constructed. The model treats helix formation with the Lifson‐Roig formalism, which describes helix initiation and propagation through cooperative local interactions. The model postulates an additional parameter representing participation of a site in a tertiary contact. In the model, greater helix stability can be achieved through combinations of these short‐range and long‐range interactions. For instance, stronger tertiary contacts can compensate for helices with little intrinsic stability. By varying the strength of the nonlocal interactions, the model can exhibit behavior consistent with a variety of qualitative models describing the relative importance of secondary and tertiary structure. Moreover, the model is explicit in that it can be used to fit experimental data to individual peptide sequences, providing a means to quantify the two contributions on a common energetic basis.
The product complex of M. tuberculosis malate synthase revisited
Authors: Anstrom David M. , Remington S. James 
Published: July 2006

AbstractEnzymes of the glyoxylate shunt have been implicated as virulence factors in several pathogenic organisms, notably Mycobacterium tuberculosis and Candida albicans. Malate synthase has thus emerged as a promising target for design of anti‐microbial agents. For this effort, it is essential to have reliable models for enzyme:substrate complexes. A 2.7 Å resolution crystal structure for M. tuberculosis malate synthase in the ternary complex with magnesium, malate, and coenzyme A has been previously described. However, some unusual aspects of malate and Mg++ binding prompted an independent determination of the structure at 2.3 Å resolution, in the presence of saturating concentrations of malate. The electron density map of the complex reveals the position and conformation of coenzyme A to be unchanged from that found in the previous study. However, the coordination of Mg++ and orientation of bound malate within the active site are different. The revised position of bound malate is consistent with a reaction mechanism that does not require reorientation of the electrophilic substrate during the catalytic cycle, while the revised Mg++ coordination is octahedral, as expected. The results should be useful in the design of malate synthase inhibitors.
Crystal structure of the human TRPV2 channel ankyrin repeat domain
Authors: McCleverty Clare J. , Koesema Eric , Patapoutian Ardem , Lesley Scott A. , Kreusch Andreas 
Published: August 2006

AbstractTRPV channels are important polymodal integrators of noxious stimuli mediating thermosensation and nociception. An ankyrin repeat domain (ARD), which is a common protein–protein recognition domain, is conserved in the N‐terminal intracellular domain of all TRPV channels and predicted to contain three to four ankyrin repeats. Here we report the first structure from the TRPV channel subfamily, a 1.7 Å resolution crystal structure of the human TRPV2 ARD. Our crystal structure reveals a six ankyrin repeat stack with multiple insertions in each repeat generating several unique features compared with a canonical ARD. The surface typically used for ligand recognition, the ankyrin groove, contains extended loops with an exposed hydrophobic patch and a prominent kink resulting from a large rotational shift of the last two repeats. The TRPV2 ARD provides the first structural insight into a domain that coordinates nociceptive sensory transduction and is likely to be a prototype for other TRPV channel ARDs.
Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis
Authors: Okano M. , Fujiwara T. , Yamamoto M. , Sugata Y. , Matsumoto R. , Fukushima K. , Yoshino T. , Shimizu K. , Eguchi N. , Kiniwa M. , Urade Y. , Nishizaki K. 
Published: August 2006

SummaryBackground
Prostaglandin (PG)D2 and E2, two major cyclooxygenase (COX) products, are generated by PGD2 synthase (PGDS) and PGE2 synthase (PGES), respectively, and appear to mediate airway inflammation.Objective
We sought to determine the role of PGDS and PGES in the pathophysiology of chronic rhinosinusitis (CRS).Methods
The study examined the expression of PGDS and PGES in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were obtained from 12 CRS patients not having nasal polyps and five subjects without sinusitis. Immunohistochemistry and quantitative real‐time PCR were used to evaluate the expression.Results
Both PGDS and PGES were detected in nasal polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and lesser levels of PGES mRNA were observed in the nasal polyps as compared with uncinate process mucosae, and an inverse correlation between PGDS and PGES expression was observed. Levels of PGDS mRNA in nasal polyps were positively correlated with degree of infiltration by EG2+ eosinophils, whereas the levels of PGES were inversely correlated. Significantly increased levels of PGDS and conversely decreased levels of PGES were observed in asthmatics as compared with non‐asthmatics. In addition, PGDS and PGES levels were positively and inversely correlated with the radiological severity of sinusitis, respectively.Conclusions
These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation.
Associations between antioxidant status, markers of oxidative stress and immune responses in allergic adults
Authors: Dunstan J. A. , Breckler L. , Hale J. , Lehmann H. , Franklin P. , Lyonso G. , Ching S. Y. L. , Mori T. A. , Barden A. , Prescott S. L. 
Published: August 2006

SummaryBackground
There has been growing interest in the role of antioxidant function in controlling inflammatory disease states, such as allergy. This study investigated the relationship between antioxidant status, markers of airways inflammation [exhaled nitric oxide (eNO)], oxidative stress (F2 isoprostanes) and immune responses in allergic adults.Methods
Antioxidants (vitamins C, E, β‐carotene and selenium) and total antioxidant capacity (tAC) in serum were examined in relation to eNO, plasma F2 isoprostanes and peripheral blood mononuclear cell (PBMC) cytokine and lymphoproliferative response to house dust mite (HDM) allergen, Staphylococcus enterotoxin B (SEB), phytohaemaglutinin (PHA) and lipopolysaccharide (LPS) in 54 allergic adults.Results
Firstly, levels of specific vitamins did not correlate with tAC. Secondly, we did not see any evidence that specific vitamin levels (or tAC) were associated with either polarization or attenuation of in vitro immune responses. If anything, there were positive correlations between antioxidant (vitamin C and selenium) levels and HDM allergen responses [lymphoproliferation (selenium; r=0.35, P=0.013) and both Th2 IL13 (vitamin C; τ=0.254, P=0.028) and Th1 IFN‐γ (vitamin C; τ=0.302, P=0.009) responses]. There were also significant positive relationships between antioxidant levels and IL‐10 responses to polyclonal stimulation by SEB (r=0.292, P=0.036) and LPS (r=0.34, P=0.015) (β‐carotene) and PHA (r=0.34, P=0.021) (tAC). Thirdly, although airways inflammation (eNO) was associated with both in vitro and in vivo (skin test reactivity) to HDM, we did not see any correlation between eNO and oxidative stress (F2‐isoprostanes). Finally, there were no consistent relationships between oxidative stress and immune responses.Conclusion
There was no evidence that higher antioxidant levels were associated with reduced allergen responsiveness in allergic adults. If anything, antioxidant status was associated with increased immune responsiveness. The significance of this needs to be addressed in future intervention studies.
Associations between ghrelin levels in serum of preterm infants and enteral nutritional state during the first 6 months after birth
Authors: Hübler Axel , Rippel Constance , Kauf Eberhard , Hoyer Heike , Mainz Jochen , Schlenvoigt Dorothea , Schramm Dirk 
Published: July 2006

SummaryBackground  Previous studies have suggested a possible influence of ghrelin on foetal growth. After birth, the regulation of this newly discovered orexigenic peptide is largely unknown.Objective  To study the relationship between circulating levels of ghrelin and enteral nutritional state in preterm infants during the first months of life.Methods  Ghrelin levels were measured in a cross‐sectional study by radioimmunoassay on the second day after birth (n = 51), at 3 months (n = 63) and at 6 months (n = 53) of corrected postnatal age. Complete data sets of auxological parameters, biochemical values, perinatal diseases, nutritional management and therapy were determined.Results  All infants showed levels of ghrelin in postnatal serum. In correlation analyses and multivariable linear regression models, ghrelin was strongly related to enteral caloric intake on the second day after birth (all P < 0·01). At 6 months of corrected postnatal age, infants who were exclusively breastfed/formula fed had significantly lower ghrelin levels than infants with solid foods (Mann–Whitney U‐test: P = 0·027).Conclusion  Ghrelin levels were positively correlated with the enteral nutritional state in preterm infants on the second day after birth. The introduction of solid foods increased the ghrelin levels in a group of preterm infants at 6 months of corrected postnatal age.
A TECHNIQUE FOR SELECTIVE SOLUTION OF IRON OXIDES IN THIN SECTIONS OF SOIL
Authors: BULLOCK P. , LOVELAND P. J. , MURPHY C. P. 
Published: July 2006

SummaryA technique to study optically the effects of three different extraction procedures for removing iron from thin sections of soil is described. The distribution of iron in each section is recorded before treatment. Silicone grease is then applied to all parts of the sections except those to be treated. The areas selected for treatment are immersed for 24 hours in one of three beakers containing dithionite‐citrate‐bicarbonate, 02M ammonium oxalate at pH3 and 01M K‐pyrophosphate at pH10. After treatment, the sections are degreased and the effects of the various treatments examined optically.
Vertical, lateral and longitudinal movement of zooplankton in a large river
Authors: JACK JEFFREY D. , FANG WEI , THORP JAMES H. 
Published: July 2006

Summary1. The spatial distribution and movement patterns of zooplankton in large rivers are little known compared with those in lake environments. We conducted a series of studies in the Ohio River (U.S.A.) during the low flow period to assess diel vertical (DVM), longitudinal and lateral movement of crustacean zooplankton.2. The dominant large zooplankter, the copepod Eurytemora affinis, showed a consistent vertical migration pattern of daytime ascent and night‐time descent during all sampling periods – the reverse of the most common migratory pattern of zooplankton in lakes. The cladoceran Bosmina migrated in a similar way in two of the three sampling periods. Surveys taken longitudinally in the river showed similar trends for both taxa.3. During the lateral surveys, E. affinis was significantly more abundant in the shallow littoral zone during the night than in the daytime. The combination of vertical and lateral movement patterns along with the diel distribution of zooplanktivorous fish suggest that these movements are a predator‐avoidance mechanism.4. Sampling programmes in large rivers should consider that larger zooplankton such as E. affinis may not be randomly distributed in the river channel and behaviours such as diel vertical migration may be just as evident in river habitats as in lakes.
Mechanical branch constraints contribute to life‐history variation across tree species in a Bolivian forest
Authors: STERCK FRANK J. , VAN GELDER H. ARNOLD , POORTER LOURENS 
Published: July 2006

Summary

Trade‐offs among plant traits may contribute to specialization for different environments and coexistence of plant species. This may be the first study that shows how trade‐offs among branch traits contribute to variation in crown size, light requirements and maximum height across multiple sympatric tree species in a tropical rain forest.
Ten saplings were selected for each of 30 tree species in a Bolivian rain forest. Sapling height and crown dimensions were measured and branch and stem samples were harvested. Fresh density, dry density, modulus of rupture, centre of mass, biomass and diameters were determined for those samples. For each species, cantilever theory predicted the mass needed to produce a stable 1‐m long horizontal branch.
Generally, shade‐tolerant species had denser and stronger branches, and produced a stable horizontal branch at lower resource costs. These species had branches with a higher resistance against mechanical failure, and a wide crown that favours effective light acquisition. Less shade‐tolerant species had low density and weak branches, short branches, high resource costs per unit branch length, and low resource costs per unit stem length. These traits seem advantageous under conditions of prolonged exposure to direct sunlight, where such species grow rapidly to reproductive size, while mechanical risks are low and light levels are favourable.
Branch (wood and bark) traits are good predictors for performance differences across tree species in heterogeneous forest light environments. Physical trade‐offs among branch traits contribute to the specialization of tree species for different light habitats and to tree species coexistence in tropical rain forests, even within classical functional groups such as pioneers and shade tolerants.
Microfauna associated with amoebic gill disease in sea‐farmed Atlantic salmon, Salmo salar L., smolts
Authors: Bermingham M L , Mulcahy M F 
Published: August 2006

AbstractA study of microfauna, associated with pathological changes in the gills of Atlantic salmon, Salmo salar L., was conducted over 2001–2002. Monthly samples of 1+ salmon smolts were taken, protozoan populations were quantified and gill health was assessed histologically. Protozoan densities were correlated with pathological changes, in order to determine their possible role in lesions in the gills. The most severe gill tissue changes were observed in summer/autumn and the least in spring. A diverse polyphyletic protozoan community was observed colonizing the gills, including Neoparamoeba sp., other amoebae, scuticociliates, Ichthyobodo‐like flagellates, trichodinid ciliates and prostomatean ciliates. The earlier gill tissue changes in the gill were not always associated with the presence of these microorganisms, whereas amoebae (other than Neoparamoeba sp.), Ichthyobodo‐like flagellates and trichodinid ciliates correlated with augmenting gill lesions. Neoparamoeba sp. was present, but its abundance did not correlate with the disease. This study suggests that a diversity of protozoans including Ichthyobodo‐like flagellates, trichodinid ciliates and amoebae other than Neoparamoeba sp. are involved in the aetiology of amoebic gill disease in the Irish situation.
The Metabolic Syndrome: A Brain Disease?
Authors: Buijs Ruud M , Kreier Felix 
Published: July 2006

SummaryThe incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia − the metabolic syndrome − is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each morning for the coming activity period is altered due to a modern life style of low activity during the day and late‐night food intake. Furthermore, we review the anatomical evidence supporting the proposal that an unbalanced autonomic nervous system output may lead to the simultaneous occurrence of diabetes type 2, dyslipidemia, hypertension and visceral obesity.
Untersuchungen zum Abbau des Herbizids Chlorphenpropmethyl im Boden und durch Mikroorganismen
Authors: KÖCHER HELMUT , LINGENS FRANZ , KOCH WERNER 
Published: August 2006

Zusammenfassung:Das Herbizid 2‐Chlor‐3‐(4‐chlorphenyl)propionsauremethylester (Chlorphenprop‐methyl) wurde in Sand‐und Lehmboden bei 21°C innerhalb weniger Stunden hydrolysiert. Das Hydrolyseprodukt 2‐Chlor‐3‐(4‐chlorphenyl)propionsäure (CPP) wurde in beiden Böden bei 22.0 ppm Anfangskonzentration mit einer Halbwertszeit von 4 bis 8 Tagen. bei 4.4 ppm Anfangskonzenlralion mit einer Halbwertszeit von knapp einem Tag abgebaut. Als Zwischenprodukt des CPP‐Abbaus in Boden wurde 4‐Chlorbenzoesaure, in Mischkulturen von Bodenmikroorganismen ausserdem 4‐Chlorzimtsäure identifiziert. Tn autoklaviertem und mit NaN3 sterilisiertem Boden unterblieb der Abbau von CPP. Die Anreicherung und Isolierung von Mikroorganismen, die den ersten Schritt des CPP‐Abbaus vollziehen, war nicht möglich. Zwei aus den VersuchsbÖden isolierte und vorläufig den Gattungen Flavobacterium bzw. Brevibacterium zugeordnete Bakterienstämme bauten den Metaboliten 4‐Chlorzimtsäure zu 4‐ Chlorbenzoesäure ab, zwei de r Gattung Arthrobacter Zugeordnete Bakterienstämme wuchsen auf der 4‐Chlorbenzoesäure als alleiniger Kohlenstoffquelle. Die Ergebnisse sprechen insgesaml dafär, dass Chlorphenprop‐methyl im Boden zunächst zu CPP hydrolysiert wird, welches anschliessend über 4‐Chlorzimtsäure zu 4‐Chlorbenzoesäure abgebaut wird. Von der 4‐Chlorbenzoesäure aus erfolgt dann weiterer Abbau unter Ringspaltung.